Abstracts
e1
ORAL SESSION
ORAL SESSION 1A
DIABETES
1A.01
ROADMAP OBSERVATIONAL FOLLOW-UP STUDY:
BENEFITS OF RAAS BLOCKADE WITH OLMESARTAN
TREATMENT ARE SUSTAINED AFTER STUDY
DISCONTINUATION
J. Menne 1, E. Ritz 2, L.M. Ruilope 3, C. Chatzikyrkou 1, G. Viberti 4, H. Haller 1.
Medical School Hannover, Hannover, GERMANY, 2 University of Heidelberg,
Heidelberg, GERMANY, 3 Hospital 12 de Octubre, Madrid, SPAIN, 4 Kings
College London School of Medicine, London, UNITED KINGDOM
1
Objective: The ROADMAP study showed that 40 mg Olmesartan medoxomil
(OM) versus placebo delayed microalbuminuria onset in patients with type 2
diabetes and normoalbuminuria.
Design and method: 1758 ROADMAP patients (877 patients from the placebo
and 881 from the OM arm) were assigned for observational follow up (OFU)
after study termination. During a mean follow-up of 3.3 years they received
standard medical care and micro- and macrovascular events were documented.
Results: In both groups an increase of the blood pressure was observed after
stoppage of the study medication to mean values of 135 mmHg. This increase
was more pronounced in the OM group, despite the fact that during observational follow-up 62.9% and 60.1% in the former OM and placebo group reFHLYHGWUHDWPHQWZLWKD5$6EORFNLQJDJHQW$VLJQL¿FDQWO\KLJKHUQXPEHURI
patients who had developed microalbuminuria during ROADMAP had a cardio- or cerebrovascular event (15.9% vs. 8.5%; OR 2.0, p=0.005) during the
OFU period compared to patients who had not developed microalbuminuria.
'LDEHWLF UHWLQRSDWK\ ZDV VLJQL¿FDQWO\ UHGXFHG LQ WKH IRUPHU 20 JURXS (0.9%) vs. 23 (2.6%), p=0.009) and the rate of microalbuminuria was numeriFDOO\UHGXFHG7KHUHZHUHVLJQL¿FDQWO\IHZHUQRQIDWDOVWURNHV YV
(2.1%), p=0.03) or congestive heart failure requiring hospitalization (3 (0.3%)
vs. 12 (1.2%), p=0.02) in the former OM group and there was a trend of reduced
cardio-/cerebrovascular events (OM vs. Pb: 73 (8.3%) vs. 86 (9.8%) patients).
7 deaths (including 2 CV events) were reported in former placebo patients vs. 3
(non CV events) in former OM patients.
Conclusions: Development of microalbuminuria is a valid marker for future CV
events. Overall the number of events were small. However, RAS blockade with
Olmesartan for several years may be associated with reduction (legacy effect) of
micro- and macrovascular events.
1A.02
RISK FACTORS OF SEXUAL DYSFUNCTION ON
HYPERTENSION AND TYPE 2 DIABETES MELLITUS
E. Gavriilaki, C. Nouris, B. Nikolaidou, A. Triantafyllou, G. Triantafyllou,
P. Anyfanti, A. Dimakopoulou, A. Lazaridis, A. Reklou, E. Gkaliagkousi,
C. Sampanis, M. Doumas, S. Douma.
Aristotle University, Thessaloniki, GREECE
Objective: Hypertension and diabetes mellitus are highly prevalent diseases
with detrimental effects on several physical functions, like sexual performance.
Many risk factors of sexual dysfunction either physical or psychological, like
anxiety and depression, have been recognized in the general population. However, the predictive role of each independent risk factor regarding sexual dysfunction in hypertensive patients with comorbid type 2 diabetes mellitus has not
been elucidated. We aimed at investigating the effect of several risk factors on
prevalence of sexual dysfunction in patients suffering concurrently from hypertension and type 2 diabetes mellitus.
Design and method: Consecutive hypertensive patients suffering from type 2
diabetes mellitus who attended the Hypertensive Outpatient Clinic of the 2nd
Propedeutic Department were included in the study. A thorough medical history was taken and a blood sample was drawn. The Female Sexual Dysfunction
Index (FSFI) and the International Index of Erectile Function (IIEF) questionnaires were used to detect cases of sexual dysfunction. Depression and anxiety
were evaluated using the Zunk and the Hamilton questionnaires respectively.
Results: Our study sample consisted of 281 patients, 60.5% females and 39.5%
males. Patients’ mean age was 67±10 years, mean systolic blood pressure was
151±20mmHg and mean diastolic blood pressure was 81±11mmHg. The vast
majority of our patients (88.6%) were diagnosed with sexual dysfunction. Logistic regression analysis showed that the prevalence of sexual dysfunction is affected by female gender (OR: 3.73 [CI: 1.56-7.31], p=0.002), age (OR: 1.1 [CI:
1.05-1.36], p<0.001), anxiety (OR: 3.69 [CI: 1.37-9.89], p=0.01) and depression
(OR: 1.13 [CI: 1.07-1.20], p=0,001).
Conclusions: Female gender, aging, anxiety and depression are independent
risk factors of sexual dysfunction. Clinicians should be aware of this likelihood
and screen their patients, especially females, for depression and anxiety in order
to proceed with necessary therapeutic interventions and alleviate the burden of
sexual dysfunction in hypertensive patients with type 2 diabetes mellitus.
1A.03
VALIDATION OF A URINARY PROTEOMIC CLASSIFIER
FOR DIAGNOSIS OF DIABETIC NEPHROPATHY
G. Currie 1, J. Siwy 2,3, M. Lindhardt 4, C. Delles 1, J. Jankowski 3, H. Mischak 1,2,
P. Rossing 4,5, Priority Investigators. 1 Institute of Cardiovascular and Medical
Sciences, University of Glasgow, Glasgow, UNITED KINGDOM, 2 Mosaiques
Diagnostics GmbH, Hannover, GERMANY, 3 Charite-Universitaetsmedizin
Berlin, Medizinische Klinik IV, Berlin, GERMANY, 4 Steno Diabetes Center,
Gentofte, DENMARK, 5 Faculty of Health, University of Copenhagen,
Copenhagen, DENMARK
Objective: Current practice uses urinary albumin as a clinical marker of early
diabetic nephropathy (DN) but tools for preclinical disease detection are lackLQJ:HKDYHSUHYLRXVO\HVWDEOLVKHGDXULQDU\SURWHRPLFFODVVL¿HURISHStides (“CKD273”) to successfully predict progression from normo- to macroalbuminuria in diabetic patients 3-5 years before onset of microalbuminuria. In a
multicentre cross-sectional study we evaluated the performance of CKD273 in
differentiating between normoalbuminuria and DN.
Design and method: Spot urine samples were obtained from 165 type 2 diabetic
patients (87 with DN, 78 without) across 9 European centres. Blinded sample
analysis was performed using capillary electrophoresis coupled to mass specWURPHWU\ &(06 6HQVLWLYLW\DQGVSHFL¿FLW\RI&.'ZDVFDOFXODWHGXVLQJ
receiver operating characteristic (ROC) curves.
Results: ROC curves for each centre resulted in area under the curve (AUC)
YDOXHVEHWZHHQDQGZLWKQRVLJQL¿FDQWGLIIHUHQFHVEHWZHHQFHQWUHV7DNLQJDFODVVL¿HUVFRUHRIDVWKHFXWRIIIRU'1FRPELQHGDQDO\VLVRIDOO
samples resulted in AUC of 0.95 (95% CI 0.90-0.98) as shown below. Logistic
UHJUHVVLRQFRQ¿UPHGQRLQÀXHQFHRIDJHRUJHQGHURQ&.'FODVVL¿HUVFRUH
(p=0.269 for age, p=0.312 for gender).
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Journal of Hypertension Volume 32, e-Supplement 1, 2014
Conclusions: 7KHVH GDWD VXJJHVW WKDW WKH &.' FODVVL¿HU LV DFFXUDWH DQG
reproducible in differentiating between patients with and without DN. Its utility
for prediction of DN in normoalbuminuric diabetic patients with normal renal
function and subsequent impact on therapeutic decisions will now be evaluated
in a multicentre trial (PRIORITY study).
1A.04
PROGNOSTIC INTERACTION BETWEEN CLINIC AND
AMBULATORY BLOOD PRESSURES AND GLYCATED
HEMOGLOBIN IN PATIENTS WITH TYPE 2 DIABETES
C. Cardoso, N. Leite, G. Salles. School of Medicine, Federal University of Rio
de Janeiro, Rio de Janeiro, BRAZIL
Objective: High blood pressure (BP) and poor glycemic control are wellaccepted determinants of worse cardiovascular prognosis in diabetic patients.
However, their potential interactions in increasing cardiovascular risk remains
unsettled. The aim was to evaluate the prognostic interactions of clinic and
ambulatory systolic BPs and glycated hemoglobin (HbA1c) for cardiovascular
morbidity and mortality.
Design and method: In a prospective cohort study, 565 type 2 diabetic patients
were followed-up for a median of 5.75 years. All had clinic and 24-hour ambulatory BPs obtained at entry. Clinic SBP was dichotomized at 140 mmHg and
24-hour SBP at 120 mmHg. Glycemic control was evaluated as mean HbA1c
GXULQJWKH¿UVW\HDURIIROORZXSGLFKRWRPL]HGDW3ULPDU\HQGSRLQWZDV
WKHRFFXUUHQFHRI¿UVWIDWDORUQRQIDWDOFDUGLRYDVFXODUHYHQW6WDWLVWLFDODQDO\VHV
included Kaplan-Meier curves and Cox multivariate models.
Results: Eighty-eight cardiovascular events occurred (38 fatal events). Both
high SBP (for clinic HR: 1.68; 95%CI: 1.00-2.85; p=0.05; and for 24-hour SBP
HR: 2.08; 95%CI: 1.11-3.90; p=0.023) and elevated HbA1c (HR: 1.77; 95%CI:
1.07-2.94; p=0.028; and HR: 1.74; 95%CI: 1.03-2.94; p=0.038, respectively in
the models with clinic and 24-hour SBP) predicted cardiovascular outcomes.
There was no interaction (p=0.66) between clinic SBP and HbA1c, which means
that high clinic SBP and HbA1c had independent and additive effects on cardiovascular prognosis. Otherwise, there was a borderline interaction (p=0.13)
between 24-hour SBP and HbA1c: the prognostic impact of high HbA1c was
only observed in patients with high 24-hour SBP (HR: 2.16; 95%CI: 1.18-3.94;
p=0.012), but not in those with lower 24-hour SBP (HR: 0.71; 95%CI: 0.22S .DSODQ0HLHUDQDO\VLVRIVXUYLYDOFXUYHVFRQ¿UPHGWKHVH¿QGLQJV ZKHQ FURVVFODVVL¿HG DFFRUGLQJ WR FOLQLF 6%3 DQG +E$F WKHUH ZDV D
JUDGHGLQFUHDVLQJULVNLQWKHVXEJURXSVZKHUHDVZKHQFURVVFODVVL¿HGDFFRUGLQJWRKRXU6%3RQO\WKHVXEJURXSZLWKKLJK6%3DQG+E$FKDGVLJQL¿cantly higher cardiovascular risk.
Conclusions: Controlling 24-hour ambulatory SBP abolished the adverse impact of poor glycemic control on cardiovascular prognosis in patients with type
2 diabetes, which was not observed for clinic SBP levels. This reinforces the
importance of ambulatory BP monitoring in type 2 diabetes management.
1A.05
EVOLUTION OF GLOMERULAR FILTRATION RATE IN
PATIENTS WITH ESSENTIAL HYPERTENSION: IMPACT
OF TYPE 2 DIABETES
J. Segura, C. Cerezo, E. Morales, G. Ruiz, L. Fernandez, L. Guerrero,
M. Praga, L.M. Ruilope. Hypertension Unit, Department of Nephrology,
Instituto de Investigación 12, Hospital 12 de Octubre, Madrid, SPAIN
Objective: It has been described the relationship between aging and the estiPDWHGJORPHUXODU¿OWUDWLRQUDWH H*)5 GHFOLQHZKLFKLVDURXQGPOPLQ\HDU
Different processes have been described in which the annual decline in eGFR is
faster, particularly in diabetes.
The aim of this study was to analyze the eGFR decline in a cohort of patients
with essential hypertension and to analyze the impact of diabetes on the progression of renal disease.
Design and method: 2314 patients with essential hypertension, 46.1 % male,
mean age 57.0±14.6 years, 20.8 % diabetic, were analyzed. Mean follow-up
time was 6.5 ± 3.6 years.
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H*)5GHFOLQHZDVDQDO\]HGERWKDEVROXWHO\ ¿QDOH*)5LQLWLDOH*)5 \HDUV
RIIROORZXS DQGUHODWLYHO\ ¿QDOH*)5±LQLWLDOH*)5 LQLWLDOH*)5 \HDUV
of follow-up)x100).
Results: The whole group showed a mean eGFR of 76.9±21.6 ml/min/1.73m2.
The distribution of patients with normo- , micro- and macroalbuminuria was
78.6% , 18.5% and 2.8%. The absolute eGFR decline was 0.29 ml/min/1.73m2/
year, representing a relative reduction of 0.11% per year.
According the presence or absence of diabetes, the absolute eGFR decline was
0.54 and 0.23 ml/min/1.73m2/year, respectively (p=0.146), representing relative reductions of 0.64% and 0.03% per year (p=0.035). At baseline, diabetic
patients had higher age (63.4±10.9 vs 55.4±15.0 years), higher body mass index (31.2±5.2 vs 28.6±4.8 kg/m2), higher systolic blood pressure (157 vs 148
mmHg), higher requirements of antihypertensive drugs (2.4±1.2 vs 1.7±1.1) and
higher percentages of patients with micro- and macroalbuminuria (24.6% vs
16.7%, and 7.3% vs 1.5% ) (p<0.001 for all comparisons).
Conclusions: In conclusion, in a cohort of essential hypertensive patients regularly followed at our center, the decline in eGFR is lower than the classically
GHVFULEHGLQWKHOLWHUDWXUH7KHGLDJQRVLVRIGLDEHWHVLGHQWL¿HVSDWLHQWVZLWKD
worse renal prognosis, with a faster loss of renal function.
1A.06
C-PEPTIDE AND A PDE5 INHIBITOR RESTORE THE
ABILITY OF ERYTHROCYTES OF HUMANS WITH
TYPE 2 DIABETES (DM2) TO RELEASE ATP AND
STIMULATE LOCAL VASODILATION WHEN EXPOSED
TO LOW OXYGEN
J. Richards, W. Gordon, D. Achilleus, E. Bowles, A. Stephenson, M. Ellsworth,
R. Sprague. Saint Louis University, Department of Pharmacological and
Physiological Science, Saint Louis, MO, USA
Objective: ATP release from erythrocytes in response to low oxygen tension
induces local vasodilation, enabling these cells to direct perfusion to areas with
increased metabolic demand. This critical physiological function is defective
in type 2 diabetes (DM2). Previously we demonstrated that incubation of DM2
erythrocytes with cilostazol, a phosphodiesterase 3 (PDE3) inhibitor, restored
both low oxygen-induced ATP release and vasodilation. The ability of erythrocytes to release ATP and dilate arterioles in response to low oxygen is also lost in
healthy human erythrocytes exposed to postprandial insulin levels. Importantly,
cilostazol prevents cAMP degradation counteracting insulin-induced inhibition
of ATP release. Co-incubation of erythrocytes with insulin and C-peptide, which
are co-released, also prevented these adverse effects of insulin. The similar effects of C-peptide and cilostazol suggest a common mechanism of action investigated here.
Design and method: Erythrocytes were isolated and incubated with either the
PDE5 inhibitor, zaprinast, or C-peptide ± insulin ± the soluble guanylyl cyclase
V*& LQKLELWRU 2'4 DQG H[SRVHG WR QRUPDO DQG UHGXFHG R[\JHQ WKLQ¿OP
tonometer). ATP was measured by chemiluminescence. Isolated skeletal muscle
arterioles perfused with fully oxygenated erythrocytes were used to evaluate the
effect of these peptides on low oxygen-induced vasodilation.
Results: Healthy human erythrocytes incubated with a 4:1 ratio of C-peptide
to insulin stimulated vasodilation of isolated arterioles in response to reduced
extraluminal oxygen. Importantly, incubation of DM2 erythrocytes with C-peptide in the presence and absence of insulin rescued low oxygen-induced ATP
release from these cells as did the PDE3 inhibitor, cilostazol. Since cGMP inhibits PDE3, as does cilostazol, we next determined that an inhibitor of sGC,
ODQ, prevented the C-peptide-induced rescue of low oxygen-induced ATP release from erythrocytes suggesting that the effects of C-peptide are mediated by
cGMP. Finally, the PDE5 inhibitor, zaprinast, which decreases cGMP hydrolysis, restored ATP release from DM2 erythrocytes producing results similar to
C-peptide.
e3
Journal of Hypertension Volume 32, e-Supplement 1, 2014
Conclusions: These results suggest that C-peptide inhibits PDE3, permitting the
ATP release necessary for vasodilation in response to this important physiological stimulus thereby facilitating the appropriate delivery of oxygen to skeletal
muscle. Thus, administration of C-peptide to individuals with DM2 may mitigate vascular complications.
1A.07
TYPE 2 DIABETIC MICE EXHIBIT AN IMPAIRMENT
OF MUSCLE REGENERATION WITH AN INCREASE IN
ECTOPIC FAT DEPOSITION
M. Mogi, K. Kohara, H. Nakaoka, K. Tsukuda, X. Wang, K. Ohshima,
T. Chisaka, H. Bai, H. Kan-No, L. Min, J. Iwanami, T. Miki, M. Horiuchi.
Ehime University Graduate School of Medicine, Toon, JAPAN
Results: The rates of risk factors such as hyperlipidemia, smoking, stroke, and
IDPLO\ KLVWRU\ RI FRURQDU\ DUWHU\ GLVHDVH GLG QRW VKRZ VLJQL¿FDQW GLIIHUHQFHV
between the 2 groups. Increases in baFMD (0.33 ± 0.34mm vs. 0.02 ± 0.25mm,
p<0.05, respectively) and in the level of circulating microRNA-21 (0.23 ± 0.05
YV“SUHVSHFWLYHO\ ZHUHVLJQL¿FDQWO\JUHDWHULQWKHSLRJOitazone group when compared to the placebo group during the 6-month followXS1RVLJQL¿FDQWGLIIHUHQFHVLQWKHUDWHVRIQHZRQVHWKHDUWIDLOXUHIUDFWXUH
and bladder cancer were noted during the follow-up between the 2 groups. DeFUHDVHV LQ WKH OHYHOV RI LQÀDPPDWRU\ PDUNHU VXFK DV ,/ “SJP/
vs. -1.34±2.12pg/mL, p<0.05, respectively), TNF-alpha (-1.54±1.51pg/mL vs.
0.14±1.12pg/mL, p<0.05, respectively), sICAM-1 (-39±52ng/mL vs. 6±72ng/
mL, p<0.05, respectively), and sVCAM-1 (-154±198ng/mL vs. -11±356ng/mL,
SUHVSHFWLYHO\ ZHUHVLJQL¿FDQWO\JUHDWHULQWKHSLRJOLWD]RQHJURXSFRPpared to the placebo group during the follow-up.
Objective: Sarcopenic obesity is a loss of muscle and a concomitant increase
in fat associated with life-style related diseases and impairs quality of life in
the elderly. Especially the prevalence of sarcopenia is greater in patients with
type 2 diabetes mellitus (T2DM) than in non-diabetic subjects. However, the
detailed mechanism of muscle degeneration associated with diabetes has not
been well established. Here, we investigated the pathogenesis of muscle regeneration using cardiotoxin (Ctx)-induced muscle-injured models in obese T2DM
mice, KKAy.
Conclusions: In hypertensive type 2 diabetic patients, pioglitazone may inFUHDVH ED)0' DQG FLUFXODWRU\ PLFUR51$ DQG GHFUHDVH LQÀDPPDWRU\ F\tokines including IL-6, TNF-alpha, sICAM-1 and sVCAM-1.
Design and method: Muscle atrophy and ectopic fat deposition were evaluated by magnetic resonance imaging (MRI) in male 18-week-old wild-type mice
(C57BL6) and KKAy. Male eight-week-old C57BL6 and KKAy were undergone intramuscular injection of cardiotoxin (Ctx) (100uL/10uM) into tibialis
anterior (TA) muscles. After two weeks, muscles were removed and stained
with hematoxylin and eosin. Bone marrow prepared from GFP-transgenic mice
was replaced into KKAy mice after 8 Gy whole-body X-ray irradiation. Some
mice were treated with all-trans retinoic acid (ATRA) for two weeks after Ctxinjection.
C. Ott 1, U. Raff 1, S. Schmidt 1, I. Kistner 1, S. Friedrich 1, P. Bramlage 2,
J. Harazny 1, R.E. Schmieder 1. 1 Department of Nephrology and Hypertension,
University of Erlangen-Nuremberg, Erlangen, GERMANY, 2 Institute for
Pharmacology and Preventive Medicine, Mahlow, GERMANY
Results: KKAy exhibited muscle atrophy and intramuscular fat deposition.
Treatment with Ctx showed increased muscle satellite cells where nucleuses
were observed in the center of cells. KKAy mice exhibited impaired muscle
regeneration. TA muscle weight was approximately a half in Ctx-injected KKAy
compared with Ctx non-injected KKAy, and Ctx-injected and non-injected
C57BL6 TA muscles. Moreover, remarkable fat deposition was observed in Ctxtreated muscle of KKAy. Such change was also observed in another diabetic
mouse model, db/db, but not in streptozocin-induced diabetic mice. Fat deposition was remarkably increased in aged KKAy (6-month-old) compared with
younger mice (8-week-old). In GFP-chimeric mice, fat tissue showed highly
GFP-positive cells indicating that fat deposition was generated from marrow
cells. Finally, KKAy treated with ATRA exhibited a prevention of fat formation
in the lower limbs after Ctx treatment, but impaired muscle mass weight in TA
muscles of KKAy after Ctx treatment.
Conclusions: 7\SHGLDEHWHVPHOOLWXVPLFHVKRZHGVLJQL¿FDQWO\LPSDLUHGPXVcle regeneration, suggesting that diabetes enhances sarcopenic obesity possibly
due to anomalous marrow cell differentiation.
1A.08
PIOGLITAZONE INCREASED BRACHIAL ARTERY
FLOW-MEDIATED DILATION AND CIRCULATING
LEVEL OF MICRORNA-21 IN HYPERTENSIVE TYPE 2
DIABETIC PATIENTS
S. Hong, H. Joo, J. Park, C. Yu, D. Lim.
Korea University Anam Hospital, Seoul, SOUTH KOREA
Objective: Endothelial dysfunction has been documented in patients with type 2
diabetes especially when combined with hypertension. We prospectively investigated the effects of pioglitazone in improving endothelial function in hypertensive type 2 diabetic patients during the 6-month follow-up.
Design and method: Hypertensive type 2 diabetic patients were randomly
assigned to pioglitazone (n=25) or placebo (n=25). Primary endpoint was to
FRPSDUH FKDQJHV LQ EUDFKLDO DUWHU\ ÀRZPHGLDWHG GLODWLRQ ED)0' EHWZHHQ
the 2 groups during the 6-month follow-up. Secondary endpoints were to compare changes in the circulating levels of microRNA-17, -21, 92a, -126 and -145
which have been known as indicators of endothelial cell migration and atheroVFOHURVLVSURJUHVVLRQGXULQJWKHPRQWKIROORZXS,QÀDPPDWRU\PDUNHUVVXFK
as IL-6, TNF-alpha, high-sensitive C-reactive protein, adiponectin, sICAM-1,
and sVCAM-1 were compared during the follow-up.
1A.09
EFFECTS OF THE DPP-4 INHIBITOR SAXAGLIPTIN ON
EARLY VASCULAR CHANGES IN THE RETINAL AND
SYSTEMIC CIRCULATION
Objective: Patients with diabetes mellitus are at increased risk for microvascular complications. Early changes in microcirculation are characterized by hySHUSHUIXVLRQ HJLQWKHUHWLQDDQGNLGQH\ DQGLQFUHDVHGSXOVHZDYHUHÀHFWLRQ
leading to increased aortic pressure. We investigated the effects of the DPP4-inhibitor saxagliptin on early retinal microvascular changes.
Design and method: In this double-blind, controlled, cross-over trial 42 patients (without clinical signs of microvascular alterations) with type-2 diabetes
(mean duration of 4 years) were randomized to receive placebo or 5mg saxaglipWLQIRUZHHNV5HWLQDODUWHULRODUVWUXFWXUHDQGUHWLQDOFDSLOODU\ÀRZ 5&) DW
EDVHOLQHDQGGXULQJÀLFNHUOLJKWH[SRVXUHZDVDVVHVVHGE\VFDQQLQJODVHU'RSSOHUÀRZPHWU\&HQWUDOKHPRG\QDPLFVZHUHDVVHVVHGE\SXOVHZDYHDQDO\VLV
The study was registered at www.clinicaltrials.gov (ID: NCT01319357).
Results: Postprandial blood glucose (167±7.5 versus 182±7.7 mg/dl; p=0.001)
DQG+E$F “YHUVXV“S ZHUHVLJQL¿FDQWO\UHGXFHG
ZLWKVD[DJOLSWLQWUHDWPHQWFRPSDUHGWRSODFHER5&)ZDVVLJQL¿FDQWO\UHGXFHG
after treatment with saxagliptin (288±13.2 versus 314±14.1 AU; p=0.033). This
was most pronounced in a subgroup of patients (n=32) with a fall in postprandial
EORRGJOXFRVH “YHUVXV“$8S 1RVLJQL¿FDQWFKDQJHV
LQ5&)ZHUHVHHQGXULQJÀLFNHUOLJKWH[SRVXUHEHWZHHQSODFHERDQGVD[DJOLStin, but the vasodilatory capacity increased two-fold with saxagliptin treatment.
Central augmentation pressure tended to be lower after treatment with saxaJOLSWLQ S DQGFHQWUDOV\VWROLFEORRGSUHVVXUHZDVVLJQL¿FDQWO\UHGXFHG
(119±2.3 versus 124±2.3 mmHg; p=0.038).
Conclusions: Our data suggest that treatment with saxagliptin for 6 weeks norPDOL]HV UHWLQDO FDSLOODU\ ÀRZ DQG LPSURYHV FHQWUDO KHPRG\QDPLFV LQ W\SH
diabetes.
1A.10
GENETIC SUSCEPTIBILITY OF THE TYPE 2 DIABETES
IN A PORTUGUESE POPULATION
A. Pereira 1, M. Mendonca 1, S. Gomes 1, R. Rodrigues 1, A. Sousa 1, G. Guerra 1,
M. Rodrigues 1, E. Henriques 1, D. Pereira 1, R. Palma Reis. 2 1 Research Unit,
Funchal Hospital Center, Funchal, PORTUGAL, 2 New University of Lisbon,
Faculty of Medical Sciences, Lisbon, PORTUGAL
Objective: The prevalence of type 2 Diabetes Mellitus (T2D) has increased
sharply around the world and the actual estimation suggests that this trend will
continue to rise over the next decade. GWAS have illustrated novel pathways
pointed toward fundamental biology. By gaining further knowledge of the underlying biology and promoting potential therapeutic and preventive approaches, these insights are likely to be the most important outcome from these studies.
2XU DLP ZDV WR DVVHVV ZKHWKHU D JURXS RI JHQHWLF YDULDQWV LGHQWL¿HG WKURXJK
*:$6LQÀXHQFHV7'VXVFHSWLELOLW\LQWKH3RUWXJXHVHSRSXODWLRQ
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Journal of Hypertension Volume 32, e-Supplement 1, 2014
Design and method: Case-control study with 1405 participants, 621 diabetics selected according to the IDF criteria and 784 controls, adjusted for age
and gender. Eight variants were genotyped: rs7903146, rs4402960, rs1326634,
rs266729, rs17782313, rs1884613, rs8050186 and rs1801282. Data was presented by mean ± SD or median. Quantitative variables were assessed by Student’s t-test and Mann-Whitney, while qualitative were assessed by Chi-square
test. The power of association was expressed by OR and 95% CI. A p-value
ZDVFRQVLGHUHGVLJQL¿FDQW$ORJLVWLFUHJUHVVLRQGHWHUPLQHGZKLFKYDULDQWVZHUHVLJQL¿FDQWO\DQGLQGHSHQGHQWO\DVVRFLDWHGZLWK7'D52&FXUYH
estimated T2D susceptibility and Hosmer-Lemeshow tested the model calibration.
Results: 7KH JHQH YDULDQWV WKDW VKRZHG VWDWLVWLFDO VLJQL¿FDQFH DV ULVN IDFtors of T2D were: ADIPOQ rs266729 GG (OR=1.72; CI 1.06-2.77; p=0.025)
and TCF7L2 rs7903146 TT (OR=1.48; CI 1.09-2.00; p<0.011). After logistic
regression, adjusted for other confounding, the ADIPOQ GG and TCF7L2
TT genotypes remained in the equation, with an increased risk of T2D (OR
1.81;CI 1.07-3.08; p=0.027 and 1.59; CI 1.12-2.27;p=0.010, respectively)
as well as BMI, AHT, smoking, dyslipidemia and sedentary life. The AUC
indicated a good discriminatory power of the model (72%) and the HosmerLemeshow estimated an adequate calibration (p=0.262).
Conclusions: In our population, ADIPOQ GG and TCF7L2 TT were found to
DIIHFWWKHVXVFHSWLELOLW\WR7',QGLYLGXDOVFDUU\LQJWKHVHYDULDQWVWKH¿UVW
implicated in obesity and insulin resistance and the second associated with
lower insulin secretion, should be advised to adopt a healthy lifestyle in order
to alter the genetic predisposition, especially in younger age groups.
Abstracts
e5
ORAL SESSION
ORAL SESSION 1B
ATRIAL FIBRILLATION
1B.01
INCREASE EXERCISE CAPACITY LOWERS THE RISK
FOR ATRIAL FIBRILLATION IN MEN WITH TYPE 2
DIABETES MELLITUS
A. Pittaras 1, C. Faselis 2, M. Doumas 2, A.J. Manolis 3, J. Kokkinos 2,
H. Grassos 3, M.V. Papavasileiou 2, M. Kallistratos 3, K. Kifnidis 3,
N. Kouremenos 3, P. Kokkinos 2. 1 Mediton Medical Center, Department of
Cardiology, Athens, GREECE, 2 Va and George Washington University
Medical Centers, Department of Cardiology, Washington, DC, USA,
3
Asclepeion Voulas Hospital, Department of Cardiology, Athens, GREECE
Objective: 7\SH GLDEHWHV PHOOLWXV '0 LV D SUHYDOHQW ULVN IRU DWULDO ¿EULOODWLRQ $) 6RPH VWXGLHV LQGLFDWH WKDW HQGXUDQFH WUDLQLQJ PD\ LQÀXHQFH WKH
GHYHORSPHQWRIDWULDO¿EULOODWLRQ+RZHYHU¿WQHVVVWDWXVDQGDWULDO¿EULOODWLRQ
in diabetic individuals has not been investigated.
to look for correlation between hypertension severity and CHA2DS-VASC2score.
Results: 7KHUHLVVWDWLVWLFDOO\VLJQL¿FDQWFRUUHODWLRQEHWZHHQ&+$'69$6&
VFRUHDQGQXPEHURIDQWLK\SHUWHQVLYHVȡ S 7KHSRVLWLYHFRUrelation between number of antihypertensives and CHA2DS2-VASC score
means that in this population, patients with more severe hypertension had higher
CHA2DS2-VASC score and thus, higher annual risk of stroke. While relatively
VPDOO VDPSOH VL]H OHDGV WR D ORZ FRUUHODWLRQ FRHI¿FLHQW LQGLFDWLQJ VWDWLVWLFDO
³QRLVH´WKHUHLVVLJQL¿FDQWGHSHQGHQFH
Conclusions: As hypertension scores one point of the CHA2DS2-VASC score
irrespective of severity, the higher score of more severely hypertensive patients
derives from other risk factors, all of which are associated biologically with
hypertension. As relaxation of hypertension treatment targets is likely to further
the incidence, prevalence and severity of these risk factors (except for age and
gender), we postulate a future need to revise guidelines for stroke prevention
based on CHA2DS2-VASC score. While there is need to consolidate these preOLPLQDU\ ¿QGLQJV LQ ODUJHU DQG HWKQLFDOO\ GLYHUVH SRSXODWLRQV ZH VXJJHVW DQ
evidence based approach similar to the “Sicilian Gambit” to forestall negative
effects on stroke prevention.
Design and method: From 1986 to 2011, a total of 1,787 men with type 2 DM
and normal sinus rhythm (mean age 58±9) underwent a routine exercise tolerance testing. During a mean follow-up period of 7.7±4.9 years, 128 (7.2%)
GHYHORSHG$)7RDVVHVVWKHUROHRI¿WQHVVVWDWXVLQWKHGHYHORSPHQWRI$)ZH
IRUPHGWKHIROORZLQJWKUHH¿WQHVVFDWHJRULHVEDVHGRQSHDNZRUNORDGDFKLHYHG
PHWDEROLFHTXLYDOHQWV0(7V /RZ)LW0(7V ”Q 0RGHUDWH)LW0(7V Q DQG+LJK)LW!0(7V •
n=436). Cox proportional hazard models were applied after adjusting for age,
BMI, race, CV disease, CV medications, and risk factors. P-values <0.05 using
WZRVLGHGWHVWVZHUHFRQVLGHUHGVWDWLVWLFDOO\VLJQL¿FDQW
Results: The association between exercise capacity and the risk for developing AF was inverse and graded. For every 1-MET increase in exercise capacity
the AF-risk was 33% lower (HR=0.67; CI: 0.60-0.75; p<0.001). When compared to the Low-Fit category, the risk was 46% lower (HR=0.54; CI: 0.37-0.79;
p<0.001) in Moderate-Fit; and 72% (HR=0.28; CI: 0.15-0.50; p<0.001) in HighFit individuals.
Conclusions: $HURELF¿WQHVVLVDVVRFLDWHGZLWKORZHUULVNIRUGHYHORSLQJDWULDO
¿EULOODWLRQLQLQGLYLGXDOVZLWKW\SH'0
1B.02
SEVERITY OF HYPERTENSION CORRELATES
WITH CHA2DS2-VASC SCORE IN PATIENTS WITH
ATRIAL FIBRILLATION: IMPLICATIONS OF RELAXED
HYPERTENSION TREATMENT TARGETS FOR STROKE
PREVENTION
A. Mondry 1, Z. Ng 2, Y. Li 2, Z. Low 2, D. Huang 2, M. Loh 3,4. 1 National
University Hospital, Department of Medicine, Singapore, SINGAPORE,
2
National University of Singapore, Yong Loo Lin School of Medicine,
Singapore, SINGAPORE, 3 Imperial College, Department of Epidemiology and
Biostatistics, London, UNITED KINGDOM, 4 University of Oulu, Institute of
Health Sciences, Oulu, FINLAND
Objective: Current international guidelines use the CHA2DS-VASC2- score
WRDVVHVVZKHWKHUDSDWLHQWZLWKDWULDO¿EULOODWLRQ $) VKRXOGEHRIIHUHGDQWLcoagulation to reduce stroke risk. As prevalence of hypertension regardless of
severity is a contributor to the CHA2DS-VASC2- score, no immediate effect
of hypertension control on anticoagulation recommendations is expected. Hypertension, however, is also closely associated with all other contributors to the
&+$'69$6& VFRUH +\SHUWHQVLRQ FRQWURO PD\ WKXV LQGLUHFWO\ LQÀXHQFH
the CHA2DS-VASC2- score. In this pilot study, we aim to establish whether
severity of hypertension is correlated to the CHA2DS-VASC2- score.
Design and method: We prospectively assessed 100 consecutive patients with
AF warded at National University Hospital, Singapore. Data collected included
age, gender, prevalence of chronic heart failure, hypertension, diabetes mellitus,
prior stroke or transient ischemic attack, vascular disease as well as antihypertensive medications. The number of antihypertensive agents was used as a surrogate marker for severity of hypertension. We then applied Spearman’s test
1B.03
ASSOCIATION BETWEEN LEFT ATRIAL VOLUME
INDEX AND HEART RATE VARIABILITY IN ATRIAL
FIBRILLATION PATIENTS WITH ARTERIAL
HYPERTENSION AND CORONARY ARTERY DISEASE
A. Shavarov, A. Yusupov, G. Kiyakbaev, V. Moiseev.
Peoples Friendship University of Russia, Moscow, RUSSIA
Objective: Evaluation of the left atrium (LA) remodeling is very important in
GHWHUPLQLQJWKHULVNRIDWULDO¿EULOODWLRQ $) LQFLGHQFHLQSDWLHQWVZLWKDUWHULDO
hypertension (AH) and coronary artery disease (CAD). It is still unclear how left
atrial volume index (LAVI) is related to heart rate variability (HRV) in patients
with persistent AF. The purpose of our study was to evaluate the relationship
between LAVI and HRV in paroxysmal or persistent AF patients with AH and
CAD.
Design and method: A total of 40 patients with the history of AH and myocardial infarction (mean age 65±6 years), either paroxysmal (n=18) or persistent
(n=22) AF within 5,2±3,1 years were studied in the sinus rhythm period. LAVI
was calculated by biplane method. To assess HRV the following time domain
indices were analyzed: standard deviation of RR-intervals (SDNN), the standard
deviation of the mean RR-interval (SDANN) and the standard deviation of RRintervals (rMSSD).
Results: LA volume in paroxysmal AF was lower than in persistent AF (73±24
vs 94±23 ml, p=0,01), as well as LAVI (32±4 vs 48±11 ml/m², p=0,001) respec-
S
A
T
U
R
D
A
Y
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A
L
S
e6
Journal of Hypertension Volume 32, e-Supplement 1, 2014
WLYHO\6'11ZDVVLJQL¿FDQWO\KLJKHULQSDUR[\VPDO$)FRPSDUHGWRSDWLHQWV
with persistent AF (117±18 vs 95±26 ms, p=0,01), as well as SDANN (101±20
vs 76±23 ms, p=0,01). There was correlation between LAVI and both SDNN
(r=0,61; p=0.007) and SDANN (r=0,49; p=0.004). However, there was no correlation between LAVI and rMSSD.
Conclusions: Correlation analysis demonstrated an association between LAVI and
indices of HRV sympathetic activity in recurrent AF patients with AH and CAD.
1B.04
CRP AND PTX3 REFLECT DIFFERENT ASPECTS
OF HEMODYNAMIC STATUS AND RISK IN
HYPERTENSIVE PATIENTS WITH ACUTE ATRIAL
FIBRILLATION
K. Rewiuk, T. Grodzicki. Internal Medicine and Gerontology, Jagiellonian
University, Medical College, Kraków, POLAND
Objective: $WULDO ¿EULOODWLRQ $) LV FRPPRQ FRPSOLFDWLRQ RI K\SHUWHQVLRQ
%RWKRIWKHPDUHFRQQHFWHGZLWKDFWLYDWLRQRILQÀDPPDWRU\UHDFWLRQ3HQWUD[LQ
37; LVRQHRIQHZGHVFULEHGLQÀDPPDWRU\PDUNHUVSURGXFHGE\HQGRWKHOLXPDQGFRQQHFWHGZLWKPRUHORFDODFWLYDWLRQRILQÀDPPDWLRQWKDQ&UHDFWLYH
protein (CRP). Objective of the study is to determine the relationship between
ELRFKHPLFDO PDUNHUV RI LQÀDPPDWLRQ DQG KHPRG\QDPLF VWDWXV DQG ULVN RI
stroke in patients with acute onset of AF.
Design and method: We included 50 hypertensive patients (mean age 68±8
years, 52% male) with episode of AF lasting <48 hours, without acute coronary
HSLVRGH KHPRG\QDPLFDO LQVWDELOLW\ RU FOLQLFDO PDQLIHVWDWLRQ RI DFXWH LQÀDPmation, who were candidates for pharmacological cardioversion. We measured
levels of hsCRP and PTX3 in peripheral blood specimens at the day of inclusion
DQGGD\VODWHU±SDWLHQWVFRQVWLWXWHGVXEJURXSVUHJDUGLQJWRIDFWRIVLQXV
rhythm return or AF persistence.
Results: PTX3 and hsCRP concentrations did not correlate to each other. Both
markers correlated with ejection fraction of left ventricle (r=-0,40 and -0,41;
p<0,01). hsCRP but no PTX3 correlated with left atrium size (r=0,32; p<0,05)
and intima-media thickness of carotid artery (r=0,36; p<0,05). It was also more
elevated in patients with high risk of stroke calculated with CHADS2 (5,44
[1,31; 14,10]mg/l vs 1,43 [0,83; 4.04]mg/l; p<0,05) and Framingham scores
(9,28 [4,65; 14,1]mg/l vs 1,77 [0,99; 6,24]mg/l; p<0,05). PTX3 but no hsCRP
was higher in patients with lower blood pressure (1,12 [0,57; 1,73]ng/ml vs
0,53 [0,36; 0,64]ng/ml; p<0,01) and faster ventricle response during AF paroxysm (0,76 [0,58; 1,77]ng/ml vs 0,51 [0,36; 1,32]ng/ml; p<0,05). Successful cardioversion was connected with the decrease of PTX3 concentration
(0,64 [0,50; 1,62]ng/ml vs 0,58 [0,41; 0,73]ng/ml; p<0,05), without changes
in hsCRP level.
Conclusions: 0DUNHUVRILQÀDPPDWLRQDUHFRQQHFWHGZLWKKHPRG\QDPLFVWDWXV
RIK\SHUWHQVLYHSDWLHQWVZLWKDFXWH$)KV&53UHÀHFWVUDWKHUFKURQLFEXUGHQRI
left atrium and it can help in determination of patients with indications for oral
anticoagulation. PTX3, in turn, correlates with acute state of hemodynamics and
is normalized after successful cardioversion.
1B.05
HYPERTENSION AND ATRIAL FIBRILLATION:
PROGNOSTIC ASPECTS OF TROPONIN ELEVATIONS
IN CLINICAL PRACTICE
A. Conti, A. Alesi, E. Angeli, M. Scorpiniti, F. Trausi, C. Donnini, C. Grifoni,
D. Lazzeretti, S. Bigiarini, S. Bianchi, A. Coppa, S. Gualtieri. Emergency
Medicine and Atrial Fibrillation Outpatient Clinic, Careggi University
Hospital, Florence, ITALY
Objective: 7KHSUHYDOHQFHRIK\SHUWHQVLRQDQGDWULDO¿EULOODWLRQ $)LE LQDGXOW
SRSXODWLRQKDVUHDFKHGVLJQL¿FDQWLPSDFWRQPRUELGLW\DQGPRUWDOLW\7RUHFRJnize and treat coronary heart disease (CHD) in patients with hypertension, AFib
and troponin (cTnI) elevations.
Design and method: Patients with long-standing hypertension and recent onset
AFib were enrolled. The exclusion criteria were acute coronary syndrome and severe comorbidities. Patients managed with standard care (Group 1, n=636, 20102011 years) were compared to patients managed with tailored care inclusive of echocardiography and stress testing when required (Group 2, n=663, 2012-2013 years).
Endpoint was the composite of ischaemic vascular events inclusive of stroke, acute
coronary syndrome, revascularisation and death at six-month follow-up.
Results: Out of 3448 patients with AFib, 1299 with hypertension were enrolled (mean age 72±10 years). Overall, 58 patients with hypertension and AFib
reached the endpoint versus 24 without (p=0.065). Among patients with hypertension, AFib and cTnI elevations (n=113), 15 reached the endpoint versus 43
without (n=1186; p<0.001).
cTnI elevations, known CHD and age were predictors of the endpoint at multivariate analysis. Patients with cTnI elevations (57 in group 1 and 56 in group 2,
p=0.768) more likely were admitted for further evaluation in group 1 (32 versus
21, in group 1 and 2, respectively, p=0.60). In group 2 patients more likely underwent stress testing (15 versus 1, in group 2 and 1, respectively, p<0.001) and
were considered for angiography (14 versus 11, in group 2 and 1, respectively,
p=0.504). Patients of group 2 were admitted (n=21) with positive stress testing
(n=9) or high cTnI values (n=12; mean cTnI values: 1.04±1.98 ng/mL). Patients were discharged (n=35) with negative stress testing (n=6) or very low cTnI
values (n=29, mean cTnI values 0.27±0.22 ng/mL). Revascularisation was performed in 7 patients of group 2 versus 1 patient in group 1 (p=0.032). Finally, 15
patients (13%) reached the endpoint, 12 in group 1 and 3 in group 2 (p=0.024).
Conclusions: In patients with hypertension, AFib, and cTnI elevations, tailored
care inclusive of echocardiography and stress testing succeeded in recognizing
and treating hidden CHD avoiding adverse events.
1B.06
ARTERIAL HYPERTENSION: MAIN ETIOLOGIC
FACTOR OF ATRIAL FIBRILLATION IN PATIENTS
HOSPITALIZED TO THERAPEUTIC CLINIC
E. Baranova 1, O. Listopad 1, D. Jatsuk 1, A. Soboleva 1, E. Shlyakhto 2.
Pavlov State Medical University of Saint-Petersburg, Saint-Petersburg,
RUSSIA, 2 Federal Almazov Medical Research Centre, Saint-Petersburg,
RUSSIA
1
Objective: $WULDO¿EULOODWLRQLVWKHDUUK\WKPLDZKLFKREYLRXVO\LQFUHDVHVPRUELGLW\DQGPRUWDOLW\7RDQDO\]HIUHTXHQF\RIDWULDO¿EULOODWLRQDQGPDLQHWLRORJLFIDFWRUVRIDWULDO¿EULOODWLRQ $) LQSDWLHQWVKRVSLWDOL]HGWRWKHUDSHXWLFFOLQLF
in 1985-1990 and in 2005-2010 years.
Design and method: 14,595 clinical forms of patients hospitalized to therapeutic clinic (7 837 for the period 1985-1990 and 6 758 for 2005-2010 years)
were analyzed.
Results: In 1985-1990 years 748 hospitalized patients (9.5%) had AF and in
2005-2010 - 1110 patients (16.4%), frequency of AF increased 1.7 times (p
<0.001). Causes of AF are numerous and every patient with AF could have
several causes of this arrhythmia.We analized all possible causes of AF in hospitalised patients. Non valvular AF occured in 73.7% (1985-1990) and 86.0%
(2005-2010) (p<0.0001). Arterial hypertension was registered in 316 patients
with AF - 42.2% (1985-1990) and in 866 patients - 78.7% (2005-2010) (p
<0.0001). Coronary artery disease occured 35.8% patients with AF (19851990) and 60.6% (2005-2010) (p <0.0001). Pulmonary thromboembolism was
more frequent in 2005-2010 than in 1985-1990 - 199 patients and 27 patients
with AF (18.1% and 3.6%), (p <0.0001) - due to more effective methods of diagnosis of pulmonary thromboembolism. Thyrotoxicosis was registered in 29
patients with AF (3.9%) in 1985-1990 and in 83 patients (7.6%) in 2005-2010
years (p <0.0001). Diabetes mellitus type 2 was evalueted more often in 20052010, than in 1985-1990 (19.7% and 6.8%) patients with AF (p <0.0001).
Valvular heart diseses in 2005-2010 were registered in patients with AF more
rare than in 1985-1990 - 154 patients (14.0%) vs 197 patients (26.3%) (p
<0.0001).
Frequency of congestive heart failure, cardiomyopathies, chronic obstructive
pulmonary diseases and diabetes mellitus type 1 did not differ among patients
with AF in 1985-1990 and 2005-2010.
Conclusions: $WULDO¿EULOODWLRQIUHTXHQF\DPRQJSDWLHQWVKRVSLWDOL]HGWRWKHUDpeutic clinic in 2005-2010 as compared to 1985-1990 years increased 1.7 times.
$UWHULDOK\SHUWHQVLRQLVWKHPRVWFRPPRQHWLRORJLFDOIDFWRURIDWULDO¿EULOODWLRQ
in patients hospitalized to therapeutic clinic. In 2005-2010 compared to 1985\HDUVIUHTXHQF\RIDUWHULDOK\SHUWHQVLRQLQSDWLHQWVZLWKDWULDO¿EULOODWLRQ
increased 1.8 times.
1B.07
THE PREVALENCE, INCIDENCE, MANAGEMENT AND
RISKS OF ATRIAL FIBRILLATION IN AN ELDERLY
CHINESE POPULATION
L. Li 1, C. Sheng 1, B. Hu 1, Q. Huang 1, W. Zeng 1, G. Li 1, M. Liu 1,
F. Wei 1, L. Zhang 1, Y. Kang 1, J. Song 1, S. Wang 1, Y. Li 1, S. Liu 2, J. Wang 1.
1
The Shanghai Institute of Hypertension, Ruijin Hospital, Shanghai Jiaotong
University School of Medicine, Shanghai, CHINA, 2 Department of Cardiology,
Shanghai First People’s Hospital, Shanghai Jiaotong University School of
Medicine, Shanghai, CHINA
Objective: $WULDO¿EULOODWLRQFRQIHUVDQLQFUHDVHGULVNRIVWURNHDQGPRUWDOLW\
7KHUHLVOLPLWHGLQIRUPDWLRQRQSUHYDOHQWDQGLQFLGHQWDWULDO¿EULOODWLRQLQ&KLnese. To investigate the prevalence, incidence, management and risks of atrial
¿EULOODWLRQLQDQHOGHUO\&KLQHVHSRSXODWLRQ
e7
Journal of Hypertension Volume 32, e-Supplement 1, 2014
Design and method: In a population-based prospective study in elderly (>=60
years) Chinese, we performed cardiovascular health examinations including 12lead electrocardiogram at baseline in 3,922 participants and biennially during
follow-up in 2,017 participants. We collected information on vital status during
the whole follow-up period.
Results: 7KHSUHYDOHQFHRIDWULDO¿EULOODWLRQZDV Q LQPHQ
and 1.6% (n = 36) in 2,204 women. During a median 3.8 years of follow-up, the
LQFLGHQFHUDWHRIDWULDO¿EULOODWLRQ Q ZDVSHUSHUVRQ\HDUV FRQ¿GHQFHLQWHUYDO>&,@ %RWKWKHSUHYDOHQFHDQGLQFLGHQFHRIDWULDO
¿EULOODWLRQZHUHKLJKHUZLWKDJHDGYDQFLQJ 3 DQGLQWKHSUHVHQFHRI
coronary heart disease (P <=0.02) in univariate analysis. Of the 104 prevalent
DQG LQFLGHQW FDVHV RI DWULDO ¿EULOODWLRQ RQO\ UHFHLYHG DQWLFRDJXODQW
therapy (warfarin). After adjustment for confounders, these patients with atrial
¿EULOODWLRQ FRPSDUHG ZLWK WKRVH ZLWK VLQXV UK\WKP KDG VLJQL¿FDQWO\ KLJKHU
risks of cardiovascular (n = 136, hazard ratio [HR] 2.16, 95% CI 1.23-3.80, P
= 0.007) and stroke mortality (n = 44, HR 3.86, 95% CI 1.69-3.85, P = 0.001).
Conclusions: $WULDO¿EULOODWLRQZDVSUHYDOHQWLQHOGHUO\&KLQHVHSRRUO\PDQaged and associated with higher risks of mortality.
1B.08
COMBINED EFFECT OF SYSTOLIC BLOOD
PRESSURE AND PROTEINURIA ON THE RISK OF
INCIDENT ATRIAL FIBRILLATION IN AN URBAN
JAPANESE COHORT: THE SUITA STUDY
Y. Kokubo 1, M. Watanabe 1, T. Kobayashi 1, K. Kusano 1, S. Kamakura 1,
K. Kawanishi 2, Y. Miyamoto 1. 1 National Cerebral and Cardiovascular
Center, Suita, JAPAN, 2 The Suita Medical Association, Suita, JAPAN
Objective: No prospective study has examined the association between proWHLQXULDDQGDWULDO¿EULOODWLRQ $) LQFLGHQFHDFFRUGLQJWREORRGSUHVVXUH %3 categories in general populations. We assessed the combined association of proteinuria and blood pressure (BP) on the risk of incident AF in an urban Japanese
population.
Design and method: In the Suita Study, 6,868 initially AF-free participants
(30-84 years old at the baseline survey) were prospectively followed for inFLGHQW$)7KH\ZHUHGLDJQRVHGZLWK$)LI$)RUDWULDOÀXWWHUZDVSUHVHQWRQ
an electrocardiogram or if present illness or medical records indicated AF.
Health check-up examinations were conducted every 2 years. BP was taken
as the average of the second and third measurements by sphygmomanometer.
&KURQLFNLGQH\GLVHDVH &.' ZDVGH¿QHGDVJORPHUXODU¿OWUDWLRQUDWH
P/PLQ Pð ZKLFK ZDV HVWLPDWHG XVLQJ WKH 0'5' HTXDWLRQ PRGL¿HG
E\WKH-DSDQHVHFRHI¿FLHQW3URWHLQXULDZDVGHWHUPLQHGE\DGLSVWLFNPHWKRG
3URWHLQXULDUHVXOWVRIµ“¶RUPRUHJUDGHZHUHGH¿QHGDVSURWHLQXULD:HXVHG
the Cox proportional hazard model for the incident AF with estimated hazard
UDWLRV +5V DQGFRQ¿GHQFHLQWHUYDOV &,V DFFRUGLQJWRWKHFRPELQDWLRQV
of proteinuria and BP categories.
Results: During the mean 12.8 years of follow-up, 253 incident AF events occurred (4.2 and 1.6 per 1,000 person-years for men and women, respectively).
Compared with non-proteinuria, the adjusted HR (95% CIs) for incident AF
was 1.48 (1.10-1.99) in proteinuria. No association was revealed between CKD
and incident AF. The adjusted HRs (95% CIs) for AF were 1.29 (0.90-1.84) in
systolic prehypertension (systolic BP=120-139 mmHg) and 1.74 (1.22-2.49)
in systolic hypertension (systolic BP>=140 mmHg or antihypertensive drug
use). The adjusted HRs (95% CIs) of incident AF were 1.95 (1.12-3.40) for
systolic prehypertension with proteinuria and 2.63 (1.63-4.25) and 1.88 (1.272.80) for systolic hypertension with and without proteinuria, respectively.
Conclusions: 3URWHLQXULDDQGV\VWROLFK\SHUWHQVLRQZHUHLGHQWL¿HGDVULVNIDFtors for incident AF independently of each other. The presence of proteinuria
could be a screening marker for predicting incident AF.
1B.09
VARIABILITY OF A.B.P.M. IN PATIENTS WITH ATRIAL
FIBRILLATION
M. D’Avino 1, G. Caruso 2, R. Muscherà 1, A. Ilardi 1, F. Capasso 1,
G. Buonomo 3, C. Simone 3. 1 Unit of Hypertension, Cardarelli Hospital,
Naples, ITALY, 2 Emergency Unit Cardarelli Hospital, Naples, ITALY,
3
Samnium Medical Center, Benevento, ITALY
Objective: ,Q K\SHUWHQVLYHV ZLWK DWULDO ¿EULOODWLRQ $) LW¶V UHFRPPHQGHG
that repeated measurements should be performed for the accurate assessment
of BP. Ambulatory BP monitoring (ABP) appears to be ideal in this respect
by providing a large number of measurements over a relatively short period.
The aim of this study was to investigate the ABP variability in patients with
crhonic AF.
Design and method: We examined 24H ABP variability (standard deviation
6'FRHI¿FLHQWRIYDULDWLRQ&9 ZDVH[DPLQHGLQK\SHUWHQVLYHVXEMHFWVZLWK
AF and in hypertensive subjects with sinus rhythm (SR) matched for age, gender, systolic ABP levels, antihypertensive treatment, presence of cardiovascular disease, diabetes, smoking and ABP monitor type.
Results: 135 subjects (76 F) were included with mean age 69.7±6.9 years.
We used for all Spacelabs 90217). The average number of valid readings
was more high in SR than AF subjects (n=60.1±7.6 vs. 54±8.9, p<0.05). For
SBP in AF compared to SR subjects there wasn’t difference in awake/asleep
ABP levels (125.6±9,118.1±12.1,vs. 126.3±9.4/116.3±12.2 mmHg), as well
as in awake/asleep SD (12,6±4.3/11.6±4,1vs. 12.3±3/11.5±4,3 mmHg), CV
(0.10±0.03/0.9±0.03 vs. 0.10±0.03/0.10±0.02).For diastolic ABP, AF compared to SR subjects demonstrated higher values of awake/asleep diastolic
ABP levels (82.5±9.8/74±11.6 vs. 73.3±8.5/64.5±6.9 mmHg), as well as
higher awake SD (11.3±3,1 vs. 9,1±1.9 mmHg), awake CV (0.12±0.06 vs.
0.10±0.03).
Conclusions: $)VXEMHFWVKDYHVLJQL¿FDQWO\KLJKHU$%3YDULDELOLW\WKDQ65
VXEMHFWVIRUGLDVWROLFEXWQRWV\VWROLF%37KLV¿QGLQJFRQ¿UPVWKDWLWLVHVpecially appropriate using the standard ABP monitoring protocol in elderly
patients suffering from AF to evaluate SBP behaviour.
1B.10
CHARACTERISTICS OF AN ASYMPTOMATIC
ATRIAL FIBRILLATION DETECTED WITH AFIBTECHNOLOGY DEVICE FOR BLOOD PRESSURE
MEASUREMENT IN BULGARIAN URBAN
POPULATION
S. Torbova 1, A. Postadjian 2, Y. Yotov 3, S. Tisheva 4, S. Georgiev 5,
S. Tsonev 6, S. Naidenov 6, V. Ivanova 7, A. Nikolova 7, E. Anev 8.
1
7RNXGD+RVSLWDO6R¿D%8/*$5,$28QLYHUVLW\+RVSLWDO6W$QQD6R¿D
BULGARIA, 3 Medical University, Varna, BULGARIA, 4 Medical University,
Pleven, BULGARIA, 5 Medical University, Plovdiv, BULGARIA, 6 Medical
8QLYHUVLW\6R¿D%8/*$5,$70HGLFDO)DFXOW\RI6R¿D8QLYHUVLW\6R¿D
BULGARIA, 80LOLWDU\0HGLFDO$FDGHP\6R¿D%8/*$5,$
Objective: We performed a screening for asymptomatic AF in Bulgarian urban population on the World Hypertension Day (May 17th 2013) with motto
±+HDOWK\%ORRG3UHVVXUH±+HDOWK\+HDUW%HDW
Design and method: A cross sectional pilot study was performed by BulJDULDQ+\SHUWHQVLRQ/HDJXHXVLQJRSHQ±DLUVWDQGVLQELJ%XOJDULDQFLWies. Blood Pressure (BP) was measured by automatic devices with AFIB
technology of Microlife giving the opportunity to diagnose atrial fibrillation
(AF) without ECG. 2019 persons participated voluntarily, aged 18÷90 yr.
with mean age 60.69 yr., 59% females and 41% males. Structured questionnaires were filled up with separate question about subjective feeling of
palpitations.
Results: From 2019 investigated persons, 4.54% had previously diagnosed
(PD) AF and 61 persons (3.02%, mean age 61,3 years, 21 females and 40
males) were found to have newly diagnosed (ND) AF. With diagnosed arterial
hypertension (AH) were 67.21% .The mean last BP measured at home: 137/83
mmHg for participants with ND AF and 147.5/85 mm Hg for participants with
3'$) 0HDQ %3 DW RI¿FH PP+J IRU SDUWLFLSDQWV ZLWK 1'$)
and 165/103 mmHg for participants with PD AF. Among participants with ND
AF the following prevalence of palpitations were found: a) short lasting (1-2
PLQ DQGE ORQJODVWLQJ !PLQ ±DVWKHSDUWLFLSDQWVZLWK
normal BP in the screened population.
Conclusions: The prevalence of the asymptomatic AF in Bulgarian population is smaller than the diagnosed. Persons with asymptomatic AF have a
better control of arterial hypertension and less heart beat symptoms compared to the persons with previously diagnosed AF, but need antithrombotic
drugs.
Abstracts
e8
ORAL SESSION
ORAL SESSION 1C
GENETICS, GENOMICS, PROTEOMICS,
METABOLOMICS
1C.01
RESEQUENCING OF RENIN-ANGIOTENSINALDOSTERONE-SYSTEM GENES IDENTIFIES RARE
VARIANTS ASSOCIATED WITH BLOOD PRESSURE
SALT-SENSITIVITY: THE GENSALT STUDY
T. Kelly 1, J. Hixson 2, D. Rao 3, D. Gu 4, C. Li 1, L. Shimmin 2, Q. Zhao 1,
J. He 1. 1 Tulane University, New Orleans, LA, USA, 2 University of Texas
School of Public Health, Houston, TX, USA, 3 Washington University, St. Louis,
MO, USA, 4 Chinese Academy of Medical Sciences and Peking Union Medical
College, Beijing, CHINA
Objective: To identify rare functional variants in genes of the renin-angiotensinaldosterone system (RAAS) associated with salt-sensitivity of blood pressure
(BP) among participants of the Genetic Epidemiology Network of Salt-Sensitivity (GenSalt) study.
Design and method: The GenSalt study was conducted among 1,906 participants who underwent a 7-day low-sodium (51.3 mmol sodium/day) followed
by a 7-day high-sodium feeding-study (307.8 mmol sodium/day). We selected
300 GenSalt subjects with the highest and 300 GenSalt subjects with the lowest
mean arterial pressure responses to the high sodium intervention to participate
in the current resequencing study. Functional regions of seven RAAS genes,
including ACE2, APLN, AGTR1, HSD11B1, HSD11B2, NR3C2, and RENBP
were resequenced using the VariantSEQrTM system (Applied Biosystems;
Foster City, CA). RAAS variants with minor allele frequencies less than 5%
were collapsed according to gene and analyzed using the cohort allelic sums
test (CAST).
Results: :H LGHQWL¿HG VLJQL¿FDQW DVVRFLDWLRQV EHWZHHQ UDUH YDULDQWV LQ WKH
APLN, AGTR1, and HSD11B2 genes and BP salt-sensitivity, with p-values of
0.05, 0.03, and 0.03, respectively. Within the promoters, splice sites, exons, and
¶XQWUDQVODWHGUHJLRQVRIWKHVHJHQHVZHLGHQWL¿HGUDUH$3/1YDULDQWV
rare AGTR1 variants, and 19 rare HSD11B2 variants. Nine percent of GenSalt
participants with high salt-sensitivity were carriers of at least one of the rare
APLN variants, while only 4% of salt-resistant participants were carriers. In addition, approximately 17% of participants with high salt-sensitivity were carriers
of rare AGTR1 variants compared to only 11% of salt-resistant subjects. Further,
8% of those who were highly salt-sensitive compared to only 4% of those who
were salt-resistant were carriers of HSD11B2 variants.
Conclusions: ,QVXPPDU\ZHSURYLGHWKH¿UVWHYLGHQFHIRUDUROHRIUDUHDQG
potentially functional RAAS variants in BP salt-sensitivity. Validation study will
EHQHHGHGWRFRQ¿UPWKHVH¿QGLQJV
1C.02
INTEGRATED GENOME SEQUENCING AND GENE
EXPRESSION ANALYSIS IN THE STROKE-PRONE
SPONTANEOUSLY HYPERTENSIVE RAT
M. McBride 1, M. Dashti 1, K. Maratou 2, S. Atanur 2, T. Aitman 2, W. Beattie 1,
R. Breitling 3, A.F. Dominiczak 1, J. McClure 1, D. Graham 1. 1 University
of Glasgow, Glasgow, UNITED KINGDOM, 2 Imperial College, London,
UNITED KINGDOM, 3 University of Manchester, Manchester, UNITED
KINGDOM
Objective: The stroke-prone spontaneously hypertensive rat (SHRSP) is
an excellent model for human cardiovascular disease. Quantitative trait loci
ZHUH SUHYLRXVO\ LGHQWL¿HG RQ FKURPRVRPHV DQG IRU EORRG SUHVVXUH
regulation and cardiac mass and validated by construction of congenic strains.
This study aims to identify positional candidate genes which contribute to the
SHRSP phenotypes by analysing whole genome sequencing and gene expression data.
Design and method: Illumina paired-end reads from our SHRSPGla and
WKYGla were mapped to the Brown Norway (BN) rat reference genome with
Burrows Wheeler Aligner. The Genome Analysis Tool kit was used to discover
sequence variants and annotated with Ensembl Variant Effect Predictor. SigQL¿FDQWO\GLIIHUHQWLDOO\H[SUHVVHGSRVLWLRQDOFDQGLGDWHJHQHVZHUHLGHQWL¿HGE\
Partek® (FDR< 0.05) and protein coding sequence variants were prioritised.
)XUWKHUFDQGLGDWHJHQHVZHUHLGHQWL¿HGE\%LROD\RXW([SUHVV'FOXVWHUDQDO\ses and Ingenuity pathway analysis (IPA) was used to provide biological insights
into the impact of SHRSPGla and WKYGla genome and gene expression variants.
Results: Approximately, 90% of reads were mapped to the BN reference genome for SHRSP at 27x and WKY at 26x coverage. Genomic difference distribution of 1,163,332 single nucleotide polymorphisms and 213,130 insertions or
deletions of DNA segments between SHRSP and WKY were not uniform. There
were 769 non-synonymous coding, 5 stop gained, 24 frame shift coding variDQWVZLWKLQWKHFRQJHQLFUHJLRQVDQGVLJQL¿FDQWO\GLIIHUHQWO\H[SUHVVHGJHQHV
were prioritised from kidney and heart. In one analysis, Gstm1 was highlighted,
a previously validated positional and functional candidate for hypertension in
the SHRSPGla. Furthermore, Gstm7, Ampd2, Atp11b, Pik3r1 were positional
FDQGLGDWHJHQHVLGHQWL¿HGLQWKHFOXVWHUDQDO\VLVRI*VWP
Conclusions: The integration of sequence variants and gene expression data
has implicated and prioritised positional candidate genes within the congenic
intervals that may contribute to blood pressure regulation and cardiac mass in
the SHRSPGla.
1C.03
THE INVOLVEMENT OF GENES FOR HUMAN
HYPERTROPHIC DILATED CARDIOMYOPATHY
TO EXPERIMENTAL POLYGENIC CARDIAC
HYPERTROPHY
P. Prestes 1, F. Marques 1, G. Lopez-Campos 2, F.J. Charchar 1, S.B. Harrap 3.
Federation University Australia, School of Health Sciences, Ballarat,
AUSTRALIA, 2 University of Melbourne, Health and Biomedical Research
Unit, Melbourne, AUSTRALIA, 3 University of Melbourne, Department of
Physiology, Melbourne, AUSTRALIA
1
Objective: Genes implicated in monogenic human cardiac hypertrophy (CH)
might also be involved in the more common polygenic forms. The Hypertrophic
Heart Rat (HHR) is a unique normotensive model of spontaneous polygenic
ventricular hypertrophy leading to cardiac failure and premature death. Our aim
was to survey mRNA expression and genetic variants in genes previously associated with monogenic forms of dilated and hypertrophic cardiomyopathy in
humans utilising the HHR.
Design and method: We used Affymetrix GeneChip® Rat Gene 1.0 ST arrays
to measure whole-genome mRNA in left ventricles of HHR and its normal control, the Normal Heart Rat (NHR) (n=8 per group). We also performed wholegenome DNA sequencing of both strains using the HiSeq 2000 platform. We
aligned and compared sequences to the Rat Genome Database v3.4 and identi¿HGIRXUW\SHVRIYDULDQWV613VLQVHUWLRQVDQGGHOHWLRQV ,Q'HOV FRS\QXPEHU
variations (CNVs) and structural variants (SVs).
Results: We found 15 (Cryab, Dsg2, Lama4, Mybpc3, Myh6, Myh7,Myl2,
Nexn, Psen2, Rbm20, Tnnc1, Tnni3, Tnnt2, Tpm1, Ttn) of the initial known 40
FDQGLGDWHJHQHVVLJQL¿FDQWO\GLIIHUHQWLDOO\H[SUHVVHGLQWKH++5 )'5 Their fold change was small (~1.3) consistent with a polygenic contribution.
Overall, we found 182 variants unique to the HHR in our gene subset. Most
variants were SNPs (n=101), followed by InDels (n=67), CNVs (n=12) and SVs
(n=2). No major mutations typical of human monogenic cardiomyopathies were
found. The majority of SNPs are located in non-coding regions (n=98) except
for two variants in the coding region for the gene for troponin T type 2 (Tnnt2)
and one in its 3’ untranslated region. Interestingly, both mutations in the coding
region are synonymous and do not cause a change in the amino acid or protein
sequence. Although the variants found in gene for Tnnt2 are synonymous, silent
mutations may alter gene expression levels by transfer RNA availability and
LQÀXHQFHSKHQRW\SLFDOO\YDULDELOLW\
Conclusions: 2XUVWXG\LVWKH¿UVWWRVKRZWKDWJHQHVLQYROYHGLQPRQRJHQLF
human forms of hypertrophy may also contribute through changed expression
and subtle variants in DNA sequence to the common polygenic form of left
ventricular hypertrophy.
S
A
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e9
Journal of Hypertension Volume 32, e-Supplement 1, 2014
1C.04
CIRCULATING LEVELS OF A DICARBOXYLIC ACID
ASSOCIATE WITH BLOOD PRESSURE, PREDICT
MORTALITY AND RESPONSE TO CALCIUM CHANNEL
BLOCKERS. A MULTI-OMICS STUDY
S. Padmanabhan 1, C. Menni 2, S.M. Alsanosi 1, G. Kastenmüller 3,
M. McBride 1, M. Mangino 2, M. Brosnan 5, J. Trimmer 5, R. Mohney 6,
K. Suhre 3, C. Gieger 3, O. Melander 4, A.F. Dominiczak 1, T. Spector 2,
A. Valdes 2. 1 University of Glasgow, Glasgow, UNITED KINGDOM, 2 King’s
College, London, UNITED KINGDOM, 3 Helmholtz Zentrum München, Munich,
GERMANY, 4 Lund University, Malmö, SWEDEN, 53¿]HU:RUOGZLGH5HVHDUFK
and Development, Cambridge, MA, USA, 6 Metabolon, Inc, Durham, NC, USA
Objective: The aim of the current study was to use a systems approach combining
metabolomics/genomics/transcriptomics and epidemiology to discover molecular
markers associated with blood pressure regulation and response to antihypertensive drugs.
Design and method: We tested the association between 280 known metabolites and blood pressure in 3980 adult female from the TwinsUK cohort after
adjustment for conventional covariates. We run replication replication in the independent KORA study comprising both males and females. Survival analysis
was performed using Cox proportional hazards model. We tested gene expression and metabolite correlations in 586 adipocyte samples. We then tested SNPs
within the metabolite-associated genes for association with hypertension and
drug response in the BP-extremes GWAS (1621/1699 cases/hypercontrols) and
the Nordic Diltiazem study (n=4039) respectively.
Results: :H LGHQWL¿HG D GLFDUER[\OLF DFLG DVVRFLDWHG ZLWK 6%3
(Beta[95%CI]=1.31[0.83;1.78], P=6.81x10-8) and DBP (0.81[0.5;1.11],
P=2.96x10-7) in the Twins study and KORA study (SBP:1.42[0.37; 2.47],
P=0.01; DBP:0.64[0.09,1.19], P=0.02). In Twins, the highest tertile was also
associated with 50% higher mortality (Figure, left panel) compared to the lowest tertile (HR[95%CI]= 1.49[1.08; 2.05], P=0.02). Levels of the acid correlated
with adipocyte gene-expression levels of a gene on chromosome 11 (-0.15[-0.2;0.11]; P<1.01x10-9). The minor T allele of an intronic SNP on that gene was
associated with high metabolite levels (0.03[0.002; 0.02], P=0.04), hypertension
(0.22[0.08; 0.36], P=0.01), poorer DBP response to calcium channel blockers
(CCB) (-2.16[-3.65; -0.67], P=0.005) and consequent higher cardiovascular
mortality (HR=2.68[1.04; 6.9]; P=0.04) (Figure, right panel).
Conclusions: 2XU¿QGLQJVLQGLFDWHDQRYHOSDWKZD\DQGSRWHQWLDOELRPDUNHUIRU
K\SHUWHQVLRQLQYROYLQJDGLFDUER[\OLFDFLGDQGLQÀXHQFHGE\&&%7KLVFDQSRWHQWLDOO\EHXVHGIRUGLDJQRVLVDQGVWUDWL¿FDWLRQIRUK\SHUWHQVLRQPDQDJHPHQW
Objective: Familial hyperkalaemic hypertension (FHHt, Gordon’s syndrome) is
an inherited form of salt dependent hypertension caused by mutations in genes
encoding proteins regulating the NaCl co-transporter (NCC) in the distal tubule.
Mutations have previously been documented in ‘With no lysine (K)’ kinases
(WNK1 and WNK4) and recently mutations in two more genes, Kelch-like 3
(KLHL3) and Cullin 3 (CUL3), have also been implicated.
Design and method: To examine whether mutations in KHLH3, CUL3 or
SLC4A8 (an alternative thiazide sensitive sodium transporter) are present in
our FHHt pedigrees previously screened and found negative for WNK1 and
WNK4 mutations, 25 affected individuals from 16 families with unexplained
FHHt underwent genetic analysis by next generation sequencing. Validation of
results was by Sanger sequencing.
Results: Affected individuals from 10 of 16 families were found to have
CUL3 or KLHL3 variants not reported in the general population. Eight
pedigrees carried variants previously associated with FHHt; two in CUL3
(c.1377+1G>C, c.1207-1G>A) and four in KLHL3 (c.1499G>T, c.1160T>C
in three pedigrees, c.1019C>T, c.1480G>A). Two pedigrees had previously
unreported variants in CUL3 (c.1377+1G>T, c.1207-12T>A) and one individual was homozygous for a previously reported heterozygous KLHL3 variant
(c.1499G>T). We found no evidence for disease causing variants in SLC4A8.
Conclusions: 7KLVVWXG\FRQ¿UPVUHFHQW¿QGLQJVRI&8/DQG./+/PXWDWLRQVLQ)++WDQGLGHQWL¿HVQRYHOGLVHDVHFDXVLQJYDULDQWVVWUHQJWKHQLQJWKH
argument that these gene products are physiologically important regulators of
distal nephron NaCl reabsorption via thiazide-sensitive pathways, and hence
are potentially interesting novel anti-hypertensive drug targets. Overall 63%
of our WNK negative pedigrees now have a genetic diagnosis; implying mutations in other as yet unknown regulators of the NCC may exist.
1C.06
A NOVEL P.Y152C KCNJ5 MUTATION
IS RESPONSIBLE FOR FAMILIAL
HYPERALDOSTERONISM TYPE III
S. Monticone 1, N. Hattangady 2, D. Penton 3, C. Isales 4, M. Edwards 4,
T. Williams 1, C. Sterner 3, R. Warth 3, F. Buffolo 1, P. Mulatero 1, W. Rainey 2.
1
Department of Medical Sciences, University of Turin, Turin, ITALY, 2
Department of Molecular and Integrative Physiology, University of Michigan
Medical School, Ann Arbor, MI, USA, 3 Medical Cell Biology, University of
Regensburg, Regensburg, GERMANY, 4 Georgia Regents University, Augusta,
GA, USA
Objective: Primary aldosteronism (PA) encompasses a broad spectrum of disorders including both sporadic and familial forms. Mutations in the KCNJ5
JHQH HQFRGLQJ IRU WKH * SURWHLQDFWLYDWHG LQZDUG UHFWL¿HU . FKDQQHO (GIRK4) have been implicated in the pathogenesis of both familial hyperaldosteronism type III and sporadic aldosterone producing adenomas. The objecWLYHRIWKHVWXG\ZDVWRFKDUDFWHUL]HWKHHIIHFWRIDQHZO\LGHQWL¿HG.&1-
mutation in vitro.
Design and method: The index case is a 62 year old female affected by PA,
who underwent left adrenalectomy after work-up for adrenal adenoma. Exon
RI.&1-ZDV3&5DPSOL¿HGIURPDGUHQDOWLVVXHDQGSHULSKHUDOEORRGDQG
sequenced. The p.Y152C mutant channel was expressed in both HEK293 and
HAC15 cells to explore, through electrophysiological and gene expression
studies, its functional effects on the membrane potential and aldosterone production.
1C.05
PREVALENCE OF KELCH-LIKE 3 AND CULLIN
3 MUTATIONS IN FAMILIAL HYPERKALAEMIC
HYPERTENSION
M. Wolley 1, M. Glover 2, J. Ware 3,4, A. Henry 2, R. Walsh 3, L. Wain 5,
S. Xu 1, W. Van’t Hoff 6, M. Tobin 5, I. Hall 2, S. Cook 4,7,8, R. Gordon 1,
K. O’Shaughnessy 9, M. Stowasser 1. 1 Endocrine Hypertension Research
Centre, Univ. Queensland School of Medicine, Greenslopes and Princess
Alexandra Hospitals, Brisbane, AUSTRALIA, 2 Division of Therapeutics
and Molecular Medicine, University of Nottingham, Nottingham, UNITED
KINGDOM, 3 Nihr Royal Brompton Cardiovascular Biomedical Research
Unit, Imperial College, London, UNITED KINGDOM, 4 National Heart
and Lung Unit, Imperial College, London, UNITED KINGDOM, 5 Genetic
Epidemiology Group, University of Leicester, Leicester, UNITED KINGDOM,
6
Great Ormond Street Hospital for Children, London, UNITED KINGDOM,
7
Duke National University, Singapore, SINGAPORE, 8 National Heart
Centre, Singapore, SINGAPORE, 9 Clinical Pharmacology Unit, University of
Cambridge, Cambridge, UNITED KINGDOM
Results: KCNJ5 sequencing in the index case revealed a novel heterozygous
point substitution (c.455A>G) resulting in a tyrosine (Y) to cysteine (C) mutation at amino acid position 152. Notably, the phenotype of the patient was
milder than most of the FH-III families reported so far. We also searched for
the p.Y152C mutation by SNP assays on genomic DNA extracted from patients (n=100) affected by BAH; we could not identify the 455A>G substitution in any of the analyzed samples. Immunohistochemical staining of the
adrenal tissue showed nodular structures with diffuse KCNJ5 expression and
variable aldostherone synthase (CYP11B2) expression. The adjacent cortex
showed a variable degree of glomerulosa hyperplasia. In HEK293 cells the
p.Y152C substitution resulted in pathological Na+ permeability, cell membrane depolarization (-37 mV in KCNJ5Y152C vs. -74 mV in KCNJ5WT
transfected cells) and subsequent increase in intracellular calcium concentraWLRQ,QDGUHQRFRUWLFDOFHOOVWKH&DLQÀX[LQGXFHGE\WKHS<&PXWDWLRQ
is responsible for increased transcription of CYP11B2 and of the associated
UHJXODWRU\IDFWRUV15$ HIIHFWWKDWLVVSHFL¿FDOO\LQKLELWHGE\WKHFDOFLXP
channel blocker nifedipine).
Conclusions: We describe a new germline mutation in KCNJ5 responsible for
FH-III.
e10
Journal of Hypertension Volume 32, e-Supplement 1, 2014
1C.07
A NOVEL LONG NONCODING RNA TARGETING
RIFIFYLIN IS MECHANISTICALLY LINKED TO THE
REGULATION OF BLOOD PRESSURE, CARDIAC
FUNCTION AND SURVIVAL IN A RAT GENETIC MODEL
OF HYPERTENSION
B. Joe, K. Gopalakrishnan, S. Kumarasamy, B. Mell.
University of Toledo College of Medicine, Toledo, OH, USA
Objective: Using the Dahl Salt-sensitive (S) rat as a genetic model of hypertension, a <42.5kb genomic segment on chromosome 10 was previously mapped
as a blood pressure (BP) quantitative trait locus (QTL). The critical interval has
DVLQJOHJHQH5L¿I\OLQZLWKQRSURWHLQFRGLQJYDULDQWV5L¿I\OLQLVH[SUHVVHG
higher in the strain with higher blood pressure. This study was conducted to address the question of what genomic element caused the differential expression of
5IÀEHWZHHQWKH6/(:FRQJHQLFUDWDQGWKH6UDW
Design and method: We used a combinatorial approach of whole genome rat
/QF51$SUR¿OLQJQH[WJHQHUDWLRQ/QF51$VHTXHQFLQJDQGH[WHQVLYHELRLQIRUmatic and comparative genomic analysis.
Results: 7ZR QRYHO UDW /QF51$V ZHUH LGHQWL¿HG ZLWKLQ WKH NE FULWLFDO
interval. Further, systematic 3’ and 5’ mapping data extended the transcribed
ORFDWLRQRIWKHVH/QF51$VWRZLWKLQWKHVHQVHVWUDQGRIWKH5IÀJHQHORFXV
ZKLFKLVRSSRVLWHWRWKHVWUDQGIURPZKLFK5IÀLVWUDQVFULEHG:HUHIHUWRWKHVH
QRYHO/QF51$VDV6HQVHORQJ1RQFRGLQJ51$VZLWKLQWKH5IÀ/RFLRU61RRL1 and SNRRL2. The rat LncRNA-SNRRL1 is homologous to mouse long
non coding RNA- AK037080 (fRNAdb) which overlaps with the last intron, last
H[RQDQG¶875RIWKHPRXVH5IÀJHQH5DW/QF51$6155/LVKRPRORJRXV
to another mouse long noncoding RNA- AK157675 (fRNAdb) which overlaps
ZLWKWKH¶875UHJLRQRIWKHPRXVH5IÀJHQH%RWK/QF51$V6155/DQG
SNRRL2 contain sequence variants between S and LEW. There is one variant
within the LncRNA-SNRRL1 and a 19bp deletion within LncRNA-SNRRL2
in the LEW sequence compared with S. S and LEW sequences of LncRNASNRRL1 were cloned into Pcmv6-Ac-GFP vector and overexpressed in NRK( FHOOV 5L¿I\OLQ H[SUHVVLRQ LQ FHOOV H[SUHVVLQJ 6 DOOHOHV RI 6155/ ZDV
ORZHUWKDQWKHUL¿I\OLQH[SUHVVLRQLQFHOOVH[SUHVVLQJ/(:DOOHOHVRI6155/
Conclusions: These data demonstrate that the novel long noncoding RNA,
/QF51$6155/ WDUJHWV 5IÀ 7KH YDULDQWV ZLWKLQ /QF51$6155/ DUH
therefore putative BP quantitative trait nucleotides that are linked to BP regulation, cardiac function and survival by their ability to differentially regulate the
H[SUHVVLRQRIUL¿I\OLQ
1C.08
THE FUNCTIONAL CONSEQUENCES OF UMOD
PROMOTER VARIANTS ON SODIUM TRANSPORTERS
AND BLOOD PRESSURE CONTROL IN HUMANS
L. Graham 1, D. Graham 1, M. Denniff 2, M. Tomaszewski 2, A.F. Dominiczak 1,
S. Padmanabhan 1, M. McBride 1. 1 Univeristy of Glasgow, Institute of
Cardiovascular and Medical Science, Glasgow, UNITED KINGDOM,
2
University of Leicester, Department of Cardiovascular Sciences, Leicester,
UNITED KINGDOM
Objective: To biologically assess UMOD SNPs within the 2Kb human promoter region to functionally follow up the hypertension signal associated with
the minor G allele of rs13333226.
Design and method: rs13333226 genotype was determined in three human renal cell lines; TK-10 (AA), 786-0 (AA) and ACHN (GG). 2Kb promoter constructs were generated in pGL4.10 luciferase vectors and transfected into human renal cell lines. Promoter activity was assessed by site direct mutagenesis.
In Silico analysis using Transcriptional element search software (TESS) was
utilized to predict differential putative transcription binding (TF) sites at position 16:20365234 (rs4997081). Ingenuity pathway analysis (IPA) was used to
explore known biological connections between UMOD and predicted TFs, then
assessed using ChromotinImmunoprecipitation (ChIP). Genotyping assays and
Gene expression analysis were performed on human renal tissue samples from
the Silesian Renal Tissue bank (SRTB), which includes samples from normotensive and hypertensive individuals.
Results: 2Kb TK10 (AA) promoter construct, demonstrated a 6 fold increase of luciferase activity, compared with ACHN (GG) and 785-0 (AA)
S LPSOLFDWLQJ613UV6LWHGLUHFWHGPXWDJHQHVLVYHUL¿HG
rs4997081 as a functional SNP in the 2Kb UMOD promoter region (14 fold
increased luciferase activity, ***p<0.0001). TESS analysis revealed one differHQWLDO7) 7)$3$ RQWKH&DOOHOHRIUV&K,3FRQ¿UPHGWKHELQGLQJ
RI7)$3$,3$GRFXPHQWHGWKDW7)$3$VLJQDOVGRZQVWUHDPWR71)Į,W
has been shown that UMOD regulates sodium uptake in the TAL by modulating
WKHHIIHFWRI71)ĮRQ1.&&H[SUHVVLRQ+HUH802'1.&&DQG1+(
mRNA abundance was increased in hypertensive subjects of AA genotype for
rs13333226 (**p<0.001, ***p<0.0001). Subjects of AG and GG genotype for
rs13333226 demonstrated no differences in gene expression levels between
K\SHUWHQVLYHDQGQRUPRWHQVLYHLQGLYLGXDOV71)ĮZDVQRWGLIIHUHQWLDOO\H[pressed (p>0.05).
Conclusions: :H LGHQWL¿HG UV DV D IXQFWLRQDO YDULDQW LQ WKH KXPDQ
UMOD promoter. Our computational and experimental data suggest that modulation of UMOD plays a vital role in blood pressure regulation via Na+ homeostasis. The minor G allele of rs13333226 appears to be protective against
K\SHUWHQVLRQFRQ¿UPLQJWKHRULJLQDO*:$6¿QGLQJV
1C.09
NEW CANDIDATE GENES FOR SALT SENSITIVE
HYPERTENSION
M. Simonini 1, M. Devoto 2, C. Lanzani 1, G. Gatti 1, N. Casamassima 1,
L. Citterio 1, S. Tentori 1, S. Pozzoli 1, P. Manunta 1. 1 San Raffaele University,
6FLHQWL¿F,QVWLWXWH0LODQ,7$/<2 Penn University, Philadelphia, PA, USA
Objective: Hypertension is an important public health problem affecting more
than 60 million individuals in the USA alone. The most common form, salt sensitive hypertension (SSH), results from the complex interplay between genetic
SUHGLVSRVLWLRQDQGHQYLURQPHQWDOLQÀXHQFHV2XUDLPLVWRLGHQWLI\QHZJHQHV
involved in SSH that explain the different individual variability of to a load/
restriction of Na in the everyday diet.
Design and method: A GWA study was performed on 321 never treated hypertensive patients, who underwent a Salt-Load test. We performed a case-control
analysis by comparing the most salt-sensitive vs. most salt-resistent patients.
From this analysis, a list of top hits was obtained; we considered top SNPs those
ZLWK SYDOXH 7KH PRVW LQWHUHVWLQJ UHVXOWV ZHUH FRQ¿UPHG RQ D VHFRQG
population (120 pts).
Results: The best result was located on chr. 11 (p=4.38E-07) in the upstream region of DGAT2 gene. In the same region we found, after a process of imputation,
4 different SNPs with p-value <1E-06 not in linkage disequilibirum with the top
SNP. Another interesting association was located on chr. 13 (p=5.20E-06). This
SNP is on the 5’ region of the gene Myosin XVI (MYO-XVI). Also in this region
imputation process showed other 3 different SNPs with p-value <1E-04 associated with SSH. Finally, to understand the power on BP regulation, we performed a
regression analysis (441 pts) of the difference between diastolic/systolic BP from
the baseline to the end of Na-load. This analysis showed a r2 > 4% for both genes.
Conclusions: Our results suggest that DGAT2 and MYO-XVI are involved in
regulation of BP after acute saline infusion in primary hypertension. DGAT2
is implicated in the development of Metabolic Syndrome (insulin resistance/
diabetes, obesity, increase of blood cholesterol), which makes it a good candidate for salt-sensitivity hypertension. MYO-XVI is a non conventional myosin
expressed in many organs. Since the protein has a double kind of expression into
cells: perinuclear, most represented, and peripheral, has a structural function
that regulates other protein activity. Further investigation will need to understand the gene-gene interaction between these gene and others structural genes
responsible of SSH.
1C.10
MAPPING OF CHROMOSOME 2 REGIONS LINKED
TO VASCULAR INJURY AND INFLAMMATION USING
CONGENIC RATS
P. Paradis 1, A. Rehman 1, N. Idris-Khodja 1, M. Mian 1, T. Barhoumi 1,
N. Yamamoto 1, A. Kwitek 3, E.L. Schiffrin 1,2. 1 Lady Davis Institute for
Medical Research, SMBD Jewish General Hospital, McGill University,
Montreal, CANADA, 2 Department of Medicine, SMBD-Jewish General
Hospital, McGill University, Montreal, CANADA, 3 Department of Internal
Medicine, University of Iowa, Iowa City, IA, USA
Objective: Chromosome 2 introgression from normotensive Brown Norway
rats (BN) into hypertensive Dahl salt sensitive (SS) background (consomic SB2)
UHGXFHGYDVFXODULQÀDPPDWLRQDQGUHVWRUHG7UHJIXQFWLRQ:HK\SRWKHVL]HGWKDW
WKH%1FKURPRVRPHFRQWDLQVJHQHVWKDWUHGXFHYDVFXODULQÀDPPDWLRQZKLFK
could be mapped using congenic rats containing portions of BN-chromosome 2
on the SS background.
Design and method: Twelve-to-13 week old male BN, SS, SB2, congenic (SB)
A, SBB and SBE rats were studied. Systolic blood pressure (SBP) was measured
E\WHOHPHWU\$RUWLFYDVFXODUFHOODGKHVLRQPROHFXOH 9&$0 DQG¿EURQHFtin expression, collagen content and reactive oxygen species (ROS) production
were determined. Spleen Treg (CD4+CD25hi) and CD4+CD25- T lymphocytes
were characterized and cultured in order to measure interferon (IFN)-gamma,
tumor necrosis factor (TNF)-alpha, interleukin (IL)-10, IL-17 and IL-6 production.
e11
Journal of Hypertension Volume 32, e-Supplement 1, 2014
Results: SS, SB2 and SBE exhibited 20mmHg higher SBP compared to BN,
SBA, and SBB (P<0.05). Aortic ROS production and VCAM-1 expression were
>=2.7- and nearly1.5-fold greater, respectively, in SS and SBB (P<0.05) compared to BN, SB2, SBA and SBE. Collagen content was nearly 2.4-fold greater
in SS, SB2 and SBB (P<0.05) compared to BN, SBA and SBE. Fibronectin expression was nearly 1.5-fold higher in SS and SBE (P<0.05) compared to SB2,
SBA or BN. SS, SB2 and SBE spleens had more CD4+CD25- cells (nearly 16%)
compared to BN, SBA and SBB (nearly 12%, P<0.05). SBA spleens had less
Treg (2%) compared to SS and SB2 (3%, P<0.05). SS or SBB CD4+CD25- cells
produced less TNF-alpha, IFN-gamma and IL-6 (P<0.05), compared to SB2,
SBE or BN. Treg-IL-10 and IL-17 production was greater in SB2, and SS and
SB2, respectively (P<0.05), compared to congenic rats or BN.
Conclusions: *HQHVUHJXODWLQJYDVFXODULQMXU\DQGLQÀDPPDWRU\UHVSRQVHVDUH
contained within the fragment of BN-chromosome 2 present in congenic SBA
and SBE rats.
Abstracts
e12
ORAL SESSION
ORAL SESSION 1D
BLOOD PRESSURE MEASUREMENT
1D.01
PROGNOSTIC VALUE OF AMBULATORY HEART RATE
CIRCADIAN RHYTHM IN HYPERTENSIVES OLDER
THAN 60 YEARS
P. Cuffaro, J. Barochiner, M. Morales, M. Marin, L. Aparicio, M. Rada,
-$O¿HC. Galarza, G. Waisman. Hospital Italiano de Buenos Aires, Buenos
Aires, ARGENTINA
Objective: To determine if heart rate (HRate) circadian rhythm predicts cardiovascular events (CVEs), cerebrovascular events (CerVEs) and death in elderly
hypertensives.
Design and method: Retrospective cohort of patients >= 60 years old who underwent an ambulatory blood pressure monitoring during the period 2003-2008
in the Italian Hospital of Buenos Aires, Argentina. Subjects treated with betablockers were excluded from analysis. We calculated night/day HRate ratio and
HRate circadian rhythm; the latter as percentage of night fall [(diurnal HRate
±QRFWXUQDO+5DWH GLXUQDO+5DWH@[:HFODVVL¿HG+5DWHJURXSVDV'LSSHUV
(10-20% fall), extreme dippers (>20% fall), Non-Dippers (0-9% fall) and risers
(< 0%). We used the Hospital`s database to obtain event occurrence in medical
records. We used a Cox proportional hazards model to estimate Hazard Ratios
(HRs) adjusted for potential confounders (age, sex, diabetes, smoking, dyslipiGHPLDPHGLFDWLRQKV\VWROLF%3DQGK+5DWH DQGWKHLUFRQ¿GHQFHLQtervals (95% CI).
events (CVEs) independent of nighttime systolic blood pressure (NSBP) and
clinic systolic blood pressure (CSBP). To address this question we conducted a
comprehensive systematic review and meta-analysis.
Design and method: The literature was reviewed systematically using PUBMED and Ovid databases. Inclusion criteria were a diagnosis of hypertension,
1+ years of follow up, and CVEs as outcomes. Lead investigators for each cohort were contacted, and the ABC-H collaboration was formed. Dispersion was
PHDVXUHGE\WKHFRHI¿FLHQWRIYDULDWLRQDQGLWVFRQ¿GHQFHLQWHUYDOVZHUH
computed. Random effects meta-analyses were used throughout.
Results: Nine Cohorts (N=13,844) were from Europe, Brazil and Japan. Six of
these had 5 out of 5 features of data quality. In particular, to distinguish NSBP
IURP'6%3WKHVHFRKRUWVXVHGSDWLHQWVSHFL¿FLQIRUPDWLRQIRUHDFKSDWLHQW
IRUH[DPSOHSDWLHQWGLDULHV UDWKHUWKDQ¿[HGFORFNWLPHLQWHUYDOVIRUDOOSDtients within a cohort (for example, 24:00-6:00 for NSBP and 10:00-20:00 for
DSBP). Follow up was 3.5 to 8.2 years. Dispersions for NSBP and DSBP (95%
FRQ¿GHQFH OLPLWV ZHUH DQG respectively, with the former exceeding the latter by 21.7%. For a 10 mmHg
increase in NSBP, DSBP, AND CSBP, each measure predicted CVEs when conVLGHUHGLQGLYLGXDOO\+D]DUGUDWLRV +5V FRQ¿GHQFHLQWHUYDOV ZHUH
(1.22-1.29), 1.20 (1.15-1.26) and 1.11 (1.06-1.16), respectively. However, after
simultaneous adjustment for all 3 blood pressures, HRs were 1.26 (1.20-1.31),
1.01 (0.94-1.08) and 1.00 (0.95-1.05), respectively. For the 6 cohorts with the
highest quality, HRs were 1.27 (1.20-1.34), 1.01 (0.91-1.11) and 1.00 (0.971.04), respectively. HRs for coronary artery disease and stroke for NSBP were
1.22 and 1.26, respectively, while for DSBP HRs were 0.97 and 1.04, respectively.
Results: 2827 patients were included, mean age 72.3 (6.9), 65.5% women,
9.1% diabetics, 37.4% dyslipidemics, 14% smokers and 51.9% medicated.
Average ambulatory BP values (mmHg) were: 24-h BP 136.5/77.5, diurnal BP
140.1/80.6, nocturnal BP 125.9/68. Ambulatory HRate (bpm) values were: 24-h
HRate 71.2 (9.2), diurnal HRate 73.5 (9.9), nocturnal HRate 64 (8.7), Night/
day HRate ratio 0.87 (0.07). HRate circadian rhythm proportions were: Dippers 51.2%, Nondippers 30.2%, extreme dippers 14.9%, risers 3.6%. During
follow-up (median 4.7 years) 223 CVEs (7.1%), 83 CerVEs (2.9%) and 200
deaths (7.1%) occurred. In multivariable analysis of circadian rhythm categories
(compared with HRate dippers and adjusted for confounders) only the group of
HRate risers was associated with CVEs, HR 1.50 (95% CI [1.02-2.2]; p=0.039),
CerVEs HR 2.13 (95% CI [1.18-1.07]; p =0.012) and death HR 1.99 (95% CI
[1.35- 2.94]; p < 0.001).
Conclusions: In hypertensive patients >= 60 years of age, inverted HRate circadian rhythm was associated with a higher risk of mortality, cardiovascular and
cerebrovascular events, independently of blood pressure, 24-h heart rate and
known risk factors, although reverse causality cannot be discarded.
1D.02
PROGNOSTIC IMPACT OF CLINIC, DAYTIME,
AND NIGHTTIME SYSTOLIC BLOOD PRESSURE
IN 9 COHORTS OF 13,844 PATIENTS WITH
HYPERTENSION: SYSTEMATIC REVIEW AND METAANALYSIS
G. Roush 1, R.H. Fagard 2, G. Salles 3, S. Pierdomenico 4, G. Reboldi 5,
P. Verdecchia 6, K. Eguchi 7, K. Kario 7, J. Polonia 8, A. De La Sierra 9,
R. Hermida 10. 1 UCONN, Medicine, Farmington, CT, USA, 2 University of
Leuven, Medicine, Leuven, BELGIUM, 3 Universidade Federal do Rio de
Janeiro, Medicina, Rio de Janeiro, BRAZIL, 4 Università Gabriele d’Annunzio,
Medicina, Chieti, ITALY, 5 University of Perugia, Medicine, Perugia, ITALY,
6
Ospedale di Assisi, Medicina, Assisi, ITALY, 7 Jichi University School
of Medicine, Medicine, Tochigi, JAPAN, 8 Universidade do Porto, Porto,
PORTUGAL, 9 University of Barcelona, Medicine, Terrassa, SPAIN,
10
University of Vigo, Bioengineering and Chronobiology Laboratories, Vigo,
SPAIN
Objective: In patients with hypertension, data are contradictory as to whether
ambulatory daytime systolic blood pressure (DSBP) predicts cardiovascular
Conclusions: In this meta-analysis of hypertensive patients (with the greatest
number of participants of its kind), NSBP had greater dispersion than DSBP and
independently predicted CVEs, while neither DSBP nor CSBP did so. These
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e13
Journal of Hypertension Volume 32, e-Supplement 1, 2014
1D.03
OFFICE, HOME, AND AMBULATORY BLOOD
PRESSURE AS PREDICTORS OF CARDIOVASCULAR
RISK
T. Niiranen, J. Mäki, P. Puukka, H. Karanko, A. Jula. National Institute for
Health and Welfare, Department of Chronic Disease Prevention, Turku,
FINLAND
Objective: Previous studies have shown that home and ambulatory blood presVXUH %3 DUH SURJQRVWLFDOO\ VXSHULRU WR RI¿FH %3$PEXODWRU\ %3 LV ZLGHO\
considered to be the golden standard of BP measurement although it has not
been shown to be more strongly associated with cardiovascular risk than home
%3 2XU REMHFWLYH ZDV WR FRPSDUH WKH SURJQRVWLF YDOXH RI RI¿FH KRPH DQG
ambulatory BP.
Design and method: 2I¿FHKRPHDQGKRXUDPEXODWRU\%3VZHUHPHDVXUHG
along with other cardiovascular risk factors in 464 participants in 1992-1996.
The primary end point was incidence of a composite cardiovascular event (cardiovascular mortality, nonfatal myocardial infarction, nonfatal stroke, hospitalization for heart failure, percutaneous coronary intervention, or coronary artery
bypass graft surgery). We assessed the independent prognostic value of each BP
variable with Cox proportional hazard models adjusted for other cardiovascular
risk factors. The likelihood chi-square ratio value was used as a measure of the
LPSURYHPHQWRIJRRGQHVVRI¿WEHWZHHQPRGHOVFRQWDLQLQJRQHWZRRUWKUHH
BP variables.
Results: The follow-up ended on December 31, 2011. After a mean followup of 16.1±3.9 years, 70 participants (13.9%) had experienced at least one
FDUGLRYDVFXODU HYHQW 2I¿FH V\VWROLFGLDVWROLF KD]DUG UDWLR >+5@ SHU PP
+J LQFUHDVH LQ %3 V\VWROLFGLDVWROLF FRQ¿GHQFH LQWHUYDO
[CI], 1.009-1.040/0.994-1.043), home (HR, 1.029/1.028; 95% CI, 1.0131.045/1.005-1.052), and 24-hour ambulatory BP (HR, 1.033/1.049; 95% CI,
1.019-1.047/1.023-1.077) were predictive of cardiovascular events. The risk of
FDUGLRYDVFXODU HYHQWV LQFUHDVHG PRUH VWHHSO\ IURP RI¿FH WR KRPH DQG DPEXlatory BP (Figure). When all three BP variables were included in the model
VLPXOWDQHRXVO\RQO\V\VWROLFGLDVWROLFDPEXODWRU\%3ZDVDVLJQL¿FDQWSUHGLFWRU RI FDUGLRYDVFXODU HYHQWV 3 ZKHUHDV RI¿FH 3 and home (P=0.64/0.70) BP were not. Home systolic/diastolic BP improved the
JRRGQHVV RI ¿W RI WKH PRGHO RQO\ VOLJKWO\ ZKHQ DGGHG WR D PRGHO LQFOXGLQJ
RI¿FH%3 3 6\VWROLFGLDVWROLFDPEXODWRU\%3LPSURYHGWKH¿WRI
PRGHOPRUHFOHDUO\ZKHQDGGHGWRDPRGHOLQFOXGLQJERWKRI¿FHDQGKRPH%3
(P=0.001/<0.001).
Conclusions: 2XU¿QGLQJVVXJJHVWWKDWDPEXODWRU\%3LVSURJQRVWLFDOO\VXSHULRUWRRI¿FHDQGKRPH%3
HYDOXDWLRQDQGUHSRUWLQJ,QHDFKVXEMHFWDQDXWRPDWLFRI¿FH%3PHDVXUHPHQW
was obtained before starting the ABPM and information about drug treatment
recorded.
Results: Recordings obtained in 5645 subjects (mean age 57±15 years; 53% females; 90% untreated) referred to 365 local Pharmacies were analyzed. 24-h BP
control (<130/80 mmHg) was poor, with 50% of subjects at target (51% untreated vs. 47% treated; p=0.139). Nocturnal hypertension (night-time BP >=120/70
mmHg) was more common (p<0.001) than diurnal hypertension (day-time BP
>=135/85 mmHg): 52% vs. 46%. Additionally, 16% of subjects displayed elevated average BP values exclusively at night and 10% at day (p<0.001). The
most common BP phenotype was sustained hypertension (42%), followed by
sustained normotension (31%), isolated clinic hypertension (19%) and masked
hypertension (9%).
Conclusions: Our preliminary results suggest that a telemedicine service providing medical reporting of ABPM tests carried out in Pharmacies may facilitate
high BP screening and detection. It may also help to describe the complex 24-h
BP features and guide physician’s intervention. Further studies are needed to
H[SORUHWKHSRWHQWLDOSXEOLFKHDOWKEHQH¿WVRIVXFKDQDSSURDFK
1D.05
ATRIAL FIBRILLATION DETECTION USING
OSCILLOMETRIC 24-HOUR AMBULATORY BLOOD
PRESSURE MONITORING VERSUS 24-HOUR HOLTER
ELECTROCARDIOGRAPHY
A. Kollias 1, P. Kalogeropoulos 2, A. Ntineri 1, K. Dimitriadis 3, M. Zeniodi 1,
G.S. Stergiou 1. 1 Hypertension Center, STRIDE Hellas-7, Third University
Department of Medicine, Sotiria Hospital, Athens, GREECE, 2 Cardiology
Department, Agioi Anargiroi General Hospital, Athens, GREECE, 3 First
University Department of Cardiology, Hippokration Hospital, Athens,
GREECE
Objective: A non-invasive oscillometric 24-hour ambulatory blood pressure
%3 PRQLWRU $%30 ZLWKLPSOHPHQWHGDOJRULWKPIRUDXWRPDWHGDWULDO¿EULOlation (AF) detection has been developed. This study validated the diagnostic
accuracy of this monitor (Microlife WatchBP O3) versus 24-hour Holter electrocardiography (ECG).
Design and method: Forty-six subjects (mean age 70.8±9 years; 22 men) were
subjected to simultaneous 24-hour ABPM and Holter ECG. False negative BP
measurements in permanent AF subjects and false positive in nonAF were evaluated.
1D.04
TELEMONITORING OF 24-H BLOOD PRESSURE
IN LOCAL PHARMACIES AND BLOOD PRESSURE
CONTROL IN THE COMMUNITY: RESULTS FROM THE
TEMPLAR PROJECT
S. Omboni, M. Caserini. Italian Institute of Telemedicine, Clinical Research
Unit, Varese, ITALY, on behalf of the TEMPLAR Project Group
Objective: The recent availability in several Italian Pharmacies of ambulatory blood pressure monitoring (ABPM) facilities, with telemedical reporting,
has ensured ready access to this important diagnostic technique by patients
suspected of having hypertension. It also provided the referring physicians
with a remarkable and timely tool for screening and management of arterial
hypertension. The aim of the TEMPLAR Project was to analyze the data collected in such a real-life context, in order to evaluate the level of BP control
in the community.
Design and method: ABPMs were performed by an electronic, clinically validated, BP monitor (Microlife WatchBP 03) at the local Pharmacy. At the end
of the 24-h each recording was downloaded on-site on a PC and sent through
a web-based telemedicine platform to a Central Core Laboratory for medical
Results: According to medical history and 24-h ECG recordings, the particiSDQWVZHUHFODVVL¿HGDVSHUPDQHQW$) Q SDUR[\VPDO$) Q DQGQRQ$)
(n=36). The number of valid BP readings and those indicating AF in the participants’ groups with AF and nonAF are shown in table. In the subject with
paroxysmal AF (Holter) the proportion of ABPM readings detecting AF was
29%. Seven nonAF (Holter) subjects had >15% of readings with false positive
AF (mean 33±17%). One of them had constant Mobitz I atrioventricular block,
whereas in the others the main arrhythmia was frequent supraventricular premature beats (6% of total beats; in 2 subjects in triplets). In the nonAF subjects
WKHUHZDVDVLJQL¿FDQWDVVRFLDWLRQEHWZHHQWKHSHUFHQWDJHRIIDOVHSRVLWLYH$)
readings and that of supraventricular premature beats (r=0.59, p<0.01).
e14
Journal of Hypertension Volume 32, e-Supplement 1, 2014
Conclusions: 7KHVH ¿QGLQJV VXJJHVW WKDW D QRYHO$%30 PRQLWRU ZLWK DXWRmated AF detector might be a useful screening tool during routine ABPM in
elderly hypertensives, in whom the detection of AF in >15% of the readings
should mandate conformation with 24h Holter ECG.
1D.06
PREDICTIVE CAPACITY OF AMBULATORY VERSUS
CLINIC BLOOD PRESSURE IN THE OBESE AND NONOBESE PARTICIPANTS OF THE ABP-INTERNATIONAL
STUDY
S HYHQDIWHUDGMXVWPHQW ȕ S IRUDJHDYHUDJHV\VWROLF%3
body mass index, BP lowering drugs and statin use. Among subjects with preserved RHI, the slope between BP reactivity and RHI was greater for patients
ZLWK7'0WKDQIRUQRQGLDEHWLFV LQWHUDFWLRQȕ S )LJXUH 7KHDVsociation of BP reactivity with RHI was stronger for diabetics with preserved
5+,WKDQIRUGLDEHWLFVZLWKLPSDLUHG5+, LQWHUDFWLRQȕ S ZKHQ
analysis was repeated in all patients with T2DM.
Conclusions: The relationship between reactive hyperemia and BP reactivity
differs between people with T2DM and those without T2DM. Endothelial function appears to have some bearing on BP reactivity in the presence of T2DM.
P. Palatini 1, G. Reboldi 2, L. Beilin 3, K. Eguchi 4, Y. Imai 5, K. Kario 4,
T. Ohkubo 5, S. Pierdomenico 6, J. Schwartz 7, L. Wing 8, P. Verdecchia 9.
1
University of Padua, Padua, ITALY, 2 University of Perugia, Perugia, ITALY,
3
University of Western Australia, Perth, AUSTRALIA, 4 Jichi University,
Tochigi, JAPAN, 5 Tohoku University, Sendai, JAPAN, 6 University of Chieti,
Chieti, ITALY, 7 Columbia University, New York, NY, USA, 8 Flinders
University, Adelaide, AUSTRALIA, 9 Town Hospital, Assisi, ITALY
Objective: Ambulatory blood pressure (BP) monitoring (ABPM) is often reTXLUHG LQ REHVH LQGLYLGXDOV EXW WHFKQLFDO GLI¿FXOWLHV LQFOXGLQJ PLVFXI¿QJ DUH
common in these subjects. However, little data are available on the performance
of ABPM in obese individuals. The purpose of this study was to evaluate the
predictive value of ABPM versus clinic BP measurement in the obese and nonobese participants of the ABP-International study.
Design and method: We performed 24-hour ABPM in 10,846 participants
(52.6% men, 27.5% ambulatory normotensive) aged 53±15 years enrolled in 8
prospective studies in Australia, Italy, Japan, and U.S.A. The predictive power
of ambulatory BP versus clinic BP for cardiovascular events (CVE) was evaluDWHGIURPPXOWLYDULDEOH&R[PRGHOVLQWKHVXEMHFWVVWUDWL¿HGE\%0, NJ
m2, n=9428 or >= 30 Kg/m2, n=1418).
Results: Obese individuals (BMI >= 30 Kg/m2) were younger (51±14 versus
53±16 years) and had a higher clinic BP (154±18/95±10 versus 149±20/90±12
mmHg) and ambulatory BP (137±16/84±10 versus 134±15/82±10 mmHg) than
the non-obese ones (all p<0.0001). Gender distribution was similar in the two
groups. During a median follow-up of 5.8 years there were 820 CVE, 8.8% in the
obese and 7.4% in the non-obese individuals (P=0.06). In age-and-sex-adjusted
models, 24-h ambulatory systolic and diastolic BPs (in separate analyses) were
predictive of outcome in both groups whereas clinic BPs were not associated
with outcome in any multivariable model. Among the obese subjects, the hazard ratios (HR) for a 10 mmHg increase in 24-h and clinic systolic BPs were
1.38(95%CI, 1.24-1.53) and 0.95(0.83-1.07), respectively, and for 24-h and clinic
diastolic BPs were 1.39(95%CI, 1.17-1.61) and 0.95(0.75-1.15), respectively.
Among the non-obese subjects, the corresponding HR values were 1.32(95%CI,
1.26-1.38) and 1.01(0.96-1.06) for 24-h and clinic systolic BPs, respectively, and
were 1.40(95%CI, 1.30-1.50) and 1.06(0.99-1.14) for 24-h and clinic diastolic
BPs, respectively. Inclusion of other risk factors in the models gave similar results.
Conclusions: These data show that ambulatory BP is a better predictor of CVE
than clinic BP with similar predictive capacity in obese and non-obese subjects.
This suggests that ABPM can be reliably performed in obese individuals.
1D.07
IN-CLINIC BLOOD PRESSURE REACTIVITY IS
ASSOCIATED WITH PRESERVED ENDOTHELIAL
FUNCTION AMONG PATIENTS WITH DIABETES
P. Veloudi 1, L. Blizzard 1, V. Srikanth 2, J. Sharman 1. 1 Menzies Research
Institute Tasmania, Hobart, AUSTRALIA, 2 Monash Medical Centre,
Melbourne, AUSTRALIA
Objective: In-clinic blood pressure (BP) usually drops with repeated measures
over time. Whether this BP reactivity is due to endothelial function has not been
investigated. The aim of this study was to investigate the relationship between
BP reactivity (the change in systolic BP on repeated measurements) and endothelial function (reactive hyperaemia) among people with and without type
2 diabetes (T2DM).
Design and method: ,QFOLQLF%3UHDFWLYLW\ WKHGLIIHUHQFHEHWZHHQWKH¿UVWDQG
third systolic BP measurements over 10 minutes) and reactive hyperaemia index
(RHI; EndoPAT) were measured for 245 patients with T2DM (aged 71±7, males
61%) and 164 non-diabetics (aged 68±7, males 59%). Patients with T2DM were
VWUDWL¿HG DFFRUGLQJ WR SUHVHUYHG 5+, ! DX Q RU LPSDLUHG 5+,
<1.67 au; n=110) reactive hyperemia, and all non-diabetics had preserved RHI.
Linear regression analysis was used to estimate the associations between BP
reactivity and RHI.
Results: %3UHDFWLYLW\ZDVVLJQL¿FDQWO\DVVRFLDWHGZLWK5+,RQO\DPRQJ7'0
SDWLHQWVZLWKSUHVHUYHG5+, FRUUHODWLRQU UHJUHVVLRQFRHI¿FLHQWȕ 1D.08
COMPARISON OF WRIST-TYPE AND ARM-TYPE
AMBULATORY BLOOD PRESSURE MONITORING
DEVICES
W. Zeng, T. Chu, B. Fok, M. Hu, B. Tomlinson. Department of Medicine and
Therapeutics, the Chinese University of Hong Kong, Shatin, HONG KONG
Objective: Ambulatory blood pressure monitoring (ABPM) is important in
evaluating average 24-hour BP levels, circadian rhythm and BP variability but
many patients are reluctant to use standard ABPM devices. We evaluated two
validated devices; a wrist monitor (BPro, HealthSTATS International, Singapore) and an upper arm monitor (A&D TM-2430, Tokyo, Japan) for agreement
of recordings and acceptability.
Design and method: ABPM was performed in 27 hypertensive patients (aged
55±10 years) with the wrist and arm monitors attached to the left and right arm, respectively. The wrist monitor measured BP at 15-min intervals over 24 hours and
the arm monitor measured BP at 15-min intervals in the daytime and hourly from
22:00 to 07:00. Waking and sleeping periods were analyzed based on patients’ diaULHV$%30SUR¿OHVZHUHHGLWHGDFFRUGLQJWRFRQYHQWLRQDOFULWHULDWRFRUUHFWIRU
measurement errors and outliers. Valid readings measured within 5 minutes by the
2 monitors and with a difference in heart rate of < or = 5 beats/min were compared.
Results: Fewer successful BP measurement were obtained with the wrist monitor
(total 53±15%, awake 54±16%, sleeping 61±31%) compared to the arm monitor (total 94±4%, awake 93±5%, sleeping 94±6%, all P<0.01). From 673 readings (498 awake, 175 asleep readings) that could be compared between moniWRUVWKHUHZDVQRVLJQL¿FDQWGLIIHUHQFHLQKRXU6%3 “YV“
mmHg, P=0.60), or awake and sleeping values. DBP values were higher with the
wrist compared to the arm monitor (24-hour 89±13.6 vs. 85±14.4 mmHg, awake
91±13.5 vs. 88±13.4 mmHg, sleeping 83±12.0 vs. 77±14.3 mmHg, all P<0.01).
Bland-Altman analysis showed the differences between arm and wrist monitors
for SBP and DBP were 0.4±18.1 (range -47 to 49) mmHg and -3.9±12.9 (-46 to
39) mmHg (Figure 1).
e15
Journal of Hypertension Volume 32, e-Supplement 1, 2014
Conclusions: The wrist monitor showed reasonable agreement with the arm
monitor for ABPM and patients found it more comfortable to use but the successful recoding rate was considerably lower.This study supports the use of the
BPro device to obtain ABPM data to increase patient acceptability, but insuf¿FLHQW%3UHFRUGLQJVPD\EHDSUREOHP
1D.09
NOT CASUAL BLOOD PRESSURE BUT AMBULATORY
BLOOD PRESSURE IS CORRELATED WITH 24 HOUR
URINARY SODIUM EXCRETION
J. Shin 1, Y. Yamori 2, B. Choi 3, M. Kim 3, B. Kim 4, Y. Lee 5. 1 Department of
Internal Medicine, Hanyang University College of Medicine, Seoul, SOUTH
KOREA, 2 Institute for World Health Development, Mukogawa Women’s
University, Hyogo, JAPAN, 3 Department of Preventive Medicine, Hanyang
University College of Medicine, Seoul, SOUTH KOREA, 4 Department of
Internal Medicine, Sung-Ae Hospital, Seoul, SOUTH KOREA, 5 Department of
Medicine, Myung-Ji Hospital, Seoul, SOUTH KOREA
Objective: Salt intake is associated with high blood pressure (BP). But the relationship between salt intake and the BP is affected by many factors such as absolute level of salt intake, salt sensitivity, and the accuracy or the timing of the BP
measurement. But the association between salt intake and the daytime or nighttime
BP was not clearly known.
Design and method: In the rural area, Yeojoo, Gyunggi Province in South Korea,
218 subjects with age between 30 and 60 years old were measured with ambulatory blood pressure monitoring (ABPM) and 24 hour urine sample to measure
salt intake. ABPM device was TM2430, AND and the 24 hour urine sample was
collected using the aliquot cup. Urine collection was regarded as acceptable only
when one missed collection was related to defecation.
Results: For both ABPM and 24 hour urine collection, 112 subject data was acceptable for the analysis. Age was 48.5± 8.2 (30-61) and female was 66(59%).
In multiple linear regression models including age, gender, salt intake, and the
score of metabolic syndrome (Mets) other than BP for BPs, casual BPs were
not associated with salt intake but with MetS score. For daytime SBP, salt intake was the only independent factor (beta=1.123 +/- 0.528, p=0.035) whereas
the salt intake was negatively associated with daytime DBP (beta=0.892 +/0.368,p=0.017). For nighttime SBP, salt intake was the only positively associated
factor (beta=1.484+/-0.614, p=0.017). For nighttime DBP, MetS score was the
only factor (beta=1.879+/-0.822, p=0.024).
Conclusions: As for the relationship between sodium intake and the blood pressure, ambulatory blood pressure is more useful than casual blood pressure so
that the relationship between salt intake by 24 hour urine and blood pressure
could be demonstrated in a small sized general population by using ABPM.
1D.10
INVASIVE VALIDATION OF THE COMPLIOR® ANALYSE
IN THE ASSESSMENT OF CENTRAL ARTERY
PRESSURE CURVES: A METHODOLOGICAL STUDY
T. Pereira 1, J. Maldonado 2. 1 Instituto Politécnico de Coimbra, ESTESC,
DCPL, Coimbra, PORTUGAL, 2 Instituto de Investigação e Formação
Cardiovascular, Coimbra, PORTUGAL
Objective: Arteries are the target, the place and the common denominator of
cardiovascular diseases, hence studying arterial function is of greatest importance in clinical practice. The purpose of this study was to evaluate the accuracy
RIFDURWLGSXOVHZDYHDQDO\VLVZLWKWKHQHZYHUVLRQRIWKH&RPSOLRUGHYLFH±WKH
Complior Analyse (ALAM, Paris).
Design and method: Cross-sectional study including 15 patients (7 female gender), mean age 62.07±10.59 years, referenced for cardiac catheterization. Pressure curves were simultaneously obtained in the ascending aorta (invasively)
and in the right common carotid artery (using the Complior Analyse). Mean
central arterial pressures, augmentation indexes and wave morphology obtained
with both methods were compared.
Results: A good concordance between methods was obtained for all the
PHDVXUHG SDUDPHWHUV ZLWK LQWUDFODVV FRUUHODWLRQ ,&& FRHI¿FLHQWV DERYH
%ODQG$OWPDQ¶V DQDO\VLV DOVR GHQRWHG D JRRG DFFXUDF\ SUR¿OH RI WKH
Complior device, with small mean differences observed for all parameters
DQG PRVW YDOXHV FRQ¿QHG ZLWKLQ VWDQGDUG GHYLDWLRQV RI WKH PHDQ GLIIHUence. This aspect was further reinforced by the strong Pearson correlation
FRHI¿FLHQWVZLWKUFRHI¿FLHQWVDERYHIRUDOOWKHVWXGLHGYDULDEOHV7KH
observed correlations were independent of gender, age, arterial pressure and
body mass index.
Conclusions: The presented results and available research clearly indicate that the
Complior Analyse device measures accurately carotid pressure waves; therefore,
it’s a simple and reliable non-invasive alternative for pressure wave analysis.
1D.11
CHARACTERISTICS OF SELF-MEASURED HOME AND
OFFICE-MEASURED BLOOD PRESSURE AMONG
BLACK AFRICANS: A PILOT STUDY IN A NIGERIAN
URBAN COMMUNITY
A. Odili 1, V. Ameh 3, K. Asayama 2, L. Thijs 2, J. Staessen 2,4. 1 Centre for
Population Health Research, College of Health Sciences, University of Abuja,
Abuja, NIGERIA, 2 Studies Coordinating Centre, Research Unit Hypertension
and Cardiovascular Epidemiology, University of Leuven, Leuven, BELGIUM, 3
Department of Family Medicine, University of Abuja Teaching Hospital, Abuja,
NIGERIA, 4 Department of Epidemiology, Maastricht University, Maastricht,
NETHERLANDS
Objective: Home blood pressure is reported to have a better prognostic accuracy as compared to clinic blood pressure. Until now, there is no report on home
self-measured blood pressure among black people born and living in Africa.
:H KHUHE\ SUHVHQW WKH FKDUDFWHULVWLFV RI KRPH DQG RI¿FH EORRG SUHVVXUH RI D
randomly selected population of Nigerians.
Design and method: %ORRGSUHVVXUH %3 UHDGLQJVPHDVXUHG¿YHFRQVHFXWLYH
times with the mercury sphygmomanometer by trained observers were averDJHG DV RI¿FH EORRG SUHVVXUH 3DUWLFLSDQWV ZHUH WUDLQHG LQGLYLGXDOO\ DIWHU WKH
RI¿FH H[DPLQDWLRQ RQ WKH WHFKQLTXHV RI VHOI%3 PRQLWRULQJ XVLQJ DXWRPDWHG
oscillometric device. Each participant obtained 24 readings comprising duplicate morning and evening readings over a 6 day period; the overall average of
which is the home BP.
Results: The 160 participants included 72(45%) women, mean age (SD)
\HDUV+RPHEORRGSUHVVXUHZDVVLJQL¿FDQWO\KLJKHUWKDQRI¿FH%3
117.3mmHg vs 113.0 mmHg (p<0.0001), and 76.0 vs 73.5mmHg (p<0.01) for
systolic and diastolic BP respectively. 43(26.8%) participants were hypertenVLYH HLWKHU SUHYLRXVO\ RQ DQWLK\SHUWHQVLYH PHGLFDWLRQV RU KDG RI¿FH %3! 140/90mmHg); 9(5.6%) had masked hypertension and 13(8.1%) had isolated of¿FHK\SHUWHQVLRQ7KHPRUQLQJ%3OHYHOVZHUHPP+J &,PP+J
p=0.005) and 1.89mmHg (CI, 1.06 to 2.7mmHg, p<0.0001) higher than the
evening systolic and diastolic BP respectively.
Conclusions: 7KHUHDUHREYLRXVGLVWLQFWSHFXOLDULWLHVRIKRPHDQGRI¿FHEORRGSUHVsure among African Nigerians. The extent to which this alters diagnostic threshold
derived from studies conducted among other ethnic populations needs to be explored.
1D.12
THE MORNING BLOOD PRESSURE SURGE
VELOCITY AND SALT-SENSITIVITY IN PATIENTS WITH
ESSENTIAL HYPERTENSION
G. Abdullaeva, R. Kurbanov, G. Khamidullaeva.
Republic Specialized Center of Cardiology, Tashkent, UZBEKISTAN
Objective: 7R VWXG\ GDLO\ EORRG SUHVVXUH SUR¿OH '%33 UDWHV LQ DVVRFLDWLRQ
with salt-sensitivity in patients with essential hypertension (EH).
Design and method: The study included 79 male and female patients with stage
I-III EH (WHO,2007) with an average age of 58.48±11.48 years. Mean duration of
EH was 12.34± 6.49 yr. To identify salt taste sensitivity threshold all patients were
tested by R. Henkin`s method. DBPP was assessed by TONOPORT V computer
system (“GE Medical Systems”, Germany). Results were expressed as mean±SD.
Results: Patients were randomized according to carrying of variants of salt taste
sensitivity threshold (STST). Distribution of taste threshold of salt-sensitivity
ZDVIROORZLQJKLJK6767±PHGLXP±6767±ORZ6767±
S [ +LJK7766ZDVSUHYDOHQW7KHUHZHUHQRVLJQL¿cant differences in means of ambulatory blood pressure(BP) measurements into
DFFRXQWRI67677KHUHZHUHQRVLJQL¿FDQWGLIIHUHQFHV S! LQWKHYHORFLW\
of systolic morning BP surge (MBPS) between high STST patients and middle
STST patients (30.13±21.77 and 28.34±22.72 mm Hg/h respectively), whereas
there was a trend to increase of systolic MBPS in high STST patients versus
ORZ6767SDWLHQWV“PP+JK S 7KHUHZHUHVLJQL¿FDQWGLIferences in velocity of morning diastolic BP surge into account of STST. The
velocity of morning diastolic BP surge was increased in high STST patients:
26.65±20.26 mm Hg/h and 28.12±20.70 mm Hg/h in medium STST patients
versus 10.93±22.21 in low STST patients(p<0.05).
Conclusions: Prevalence of high STST took place in patients with EH. ComSDUDWLYHVWXG\RIGDLO\%3SUR¿OHUDWHVLQWRDFFRXQWRIVDOWVHQVLWLYLW\UHYHDOHGD
greater velocity of morning diastolic BP surge in patients with high and medium
STST.
Abstracts
e16
ORAL SESSION
ORAL SESSION 2A
INFLAMMATION AND URIC ACID
2A.01
MATRIX METALLOPROTEINASE-2 IS ESSENTIAL
FOR ANGIOTENSIN II TO INDUCE ENDOTHELIAL
DYSFUNCTION AND VASCULAR REMODELING,
OXIDATIVE STRESS AND INFLAMMATION
M. Mian 1, T. Barhoumi 1, A. Rehman 1, N. Idris-Khoja 1, Y. Rautureau 1,
P. Paradis 1, E.L. Schiffrin 1,2. 1 Vascular and Hypertension Research Unit, Lady
Davis Institute for Medical Research, McGill University, Montreal, CANADA,
2
Department of Medicine, Sir Mortimer B. Davis Jewish General Hospital,
McGill University, Montreal, CANADA
Objective: Matrix metalloproteinase-2 (MMP2) is involved in vascular remodeling in atherosclerosis. Whether MMP2 plays a role in angiotensin (Ang) IILQGXFHG K\SHUWHQVLRQ YDVFXODU UHPRGHOLQJ R[LGDWLYH VWUHVV DQG LQÀDPPDWLRQ
is unknown. We hypothesized that Mmp2 knockout will prevent Ang II-induced
vascular injury.
Design and method: Ten to 12-week-old male Mmp2 knockout (Mmp2-/-) and
wild-type mice were infused or not with Ang II (1000 ng/kg/min, sc) for 14 days.
Systolic blood pressure (BP) was measured by telemetry. Mesenteric arteries
(MA) were studied by pressurized myography. NADPH oxidase activity was
evaluated by lucigenin chemiluminescence in the aorta, cardiac apex and renal
cortex.Reactive oxygen species (ROS) generation was determined in the aorta
using dihydroethidium staining. Aortic expression of vascular cell adhesion protein 1 (VCAM-1) and monocyte chemotactic protein-1 (MCP-1), and monocyte/
PDFURSKDJHLQ¿OWUDWLRQZHUHDVVHVVHGE\LPPXQRÀXRUHVFHQFH6SOHHQ7FHOOV
DQGPRQRF\WHVZHUHDVVHVVHGE\ÀRZF\WRPHWU\
Results: Ang II increased systolic BP by 50 mmHg (P<0.01), decreased vasodilatory responses to acetylcholine by 70 % (P<0.01), induced MA hypertrophic
remodeling, indicated by a 1.5-fold increase (P<0.01) in media-to-lumen ratio
and 1.3-fold increase (P<0.05) in media cross-sectional area, and enhanced MA
stiffness (P<0.01), as shown by a leftward shift of the stress/strain relationship,
in wild-type mice. Ang II increased NADPH oxidase activity 1.4-fold in aorta
(P<0.05), 2-fold in the cardiac apex (P<0.01) and 2.6-fold in the renal cortex
(P<0.01), and aortic ROS generation 25-fold in wild-type mice (P<0.01). Ang
II increased aortic VCAM-1 and MCP-1 expression 3- and 6-fold, respectively,
DQG PRQRF\WHPDFURSKDJH LQ¿OWUDWLRQ IROG LQ ZLOGW\SH 3 $QJ ,,
LQFUHDVHG ! IROG VSOHHQ DFWLYDWHG &'&' DQG &'&'7 FHOOV
DQGSURLQÀDPPDWRU\/\&KLPRQRF\WHV 3 LQZLOGW\SHPLFH0PS
knockout prevented or reduced all of the above except BP elevation (P<0.05).
Conclusions: MMP2 plays a role mediating Ang II-induced endothelial dysIXQFWLRQ YDVFXODU UHPRGHOLQJ R[LGDWLYH VWUHVV DQG LQÀDPPDWLRQ EXW KDV QR
effect on Ang II-induced BP elevation.
2A.02
COMPLEMENTS REGULATE PERIVASCULAR
ADIPOSE TISSUE MACROPHAGE POLARIZATION
IN DEOXYCORTICOSTERONE ACETATE-SALT
HYPERTENSIVE MICE
P. Gao, C. Ruan. Shanghai Institute of Hypertension, Shanghai, CHINA
Objective: Macrophage polarization plays a pivotal role in the pathogenesis of hypertensive vascular remodeling. Pervious studies have demonstrated complement
C3 expression dramatically increased around the perivascular adipose tissue in
deoxycorticosterone acetate (DOCA)-salt hypertensive model. However, its role
in regulating macrophage function contributing to vascular injury has not been
investigated. We hypothesized that complements regulate perivascular adipose tissue macrophage polarization, thus leading to hypertensive vascular damage.
Design and method: A hypertensive model was established in uninephrectomized C57BL6/J mice after bone marrow transplantation using DOCA-salt.
)ORZ F\WRPHWU\ DQG LPPXQRÀXRUHVFHQFH ZHUH SHUIRUPHG WR LGHQWLI\ PDFrophage polarization. Peritoneal macrophage was used to assess the macrophage
phenotype.
Results: DOCA-salt treatment led to macrophage accumulation and collocation
ZLWK & LQ WKH SHULYDVFXODU DGLSRVH WLVVXH ,QÀDPPDWRU\ IDFWRU &D DQG &D
LQFUHDVHGDQWLLQÀDPPDWRU\DGLSRNLQHDGLSRQHFWLQ $31 UHGXFHG,QYLWUR&
GH¿FLHQF\LQKLELWHG0PDFURSKDJHSRODUL]DWLRQDQGHQKDQFHG0PDFURSKDJH
SRODUL]DWLRQ,QYLYR&RU&ERQHPDUURZZDVWUDQVSODQWHGWRZLGHW\SH
mice with subsequent DOCA-salt treatment. Although total macrophage content
had no difference between two groups, C3-/- donor group had fewer M1 and
more M2 macrophage phenotype, and protected against vascular damage. However, C3-/- bone marrow transplanted to APN knock out mice did not affect macrophage polarization and had no protection against vascular damage after DO&$VDOWWUHDWPHQW,QYLWUR&GH¿FLHQF\EORFNHG0PDFURSKDJHFRQGLWLRQHG
medium induced APN down-regulation in adipocyte. APN attenuated M1 and
promoted M2 macrophage phenotype. Further, C3a did not affect macrophage
polarization, C5a enhanced M1 and inhibited M2 macrophage phenotype. In
YLYR&DLQIXVLRQVLJQL¿FDQWO\LQFUHDVHGPDFURSKDJH¿OWUDWLRQLQWKHSHULFYDVcular adipose tissue and accelerated vascular damage after DOCA-salt treatment.
Conclusions: Complements of bone marrow-derived macrophages worsen the
extent of DOCA-salt hypertensive vascular damage by shifting the perivascular
adipose tissue macrophage phenotype to more M1 and less M2 through mechanisms that include increased C5a and impaired APN.
2A.03
ATTENUATION OF HYPERTENSION IN THE
SPONTANEOUSLY HYPERTENSIVE RAT BY BONE
MARROW RECONSTITUTION WITH NORMOTENSIVE
WKY CELLS
M. Santisteban, J. Zub, Y. Qi, J. Marulanda Carvajal, M. Zingler.
University of Florida, Gainesville, FL, USA
Objective: Bone marrow (BM) is a crucial meeting point for the sympathetic inQHUYDWLRQ DQG KHPDWRSRLHWLFVWHP FHOOV LQFOXGLQJ WKH LQÀDPPDWRU\ FHOOV ,&V +RZHYHUWKHUROHRIWKH%0LQK\SHUWHQVLRQ +71 LVQRWZHOOGH¿QHG:HUHcently demonstrated that a dysfunctional brain-BM communication in rat models
of neurogenic HTN may be associated with an impaired BM activity, characterized
by elevated levels of ICs in the blood and BM when compared to the normotensive
controls. Therefore, we hypothesized that BM of the spontaneously hypertensive
UDW 6+5 LVSURLQÀDPPDWRU\DQGWKDWLWFRQWULEXWHVWR+71LQWKLVUDWPRGHO
Design and method: 6-week old female SHR and WKY rats underwent BM ablation by irradiation, followed by reconstitution with BM mononuclear cells (10E6
FHOOVSHUUDW GHULYHGIURPHLWKHUWKH6+5RU:.<PDOHUDWV 6+56+5Q 6+5:.< Q :.<:.< Q :.<6+5 Q )ROORZLQJ D WKUHHPRQWK
recovery period, blood pressure was measured by tail-cuff for 4 weeks. Blood
ZDVFROOHFWHGIRULVRODWLRQRI01&VDQG &'&' ÀRZF\WRPHWU\%UDLQWLVsue was collected and immunohistochemistry was performed using the microglial
VSHFL¿FPDUNHU,ED0LFURJOLDODFWLYDWLRQZDVTXDQWL¿HGLQK\SRWKDODPLFSDUDventricular nucleus (PVN).
Results: Adoptive transfer of the WKY BM led to approximately 10% decrease
LQ0$3 “PP+JS DQGGHFUHDVHLQWKHFLUFXODWLQJ7FHOOOHYHOV
LQWKH6+5:.<ZKHQFRPSDUHGWRWKH6+56+5JURXS 0$3 “PP+J Microglial activation, as measured by total number of microglia per 40,000µm2,
percent activated microglia, and cell body area, was decreased in SHR-WKY vs
SHR-SHR group, (p<0.05). Adoptive transfer of SHR BM elevated the MAP in
WKH:.<6+5JURXS :.<6+5“PP+J FRPSDUHGWRWKRVHUHFRQVWLWXWHGZLWK:.<FHOOV :.<:.<“PP+J )XUWKHUPRUHWKHUHZDVD
aHOHYDWLRQLQFLUFXODWLQJ&'FHOOVDQGDLQFUHDVHLQP51$H[SUHVsion of Iba1 in PVN of WKY-SHR vs WKY-WKY rats (p<0.05).
Conclusions: 7KHVH GDWD VXJJHVW WKDW WKH SURLQÀDPPDWRU\ SURSHUWLHV RI 6+5
%0FRQWULEXWHWR+71E\LQFUHDVLQJERWKWKHSHULSKHUDODQGFHQWUDOLQÀDPPDWRU\
status in SHR. These observations support the role of the BM in HTN, especially
LQDIIHFWLQJWKHLQÀDPPDWRU\VWDWXVZKLFKLVDKDOOPDUNRI+71LQ6+5
S
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e17
Journal of Hypertension Volume 32, e-Supplement 1, 2014
2A.04
INFLAMMATORY CHANGES AND COAGULATION IN
CORONARY HEART DISEASE ASSOCIATED WITH
SUBCLINICAL HYPOTHYROIDISM
I. Shatynska-Mytsyk, Y. Mytsyk, O. Makar.
Lviv National Medical University, Lviv, UKRAINE
Objective: Subclinical hypothyroidism (SH) is associated with high incidence of
coronary heart disease (CHD). Purpose. Evaluation of pituitary-thyroid axis, lipid
PHWDEROLVPDQWLWURPELQ,,, $,,, ¿EULQRO\WLFDFWLYLW\ )$ KLJKO\VHQVLWLYH&UHactive protein (hsC-RP) and treatment outcomes following hormone replacement
therapy (HRT) with low-dosed thyroxin in patients with CHD and SH analysis.
Design and method: Levels of thyroid stimulating hormone (TSH), free
thyroxin (fT4), gonadotropins were measured by RIA, hsC-RP by immuneenzyme assay, FA and A III, lipid metabolism were assessed in 123 women
in menopause. Patients were randomized into 4 age-comparable groups. 1st
JURXSLQFOXGHGZRPHQZLWK6+PDQDJHGZLWK+57 SDWLHQWV QGZRPen with SH managed by standard therapy (30 patients). Patients were evaluated after 3, 6 months of therapy. 3rd group included women with CHD without known thyroid disorders (30 patients), control group- 33 healthy women.
Results: Gonadotropins evidenced menopause in all patients: high levels of
luteinizing (LH) and follicle stimulating (FSH) hormones were equivocal in
JURXSV S! 76+ “ ,8/ DQG I7 “ SPRO/ OHYHOV
LQ VW DQG QG JURXSV FRQ¿UPHG 6+ /+)6+ UDWLR KDG QHJDWLYH FRUUHODWLRQZLWK76+ U ±S $WKHURJHQLFFKDQJHVRIOLSLGPHWDEROLVP
were registered in 3 groups with CHD, 1st and 2nd groups showed reliable
increase in triglycerides and total cholesterol (TC) level (p<0,01). TC and
WULJO\FHULGHVOHYHOVKDGSRVLWLYHFRUUHODWLRQZLWK76+ U U p<0,01) accordingly. hs C-RP, FA and A III activity were higher in patients
with SH (p<0,01). Following 6 months of HRT lipid metabolism showed
VLJQL¿FDQW LPSURYHPHQW7& ¨ ORZ GHQVLW\ OLSRSURWHLQV /'/ ¨ WULJO\FHULGHV OHYHOV ¨ UHOLDEO\ GHFUHDVHG S ZKLOH RQ VWDQGDUG WKHUDS\ FKDQJHV ZHUH OHVV VLJQL¿FDQW 7& ¨ /'/ ¨ WULJO\FHULGHV ¨ S )$ DQG $ ,,, DFWLYLW\
showed more reliable decrease in 1st group (p<0,01) than in 2nd (p<0,05),
hs C-RP reliably decreased only following HRT.
Conclusions: TSH level and serum lipids should be included into screening
programs for individual CHD risk evaluation in menopausal women. HRT with
low dosed thyroxin may be recommended for enhancement of lipid lowering
therapy with statins in women with SH and CHD.
2A.06
R. Nosalski 1, T. Mikolajczyk 1, J. Maciag 1, T. Guzik 1,2. 1 Jagiellonian
University Collegium Medicum, Department of Internal and Agricultural
Medicine, Kraków, POLAND, 2 University of Glasgow, Institute of
Cardiovascular and Medical Sciences, Glasgow, UNITED KINGDOM
Objective: Recent studies show that immune system is involved in the pathogenesis of hypertension. During progression of hypertension immune cells accumulate around vasculature, mainly in perivascular adipose tissue (PVAT).
However, while aging is a major factor in the development of hypertension, it’s
HIIHFWVRQSHULYDVFXODULQÀDPPDWLRQUHPDLQXQFOHDU
Design and method: 8VLQJÀRZF\WRPHWU\ZHVWXGLHGOHXNRF\WHVLQ¿OWUDWLQJ
perivascular adipose tissue (PVAT) in 6- and 12-month-old SHR (Spontaneously
Hypertensive Rats) and WKY (Wistar-Kyoto) rats.
Results: 7RWDOQXPEHURIOHXNRF\WHV &' LQ¿OWUDWLQJ39$7LQPRQWKROG
UDWVZDVVLJQL¿FDQWKLJKHULQ6+5WKDQLQ:.< “YV“
FHOOPJ S 7KH VDPH WUHQG ZDV REVHUYHG LQ PRQWKROG DQLPDOV
“ YV “ FHOOPJ S UHVSHFWLYHO\ ,QWHUHVWLQJO\ WKH OHXNRF\WHLQ¿OWUDWLRQZDVFRPSDUDEOHEHWZHHQ6+5DQG:.<LQYLVFHUDOIDW$V
HYLGHQWDJLQJDIIHFWHGSHULYDVFXODUOHXNRF\WHLQ¿OWUDWLRQLQERWK:.<DQG6+5
although in SHR the increase was more dynamic. Virtually, all studied leukocyte
VXEVHWVVXFKDV1.FHOOV “YV“FHOOPJS PDFURSKDJHV
“ YV “ FHOOPJ S GHQGULWLF FHOOV “ YV “ FHOO
PJS DQG7FHOOV “YV“FHOOPJS ZHUHLQFUHDVHGLQ
6-month-old hypertensive animals in comparison to 6month-old normotensive
DQLPDOVDQGZHUHIXUWKHULQFUHDVHGLQPRQWKROGUDWV1. “YV“
FHOOPJS PDFURSKDJHV “FHOOPJYV“FHOOPJS GHQGULWLFFHOOV “YV“FHOOPJS 7FHOOV “YV“
FHOOPJS UHVSHFWLYHO\7KHDJHUHODWHGLQFUHDVHLQFUHDVHVZHUHVLJQL¿cant only in respect to T cells (p<0.01) and NK cells (0.01) in SHR, but not in
FRQWUROUDWVZKLOHQXPEHURIPDFURSKDJHVVLJQL¿FDQWO\LQFUHDVHGLQERWKJURXSV
in context of aging.
Conclusions: 3HULYDVFXODU LQÀDPPDWLRQ LV LQFUHDVHG LQ K\SHUWHQVLRQ :KLOH
perivascular leukocyte content increases in both SHR and control rats, it’s
changes in hypertension are more dynamic and related preferentially to NK cells
and T cells.
2A.07
2A.05
ASSOCIATION OF URIC ACID GENETIC RISK SCORE
WITH SYSTOLIC AND DIASTOLIC BLOOD PRESSURE:
THE ROTTERDAM STUDY
S. Sedaghat 1, R. Pazaki 1, $8LWWHUOLQGHQ2, A. Hofman 1, M. Ikram 1,3,4,
O. Franco 1, A. Dehghan 1. 1 Department of Epidemiology, Erasmus Medical
Center, Rotterdam, NETHERLANDS, 2 Department of Internal Medicine, Erasmus
Medical Center, Rotterdam, NETHERLANDS, 3 Department of Radiology,
Erasmus University Medical Center, Rotterdam, NETHERLANDS, 4 Department of
Neurology, Erasmus University Medical Center, Rotterdam, NETHERLANDS
Objective: High levels of serum uric acid associates with hypertension in observational studies. The aim of this study was to investigate the association of uric
acid genetic risk score with systolic and diastolic blood pressure.
Design and method: :HLQFOXGHGSDUWLFLSDQWVDJHG\HDUVDQGROGHU
IURPWKHSRSXODWLRQEDVHG5RWWHUGDP6WXG\*HQHVLGHQWL¿HGIURPJHQRPHZLGH
association studies (GWAS) modulating uric acid (n=30) were used to compile
a genetic risk score (GRS). We used linear regression models to investigate the
association of the uric acid GRS with systolic and diastolic blood pressure in the
whole study population and separately in participants with and without comorbidities and anti-hypertensive medication use.
Results: In the age and sex adjusted model, each standard deviation increase
in uric acid GRS was associated with 0.75 mmHg lower systolic blood presVXUH FRQ¿GHQFHLQWHUYDO &, DQGPP+JORZHUGLDVWROLFEORRGSUHVVXUH &, 7KHDVVRFLDWLRQGLGQRWDWWHQXDWHDIWHU
IXUWKHU DGMXVWPHQW IRU HVWLPDWHG JORPHUXODU ¿OWUDWLRQ UDWH VHUXP XULF DFLG
anti-hypertensive medication use and conventional cardiovascular risk factors.
7KH DVVRFLDWLRQ RI XULF DFLG *56 ZLWK V\VWROLF EORRG SUHVVXUH ZDV VLJQL¿cantly stronger in participants on diuretic treatment (P for interaction: 0.007).
Conclusions: Despite previous reports on the relationship between serum uric acid
and hypertension, we demonstrated that uric acid GRS is associated with lower systolic and diastolic blood pressure. Diuretic treatment might moderate this association.
Numerous genes are known to be associated with multiple phenotype. Pleiotropic asVRFLDWLRQRIXULFDFLGJHQHVZLWKGLXUHWLFWUHDWPHQWPLJKWH[SODLQRXU¿QGLQJV
PERIVASCULAR INFLAMMATION IN AGEING
SPONTANEOUSLY HYPERTENSIVE RATS
RENAL SYMPATHETIC DENERVATION AND
INFLAMMATORY PARAMETERS
D. Lang 1, C. Primus 2, T. Lambert 3, C. Steinwender 3, R. Berent 4,
J. Auer 1,2,3. 1 Medical University Graz, Graz, AUSTRIA, 2 General Hospital
Braunau, Braunau, AUSTRIA, 3 General Hospital Linz, Linz, AUSTRIA,
4
Cardiac Rehabilitation Center, Bad Schallerbach, AUSTRIA
Objective: Renal sympathic denervation with radiofrequency ablation substantially reduces blood pressure in patients with treatment-resistant hypertension.
:H LQYHVWLJDWHG FKDQJHV RI LQÀDPPDWRU\ SDUDPHWHUV DIWHU UHQDO V\PSDWKHWLF
denervation and their association with ambulatory blood pressure changes.
Design and method: :H FRQGXFWHG D UHWURVSHFWLYH DQDO\VLV RI LQÀDPPDWRU\
SDUDPHWHUVDPRQJSDWLHQWVWUHDWHGZLWKUHQDOV\PSDWKHWLFGHQHUYDWLRQ6Hrum C-reactive protein concentration, interleukin-6 concentration and leukocyte
count were assessed before, 6 and 12 months after denervation. Separate analyVHVZHUHFRQGXFWHGIRUUHVSRQGHUV GH¿QHGDVGHFUHDVHLQDPEXODWRU\V\VWROLF
blood pressure of 5mm or more) and non-responders.
Results: There were no meaningful differences between baseline, 6 and 12
PRQWKV&53FRQFHQWUDWLRQV S DQGS UHVSHFWLYHO\ 7KHUHZDVQR
VLJQL¿FDQWLQWHUDFWLRQIRUUHVSRQGHUVWDWXVIRUEDVHOLQHDPEXODWRU\EORRGSUHVsure (ABP) levels, and for ABP-changes at 6 months.
We observed a reduction in interleukin-6 concentrations at 6 and 12 months
SJPODQGSJPOUHVSHFWLYHO\S 7KHUHZDVD
VLJQL¿FDQW LQWHUDFWLRQ EHWZHHQ FKDQJHV LQ VHUXP LQWHUOHXNLQ FRQFHQWUDWLRQV
DQGUHVSRQGHUVWDWXV SJPOYHUVXVSJPOIRUUHVSRQGHUDQGQRQUHVSRQGHUUHVSHFWLYHO\S ,QWHUOHXNLQFKDQJHVDWPRQWKVVLJQL¿FDQWO\
correlated with ambulatory blood pressure changes at 6 months (p=0.01).
:KLWHEORRGFHOO :%& FRXQWVVLJQL¿FDQWO\GHFUHDVHGDQGPRQWKVDIWHU
UHQDOV\PSDWKHWLFGHQHUYDWLRQ [ñȝOSDQG
[ñȝO S :H GLG QRW ¿QG DQ\ LQWHUDFWLRQ EHWZHHQ :%& FRXQW
DQGUHVSRQGHUVWDWXV7KHUHZDVQRVLJQL¿FDQWFRUUHODWLRQEHWZHHQFKDQJHVLQ
WBC counts and baseline ambulatory blood pressure (ABP) levels, and ABP
changes at 6 months.
Conclusions: Renal sympathetic denervation may be associated with a substanWLDOGHFUHDVHRIVHUXPLQÀDPPDWRU\PDUNHUFRQFHQWUDWLRQV
Abstracts
e18
ORAL SESSION
ORAL SESSION 2B
AGEING
2B.01
ASSOCIATION BETWEEN MORTALITY AND
BLOOD PRESSURE LEVELS IN ELDERLY LIVING
NURSING HOME SUBJECTS. ARE FRAIL SUBJECTS
OVERTREATED (PARTAGE STUDY)?
A. Benetos 1, S. Gautier 1, P. Salvi 2, F. Valbusa 3, O. Toulza 4, D. Agnoletti 5,
M. Zamboni 3, P. Manckoundia 6, O. Hanon 7, C. Labat 1. 1 Department of
Geriatrics, University Hospital of Nancy, UHP-INSERM U 1116,
Vandoeuvre-lès-Nancy, FRANCE, 2 Department of Cardiology, IRCCS Istituto
Auxologico Italiano, Milan, ITALY, 3 Division of Internal Medicine Sacro
Cuore Hospital, Negrar, Verona, ITALY, 4 Department of Geriatrics and Inserm
U1027, Toulouse University Hospital, Toulouse, FRANCE, 5 Diagnosis Center,
Hôtel-Dieu Hospital, Paris, FRANCE, 6 Department of Geriatrics, University
Hospital of Dijon, Dijon, FRANCE, 7 Broca Hospital, University Descartes
Paris 5, EA 4468, Paris, FRANCE
Objective: :H KDYH UHFHQWO\ UHSRUWHG WKDW LQ YHU\ ROG LQGLYLGXDOV !\ OLYing nursing homes (PARTAGE study), total mortality rates were higher in those
individuals with lower SBP or DBP. These results persisted after adjustment for
age, sex, BMI, idexes of autonomy and co-morbidities and history of CV disease.
These results question about possibility of overtreating hypertensive frail subjects
who are vulnerable to polymedication and iatrogenic problems. The aim of the
present analysis was to study whether this negative association between BP and
mortality is observed similarly in both individuals with or without antihypertensive treatment.
Design and method: $ WRWDO RI VXEMHFWV ZRPHQ ! \HDUV ROG
PHDQDJH“\ OLYLQJLQ)UHQFKDQG,WDOLDQQXUVLQJKRPHVZHUHHQUROOHG
'XULQJWKH\HDUIROORZXSGLHG,QGLYLGXDOVZHUHVWUDWL¿HGDFFRUGLQJWR
WKHSUHVHQFH Q RUWKHDEVHQFH Q RIDQWLK\SHUWHQVLYHWUHDWPHQWDQG
according to their SBP or DBP levels (tertiles). Blood pressure values (baseline)
ZHUHWKHPHDQRIVHOIPHDVXUHPHQWVSHUIRUPHGRYHUFRQVHFXWLYHGD\V
Results:7KH¿JXUHEHORZVKRZVQRDVVRFLDWLRQEHWZHHQ6%3DQGWRWDOPRUWDOity in individuals without antiHtn treatment (left panel). By contrast, as shown
LQWKHULJKWSDQHOVXEMHFWVZLWKWUHDWPHQW PHDQ“GUXJVIRUK\SHUWHQVLRQ and being in the 1st tertile (SBP levels <120 mmHg) showed higher mortality
UDWHVE\DQGWKDQWKHVHFRQGDQGWKHWKLUG6%3WHUWLOHVUHVSHFWLYHO\
(p<0.02 for both). Similar results were observed for the DBP tertiles. All these
UHVXOWVZHUHXQPRGL¿HGDIWHUDGMXVWPHQWIRUDJHVH[DQGPDMRUFRIRXQGHUV
Figure: Survival curves according to the SBP tertiles. In parenthesis the number
of individuals in each tertile.
Conclusions: In very old frail individuals treated for hypertension an SBP<120mmHg is associated with about 50% increase in total mortality as compared to treated individuals having higher BP levels. A key question is whether
an aggressive lowering of SBP through the use of multiple drugs might be deleterious in very old frail subjects, tipping their delicate balance of survival.
2B.02
EXERCISE CAPACITY AND MORTALITY IN
HYPERTENSIVE MEN 70 YEARS AND OLDER
A. Pittaras 1, C. Faselis 2, M. Doumas 2, A.J. Manolis 3, L.E. Poulimenos 3,
7=DP¿U3, O. Diakoumakou 3, K. Kifnidis 3, P. Kalogeropoulos 3, H. Grassos 3,
D. Lovic 2, P. Kokkinos 2. 1 Mediton Medical Center, Department of
Cardiology, Athens, GREECE, 2 Va and George Washington University Medical
Centers, Department of Cardiology, Washington DC, GREECE, 3 Asclepeion
Voulas Hospital, Department of Cardiology, Athens, GREECE
Objective: Chronological aging in healthy subjects is associated with declines
LQPXVFOHPDVVVWUHQJWKHQGXUDQFHDQGDHURELF¿WQHVV2OGHULQGLYLGXDOVUHspond favorably to exercise, suggesting that physical inactivity plays an important role in age-related dysfunctions. Conversely, physical activity and improved
exercise capacity is associated with lower mortality risk in hypertensive individuals. However, the impact of increased exercise capacity in older hypertensive
individuals has not been investigated extensively.
Design and method: $WRWDORIK\SHUWHQVLYHPHQDJH•\HDUVRIDJH
PHDQ DJH “ XQGHUZHQW URXWLQH H[HUFLVH WROHUDQFH WHVWLQJ 3HDN ZRUNORDG
was estimated in metabolic equivalents (METs). Fitness categories were estabOLVKHG EDVHG RQ SHDN 0(7V DFKLHYHG DGMXVWHG IRU DJH /RZ)LW ” 0(7V
Q 0RGHUDWH)LW 0(7V Q DQG +LJK)LW
!0(7V !Q $OOFDXVHPRUWDOLW\LVUHSRUWHGZLWKDPHDQIROORZXS
SHULRGRI&R[SURSRUWLRQDOKD]DUGPRGHOVZHUHDSSOLHGDIWHUDGMXVWLQJ
for age, BMI, race, CV disease, CV medications, and risk factors. P-values <0.05
XVLQJWZRVLGHGWHVWVZHUHFRQVLGHUHGVWDWLVWLFDOO\VLJQL¿FDQW
Results: 7KHUH ZHUH D WRWDO RI GHDWKV RU GHDWKV SHU person-years of follow-up. For every 1-MET increase in exercise capacity, the
PRUWDOLW\ULVNZDVORZHUHGE\ +5 &,S0RUWDOLW\
ULVNZDVORZHU +5 &,S IRUWKH0RGHUDWH)LWDQG
IRUWKH+LJK)LWLQGLYLGXDOV +5 &,S Conclusions: Aerobic capacity is associated with lower mortality risk in hyperWHQVLYHLQGLYLGXDOV•\HDUVROG
2B.03
PROGRESSION OF RENAL FUNCTION IN ELDERLY
TREATED HYPERTENSIVE PATIENTS: FINDINGS
FROM SECOND AUSTRALIAN NATIONAL BLOOD
PRESSURE STUDY
E. Chowdhury 1, R. Langham 2, Z. Ademi 1,3, A. Owen 1, H. Krum 1, L.M. Wing 4,
M.R. Nelson 5, C.M. Reid 1. 1 Department of Epidemiology and Preventive
Medicine, Monash University, Melbourne, AUSTRALIA, 2 Department of
Nephrology, St. Vincent’s Hospital, Melbourne, AUSTRALIA, 3 Melbourne
EpiCentre, Department of Medicine, The University of Melbourne,
Melbourne, AUSTRALIA, 4 School of Medicine, Flinders University, Adelaide,
AUSTRALIA, 5 Menzies Research Institute Tasmania, University of Tasmania,
Hobart, AUSTRALIA
Objective: Evidence of renal function decline and its relation to fatal events in
treated elderly hypertensive patients are sparse. We conducted a post-hoc analysis of elderly treated hypertensive patients who participated in a clinical trial
to assess the progress of renal function and its association with all-cause and
cardiovascular mortality, and determine factors that could be associated with
renal function deterioration.
Design and method: K\SHUWHQVLYH SDUWLFLSDQWV DJHG ! \HDUV ZHUH
randomly assigned to either angiotensin-converting enzyme inhibitor (ACEI)
or diuretic-based treatment and followed for a median of 4.1-years in the Second Australian National Blood Pressure Study (ANBP2). Following ANBP2
SDUWLFLSDQWVZHUHWUDFNHGIRUVXUYLYDORYHUDPHGLDQ\HDUV(VWLPDWHG*ORPHUXODU¿OWUDWLRQUDWH H*)5 ZDVXVHGWRPHDVXUHUHQDOIXQFWLRQDQGFKDQJHV
in eGFR overtime were calculated from the slope of the regression of individual
eGFRs against visit dates from randomization. An annual eGFR decline >3ml/
PLQPðZDVFODVVL¿HGDVµUDSLGGHFOLQH¶
Results: $ERXW RI SDUWLFLSDQWV ZLWK SODVPD FUHDWLQLQH OHYHOV GXUing the ANBP2 trial had a rapid renal function decline annually. The hazard
UDWLR FRQ¿GHQFHLQWHUYDO IRUDOOFDXVHPRUWDOLW\ &,
S DQGFDUGLRYDVFXODUPRUWDOLW\ &,S ZHUH
VLJQL¿FDQWO\KLJKHULQWKRVHZKRKDGDUDSLGGHFOLQHLQH*)5FRPSDUHGWRWKRVH
who did not have a rapid decline during the ANBP2 study period. A similar association was observed when a longer follow-up period was considered (all-cause
PRUWDOLW\&,SDQGFDUGLRYDVFXODUPRUWDOLW\
&, S &RQWURO RI %3 PP+J LQ WKH HOGHUO\
caused a rapid decline in eGFR, so was being male, elderlyolder, leaving in re-
S
A
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e19
Journal of Hypertension Volume 32, e-Supplement 1, 2014
gional area, wider pulse pressure, having diabetes and being a smoker at baseline
and using diuretics and multiple anti-hypertensive drugs during the trial period.
Conclusions: In elderly persons with hypertension, a rapid decline in eGFR is
associated with increased risk of mortality. Selecting the appropriate antihypertensive drug class along with a focus on clinical and demographic factors may
reduce renal function decline and promote survival.
2B.04
IMPAIRED BASELINE AORTIC STIFFNESS PREDICTS
PULSE WAVE VELOCITY IMPROVEMENT IN
RECENTLY DIAGNOSED PATIENTS WITH MILD TO
MODERATE ESSENTIAL HYPERTENSION: A 3-YEAR
FOLLOW-UP STUDY
H. Triantafyllidi, P. Trivilou, I. Ikonomidis, K. Kontsas, S. Tzortzis,
G. Pavlidis, A. Sxoinas, D. Kremastinos, M. Anastasiou-Nana, J. Lekakis.
Attikon Hospital, 2nd Department of Cardiology, Medical School, University of
Athens, Athens, GREECE
Objective: Aortic stiffness as an index of subclinical organ damage due to hypertension disease is an important determinant of cardiovascular risk. We aimed to study
WKHORQJWHUPLQÀXHQFHRIVXFFHVVIXOWUHDWPHQWDIWHUDWKUHH\HDUIROORZXSUHJDUGing aortic stiffness improvement from baseline evaluation in recently diagnosed and
never treated middle-aged patients with mild to moderate essential hypertension.
Design and method: We studied 132 non-diabetic, recently diagnosed and nevHUWUHDWHGSDWLHQWVZLWKHVVHQWLDOK\SHUWHQVLRQ PHDQDJH\HDUVPDOHV At baseline, we performed 24h ambulatory blood pressure monitoring (ABPM)
and carotid-femoral artery pulse wave velocity (PWV) in order to evaluate aortic stiffness. After baseline evaluation, all patients started antihypertensive treatPHQW WDUJHWLQJ RI¿FH EORRG SUHVVXUH PP+J$ VHFRQG HYDOXDWLRQ ZDV
SHUIRUPHGDSSUR[LPDWHO\WKUHH\HDUVODWHUUHJDUGLQJRI¿FHEORRGSUHVVXUH %3 ABPM and PWV. We characterized as well controlled patients those patients with
KPHDQV\VWROLFDQGGLDVWROLFEORRGSUHVVXUHDIWHUWUHDWPHQWPP+J
Results: 3:9DIWHUWUHDWPHQWZDVVLJQL¿FDQWO\LQFUHDVHGLQDOOK\SHUWHQVLYHV
(p<0.01) and uncontrolled hypertensives (p<0.001) and it was remained unchanged in controlled hypertensives. PWV was decreased only in controlled
hypertensives with baseline PWV >12.4 m/sec (p=0.004), independently from
the corresponding mean BP decrease.
Conclusions: The present longitudinal study provides substantial evidence that
PWV improvement due to successful antihypertensive treatment by RAAS inhibitors, is depending on increased aortic stiffness at baseline while the magnitude of
PWV decrease is independent from the observed blood pressure decrease.
“3Q WR8LQDRUWDVIURPVKDPJURXSV,Q6$03RYDriectomized group, COX-2 protein expression and the inhibitory effects of celecoxib
were increased. Estradiol supplementation prevented the effects of ovariectomy.
Conclusions: Both ovariectomy and aging increase COX-2 protein expression
and activity, resulting in an increased contraction to TXA2 in aorta from female
senescent mice. Estradiol supplementation reverted the effects of ovariectomy.
2B.06
C. Loue 1, L. Bourguignon 1,2, )*XH\I¿HU2, J. Fauvel 3, M. Ducher 1,3.
Hospices Civils de Lyon, Hôpital Antoine Charial, Service Pharmaceutique,
Francheville, FRANCE, 2 UMR CNRS 5558, Lyon, FRANCE, 3 Hospices Civils
de Lyon, Hôpital E. Herriot, Pavillon P, Lyon, FRANCE
1
Objective: Sudden cardiac death (SCD) incidence - estimated from 50 to 100
SHULQWKHJHQHUDOSRSXODWLRQLQFUHDVHVZLWKDJH(DUO\LGHQWL¿FDWLRQ
of subjects at risk is crucial, implying better knowledge of SCD determinants.
The objective of this study was to identify the main risk factors of the SCD in
the elderly and to estimate their individual risk.
Design and method: From the INDANA database (INdividual Data ANalysis
RI$QWLK\SHUWHQVLYHLQWHUYHQWLRQWULDOV GDWDIURPWKHK\SHUWHQVLYHSDWLHQWV
aged over 70 years were extracted.
Twenty variables were analyzed: history of cardiovascular disease (angina, myocardial infarction, stroke, lower limb claudication), age, smoking, creatininemia,
plasma uric acid, kaliemia, blood glucose, total cholesterolemia, gender, height/
weight, SBP/DBP, HR, diabetes, treatment (previous/current) using a Bayesian
network (Netica® 2.05 software).
Results: 'XULQJDPHDQIROORZXSRI\HDUV>@SDWLHQWV died from SCD. The Kullback–Leibler distance that assesses the strength of dependence between variables revealed that lower limb claudication, age, history
of angina, history of myocardial infarction, smoking and creatininemia were
variables the more related to SCD. The area under the ROC curve of the BayesLDQPRGHOZDV VHQVLWLYLW\VSHFL¿FLW\ 7KHRQVHWRIDQDQWLhypertensive treatment reduced incidence of SCD by 10%. However, previous
RUQHZRQHDQWLK\SHUWHQVLYHWUHDWPHQWGLGQRWLQÀXHQFH6&'LQFLGHQFH
Conclusions: As in younger hypertensive patients, history of cardiovascular disease
DQG&9ULVNIDFWRUVPDLQO\LQÀXHQFHULVNRI6&'LQHOGHUO\+RZHYHURXUDQDO\VLVVXJJHVWVWKDWRQVHWRIK\SHUWHQVLYHWUHDWPHQWRYHU\HDUVGLGQRWLQÀXHQFHULVNRI6&'
2B.07
2B.05
EFFECTS OF NONSTEROIDAL ANTI-INFLAMMATORY
DRUGS AND ESTROGEN SUPPLEMENTATION ON
CONTRACTIONS TO THROMBOXANE A2 IN AORTA
FROM SENESCENCE ACCELERATED MICE
G. Segarra 1, X. Vidal-Gomez 2, D. Perez-Cremades 1, C. Alite 1, A. Dantas 3,
C. Hermenegildo 1,2, P. Medina 1, S. Novella 1,2. 1 Dep. Physiology, Univ.
Valencia, Valencia, SPAIN, 2 INCLIVA Biomedical Research Institute, Valencia,
SPAIN, 3 IDIBAPS and Ins. Clinic Torax, Barcelona, SPAIN
Objective: Suppression of prostacyclin (PGI2) is implicated in the cardiovascular
hazard from inhibitors of cyclooxygenase (COX)-2. Furthermore, estrogen confers vascular protection via COX-2–dependent PGI2, raising the possibility that
COX inhibitors may challenge the protection of endogenous or exogenous estrogens. This study investigates the effects of aging and/or ovariectomy on vascular
UHDFWLYLW\WRWKURPER[DQH$ 7;$ UHFHSWRUVWLPXODWLRQZLWK8DQGWKH
PRGXODWLRQE\&2;VLQDRUWDIURPIHPDOHVHQHVFHQFHDFFHOHUDWHGPLFH 6$03 and from senescence resistant mice (SAMR1), a murine model of aging.
Design and method: )LYHPRQWKVROGIHPDOH6$05 Q DQG6$03 Q were divided into three groups: sham-operated, ovariectomized and ovariectoPL]HGSOXVHVWUDGLROGD\VDIWHUVXUJHU\PLFHZHUHVDFUL¿FHGDQGWKRUDFLFDRUtas were collected. Vascular rings (4 mm long) were mounted for isometric recordLQJRIWHQVLRQLQRUJDQEDWKVDQGFRQFHQWUDWLRQUHVSRQVHFXUYHVIRU8 nM-10 µM) were performed in the absence and in the presence of the COX-1 inhibitor SC-560 (10 nM) and/or COX-2 inhibitor celecoxib (10 µM). A segment of
thoracic aorta from mice of each group was frozen for protein expression studies.
Results: 8 HYRNHG KLJKHU FRQWUDFWLOH UHVSRQVHV LQ DRUWLF VHJPHQWV IURP
6$03 WKDQ 6$05 3 ,Q 6$03 RYDULHFWRP\ LQFUHDVHG FRQWUDFWLOLW\
WR8ZKHUHDVWKHSUHVHQFHRIHVWUDGLROSUHYHQWHGLW&RQWUDFWLOHUHVSRQVHWR
8RIDRUWLFULQJVIURPDOOJURXSVZHUHXQDIIHFWHGE\6& Q0 3! indicating that COX-1 does not modulate the response to TXA2 in aorta from
SAM mice. Celecoxib (10 µM) decreased the sensitivity and maximal contraction
ASSESSMENT OF SUDDEN CARDIAC DEATH RISK
IN ELDERLY HYPERTENSIVE PATIENTS USING
BAYESIAN NETWORK MODELISATION
ACTIVATION OF HYPOXIC CARDIAC STEM CELLS
REVERSING MYOCARDIAL AGING
F. Sanada 1, Y. Taniyama 1,2, Y. Kanbara 1, Y. Ikeda-Iwabe 1, J. Azuma 1,
M. Iwabayashi 1, H. Rakugi 2, R. Morishita 1. 1 Department of Clinical Gene
Therapy, Osaka University Graduate School of Medicine, Suita, JAPAN,
2
Department of Geriatric and Nephrology, Osaka University Graduate School
of Medicine, Suita, JAPAN
Objective: In self-renewing organs, low O2 tension favors stem cell quiescence
while normoxia is required for cell activation. Whether cardiac stem cell (CSC)
function is regulated by O2 content is an important question. A balance between
hypoxic and normoxic CSCs may be present in the young heart but might be
disrupted with aging when defects in tissue oxygenation due to dysfunction of
capillary artery may expand the pool of hypoxic-CSCs, which are no longer
involved in myocyte replacement.
Design and method: Mice at 3, 24, and 30 months of age were used for the analyVLV+\SR[LFPDUNHU3LPRQLGD]ROH+,)ĮDQG&$,;ZHUHH[DPLQHGWRLGHQWLI\
hypoxic-CSCs by immunocytochemistry and FACS. Telomere length and newly
IRUPHGP\RF\WHVZHUHGHWHUPLQHGE\4),6+DQG%UG8VWDLQLQJUHVSHFWLYHO\
Stem cell factor (SCF) was injected directly into myocardium under echo-guide.
Results: Here we show that the senescent heart is characterized by an increased
number of quiescent-CSCs with intact telomeres, while myocyte renewal is conWUROOHGRQO\E\IUHTXHQWO\GLYLGLQJ&6&VZLWKVKRUWHQHGWHORPHUHVWKHVH&6&VJHQerate a myocyte progeny that is chronologically young, but lacks the characteristics
of young cells. Telomere dysfunction dictates their actual age and mechanical behavior. Importantly, the compartment of quiescent, young, CSCs can be stimulated
in situ by SCF as well as 70% hyperoxia, and these protocols promote the formation
of young functionally-competent cardiomyocytes and coronary vessels reversing the
cardiac senescent phenotype. Ventricular dilation is attenuated, wall thickness is inFUHDVHGDQGGLDVWROLFDQGV\VWROLFZDOOVWUHVVDUHVLJQL¿FDQWO\UHGXFHG
Conclusions: Thus, strategies targeting CSCs may interfere with the aging myopathy improving health-span in the elderly.
Abstracts
e20
ORAL SESSION
ORAL SESSION 2C
CEREBROVASCULAR DISEASES AND
COGNITIVE DYSFUNCTION
2C.01
SYSTEMIC CIRCULATION AND CEREBRAL BLOOD
FLOW: THE ROTTERDAM STUDY
S. Sedaghat 1, M. Vernooij 1,2, F. Mattace-Raso 3, A. Hofman 1,
A. Van Der Lugt 2, O. Franco 1, A. Dehghan 1, M. Ikram 1,2,4. 1 Department of
Epidemiology, Erasmus Medical Center, Rotterdam, NETHERLANDS,
2
Department of Radiology, Erasmus University Medical Center, Rotterdam,
NETHERLANDS, 3 Division of Geriatric Medicine, Department of Internal
Medicine, Erasmus Medical Center, Rotterdam, NETHERLANDS,
4
Department of Neurology, Erasmus University Medical Center, Rotterdam,
NETHERLANDS
ine separately the effect of BMI and WHR on each neuropsychological test
while accounting for the above mentioned covariates. Analysis of covariance
was used to compared quintiles of BMI (n=100 in each quintile).
Results: After adjustment for confounders, MMSE (F=3.66, p<0.006), TMTA
) S FORFNWHVW ) S DQGYHUEDOÀXHQF\ ) S ZHUHVLJQL¿FDQWO\DVVRFLDWHGWR%0,$IWHUDGMXVWPHQWIRUWKHDERYH
PHQWLRQHG FRQIRXQGHUV 006( DQG FORFN WHVW ZHUH VLJQL¿FDQWO\ EHWWHU SHUIRUPHGDQG707$VLJQL¿FDQWO\IDVWHUSHUIRUPHGLQWKH¿IWKWKDQLQWKH¿UVW
TXLQWLOHVRI%0,9HUEDOÀXHQF\ZDVVLJQL¿FDQWO\EHWWHULQWKH,9DQG9WKDQLQ
WKH¿UVWTXLQWLOHV )LJXUH 7KHRWKHUWHVWVZHUHQRWDVVRFLDWHGWR%0,:+5
GLGQRWLQÀXHQFHDQ\QHXURSV\FKRORJLFDOWHVWV%3GLGQRWHQWHUDQ\PRGHOV
Objective: The brain is a metabolically demanding organ and dependent on a
FRQVWDQWDQGDGHTXDWHDPRXQWRIEORRGÀRZ'HVSLWHVWULQJHQWDXWRUHJXODWLRQ
DOWHUDWLRQVLQWKHV\VWHPLFFLUFXODWLRQKDYHEHHQVXJJHVWHGWRLQÀXHQFHFHUHEUDO
EORRGÀRZ:HLQYHVWLJDWHGWKHDVVRFLDWLRQRIWKUHHPHDVXUHVRIV\VWHPLFFLUculation, including cardiac function, vascular stiffness and renal function with
FHUHEUDOEORRGÀRZ
Design and method: )URPWRZHLQFOXGHGSDUWLFLSDQWVZLWK
mean age of 56.7 years (44% men) from the population based Rotterdam
Study. Fractional shortening and left ventricular volume from cardiac echocardiography were used to evaluate cardiac function. Pulse pressure and pulse
wave velocity were used as indicators of arterial stiffness. Renal function was
DVVHVVHG E\ HVWLPDWHG JORPHUXODU ¿OWUDWLRQ UDWH H*)5 DQG DOEXPLQ FUHDWLnine ratio. Phase-contrast magnetic resonance imaging of basilar and carotid
DUWHULHV ZDV SHUIRUPHG WR PHDVXUH WRWDO FHUHEUDO EORRG ÀRZ7R VWDQGDUGL]H
WKHFHUHEUDOEORRGÀRZYDOXHVWKH\ZHUHGLYLGHGE\HDFKLQGLYLGXDO¶VEUDLQ
volume (mL).
Results: ,QDJHDQGVH[DGMXVWHGPRGHOKLJKHUSXOVHSUHVVXUH %HWD
&RQ¿GHQFHLQWHUYDO &, ORZHUH*)5 %HWD&,
DQG KLJKHU DOEXPLQ FUHDWLQLQH UDWLR %HWD &, ZHUHDVVRFLDWHGZLWKORZHUOHYHOVRIFHUHEUDOEORRGÀRZ)XUWKHUDGMXVWPHQWVIRU
cardiovascular risk factors did not essentially change the association. There was
QRDVVRFLDWLRQEHWZHHQPHDVXUHVRIFDUGLDFIXQFWLRQDQGFHUHEUDOEORRGÀRZ
Conclusions: Vascular stiffness and impaired renal function are associated with
ORZHUFHUHEUDOEORRGÀRZ7KLVVXJJHVWVWKDWUHJXODWLRQRIFHUHEUDOEORRGÀRZ
FDQEHLQÀXHQFHGQRWRQO\E\WKHEUDLQYHVVHOVEXWDOVRE\V\VWHPLFFLUFXODWLRQ
2C.02
HIGH BODY MASS INDEX IS ASSOCIATE TO BETTER
COGNITIVE FUNCTION AT A POPULATION LEVEL
V. Tikhonoff 1, N. Giordano 1, F. Guidotti 1, A. Bascelli 2, G. Boschetti 1,
S. Crociani 1, A. Mazza 3, P. Palatini 1, E. Casiglia 1. 1 Department of Medicine,
University of Padua, Padua, ITALY, 282$FFHWWD]LRQHH3LDQL¿FD]LRQH
Attività Assistenziale, Polo Unico Ospedaliero Alto Vicentino, Vicenza, ITALY, 3
Department of Internal Medicine, Hospital of Rovigo, Rovigo, ITALY
Objective: To ascertain whether body adiposity, measured through body mass
index (BMI) and waist-hip ratio (WHR), is associated to cognitive function.
Design and method: Five-hundred and one unselected participants (mean
DJH“\HDUVZRPHQ UHSUHVHQWDWLYHRIJHQHUDOSRSXODWLRQZHUH
taken into consideration in the frame of the Growing Old with Less Disease
Enhancing Neurofunctions (GOLDEN) study performed in 4 little towns of
Norhern Italy. Mini mental state examination (MMSE), trail making test A
707$ FORFNWHVWYHUEDOÀXHQF\WHVWVWUDLOPDNLQJWHVW%PHPRU\ZLWK
interference at 10 and 30 seconds, and prose memory were performed in
all subjects. Anthropometrics (BMI and WHR), systolic and diastolic blood
pressure (BP), pulse heart rate, pulse wave velocity, history of diabetes,
education attainment and plasma serum levels of lipids, glucose, uric acid
and leptin were detected. Multivariable linear regression was used to exam-
Conclusions: Apart from its negative effects on metabolism, BP and cardiovascular events, high BMI is favourable in terms of neuropsychological performance, at least limitedly to attention, executive functions and language. The
reasons of this association can only be speculative. Higher adrenergic activation
present (also deriving from higher leptin, higher glucose and caloric intake) is a
potential cognitive enhancer, particularly for learning and memory.
2C.03
PULSE PRESSURE AS PREDICTOR OF OUTCOME IN
ISCHEMIC STROKE PATIENTS
L. Brescacin, C. Alonzo, M. Zurru, S. Pigretti, L. Camera, E. Cristiano,
G. Waisman. Hospital Italiano de Buenos Aires, Buenos Aires, ARGENTINA
Objective: High pulse pressure (PP), associated with vascular stiffening of the
large arteries, increases pulsatile stress leading to small vessels damage and vascular morbimortality. Our objective was to evaluate the relationship between
elevated PP in the year before the event and stroke outcomes, as well to assess
the incremental value of PP over SBP as a potential predictor of bad outcome.
Design and method: Acute ischemic stroke patients were prospectively included in a multidisciplinary secondary stroke prevention program. Pre-stroke
YDVFXODUULVNIDFWRUSUR¿OHDQGFRQWUROZHUHREWDLQHGIURPHOHFWURQLFPHGLFDOUHFRUGV)XQFWLRQDORXWFRPHZDVGHWHUPLQHGDFFRUGLQJWRPRGL¿HG5DQNLQVFDOH
one month after stroke (> 1= disability), and mortality and recurrence were evalXDWHGDIWHU“ PHGLDQ GD\VRIIROORZXS2XWFRPHVZHUHDQDO\]HG
according to pre-stroke PP values (over and below 60 mmHg) in the univariate
analysis and a logistical regression model.
Results: SDWLHQWV IHPDOHVPHDQDJH“\HDUV ZHUHLQFOXGHG
from December 2006 to April 2013. Patients with PP > 60 mmHg (n 455, 42%)
were older, had higher SBP and fasting glucose, lower e-GFR and higher inciGHQFHRI72' /9+DQG&.' WKH\DOVRUHFHLYHGPRUHDQWLSODWHOHWVDQGDQWLhypertensive drugs, mainly diuretics and CCB (table). We found no difference in
PRUWDOLW\ YVS EXWVWURNHUHFXUUHQFHZDVKLJKHU YVS
0.05) and more patients had worse functional outcome (64% vs 56%, p 0.01) in
the group with PP > 60 mmHg.
S
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e21
Journal of Hypertension Volume 32, e-Supplement 1, 2014
FHUHEUDOEORRGÀRZVHFRQGDU\WRDSQHDLQGXFHGEORRGSUHVVXUHVZLQJV1RQHWKHOHVVLQWUDFUDQLDOSUHVVXUHÀXFWXDWLRQVGXULQJDSQHDVPD\GHWHULRUDWHFHUHEUDO
hemodynamics instability which conceivably may translate to higher cerebrovascular events risk.
2C.05
ELEVATED CENTRAL PULSE PRESSURE AND
MILD COGNITIVE IMPAIRMENT INCIDENCE IN
HYPERTENSIVE PATIENTS
T. Yaneva-Sirakova 1, R. Tarnovska-Kadreva 1, L. Traykov 2. 1 Medical
8QLYHUVLW\6R¿D'HSDUWPHQWRI,QWHUQDO0HGLFLQH&DUGLRORJ\&OLQLF6R¿D
BULGARIA, 20HGLFDO8QLYHUVLW\6R¿D'HSDUWPHQWRI1HXURORJ\6R¿D
BULGARIA
Objective: There is correlation between brachial pulse pressure and mild cognitive impairment. Central aortic pressure may be a better predictor for target
RUJDQGDPDJHDQGPD\GH¿QHPRUHSUHFLVHO\WKHULVNIRUFRJQLWLYHLPSDLUPHQW
than the brachial pressure. We tested the hypothesis weather elevated central
pulse pressure is a risk factor for mild cognitive impairment in hypertensive
patients (Pts), who receive combination medical therapy.
Conclusions: In our cohort PP was an independent predictor of post-stroke disability. This hemodynamic variable should be considered by practitioners, along
with other traditional risk factors, in treatment strategies after stroke.
2C.04
BIPHASIC PIAL ARTERY AND SUBARACHNOID WIDTH
RESPONSE TO SHORT APNEA IN NORMOTENSIVE
SUBJECTS
Design and method: 70 hypertensive Pts were included in the study. The mean
DJH ZDV “ \HDUV ZHUH PDOHV DQG IHPDOHV
They underwent complete anamnesis and physical examination, registration of
home-measured blood pressure, basic laboratory testing, instrumental evaluaWLRQRI¿FHEORRGSUHVVXUHFHQWUDODRUWLFSUHVVXUHDPEXODWRU\EORRGSUHVVXUH
monitoring and echocardiography. The screening for mild cognitive impairment
was conducted via Mini Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA). Other tests were used as well: Hachinski ischemic
score, Geriatric Depression Scale and the Four Instrumental Activities of Daily
Living Score. We used descriptive statistics, correlation analysis and t-test, deSHQGLQJRQWKHVSHFL¿FTXHVWLRQ
M. Wszedybyl-Winklewska 1, J. Wolf 2,3, E. Swierblewska 2, K. Kunicka 2,
P. Winklewski 1, A. Frydrychowski 1, L. Bieniaszewski 2, K. Narkiewicz 2,3.
1
Institute of Human Physiology, Medical University of Gdansk, Gdansk,
POLAND, 2 Department of Hypertension and Diabetology, Medical
University of Gdansk, Gdansk, POLAND, 3 Dept. of Cardiovascular Diseases,
International Clinical Research Center, St. Annes University Hospital in Brno,
FNUSA, Brno, CZECH REPUBLIC
Results: The mean central pulse pressure values of patients with cognitive imSDLUPHQWZHUHVLJQL¿FDQWO\ S KLJKHUWKDQWKRVHRIWKH3WVZLWKRXWFRJnitive impairment. The group of Pts with central pulse pressure above 40 mmHg
KDGVWDWLVWLFDOO\VLJQL¿FDQW S ORZHUPHDQQHXURSV\FKRORJLFDOWHVWV¶UHsults than the group with central pulse pressure below 40 mmHg. There was a
weak negative correlation between central pulse pressure and the results from
0R&$DQG006( U S DQGU S UHVSHFWLYHO\ Objective: The patomechanism explaining higher cerebrovascular complications
rate in sleep apnea is not fully understood, and goes beyond elevated average
blood pressure values.
Recently developed method based on near-infrared transillumination/backscattering sounding (NIR-T/BSS) allows to non-invasively measure the changes in pial
artery pulsation (cc-TQ) as well as the subarachnoid width (sas-TQ) in humans. It
has been just recently demonstrated that cc-TQ and sas-TQ translate to pial artery
FRPSOLDQFHDQGLQWUDFUDQLDOSUHVVXUH ,&3 ÀXFWXDWLRQVUHVSHFWLYHO\
Apnea-induced hypercapnia, hypoxia and related changes in the heart rate (HR),
EORRGSUHVVXUHDQGFHUHEUDOEORRGÀRZYHORFLW\ &%)9 DIIHFWEUDLQPLFURFLUFXODtion and ICP.
Therefore, we tested the complex response of pial artery and subarachnoid width
to apneas using novel NIR-T/BSS method.
Conclusions: Central pulse pressure is correlated with cognitive impairment in
hypertensive Pts: the higher the central pulse pressure, the more impaired is cognitive functioning. Central pulse pressure may become a new treatment target in
hypertensive Pts with clinically manifested target organ damage.
Design and method: The pial artery and subarachnoid width response to 30
VHFRQGVDSQRHDZDVVWXGLHGLQKHDOWK\YROXQWHHUV DJH“%0,
“ FF74DQGVDV74ZHUHPHDVXUHGXVLQJ1,57%66&%)9SXOVDWLOLW\
index (PI) and resistive index (RI) were measured using Doppler ultrasound in
WKHOHIWLQWHUQDOFDURWLGDUWHU\V\VWROLFDQGGLDVWROLFEORRGSUHVVXUH 6%3DQG
DBP, respectively) and HR were recorded using Finometer, while end-tidal CO2
was measured using medical gas analyser.
Results: 30 sec. apneas evoked biphasic response with initial SDP decrease associated with cc-TQ and sas-TQ increase followed by SBP increase associated with
FF74DQGVDV74UHWXUQWREDVHOLQH WDEOH (QGWLGDO&2ZDVKLJKHUGXULQJ¿UVW
H[SLUDWLRQDIWHUDSQHDFRPSDULQJWREDVHOLQH “S ,QWKHHQG
of apnea change in sas-TQ was associated with increase in SBP (r=0.74, P<0.01).
Conclusions: A biphasic response of the pial artery aims at the stabilization of
2C.06
ACUTE-PHASE BLOOD PRESSURE VARIABILITY AND
SHORT-TERM OUTCOME IN PATIENTS HOSPITALIZED
FOR ISCHEMIC STROKE
K. Tziomalos, S. Bouziana, M. Spanou, M. Papadopoulou, V. Giampatzis,
V. Dourliou, P. Kazantzidou, S. Kostaki, C. Savopoulos, A. Hatzitolios. First
Propedeutic Department of Internal Medicine, Medical School, Aristotle
University of Thessaloniki, AHEPA Hospital, Thessaloniki, GREECE
Objective: Recent data suggest that increased visit-to-visit variability in blood
pressure (BP) is associated with increased risk for stroke in the general population. On the other hand, contradictory results have been reported regarding the
prognostic role of BP during the acute phase of ischemic stroke. We aimed to
evaluate the association between BP variability and in-hospital outcome in this
population.
Design and method: :HSURVSHFWLYHO\VWXGLHGFRQVHFXWLYHSDWLHQWV PDOHV DJH “ \HDUV ZKR ZHUH KRVSLWDOL]HG IRU DFXWH LVFKHPLF VWURNH
Stroke severity was assessed with the National Institutes of Health Stroke Scale
1,+66 RQ DGPLVVLRQ7KH RXWFRPH ZDV DVVHVVHG ZLWK WKH PRGL¿HG 5DQNLQ
scale (mRS) and dependency rates at discharge (i.e. mRS 2-5) and with in-hospital mortality rates. Variability in BP was assessed with the standard deviation
6' DQGZLWKWKHFRHI¿FLHQWRIYDULDWLRQ GH¿QHGDVPHDQ6' RIV\VWROLFDQG
GLDVWROLF%3PHDVXUHPHQWVLQWKH¿UVWDQGLQWKH¿UVWGD\VRIKRVSLWDOL]DWLRQ
Results: At discharge, the mRS did not correlate with any of the indices of BP
variability. Patients who were dependent at discharge did not differ from patients
who were independent in any of the indices of BP variability. Patients who died
during hospitalization also did not differ in any of the indices of BP variability
from patients who were discharged. In contrast, patients who died during hospitalization had higher diastolic BP (DBP) on admission compared with those
ZKRZHUHGLVFKDUJHG “YV“PP+JUHVSHFWLYHO\S ,QELnary logistic regression analysis, independent predictors of in-hospital mortality
e22
Journal of Hypertension Volume 32, e-Supplement 1, 2014
ZHUHWKH1,+66RQDGPLVVLRQ UHODWLYHULVN 55 FRQ¿GHQFHLQWHUYDO
&, S DQG'%3RQDGPLVVLRQ 55&,
p<0.001).
Conclusions: Variability in either systolic or diastolic BP during the acute phase
of stroke does not appear to have predictive value additional to that of BP measurement on admission.
2C.07
INCREASED PULSE PRESSURE IS RELATED TO
HIGHER BURDEN OF MICROVASCULAR BRAIN
DAMAGE IN ISCHEMIC STROKE PATIENTS
C. Alonzo, L. Brescacin, M. Zurru, A. Luzzi, L. Camera, E. Cristiano,
G. Waisman. Hospital Italiano de Buenos Aires, Buenos Aires, ARGENTINA
Objective: Pulse pressure (PP), a marker of arterial stiffness, is a useful tool
for measuring vascular aging. White matter hyperintensities (WMH) and microbleeds (MB) are the expression of subclinical ischemic brain damage. Our
objective was to evaluate the relationship between elevated PP and the burden of
WMH and MB in a cohort of ischemic stroke patients.
Design and method: Acute ischemic stroke patients were prospectively included in a multidisciplinary secondary stroke prevention program. Pre-stroke
YDVFXODUULVNIDFWRUSUR¿OHDQGFRQWUROZHUHREWDLQHGIURPHOHFWURQLFPHGLFDO
records and the presence of MB and WMH was evaluated on admission MRI.
WMH (periventricular –PVH- and deep white matter hyperintensities –DWMHZHUHFODVVL¿HGDFFRUGLQJWR)D]HNDVVFDOH DQG0%LQIRXUJURXSVDFFRUGing to the number of lesions: 0 (0 MB), 1 (1-5 MB), 2 (6-10 MB), 3 (> 10 MB).
Results: SDWLHQWV IHPDOHVPHDQDJH“\HDUV ZHUHLQFOXGHGEHWZHHQ-DQXDU\DQG$SULO7KHUHZDVDGLUHFWUHODWLRQVKLSEHWZHHQ33
values and the severity of chronic microvascular lesions. (table)
Objective: Numerous studies have demonstrated the existence of a relationship
between echogenicity of carotid plaque and cerebral ischemic events, both silent
and clinically manifested. These, in turn, expose the patient to increased risk
of developing cognitive impairment and dementia in advanced age. Based on
WKLVVFLHQWL¿FHYLGHQFHZHGHFLGHGWRLQYHVWLJDWHWKHUHODWLRQVKLSEHWZHHQHFKRgenicity of carotid plaques and cognitive performance in patients with carotid
atheromatous plaques but no history of cerebrovascular events and/or clinical
evidence for dementia.
Design and method: :HVWXGLHGSDWLHQWVDJHG\HDUVRUPRUH “
years) from our angiology unit. At enrolment, patients underwent ultrasonograSK\RIWKHQHFNYHVVHOVXVLQJD0+]OLQHDUSUREHLPDJHVZHUHVWRUHGRQ
magneto-optical disk and subsequently used to calculate the grey scale median
(GSM) using Adobe Photoshop 5.0. The calculation of the GSM was performed
by researchers blinded to the clinical characteristics of patients. All participants
were also subjected to the study of cognitive function by Mini Mental State ExDPLQDWLRQ 006( 7UDLO0DNLQJ7HVW 707 $DQG%DQGYHUEDOÀXHQF\WHVW
(VFT). The results of psychometric tests were logarithmically transformed and
used to calculate a composite cognitive score.
Results: Patients were divided into two groups according to echolucency of
carotid plaques using as a discriminating factor the median GSM obtained in the
VWXG\ SRSXODWLRQ “ YV “ UHVSHFWLYHO\ S &RJQLWLYH
performance was on average worse in patients with more plaque echolucency
006( “ YV “ S QV 707$ “ YV “ S707%“YV“S9)7“YV
“S]VFRUH“YV“S &RQVLGHULQJ
the study population as a whole, we observed a direct correlation between GSM
and cognitive performance (r: 0.460, p<0.001).
Conclusions: The results of our study demonstrate the existence of an inverse
relationship between echolucency of carotid plaques and cognitive function in
the elderly and suggest the possible use of this method to identify subjects at
increased risk of developing dementia.
2C.09
LOW MEAN BLOOD PRESSURE DURING THE ACUTE
PERIOD OF ISCHEMIC STROKE IS ASSOCIATED WITH
DECREASED SURVIVAL
P. Wohlfahrt 1, A. Krajcoviechova 1, M. Jozifova 1, O. Mayer 2, J. Vanek 2,
J. Filipovsky 2, R. Cifkovà 1. 1 Center for Cardiovascular Prevention of
the First Faculty of Medicine, Charles University and Thomayer Hospital,
Prague, CZECH REPUBLIC, 2 2nd Department of Internal Medicine, Charles
University, Center for Hypertension, Pilsen, CZECH REPUBLIC
Objective: Because studies on the relation between blood pressure (BP) in the
acute phase of stroke and stroke outcome have shown contradicting results, there
is no agreement on optimal BP level during the acute phase of stroke. The purpose of this study was to compare the relationship between admission, maximal
DQGGLVFKDUJH%3DQGLWVFRPSRQHQWVGXULQJWKHKRVSLWDOL]DWLRQIRUWKH¿UVWDFXWH
ischemic stroke and total mortality.
Conclusions: Different blood pressure components may have different effects
RQODUJHDQGVPDOOYHVVHOV3XOVHSUHVVXUHDSXOVDWLOHFRPSRQHQWPDLQO\UHÀHFWLQJODUJHDUWHU\VWLIIQHVVDQGZDYHUHÀHFWLRQVKDVDGLUHFWUHODWLRQVKLSZLWKWKH
burden of WMH and MB. As the world is aging, is mandatory to identify predictors of subclinical brain damage, which is related to increased risk of dementia,
depression, stroke and gait disorders.
2C.08
ENHANCED CAROTID PLAQUE ECHOLUCENCY
IS ASSOCIATED WITH WORSE COGNITIVE
PERFORMANCE IN ELDERLY PATIENTS WITH
ATHEROSCLEROTIC DISEASE
D. Mastroiacovo 1,3, D. Grassi 2, M. Pinelli 3, G. De Blasis 4, G. Turco 4,
A. Camerota 1,2, M. Andriulli 1, F. Cipollone 5, C. Marini 1, C. Ferri 1,
G. Desideri 1,2. 1 Geriatric Division, S.S. Filippo e Nicola Hospital, Avezzano,
L’Aquila, ITALY, 2 Department of Life, Health and Environmental Sciences,
University of L’Aquila, L’Aquila, ITALY, 3 Angiology Unit, S.S. Filippo e Nicola
Hospital, Avezzano, L’Aquila, ITALY, 4 Vascular Surgery Unit, S.S. Filippo e
Nicola Hospital, Avezzano, L’Aquila, ITALY, 5 Center of Excellence on Aging
(Ce.S.I.), G. D’Annunzio University, Chieti, ITALY
Design and method: ,QFRQVHFXWLYHSDWLHQWV PHDQDJH“\HDUV
RIPHQ KRVSLWDOL]HGIRUWKHLU¿UVWHYHULVFKHPLFVWURNHWKHDVVRFLDWLRQEHWZHHQ
e23
Journal of Hypertension Volume 32, e-Supplement 1, 2014
%3 DQG WRWDO PRUWDOLW\ GXULQJ D PHGLDQ IROORZXS RI ZHHNV ,45 weeks) was analyzed.
Results: In multivariate analysis, both admission mean blood pressure (MBP)
and discharge systolic blood pressure (SBP) quartiles were independent predictors of mortality and outperformed other parameters of BP. After multivariate
adjustments, patients with admission MBP <100 mmHg had a higher risk of
death than subjects with MBP between 100-110 mmHg and 110-121 mmHg,
while the risk of mortality did not differ from the group with admission MBP
>122 mmHg. Similarly, subjects with discharge SBP <120 mmHg had an increased risk of death as compared to groups with SBP between 120-130 mmHg
and 130-141 mmHg, while the risk of death was similar to that with discharge
SBP >141 mmHg.
Conclusions: $PRQJSDWLHQWVKRVSLWDOL]HGIRUWKHLU¿UVWHYHULVFKHPLFVWURNH
WKH ULVN RI DOOFDXVH GHDWK LV VLJQL¿FDQWO\ LQFUHDVHG LQ WKRVH ZLWK DGPLVVLRQ
MBP <100 mmHg and discharge SBP <120 mmHg, even after adjustments for
other confounders.
Abstracts
e24
ORAL SESSION
ORAL SESSION 2D
CLINICAL TRIALS
2D.01
ORTHOSTATIC HYPERTENSION IS ASSOCIATED WITH
INCREASED CARDIOVASCULAR AND ALL CAUSE
MORTALITY IN PATIENTS WITH ISOLATED SYSTOLIC
HYPERTENSION
J.B. Kostis 1, J. Sedjro 1, W. Kostis 2, J. Cabrera 3, S. Pressel 4, N. Cosgrove 1,
B. Davis 4. 1 Rutgers Robert Wood Johnson Medical School, New Brunswick,
NJ, USA, 2 Massachusetts General Hospital, Boston, MA, USA, 3 Rutgers
University, Piscataway, NJ, USA, 4 University of Texas Health Sciences,
Houston, TX, USA
Objective: To examine the relationship of an increase in systolic blood pressure
(SBP) upon standing to 17 year mortality in the Systolic Hypertension in the
Elderly Program (SHEP).
Design and method: We examined the relationship between orthostatic hypertension (oHYPER) with cardiovascular (CV) and all-cause mortality in the
randomized double blind placebo controlled SHEP. Orthostatic change data,
after standing 1 minute, were collected at baseline visit. Of the 3142 participants who did not cross over from placebo to active therapy or vice versa, 7 did
not have data on orthostatic change, 102 had oHYPER (SBP increase by >15
PP+J KDGDQRUPDOUHVSRQVH GHFUHDVHE\PP+JR1250 DQG
KDGRUWKRVWDWLFK\SRWHQVLRQ GHFUHDVHE\ !PP+JR+<32 7KH
participants with SBP change ranging between 15 mmHg increase and 4 mmHg
GHFUHDVHGLGQRWEHORQJWRDQ\RIWKHFDWHJRULHVGH¿QHGDERYHDQGZHUHQRW
included in this analysis.
Results: Higher rate of CV death was observed in the oHYPER group compared
to the oNORM group in both unadjusted analysis and in analysis adjusted for
gender, age, serum creatinine, body mass index, diabetes, smoking, left ventricular failure, high density lipoprotein cholesterol and seated SBP at baseline
(table).
1
Morinomiya University of Medical Sciences, Osaka, JAPAN, 2 Keio
University, Tokyo, JAPAN, 3 Osaka University Graduate School of Medicine,
Osaka, JAPAN, 4 Sapporo Medical University, Sapporo, JAPAN, 5 Dokkyo
Medical University, Tochigi, JAPAN, 6 Kanazawa University Hospital,
Ishikawa, JAPAN, 7 Ehime University Graduate School of Medicine, Ehime,
JAPAN, 8 Tohoku University Graduate School of Medicine, Miyagi, JAPAN, 9
Shin-Oyama City Hospital, Tochigi, JAPAN
Objective: The aim of this subgroup analysis of the COLM trial is to compare
the cardiovascular effects and safety of two combinations, i.e., an ARB olmesartan (OLM) combined with a dihydropyridine CCB or a diuretic in elderly (65\R DQGYHU\HOGHUO\ \R -DSDQHVHKLJKULVNK\SHUWHQVLYHSDWLHQWV
Design and method: +\SHUWHQVLYHSDWLHQWVDJHG!WR\HDUVZLWKDKLVWRU\
of and/or risk factors for cardiovascular disease were randomized to receive olmesartan with either a CCB (amlodipine or azelnidipine) or a low dose thiazide
IRUDWOHDVW\HDUV7KHWDUJHW%3ZDVPP+J7KHSULPDU\HQGSRLQW
was a composite of fatal and non-fatal cardiovascular events. [Clinical Trials.
gov. number NCT00454662]. In this subgroup analysis we evaluated the reVXOWVDFFRUGLQJWRDJHHOGHUO\DJHJURXS \RQ RUYHU\HOGHUO\DJH
JURXS \RQ Results: Average BP at entry and the end of the trial did not differ between
the two treatment groups in either age group. For the primary endpoint, the
UHVSHFWLYH KD]DUG UDWLR &, LQ WKH HOGHUO\ DJH JURXS DQG LQ WKH YHU\ HOGHUO\ DJH JURXS ZHUH 2/0&&% YV 2/0GLXUHWLF S DQG S LQWHUDFWLRQS 7KHKD]DUGUDWLRIRUVWURNH
2/0&&% YV 2/0GLXUHWLF ZDV S DQG S LQWHUDFWLRQS LQWKHHOGHUO\JURXSDQGLQWKHYHU\HOGHUO\
group, respectively. The rates of withdrawal from the trial were higher and the
incidence of adverse events were more frequent in the OLM-diuretic group than
in the OLM-CCB group in both age groups.
Conclusions: For the reduction of stroke risk, ARB and CCB combination may
be preferable to ARB and diuretic combination in elderly hypertensives, particularly those aged 75 years and older.
2D.03
DIFFERENTIAL EFFECTS OF ANTIHYPERTENSIVE
DRUGS ON CENTRAL BLOOD PRESSURES IN BLACK
HYPERTENSIVE PATIENTS LIVING IN SUB-SAHARAN
AFRICA: INSIGHT FROM NOAAH STUDY
D. Lemogoum 1, L. Jacobs 2, B. Anisiuba 3, M. Kamdem 1, J. Kaptue 1,
B. Ezeala-Adikaibe 3, L. Thijs 2, ,8ODVL3, J. Staessen 2,
J. M’Buyamba-Kabangu 4. 1 Department of Clinical Sciences, Douala
School of Medicine, University of Douala, Douala, CAMEROON, 2 Study
Coordinating Centre, KU Leuven Department of Cardiovascular Sciences,
University of Leuven, Leuven, BELGIUM, 3 Department of Medicine, College
of Medicine, University of Nigeria Teaching Hospital, Enugu, NIGERIA, 4
Hypertension Unit, Department of Internal Medicine, University of Kinshasa
Hospital, Kinshasa, CONGO (DRC)
The effects of high CV death in the oHYPER group compared to oHYPO were
more pronounced (table). Also, compared to oNORM, the effects were more pronounced among oHYPER participants who increased their SBP upon standing, but
DOVRSDUDGR[LFDOO\LQFUHDVHGWKHLUKHDUWUDWHXSRQVWDQGLQJDVZHOO +5
&,S 6LPLODU¿QGLQJVZHUHREVHUYHGIRUDOOFDXVHPRUWDOLW\
Conclusions: Orthostatic hypertension is associated with increased CV and
all-cause mortality in older persons with isolated systolic hypertension. This
effect may be mediated through autonomic dysregulation, vascular aging and
increased arterial stiffness.
2D.02
COMBINATION THERAPY FOR ELDERLY
HYPERTENSION: A SUB-ANALYSIS OF COMBINATION
OF OLMESARTAN AND CALCIUM CHANNEL
BLOCKER OR DIURETIC IN THE ELDERLY
HYPERTENSION (COLM) TRIAL
T. Ogihara 1, T. Saruta 2, H. Rakugi 3, I. Saito 2, K. Shimamoto 4, H. Matsuoka 5,
S. Teramukai 6, J. Higaki 7, S. Ito , K. Shimada , for the Colm Investigator.
Objective: Emerging evidence from clinical trial in Caucasian patients indicates that various classes of blood pressure (BP)-lowering drugs can have different impacts on central aortic pressures despite similar effects on peripheral
BP. However, there are no studies in black hypertensive patients born and
living in sub-Saharan Africa (SSA). To meet the challenge, the Newer versus
Older Antihypertensive agents in African Hypertensive patients (NOAAH)
trial ancillary study on arterial properties was designed to compare the ef¿FDF\RIVLQJOHSLOOFRPELQDWLRQVRI$PORGLSLQH9DOVDUWDQ PJ DQG
Bisoprolol-Hydrochlorothiazide (5/6.25mg) drugs on central aortic pressures
in black patients.
Design and method: NOAAH trial was an open, propective, randomized, investigator-led multicenter study implemented in six SSA centers from which
WZR 'RXDOD&DPHURRQDQG(QXJX1LJHULD WRRNSDUWLQWKLVDQFLOODU\VWXG\
RIUDQGRPL]HG12$$+VWXG\SDUWLFLSDQWV SHUGUXJDUP DJHG±
\HDUV ZLWK XQFRPSOLFDWHG K\SHUWHQVLRQ ±± PP+J HQWHUHG WKH
substudy. Central aortic pressures, systolic augmentation, and augmentation inGH[ $,[ D PHDVXUH RI ZDYH UHÀHFWLRQV ZHUH GHULYHG IURP FHQWUDO SUHVVXUH
ZDIRUPVXVLQJDSSODQDWLRQWRQRPHWU\ 6SK\JPR&RU DWLQFOXVLRQDIWHUDQG
16 weeks of treatment.
S
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S
e25
Journal of Hypertension Volume 32, e-Supplement 1, 2014
Results: At randomization age, sex, BP, AIx, and heart rate (HR) were comparable in both regimens (all p>0.05). Despite similar changes in brachial BP
between treatment groups, there were substantial reductions in aortic pressures
with Amlodipine-Valsartan compared to Bisoprolol-Hydrochlorothiazide regiPHQ DRUWLF V\VWROLF DXJPHQWDWLRQ ¨ PP+J &, WR 3 DRUWLFV\VWROLFSUHVVXUH ¨ PP+J&,WR3 DRUWLFSXOVHSUHVVXUH PHDQFKDQJHV “PP+JYV“PP+J
3 &HQWUDODRUWLF$,[VWDQGDUGLVHGIRU+5PDUNHGO\GHFUHDVHGLQ$PORGLSLQH9DOVDUWDQFRPELQDWLRQZKHUHDVLWLQFUHDVHGVLJQL¿FDQWO\LQ%LVRSURORO+\GURFKORURWKLD]LGHUHJLPHQPHDQFKDQJHV “YV“
3 0RUHRYHUSXOVHSUHVVXUHDPSOL¿FDWLRQZDVJUHDWHULQ$PORGLSLQH
9DOVDUWDQDUPWKDQLQ%LVRSURORO+\GURFKORURWKLD]LGHUHJLPHQ S Conclusions: In native black hypertensive patients living in SSA, AmlodipineValsartan regimen decreases central systolic pressures, and augmentation index
DQG LQFUHDVHV SXOVH SUHVVXUH DPSOL¿FDWLRQ PRUH HIIHFWLYHO\ WKDQ %LVRSURORO
Hydrochlorothiazide combination.
2D.04
RANDOMISED EVALUATION OF A NOVEL, FIXEDDOSE COMBINATION OF PERINDOPRIL 3.5 MG/
AMLODIPINE 2.5 MG AS A FIRST-STEP TREATMENT
IN HYPERTENSION
S. Laurent 1, I. Chazova 2, Y. Sirenko 3, A. Erglis 4, A. Laucevicius 5, C. Farsang 6.
Departement of Pharmacology, European Georges Pompidou Hospital, Paris,
FRANCE, 2 Ministry of Health of Russian Federation, Moscow, RUSSIA,
3
1DWLRQDO6FLHQWL¿F&HQWHU6WUD]KHVNR,QVWLWXWHRI&DUGLRORJ\.LHY
UKRAINE, 4 Pauls Stradins Clinical University Hospital, Riga, LATVIA,
5
University Hospital Santariskiu Clinics, Vilnius, LITHUANIA, 6 Semmelweis
University, Budapest, HUNGARY
GLDEHWHV GLDEHWHV PHOOLWXV PLFURDOEXPLQXULD FKURQLF UHQDO GLVHDVH OHIW YHQWULFXODU K\SHUWURSK\ LVFKHPLF
KHDUWGLVHDVH FKURQLFKHDUWIDLOXUH DQGNQRZQSHULSKHUDODUtery disease (17.6%). Reasons for the prescription of PI were: large oscillations
LQ%3 XQFRQWUROOHG%3 RUVLGHHIIHFWVRISUHYLRXVWUHDWPHQW
2%3GHFUHDVHGIURPPP+JWRPP+J DYHUDJHV\VWROLF
GLDVWROLF%3UHVSHFWLYHO\ :LWK$%30KRXUDYHUDJH%3GHFUHDVHGE\
PP+J 3 3ODVPDOHYHOVRIWRWDOFKROHVWHUROGHFUHDVHGE\PPRO/
/'/FE\PPRO/WULJO\FHULGHVE\PPRO/DQGIDVWLQJEORRGJOXFRVHE\PPRO/ZKLOHOHYHOVRIXULFDFLG1D.FUHDWLQLQH+'/FDQG
WULJO\FHULGHVGLGQRWFKDQJHVLJQL¿FDQWO\3UHYLRXVXVHRIQHELYRORO IURP
WR DQGFDUYHGLORO IURPWR LQFUHDVHGZKLOHWKDWRIPHWRSURORO IURP WR IXURVHPLGH IURP WR DQG +&7=
IURPWR GHFUHDVHGVLJQL¿FDQWO\3UHYLRXV$&(LQKLELWRUVRU$5%V
ZHUHUHSODFHGE\SHULQGRSULO8VHRIVWDWLQV YV ¿EUDWHV YV RUDO DQWLGLDEHWLFV YV RU LQVXOLQ YV GLG
not change.
Conclusions: 6ZLWFKLQJ IURP SUHYLRXV DQWLK\SHUWHQVLYH WKHUDS\ WR WKH ¿[HG
combination of perindopril 10 mg/indapamide 2.5 mg was successful and safe
LQWKHVHHOGHUO\SDWLHQWVZLWKSUHYLRXVVWURNHRU7,$7KHREVHUYHGEHQH¿FLDO
changes in metabolic parameters can be explained by the cessation of previous
GUXJVZLWKXQZDQWHGPHWDEROLFVLGHHIIHFWV ȕEORFNHUV+&7= DQGE\PRUH
frequent visits improving adherence of patients.
1
Objective: To evaluate perindopril 3.5 mg/amlodipine 2.5 mg once daily, a novHO¿[HGGRVHFRPELQDWLRQZLWKGRVHVVHOHFWHGWRDFKLHYHDSSUR[LPDWHO\HTXDO
EORRGSUHVVXUHORZHULQJHIIHFWE\HDFKFRPSRQHQWDVDSRWHQWLDO¿UVWVWHSWUHDWment in patients with hypertension.
Design and method: An international, randomised, double-blind, placebo-conWUROOHG VWXG\ ZLWK HTXDO SDUDOOHO WUHDWPHQW DUPV DQG DQ ZHHN UDQGRPLVHG
WUHDWPHQWSHULRGZKRVHGHVLJQFOLQLFDOVLJQL¿FDQFHDQGQRQLQIHULRULW\FULWHULD
were in accordance with European guidelines.
Results: SDWLHQWV ZLWK PLOGWRPRGHUDWH XQFRPSOLFDWHG K\SHUWHQVLRQ
PHDQ DJH \HDUV ZHUH UDQGRPLVHG DQG FRPSOHWHG WKH VWXG\ 7KH
combination was statistically and clinically superior to placebo (between-group
differences: SBP: -7.22 mmHg, DBP: -4.12 mmHg, p <0.001 for both). Rates
of response and normalisation of blood pressure were greater with the combination (p <0.001 for both) and numerical differences relative to placebo were
apparent at 2 weeks. The combination was superior to either component given
singly (p <0.001 for both drugs, for SBP and DBP), and was non-inferior to
both component drugs given singly at their lowest clinically-approved doses.
The components of the combination had approximately equal effects on SBP
SHULQGRSULOPJPP+JDPORGLSLQHPJPP+J $GYHUVH
events relating to peripheral oedema were less frequent with the combination
than with amlodipine 5 mg.
Conclusions: 7KHREVHUYHGEORRGSUHVVXUHORZHULQJHI¿FDF\UDSLGLW\RIRQVHW
RIHIIHFWDQGIDYRXUDEOHVDIHW\SUR¿OHRIWKHFRPELQDWLRQSHULQGRSULOPJ
DPORGLSLQHPJLQGLFDWHLWVSRWHQWLDOVXLWDELOLW\IRUXVHDV¿UVWVWHSWUHDWPHQW
in uncomplicated hypertension.
2D.05
EFFECTS OF FIXED COMBINATION OF PERINDOPRIL
10 MG/INDAPAMIDE 2.5 MG IN HYPERTENSIVE
PATIENTS POST STROKE/TIA: A PICASSO SUBSTUDY
C. Farsang. St. Imre University Teaching Hospital, Budapest, HUNGARY
Objective: To investigate the hemodynamic and cardiometabolic effects of
3-month treatment with perindopril 10 mg/indapamide 2.5 mg (PI) in hypertensive patients who have suffered a stroke or TIA, being not at target despite
therapy.
Design and method: K\SHUWHQVLYHSDWLHQWV SWV ZHUHLQFOXGHGLQWKH3,CASSO open, multicenter, observational study. Medical history, cardiovascular
&9 ULVNIDFWRUVRI¿FHEORRGSUHVVXUH 2%3 DPEXODWRU\EORRGSUHVVXUHPRQLtoring (ABPM), heart rate, and metabolic parameters were recorded.
Results: 'DWD IURP SRVWVWURNH SWV ZRPHQ PHQ DYHUDJH DJH \HDUV ZHUH DQDO\]HG &KDUDFWHULVWLFV DJH ! \HDUV REHVLW\ VPRNLQJ SRVLWLYH &9 IDPLO\ KLVWRU\ SUH-
2D.06
EFFECTS OF SODIUM AND POTASSIUM
SUPPLEMENTATION ON BLOOD PRESSURE,
ARTERIAL STIFFNESS AND RENAL FUNCTION IN
UNTREATED (PRE)HYPERTENSIVES ON A FULLY
CONTROLLED DIET
L. Gijsbers 1,2, J. Dower 1,2, M. Mensink 2, S. Bakker 1,3, J. Geleijnse 1,2.
Top Institute Food and Nutrition, Wageningen, NETHERLANDS, 2 Division
of Human Nutrition, Wageningen University, Wageningen, NETHERLANDS,
3
Department of Internal Medicine, University Medical Center Groningen,
Groningen, NETHERLANDS
1
Objective: We performed a 12-week randomized placebo-controlled crossover
study to examine the effects of sodium and potassium supplementation on blood
pressure (BP), arterial stiffness and renal function in untreated (pre)hypertensive
individuals.
Design and method: During the study, subjects were on a fully controlled
diet that provided on average 2.4 g/d of sodium (~6 g/d of salt) and 2.2 g/d of
potassium. After a 1-week run-in period, 37 subjects received capsules with
supplemental sodium (3 g/d, equals 7.5 g/d of salt), supplemental potassium
(3 g/d), or placebo, for four weeks each (not separated by wash-out), in ranGRPRUGHU)DVWLQJRI¿FH%3KDPEXODWRU\%3PHDVXUHVRIDUWHULDOVWLIIQHVV 6SK\JPR&RUŠ DQG HVWLPDWHG JORPHUXODU ¿OWUDWLRQ UDWH H*)5 ZHUH
assessed at baseline and after each treatment. Data were analysed using linear
mixed-effects models.
Results: 6XEMHFWVKDGDPHDQSUHWUHDWPHQW%3RIPP+JDQGKDG
a systolic BP of 140 mmHg or higher. In 36 subjects who completed the study,
urinary sodium increased from 105 mmol/24h on placebo to 203 mmol/24h
GXULQJVRGLXPVXSSOHPHQWDWLRQZKLFKFDXVHGVLJQL¿FDQWLQFUHDVHVLQ%3DQG
H*)5 7DEOH 8ULQDU\SRWDVVLXPLQFUHDVHGIURPWRPPROKGXULQJ
potassium supplementation, which was related to BP reduction and an increase
in 24h-heart rate. Central augmentation index and pulse wave velocity did not
VLJQL¿FDQWO\FKDQJHGXULQJVRGLXPRUSRWDVVLXPLQWHUYHQWLRQ
e26
Journal of Hypertension Volume 32, e-Supplement 1, 2014
Conclusions: Doubling the intake of sodium strongly raises BP in subjects with
XQWUHDWHG SUH K\SHUWHQVLRQZKHUHDVKLJKHUSRWDVVLXPLQWDNHKDVDEHQH¿FLDO
effect on BP. Arterial stiffness did not respond to 4-week changes in sodium and
potassium intake.
2D.07
EFFECTS OF CALCIUM CHANNEL BLOCKER
BENIDIPINE-BASED COMBINATION THERAPY ON
TARGET BLOOD PRESSURE CONTROL RATE AND
CARDIOVASCULAR OUTCOME: A SUB-ANALYSIS OF
THE COPE TRIAL
68PHPRWR1, T. Ogihara 2, H. Rakugi 3, M. Matsuzaki 4, Y. Ohashi 5,
T. Saruta 6, the Cope Trial Group. 1 Yamaguchi University Hospital, Ube,
JAPAN, 2 Morinomiya University of Medical Sciences, Osaka, JAPAN,
3
Department of Geriatric Medicine and Nephrology, Osaka University
Graduate School of Medicine, Suita, JAPAN, 4 Yamaguchi University, Ube,
JAPAN, 5 Department of Biostatistics, School of Public Health, University of
Tokyo, Tokyo, JAPAN, 6 Keio University, Tokyo, JAPAN
Objective: The Combination Therapy of Hypertension to Prevent Cardiovascular Events (COPE) trial was a PROBE design with three dihydropyridine calcium channel blocker benidipine-based regimens—angiotensin
UHFHSWRU EORFNHU $5% ȕEORFNHU RU WKLD]LGH²GHPRQVWUDWLQJ WKDW WKH
EHQLGLSLQHȕEORFNHUFRPELQDWLRQZDVOHVVEHQHILFLDOLQUHGXFLQJWKHULVNRI
stroke than the benidipine-thiazide combination. In this sub-analysis, we exDPLQHGWKHHIIHFWVRIWKHDFKLHYHPHQWRIWDUJHWEORRGSUHVVXUH %3
mmHg) on cardiovascular outcome among the three benidipine-based treatment groups.
Design and method: This sub-analysis included 3001 patients who were able
to evaluate the achievement of target BP by at least 3 points from 6 monthinterval clinic BP measurements during the study period after randomization.
7KHJRRGFRQWURO *& DQGSRRUFRQWURO 3& JURXSVZHUHGH¿QHGDVSDWLHQWV
that achieved target BP over 66.7%, and patients that achieved target BP less
than 66.6% of the mean on-treatment BPs obtained at 6-month intervals (ARB,
ȕEORFNHU WKLD]LGH SDWLHQWV UHVSHFWLYHO\ IURP PRQWKV RI
study treatment onwards, respectively. Hazard ratios of cardiovascular outcome
in GC and PC groups among the 3 treatment groups were evaluated.
Results: Median percentage of achieved target BP in the sub-study subjects
was 66.7%. During a median 3.67 years of follow-up from randomization, the
event rate of the cardiovascular composite endpoint, stroke and hard cardiovascular event were higher in the PC group than the GC group (P = 0.041, P
DQG 3 UHVSHFWLYHO\ KD]DUG UDWLRV RI WKH LQFLGHQFH RI FRPposite cardiovascular events, stroke and hard cardiovascular events were lower
LQWKHEHQLGLSLQHWKLD]LGHJURXSWKDQLQWKHEHQLGLSLQHȕEORFNHUJURXSLQWKH
3&JURXS FRPSRVLWHFDUGLRYDVFXODUHYHQWV3 VWURNHLQFLGHQFH
3 DQGKDUGFDUGLRYDVFXODUHYHQWV3 UHVSHFWLYHO\ The incidence of cardiovascular events was not different among the 3 treatment
regimens in the GC group.
Conclusions: The benidipine-thiazide combination may provide better cardiovasFXODURXWFRPHWKDQWKHEHQLGLSLQHȕEORFNHUFRPELQDWLRQHYHQLQSRRU%3FRQWURO
Abstracts
e27
ORAL SESSION
ORAL SESSION 3A
RESISTANT HYPERTENSION
3A.01
ADJUSTED DRUG TREATMENT IS SUPERIOR TO
RENAL SYMPATHETIC DENERVATION IN PATIENTS
WITH TRUE TREATMENT RESISTANT HYPERTENSION
F. Fadl Elmula, P. Hoffmann, A. Larstorp, M. Brekke, E. Fossum, E. Gjønnæss,
U. Hjørnholm, V. Kjær, I. Os, A. Stenehjem, M. Rostrup, A. Høieggen,
S.E. Kjeldsen. Oslo University Hospital, Ullevaal, Oslo, NORWAY
University Chicago Medicine, Chicago, IL, USA, 3 University of Southern
California, Los Angeles, CA, USA, 4 Medizinische Hochschule Hannover,
Hannover, GERMANY, 5 CVRx, Inc., Minneapolis, MN, USA, 6 University of
Rochester, Rochester, NY, USA
Objective: We have previously reported our single-center feasibility experience
LQ ZKLFK EDURUHÀH[ DFWLYDWLRQ WKHUDS\ %$7 UHGXFHG EORRG SUHVVXUH %3 LQ
SDWLHQWVZLWKUHVLVWDQWK\SHUWHQVLRQZLWKEHQH¿WHQGXULQJDWOHDVW\HDUV0XOWL
center results from the Rheos Pivotal Trial indicate that BP reductions in a large
cohort are preserved for at least 2 years. The purpose of this investigation is to
determine if the reductions are maintained longer.
Objective: Renal sympathetic denervation (RDN) has been introduced as a new
treatment of hypertension that is resistant to drug treatment. It is however unknown to what degree the decline in blood pressure (BP) following RDN is caused
by denervation itself or concomitantly improved drug adherence or placebo effect.
:HDLPHGWRLQYHVWLJDWHIRUWKH¿UVWWLPHWKHEORRGSUHVVXUH %3 ORZHULQJHIIHFW
of renal sympathetic denervation (RDN) vs. clinically adjusted drug treatment in
true treatment resistant hypertension (TRH) after excluding patients with confounding poor drug adherence.
Design and method: Patients with apparent TRH (n=65) were referred for RDN
and those with secondary and spurious hypertension (n=26) were excluded. TRH
ZDVGH¿QHGDVRI¿FHV\VWROLF%3!PP+JGHVSLWHPD[LPDOO\WROHUDWHGGRVHV
of at least 3 antihypertensive drugs including a diuretic. Additionally, ambulatory
GD\WLPHV\VWROLF%3!PP+JIROORZLQJZLWQHVVHGLQWDNHRIDQWLK\SHUWHQVLYH
GUXJVZDVUHTXLUHGDIWHUZKLFKSDWLHQWVKDGQRUPDOL]HG%3DQGZHUHH[FOXGHG
3DWLHQWVZLWKWUXH75+ZHUHUDQGRPL]HGDQGXQGHUZHQW5'1 Q SHUIRUPHG
with Symplicity™ Catheter System vs. clinically adjusted drug treatment guided
E\LPSHGDQFHFDUGLRJUDSK\ Q 7KHVWXG\ZDVVWRSSHGHDUO\IRUHWKLFDOUHDsons because RDN had uncertain BP lowering effect in a population with a very
high risk of cardiovascular diseases (CVD).
Results: 2I¿FHV\VWROLFDQGGLDVWROLF%3VLQWKHGUXJDGMXVWPHQWJURXSFKDQJHG
IURP““PP+J “6' DWEDVHOLQHWR““PP+JDWPRQWKV
SDQGS V\VWROLFDQGGLDVWROLF%3UHVSHFWLYHO\ DQGLQWKH5'1
JURXS IURP ““ WR ““ PP+J S DQG S V\VWROLF
DQGGLDVWROLF%3UHVSHFWLYHO\ 6\VWROLFDQGGLDVWROLF%3VZHUHVLJQL¿FDQWO\ORZHU
LQWKHGUXJDGMXVWPHQWJURXSDWPRQWKV S DQGS UHVSHFWLYHO\ DQG
DEVROXWHFKDQJHVLQV\VWROLF%3ZHUHODUJHULQWKHGUXJDGMXVWHGJURXS S $PEXODWRU\%3VFKDQJHGLQSDUDOOHOWRRI¿FH%3V
Design and method: Patients enrolled in the Rheos Pivotal Trial transitioned
WRELDQQXDOIROORZXSDIWHUFRPSOHWLQJWKHPRQWKHQGSRLQW%3DQGVDIHW\
data were collected.
Results: 2IWKHSDWLHQWVRULJLQDOO\HQUROOHG ZHUHFRQ¿UPHGUHVSRQGHUV WR %$7 DFFRUGLQJ WR )'$PDQGDWHG FULWHULD DQG UHPDLQ DFWLYH
%3ZDVVLJQL¿FDQWO\UHGXFHGRYHUDWOHDVW\HDUVRIIROORZXS DOOS Magnitude of BP reduction was consistent over time. Long-term impact of the
FDURWLG VLQXV OHDGV DSSHDUHG EHQLJQ DV SUHYDOHQFH RI VLJQL¿FDQW FDURWLG VWHQRVLV UHPDLQHG UDUH )ROORZLQJ \HDU RI WKHUDS\ WKH UDWH RI V\VWHP DQGRU
SURFHGXUHUHODWHG FRPSOLFDWLRQV ZDV SHU SDWLHQW\HDU 6WURNH UDWH ZDV
SHUSDWLHQW\HDUVLPLODUWRWKHJHQHUDOSRSXODWLRQDWVLPLODUDJHDQG%3
5DWH RI P\RFDUGLDO LQIDUFWLRQ ZDV SHU SDWLHQW\HDU FRQVLVWHQW ZLWK WKH
age-matched population.
Conclusions: /RQJWHUPUHVXOWVIURPWKH5KHRV3LYRWDOWULDOFRQ¿UPRXUVLQJOH
center observations that BP reductions resulting from BAT are maintained over
the long term. Reduced BP endures for at least 5 years, with important implications for improving patient outcomes. Long-term presence of system compoQHQWVZDVVDIHLPSO\LQJDIDYRUDEOHULVNEHQH¿WSUR¿OH
3A.03
TREATMENT RESISTANT HYPERTENSION: RESULTS
OF A 2-YEAR FOLLOW-UP IN REAL WORLD
S. Friedrich , S. Schmidt , R. Dechend 2, T. Riemer 3, I. Hagedorn ,
U. Zeymer 5, R.E. Schmieder . 1 Universitätsklinikum Erlangen, Nephrologie und
Hypertensiologie, Erlangen, GERMANY, 2 Experimental and Clinical Research
Center, Charité-Campus Buch und HELIOS Klinikum Berlin-Buch, Berlin,
GERMANY, 3 IHF GmbH, Institut für Herzinfarktforschung, Ludwigshafen,
GERMANY, 4 Novartis Pharma GmbH, Nürnberg, GERMANY, 5 Medizinische
Klinik B, Klinikum der Stadt Ludwigshafen, Ludwigshafen, GERMANY
Conclusions: Our data suggest that adjusted drug treatment has superior BP lowering effects compared to RDN in patients with true treatment resistant hypertension.
3A.02
VALIDATION OF LONG-TERM BLOOD PRESSURE
CONTROL WITH BAROREFLEX ACTIVATION
THERAPY IN A LARGE COHORT OF RESISTANT
HYPERTENSION PATIENTS
P.W. de Leeuw , G.L. Bakris 2, M. Nadim 3, H. Haller , E. Lovett 5, J. Bisognano 6.
1
Maastricht University Medical Center, Maastricht, NETHERLANDS, 2 The
Objective: There are few data about the prevalence and the outcome of patients
with treatment resistant hypertension (TRH), even less data about patients with
TRH in combination with diabetes. The aim of the analysis was to determine the
prevalence of TRH among patients with diabetes and to elucidate the prognostic
impact of TRH coexisting with diabetes.
Design and method: ,QWKH$5HJLVWU\DQRQUDQGRPL]HGQRQLQWHUYHQWLRQDO REVHUYDWLRQDO UHJLVWU\ *HUPDQ JHQHUDO SUDFWLWLRQHUV LQFOXGHG SDWLHQWV
with known or newly diagnosed arterial hypertension, whose blood pressure
%3 ZDVQRWFRQWUROOHG ! PP+J DQGLQZKRPWKHSK\VLFLDQVGHFLGHG
WRLQLWLDWHRUHVFDODWHDQWLK\SHUWHQVLYHPHGLFDWLRQVXEMHFWV RIWKH
WRWDOFRKRUWKDGW\SHGLDEHWHV:HGH¿QHG75+DWEDVHOLQHDV%3! mmHg (for diabetic and non-diabetic patients) despite treatment with at least 3
antihypertensive drugs including a diuretic. The 2- year follow-up took place
IURP2FWREHUWR-XQHDQGZDVFRPSOHWHGLQSDWLHQWV
S
A
T
U
R
D
A
Y
O
R
A
L
S
e28
Journal of Hypertension Volume 32, e-Supplement 1, 2014
Results: 2XW RI D WRWDO RI SDWLHQWV ZLWK D \HDU IROORZXS KDG75+RIZKRPKDGGLDEHWHV RIDOOGLDEHWLFSDWLHQWV DQG
GLG QRW KDYH GLDEHWHV RI DOO QRQGLDEHWLF SDWLHQWV LQGLFDWLQJ WKDW75+
ZDVPRUHIUHTXHQWLQGLDEHWHV S 7KHLQFLGHQFHRIFOLQLFDOHYHQWVZDV
markedly increased in patients with coexistence of TRH and diabetes. The total
mortality in patients with TRH and diabetes was higher than in non-diabetic
SDWLHQWV \HDUUDWHYVS 7KHLQFLGHQFHRI0$&&( PDMRU
cardiovascular and cerebrovascular events) was nearly doubled in patients with
TRH and diabetes compared to non- diabetic patients with TRH (2-year rate: 6.2
YVS Conclusions: Resistant hypertension is common in outpatients, in particular
with diabetes. TRH coexisting with diabetes is associated with an increased
incidence of allcause-mortality and cardiovascular and cerebrovascular events
during 2-year follow- up.
3A.04
THE PREVALENCE AND FACTORS ASSOCIATED WITH
RESISTANT HYPERTENSION IN A LARGE HEALTH
MAINTENANCE ORGANIZATION IN ISRAEL
':HLW]PDQ, G. Chodick , V. Shalev , C. Grossman 2,3, E. Grossman .
Primary Care Division, Maccabi Healthcare Services, Tel-Aviv, ISRAEL,
2
Sackler Faculty of Medicine, Tel Aviv University, Tel-Aviv, ISRAEL,
3
Rheumatology Unit, Tel Hashomer, ISRAEL, 4 Internal Medicine D and
Hypertension Unit, The Chaim Sheba Medical Center, Tel Hashomer, ISRAEL
FXUUHQFHRI¿UVWIDWDORUQRQIDWDOFDUGLRYDVFXODUHYHQW &9( PDMRU&9(V
(non-fatal myocardial infarction and stroke plus cardiovascular deaths),
all-cause and cardiovascular mortality. Multivariate Cox survival analyses
assessed the associations between cfPWV (as a continuous variable and diFKRWRPL]HGDWPV DQGWKHHQGSRLQWV
Results: 0HDQFI3:9ZDV 6' PVSDWLHQWV KDGFI3:9
!PV$IWHUDPHGLDQIROORZXSRIPRQWKV¿UVW&9(VRFFXUUHG ZHUH PDMRU &9(V DQG SDWLHQWV GLHG IURP FDUGLRYDVFXODU GLVHDVHV
$IWHUDGMXVWPHQWVIRUDJHDQGVH[FRQWLQXRXVFI3:9 PVLQFUHPHQW SUHGLFWHGDOOHQGSRLQWVZLWKKD]DUGUDWLRV +5 EHWZHHQDQG &,
DOO S +RZHYHU DIWHU DGMXVWPHQWV IRU RWKHU FDUGLRYDVFXODU
ULVN IDFWRUV LQFOXGLQJ KRXU V\VWROLF %3 WKH +5V DWWHQXDWHG DQG EHFDPH
QRQVLJQL¿FDQW WR &, DOO S! :LWK GLFKRWRPL]HG FI3:9 DGMXVWHG IRU DJH DQG VH[ LW RQO\ SUHGLFWHG DOOFDXVH PRUWDOLW\ +5&, KRZHYHULWDOVRORVWVLJQL¿FDQFHDIWHUIXOO
statistical adjustment.
Conclusions: Increased aortic stiffness is not a risk marker of adverse cardiovascular prognosis in patients with resistant hypertension. Most of its predictive performance is attenuated by adjustments for other cardiovascular risk
factors.
1
Objective: 5HVLVWDQWK\SHUWHQVLRQ 5+ KDVEHHQGH¿QHGDVEORRGSUHVVXUH %3 that remains elevated despite treatment with three antihypertensive agents of
different classes, one being a diuretic, at optimal dose. It is thought that RH is a
common problem among hypertensive patients. This study assesses the prevalence of RH in Maccabi Healthcare Services (MHS), a large HMO in Israel,
XVLQJDFRPSUHKHQVLYHFRPSXWHUL]HGGDWDEDVH
Design and method: Patients included in the MHS hypertension registry were
eligible for the study if they had at least two recorded BP measurements over a
SHULRGRI! PRQWKVLQ3DWLHQWVZHUHUHJDUGHGXQFRQWUROOHGLIWKHLU
most recent BP during the study period and their mean systolic or diastolic BP
RYHUDSUHFHGLQJSHULRGRIDWOHDVWPRQWKVZHUH! PP+JRU! PP+J
! PP+JRU! PP+JLQFKURQLFNLGQH\GLVHDVHDQGGLDEHWLFSDWLHQWV respectively. Treatment was assessed with drug-purchase data including class,
GRVHDQGQXPEHURIWUHDWPHQWGD\V5+ZDVGH¿QHGZKHQ! RIGD\VZHUH
FRYHUHGE\DGLXUHWLFDQG! RWKHUGUXJFODVVHVLQWKHGD\VSHULRGSULRUWR
ODVW %3 PHDVXUHPHQW 3URSRUWLRQ RI 5+ ZDV ¿QDOO\ FDOFXODWHG RXW RI DOO XQcontrolled hypertensive patients. Demographic data and co-morbidities were
described as well.
Results: 2IWKHSDWLHQWVLQWKH0+6¶K\SHUWHQVLRQUHJLVWU\
ZHUH HOLJLEOH IRU WKH VWXG\ 7RWDO SURSRUWLRQ RI SDWLHQWV ZLWK XQFRQWUROOHG %3 ZDV 1 7UHDWPHQW SDWWHUQV RI DOPRVW 1 RIWKHXQFRQWUROOHGSDWLHQWVGLGQRWIXO¿OOWKHGH¿QLWLRQRI5+
2QO\ 1 RIWKHXQFRQWUROOHGJURXS RIWKHHQWLUHFRKRUW met the criteria of true RH. Patients with true RH were older, had higher
mean BMI and more comorbidities than those with controlled HTN. Patients
ZLWK5+DOVRKDGORZHUJORPHUXODU¿OWUDWLRQUDWHORZHUOHYHOVRI+'/FKRlesterol and higher levels of glucose, potassium, and LDL cholesterol.
Conclusions: Most patients with uncontrolled BP are noncompliant or use less
than maximal recommended antihypertensive treatment. True RH is less common than thought. Patients with true RH should be evaluated to exclude reversible causes for hypertension
3A.05
PROGNOSTIC IMPACT OF AORTIC STIFFNESS IN
PATIENTS WITH RESISTANT HYPERTENSION
3A.06
SOLUBLE VASCULAR ENDOTHELIAL GROWTH
FACTOR RECEPTOR IS REDUCED IN PATIENTS
WITH RESISTANT HYPERTENSION AFTER RENAL
DENERVATION
N. Eikelis , D. Hering , P. Marusic , A. Walton 3, G. Lambert , M. Esler ,
M. Schlaich . 1 Neurovascular Hypertension and Kidney Disease Laboratory,
Baker IDI Heart and Diabetes Institute, Melbourne, AUSTRALIA, 2
Department of Hypertension and Diabetology, Medical University of Gdansk,
Gdansk, POLAND, 3 Heart Centre, Alfred Hospital, Melbourne, AUSTRALIA
Objective: 5HQDO GHQHUYDWLRQ 5'1 LV DVVRFLDWHG ZLWK D VLJQL¿FDQW IDOO
in blood pressure in patients with resistant hypertension. While a reduction
in sympathetic activity has been documented, other mechanisms related to
endothelial function may contribute. Vascular adhesion molecules, growth
factors and their receptors such as soluble vascular endothelial growth facWRU UHFHSWRU V9(*)5 DUH DVVRFLDWHG ZLWK HQGRWKHOLDO G\VIXQFWLRQ DQG
KDYH EHHQ OLQNHG WR K\SHUWHQVLRQ:H K\SRWKHVL]HG WKDW WKHVH IDFWRUV PD\
be altered by RDN.
Design and method: 2I¿FH EORRG SUHVVXUH KHDUW UDWH DQG VHYHUDO PDUNHUVRIHQGRWKHOLDOIXQFWLRQ V,&$0V9&$00&39(*)V9(*)5
DQGQLWULFR[LGH ZHUHPHDVXUHGLQSODVPDRISDWLHQWVZLWKUHVLVWDQWK\SHUWHQVLRQ DJH “ \HDUV %0, “ NJPð PHDQ“6(0 EHIRUH DQG months after RDN.
Results: 2I¿FH EORRG SUHVVXUH ZDV VLJQL¿FDQWO\ UHGXFHG V\VWROLF “
YV“ PP+J S GLDVWROLF “ YV“ PP+J S DW month follow up without changes in heart rate. There were no changes in
SODVPD OHYHOV RI V,&$0 V9&$0 RU 0&3 IROORZLQJ WKH SURFHGXUH
,QWHUHVWLQJO\DVLJQL¿FDQWGHFUHDVHLQV9(*)5ZDVREVHUYHGDWPRQWKV
IROORZ XS IURP “ WR “ SJPO S ZLWK QR VLJQL¿FDQW
FKDQJHV LQ 9(*) OHYHOV )XUWKHUPRUH QLWULF R[LGH ZDV VLJQL¿FDQWO\ LQFUHDVHG DIWHU 5'1 “ YV “ X0 S 1RQH RI WKH PDUNHUV
measured at baseline were predictive of the BP reduction associated with
RDN.
Conclusions: $Q5'1LQGXFHGUHGXFWLRQLQV9(*)5SODVPDOHYHOVLQWKH
DEVHQFHRIFKDQJHVLQ9(*)OHYHOVZRXOGUDLVHWKH9(*)V9(*)5UDWLR
thereby increasing VEGF bioavailability to act on its full length receptor and
contribute to the blood pressure lowering effect via nitric oxide mediated
pathways.
G. Salles, C. Roderjan, M. Ferreira, E. Muxfeldt. School of Medicine, Federal
University of Rio de Janeiro, Rio de Janeiro, BRAZIL
Objective: Increased aortic stiffness, measured by its gold-standard, the carotidfemoral pulse wave velocity (cfPWV), has been demonstrated to be a risk marker for worse cardiovascular outcomes in patients with hypertension and diabetes
and in general populations. However, its prognostic importance in patients with
resistant hypertension has never been evaluated.
Design and method: ,QDSURVSHFWLYHVWXG\UHVLVWDQWK\SHUWHQVLYHSDWLHQWVKDGFI3:9PHDVXUHGEHWZHHQDQGDQGZHUHIROORZHGXS
XQWLO $OO KDG DPEXODWRU\ EORRG SUHVVXUH %3 PRQLWRULQJ SHUIRUPHG
within one month of cfPWV measurement. Primary endpoints were the oc-
3A.07
AMBULATORY BLOOD PRESSURE CHANGES
AFTER RENAL DENERVATION IN SUBJECTS WITH
RESISTANT HYPERTENSION: EARLY OUTCOMES
FROM THE GLOBAL SYMPLICITY REGISTRY
G. Mancia , M. Schlaich 2, .1DUNLHZLF]3, L.M. Ruilope , B. Williams 5,
R.E. Schmieder 6, F. Mahfoud , M. Böhm . 1 Università degli Studi di
Milano-Bicocca, Milan, ITALY, 2 Baker IDI Heart and Diabetes Institute,
Melbourne, AUSTRALIA, 3 Medical University of Gdansk, Gdansk, POLAND,
4
Universidad Autonoma Madrid, Madrid, SPAIN, 5 University of Leicester
e29
Journal of Hypertension Volume 32, e-Supplement 1, 2014
School of Medicine, Leicester, UNITED KINGDOM, 6 University Hospital
Erlangen, Erlangen, GERMANY, 7 Universitätsklinium des Saarlandes,
Homburg/Saar, GERMANY
Objective: 2XUDLPZDVWRFRPSDUHFKDQJHVLQERWKRI¿FHEDVHGEORRGSUHVVXUH DQG KRXU DPEXODWRU\ EORRG SUHVVXUH PRQLWRULQJ $%30 EHWZHHQ
patients with true and pseudo-resistant hypertension in a real world population of patients undergoing percutaneous renal denervation.
Design and method: The Global SYMPLICITY Registry is a prospective,
PXOWLFHQWHU VLQJOHDUP RSHQODEHO VWXG\ 2I¿FH DQG DPEXODWRU\ EORRG
pressure (BP) measurements were performed in accordance with published
JXLGHOLQHV$%30UHDGLQJVZHUHUHFRPPHQGHGWREHWDNHQHYHU\PLQXWHV
LQ GD\WLPH DQG HYHU\ PLQXWHV DW QLJKWWLPH$%30 UHDGLQJV ZHUH DYHUDJHG IRU KRXUV GD\WLPH DQG QLJKWWLPH $PRQJ K\SHUWHQVLYH VXEMHFWV
RI¿FHV\VWROLF%3! PP+J WUXHUHVLVWDQFHZDVGH¿QHGDVKRXU
V\VWROLF$%30! PP+JRUGD\WLPHV\VWROLF$%30! PP+JDQG
SVHXGRUHVLVWDQFH ZDV GH¿QHG DV KRXU V\VWROLF$%30 PP +J RU
GD\WLPHV\VWROLF$%30PP+J
Results: $PRQJK\SHUWHQVLYHSDWLHQWV KDGSVHXGRUHVLVWDQFH%DVHline characteristics (other than BP measurements) and antihypertensive medication
XVHZHUHVLPLODUEHWZHHQWKHJURXSV),/(,0$*( ¶B
MSJ¶! 3DWLHQWV ZLWK WUXH UHVLVWDQW K\SHUWHQVLRQ KDG VLJQL¿FDQWO\ KLJKHU EDVHOLQH
$%30DQGRI¿FH%3PHDVXUHPHQWV
Conclusions: The Global SYMPLICITY Registry will provide data on the effect
of radiofrequency renal denervation in patients with true resistant hypertension and
SVHXGRUHVLVWDQWK\SHUWHQVLRQ$QDO\VLVRIRI¿FH%3DQG$%30FKDQJHVDWDQG
PRQWKVIRUWKH¿UVWSDWLHQWVFRPSOHWLQJPRQWKIROORZXSZLOOEHDYDLODEOH
for presentation.
Abstracts
e30
ORAL SESSION
ORAL SESSION 3B
LARGE ARTERIES
3B.01
ULVNLQFUHDVHRI ¿JXUH 7KHUHVSHFWLYHSRROHG55RI&9PRUWDOLW\ZDV
&,WRSVWXGLHV FRUUHVSRQGLQJWRDULVNLQFUHDVH
RI ¿JXUH )LQDOO\ WKH UHVSHFWLYH SRROHG 55 RI DOOFDXVH PRUWDOLW\ ZDV
&,WRSVWXGLHV FRUUHVSRQGLQJWRDULVNLQFUHDVH
RI ¿JXUH INTER-ARM BLOOD PRESSURE DIFFERENCE AND
ARTERIAL STIFFNESS
C. Clark, F. Casanova, K. Gooding, N. Pamphilon, .$L]DZDD. Mawson,
D. Adingupu, C. Ball, F. Worthington, S. Elyas, D. Strain, P. Gates, A. Shore,
J. Campbell. University of Exeter Medical School, Exeter, UNITED KINGDOM
Objective: Inter-arm differences in systolic blood pressure are assumed to
be caused by obstructive upper limb arterial disease (subclavian stenosis),
KRZHYHU UDGLRORJLFDOO\ FRQ¿UPHG VWHQRVHV KDYH RQO\ EHHQ GHPRQVWUDWHG
ZLWKODUJH !PP+J LQWHUDUPGLIIHUHQFHV7KHDVVRFLDWLRQEHWZHHQLQWHU
arm differences and mortality is unexplained but could be causally related
to non-homogenous arterial stiffness. We examined the associations between
the inter-arm difference in blood pressure, central and peripheral pulse pressures, and established central arterial stiffness (carotid-femoral pulse wave
velocity).
Design and method: A mixed population of volunteers with and without cardiovascular risk factors, recruited to studies by the Clinical Research Facility,
University of Exeter, underwent a series of vascular assessments to determine
arterial stiffness and blood pressures. Pulse wave velocity and central arterial
pressure were derived using arterial tonometry. Brachial blood pressure was
measured simultaneously six times bilaterally using a repeated cross-over method to minimise machine and operator bias. For each arm, blood pressures were
determined as the mean of six consecutive measurements.
Results: )RU VXEMHFWV KDG D V\VWROLF LQWHUDUP GLIIHUHQFH
! PP+J DQG ! PP+J 6\VWROLF LQWHUDUP GLIIHUHQFHV ZHUH
SRVLWLYHO\ FRUUHODWHG RQ XQLYDULDWH DQDO\VLV ZLWK SXOVH ZDYH YHORFLW\ U S DRUWLFSXOVHSUHVVXUH U S DQGULJKWEUDFKLDOSXOVHSUHVVXUH U S )ROORZLQJ DGMXVWPHQW IRU DJH VPRNLQJ DQG GLDEHWHV
status, systolic blood pressure, total cholesterol and renal function, correlations
RQPXOWLYDULDWHDQDO\VLVUHPDLQHGIRUSXOVHZDYHYHORFLW\ U S DQG
ULJKW EUDFKLDO SXOVH SUHVVXUH U S EXW QRW DRUWLF SXOVH SUHVVXUH
U S 2QVXEJURXSDQDO\VLVRIFRQWUROVXEMHFWVZLWKRXWGLDEHWHVFDUGLRYDVFXODU
disease or hypertension, systolic inter-arm difference after adjustment for age,
systolic blood pressure, renal function, total cholesterol and smoking status, was
PRGHUDWHO\FRUUHODWHGZLWKSXOVHZDYHYHORFLW\ U S Conclusions: Aortic stiffness expressed by aPWV is an important predictor of
future CV events, CV mortality and all-cause mortality.
3B.03
LONG TERM CHANGES IN CAROTID INTIMA-MEDIA
THICKNESS AND ARTERIAL REMODELING ARE
ASSOCIATED WITH ANTIHYPERTENSIVE TREATMENT
STATUS
B. Van Varik , R. Rennenberg , H. Stoffers 2, P.W. de Leeuw , A. Kroon .
Maastricht University Medical Centre, Maastricht, NETHERLANDS,
2
Maastricht University, Maastricht, NETHERLANDS
1
Objective: Hypertension is strongly associated with vascular stiffness, arterial
remodeling, and atherosclerotic disease. Treatment guidelines recommend a
JRDOEORRGSUHVVXUH %3 RIPP+J+RZHYHULWLVQRWIXOO\FOHDUZKHWKer treatment of hypertension has an effect on arterial remodeling apart from the
outcome. Therefore, we aimed to prospectively investigate whether achieving
the recommended BP goal is associated with changes in (carotid) arterial remodeling and progression of carotid intima media thickness (cIMT).
Conclusions: These results suggest a potential association between stiffness in
central and peripheral arteries and inter-arm blood pressure differences. Therefore, the aetiology of the inter-arm difference in blood pressure may involve
ORFDOLVHGFKDQJHVWRWKHPHFKDQLFDODQGRUSK\VLRORJLFDOSURSHUWLHVRISUR[LPDO
DUWHULHV7RRXUNQRZOHGJHWKLVLVWKH¿UVW(XURSHDQVWXG\WRUHSRUWWKHVHREservations.
3B.02
AORTIC STIFFNESS FOR CARDIOVASCULAR RISK
PREDICTION: AN UPDATED SUMMARY DATA METAANALYSIS
C. Vlachopoulos, .$]QDRXULGLVC. Stefanadis. 1st Department of Cardiology,
Athens Medical School, Hippokration Hospital, Athens, GREECE
Objective: $RUWLFVWLIIQHVVDQGVSHFL¿FDOO\DRUWLFSXOVHZDYHYHORFLW\ D3:9 KDVEHHQLQFUHDVLQJO\UHFRJQL]HGDVDYDOXDEOHELRPDUNHUIRU&9ULVNSUHGLFWLRQ
Aim of the present study was to calculate robust quantitative estimates of the
predictive value of aPWV for future CV events and all-cause mortality.
Design and method: :HPHWDDQDO\]HGDOOORQJLWXGLQDOVWXGLHVSXEOLVKHGXQWLO6HSWHPEHU VWXGLHV ZKLFKKDGHYDOXDWHGD3:9DQGKDGIROORZHG
VXEMHFWVIRUDPHDQIROORZXSRI\HDUV
Results: 7KHSRROHG55RIWRWDO&9HYHQWVIRUDVWDQGDUGGHYLDWLRQLQDRUWLF
3:9ZDV &,WRSVWXGLHV FRUUHVSRQGLQJWRD
Design and method: 3DUWLFLSDQWVDJHG\HDUVRUROGHUZHUHUHFUXLWHGIURPD
single general practice and were invited for baseline and follow-up study visits. At
each study visit, we interviewed participants regarding medical history, life-style
habits and cardiovascular drug use. We measured height, weight, body mass index,
systolic and diastolic BP, and assessed mean arterial pressure, and pulse pressure.
We divided the population in subgroups according to hypertensive treatment status. For prospective measurements, we divided the population based on change in
hypertensive status. We measured cIMT with B-mode ultrasonography using an
automated wall-track system (Artlab, Esaote, Maastricht, the Netherlands), and
assessed markers of arterial remodeling: lumen diameter (LD), cross-sectional
area (CSA), circumferential wall tension (CWT), and circumferential wall stress
(CWS). Finally, as marker of aortic stiffness, we measured carotid-femoral Pulse:DYH9HORFLW\ 3:9&RPSOLRU>$UWHFK3DQWLQ)UDQFH@ S
A
T
U
R
D
A
Y
O
R
A
L
S
e31
Journal of Hypertension Volume 32, e-Supplement 1, 2014
Results: 7KHEDVHOLQHFRKRUWFRQVLVWHGRISDUWLFLSDQWV IHPDOHVPHDQ
DJH“\HDUV SDUWLFLSDQWVZHUHQRUPRWHQVLYH DGHTXDWHO\WUHDWHG LQDGHTXDWHO\WUHDWHGDQG XQWUHDWHG+\SHUWHQVLYHWUHDWPHQWVWDWXVZDVSURJUHVVLYHO\DQGVLJQL¿FDQWO\DVVRFLDWHG
with IMT, LD, CSA, CWT, CWS and PWV compared to normotensives (ANO9$S ,QWRWDOSDUWLFLSDQWVFRQVHQWHGWRIROORZXS0HDQIROORZXS
GXUDWLRQZDV\HDUV3HUVLVWHQWDQGLQFLGHQWK\SHUWHQVLRQKDGKLJKHUOHYHOVRI
arterial remodeling, whereas recovery to normotension resulted in improvement
RISDUDPHWHUVRIDUWHULDOUHPRGHOLQJ 6HH¿JXUHRQWKHSUHYLRXVSDJH Conclusions: These data show that achieving the treatment goal in hypertension affects carotid artery remodeling. This suggests that adequate treatment of
hypertension is important in preventing (outward) remodeling.
3B.04
PROXIMAL AORTIC REMODELING IN ESSENTIAL
HYPERTENSION IS ASSOCIATED TO LEFT
VENTRICULAR MASS AND PULSE WAVE VELOCITY
F. Tosello, D. Leone, G. Bruno, A. Ravera, L. Sabia, R. Ayamuang, I. Losano,
F. Veglio, A. Milan. Department of Medical Sciences, Hypertension Center,
Turin, ITALY
Objective: Vascular ageing is accelerated by arterial hypertension, leading to
aortic stiffening and dilatation. While we have a lot of data concerning aortic
stiffening, less is known about proximal aortic diameter (AoAsc) remodeling in
hypertension. Our aim was to evaluate the association between the aortic remodeling and cardiac (left ventricular mass - LVM) and vascular damage (carotidfemoral pulse wave velocity - cfPWV) in hypertensive patients.
$R$VFIXUWKHUPRUH$R$VFUHPRGHOLQJZDVUHODWHGWRERWKOHIWYHQWULFXODUK\pertrophy and aortic stiffness independently from blood pressure. AoAsc remodeling could be a marker of alterations in ventricular-vascular interaction and
organ damage in essential hypertension.
3B.05
BRACHIAL-ANKLE PULSE WAVE VELOCITY AS A
PREDICTOR OF MORTALITY IN ELDERLY CHINESE
C. Sheng, Y. Li, L. Li, J. Wang. The Shanghai Institute of Hypertension, Ruijin
Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, CHINA
Objective: Pulse wave velocity (PWV) is a measure of arterial stiffness and predicts cardiovascular events and mortality in the general population and various
patient populations. In the present study, we investigated the predictive value of
brachial-ankle PWV for total and cardiovascular mortality in an elderly Chinese
population.
Design and method: 2XUVWXG\VXEMHFWVZHUHROGHU ! \HDUV SHUVRQVOLYLQJ
in a suburban town of Shanghai. At baseline, we measured brachial-ankle PWV
using an automated oscillometric device. During follow-up, vital information
ZDVFROOHFWHGWLOO-XQH
Results: 7KH VWXG\ SDUWLFLSDQWV PHQ >@ DW EDVHOLQH KDG D
PHDQDJHRI\HDUV “>6'@ DQGLQFOXGHG K\SHUWHQVLYHSDWLHQWVDQG SDWLHQWVZLWKGLDEHWHVPHOOLWXV%UDFKLDODQNOH3:9ZDV
RQDYHUDJHPV “ DQGZDVVLJQL¿FDQWO\DVVRFLDWHGZLWKDJH U 3 DQGLQXQDGMXVWHGDQDO\VLVZLWKWRWDO Q KD]DUGUDWLRSHUPV
LQFUHDVHLQ3:93 DQGFDUGLRYDVFXODUPRUWDOLW\ Q KD]DUG
UDWLR3 GXULQJDPHGLDQIROORZXSRI\HDUV%HFDXVHRIKLJK
colinearity between age and brachial-ankle PWV, in further adjusted analysis,
we studied the risk of mortality according to the decile distributions of PWV.
2QO\LQWKHWRSGHFLOHRI3:9 PV WKHVXEMHFWVKDGVLJQL¿FDQWO\
KLJKHUULVNRIWRWDOPRUWDOLW\,QGHHGWKHKD]DUGUDWLRLQWKHWRSGHFLOHYHUVXVWKH
RWKHU GHFLOHV ZDV FRQ¿GHQFH LQWHUYDO 3 6LPLODU
WUHQGV ZHUH REVHUYHG IRU FDUGLRYDVFXODU PRUWDOLW\ EXW VWDWLVWLFDO VLJQL¿FDQFH
ZDVQRWUHDFKHG 3 Conclusions: %UDFKLDODQNOH3:9VLJQL¿FDQWO\EXWZHDNO\SUHGLFWVPRUWDOLW\
in the elderly.
3B.06
FUNCTIONAL AND STRUCTURAL ARTERIAL
CHANGES AND ITS DETERMINANTS IN PATIENTS
WITH ACROMEGALY
L. Bortolotto , V. Costa-Hong , A. Amaro 2, M. Bronstein 2, F. Gaia 2,
R. Soares 2*/RUHQ]L)LOKR, R. Pedrosa , L. Drager . 1 Hypertension Unit,
Heart Institute (InCor) Hospital das Clínicas da Faculdade de Medicina,
Universidade de São Paulo, São Paulo, BRAZIL, 2 Endocrinology Department,
Hospítal das Clinicas da Faculdade de Medicina da Universidade de São
Paulo, São Paulo, BRAZIL
Objective: To evaluate functional and structural vascular changes in subjects
ZLWKDFURPHJDO\DQGWKHGHWHUPLQDQWIDFWRUVRIWKHVHPRGL¿FDWLRQV
Design and method: HVVHQWLDOK\SHUWHQVLYHVVXEMHFWV PHDQDJH“
\PHQ6\VWRGLDVWROLFEORRGSUHVVXUH“PP+J XQGHUwent to a transthoracic echocardiography: we evaluated LVM and maximal aorWLFGLDPHWHUDWWKHDVFHQGLQJOHYHO $R$VF ZHDOVRPHDVXUHGDRUWLFVWLIIHQLQJ
as cfPWV at the same visit with validated tonometric device (SphygmoCor).
$R$VF GLDPHWHU UHPRGHOLQJ ZDV GH¿QHG DV WKH GLIIHUHQFH EHWZHHQ PHDVXUHG
aortic diameter and expected aortic diameters in relation to age, BSA and sex
according to published equations for normal values.
Results: In this cohort of essential hypertensives mean AoAsc diameter was
“PPZLWKDPHDQGLIIHUHQFHEHWZHHQREVHUYHGDQGSUHGLFWHG$R$VF
GLDPHWHU RI “ PP ,Q XQLYDULDWH DQDO\VLV $R$VF UHPRGHOLQJ ZDV
UHODWHG WR DJH U S DQG WR 0HDQ %ORRG 3UHVVXUH 0%3 U S /90 U S DQG FI3:9 U S ZHUH DVVRFLDWHG ZLWK$R$VF 5HPRGHOLQJ WKLV DVVRFLDWLRQ ZDV FRQ¿UPHG LQ PXOWLYDULDWHDQDO\VLVLQGHSHQGHQWO\RI0%3 EHWDIRU/90EHWDIRUFI3:9
S $R$VFUHPRGHOLQJSURJUHVVLYHO\LQFUHDVHGIURPVXEMHFWVZLWKQRUPDO
left ventricular mass and geometry to patients with left ventricular concentric
UHPRGHOLQJHFFHQWULFDQGFRQFHQWULFK\SHUWURK\ $129$S)LJXUH Conclusions: Essential hypertensive subjects showed a 3 mm remodeling of
Design and method: :HHYDOXDWHGSDWLHQWVZLWKGLDJQRVLVRIDFURPHJDO\
PHDQ DJH RI “ \HDUV PDOHV JURZWK KRUPRQH OHYHO *+ “
QJPO JURZWK IDFWRU VLPLODU WR LQVXOLQ W\SH ,*) “ QJ
PO7KH FRQWURO JURXS FRQVLVWHG RI DJH DQG VH[PDWFKHG VXEMHFWV$UWHULDO
stiffness was evaluated by carotid-femoral pulse wave velocity (PWV) by Complior® and functional and structural evaluation of carotid artery by ultrasound
echotracking device (Wall-Track System2®).
Results: 3DWLHQWVZLWKDFURPHJDO\SUHVHQWHGKLJKHUYDOXHVRIZHLJKW “
YV“.JS ERG\PDVVLQGH[ %0, “YV“.JPS
V\VWROLFEORRGSUHVVXUH “YV“PP+JS 3:9
“YV“PVS DQGLQWLPDPHGLDWKLFNQHVV ,07 “
YV“—PS WKDQWKHFRQWUROJURXS,QWKHPXOWLYDULDWHDQDO\VLV
LWZDVREVHUYHGDVLJQL¿FDQWDQGSRVLWLYHFRUUHODWLRQEHWZHHQ%0,DQG3:9
Uð S DQGEHWZHHQ%0,DQG,07 Uð S DQGDOVR
EHWZHHQ*+DQG,07 Uð S Conclusions: Patients with acromegaly had greater aortic stiffness and carotid
IMT than healthy subjects. The main determinant factors of arterial stiffness in
patients with acromegaly was BMI while the thickening of the carotid artery was
correlated with GH and BMI.
Abstracts
e32
ORAL SESSION
2
ORAL SESSION 3C
CARDIOVASCULAR RISK FACTORS
3C.01
GENETIC FACTORS AS PREDICTORS OF LATE
CARDIOVASCULAR MORTALITY IN CORONARY
PATIENTS
A. Pereira , M. Mendonca , S. Gomes , R. Rodrigues , A. Sousa , A. Freitas 2,
S. Borges , M. Rodrigues , D. Pereira , R. Palma Reis 3. 1 Research Unit,
Funchal Hospital Center, Funchal, PORTUGAL, 2 Research Unit, Funchal
Hospital Center, Madeira University, Funchal, PORTUGAL, 3 New University
of Lisbon, Faculty of Medical Sciences, Lisbon, PORTUGAL
Objective: 6HYHUDOVWXGLHVKDYHDWWHPSWHGWRDVVRFLDWHJHQHWLFSUR¿OHVEDVHG
on either candidate gene approach or genome-wide association studies (GWAS)
with the development of Coronary Artery Disease (CAD). However, few studies
KDYHHYDOXDWHGJHQHWLFSUR¿OHVDVVRFLDWHGWRWKHFDUGLRYDVFXODUPRUWDOLW\
Our aim is to identify the genetic variants associated to the late cardiovascular
mortality.
Design and method: $ FDVHFRQWURO VWXG\ ZLWK D WRWDO RI FRURQDU\ SDWLHQWVFDVHV SDWLHQWVZKRVXEVHTXHQWO\GLHGRIFDUGLRYDVFXODUGHDG DQG
controls (coronary patients who survived) was performed during a follow up
SHULRGRI“\HDUVWRHYDOXDWHWKHFDUGLRYDVFXODUPRUWDOLW\7KHFOLQLFDO
ELRFKHPLFDODQGJHQHWLFSUR¿OHVZHUHDQDO\]HGLQERWKJURXSV7KHJHQHWLFYDULDQWVDOUHDG\DVVRFLDWHGWR&$'ZHUH(&$,!'UV$*77!0UV
$*70!7UV$7,5$!&UV$32(UV$32(UV
07+)5 &!7 UV07+)5 $!& UV S*!&
UV*-$&!7UV3&6.UV.,)$!*UV,*)%3*UV3214!5UV321/!0UV&'.1%$!*
UV $'$076 $!* ,*)%3 *!7 UV 8QLYDULDWH DQDO\VLV
was performed in order to determine the mortality risk of the studied variants.
7KH2GGV5DWLR 25 DQG&RQ¿GHQFH,QWHUYDOV &, ZHUHGHWHUPLQHGDQG
SYDOXHV OHVV WKDQ ZHUH FRQVLGHUHG VLJQL¿FDQW )LQDOO\ D &R[ UHJUHVVLRQ
was performed to estimate the independent variables associated to mortality and
the survivals curves were constructed using the Kaplan-Meier method.
Results: $IWHUDIROORZXSSHULRGRI“\HDUVFRURQDU\SDWLHQWVVKRZHGD
FDUGLRYDVFXODUPRUWDOLW\RI7KHUHZHUHVLJQL¿FDQWGLIIHUHQFHVLQWKHJHQH
YDULDQWV QDPHO\ 07+)5 $$ 25 S DQG $'$076$$
25 S DVZHOODVDJHGLDEHWHVSODWHOHWVDQGKRPRF\VWHLQHOHYHOV
Conclusions: 2XU VWXG\ VKRZHG WKDW 07+)5 $$ DQG $'$076 $$ LQcreased the risk of late cardiovascular mortality in CAD. Since these genes are
OLQNHGWRWKHHQGRWKHOLDOG\VIXQFWLRQDQGLQÀDPPDWRU\FHOOXODUSURFHVVHVFDUriers of these 2 variants should have a particularly careful secondary prevention, which may justify a search for new therapeutic approaches that are not yet
clearly established.
3
National Research Center for Preventive Medicine, Moscow, RUSSIA,
Vitebsk State Medical College, Vitebsk, BELARUS
Objective: Increases in prevalence of arterial hypertension were reported in the
SRSXODWLRQ OLYLQJ LQ WKH UDGLRDFWLYH FRQWDPLQDWHG WHUULWRU\ 5&7 WKURXJK years after the Chernobyl catastrophe. The aim of this research was to study
WKHK\SHUWHQVLRQSUHYDOHQFHLQSRSXODWLRQOLYLQJLQWKH5&7ZLWKFDHVLXP
GHQVLW\PRUHWKDQN%TPðFRPSDUHGZLWKWKHFRQWUROJURXSRI©FOHDUªUHJLRQ
DQGWRGH¿QHVLJQL¿FDQWULVNIDFWRUVRIWKLVGLVHDVH
Design and method: During the expeditions three representative groups from
5&7ZHUHIRUPHGWKH¿UVWFRQVLVWLQJRIDGXOWVZLWKFDHVLXPGHQVLW\
IURPN%TPðWKHVHFRQG±DGXOWVZLWKFDHVLXPGHQVLW\IURP
N%TPðWKHWKLUG±DGXOWVZLWKFDHVLXPGHQVLW\IURP
N%TPð&RQWUROJURXSIURP©FOHDUªUHJLRQZDVFRQVLVWHGDGXOWV7KHVXUvey included standard questionnaires (WHO) for detection of cardiovascular
risk factors, measurements of blood pressure and gustatory sensitivity to sodium
chloride, electrocardiography, level of Lusher anxiety and total cholesterol.
Results: All groups were of similar mean age. Higher prevalence of hypertenVLRQLQWKH¿UVWJURXSIURP5&7± 3 DQGVHFRQGJURXSIURP5&7
± 3 WKHQLQFRQWUROJURXS±ZDVIRXQG1RFKDQJHZDV
noted in prevalence of hypertension between third group from RCT and control
JURXS YV3! 7KHH[SRVXUHVRIK\SHUWHQVLRQULVNIDFWRUV
were determined in the logistic regression analysis. The hypertension with adjustment for age and sex was positively associated with gustatory sensitivity to
VRGLXPFKORULGH 3 ERG\PDVVLQGH[ 3 IDPLO\KLVWRU\RISUHPDWXUHFDUGLRYDVFXODUGLVHDVH 3 UHVLGHQFHLQ5&7ZLWKFDHVLXP
GHQVLW\PRUHWKDQN%TPð 3 /XVKHUDQ[LHW\ 3 KHDUWUDWH
3 DOFRKRO DEXVH 3 VPRNLQJ PRUH WKDQ FLJDUHWWHV LQ GD\
3 WRWDOFKROHVWHURO 3 Conclusions: Gustatory sensitivity to sodium chloride, body mass index, family
KLVWRU\RISUHPDWXUHFDUGLRYDVFXODUGLVHDVHUHVLGHQFHLQ5&7ZLWKFDHVLXP
GHQVLW\PRUHWKDQN%TPð/XVKHUDQ[LHW\KHDUWUDWHDOFRKRODEXVHVPRNLQJPRUHWKDQFLJDUHWWHVLQGD\DQGWRWDOFKROHVWHUROOHYHODUHOLNHO\LQYROYHG
in the Chernobyl-associated hypertension.
3C.03
CLINICAL IMPACT OF LEFT AXIS DEVIATION ON THE
RISK OF CARDIOVASCULAR DISEASE IN JAPANESE
SUBJECTS FROM A BLOOD PRESSURE POINT OF
VIEW: THE SUITA STUDY
T. Kobayashi , M. Watanabe , Y. Kokubo , S. Kamakura 2, K. Kusano 2,
Y. Miyamoto . 1 Division of Preventive Cardiology, Department of Internal
Medicine, National Cerebral and Cardiovascular Center, Suita, JAPAN,
2
Division of Cardiology, Department of Internal Medicine, National Cerebral
and Cardiovascular Center, Suita, JAPAN
Objective: /HIWD[LVGHYLDWLRQ /$' LVDVLPSOHGLVWLQFWDQGFRPPRQ¿QGLQJ
of electrocardiogram. Although studies indicated that LAD is related to hypertension and death, the clinical impact of LAD on the risk of cardiovascular disease (CVD) is not yet to be clearly understood. We aimed to examine the effect
of prognostic values of LAD on the risk of CVD using a long-term prospective
cohort study in a Japanese urban population.
Design and method: :HHYDOXDWHG6XLWD6WXG\SDUWLFLSDQWV DJHG
\HDUVPHQ ZLWKRXWSULRU&9'ZKRDWWHQGHGDURXWLQHH[DPLQDWLRQ6LQgle electrocardiogram recordings and biochemical examinations were taken in
WKHEDVHOLQHVXUYH\3DUWLFLSDQWVZHUHFODVVL¿HGLQWRJURXSVZLWKDQGZLWKRXW
/$'/$'ZDVGH¿QHGDVKDYLQJ0LQQHVRWD&RGH&R[UHJUHVVLRQDQDO\VLV
ZDVFDUULHGRXWWRHVWLPDWHWKHKD]DUGVUDWLRV +5V RI&9'DIWHUDGMXVWLQJIRU
other risk factors.
3C.02
ARTERIAL HYPERTENSION PREVALENCE AND RISK
FACTORS OF THIS DISEASE IN THE POPULATION
LIVING IN THE RADIOACTIVE CONTAMINATED
TERRITORY
A. Schastlivenko , V. Podpalov , A. Deev 2, I. Stchastlivenka 3,
N. Prakoshyna . 1 Vitebsk State Medical University, Vitebsk, BELARUS,
Results: 'XULQJDQDYHUDJHRI\HDUVRIIROORZXS&9'HYHQWV LQPHQLQZRPHQ FRURQDU\KHDUWGLVHDVHV &+' LQPHQLQ
ZRPHQ DQGVWURNHV LQPHQLQZRPHQ ZHUHREVHUYHG,QERWK
men and women, prevalence of LAD became higher and prevalence of other
deviation group became lower as age increased. After further adjustment of age,
body mass index, hypertension, hypercholesterolemia, diabetes, smoking, alcoKRODQGHVWLPDWHGJORPHUXODU¿OWUDWLRQUDWHWKH+5RI&9'IRU/$'ZDV
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Journal of Hypertension Volume 32, e-Supplement 1, 2014
LQZRPHQ+5RIFHUHEUDOLQIDUFWLRQIRU/$'ZDV &,V
S LQPHQDQG &,VS LQZRPHQ$GGLWLRQDOO\
LQQRUPDOEORRGSUHVVXUHPHQDQGZRPHQWKH+5RI&+'IRU/$'ZDV
&,VS DQG &,VS UHVSHF
tively.
WR 6HOIPRQLWRULQJPLJKWEHFRVWHIIHFWLYHIRUIHPDOHVDQGKLJKHU
HGXFDWHGSDUWLFLSDQWVKRZHYHUFRQ¿GHQFHLQWHUYDOVZHDUHZLGH
Conclusions: 7KHSUHVHQWVWXG\VXJJHVWVWKDW/$'LQOHDG(&*LVXVHIXOWR
identify the higher risk of CVD among Japanese women. Moreover, in normal
EORRGSUHVVXUHZRPHQWKHULVNRI&+'ZDVDVLJQL¿FDQWDVVRFLDWLRQRI/$'
independent of confounding factors.
3C.04
BASELINE MEAN PLATELET VOLUME IS
ASSOCIATED WITH RESIDUAL PLATELET
REACTIVITY IN PATIENTS WITH UNSTABLE ANGINA
AND ARTERIAL HYPERTENSION
I. Markava, $0LDG]YHG]HYDL. Helis, ,/D]DUHYD.
Republican Science Practical Center, Minsk, BELARUS
Objective: Response to platelet inhibitors are in demand. We sought to evaluate the correlation between baseline mean platelet volume (MPV), residual
platelet reactivity and platelet aggregation indices. If such association exists,
MPV might help to identify patients at increased risk of atherothrombosis.
Design and method: :HHYDOXDWHGFRQVHFXWLYHSDWLHQWV PHQPHDQ
DJH“\U GLDJQRVHGZLWKXQVWDEOHDQJLQD 8$ DQGDUWHULDOK\SHUWHQ
sion (AH) and 36 matched controls with coronary artery disease (CAD) and
AH. MPV was determined on admission. EDTA blood samples, drawn at adPLVVLRQZHUHDQDO\]HGE\DXWRPDWHGKHPDWRORJ\DQDO\VLVV\VWHPV0LFURV
7KHVDPSOHVZHUHSURFHVVHGZLWKLQKRXUVDIWHUYHQLSXQFWXUH3ODWHOHW
UHDFWLYLW\ZDVDVVHVVHGZLWK9HULI\1RZ VSHFL¿FWRDVSLULQ DVSLULQUHDFWLRQ
XQLWV$58 DQGFORSLGRJUHO 3<UHDFWLRQXQLWV358 DQGZLWK$5
µ62/$5¶ VWLPXODWHGDJJUHJDWLRQWHVWLQJ Results: 039 ZDV VLJQL¿FDQWO\ KLJKHU LQ SDWLHQWV ZLWK 8$ DQG$+ FRP
SDUHGZLWKFRQWUROV ÀYV3 UHVSHFWLYHO\ 1RGLIIHUHQFHZDV
observed for aspirin or clopidogrel poor-responsiveness in both groups. A
VWURQJ FRUUHODWLRQ ZDV IRXQG EHWZHHQ 039 DQG $58 U 3 whereas no correlation was observed for clopidogrel poor-responsiveness. A
higher degree of ADF 2,5 mcM stimulated aggregation was associated with
358 U 3 Conclusions: MPV is increased in patients with UA and correlates with aspirin poor-responsiveness. Unlike more expensive or time-consuming methods
RIDVVHVVLQJSODWHOHWIXQFWLRQWKHGHWHUPLQDWLRQRISODWHOHWVL]HE\TXDQWL¿
cation of the MPV, using automated hemograms, is simple and inexpensive.
The biologic rationale linking MPV to progression of atherosclerosis has
made it a promising indirect marker of platelet reactivity.
3C.05
COST-EFFECTIVENESS OF CARDIOVASCULAR RISK
MANAGEMENT BY PRACTICE NURSES, WITH AND
WITHOUT SELF-MONITORING, IN PRIMARY CARE
A. Smit , A. Tiessen 2, K. Vermeulen 3, J. Broer , K. Van Der Meer 2.
Department of Internal Medicine, University Medical Center Groningen,
Groningen, NETHERLANDS, 2 Department of General Practice, University
Medical Center Groningen, Groningen, NETHERLANDS, 3 Department
of Epidemiology, University Medical Center Groningen, Groningen,
NETHERLANDS, 4 Municipal Public Health Service Groningen, Groningen,
NETHERLANDS
1
Objective: The randomised SPRING-trial (SPRING-RCT) showed that cardiovascular risk management (CRM) by practice nurses in general practice, with
and without self-monitoring, both decreasesd cardiovascular risk, with no additional effect of self-monitoring. The aim was to perform cost effectiveness analyses (CEA) of regular care and additional self-monitoring in the SPRING-RCT.
Design and method: Direct medical and productivity costs were analysed,
VWXG\LQJ635,1*5&7SDUWLFLSDQWV PHQDJHG\HDUVZRPHQDJHG
\HDUV ZLWKDQHOHYDWHGFDUGLRYDVFXODUULVNLQJHQHUDOSUDFWLFHVLQWKH
Netherlands. Standard CRM, according to Dutch guidelines was compared to
CRM with additional counselling based on self-monitoring at home (pedometer,
ZHLJKLQJVFDOHDQGRUEORRGSUHVVXUHGHYLFH ERWKE\WUDLQHGSUDFWLFHQXUVHV
CEA wais evaluated for both treatment groups and patient categories (age, sex,
education).
Results: &RVWVZHDUH¼DQG¼SHUSHUFHQWGHFUHDVHLQ\HDU6&25(
cardiovascular mortality estimation, for the control and intervention group respectively. In both groups lost productivity causesd the majority of the costs.
7KH LQFUHPHQWDO FRVWHIIHFWLYHQHVV UDWLR ZDV DSSUR[LPDWHO\ ¼ &,
Conclusions: In this study population, standard CRM by practice nurses regular
treatment is more cost effective than additional intensive counselling based on
self-monitoring, with the majority of costs caused by lost productivity.
3C.06
DEVELOPMENT OF A CARDIOVASCULAR MORTALITY
RISK PREDICTION MODEL FOR PARTICIPANTS IN
THE OHASAMA STUDY
C. Reid , M. Huq , A. Owen , Z. Ademi , T. Ohkubo 2, Y. Imai 2, G.A. Head 3.
CCRE Therapeutics, Monash University, Melbourne, AUSTRALIA, 2 Teikyo
University, Tokyo, JAPAN, 3 Baker IDI, Melbourne, AUSTRALIA
1
Objective: Ambulatory blood pressure monitoring provides a more accurate
blood pressure (BP) assessment than isolated clinic measurements, but can be
more intensive and expensive than clinic measures. The extent to which novel
BP indices from ambulatory monitoring improve cardiovascular risk prediction
is less clear. The aim of the study was to develop a cardiovascular mortality risk
prediction model for participants in the Ohasama Study from Japan examining
conventional and ambulatory blood pressure novel indices.
Design and method: 7KLVVWXG\XVHG\HDUVIROORZXSGDWDRISDUWLFL
pants in Ohasama study in Japan. Our risk model was developed using univariDWHDQGPXOWLYDULDEOH&R[SURSRUWLRQDOKD]DUGVPRGHO9DULDEOHVHOHFWLRQZDV
GRQH XVLQJ ERRWVWUDS PHWKRGV RQ ERRWVWUDS VDPSOHV$IWHU GHYHORSPHQW
PRGHOZDVYDOLGDWHGXVLQJIROGERRWVWUDSYDOLGDWLRQPHWKRGV
Results: Ambulatory and conventional blood pressure values were obtained
IURPSDUWLFLSDQWVZLWKDYHUDJHDJH“\DQGRIZKRPZHUH
ZRPHQ SRSXODWLRQ H[SHULHQFHG D IDWDO FDUGLRYDVFXODU HYHQW 7KH ¿QDO
cardiovascular risk prediction model included risk factors such as age, smoking status, number of antihypertensive medications, mean daytime ambulatory
systolic arterial blood pressure and difference between day and night ambulatory
V\VWROLFDUWHULDOEORRGSUHVVXUH &VWDWLVWLFZDV 7KHDPEXODWRU\YDULDEOHV
predicted cardiovascular mortality better than conventional BP variables. The
LQWHUQDOERRWVWUDSYDOLGDWLRQSURYLGHGXVZLWKD&VWDWLVWLFRI
Conclusions: This risk prediction model incorporating novel indices from
ABPM provides a direct risk assessment of cardiovascular mortality in Ohasama
study participants. It could be externally validated and compared with other relevant cardiovascular mortality risk prediction models.
3C.07
TEN-YEAR CORONARY ARTERY DISEASE RISK
ASSESSMENT IN NIGERIAN HYPERTENSIVE
SUBJECTS
D. Ojji , A. Falase 2, S. Ajayi 3, M. Mamven , M. Ngabea , K. Sliwa 5.
Cardiology Unit, Department of Medicine, University of Abuja Teaching
Hospital, Gwagwalada, Abuja, NIGERIA, 2 Cardiology Unit, Department of
Medicine, University College Hospital, Ibadan, NIGERIA, 3 Nephrology Unit,
Department of Medicine, University College Hospital, Ibadan, NIGERIA,
4
Nephrology Unit, Department of Medicine, University of Abuja Teaching
Hospital, Gwagwalaa, Abuja, NIGERIA, 5 Hatter Insitute of Cardiovascular
Research in Africa, University of Cape Town, Cape Town, SOUTH AFRICA
1
Objective: It is a well known fact that the presence of hypertension doubles
the risk of coronary artery disease (CAD). In spite of the high prevalence of
hypertension in Nigeria, the prevalence of CAD is relatively uncommon in this
population group. It has however been projected that with the epidemiological
transition in disease pattern being experienced in many parts of sub-Saharan
e34
Journal of Hypertension Volume 32, e-Supplement 1, 2014
$IULFD&$'LVOLNHO\JRLQJWRSOD\DPRUHVLJQL¿FDQWUROHLQWKHGLVHDVHSDWWHUQ
in Nigeria. To ascertain the future role of CAD in Nigeria, we decided to risk
stratify every consecutive hypertensive subject referred to the Cardiology unit of
8QLYHUVLW\RI$EXMD7HDFKLQJ+RVSLWDOIURP$SULOWR-XO\
Design and method: FRQVHFXWLYHK\SHUWHQVLYHVXEMHFWVSUHVHQWLQJWR&DUdiology Unit, Department of Medicine, University of Abuja Teaching Hospital,
$EXMDZHUHULVNVWUDWL¿HGDFFRUGLQJWRWKH)UDPLQJKDP\HDU5LVN6FRUH
Results: RIWKHVXEMHFWVZHUHPDOHZKLOHZHUHIHPDOH
The mean age, mean body mass index and mean arterial pressure of the subMHFWV ZHUH “\HDUV“NJP DQG“PP+J UHVSHF-
tively, while mean total cholesterol, mean HDL cholesterol, mean fasting blood
VXJDUDQGPHDQFUHDWLQLQHFOHDUDQFHZHUH“PPROO“PPROO
“PPROODQG“POVPLQUHVSHFWLYHO\ RIWKHVWXG\
SRSXODWLRQ ZHUH KLJK ULVN LQGLYLGXDOV ZHUH PHGLXP ULVN ZKLOH
ZHUHORZULVNLQGLYLGXDOV
Conclusions: Even though majority of hypertensive subjects in this part of
the world have a low risk for the development of coronary artery disease in
WKH QHDUHVW IXWXUH D SURSRUWLRQ DV KLJK DV LQ WKH PRGHUDWH DQG KLJK
ULVNFDWHJRULHVFDQQRWEHLJQRUHG7KHUHIRUHWKHQHHGIRUOLIHVW\OHPRGL¿FDtion and emphasis on primary prevention in this population group cannot be
over-emphasised.
Abstracts
e35
ORAL SESSION
ORAL SESSION 3D
EXPERIMENTAL HYPERTENSION
3D.01
THE KIDNEY CYP2C44 EPOXYGENASE REGULATES
EPITHELIAL SODIUM CHANNEL (ENAC) ACTIVITY
AND THE BLOOD PRESSURE RESPONSES TO
INCREASE DIETARY SALT
J. Capdevila , W. Wang 2. 1 Vanderbilt University Medical School, Nashville,
TN, USA, 2 New York Medical College, Valhalla, NY, USA
Objective: 7RGH¿QHD WKHUROHRIWKH&\SFHSR[\JHQDVHDQGLWVHSR[\HLcosatrienoic acid (EET) metabolites in the blood pressure responses to increases
in salt intake, and b) mechanisms by which the EETs regulate ENaC activity and
renal distal sodium excretion.
Design and method: 0LFHFDUU\LQJDGLVUXSWHG&\SFJHQHZHUHGHYHORSIRU
VWXGLHVRIWKHD UROHSOD\HGE\WKH&\SFHSR[\JHQDVHLQWKHEORRGSUHVVXUH
responses to a high salt intake, b) regulation of ENaC gating in collecting ducts
IURPZLOGW\SH :7 DQG&\SF .2 PLFHDQGE PHFKDQLVPVRI((7
mediated ENaC inhibition. Adult WT and KO mice were fed diets containing
RU1D&O QRUPDORUKLJKVDOWUHVSHFWLYHO\ IRUGD\V6\VWROLFEORRG
pressures (BP) were measured in conscious mice by means of a carotid artery
catheter and a remote pressure sensor. ENaC activity was determined by patch
clamp analyses of dissected collecting ducts from WT and KO mice (fed high
K+ or low Na+ for 3 days to increase ENaC expression). Standard immuno-elecWURSKRUHVLVLPPXQRÀXRUHVFHQFH PHWKRGV ZHUH XVHG WR FKDUDFWHUL]H &\SF
JHQRW\SHGHSHQGHQWGLIIHUHQFHVLQ(5.DQG(1D&JDPPDSKRVSKRU\ODWLRQ
Results: 0LFHODFNLQJD&\SFHSR[\JHQDVHGHYHORSVDOWVHQVLWLYHK\SHUWHQsion, a common form of the human disease. Thus, KO mice on normal salt diets
DUHQRUPRWHQVLYHDQGEHFRPHK\SHUWHQVLYHZKHQIHGKLJKVDOWGLHWV %3V“
DQG “ PP +J UHVSHFWLYHO\ $PLORULGH DQ (1D& LQKLELWRU QRUPDOL]HVWKH%3RIK\SHUWHQVLYH.2DQLPDOVSRLQWLQJWRLQYLYRUROHVIRUWKH((7V
in ENaC regulation. Compared to normotensive WT animals, hypertensive KO
PLFH VKRZ D K\SHUDFWLYH (1D& DQG LPSDLUPHQWV LQ (5. FDWDO\]HG (1D&
phosphorylation.
Conclusions: 7KHVHVWXGLHVD LGHQWLI\DQWLK\SHUWHQVLYHUROHVIRUWKH&\SF
HSR[\JHQDVHDQGWKH((7VLQWKHFRQWURORI(1D&JDWLQJDQG(5.DFWLYDtion, b) provide evidence for a mechanism of ENaC regulation involving the
((7PHGLDWHG(5.FDWDO\]HGWKUHRQLQHSKRVSKRU\ODWLRQRI(1D&JDPPD
DQG F VXJJHVW UROHV IRU WKH KXPDQ &<3&& HSR[\JHQDVHV LQ WKH SDWKRphysiology of human hypertension and diseases associate with dysfunctional
mitogenic signaling.
3D.02
EFFECTIVENESS OF INTRATRACHEAL DELIVERY
OF AUTOLOGUS BONE MARROW-DERIVED CELLS
INTO THE LUNGS OF MONOROTALINE-INDUCED
PULMONARY HYPERTENSION MODEL RATS
<<DPD]DWR, 0<DPD]DWR2, A. Ishida 2, J. Fujita , Y. Ohya 2. 1 Department
of Infectious, Pulmonary and Digestive Medicine, Graduate School of
Medicine, University of the Ryukyus, Okinawa, JAPAN, 2 Department of
Cardiovascular Medicine, Nephrology and Neurology, Graduate School of
Medicine, University of the Ryukyus, Okinawa, JAPAN
Objective: Bone marrow-derived cells (BMCs) include mesenchymal stem
cells and progenitor cells play critical role in tissue repair via paracrine effect at administrated site. Aim of this study was to investigate the effect of
intratracheal delivered BMCs into the lungs compared with intravenous administration of BMCs on monocrotaline (MCT)-induced pulmonary hypertension model rats.
Design and method: Two weeks before MCT treatment, BMCs were isolated
and plastic adhered cells were cultured for three weeks. Effect of conditioned
media from the BMC on endothelial cell (EC) proliferation was examined by
¶EURPR¶GHR[\XULGLQH %UG8 XSWDNHDVVD\
6HYHQ GD\V IROORZLQJ 0&7 PJNJ ERG\ ZHLJKW WUHDWPHQW ÀXRUHVFHQWO\
labeled autologous BMCs were delivered intratracheallly or intravenously to
male Sprague-Dawley rats. Twenty-eight days following the MCT treatment,
rats had hemodynamic studies. Hearts and lungs were removed to evaluate right
ventricular (RV) hypertrophy and lung pathologies.
Results: EC proliferation assay exhibited almost twice as higher BrdU uptake
ZLWKWKHPHGLDIURP%0&VWKDQWKHPHGLDIURP(&$WGD\VDIWHULQWUDWUDFKHDOGHOLYHU\RIDXWRORJRXV%0&VLQWRWKHOXQJVÀXRUHVFHQWSUREH'L,ODEHOHG
BMCs were detected mainly in lung parenchyma surrounding airways but not
pulmonary vascular wall, whereas intravenous administration resulted that DiIpositive cells were detected patchy appearance in pulmonary capillary area
similar to pulmonary embolism. MCT treated rats had increased RV systolic
pressure (RVSP) and RV weight as well as thickness of small pulmonary vessels
FRPSDUHGZLWKWKRVHRIYHKLFOHWUHDWHGFRQWUROUDWV DOOSYDOXHV ,QWUDWUDcheal delivery of autologous BMCs seven days after MCT treatment prevented
WKHLQFUHDVHLQ5963DWZHHNVFRPSDUHGZLWK0&7DORQH “YHUVXV
“PP+JUHVSHFWLYHO\S EXWQRWRQLQWUDYHQRXVDGPLQLVWUDWHG
MCT treated group. Furthermore, the intratracheal delivery of autologous BMCs
VLJQL¿FDQWO\DWWHQXDWHGWKHSXOPRQDU\YHVVHOZDOOWKLFNQHVVLQDFLQHUDUHD
Conclusions: Intretracheal delivery of autologous BMCs prevented MCT-induced pulmonary hypertension at least in part via paracrine effects.
3D.03
ALTERATIONS IN RENAL FUNCTION OCCUR PRIOR
TO THE INCREASE IN ARTERIAL PRESSURE IN RAT
OFFSPRING FOLLOWING SHORT-TERM EXPOSURE
TO MATERNAL GLUCOCORTICOIDS
K. Denton , D. Fong , R. Brown , R. Singh , R. Evans , .0RULW]2.
Monash University, Melbourne, AUSTRALIA, 2 Queensland University,
Brisbane, AUSTRALIA
1
Objective: Acute exposure of the fetus to elevated maternal glucocorticoids
results in reduced nephron number and hypertension in adulthood. In a kidney
with fewer nephrons, hypertrophy of the glomerulus and tubule occurs, to enable
WKHUHPQDQWQHSKURQVWRKDQGOHDODUJHUVKDUHRI(&):HK\SRWKHVL]HWKDWWKHVH
structural adaptations are accompanied by adaptations in glomerular and tubular
IXQFWLRQZKLFKLQWKHVKRUWWHUPZLOOQRUPDOL]HUHQDOIXQFWLRQEXWLQWKHORQJ
term will increase the risk of renal and cardiovascular disease. Our aim was to
examine the changes in arterial pressure, renal function and tubuloglomerular
feedback (TGF) during the postnatal period in rat offspring exposed to elevated
levels of maternal glucocorticoids in utero.
Design and method: ,QPDOHRIIVSULQJ Q 6SUDJXH'DZOH\UDWV RIPRWKHUV
WUHDWHGZLWKFRUWLFRVWHURQH &257QDWXUDOJOXFRFRUWLFRLGLQURGHQWVPJ
NJGD\LSELG RUYHKLFOH 9(+P/NJGD\ RQGD\VDQGRIJHVWDWLRQ
WHUPGD\V PHDQDUWHULDOSUHVVXUH 0$3 ZDVUHFRUGHGYLDUDGLRWHOHPHWU\
IURPZHHNVRIDJH7*)ZDVDVVHVVHGYLDUHQDOPLFURSXQFWXUHDWDQG
weeks of age under basal conditions and during intra-tubular nitric oxide (NO)
blockade with L-NAME.
Results: 0$3 ZDV QRW VLJQL¿FDQWO\ GLIIHUHQW EHWZHHQ WKH RIIVSULQJ RI 9(+
and CORT groups at a postnatal age of 25 days. MAP increased with age
3$JH LQERWKJURXSV+RZHYHUWKHLQFUHDVHLQ0$3ZDVHQKDQFHGLQ
WKHRIIVSULQJRIWKH&257WUHDWHGJURXS 3*URXS[$JH 7KHUHZDVDOHIWward shift of the TGF response curve in offspring of the CORT group at 3 weeks
of age, which was associated with a reduced contribution of NO.
Conclusions: ,QRIIVSULQJZLWKDFRQJHQLWDOQHSKURQGH¿FLWLQGXFHGE\PDWHUQDO
JOXFRFRUWLFRLGDGPLQLVWUDWLRQ7*)LVVHQVLWL]HGDWDSRVWQDWDODJHRIZHHNVWR
DOORZLQFUHDVHGUHDEVRUSWLRQRIVRGLXPDQGÀXLGDQGUHGXFLQJVLQJOHQHSKURQ
JORPHUXODU¿OWUDWLRQUDWH7KHVHFKDQJHVRFFXUSULRUWRWKHLQFUHDVHLQDUWHULDO
pressure suggesting that the alterations in TGF early in life maybe a potential
mechanism that could drive the development of hypertension later in life.
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Journal of Hypertension Volume 32, e-Supplement 1, 2014
3D.04
ANGIOGENESIS INHIBITION-INDUCED BLOOD
PRESSURE RISE AND RENAL TOXICITY ARE DOSERELATED
S. Lankhorst , M. Kappers , J. Van Esch , F. Smedts 3, S. Sleijfer ,
A.H.J. Danser , A. Van Den Meiracker . 1 Erasmus Medical Center,
Department of Internal Medicine, Division of Pharmacology and Vascular
Medicine, Rotterdam, NETHERLANDS, 2 Amphia Hospital, Department
of Internal Medicine, Breda, NETHERLANDS, 3 Reinier de Graaf Groep,
Department of Pathology, Delft, NETHERLANDS, 4 Erasmus Medical Center,
Department of Medical Oncology, Rotterdam, NETHERLANDS
Objective: Angiogenesis inhibition with the VEGF inhibitor sunitinib is an established anti-cancer therapy, inducing hypertension and nephrotoxicity in part
through activation of the endothelin pathway. The present study was aimed to
explore the dose-dependency of these side effects.
Design and method: In male WKY rats, mean arterial pressure (MAP) was
PRQLWRUHG WHOHPHWULFDOO\ GXULQJ RUDO WUHDWPHQW ZLWK D KLJK PJNJGD\
Q DQLQWHUPHGLDWH PJNJGD\ DQGDORZGRVHRIVXQLWLQLE PJNJGD\
Q HDFK RUYHKLFOH Q (LJKWGD\VDIWHUDGPLQLVWUDWLRQUDWVZHUHVDFUL¿FHG
and blood samples and kidneys were collected for biochemical measurements
DQGKLVWRORJLFDOHYDOXDWLRQ,QDGGLWLRQKXULQHVDPSOHVZHUHFROOHFWHGIRU
measurement of protein.
Results: 'XULQJKLJKGRVHRIVXQLWLQLE0$3LQFUHDVHGIURP“PP+JWR
“PP+J GHOWD“PP+JS 7KHLQWHUPHGLDWHDQGORZ
GRVHVLQGXFHGD0$3ULVHRI“PP+J S DQG“PP+J
S UHVSHFWLYHO\ :LWK WKH KLJK GRVH FLUFXODWLQJ (7 LQFUHDVHG IURP
“SJPOWR“SJPO S DQGVHUXPF\VWDWLQH&IURP“
PJ/WR“PJ/ S 7KHULVHVLQFLUFXODWLQJ(7ZHUHDOVRVHHQ
with the intermediate and low doses, whereas serum cystatine-C still increased
ZLWKWKHLQWHUPHGLDWHGRVH WR“PJ/S EXWQRWZLWKWKHORZGRVH
“PJ/S! :LWKWKHKLJKGRVHRIVXQLWLQLESURWHLQXULDLQFUHDVHG
IURP“WR“PJGD\ GHOWD“PJGD\S 7KLVULVHLQ
proteinuria was virtually absent with the intermediate and low dose. Renal histology revealed extensive glomerular ischemia and intraepithelial protein deposition with the high dose of sunitinib. This pathology was attenuated with the
intermediate dose and abolished with the low dose. Analogous to the decrease
in proteinuria, glomerular intra-epithelial protein deposition decreased with the
lower doses of sunitinib.
Conclusions: Angiogenesis inhibition-induced hypertension and nephrotoxicity
with sunitinib are dose-dependent with a lower threshold for the rise in blood
pressure than for renal toxicity. The rise in BP observed with the low dose of
sunitinib observed in normotensive rats is comparable to the sunitinib-induced
BP rise observed in patients. Therefore this low-dose model may be most representative for the human situation.
the non-clipped kidneys than in urine from clipped kidneys or urine from Sham
RSHUDWHGUDWV QJPLQYVDQGQJPLQ Conclusions: 7KHUHVXOWVVXSSRUWWKHK\SRWKHVLVWKDWWKHUHLVDORFDODPSOL¿FDWLRQPHFKDQLVPLQWKHQRQFOLSSHGNLGQH\RI.&K\SHUWHQVLRQWKDWDXJPHQWV
intrarenal AGT formation thus explaining the increased intrarenal Ang II levels,
the reduced renal function and the impairment of pressure natriuresis.
3D.06
INTRACEREBROVENTRICULAR ADMINISTRATION
OF AUTOLOGOUS BONE MARROW-DERIVED CELLS
ATTENUATES CARDIAC PERIVASCULAR FIBROSIS
IN DEOXYCORTICOSTERONE ACETATE-SALT
HYPERTENSIVE RATS
T. Nakamura , 0<DPD]DWR , A. Ishida , <<DPD]DWR2, Y. Ohya .
Department of Cardiovascular Medicine, Nephrology and Neurology,
Graduate School of Medicine, University of the Ryukyus, Okinawa, JAPAN,
2
Department of Infectious, Pulmonary and Digestive Medicine, Graduate
School of Medicine, University of the Ryukyus, Okinawa, JAPAN
1
Objective: Administration of deoxycorticosterone acetate (DOCA) in combination with salt loading and surgical removal of one kidney induces hypertension.
Overactive sympathetic nervous system is one of the mechanisms involved in
this hypertension. Bone marrow-derived cells (BMCs) include mesenchymal
VWHPFHOOVSOD\FULWLFDOUROHLQUHSDLULQJGDPDJHGWLVVXHDQGDQWLLQÀDPPDWLRQ
:HK\SRWKHVL]HGWKDWLQFUHDVHLQQXPEHURI%0&VLQWKHEUDLQZRXOGDWWHQXDWH
the DOCA-salt hypertension.
Design and method: Sprague-Dawley rats underwent unilateral nephrectomy
received either sham treatment or DOCA-salt treatment. One week later, these
rats had either intracerebroventricular (icv) administration of serum free medium
or BMCs. Time-dependent blood pressure change was measured with tail-cuff
plethysmography. Three weeks following the initiation of DOCA-salt treatment,
rats had surgery to implant arterial and venous catheters. Resting sympathetic
tone was evaluated with a peak depressor response produced by hexamethonium
& LQMHFWLRQ)LQDOO\RUJDQVZHUHUHPRYHGDQGWKHZHLJKWDQG¿EURWLFFKDQJH
ZDVHYDOXDWHG3HULYDVFXODU¿EURVLVZDVGHWHUPLQHGDVWKHUDWLRRIWKHDUHDRI
¿EURVLVVXUURXQGLQJWKHYHVVHOZDOOWRWKHWRWDOYHVVHODUHD
Results: DOCA-salt treatment caused time-dependent increase in systolic blood
presser (SBP). Icv administration of BMC attenuated the trend of increase in
6%3'2&$VDOWWUHDWPHQWVLJQL¿FDQWO\LQFUHDVHGWKHSHDNGHSUHVVRUUHVSRQVH
WR&FRPSDUHGZLWKVKDPWUHDWHGUDWV “YV“PP+J ,FYDGPLQLVWUDWLRQRI%0&VVLJQL¿FDQWO\DWWHQXDWHGWKHLQFUHDVHLQSHDNGHSUHVVRUUHVSRQVH
“PP+J '2&$VDOWWUHDWPHQWVLJQL¿FDQWO\LQFUHDVHGFDUGLDFSHULYDVFXODU¿EURVLV “YV“ DQGLFYDGPLQLVWUDWLRQRI%0&VDWWHQXDWHGWKHSHULYDVFXODU¿EURVLV “ Conclusions: BMCs in the brain would attenuate cardiac pathology in DOCAsalt hypertensive rats at least in part attenuating sympathetic overactivation.
3D.05
INCREASED URINARY ANGIOTENSINOGEN IN
THE NON-CLIPPED KIDNEYS OF 2-KIDNEY 1-CLIP
HYPERTENSIVE RATS
L. Navar, W. Shao, M. Prieto, A. Katsurada, K. Mitchell. Tulane University,
Department of Physiology and the Hypertension and Renal Center of
Excellence, New Orleans, LA, USA
Objective: Unilateral renal arterial clipping leads to a sequence of events that alters function of the contralateral kidney as a consequence of the increased circulating angiotensin II (Ang II) levels. Previous studies suggest that there is a local
DPSOL¿FDWLRQPHFKDQLVPLQWKHFRQWUDODWHUDONLGQH\WKDWOHDGVWRVWLPXODWLRQRI
DGGLWLRQDODQJLRWHQVLQRJHQ $*7 IRUPDWLRQDQGVHFUHWLRQLQWRWKHWXEXODUÀXLG
The objective of the present study was to evaluate the changes in urinary AGT in
HDFKNLGQH\IURPNLGQH\FOLS .& K\SHUWHQVLYHUDWV
Design and method: Experiments were performed on Sprague Dawley rats
VXEMHFWHGWROHIWUHQDODUWHULDOFOLSSLQJ PPJDS DQGIROORZHGIRUGD\V
prior to anesthesia and separate measurement of urinary AGT in the clipped and
non-clipped kidneys.
Results: 6\VWROLFDUWHULDOSUHVVXUH Q LQFUHDVHGSURJUHVVLYHO\VWDUWLQJDWGD\
IROORZLQJXQLODWHUDODUWHULDOFOLSSLQJDQGUHDFKHG“PP+JE\GD\V
8ULQDU\$*7LQFUHDVHGVLJQL¿FDQWO\FRPSDUHGWR6KDPUDWV Q E\GD\V
after clipping. After anesthesia, separate urine samples from each ureter were
collected to assess renal function and urinary AGT excretion rates. Although
JORPHUXODU¿OWUDWLRQUDWHZDVORZHU$*7ZDVVLJQL¿FDQWO\JUHDWHULQXULQHIURP
3D.07
DIFFERENTIAL EFFECTS OF AEROBIC TRAINING ON
PLASMA AND HEART RENIN-ANGIOTENSIN SYSTEM
IN SPONTANEOUSLY HYPERTENSIVE RATS
S. Silva Junior , D.E. Casarini 2, L.C. Michelini . 1 University of São Paulo,
São Paulo, BRAZIL, 2 Federal University of São Paulo, São Paulo, BRAZIL
Objective: To compare in hypertensive and normotensive rats the sequential
HIIHFWVRIDHURELFWUDLQLQJ 7 RQHLWKHUWKHKHPRG\QDPLFSUR¿OHWKHFKDQJHVRQ
plasma and heart renin-angiotensin system (RAS) and reactive oxygen species
(ROS) production in the left ventricle (LV).
Design and method: 0DOH6+5DQG:.<DJHGZHHNVXQGHUZHQWPD[LPDO
H[HUFLVHWHVWVDQGZHUHDOORFDWHGWR7 RIPD[LPXPH[HUFLVHFDSDFLW\
KGD\ GD\VZHHN RU VHGHQWDU\ 6 JURXSV IRU ZHHNV 6XEJURXSV RI UDWV
ZHUHFDQQXODWHGDWZHHNV 6 7 7 7 DQG 6DQG7 IRU
measurement of resting pressure (MAP) and heart rate (HR), followed by blood
FROOHFWLRQVDOLQHSHUIXVLRQDQGKHDUWKDUYHVWLQJ3ODVPD$QJ,,DQG$QJ FRQWHQWZHUHPHDVXUHGE\+3/&/95$6H[SUHVVLRQ :HVWHUQ%ORWWLQJ 526
SURGXFWLRQ 'LK\GURHWKLGLXPVWDLQLQJ DQGKHDUWK\SHUWURSK\ /9ZHLJKWWLELD
length ratio).
Results: At the beginning of protocols SHR vs WKY exhibited higher MAP
DQG+5 “PP+J“EPLQFRUUHVSRQGLQJWRDQGLQFUHDVHV KLJKHUSODVPD$QJ,, “YV“SPROPO EXWVLPLODU$QJ e37
Journal of Hypertension Volume 32, e-Supplement 1, 2014
FRQWHQW SPROPO /9$&( H[SUHVVLRQ ZDV VLPLODU LQ ERWK JURXSV EXW
6+5H[KLELWHGKLJKHU0$6UHFHSWRUH[SUHVVLRQ “YV“$8 LQFUHDVHG 526 SURGXFWLRQ “ YV “ [ $8 DQG KLJKHU /97/ UDWLR
“YV“PJPP 7LQFUHDVHGWUHDGPLOOSHUIRUPDQFH “
NPK DQGGHFUHDVHGUHVWLQJ+5 DW7 LQERWKJURXSV0$3ZDVRQO\
UHGXFHG LQ 6+5 DW 7 7 FDXVHG DQ HDUO\ IURP 7 LQFUHDVH LQ$QJ
IROORZHGE\$QJ,,UHGXFWLRQ IURP7 ZKLFKGHWHUPLQHGLQERWKJURXSV
DVLPLODUUHGXFWLRQLQSODVPD$QJ,,$QJ UDWLR7GLGQRWFKDQJH/97/
LQFUHDVHG/9H[SUHVVLRQRI$&( 77 DQG0$6UHFHSWRU DW7 DQG
UHGXFHG526SURGXFWLRQRQO\LQ6+5 “[$8DW7 1RFKDQJHVZHUH
observed in S groups.
Conclusions: T-induced improvement of heart function in SHR is primarily asVRFLDWHGZLWKFKDQJHVLQKHDUW7KHSURPSWLPSURYHPHQWRI/9$&($QJ 0DVUHFHSWRUD[LVFRQWULEXWHVWRWKHQRUPDOL]DWLRQRIKHDUWR[LGDWLYHVWUHVV
and pressure fall in the trained SHR.
Supporting: FAPESP, CNPq.
3D.08
EFFECT OF A HIGH SALT DIET ON ENDOTHELIAL
FUNCTION AND BLOOD PRESSURE IN A GENETIC
MODEL OF HYPERTENSION
S. Didion, (0H]]HWWLM. Garrett.
University of Mississippi Medical Center, Jackson, MS, USA
Objective: The BPH2 mouse is a non-angiotensin II-dependent model of genetic
hypertension. Little is known regarding vascular responses and even less is known
UHJDUGLQJWKHLQÀXHQFHRIDKLJKVDOWGLHWRQHQGRWKHOLDOIXQFWLRQRUEORRGSUHVVXUH
in this model. The goal of this study was to test the hypothesis that endothelial
function is impaired in the BPH2 mouse and that both the hypertension and endothelial dysfunction in this model can be exacerbated by high-salt.
Design and method: 0DOH K\SHUWHQVLYH %3+ Q PLFH DQG QRUPRWHQVLYH
JHQHWLFFRQWURO %31Q PLFHZHUHVWXGLHG%3+DQG%31PLFHZHUHUDQGRPO\GLYLGHGLQWRJURXSVWKDWZHUHIHGHLWKHUDQRUPDOVDOW GLHWRUD
KLJKVDOW 1D&O IRUZNV%ORRGSUHVVXUHZDVPHDVXUHGEHIRUHWKHLQLWLDtion and at the conclusion of the experimental diets. Endothelium-dependent and
±LQGHSHQGHQWUHVSRQVHVZHUHH[DPLQHGLQFDURWLGDUWHULHVLQYLWURDWWKHHQGRI
wks the dietary interventions.
Results: 6\VWROLFEORRGSUHVVXUH 6%3 ZDVVLJQL¿FDQWO\KLJKHU 3 LQ%3+
PLFH 6%3 “PP+J DVFRPSDUHGWR%31PLFH “PP+J RQDQRUmal salt diet. In contrast, SBP in either BPH2 or BPN3 mice was not affected
E\ZNVRQDKLJKVDOWGLHW HJ6%3ZDV“DQG“PP+JLQ%3+
and BPN3, respectively). Endothelium-dependent responses to acetylcholine were
PDUNHGO\UHGXFHG 3 LQDUWHULHVIURP%3+PLFHIHGDQRUPDOVDOWGLHWDV
FRPSDUHG WR WKRVH IURP %31 PLFH )RU H[DPSOH —0 DFHW\OFKROLQH SURGXFHG“DQG“UHOD[DWLRQLQ%3+DQG%31DUWHULHVSUHFRQWUDFWHGZLWK
WKHWKURPER[DQHDQDORJ8UHVSHFWLYHO\,QFUHDVHGYDVFXODUVXSHUR[LGHZDV
PRVWOLNHO\DPDMRUPHGLDWRURIHQGRWKHOLDOG\VIXQFWLRQDV7HPSRO P0DVXSHUR[LGHVFDYHQJHU VLJQL¿FDQWO\LPSURYHGHQGRWKHOLDOIXQFWLRQLQ%3+EXWQRW
BPN3 mice. A high salt diet was not associated with any additional impairment of
endothelial function in BPH2 or BPN3 mice. Likewise, responses to nitroprusside
were unaltered by genetype or diet.
Conclusions: 7DNHQ WRJHWKHU WKHVH ¿QGLQJV GHPRQVWUDWH WKDW HQGRWKHOLDO G\Vfunction is present in the carotid artery and that blood pressure and endothelial
dysfunction in the BPH2 mouse is not salt-sensitive.
3D.09
THE ROLE OF MACROPHAGE-DERIVED EXOSOMES
IN HYPERTENSION
H. Iwao 2,3, T. Yamaguchi , M. Osada-Oka 3, M. Shiota 3, M. Tanaka ,
K. Miura , M. Yoshiyama , <,]XPL3. 1 Department of Cardiovascular
Medicine, Osaka City University, Medical School, Osaka, JAPAN, 2 Faculty
of Education, Shitennoji University, Osaka, JAPAN, 3 Department of
Pharmacology, Osaka City University, Medical School, Osaka, JAPAN,
4
Applied Pharmacology and Therapeutics, Osaka City University Medical
School, Osaka, JAPAN
Objective: Hypertension is one of the most important risk factors of cardioYDVFXODUGLVHDVHV6XVWDLQHGK\SHUWHQVLRQLQGXFHVFKURQLFLQÀDPPDWLRQZKLFK
causes cardiac remodeling and dysfunction although it is a protective response
IRUSHUVLVWHQWVWUHVVHV+RZHYHULWLVIXOO\XQNQRZQWKDWWKHUROHRIWKHLQÀDPPDWRU\FHOOVVXFKDVPDFURSKDJHVRQFDUGLRYDVFXODUGLVHDVHVZKLFKLQ¿OWUDWHD
damaged cardiac tissue. It has been recently suggested that exosomes contribute to intracellular communication through the proteins and microRNAs from
excretory cells. Here, we investigated the effects of exosomes secreted from
macrophages in experimental hypertensive models.
Design and method: +\SHUWHQVLYH PRGHO UDWV ZHUH PDGH E\ FRQWLQXRXV
LQIXVLRQ RI DQJLRWHQVLQ ,, $QJ ,, ȝJNJPLQ RU D QLWULF R[LGH V\QWKDVH
LQKLELWRU 1ȦQLWUR/DUJLQLQH PHWK\O HVWHU /1$0( PJP/ LQ GULQNLQJ
ZDWHU IRUGD\V([RVRPHVIURPVHUXPZHUHSXUL¿HGE\XOWUDFHQWULIXJDWLRQ
Human coronary arterial endothelial cells (HCAECs) were treated with serum
H[RVRPHV +XPDQ7+3GHULYHGPDFURSKDJHVZHUHVWLPXODWHGE\$QJ,,
Q0 RUK\SR[LDDQGH[VRVRPHVLQFXOWXUHPHGLDZHUHSXUL¿HG+&$(&V
ZHUHWUHDWHGZLWKPHGLXPH[VRVRPHV 3URWHRPLFDQDO\VLVRI7+3GHULYHG
exosomes was performed.
Results: (OHYDWHG EORRG SUHVVXUH DQG OHIW YHQWULFXODU K\SHUWURSK\ ZHUH
detected by Ang II and L-NAME administration. An amount of proteins in
exosomes was increased in both hypertensive rats compared with that in
normotensive rats. Serum exosomes from hypertensive rats activated some
VLJQDOWUDQVGXFWLRQSDWKZD\VVXFKDVF-XQ1WHUPLQDONLQDVHSPLWRJHQ
activated protein kinase, and Akt in HCAECs. The proteins were positive for
&'DQWLERG\ZKLFKLVDVSHFL¿FPDUNHURIPDFURSKDJHV $FWLYDWHGPDFrophages increased an amount of exsosomal proteins and changed the constitutive proteins in medium exosomes. Medium exosomes collected in Ang IIand hypoxia-stimulated macrophages activated the same signal transduction
pathways as the serum exosomes. These stimulations increased intercellular
DGKHVLRQPROHFXOHLQ+&$(&VVXJJHVWLQJWKDWVWLPXODWHG7+3GHULYHG
H[RVRPHV PD\ LQGXFH SURLQÀDPPDWRU\ HIIHFWV DQG GDPDJH WKH HQGRWKHOLDO
FHOOV 3URWHRPLFDQDO\VLVUHYHDOHGWKDWWKHUHZHUHGLIIHUHQWSURWHLQSUR¿OHV
LQ 7+3GHULYHG H[RVRPHV DPRQJ QRQVWLPXODWLRQ DQG WKH VWLPXODWLRQ RI
Ang II and hypoxia..
Conclusions: Endothelial damage by hypertension may be partially associated with activated macrophages-derived exosomes.
Abstracts
e38
ORAL SESSION
ORAL SESSION
ISH NEW INVESTIGATOR
COMMITTEE AWARDS
NIC.01
BOTH ISOFORMS OF THE NITRIC OXIDE-RECEPTOR
GUANYLYL CYLCLASE PLAY AN IMPORTANT ROLE
IN THE REGULATION OF BLOOD PRESSURE AND
RENAL PERFUSION
M. Thieme, L. Rump, E. Mergia, O. Vonend, S. Potthoff, J. Stegbauer. Insitute
for Nephrology, Heinrich Heine University, Düsseldorf, GERMANY, 2 Institute
for Pharmacology and Toxicology, Ruhr University, Bochum, GERMANY
Objective: NO/cGMP signaling plays an important role in the vascular relaxation and regulation of blood pressure (BP). The NO-stimulated cGMP-forming
guanylyl-cyclase (GC) exists in two isoforms (NO-GC1, NO-GC2). Until now,
the predominat isoform controling the vascular tone in resistance arteries and
consequently renal hemodynamics is unknown. In this study we investigated
WKHLQÀXHQFHRIWKHWZRLVRIRUPVRI*&RQUHQDOSHUIXVLRQDQGEORRGSUHVVXUH
during acute AngiotensinII (AngII) infusion.
Design and method: 51$ZDVLVRODWHGE\/&0IURP=)=*DQGWXPRXU 7 of 14 APA and 7 phaeochromocytoma patients. An Affymetrix microarray analyVLV ZDV SHUIRUPHG FRPSDULQJ =* =) DQG 7 7KH ([SUHVVLRQ RI XSUHJXODWHG
genes was validated by qPCR. 2) Putative Ca2+-sensitive genes were analysed
for protein expression by IHC ± WB. 3) Subcellular localisation of a putative
&DDFWLYDWHG FKORULGH FKDQQHO ZDV GHWHUPLQHG E\ LPPXQRÀXRUHVFHQFH PLcroscopy of transfected HEK293 cells. 4) The channel’s role in regulating aldosterone production was studied by transfection of H295R cells.
Results: JHQHVZHUHDWOHDVWIROGRYHUH[SUHVVHGLQ=*YV=)961/
was 23.5-fold (p=3.6x10-23), and ANO4 19.9-fold higher (p=6.6x10-24) in ZG
WKDQ=)DOWKRXJKERWKZHUHDOVRLQFUHDVHGLQ$3$VH[SUHVVLRQZDVDQG
IROGORZHUUHVSHFWLYHO\WKDQLQ=*T3&5FRQ¿UPHGDQGIROGXSUHJXODWLRQUHVSHFWLYHO\RI961/DQG$12LQ=*YV=) ¿JD ,+&VKRZHG
VHOHFWLYHVWDLQLQJRIERWK961/ )LJXUHFDQGG DQG$12LQ=*:%EORW
was consistent with IHC. 3) Overexpression of ANO4 reduced aldosterone secretion from 27.3 to 11.8 pg/ml and CYP11B2 mRNA of 24-fold in H295R cells
+$WDJJHG$12ORFDOL]HGWRSODVPDPHPEUDQH )LJE Design and method: 6WXGLHV ZHUH SHUIRUPHG LQ PLFH ODFNLQJ HLWKHU WKH Į
*&.2 RUĮ *&.2 VXEXQLWRIWKH12*&UHFHSWRUDQGZLOGW\SHPLFH
In unconscious mice, blood pressures was meassured invasively. Boli of AnJ,, 3KHQ\OHSLQHSKULQ 3KH DQ ĮDGUHQHUJLF UHFHSWRU DJRQLVW RU /1$0(
DQXQVSHFL¿F12V\QWKDVHEORFNHUZHUHDSSOLHGYLDWKHULJKWMXJXODUYHLQ$GGLWLRQDO\UHQDOEORRGÀRZ 5%) ZDVPHDVXUHGFRQWLQXRXVO\YLDDQXOWUDVRQLF
ÀRZSUREHSODFHGDURXQGWKHOHIWUHQDODUWHU\
Results: On baseline, mice lacking either the NO-GC1 or NO-GC2 isoform
showed higher BPs compared to WT mice (GC1-KO: 108mmHg±5, GC2-KO:
PP+J“:7PP+J“ ,QFRQWUDVWEDVHOLQH5%)GLGQRWGLIIHUZLWKLQWKH
three groups. To test, whether the difference in BP is dependent on the lack of NOstimualted GC activity, mice were infused with L-NAME (32mg/kg). BP increased
VLJQL¿FDQWO\KLJKHULQ:7PLFHFRPSDUHG*&DQG*&.2PLFH PP+J“
vs. 19mmHg±2 vs. 27mmHg±1). The application of AngII and Phe in a dose deSHQGHQWPDQQHULQGXFHGDVLJQL¿FDQWKLJKHU%3HODYDWLRQLQERWK*&DQG*&
KO compared to WT mice. Interestingly, the AngII induced BP-increase was more
potent in GC1-KO than in GC2-KO mice. In contrast therefore, AngII induced reGXFWLRQLQ5%)GLGQRWGLIIHUEHWZHHQ*&DQG*&.2PLFHLQGLFDWLQJDQLPSRUtant role of both GC-isoforms in regulating renal hemodynamics.
Conclusions: Our results highlight the fundamental impact of the NO/cGMP
signalling cascade on blood pressure regulation. Moreover, both isoforms of the
NO-GC are essential for BP control under baseline conditions or during acute
infusions of AngII or Phe. Although, the GC1-isoform seems to be more important in the acute vasoconstrictor response, renal hemodynamics are regulated by
both NO-GC-isoforms in a similar fashion.
Conclusions: Two of the most ZG-selective genes are VSNL1, a Ca2+-sensor
previously reported in APAs, whose transfection protects H295R cells from
DSRSWRVLVDQG$12DPHPEHURIWKHDQRFWDPLQIDPLO\RI&DDFWLYDWHG
chloride channels. Both VSNL1 and ANO4 may function to protect normal ZG
cells from Ca2+ activation, and contribute to negative feedback of aldosterone
from APAs. Relatively lower expression in APAs may augment the consequence
of Ca2+ activation by Cav1.3 and other mutations.
NIC.03
NIC.02
PUTATIVE CALCIUM-SENSITIVE GENES, VSNL1
AND ANO4, ARE UPREGULATED IN HUMAN ZONA
GLOMERULOSA CELLS AND MAY PLAY A ROLE IN
REGULATION OF ALDOSTERONE PRODUCTION
C. Maniero 1, J. Zhou 1, E. Azizan 1, ,0F)DUODQH2, S. Neogi 2, C. Brighton 1,
P. Scudieri 3, L. Galietta 3, M. Brown 1. 1 Clinical Pharmacology Unit,
University of Cambridge, Addenbrookes Hospital, Cambridge, UNITED
KINGDOM, 2 Genomics CoreLab, Cambridge NIHR BRC, Dept. Clinical
Biochemistry, Addenbrookes Hospital, Cambridge, UNITED KINGDOM,
3
U.O.C. Genetica Medica, Istituto Giannina Gaslini, Genoa, ITALY
Objective: Somatic mutations in genes encoding Cav1.3 and Na+/K+-ATPase
delineate a zona glomerulosa (ZG) subtype of aldosterone producing adenomas
(APA).1 In order to identify molecules which are markers of a ZG-phenotype
DQG PD\ EH LQÀXHQFHG E\ JDLQRIIXQFWLRQ PXWDWLRQV LQ DQ DGUHQDOVHOHFWLYH
&D FKDQQHO ZH FRPSDUHG WKH WUDQVFULSWRPH RI DGMDFHQW =* DQG ]RQD IDVFLFXODWD =) DQGLQYHVWLJDWHGZKHWKHUJHQHVXSUHJXODWHGLQ=*PD\LQÀXHQFH
aldosterone production.
PHARMACOLOGICAL ANGIOTENSIN TYPE 2
RECEPTOR STIMULATION MODULATES ACUTE
RENAL FUNCTION IN FEMALE BUT NOT MALE
SPONTANEOUSLY HYPERTENSIVE RATS
L. Hilliard 1, C. Chow 1, U. Steckelings 3, R. Widdop 2, K. Denton 1.
Department of Physiology, Monash University, Melbourne, AUSTRALIA,
2
Department of Pharmacology, Monash University, Melbourne, AUSTRALIA,
3
Institute of Molecular Medicine, University of Southern Denmark, Odense,
DENMARK
1
Objective: Accumulating evidence suggests that the protective pathways of the
renin-angiotensin system (RAS) are enhanced in females, including the angioWHQVLQW\SHUHFHSWRU $75 :HKDYHSUHYLRXVO\VKRZQWKDWWKHKLJKO\VSHFL¿F
AT2R agonist, Compound 21 (C21), modulates acute renal haemodynamic and
excretory function in both male and female normotensive rats, inducing renal vaVRGLODWDWLRQDQGLQFUHDVHGQDWULXUHVLV+RZHYHUWKHVH[VSHFL¿FDELOLW\RI$75
agonist therapy to afford renoprotection in hypertension has not previously been
investigated. The aim of the current study was to examine the effects of acute
AT2R stimulation on renal haemodynamic and excretory function in male and
female spontaneously hypertensive rats (SHR), using the AT2R agonist C21.
S
A
T
U
R
D
A
Y
O
R
A
L
S
e39
Journal of Hypertension Volume 32, e-Supplement 1, 2014
Design and method: 18-19 week old SHR (n=6-8 per group) were anaestheWLVHG DQG LQVWUXPHQWHG IRU WKH PHDVXUHPHQW RI PHDQ DUWHULDO SUHVVXUH 0$3
FDURWLG FDWKHWHU DQG UHQDO EORRG ÀRZ 7%) 7UDQVRQLF ÀRZ SUREH 5HQDO
haemodynamic and excretory function was then examined in response to vehicle, a graded infusion of C21 (100-300 ng/kg/min), or C21 combined with the
$75DQWDJRQLVW3' PJNJKU *ORPHUXODU¿OWUDWLRQUDWH *)5 ZDV
measured via [3H]-inulin clearance.
Results: $75 VWLPXODWLRQ UHVXOWHG LQ D VLJQL¿FDQW LQFUHDVH LQ 5%) LQ IHPDOH
6+5 3YHUVXVYHKLFOHWUHDWPHQW ZLWKRXWLQÀXHQFLQJ0$3$WQJNJ
PLQ&5%)LQFUHDVHGE\“IURPEDVHOLQH)XUWKHUPRUHDVLJQL¿FDQW
LQFUHDVHLQXULQHÀRZDQGXULQDU\VRGLXPH[FUHWLRQZDVREVHUYHGLQIHPDOH&
treated SHR at the highest dose of C21 administered (P < 0.05). This was seen in
WKHDEVHQFHRIDQ\VLJQL¿FDQWFKDQJHLQ*)5LQGLFDWLQJWKDWWKHQDWULXUHWLFHIIHFWV
of AT2R stimulation were likely due to altered renal tubular function. In comSDULVRQZHGLGQRWREVHUYHDQ\VLJQL¿FDQWHIIHFWRI$75VWLPXODWLRQRQUHQDO
hemodynamic or excretory function in male SHR at any dose of C21 administered.
Conclusions: AT2R stimulation enhances renal vasodilatation and sodium exFUHWLRQZLWKRXWFRQFRPLWDQWDOWHUDWLRQVLQ*)5LQIHPDOH6+5&KURQLFVWXGLHV
of AT2R agonist therapy on renal function and arterial pressure in hypertensive
states are now required to establish whether the AT2R is a suitable therapeutic
target for the treatment of cardiovascular disease, particularly in females.
NIC.04
DACH1, A ZONA GLOMERULOSA SELECTIVE GENE
IN THE HUMAN ADRENAL, PLAYS AN IMPORTANT
ROLE IN ALDOSTERONE PRODUCTION AND
REGULATES WNT ACTIVITY
J. Zhou 1, E. Azizan 1, S. Neogi 2, ,0F)DUODQH2, C. Brighton 1, C. Maniero 1,
A. Teo 1, L. Shaikh 1, M. Brandorff 1, M. Brown 1. 1 Clinical Pharmacology
Unit, University of Cambridge, Addenbrookes Hospital, Cambridge, UNITED
KINGDOM, 2 Genomics CoreLab, Cambridge NIHR BRC, Dept. Clinical
Biochemistry, Addenbrookes Hospital, Cambridge, UNITED KINGDOM
Objective: Genetic, transcriptome and histological analyses suggest that small,
frequently overlooked aldosterone producing adenomas (APAs) resembling
normal zona glomerulosa (ZG) may be as common as the more classical zona
IDVFLFXODWD =) OLNH$3$Vï:HZLVKHGWRGHWHUPLQHZKHWKHUWKHUHDUHVLJQDWXUH
genes for ZG that might provide evidence of ZG-origin of ZG-like APAs.
NIC.05
ANGIOTENSIN II-INDUCED VASCULAR INJURY
IS COUNTERACTED BY FOXP3+ T REGULATORY
LYMPHOCYTES
M. Mian 1, T. Barhoumi 1, M. Briet 1, A. Ene 1, A. Rehman 1, P. Paradis 1,
E.L. Schiffrin 1,2. 1 Vascular and Hypertension Research Unit, Lady Davis
Institute for Medical Research, McGill University, Montreal, CANADA,
2
Department of Medicine, Sir Mortimer B. Davis Jewish General Hospital,
McGill University, Montreal, CANADA
Objective: 7 O\PSKRF\WHV YLD D ORZJUDGH LQÀDPPDWRU\ UHVSRQVH FDXVH
YDVFXODU LQMXU\ LQ DQJLRWHQVLQ ,,LQGXFHG K\SHUWHQVLRQ EXW WKH UROH RI 7
regulatory cells (Treg) is unclear. Angiotensin II-induced hypertension is
EOXQWHGLQ7DQG%FHOOGH¿FLHQW 5DJ PLFHDQGUHVWRUHGZLWKUHFRQVWLWXWLRQRI7FHOOV:HK\SRWKHVL]HGWKDWDGRSWLYHWUDQVIHURI)2;3GH¿FLHQW
(Scurfy) vs. wild-type T cells will exacerbate angiotensin II-induced vascular damage in Rag1-/- mice.
Design and method: (OHYHQZHHN ROG PDOH 5DJ PLFH ZHUH LQMHFWHG
IV with vehicle (control), 10 million wild-type or Scurfy T cells, 1 million CD4+CD25+ Treg alone or with Scurfy T cells, and 2 weeks later were
infused or not with angiotensin II (490 ng/kg/min, SC) for 14 days (n=38). Telemetric systolic (SBP) and diastolic (DBP) blood pressures, vascular
IXQFWLRQ DQG VWUXFWXUH UHDFWLYH R[\JHQ VSHFLHV 526 SURGXFWLRQ DQG ¿bronectin expression of mesenteric arteries (MA) and aortic collagen content
were determined.
Results: Angiotensin II induced a 40 mmHg SBP rise in control, wild-type
and Scurfy T cells groups, but DBP rise was ~10 mmHg greater in wild-type
DQG6FXUI\7FHOOLQMHFWHGPLFHWKDQLQFRQWUROV 3 &'&'7UHJ
LQMHFWLRQDORQHWHQGHGWRUHGXFH6%3ULVHEXWGLGQRWDIIHFW'%3FRPSDUHG
to control. Adoptive transfer of wild-type T cells restored angiotensin II
induced-endothelial dysfunction (P<0.05), which was exaggerated in Scurfy
7 FHOOLQMHFWHG PLFH 3 EXW QRW LQ PLFH UHFHLYLQJ 6FXUI\ 7 FHOOV CD4+CD25+ Treg (P<0.05). Angiotensin II increased ROS production in
0$ZDOODQGSHULYDVFXODUIDWLQ6FXUI\7FHOOLQMHFWHGPLFH 3 EXWQRW
when co-transferred with CD4+CD25+ Tregs. Angiotensin II induced vascular stiffness (P<0.01) and hypertrophic remodeling (P<0.05) in control and
6FXUI\7FHOOLQMHFWHGPLFHEXWQRWLQRWKHUJURXSV$QJLRWHQVLQ,,WHQGHG
WR LQFUHDVH 0$ ¿EURQHFWLQ H[SUHVVLRQ RQO\ LQ FRQWURO DQG 6FXUI\ 7 FHOO
LQMHFWHGPLFH$RUWLFFROODJHQFRQWHQWWKRXJKQRWDIIHFWHGE\DQJLRWHQVLQ,,
WUHDWPHQWZDVJUHDWHULQFRQWURODQG6FXUI\7FHOOLQMHFWHGPLFH 3 but not in other groups.
Conclusions: 7KHVHUHVXOWVGHPRQVWUDWHWKDW)R[S7UHJXODWRU\O\PSKRcytes have a protective role against angiotensin II-induced vascular dysfunction, remodeling and oxidative stress.
NIC.06
Design and method: $PLFURDUUD\DVVD\ZDVSHUIRUPHGXVLQJWULRVRI=)
=*DQG$3$VDQGDIXUWKHUVHYHQSDLUVRI=)DQG=*DGMDFHQWWRSKDHRFKURPRcytoma. Total RNA was extracted by laser capture microdissection. Validation
by qPCR was performed of selected genes upregulated in ZG. 2) DACH1 was
further analyzed for protein expression, determined by immunohistochemistry
and western blotting in 13 adrenals. 3) Aldosterone production was assessed in
H295R cells using ON-TARGETplus siRNA and overexpression. 4) Apoptosis
was assessed in H295R cells with overexpressed DACH1 and vector control
by TUNEL assay. 5) Wnt signaling activity was assessed by co-transfection of
7&)/()UHSRUWHUDQG'$&+SODVPLG
Results: ([SUHVVLRQRIJHQHVZDVDWOHDVWIROGKLJKHULQ=*WKDQ=)
'$&+ZDVIROGKLJKHUH[SUHVVHGLQ=*YV=) 3 î DQG
IROGXSUHJXODWHGLQ=*YV$3$ 3 î 5HDOWLPH3&5FRQ¿UPHGWKH
H[SUHVVLRQ SUR¿OHV ,+& RI '$&+ VKRZHG KLJKO\ VHOHFWLYH VWDLQLQJ RI
=*LQDOODGUHQDOV )LJD :HVWHUQEORWVXSSRUWHG,+& .QRFNGRZQRI
'$&+UHVXOWHGLQDVLJQL¿FDQWLQFUHDVHLQ&<3%P51$OHYHOV 3 DQG DOGRVWHURQH SURGXFWLRQ )LJE Q 3 [ 2YHUH[SUHVVLRQ RI
'$&+ UHVXOWHG LQ D VLJQL¿FDQW GHFUHDVH LQ DOGRVWHURQH SURGXFWLRQ )LJF
Q 3 [ 7KHDSRSWRWLFUDWHZDVVLJQL¿FDQWO\KLJKHULQ+5FHOOV
with overexpressed DACH1. 5) Overexpression of DACH1 activated Wnt signDOLQJSDWKZD\LQ+5FHOOV )LJGQ 3 [ Conclusions: Several unexpected genes, which did not feature in a recent study
of rat adrenal, are markedly over-expressed in human ZG.² We speculate that [i]
the high expression of DACH1 contributes to the apoptosis observed in human
ZG,³ and [ii] down-regulation of DACH1 may contribute to APA formation.
CD40 MEDIATES RENAL FIBROSIS IN THE DAHL
GENETICALLY HYPERTENSIVE RAT
S. Haller 1, ')ROW1, K. Evens 1, J. Tian 1, S. Kumarasamy 2, K. Gopalakrishnan 2,
J. Shapiro 3, B. Joe 2, C. Cooper 1. 1 University of Toledo, Health Science
Campus, Department of Medicine, Toledo, OH, USA, 2 University of Toledo,
Health Science Campus, Center for Hypertension and Personalized Medicine,
Toledo, OH, USA, 3 Marshall University School of Medicine, Department of
Medicine, Huntington, VA, USA
Objective: &G SOD\V D FUXFLDO UROH LQ LPPXQLW\ DQG LQÀDPPDWLRQ DQG KDV
EHHQLPSOLFDWHGLQWKHGHYHORSPHQWRIUHQDO¿EURVLVLQVRPHLQMXU\PRGHOV7KH
genetically hypertensive Dahl S rat (S rat) is highly susceptible to the development of renal disease, and provides a suitable background to investigate the
relationship between Cd40 and renal disease. We sought to create a Cd40 mutant
with the genetic background of the S rat to determine the role of Cd40 in the
development of hypertensive renal disease.
Design and method: A novel Cd40 mutant, with targeted disruption of Cd40,
ZDVFUHDWHGLQWKH6UDWXVLQJWKH]LQF¿QJHUQXFOHDVHPHWKRG0DOH&GPXtant rats weighing between 350-400 g were used (n=8). Western blot analysis
was performed on kidney tissue and renal function was determined by urinary
protein excretion (UPE). Eight Dahl S rats were used as age-matched controls.
Results: :HVWHUQEORWDQDO\VLVFRQ¿UPHGWKDWWKH6UDWVVKRZHGFURVVUHDFWLYLW\
to the Cd40 antibody, whereas the Cd40 mutants did not. There was no difference
in systolic blood pressure between the S rats and Cd40 mutants. Kidney tissue
GHULYHGIURPWKH&GPXWDQWVVKRZHGDVLJQL¿FDQWGHFUHDVHLQFROODJHQW\SH
H[SUHVVLRQDSULPDU\PDUNHURI¿EURVLVFRPSDUHGWRWKHNLGQH\WLVVXHRI6UDW
FRQWUROV S)LJXUHRQWKHIROORLQJSDJH 7KH&GPXWDQWVDOVRH[KLELWHG
DVLJQL¿FDQWGHFUHDVHLQ83(FRPSDUHGWRWKH6UDWV “YV“
mg/24hrs, p<0.01).
e40
Journal of Hypertension Volume 32, e-Supplement 1, 2014
Conclusions: A novel Cd40 mutant, using a genetic background susceptible to
UHQDOGLVHDVHGHFUHDVHVUHQDO¿EURVLVDQGLPSURYHVUHQDOIXQFWLRQLQGHSHQGHQW
of blood pressure. Our results indicate that Cd40 may play a crucial role in the
development of hypertensive renal disease.
Results: Overall, approximately 5.7 and 5 million variants are present in HHR
DQG1+5UHVSHFWLYHO\DQGWKHPDMRULW\RIWKHYDULDQWV ZHUH613V,Q
QTL Cm22, we found approximately 10 thousand variants in each strain. The
array data showed that gene for tripartite motif-containing 55 (Trim55) was sigQL¿FDQWO\GRZQUHJXODWHGLQ++5 )& )'5 :HYDOLGDWHGWKHVH
¿QGLQJV E\ UHDOWLPH SRO\PHUDVH FKDLQ UHDFWLRQ T3&5 ZKLFK VKRZHG WKDW
Trim55 mRNA is down-regulated from neonatal to late adulthood in the CH
model.
$QDO\VLVRIWKHJHQHUHJLRQRI7ULPLGHQWL¿HGDQGYDULDQWVLQ++5DQG
NHR, respectively. One missense mutation in the HHR was located in its ninth
exon. In silico studies demonstrated that this mutation may cause a change in the
protein structure which may affect function.
Conclusions: The Trim55 gene in QTL CM22 is a novel candidate gene for
polygenic hypertrophy development independent of blood pressure.
NIC.08
NIC.07
WHOLE GENOME AND TRANSCRIPTOME
APPROACH IN A POLYGENIC MODEL FOR CARDIAC
HYPERTROPHY IDENTIFIES TRIM55 AS A NEW
CANDIDATE GENE IN QUANTITATIVE TRAIT LOCUS
CARDIAC MASS 22
P. Prestes 1, )0DUTXHV1, G. Lopez-Campos 2, S.B. Harrap 3, )-&KDUFKDU1.
Federation University Australia, School of Health Sciences, Ballarat,
AUSTRALIA, 2 University of Melbourne, Health and Biomedical Research
Unit, Melbourne, AUSTRALIA, 3 University of Melbourne, Department of
Physiology, Melbourne, AUSTRALIA
1
Objective: Cardiac hypertrophy (CH) is the main risk factor for heart disease
after age. Multiple genetic factors are known to be involved but still poorly understood. We have previously described a quantitative trait locus (QTL) cardiac
PDVV &P RQFKURPRVRPHZKLFKLQÀXHQFHVKHDUWVL]HLQGHSHQGHQWO\RI
blood pressure. Our aim was to determine which genes in QTL Cm22 contribute
to CH using a polygenic genetic model.
Design and method: We used a genomic and transcriptomic approach to idenWLI\ JHQHV LQ &P FRQWULEXWLQJ WR &+ )LUVWO\ ZH XVHG WKH ,OOXPLQD +L6HT
2000 platform to sequence the whole-genome of the Hypertrophic Heart Rat
(HHR), a normotensive genetic model of CH, and its control, the Normal Heart
Rat (NHR). Both genomes were aligned and compared to Rat Genome Database
v3.4 and four types of variants were analysed: single nucleotide polymorphisms
(SNPs), insertions and deletions (InDels), copy number variations (CNVs)
and structural variants (SVs). Secondly, we investigated gene expression of all
Cm22 genes in left ventricles of HHR and NHR (n=8 per group) using Affymetrix GeneChip® Rat Gene 1.0 ST arrays. We then combined these data to
identify unique variants in genes differentially expressed in QTL Cm22.
ROLE OF GRK4 IN THE REGULATION OF ARTERIAL
AT1 RECEPTOR IN HYPERTENSION
K. Chen, &)XC. Chen, L. Liu, H. Ren, Y. Han, J. Yang, D. He, C. Zeng,
;/X. Department of Cardiology, Daping Hospital, The Third Military
Medical University, Chongqing Institute of Cardiology, Chongqing, CHINA
Objective: G protein-coupled receptor kinase 4 (GRK4) gene variants, via
impairment of renal dopamine receptor and enhancement of renin-angiotensin
system functions, cause sodium retention and increase blood pressure. Whether
or not GRK4 and the angiotensin type 1 receptor (AT1R) interact in the aorta
is not known.
Results: We report that GRK4 is expressed in vascular smooth muscle cells
(VSMCs) of the aorta. Heterologous expression of the GRK4 gamma variant
142V in A10 cells increased AT1R protein expression and AT1R-mediated
increase in intracellular calcium concentration. The increase in AT1R exSUHVVLRQZDVUHODWHGWRDQLQFUHDVHLQ$75P51$H[SUHVVLRQYLDWKH1)
kappa B pathway. As compared with control, cells expressing GRK4 gamma
9KDGJUHDWHU1)NDSSD%DFWLYLW\ZLWKPRUH1)NDSSD%ERXQGWRWKH
AT1R promoter. The increased AT1R expression in cells expressing GRK4
gamma 142V was also associated with decreased AT1R degradation, which
may be ascribed to lower AT1R phosphorylation. There was a direct interaction between GRK4 gamma wild-type (WT) and AT1R that was decreased by
GRK4 gamma 142V. The regulation of AT1R expression by GRK4 gamma
9LQ$FHOOVZDVFRQ¿UPHGLQ*5.JDPPD9WUDQVJHQLFPLFH
AT1R expression was higher in the aorta of GRK4 gamma 142V transgenic
mice than control GRK4 gamma wild-type (WT) mice. Angiotensin II-mediated vasoconstriction of the aorta was also higher in GRK4 gamma 142V
than WT transgenic mice.
Conclusions: This study provides a mechanism by which GRK4, via regulation
of arterial AT1R expression and function, participates in the pathogenesis of
conduit vessel abnormalities in hypertension.
Abstracts
e41
ORAL SESSION
LATE-BREAKERS SESSION 1
LB01.01
MICROALBUMINURIA IN PREHYPERTENSION
E. Tenekecioglu, M. Yilmaz, O. Arican Ozluk, F. Vatansever Agca,
K. Karaagac, T. Peker, A. Akgumus, B. Boyraz, F. Kahraman, U. Parlak,
M. Senturk, F. Er. Bursa Yuksek Ihtisas Education and Reserach
Hospital,Cardiology, Bursa, TURKEY
Objective: Beside hypertension(HT),prehypertension(PHT) was also a
significant independent predictor of cardiovascular diseases.Urinary albumin leakage is a manifestation of generalized vascular damage. B-type
natriuretic peptide(BNP) is a vasoactive peptide which is secreted by the
left ventricle in response to myocytic stretch and is involved in regulating volume homeostasis and cardiac remodeling.In this study we aimed to
investigate the relationship between untreated prehypertension, microalbuminuria and BNP.
Design and method: Of 105 untreated prehypertensive subjects (53 men, 52
women),100 untreated hypertensive subjects (51 men, 49 women) and 57 normotensive subjects (32 men, 25 women) none had a history of diabetes.Urine
albumin excretion was measured by an immunoradiometric assay in a morning
urine sample.
Results: The prevalence of microalbuminuria in the hypertensive group was
higher than in the prehypertensive group and in the normotensive group (Hypertensive group 33.9% , prehypertensive 25.9 %, normotensive group 10%).
Subjects with HT were older, and had higher prevalence of microalbminuria;
larger body mass index, higher levels of triglycerides, fasting blood glucose
and creatinin were more common in subjects with HT than in those with
PHT.In hypertensive group; patients with microalbuminuria had had higher
systolic blood pressure,BNP,LVMI and lower eGFR as compared to those
ZLWKRXWPLFURDOEXPLQXULD0$ZDVVLJQL¿FDQWO\FRUUHODWHGZLWK/90, U S %13 U S DQG 6%3 U S /90, ZDV VLJQL¿FDQWO\FRUUHODWHGZLWK%13 U S DQG6%3 U S ,Q PXOWLYDULDWH ORJLVWLF UHJUHVVLRQ PRGHO 6%3 25 S DQG
%13 25 S ZHUH WKH RQO\ LQGHSHQGHQW YDULDEOHV FRUUHODWHG
with microalbuminuria in hypertensive subjects. In prehypertension group;
patients with microalbuminuria had had higher SBP,BNP,LVMI and lower
H*)5DVFRPSDUHGWRWKRVHZLWKRXWPLFURDOEXPLQXULD0$ZDVVLJQL¿FDQWO\
FRUUHODWHGZLWK/90, U S %13 U S DQG6%3 U S ,Q PXOWLYDULDWH ORJLVWLF UHJUHVVLRQ DQDO\VLV 6%3 25
S %13 25 S ZHUH LQGHSHQGHQWO\ DVVRFLDWHG ZLWK PLcroalbuminuria.
Conclusions: In PHT, SBP, BNP and MA are closely associated with each other.
MA should be a part of the examination of the patient with PHT. Even in early
stages of increased blood pressure, those subjects with PHT should get medical
treatment in order to prevent the effects of prehypertension on vascular structure
and myocardium.
LB01.02
LERCANIDIPINE CONTRIBUTES TO INCREASED
REENDOTHELIALIZATON CAPACITY OF EARLY
ENDOTHELIAL PROGENITOR CELLS FROM PATIENTS
WITH ESSENTIAL HYPERTENSION
J. Tao, X. Zhang, S. Xu, H. Zhi, X. Hu, W. Xie. Department of Hypertension
DQG9DVFXODU'LVHDVH)LUVW$I¿OLDWHG+RVSLWDO6XQ<DW6HQ8QLYHUVLW\
Guangzhou, CHINA
Objective: Dysfunction of early endothelial progenitor cells (EPCs) is responsible for impaired endothelial repair capacity after arterial injury in patients
with hypertension. Here we hypothesized that diminished signaling of CXC
chemokine receptor seven (CXCR7) contributes to the reduced EPC functions.
/HUFDQLGLSLQH D GLK\GURS\ULGLQH FDOFLXP FKDQQHO DQWDJRQLVW KDV D EHQH¿FLDO
effect on vascular function. We hypothesized that lercanidipine might facilitate
the expression of CXCR7 signaling in EPCs, which contributes to EPC-mediated reendothelialization after arterial injury.
Design and method: To test these assumptions, CXCR7 signaling and its relation to endothelial repair capacity of early EPCs were examined in hypertensive
patients and normal subjects. EPCs from hypertensive patients were treated with
lercanidipine. Human EPCs were tested in vitro for the ability to affect CXCR7
signaling as well as migration and adhesion functions. We also assessed the effect of transplantation of EPCs from hypertensive patients on in vivo reendothelialization after wire-mediated injury of the carotid artery in nude mice.
Results: Compared with healthy subjects, CXCR7 expression of EPCs from hySHUWHQVLYHSDWLHQWVZDVVLJQL¿FDQWO\UHGXFHG0HDQZKLOHWKHSKRVSKRU\ODWLRQ
RISPLWRJHQDFWLYDWHGSURWHLQNLQDVH S0$3. DGRZQVWUHDPVLJQDOLQJ
of CXCR7, was elevated, which increased cleaved casepase-3 level of EPCs.
Lercanidipine augmented CXCR7 expression and decreased the phosphorylaWLRQRIS0$3.ZKLFKZDVSDUDOOHOHGWR(3&IXQFWLRQDOXSUHJXODWLRQRILQ
vitro functions and in vivo reendothelialization capacity in a nude mouse model
of carotid artery injury. The enhanced in vitro and in vivo functions of EPCs
were markedly inhibited by neutralizing monoclonal antibody against CXCR7,
ZKLFK ZDV EORFNHG E\ S 0$3. LQKLELWRU 6% 'RZQUHJXODWLRQ RI
FOHDYHG FDVHSDVH OHYHO LQGXFHG E\ OHUFDQLGLSLQH RU 6% SUHWUHDWPHQW
improved EPC functions.
Conclusions: 2XUVWXG\GHPRQVWUDWHGIRUWKH¿UVWWLPHWKDWGLPLQLVKHG&;&5
signal at least partially contributes to the reduced in vitro functions and in vivo
reendothelialization capacity of EPCs from hypertensive patients. Upregulation
of CXCR7 expression induced by lercanidipine treatment may be a novel therapeutic target for increased endothelial repair capacity in hypertension.
LB01.03
ALDOSTERONE-RENIN RATIO AND RENAL
HEMODYNAMICS IN ESSENTIAL HYPERTENSION
M. Schütten, A.J.H.M. Houben, A.A. Kroon, C.D.A. Stehouwer, P.W. de
Leeuw. 0DDVWULFKW8QLYHUVLW\&DUGLRYDVFXODU5HVHDUFK,QVWLWXWH0DDVWULFKW
'HSDUWPHQWRI,QWHUQDO0HGLFLQH0DDVWULFKW1(7+(5/$1'6
Objective: A relative aldosterone excess for a given level of renin is characteristic of hypertensive patients with idiopathic hyperaldosteronism, but can be detected to a lesser extent in a subset of essential hypertensives as well. In addition
to its tubular actions inducing sodium retention, aldosterone has been suggested
WR HOLFLW UHQDO YDVRFRQVWULFWLRQ 6LQFH UHGXFHG UHQDO EORRG ÀRZ LV D IUHTXHQW
observation in essential hypertensive patients and might contribute to sustained
blood pressure elevation, we investigated the association of aldosterone, relative
to renin levels, with renal perfusion in these patients.
Design and method: From a group of hypertensive patients who had undergone
renal angiography, we selected those with patent renal arteries and without primary aldosteronism. Antihypertensive therapy had been discontinued 3 weeks
before the procedure. Prior to contrast administration, blood samples were
drawn for determination of renin and aldosterone levels and side-selective renal
EORRGÀRZZDVPHDVXUHGXVLQJ;HQRQZDVKRXW2IDOOSDWLHQWVZHFROOHFWHG
data regarding age, sex, sodium excretion, kidney function, prior cardiovascular
events and risk factors for cardiovascular disease.
Results: We studied 94 patients (47 men and 47 women) with a mean (± SD)
EORRGSUHVVXUHRI““PP+J0HDQUHQDOEORRGÀRZ 05%) RI
WKHOHIWNLGQH\ZDVPHDVXUHGVXFFHVVIXOO\LQSDWLHQWV “P/PLQJ ULJKW05%)FRXOGEHGHWHUPLQHGLQSDWLHQWV “P/PLQJ 0XOWLple regression analysis revealed an inverse association between log aldosteroneUHQLQUDWLR $55 DQGOHIW05%) % S ZKLFKEHFDPHHYHQ
VWURQJHUDIWHUDGMXVWPHQWIRUFRQIRXQGHUV % S VHHDOVRWDEOH
,QFRQWUDVWORJ$55ZDVQRWUHODWHGWRULJKW05%) % S S
A
T
U
R
D
A
Y
O
R
A
L
S
e42
Journal of Hypertension Volume 32, e-Supplement 1, 2014
Conclusions: A higher ARR is associated with reduced perfusion of the left,
but not of the right kidney. Since aldosterone is capable of increasing sympaWKHWLFQHUYHDFWLYLW\WKHDV\PPHWU\RIWKLVDVVRFLDWLRQFRXOGEHDUHÀHFWLRQRI
a denser sympathetic innervation of the left, compared to the right renal artery,
as has been observed in animal models.
LB01.05
LB01.04
A CARDIOMYOCYTE TARGETED DELIVERY SYSTEM
OF THERAPEUTIC REGIMENS FOR THE EFFICIENT
REGRESSION OF CARDIAC HYPERTROPHY IN RAT
MODEL
S. Rana, S. Sarkar.
8QLYHUVLW\RI&DOFXWWD'HSDUWPHQWRI=RRORJ\&DOFXWWD,1',$
Objective: Diverse array of therapeutic regimens are used to regress cardiac hypertrophy, albeit in vivo dosing has been a challenge as bioactive
molecules are mostly lost in circulation before acting upon target organ of
interest. By-stander effect and lower retention of bioactive molecules within
ERG\UHGXFHSURVSHFWLYHIXQFWLRQDOHI¿FDF\RIWKHUDSHXWLFV9DULRXVH[SHULmental therapeutic strategies are limited due to toxicity at by-stander organs.
Targeted delivery of encapsulated therapeutics via nanopolymer conjugated
FDUGLRP\RF\WHVSHFL¿FOLJDQGFRXOGEULQJDERXWHIIHFWLYHVWUDWHJLHVRIWUHDWment without affecting other organs.
Design and method: The study was designed to develop a cardiac tissue
VSHFL¿F VL51$ ORDGHG QDQRSHSWLGH GHOLYHU\ V\VWHP E\ FRQMXJDWLQJ &DUboxymethyl chitosan (CMC), a cationic polymer, with a targeted 20-mer
SHSWLGHOLJDQG(I¿FLHQF\RIWKHSHSWLGHLQWDUJHWHGORFDOL]DWLRQRIFRQVWUXFW
was tested in vitro with neonatal cardiomyocytes and in vivo by intravenous
injection onto rats. CMC-peptide construct was bio-physically characterized
and release stability of p53 siRNA was analysed. Knock down of candidate
gene was checked on cardiac tissue as well as on by-stander organs. Further,
regression of cardiac hypertrophy was tested systemically by marker gene
expression and M-mode echocardiography analysis.
Results: Carboxymethyl chitosan conjugated with a peptide ligand targets
and permeabilize cardiomyocytes. This novel nanopolymer-peptide construct showed stable encapsulation and release of siRNA load. The cardioP\RF\WH WDUJHWHG FRQVWUXFW VKRZV HI¿FLHQW GHOLYHU\ RQWR FDUGLRP\RF\WHV
DORQJ ZLWK EHWWHU LQ YLYR UHWHQWLRQ HI¿FLHQF\ DQG SURWHFWLRQ IURP 51DVH
mediated serum degradation or polyanionic decomplexation of encapsulated
siRNA. Encapsulation of p53 siRNA as candidate therapeutic and its targeted delivery showed reduced by-stander effect without showing any signs of
HFWRGHUPDOWXPRULJHQHVLVLQYLYRDORQJZLWKHI¿FLHQWUHJUHVVLRQRIFDUGLDF
hypertrophy (as shown by downregulated hypertrophy marker genes and colODJHQYROXPHIUDFWLRQ DQGVLJQL¿FDQWO\LPSURYHGFDUGLDFIXQFWLRQ
Conclusions: 7KLVLVWKH¿UVWUHSRUWVKRZLQJDQRYHOFDUGLRP\RF\WHVSHFL¿F
GHOLYHU\V\VWHPWKDWHI¿FLHQWO\UHOHDVHELRDFWLYHPROHFXOHVZLWKLPSURYHGRQ
target vs. off-target action for reducing side effect to by-strander organs. The
novel nano-peptide construct could be used for developing effective therapeutic strategies within cardiac micro-environment by targeted knockdown of any
causal genes.
IN VITRO EMBRYO CULTURE: A PERICONCEPTIONAL
MANIPULATION THAT LEADS TO ALTERED
BAROREFLEX SENSITIVITY IN EARLY POSTNATAL
LIFE
M. Padhee 1, C. McMillen 1, S. MacLaughlin 1, S. Zhang 1, J. Armitage 2,
D. Kleemann 3, S. Walker 3, J. Morrison 1. 16DQVRP,QVWLWXWHRI+HDOWK
5HVHDUFK8QLYHUVLW\RI6RXWK$XVWUDOLD$GHODLGH$8675$/,$26FKRRORI
0HGLFLQH 2SWRPHWU\ 'HDNLQ8QLYHUVLW\*HHORQJ$8675$/,$37XUUHW¿HOG
5HVHDUFK&HQWUH6RXWK$XVWUDOLDQ5HVHDUFKDQG'HYHORSPHQW,QVWLWXWH
$GHODLGH$8675$/,$
Objective: Hypertension is the most common cardiovascular risk factors. Studies have highlighted the importance of the nutritional environment of the oocyte
and early embryo during the periconceptional period which can alter blood pressure and play an important role in determining cardiovascular health in later life.
We hypothesise that in vitro embryo culture and transfer as well as manipulations to the nutritional environment during the periconceptional period, result in
dysregulation of haemodynamics in young sheep.
Design and method: Embryos were either transferred to an intermediate ewe
(ET) or cultured in vitro in the absence (IVC) or the presence of human serum
,9&+6 DQGDPHWK\OGRQRU ,9&+60 IRUGD\V G &RQWUROVZHUHQDWXrally mated (NM) ewes. Mean arterial pressure (MAP) and heart rate (HR)
were measured via an indwelling carotid artery cannula under basal conditions and during phenylephrine infusion. The relationship between MAP and
HR was analysed using a linear regression plot (Graphpad, Prism) to estimate
baroreceptor function. One way ANOVA was used to analyse the slopes from
each curve.
Results: 7KHUHZDVDVLJQL¿FDQWLQYHUVHUHODWLRQVKLSEHWZHHQ0$3DQG+5LQ
response to phenylephrine in the NM, ET and IVCHS groups. However, this
UHODWLRQVKLSZDVEOXQWHGLQWKH,9& P U DQG,9&+60
P U JURXSV
Conclusions: 7KH EOXQWLQJ RI EDURUHÀH[ VHQVLWLYLW\ PD\ VXJJHVW HDUO\ LQGLcations of compromised cardiovascular function in the IVC and IVCHS+M
groups.
LB01.06
BLOOD PRESSURE AND MORTALITY RISK IN AN
OLDER POPULATION: THE CRITICAL ROLE OF
BIOLOGICAL AGE?
M. Muller 1, G. Post Hospers 2, A.B. Maier 2, D.J. Deeg 3, Y.M. Smulders 2.
/HLGHQ8QLYHUVLW\0HGLFDO&HQWHU'HSDUWPHQWRI*HURQWRORJ\DQG
*HULDWULFV/HLGHQ1(7+(5/$1'62988QLYHUVLW\0HGLFDO&HQWHU
'HSDUWPHQWRI,QWHUQDO0HGLFLQH$PVWHUGDP1(7+(5/$1'63 VU
8QLYHUVLW\'HSDUWPHQWRI(SLGHPLRORJ\$PVWHUGDP1(7+(5/$1'6
1
e43
Journal of Hypertension Volume 32, e-Supplement 1, 2014
Objective: The predictive value of high blood pressure (BP) for mortality in
older people is still debated. Some data suggest that this relation is inverted in
certain subgroups of (biologically) older individuals. We therefore investigated
whether the relation between BP and mortality depended on chronological age,
RURQSK\VLFDODQGFRJQLWLYHIXQFWLRQDVLQGLFDWRUVRIIUDLOW\ELRORJLFDODJH
Design and method: The relation between BP and all-cause mortality was
LQYHVWLJDWHGLQSDUWLFLSDQWVRIWKH/RQJLWXGLQDO$JLQJ6WXG\$PVWHUGDP
/$6$ DJHG\HDUVDQGROGHU PHDQDJH\HDUV XVLQJPXOWLSOHDGMXVWHG
FR[SURSRUWLRQDOKD]DUGPRGHOV$QDO\VHVZHUHVWUDWL¿HGIRUFKURQRORJLFDODJH
physical function (based on categories of gait speed), and cognitive function
(based on categories of the Mini Mental State Examination score).
Results: $IWHUDPHGLDQ UDQJH IROORZXSRI \HDUVSDUWLFLpants died. Systolic BP was not related to mortality risk. However, low diastolic
BP (DBP) was associated with an increased all-cause mortality risk; hazard ratio
+5 RIORZ'%3 PP+J FRPSDUHGWRQRUPDO'%3 PP+J ZDV
&, 7KLVUHODWLRQZDVSDUWLFXODUO\SUHVHQWLQWKHROGHVWROG
!\HDUV DQGLQWKRVHZKRKDGERWKORZHUOHYHOVRISK\VLFDODQGFRJQLWLYH
IXQFWLRQLQJ+5¶V &, RIORZYVQRUPDO'%3ZHUH DQG
UHVSHFWLYHO\7KHVH¿QGLQJVZHUHLQGHSHQGHQWRIIROORZXSWLPH,Q
DGGLWLRQLQSDUWLFLSDQWVZLWKORQJHUIROORZXSWLPH \UV KLJKHU'%3ZDV
related to an increased mortality risk, but only in those who were physically and
cognitively healthy at baseline; HR (95%CI) of high (>90 mmHg) vs. normal
DBP was 1.3 (1.0; 1.7).
Conclusions: In a large older population-based cohort, lower DBP was related
to an increased all-cause mortality risk, particularly in (biological) older individuals, whereas higher DBP was related to an increased mortality risk only in
\RXQJHUYLWDOLQGLYLGXDOV7KHVH¿QGLQJVFRXOGKHOSWRLQFUHDVHWKHDZDUHQHVV
of categorizing individuals based on biological instead of chronological age and
will further help to facilitate personalized BP treatment for the aging hypertensive population, leading to a patient- instead of a disease-based approach.
LB01.07
VASODILATOR PROSTANOIDS INFLUENCE
INTERACTIONS OF LOCAL HYPERINSULINEMIA
WITH ENDOTHELIN-B-RECEPTORS IN THE HUMAN
MICROCIRCULATION
A. Mitchell 1, U. Rushentsova 1, S. Becker 1,2, S. Dolff 1, N. Unger 1,2,
H. Guberina 1. 1'HSDUWPHQWIRU1HSKURORJ\(VVHQ8QLYHUVLW\+RVSLWDO
8QLYHUVLW\RI'XLVEXUJ(VVHQ*(50$1<20DULHQKRVSLWDO+HUQH8QLYHUVLW\
+RVSLWDO5XKU8QLYHUVLW\+HUQH*(50$1<
Objective: In the vasculature insulin activates two distinct signaling pathways
that result in secretion of nitric oxide (NO) and endothelin (ET-1), respectively.
NO, stimulated by higher insulin doses, is thought to be the underlying agent
in insulin-mediated, endothelium-dependent vasodilation. In earlier studies we
have shown that hyperinsulinemia in the human microcirculation causes vasoconstriction via endothelin (ET-1) receptors. We now investigated the role of
NO and prostacyclin on the interactions of insulin with ET-1 receptors in the
peripheral microcirculation.
VNLQEORRGÀRZ,8LQVXOLQ ,16,QVXPDQ5DSLGŠ6DQR¿*HUPDQ\ ZHUH
injected intradermally alone or following injection of the ET-1 type-A- (ET$ UHFHSWRUDQWDJRQLVW%4PROWKH(7%DQWDJRQLVW%4PRO
%4 %4 PRO LQ FRPELQDWLRQ DQG WRJHWKHU ZLWK WKH 12V\Qthesis-inhibitor L-NMMA 10-5mol (Bachem,Switzerland). These experiments
were repeated in the presence of prostacyclin-inhibition with acetylsalicylic acid
$6$PJLY ,QMHFWLRQVLWHVZHUHVFDQQHGRYHUPLQ'DWDDUHSUHVHQWHG
as arbitrary perfusion units (PU, mean ±SD). Two-way ANOVA was used to
analyze time-effect responses.
Results: As shown previously blockade of NO-synthesis with L-NMMA did
QRW LQÀXHQFH YDVRFRQVWULFWLRQ WR ,16 DQG YDVRGLODWLRQ WR WKH FRPELQDWLRQ RI
%4,16ZDVVLJQL¿FDQWO\UHGXFHGLQWKHSUHVHQFHRI/100$ 3 9DVRGLODWLRQ WR %4,16 ZDV QRW LQÀXHQFHG E\ 12LQKLELWLRQ EXW ZDV
VLJQL¿FDQWO\UHGXFHGLQVWKHSUHVHQFHRI$6$ 3 ,QVXOLQVLJQL¿FDQWO\
augmented vasodilation to combined blockade of ET-A and ET-B-receptors (P<
/100$DQG$6$VLJQL¿FDQWO\UHGXFHGWKLVHIIHFW 3 Conclusions: In our study interactions of insulin with ET-A- receptors were
mainly mediated via NO, as shown previously. However, to our knowledge we
DUH WKH ¿UVW WR VKRZ WKDW LQWHUDFWLRQV RI LQVXOLQ ZLWK (7%UHFHSWRUV VHHP WR
EH LQGHSHQGHQW RI 12 EXW VHHP WR EH VLJQL¿FDQWO\ LQÀXHQFHG E\ YDVRGLODWRU
prostanoids.
LB01.08
CARDIORESPIRATORY FITNESS ATTENUATES THE
PROGRESSION TO CHRONIC KIDNEY DISEASE IN
HYPERTENSIVES
P. Kokkinos 1, M. Doumas 1, A. Pittaras 1, A. Tsimploulis, 1, H. Grassos 2,
A.J. Manolis 2, C. Faselis 1. 1 Veterans Affairs Medical Center, Washington,
'&86$2 Asclepeion Hospital, Athens, GREECE
Objective: &KURQLFNLGQH\GLVHDVH &.' GH¿QHGDVDQHVWLPDWHGJORPHUXODU
¿OWUDWLRQUDWH H*)5 POPLQPHVWLPDWHGE\WKH&.'(3,HTXDWLRQ LV D VLJQL¿FDQW ULVN IDFWRU IRU HQG VWDJH UHQDO GLVHDVH DQG PDMRU FDUGLRvascular events. Hypertension is a strong risk factor for progression to CKD.
&DUGLRUHVSLUDWRU\ ¿WQHVV DV UHÀHFWHG E\ H[HUFLVH FDSDFLW\ LV LQYHUVHO\ DVVRFLated with mortality risk and progression to some chronic conditions. The impact
RI FDUGLRUHVSLUDWRU\ ¿WQHVV RQ &.' LQ K\SHUWHQVLYH LQGLYLGXDOV KDV QRW EHHQ
studied. Thus, we assessed the association between exercise capacity and the
progression to chronic kidney failure (CKD) in hypertensive individuals with
normal kidney function prior to the exercise test.
Design and method: We assessed exercise capacity by a standard treadmill test
LQ PDOHV :H IRUPHG WKH IROORZLQJ ¿WQHVV FDWHJRULHV EDVHG RQ DJHDGMXVWHGSHDNPHWDEROLFHTXLYDOHQWV 0(7V DFKLHYHG/HDVW)LW “0(7V
Q /RZ)LW “ 0(7V Q 0RGHUDWH)LW “ 0(7V
Q DQG+LJK)LW “0(7VQ $OORWKHUSHUWLQHQWGDWDZHUH
extracted from patient electronic records. Cox proportional hazard analysis was
used to assess progression to CKD. The model was adjusted for age, BMI, carGLDFDQWLK\SHUWHQVLYHPHGLFDWLRQVDQGFDUGLDFULVNIDFWRUV
Results: 7KHPHDQDJHZDV“\HDUV'XULQJWKHIROORZSHULRG PHGLDQ
\HDUV LQGLYLGXDOV GHYHORSHG &.' SHUVRQ\HDUV ,Q WKH
fully adjusted model, higher exercise capacity was inversely related to the rate
of progression to CKD. For every 1-MET increase in exercise capacity the CKD
ULVN ZDV ORZHU KD]DUG UDWLR &, S :KHQ
FRQVLGHULQJ¿WQHVVFDWHJRULHV&.'ULVNGHFUHDVHGSURJUHVVLYHO\ZLWKLQFUHDVHG
¿WQHVV 6SHFL¿FDOO\ ZLWK WKH /HDVW)LW DV WKH UHIHUHQW KD]DUG UDWLR ZDV &,WR IRU/RZ)LW &,WR IRU0RGHUDWH
Fit; and 0.45 (95%CI, 0.35 to 0.57) for High-Fit individuals.
Conclusions: Increased exercise capacity attenuates the progression to CKD in
hypertensive individuals. The association is independent and graded.
LB01.09
ANGIOTENSIN 1-7 SIGNIFICANTLY REDUCES
DIABETES-INDUCED LEUCOCYTE TRAFFICKING AND
VASCULAR INJURY
D. De Nardo 1, F. Bossi 1, F. Fischetti 1, A. Bramante 1, R. Carretta 1,
S. Bernardi 2, B. Fabris 1. 1'HSDUWPHQWRI0HGLFDO6XUJLFDODQG+HDOWK
6FLHQFHV8QLYHUVLW\RI7ULHVWH7ULHVWH,7$/<2 Department of Internal
0HGLFLQH&OLQLFDO0HGLFLQH8QLW&DWWLQDUD8QLYHUVLW\+RVSLWDO7ULHVWH
ITALY
Design and method: 10 healthy men (24±2 years) were studied. We used a
Laser-Doppler-Imager (moor LDI-V5.0, Axminister, UK) to measure changes in
Objective: Angiotensin (Ang)1-7 is a peptide generated by angiotensin converting enzyme (ACE)2, which degrades AngII to Ang1-7. Experimental evidence
supports the notion that Ang1-7 exerts peripheral opposite actions to those of
AngII whereby it protects against vascular injury.
e44
Journal of Hypertension Volume 32, e-Supplement 1, 2014
7KH DLP RI WKLV VWXG\ ZDV WR HYDOXDWH WKH DQWLLQÀDPPDWRU\ DQG DQWL¿EURWLF
effects of Ang1-7 delivery in an experimental model of type 1 diabetes mellitus
(T1DM).
Design and method: Forty male Wistar rats weighing 250 g were randomly
DOORFDWHGWRWKHIROORZLQJWUHDWPHQWJURXSVVDOLQH Q UDWVZKLFKZHUHWKH
FRQWUROV $QJ Q VWUHSWR]RWRFLQ 67= Q 67=$QJ Q 67=ZDVGHOLYHUHGLQWUDYHQRXVO\DWWKHGRVHRIPJNJRQFHEHIRUHWKHVWXG\
EHJLQQLQJZKLOH$QJZDVGHOLYHUHGLQWUDSHULWRQHDOO\DWWKHGRVHRI—J
NJGDLO\$OOWKHDQLPDOVZHUHIROORZHGIRUZHHNVDQGDWWKHHQGRIWKHVWXG\
body weight, systolic blood pressure and blood glucose were recorded. LeucoF\WHWUDI¿FNLQJZDVHYDOXDWHGE\LQWUDYLWDOYLGHRPLFURVFRS\LQWKHPHVHQWHULF
vessels of 5 rats per group. Bloods and tissues were collected from the remaining rats for histomorphometric studies and gene and protein expression analyses.
Results: $QJ VLJQL¿FDQWO\ UHGXFHG YDVFXODU UROOLQJ S DGKHVLRQ
(p<0,05), and extravasation (p<0,05) in T1DM rats. This was associated with a
VLJQL¿FDQWUHGXFWLRQRIYDVFXODUK\SHUWURSK\WRJHWKHUZLWKDVLJQL¿FDQWUHGXFWLRQ LQ WKH JHQH DQG SURWHLQ H[SUHVVLRQ RI SURLQÀDPPDWRU\ DQG SUR¿EURWLF
molecules in the mesenteric vessels and at a systemic level.
Conclusions: $QJVLJQL¿FDQWO\UHGXFHV7'0LQGXFHGOHXFRF\WHWUDI¿FNing and vascular injury, opening new therapeutic opportunities.
LB01.10
COSTS OF HYPERTENSION DETECTION WITHIN THE
NHS HEALTH CHECK PROGRAMME COMPARED TO
OPPORTUNISTIC DETECTION
C. Clark 1, J. Fordham 2, M. Greenwood 2, S. Richards 1, J. Campbell 1.
8QLYHUVLW\RI([HWHU0HGLFDO6FKRRO([HWHU81,7('.,1*'20
2
0LG'HYRQ0HGLFDO3UDFWLFH:LWKHULGJH'HYRQ81,7('.,1*'20
1
Objective: The NHS Health Check Programme (NHSHC) in England offers
5 yearly assessments to adults aged 40 to 74 years old who are free of vascuODUGLVHDVH7KH3URJUDPPH¶VHYLGHQFHEDVHKDVEHHQTXHVWLRQHGDQGLWVFRVW
effectiveness model assumes 75% uptake. Costs to primary care in identifying
new cases of hypertension are unknown. We have prospectively audited our
SUDFWLFH¶V¿UVWPRQWKVRIFKHFNVWRHVWLPDWHWKHFRVWVSHUQHZGLDJQRVLVRI
K\SHUWHQVLRQGHWHFWHGE\WKH1+6+&3URJUDPPHFRPSDUHGWRHTXLYDOHQWFRVWV
for opportunistic diagnosis of hypertension.
Design and method: (OLJLEOHSDWLHQWVZHUHLGHQWL¿HGIURPWKHSUDFWLFHGDWDbase and invited to nurse-run clinics in one rural general practice in Devon,
England. During a 30 minute appointment, delivering targeted health advice
based on lifestyle history and clinical measurements, blood pressure (BP) was
recorded as the mean of three readings with an automated sphygmomanometer
0LFUROLIH:DWFK%32I¿FH 3DWLHQWVZLWKPHDQEORRGSUHVVXUH!ZHUH
followed up by nurses and doctors according to NICE hypertension diagnostic guidelines. We used published UK consultation costs to estimate the costs
LQFXUUHGLQFRQ¿UPLQJDQHZGLDJQRVLVRIK\SHUWHQVLRQDQGFRPSDUHGWKHVH
with the estimated costs of detecting the same cases with an opportunistic
approach.
Results: SDWLHQWVZHUHLQYLWHG DWWHQGHGDQG UHTXLUHG
IROORZXSRILQLWLDOHOHYDWHG%3RIWKHVH¿YH GLGQRWUHDWWHQGDQGK\SHUWHQVLRQZDVFRQ¿UPHGLQIRXU &RVWSHUGLDJQRVLVWKURXJK1+6+&VZDV
¼ DQDGGLWLRQDOFRVWRI ¼ SHUFDVHFRPSDUHG
to opportunistic detection. If all non-attenders are assumed to have hypertension
WKHFRVWVDQGFRVWGLIIHUHQFHDUH¼DQG¼UHVSHFWLYHO\
Conclusions: Practice NHSHC uptake is low, but consistent with county-wide
uptake (34%). This is less than half the NHS predicted rate. Costs of diagnosing hypertension with NHSHCs are double those for an opportunistic approach.
5HSOLFDWLRQRIWKLV¿QGLQJIURPODUJHUQXPEHUVRISUDFWLFHVPD\FKDOOHQJHRQH
of the cost-effectiveness assumptions of the NHSHC Programme. Primary care
resources may be better utilised with opportunistic approaches to the detection
of hypertension.
WRUV7KLVVWXG\TXDQWL¿HVWKHHIIHFWRI¿HOGVWLPXODWLRQRIWKHFDURWLGEDURUHFHSWRU
nerves on aortic and renal haemodynamics and baroreceptor function.
Design and method: $QDHVWKHWLVHG6SRQWDQHRXVO\+\SHUWHQVLYH5DWV Q 21 weeks, male) were instrumented to measure heart rate and mean arterial pressure (MAP), aortic pulse wave velocity (PWV, a surrogate measure of arterial
VWLIIQHVV DEGRPLQDODRUWLFÀRZDQGUHQDODUWHU\ÀRZ5HVLVWDQFHZDVFDOFXODWHG
XVLQJPHDVXUHGSUHVVXUHDQGÀRZ%DURUHFHSWRUIXQFWLRQZDVDVVHVVHGE\TXDQtifying the heart rate response to a MAP change induced by intravenous bolus of
SKHQ\OHSKULQH —J GXULQJEDVHOLQHFRQGLWLRQVDQGGXULQJ¿HOGVWLPXODWLRQRI
WKHOHIWFDURWLGEDURUHFHSWRUFRPSOH[)LHOGVWLPXODWLRQZDVDFKLHYHGE\DVTXDUH
wave pulse of 100 Hz, 0.53 ms pulse width, pulse amplitude range 2 to 4 V.
Results: Field stimulation of the carotid baroreceptor nerve complex reduced
0$3E\PP+J S ZLWKDKHDUWUDWHUHGXFWLRQRIESP S :KLOVW V\VWROLF DQG GLDVWROLF SUHVVXUH ZHUH VLJQL¿FDQWO\ UHGXFHG SXOVH SUHVVXUH ZDV QRW S 7KHUH ZDV D UHGXFWLRQ LQ PHDQ DRUWLF ÀRZ RI PO
PLQ S DQGPHDQUHQDOÀRZRIPOPLQ S $RUWLFÀRZSXOVH
KHLJKW GLG QRW FKDQJH S EXW UHQDO ÀRZ SXOVH KHLJKW LQFUHDVHG E\ POPLQ S $RUWLF3:9GLGQRWFKDQJHVLJQL¿FDQWO\ EDVHOLQH“
PVVWLPXODWLRQ“PVS 7KHUHZDVQRFKDQJHLQDRUWLFUHVLVWDQFH
EDVHOLQH“PP+JPOPLQVWLPXODWLRQ“PP+JPOPLQS RU UHQDO UHVLVWDQFH EDVHOLQH “ PP+JPOPLQ VWLPXODWLRQ “
PP+JPOPLQ S 0D[LPDO EDURUHFHSWRU JDLQ ZLWKRXW VWLPXODWLRQ ZDV
“ ESPPP+J DQG GXULQJ VWLPXODWLRQ “ ESPPP+J S The pressure at which maximal gain occurred also did not change (152±11 and
“PP+JUHVSHFWLYHO\S Conclusions: 8QLODWHUDO¿HOGVWLPXODWLRQRIWKHFDURWLGEDURUHFHSWRUQHUYHFRPSOH[FDXVHGDUHGXFWLRQLQ0$3KHDUWUDWHDRUWLFÀRZDQGUHQDOÀRZDQGLQFUHDVHGUHQDOÀRZSXOVDWLOLW\3HDNEDURUHFHSWRUJDLQZDVFRPSOHWHO\SUHVHUYHG
as was the MAP at which it occurred.
LB01.12
LONGER TERM SAFETY AND EFFICACY OF MULTIELECTRODE RENAL DENERVATION IN PATIENTS
WITH DRUG-RESISTANT HYPERTENSION: TWENTYFOUR MONTH RESULTS OF A FIRST-IN-HUMAN,
MULTICENTER STUDY
&7VLRX¿V1, S.G. Worthley 2, M. Worthley 3, D. Chew 4, A. Sinhal 4,
I. Meredith 5, Y. Malaiapan , V. Papademetriou 7. 1 First Cardiology Clinic,
8QLYRI$WKHQV+LSSRNUDWLRQ+RVS$WKHQV*5((&(2&DUGLRYDVFXODU5HV
&WU5R\DO$GHODLGH+RVSDQG'HSWRI0HG8QLYRI$GHODLGH$GHODLGH
$8675$/,$38QLYHUVLW\RI$GHODLGH$GHODLGH$8675$/,$4)OLQGHUV8QLY
)OLQGHUV0HGLFDO&WU$GHODLGH$8675$/,$5 Monash Heart and Monash
&DUGLRYDVFXODU5HV&WU0HOERXUQH$8675$/,$60RQDVK0HGLFDO&WU
0HOERXUQH$8675$/,$79$0HG&WU:DVKLQJWRQ'&86$
Objective: 7RLQYHVWLJDWHWKHVDIHW\DQGHI¿FDF\RIDPXOWLHOHFWURGHFDWKHWHU
ablation system (EnligHTN) designed to create predetermined stereotactic lesion pattern in patients with resistant hypertension.
Design and method: 7KH(QOLJ+71,¿UVWLQKXPDQVWXG\ZDVGHVLJQHGWRDVVHVVWKHVDIHW\DQGHI¿FDF\RIWKLVPXOWLHOHFWURGHDEODWLRQV\VWHPLQSDWLHQWVZLWK
GUXJUHVLVWDQWK\SHUWHQVLRQ$WRWDORISDWLHQWV DYHUDJHDJH“\UVWDNLQJ
an average of 4.7±1.0 medications) were enrolled in this study. Of these patients
ZHUHIHPDOHZHUHZKLWHKDG&RURQDU\$UWHU\'LVHDVHKDG
hyperlipidemia, 33% had type II Diabetes Mellitus, and 30% had history of sleep
apnea. Bilateral renal nerve ablation was performed using a percutaneous femoral
DSSURDFK2QDYHUDJH“OHVLRQVZHUHFUHDWHGLQWKHULJKWUHQDODUWHU\DQG
7.4±1.4 in the left renal artery. The median procedure time was 34 minutes.
M. Butlin 1, Z. Kouchaki 1, D. Georgakopoulos 2, A. Avolio 1. 1 Macquarie
8QLYHUVLW\6\GQH\$8675$/,$2&95[,QF0LQQHDSROLV0186$
Results: %DVHOLQH DYHUDJH RI¿FH EORRG SUHVVXUH %3 ZDV PP+J DQG
DYHUDJHKUDPEXODWRU\%3ZDVPP+J$YHUDJHUHGXFWLRQV PP+J RIRI¿FH%3HDWDQGPRQWKVZHUH
DQG PP+J S UHVSHFWLYHO\ )RU WKHKU DPEXODWRU\
%3 UHGXFWLRQV DW DQG ZDV DQG PP+J
SIRUDQG3IRUPRQWKV UHVSHFWLYHO\$WPRQWKV
77% of patients were responders (at least 10 mmHg reduction in systolic BP)
and 39% had normalized BP (<140 mmHg systolic blood pressure).The study
utilized an independent Clinical Events Committee to adjudicate all adverse
HYHQWV%DVHGRQWKHLUDGMXGLFDWLRQWKHUHZHUHGHYLFHSURFHGXUHUHODWHGVHULous adverse events in 3 subjectsreported to date which include: hypertensive
renal disease progression, symptomatic hypotension, worsening of pre-existing
renal artery stenosis and new stenotic lesion.
Objective: Field stimulation of the carotid baroreceptor complex is a clinical tool
for long-term reduction in blood pressure. Baroreceptor stimulation may comproPLVHWKHEHQH¿FLDOVKRUWWHUPEORRGSUHVVXUHUHJXODWLRQIXQFWLRQRIWKHEDURUHFHS-
Conclusions: We conclude that data demonstrates that the EnligHTN ablation
system continues to besafe and effective in the treatment of patients with drugresistant hypertension.
LB01.11
AORTIC AND RENAL HAEMODYNAMICS AND
BARORECEPTOR FUNCTION DURING UNILATERAL
FIELD STIMULATION OF CAROTID BARORECEPTOR
NERVES IN SPONTANEOUSLY HYPERTENSIVE RATS
Abstracts
e45
ORAL SESSION
ORAL SESSION 4A
ORGAN DAMAGE
4A.01
AORTIC ROOT DIAMETER AND RISK OF
CARDIOVASCULAR EVENTS IN A GENERAL
POPULATION: DATA FROM THE PAMELA STUDY
BP (r=0.33, p<0.001), pulse pressure (r=0.306, p<0.001) and AIx (r=0.121,
p<0.001). After adjusting for diabetes mellitus presence, eGFR, aortic systolic
BP, total cholesterol and 10-year CVD risk, cfPWV remained an independent predictor of LVMI levels (R2=0.243, B=1.60, p<0.001). In ROC analysis,
cfPWV emerged as a better predictor of LVH (AUC: 0.735, p<0.001) compared to the Framingham Risk Score (AUC: 0.727, p<0.001), aortic systolic
BP (AUC: 0.687, p<0.001), aortic pulse pressure (AUC: 0.705, p<0.001) and
AIx (AUC: 0.649, p<0.001).
C. Cuspidi 1,2, R. Facchetti 1, M. Bombelli 1, A. Re 1, C. Sala 3, G. Seravalle 2,
G. Grassi 1,4, G. Mancia 1,2. 1 Department of Health Science, University of
Milano-Bicocca, Milan, ITALY, 2 Istituto Auxologico Italiano IRCCS, Milan,
ITALY, 3 Department of Clinical Sciences and Community Health University of
Milan and Fondazione Ospedale Maggiore Policlinico, Milan, ITALY, 4 IRCCS
Multimedica, Milan, ITALY
Objective: Data on the association of aortic root diameter (ARD), as assessed
by echocardiography, with incident cardiovascular morbidity and mortality in
the general population are scanty and limited to elderly individuals. Thus, we investigated the value of ARD in predicting cardiovascular events in the PAMELA
population.
Design and method: At entry 1860 subjects (mean age 50±14, 50.6% men)
XQGHUZHQWGLDJQRVWLFWHVWVLQFOXGLQJODERUDWRU\LQYHVWLJDWLRQVRI¿FHDQGRXWRI
RI¿FHEORRGSUHVVXUHPHDVXUHPHQWV KRPHDQGKRXUDPEXODWRU\%3PRQLtoring), and echocardiography. ARD was measured at the level of Valsalva’s
sinuses and indexed to body surface area (BSA) and height.
Results: Over a follow-up of 148 months, 139 non-fatal or fatal cardiovascular
events were documented. After adjustment for age, sex, BP, fasting blood glucose, total cholesterol, and use of antihypertensive drugs, ARD indexed to BSA
(HR for 1 unit increase = 2.48, 95%CI 1.13-5.44, p=0.02), and ARD indexed to
height (HR=2.69, 95%CI 1.21-5.97, p=0.01) but not absolute ARD (HR=1.38,
95%CI 0.85-2.24, p=0.19) predicted an increased risk of cardiovascular events.
Conclusions: 2XUUHVXOWVIRUWKH¿UVWWLPHVKRZWKDW$5'LQGH[HGWRERG\VL]H
is predictive of incident non-fatal and fatal cardiovascular events among middleaged subjects in the community and support the view that assessment of ARD
PLJKWFRQWULEXWHWRUH¿QHFDUGLRYDVFXODUULVNVWUDWL¿FDWLRQDQGSUHYHQWLYHVWUDWHgies in the general population.
4A.02
ARTERIAL STIFFNESS IS A BETTER PREDICTOR
OF LEFT VENTRICULAR HYPERTROPHY THAN
THE FRAMINGHAM RISK SCORE AND CENTRAL
HEMODYNAMICS: INSIGHTS FROM 1,141 NEVERTREATED HYPERTENSIVES
P. Xaplanteris, C. Vlachopoulos, N. Ioakeimidis, P. Pietri, M. Abdelrasoul,
G. Vyssoulis, C. Stefanadis. 1st Department of Cardiology, Hippokration
Hospital, Athens Medical School, Athens, GREECE
Objective: Left ventricular hypertrophy (LVH) heralds target organ damage and
calls for aggressive therapeutic approaches. We investigated the predictive ability of arterial stiffness, central hemodynamic indices and the Framingham Risk
Score for detecting LVH.
Design and method: 1,141 newly diagnosed, never-treated hypertensives were
recruited. Carotid-femoral pulse wave velocity (cfPWV), central (aortic) blood
pressures and augmentation index (AIx) were measured non-invasively with
validated devices. Patients were scheduled for a cardiac ultrasound; left ventricular mass index (LVMI) was calculated according to the Devereux formula.
/9+ZDVGH¿QHGDV/90,!JP ZRPHQ DQG!JP PHQ 7KH
year risk for cardiovascular disease (CVD) was calculated using the FramingKDP5LVN6FRUH&RUUHODWLRQFRHI¿FLHQWVUHJUHVVLRQDIWHUFRQWUROOLQJIRUFRQfounders and ROC curves were calculated.
Results: The cohort was young (age: 53±12 years old), with mild-moderate
hypertension (systolic BP: 151±18 mmHg, diastolic BP: 90±11 mmHg). 58%
were men, 42% smoked and 6% were diabetics. LVH was detected in 43%
of the population and the 10-year CVD risk was 16.1±9.7%. LVMI had a
stronger correlation with cfPWV (r=0.39, p<0.001) compared to aortic systolic
Conclusions: In newly diagnosed, never-treated hypertensives, aortic stiffness
is independently associated with LVMI and is a better predictor of LVH than the
)UDPLQJKDP5LVN6FRUHDRUWLFEORRGSUHVVXUHVDQGZDYHUHÀHFWLRQV(OHYDWHG
levels of cfPWV signify target organ damage, which extends beyond large artery
VWLIIQHVVDQGKHUDOG/9+7KLVKDVLPSRUWDQWLPSOLFDWLRQVIRUULVNVWUDWL¿FDWLRQ
and choice of antihypertensive therapy.
4A.03
PROGNOSTIC VALUE OF MICROALBUMINURIA
DURING ANTIHYPERTENSIVE TREATMENT IN
ESSENTIAL HYPERTENSION
J. Pascual 1,2, E. Rodilla 1, J. Costa 1, J. Martin 1, &*RQ]DOH]1, M. Garcia 1,
J. Redon 2,3. 1 Hypertension Clinic, Sagunto Hospital, Valencia, SPAIN,
2
CIBERObn, Instituto de Salud Carlos III, Madrid, SPAIN, 3 Hypertension
Unit, Hospital Clinico, University of Valencia, Valencia, SPAIN
Objective: Microalbuminuria assessment is now recommended in a risk strati¿FDWLRQVWUDWHJ\LQK\SHUWHQVLRQ:KHWKHURUQRWFKDQJHVRYHUWLPHRI8ULQDU\
albumin excretion have prognostic value is a matter of discussion since some
controversial information has been published. The objective was to assess the
prognostic value of changes in Urinary albumin excretion overtime in cardiovascular risk during usual care.
Design and method: Follow-up study in a Outpatient Clinic of a Community
+RVSLWDOLQFOXGLQJK\SHUWHQVLYHV PHDQDJH\UPDOH%3
mmHg, 19.1% diabetics and SCOREc 5 or higher 12.4%). Usual-care of antiK\SHUWHQVLYH WUHDWPHQW ZDV LPSOHPHQWHG WR PDLQWDLQ EORRG SUHVVXUH mmHg. The main outcome measures were: Urinary albumin excretion was assessed yearly and the values were expressed as the creatinine ratio. Incidence of
new cardiovascular events, fatal and nonfatal, was recorded during the followup.
Results: During a median follow-up of 4.7 years (17028 patients-year), 294
IDWDO DQG WKH ¿UVW QRQIDWDO FDUGLRYDVFXODU HYHQWV ZHUH UHFRUGHG &9'
SHU SDWLHQWV\HDU ,QGHSHQGHQWO\ RI EORRG SUHVVXUH H*)5 6&25(F DQG
antihypertensive treatment, microalbuminuria at baseline and at any time during
S
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Y
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R
A
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e46
Journal of Hypertension Volume 32, e-Supplement 1, 2014
the follow-up resulted in higher risk for events, HR 1.33 (95%CI 1.03-1.71) and
HR 1.81 (95%CI 1.21-2.70), respectively. Likewise, development of microalbuPLQXULDRUSHUVLVWHQWIURPWKHEHJLQQLQJKDGDVLJQL¿FDQWO\KLJKHUUDWHRIHYHQWV
than if remained normoalbuminuria or regression to normoalbuminuric (18%,
18%, 8% and 11% events, respectively, p<0.001). Moreover, progression at any
time resulted in a HR 1.69 (95%CI 1.12-2.54).
4A.05
THE EFFECT OF EPLERENONE ON CELL
PROLIFERATION IN CONTRALATERAL KIDNEY OF
RATS WITH UNILATERAL URETERAL OBSTRUCTION
C. Wang 1, X. Xu 2, X. Wang 3, X. Wang 3, R. Wang 2, L. Liang 2, Z. Wang 2,
D. Sun 3, T. Shimosawa 1. 1 Tokyo University, Tokyo, JAPAN, 2 Hebei Medical
University, Hebei, CHINA, 3 Hebei University of Traditional Chinese Medicine,
Hebei, CHINA
Objective: 882PRGHOQRWRQO\LQGXFHVUHQDOLQWHUVWLWLDO¿EURVLV 5,) LQREstructed kidney, but also induces injury in contralateral kidney. The precise
mechanisms to induce RIF in the contralateral kidney are not well revealed.
,QÀDPPDWLRQ DQG FHOO SUROLIHUDWLRQ SOD\V DQ LPSRUWDQW UROH LQ WKH SURFHVV RI
RIF. Proliferation appears early, even prior to the abnormal deposition of exWUDFHOOXODUPDWUL[DQGFRQWLQXHGWKURXJKRXWWKHZKROHSURFHVVRI¿EURVLV:H
K\SRWKHVL]HGWKDWDOGRVWHURQHPD\LQGXFHLQÀDPPDWLRQDQGFHOOSUROLIHUDWLRQ
Our preliminary studies showed that PCNA positive cells increased in contralateral kidney, indicating that cell proliferation plays an important role in the
process of RIF in the contralateral kidney.
The prognostic value of microalbuminuria was also present in the low-moderate
SCORE subjects (82% of the total) and in subjects with eGFR higher o equal
DQGORZHUWKDWPO PLQP Conclusions: The study supports the role of urinary albumin assessment as a
prognostic factor for cardiovascular risk, but also opens the way to consider it as
an intermediate objective in hypertension.
4A.04
IMPAIRED DIASTOLIC PARAMETERS IN
CARDIOVASCULAR REMODELING OF PSORIASIS
C. Gadaleta Caldarola 1, C. Mongiardi 1, A. Maresca 1, S. Moretti 1,
M. Agostinis 1, F. Mola 2, A. Antelmi 2, A. Motolese 2, A. Bertolini 1, L. Guasti 1,
A. Grandi 1. 1 Department of Clinical and Experimental Medicine, University
of Insubria, Varese, ITALY, 2 Department of Dermatology, Macchi Foundation
Hospital, Varese, ITALY
Objective: Psoriasis patients have a higher prevalence of cardiovascular events
WKDQJHQHUDOSRSXODWLRQ&RQÀLFWLQJGDWDDUHDYDLODEOHDERXWFDUGLRYDVFXODUUHmodeling in psoriasis in particular for the confounding presence of comorbidities (hypertension, obesity, metabolic syndrome). Aim of the study was to assess
in psoriasis patients correlations with cardiac and aortic remodeling.
Design and method: We enrolled 75 patients without known hypertension, cardiovascular disease or diabetes, not smokers: 50 with psoriasis (P) and 25 control subjects (C) matched for age, sex, body mass index and blood pressure. For
HDFKVXEMHFWZHHYDOXDWHGRI¿FHDQGKEORRGSUHVVXUH %3 3VRULDVLVVHYHULW\
ZDVFODVVL¿HGDFFRUGLQJ3$6,HYDOXDWLRQ(DFKSDWLHQWXQGHUZHQWHFKRFDUGLRJraphy with tissue Doppler imaging and arterial tonometry (central BP and pulse
wave velocity, PWV).
Results: As expected, age (C 46.7 vs P 47.1 ys), sex (male 70% vs 73%), BMI
YV NJP DQG K %3 ““ YV ““ PP+J ZHUH
similar in the two groups. Prevalence of hypertension and metabolic syndrome
was comparable. Neutrophil count was higher in psoriasis. Left ventricular diameter was normal in all and similar in the two groups. Left ventricular mass was
FRPSDUDEOHLQWKHWZRJURXSV “YV“JP (MHFWLRQIUDFWLRQ
was similar in the two groups (62±3 vs 63±6 %) Regarding diastolic parameters
we observed a longer deceleration time (193± 30 vs 167± 24 ms), a lower E’
“YV“PVS DQGKLJKHU((¶ “YV“S in psoriasis than in controls . We didn’t see any difference in aortic diameters
(root, ascending and arch) in the two groups. Right ventricular morpho-functional parameters were also overlapping. Arterial tonometry showed similar central
BP (systolic, diastolic and pulse), augmentation index and carotid-femoral PWV.
In a univariate analysis PASI didn’t correlate to cardiac and aortic parameters,
while neutrophil count had a negative correlation to E’ (r - 0.242 p 0.05).
Conclusions: ,QWKLVFURVVVHFWLRQDOVWXG\SVRULDVLVDSSHDUVWRLQÀXHQFHGLDVtolic function but not left ventricular mass and aortic morpho-functional paUDPHWHUV,QÀDPPDWLRQPD\EHDSRVVLEOHOLQNEHWZHHQSVRULDVLVDQGGLDVWROLF
dysfunction.
Design and method: 36 female Wistar rats weight 200±10g were used in this
study. After 7 days to adapt, rats are randomly divided into 3 groups: Control
group, UUO group, and UUO and Eplerenone group.
Results: 1) In UUO group, the level of serum aldosterone, MCP-1 and
71)ĮZHUHLQFUHDVHGVLJQL¿FDQWO\WKDQVKDPJURXSDQGWKH\DUHORZHUHGE\
Eplerenone. 2) Pathologic changes is determined by HE, MASSON and Sirius
UHGVWDLQLQJ7KHUHVXOWVKRZHGWKDWVHYHUHLQÀDPPDWLRQDOVRFDQEHREVHUYHG
in the contralateral kidneys. Eplerenone treatment decreased the degree of inÀDPPDWLRQ DQG LQWHUVWLWLDO ¿EURVLV LQ ERWK REVWUXFWHG DQG FRQWUDODWHUDO NLGneys. 3) Cell proliferation was examined by PCNA staining and PCNA positive cells increased markedly together with increased collagens in UUO group
than control group in contralateral kidney and those changes are attenuated
by Elperenone. 4) The expression of SGK-1 protein were upregulated in contralateral kidney in UUO group, which is suppressed by Eplerenone treatment.
1)ț%(5.DQG3(5.ZHUHDOVRLQFUHDVHGPDUNHGO\LQFRQWUDODWeral kidney of UUO than Sham group and downregulated after Eplerenone
treatment.
Conclusions: 1) Cell proliferation in contralatteral kidney of UUO may play
an important role in the process of RIF. 2) Aldosterone and its receptor (MR)
activity are increased in contralateral kidney in obstructive nephropathy and
WKH\LQGXFHLQÀDPPDWLRQWRVWLPXODWHFHOOSUROLIHUDWLRQ (IIHFWRI05RQFHOO
SUROLIHUDWLRQPD\EHDVVRFLDWHGZLWK6*.1)ț%SDWKZD\ț
4A.06
ACCUMULATION OF DIFFERENT MICRO- AND
MACROVASCULAR TARGET ORGAN DAMAGE IN
HYPERTENSIVE PATIENTS. PATHOPHYSIOLOGICAL
COMMON PATHWAYS AND CARDIOVASCULAR RISK
ASPECTS EXPLORATION
A. Triantafyllou 1, E. Gavriilaki 1, P. Anyfanti 2, X. Zabulis 3, E. Gkaliagkousi 2,
G. Triantafyllou 1, K. Petidis 2, V. Gkolias 1, A. Pyrpasopoulou 2,
)'RJUDPDW]L4, S. Aslanidis 2, S. Douma 1. 1 3rd Department of Internal
Medicine, Papageorgiou Hospital, Aristotle University, Thessaloniki,
GREECE, 2 2nd Propedeutic Department of Internal Medicine, Hippokration
Hospital, Aristotle University, Thessaloniki, GREECE, 3 Institute of Computer
Science, Foundation for Research and Technology, Hellas, Crete, GREECE,
4
Biochemistry Laboratory, Hipppokration Hospital, Thessaloniki, GREECE
e47
Journal of Hypertension Volume 32, e-Supplement 1, 2014
Objective: (DUO\ LGHQWL¿FDWLRQ RI K\SHUWHQVLYH WDUJHW RUJDQ GDPDJH 72' emerges as extremely important in terms of global cardiovascular risk assessment. Subtle retinal vascular alterations, capillary rarefaction and microalbuminuria all represent different forms of microvascular TOD. Arterial stiffness
DQGPRUHVSHFL¿FDOO\SXOVHZDYHYHORFLW\ 3:9 UHSUHVHQWVDZHOOHVWDEOLVKHG
macrovascular organ damage estimation index. However, data regarding the
concomitant presence of the above lesions in the early stages of hypertension,
especially without other comorbidities and the association of the number of affected organs with cardiovascular risk, and aldosterone effect on multiple TOD
are lacking.
PJ %,' Q ZLWKRXW VLJQLILFDQW GLIIHUHQFHV LQ JHQGHU PDOHV PHDQ DJH \HDUV %0, NJ+P %3 PP+J +E$F H*)5 POPLQP DQG
SURWHLQXULD JK $OOSDWLHQWVVLJQHGLQIRUPHGFRQVHQWDQG
were followed during 6 months. At inclusion and end follow up, we performed biochemical tests and 2D-echocardiograms with Philips SONOS
7500 with software D.2.
Results: 1R VLJQL¿FDQW GLIIHUHQFHV ZLWKLQ HDFK JURXS DQG EHWZHHQ JURXSV
in HbA1c and BMI, creatinine, eGFR and potassium levels during study. (*)
p<0.001. Table 1.
Design and method: We studied naïve, never-treated patients attending our
+\SHUWHQVLRQ 8QLW ZLWK UHFHQW GXUDWLRQ RI K\SHUWHQVLRQ \HDU FRQ¿UPHG
with 24-hour ambulatory blood pressure monitoring, and normotensive healthy
volunteers. Innovative, semi-automated software was developed to estimate 1)
retinal vascular diameters (Central retinal arterial (CRAE) and venular (CRVE)
equivalent), obtained by retinal photography and 2) capillary density obtained
by nailfold capillaroscopy. PWV was estimated by Sphygmocor Atcor device.
Biochemical parameters including microalbuminuria (in 24h urine collection
sample) and serum aldosterone were derived. Framingham Risk Score was used
to determine future cardiovascular risk.
Results: A total of 173 subjects, 84 true, 16 white coat and 23 masked hypertensives and 50 normotensives were included. Hypertensive patients exhibited a greater number of affected target organs compared to normotensives
(p<0.001), with aortic distensibity (72%) and retinopathy (39.2%) representing the most common TOD among hypertensives. Percentages of macro and
PLFURYDVFXODUGDPDJHDUHGHSLFWHGLQ¿JXUH7KHK\SHUWHQVLYHVFRPSDUH
to normotensive had increased PWV (p<0.001) and urine albumin excretion levels (p=0.025) and decreased CRAE (p<0,001) and capillary density
(p=0.05). The number of affected organs was linearly correlated with increased Framingham score (r=0.171, p=0.0.35). Aldosterone levels linearly
FRUUHODWHG U S DQGVLJQL¿FDQWO\SUHGLFWHG S WKHQXPber of affected organs even after adjusted with multivariate regression analysis for other covariates.
Conclusions: Physicians dealing with hypertensive patients should be aware of
the possibility of diffuse microvascular impairment and seek multiple TOD even
in the early stages of hypertension.
Conclusions: :LWKRXW VLJQL¿FDQW GLIIHUHQFHV LQ DQWKURSRPHWULF DQG FOLQLFDO
features along the study, patients treated with higher doses of IRB achieved a
greater reduction in proteinuria and LVMI as well as greater improvement in
diastolic function parameters
4A.08
RELATIONSHIP BETWEEN AORTIC AND LOCAL
CAROTID STIFFNESS AND CARDIAC AND VASCULAR
ORGAN DAMAGE IN A GENERAL POPULATION
SAMPLE IN NORTHERN ITALY
A. Paini, M. Salvetti, C. Aggiusti, C. Agabiti Rosei, F. Bertacchini,
G. Maruelli, G. Rubagotti, E. Colonetti, D. Stassaldi, E. Casella, E. Agabiti
Rosei, M.L. Muiesan. Internal Medicine, University of Brescia, Brescia, ITALY
Objective: Carotid-femoral pulse wave velocity (aoPWV), the ‘gold-standard’
measurement of arterial stiffness, has been found associated with cardiac and
vascular organ damage. Less information is available with regard to the correlation between local carotid stiffness (CS) and cardiac and vascular preclinical
damage.
Aim of the study was to analyse the correlation between aoPWV and CS and
cardiac and vascular preclinical organ damage in a middle age general population in Northern Italy (Vobarno Study).
4A.07
IRBESARTAN 600 MG ACHIEVES BETTER RENO
AND CARDIOPROTECTION THAN 300 MG DAILY
IN HYPERTENSIVE PATIENTS WITH ESTABLISHED
DIABETIC NEPHROPATHY
A. Esteban 1, P. Aranda Lara 2, L. Blanca Martos 2, '+HUQDQGH]0DUUHUR2,
$3HUH]&DEH]D1, )5XL]0DWHDV1. 1 Cardiology Service, Hospital Costa
del Sol, Marbella, SPAIN, 2 Hypertension and Vascular Risk Unit, Hospital
Regional Universitario de Málaga, Málaga, SPAIN
Objective: Hypotethically the higher the dose of ARBs, the greater the number
RI$7UHFHSWRUVEORFNDGHDQGWKHUHIRUHLWVEHQH¿FLDOHIIHFWVRQUHQRDQGFDUdioprotection. So, our aim was to compare effects on proteinuria, LV mass index
(LVMI) and diastolic function parameters in 2 matched groups of hypertensives
with Established Diabetic Nepropathy (EDN) treated with standard versus high
doses of Irbesartan (IRB).
Design and method: ,QDQREVHUYDWLRQDORSHQUDQGRPL]HGVWXG\ZH
compared 2 matched groups of hypertensives with EDN underwent to a
multifactorial treatment based either on IRB 300 mg OD(n-68) versus 300
Design and method: 245 subjects (57% female, mean age 56±4 years) underwent laboratory examinations, clinic and 24 hours BP measurement, cardiac and
carotid ultrasound, carotid-femoral pulse wave velocity measurement (aoPWV,
Complior system). CS was determined from the relative stroke change in diameter (measured with a high-resolution echotracking system) and carotid pulse
pressure (measured with applanation tonometry) and was expressed in the same
GLPHQVLRQVDVSXOVHZDYHYHORFLW\ PV Results: %RWK DR3:9 DQG &6 ZHUH VLJQL¿FDQWO\ UHODWHG ZLWK DJH U p<0.001 and r=0.23, p<0.001, respectively). A positive correlation was observed with clinic and 24 hours blood pressure parameters and both aoPWV
DQG &6 $R3:9 ZDV VLJQL¿FDQWO\ UHODWHG WR OHIW YHQWULFXODU PDVV LQGH[
/90LU S DQGZDVVLJQL¿FDQWO\KLJKHULQVXEMHFWVZLWK/9K\SHUWURSK\ /90L!JPLQPHQDQG!JPLQZRPHQ DVFRPSDUHG
WRVXEMHFWVZLWKRXW/9+ “YV“PVS 2QWKHFRQWUDU\
CS was not related with LVMi and no difference in CS was observed between
subjects with or without LVH (6.5±1.5 vs 6.3±1.2, p=ns). AoPWV was also
VLJQL¿FDQWO\UHODWHGWRYDVFXODURUJDQGDPDJH FDURWLG,070HDQPD[U p<0.05; CBMmax: r=0.16, p<0.05; Tmax: r=0.19, p<0.005), while CS was
not.
Conclusions: Although carotid-femoral pulse wave velocity (AoPWV) and
carotid stiffness provided similar information on the impact of aging and
blood pressure on large artery stiffness, only AoPWW, and not CS, is related to cardiac (LVM) and vascular (IMT) damage in a general population
sample.
e48
Journal of Hypertension Volume 32, e-Supplement 1, 2014
4A.09
SALT INDUCES TUBULAR EPITHELIAL-TOMESENCHYMAL TRANSITION AND RENAL FIBROSIS
IN DAHL SALT-SENSITIVE RATS
J. Mu, Y. Wang, K. Ren, D. Wang, T. Guo, F. Liu. )LUVW$I¿OLDWHG+RVSLWDORI
Medical College, Xian Jiaotong University, Xian, CHINA
Objective: Previous studies indicated that salt-sensitive subjects were more
SURQHWRSURPRWHUHQDO¿EURVLVWKDQVDOWUHVLVWDQWVXEMHFWV5HFHQWO\(SLWKHOLDO
WRPHVHQFK\PDOWUDQVLWLRQ (07 ZDVVKRZQWREHDNH\SURFHVVLQUHQDO¿EURVLV,QWKLVVWXG\ZHLQYHVWLJDWHGZKHWKHU(07FRQWULEXWHVWRUHQDO¿EURVLVLQ
Dahl salt-sensitive rats.
Design and method: Dahl salt-sensitive rats and SS-13BN rats were randRPL]HGWRDQRUPDOGLHWRUDKLJKVDOWGLHW$IWHUZHHNV6%3DQGDOEXPLQXULD
ZHUHDQDO\]HGDQGWKHUHQDO¿EURVLVZDVKLVWRSDWKRORJLFDOO\HYDOXDWHG7XEXODU
EMT was evaluated by immunohistochemistry and real-time PCR of the epithelial marker E-cadherin, and the mesenchymal marker alpha smooth muscle
DFWLQ Į60$ Results: $IWHUZHHNV6%3DQGDOEXPLQXULDZHUHVLJQL¿FDQWO\LQFUHDVHGLQ66
rats on high salt than that on normal diet. In kidneys, it showed increased MasVRQ¶VWULFKURPHSRVLWLYH¿EURVLVDUHDVLQ66KLJKVDWUDWVFRPSDUHGZLWKWKDWLQ
SS normal diet and 13BN high-salt rats, respectively. SS high-salt group showed
PDUNHGO\UHGXFHGH[SUHVVLRQRI(FDGKHULQDQGHQKDFHGH[SUHVVLRQRIĮ60$
than SS normal salt rats. Both 24h albuminuria excretion and renal interstitial
¿EURVLVZHUHQHJDWLYHO\FRUUHODWHGZLWK(FDGKHULQEXWSRVLWLYHO\ZLWKĮ60$
Conclusions: High salt might induce tubular epithelial-to-mesenchymal transiWLRQ (07 DQGDFFHOHUDWHUHQDO¿EURVLVLQ'DKOVDOWVHQVLWLYHUDWV
4A.10
ARTERIAL STIFFNESS IN WHITE COAT, MASKED AND
TRUE HYPERTENSIVES
&$QW]DS. Papakatsika, G. Kotronis, C. Dimopoulos, S. Stabouli, V. Kotsis.
Hypertension Center, 3rd Department of Medicine, Papageorgiou Hospital,
Aristotle University of Thessaloniki, Thessaloniki, GREECE
Objective: The aim of the study was to investigate differences in arterial stiffQHVVDPRQJSDWLHQWVFKDUDFWHUL]HGDVWUXHQRUPRWHQVLYHVZKLWHFRDWK\SHUWHQsives, masked hypertensives and true hypertensives.
Design and method: 542 consecutive subjects (50.2% male), mean age 42.5±26.2
years-old,were included in the study. Subjects were never treated before for hySHUWHQVLRQ$SK\VLFLDQPHDVXUHGRI¿FHEORRGSUHVVXUH 2%3 WKUHHWLPHVLQHDFK
patient, using a mercury sphygmomanometer. All the subjects underwent 24h ambulatory blood pressure monitoring (ABPM) on a normal working day. True norPRWHQVLYHVXEMHFWVZHUHGH¿QHGDVWKRVHZLWKRI¿FHDQGDPEXODWRU\QRUPRWHQVLRQ 2%3DQGK%3PP+J &RQ¿UPHGK\SHUWHQVLYHVXEMHFWV
ZHUH GH¿QHG DV WKRVH ZLWK RI¿FH DQG DPEXODWRU\ K\SHUWHQVLRQ 2%3! PP+JDQGK%3! PP+J :KLWHFRDWK\SHUWHQVLYH :&+ VXEMHFWV
ZHUHGH¿QHGDVWKRVHZLWK2%3! PP+JDQGGD\WLPH%3PP+J
0DVNHG K\SHUWHQVLYH 0+ VXEMHFWV ZHUH GH¿QHG DV WKRVH ZLWK 2%3
PP+J DQG GD\WLPH %3! PP+J &DURWLGIHPRUDO SXOVH ZDYH YHORFLW\
(cf-PWV) was measured after 15 min of rest in the supine position. PWV was calculated as the transit time of the arterial pulse along the carotid-femoral distance
divided with the distance measured directly.
Results: 43.7% of the subjects were detected as true normotensives, 19.4% as
:&+ DV 0+ DQG ¿QDOO\ DV WUXH K\SHUWHQVLYHV &DURWLG IHPRUDO
PWV was independently associated (ANCOVA analysis) with age (B=0.11,
P<0.001), true hypertension versus true normotension status (B=1.8, P<0.001)
and true hypertension versus white coat hypertension status (B=1.35, P<0.001),
EXWQRWZLWKRI¿FH%3YDOXHVDQG%0,FI3:9ZDVIRXQG“PVHF
LQWUXHQRUPRWHQVLYHV“PVHFLQ:&+“PVHFLQ0+
DQG“PVHFLQWUXHK\SHUWHQVLYHVDIWHUDGMXVWPHQWIRUDJHJHQGHU
RI¿FH%3DQGERG\PDVVLQGH[ %0, 7KHGLIIHUHQFHVLQFI3:9EHWZHHQWUXH
hypertension and true normotension and between true hypertension and WCH
ZDV“DQG“PVHFUHVSHFWLYHO\7KHVHGLIIHUHQFHVZHUHVWDWLVWLFDOO\VLJQL¿FDQWDWWKHDQGOHYHOUHVSHFWLYHO\DIWHU%RQIHUURQL¶V
adjustment for multiple comparisons.
Conclusions: $UWHULDOVWLIIQHVVZDVIRXQGLQFUHDVHGLQSDWLHQWVZLWKFRQ¿UPHG
ambulatory hypertension, while WCH was not associated with increased arterial
stiffness.
Abstracts
e49
ORAL SESSION
ORAL SESSION 4B
OBESITY AND OBSTRUCTIVE
SLEEP APNOEA
4B.01
Medicine, Inselspital, Bern, SWITZERLAND, 3 Clinic and Policlinic of Internal
Medicine, University Hospital of Zurich, Zürich, SWITZERLAND
Objective: Body weight (BW) and blood pressure (BP) have a close relationship which has been accounted for by hormonal changes. No previous study
evaluated the effect of wearing an external weight vest on BP to answer the
question whether there is a simple mechanism between BW and BP.
EXERCISE CAPACITY AND MORTALITY IN
HYPERTENSIVE, OBESE INDIVIDUALS WITH TYPE 2
DIABETES MELLITUS
A. Pittaras 1, M. Doumas 2, C. Faselis 2, A.J. Manolis 3, K. Kifnidis 3, 7=DP¿U3,
E. Hamodraka 3, O. Diakoumakou 3, M.V. Papavasileiou 2, N. Kouremenos 3,
D. Lovic 2, A. Tsimploulis 2, P. Kokkinos 2. 1 Mediton Medical Center,
Department of Cardiology, Athens, GREECE, 2 Va and George Washington
University Medical Centers, Department of Cardiology, Washington DC, USA,
3
Asclepeion Voulas Hospital, Department of Cardiology, Athens, GREECE
Objective: Hypertension (HTN) type 2 diabetes mellitus (DM2) and obesity ofWHQFRH[LVWOHDGLQJWRDQLQFUHDVHGPRUWDOLW\ULVN,QFUHDVHG¿WQHVVLVLQYHUVHO\
related to mortality for individuals with the aforementioned health conditions.
+RZHYHUWKHLPSDFWRI¿WQHVVZKHQWKHVHFRPRUELGLWLHVFRH[LVWKDVQRWEHHQ
thoroughly investigated.
Design and method: Seventeen healthy volunteers underwent weight reduction
(WR) by caloric restriction. Before and after WR, BW, body fat percentage and
BP at rest and during exercise were measured. Before and after WR, exercise
testing was performed twice with random allocation of a weight vest (10 kg) to
one of the tests. Linear regression was used to detect independent associations
between BP and weight vest, BW or body fat percentage.
Results: BW decreased from 89.4 ± 15.4 kg before to 79.1 ± 14.0 kg after WR
3 :5OHGWRVLJQL¿FDQWGHFUHDVHVRI%3DWUHVW IURPPP+J
WRPP+J3IRUV\VWROLFDQGGLDVWROLF%3 DQGGXULQJH[HUFLVH
7KHZHLJKWYHVWVLJQL¿FDQWO\LQFUHDVHG%3DWUHVW WRPP+JEHIRUH
DQGPP+JDIWHU:5 DQGGXULQJH[HUFLVH )LJXUH /LQHDUUHJUHVVLRQ
revealed evidence for independent associations of weight vest with BP (P=0.006
for systolic and P=0.009 for diastolic BP at rest).
Conclusions: This study shows that wearing of an external weight vest has immediate effects on BP at rest and during exercise independent of BW or body fat.
More research is needed to understand the physiological mechanisms between
weight and BP.
4B.03
Design and method: We assessed the association of exercise capacity and
mortality risk in 10,096 HTN men (mean age: 60±11). Of those, 5,108 were
GLDEHWLFDQGGLDEHWLFDQGREHVH %0,• )RXU¿WQHVVFDWHJRULHV TXDU
tiles) were formed based on peak metabolic equivalents (METs) achieved durLQJ D JUDGHG H[HUFLVH WHVW /HDVW)LW ” 0(7V Q /RZ)LW 0(7VQ 0RGHUDWH)LW0(7VQ DQG+LJK)LW !0(7V
Q 7RDVVHVVWKHLPSDFWRI¿WQHVVRQPRUWDOLW\ULVNLQLQGLYLGXDOVZLWK
additional co-morbidities, we formed three subgroups: HTN-Only; HTN+DM2;
and HTN+DM2+Obesity.
Results: There were 2,845 deaths (median follow-up 9.6 years). After controlling for age, smoking, the cardiovascular disease and medications, we observed
an inverse and graded association between exercise capacity and mortality risk
for the entire cohort (p<0.001 for trend). Fitness-related risk within the subgroups of HTN+DM2 and HTN+DM2+Obesity are presented in table with
Least-Fit-HTN only used as reference group.
Conclusions: $Q LQYHUVH DQG JUDGHG DVVRFLDWLRQ EHWZHHQ ¿WQHVV DQG PRUWDOLW\
risk in individuals with HTN regardless of additional co-morbidities.
4B.02
EFFECTS OF WEIGHT ON BLOOD PRESSURE AT
REST AND DURING EXERCISE
56FKRHQHQEHUJHU%HU]LQV1, A. Schoenenberger 2, P. Suter 3, P. Erne 1. 1 ESH
Hypertension Center of Excellence and Klinik St. Anna Hirslanden, Luzern,
SWITZERLAND, 2 Division of Geriatrics, Department of General Internal
PROSPECTIVE STUDY OF TOTAL SLEEP DURATION
AND INCIDENT METABOLIC SYNDROME: THE
ARIRANG STUDY
J. Kim, J. Yoon, S. Lee, B. Yoo, S. Ahn, M. Ahn, J. Lee, Y. Yoon, J. Lee,
S. Ahn, J. Park. Wonju College of Medicine, Yonsei University, Wonju, SOUTH
KOREA
Objective: Total sleep duration may play a role in the development of metabolic abnormalities, but prospective studies of the predictive value of sleep
duration to identify individuals at high risk of new-onset metabolic syndrome
are lacking. We examine the association between total sleep duration and the
incidence of metabolic syndrome in a population-based longitudinal study.
Design and method: Prospective cohort study of 2,579 adults aged 40 to 70
years without metabolic syndrome examined in 2005 – 2008 (baseline) and
± IROORZXS 6OHHSGXUDWLRQZDVFDWHJRUL]HGLQWRKWR
KWRKDQG!K6OHHSGXUDWLRQZDVDVVHVVHGE\WUDLQHGLQWHUYLHZHUV
Results: During an average of 2.6years of follow-up, 558 (21.6%) developed
metabolic syndrome. In multivariable adjusted models, the odds ratio (95%
CI) for incident metabolic syndrome comparing the 6 to <8 h to the <6 h of
total sleep duration was 1.41 (1.06-1.88). The corresponding odds ratios (95%
CI) for high waist circumference, low HDL cholesterol, high triglycerides,
high blood pressure, and high blood glucose were 1.30 (0.98 – 1.69), 0.75
(0.56 – 0.97), 0.82 (0.60 – 1.11), 1.56 (1.19 – 2.03), and 1.31 (0.96 – 1.79),
respectively
Conclusions: Short sleep duration is an independent risk factor for incident
metabolic syndrome in a population-based longitudinal study.
S
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Journal of Hypertension Volume 32, e-Supplement 1, 2014
4B.04
PREVALENCE OF OBSTRUCTIVE SLEEP APNEA
IN PATIENTS WITH RESISTANT HYPERTENSION
REFERRED FOR RENAL SYMPATHETIC
DENERVATION
T. Kara 1, M. Soucek 2, Z. Starek 1, M. Novak 1, T. Mikusova 1, M. Belehrad 1,
J. Vitovec 1, 31HX]LO3, N. Montano 4, .1DUNLHZLF]5, V.K. Somers 6.
1
St. Anne’s University Hospital Brno, ICRC, Department of Cardiovascular
Diseases, Brno, CZECH REPUBLIC, 2 St. Anne’s University Hospital Brno,
ICRC 2nd Department of Internal Medicine, Brno, CZECH REPUBLIC,
3
University Hospital Na Homolce, Department of Cardiology, Prague, CZECH
REPUBLIC, 4 University of Milan, Luigi Sacco Hospital, Division of Medicine
and Pathophysiology, Milan, ITALY, 5 Medical University of Gdansk, Department
of Hypertension and Diabetology, Gdansk, POLAND, 6 Mayo Clinic, Division of
Cardiovascular Diseases and Hypertension, Rochester, MN, USA
Objective: Obstructive sleep apnea (OSA) is one of the major factors contributing
to a chronic increase of sympathetic activity and consequently raising blood pressure. This mechanism may be particularly important role in the pathophysiology of
resistant hypertension and may thus affect individual responses to treatment, and
may conceivably blunt any hypotensive effects of renal sympathetic denervation
(RSD). However, the prevalence of OSA was not assessed in SYMPLICITY HTN 1
and SYMPLICITY HTN 2 trials, and there are only limited data available related to
the prevalence of OSA in patients with resistant hypertension (RH) treated by RSD.
Assessment of prevalence of OSA and its severity in patients with RH referred for
RSD.
Design and method: We studied 21 patients (pts) with RH (16 men), age 57+7 yrs.
participating in the RELIEF Study, none of whom were previously evaluated for OSA.
Ambulatory blood pressure (BP) values were systolic BP 157 + 14 and diastolic BP 93
+ 13 mm Hg, with an average of 5 antihypertensive drugs used per patient. Sleep apnea
ZDVDVVHVVHGE\IXOOSRO\VRPQRJUDSK\LQDVSHFLDOL]HGFDUGLRYDVFXODUVOHHSFHQWHU
of ICRC - Department of Cardiovascular Diseases of St. Anne’s University Hospital.
Results: Sleep apnea was detected in 15 pts (71%). Average apnea-hypopnea index
(AHI) was 29 events per hour of sleep, with dominance of OSA. Seven pts (33%)
KDGVHYHUH26$ $+,! Conclusions: 1. There is a high prevalence of OSA, including severe OSA, in patients with RH referred for RSD. None of the patients had OSA diagnosed in the
past.
2. Sleep evaluation with PSG or equivalent should be obtained as part of the clinical
protocol before patients undergo RSD, because OSA treatment can improve blood
pressure control in RH, and may obviate the need for invasive intervention. It is also
possible that untreated OSA may limit any therapeutic response to RSD.
26$VKRXOGEHFRQVLGHUHGDVDSRWHQWLDOIDFWRUWRLPSURYHVWUDWL¿FDWLRQRIUHVSRQGHUVQRQUHVSRQGHUVWR56'
4B.05
CHARACTERISTICS OF VESSELS WALL AND
MYOCARDIUM IN PATIENTS WITH HYPERTENSION
AND HEART FAILURE WITH PRESERVED EJECTION
FRACTION WITH AND WITHOUT METABOLIC
SYNDROME
PP DW WKH ¿UVW JURXS DQG “ PP DW WKH VHFRQG S OHIW YHQWULFOH
ZDOOWKLFNQHVV“PPDWWKH¿UVWJURXSDQG“PP±DWWKHVHFRQG
S OHIWYHQWULFOHP\RFDUGLXPPDVV“JDWWKH¿UVWJURXSDQG
201.19±58.82 g – at the second (p=0.005).
Conclusions: Among patients with HTN and HF-PEF with and without MS sigQL¿FDQWFKDQJHVLQWKHVWUXFWXUHRIYHVVHOZDOODQGP\RFDUGLXPZHUHIRXQG7KH
presence of MS lead to the more pronounced myocardial remodeling.
4B.06
BLOOD PRESSURE VARIABILITY IS A MODIFIABLE
RISK FACTOR IN THE METABOLIC SYNDROME,
INDEPENDENT OF BLOOD PRESSURE CONTROL
Y. Marcus 1, E. Segev 2, G. Shefer 1, J. Sack 1, B. Tal 1, M. Yaron 1, E. Carmeli 3,
D. Yablonka 1, T. Even-Chen 1, M. Margaliot 1, N. Stern 1. 1 Institute of
Endocrinology Metabolism and Hypertension, Tel Aviv Medical Center, Tel
Aviv, ISRAEL, 2 Holon Institute of Technology, Faculty of Science, Holon,
ISRAEL, 3 Physical Therapy, University of Haifa, Haifa, ISRAEL
Objective: Blood pressure (BP) variability contributes to target organ damage
(TOD), independent of BP levels.
To study the correlation between variability in ambulatory blood pressure moniWRULQJ $%30 PHWDEROLF SDUDPHWHUV DQG72' LQ VXEMHFWV DIÀLFWHG ZLWK WKH
metabolic syndrome (MetS).
Design and method: Eighty-two (mean age of 51) non-diabetic subjects who ful¿OOHGWKH$73,,,FULWHULDSDUWLFLSDWHGLQWKLVVWXG\%DVHOLQHDVVHVVPHQWLQFOXGHGFOLQLFDODQGELRFKHPLFDOSUR¿OLQJ$%30ERG\FRPSRVLWLRQZLWK'(;$DQGFDURWLG
intima-media thickness. The intervention targeted all risk factors through frequent
interactions with a multidisciplinary team including an endocrinologist, a dietician
and physical therapist. If needed, patients were medicated to control hypertension
and dyslipidemia. BP variability was assessed by the standard deviation (STD) of
daytime systolic BP derived from the ABPM records.
Results: Subdivided by the median of daytime STD, two population of MetS subjects were formed, people whose STD was < 11mmHg (low variability; LV) and
WKRVH ZLWK 67' ! PP+J KLJK YDULDELOLW\ +9 2I FULWLFDO LPSRUWDQFH LV WKH
fact that the two groups did not differ in terms of (LV, HV respectively): systolic
(121.5, 125.2mmHg) and diastolic (74.3, 76.6 mmHg) pressure by ABPM, age (53,
\ IDVWLQJJOXFRVH +%$,& DQG%0, NJP However, despite these similarities the HV group had higher CRP (4.79 vs. 1.51
mg%; p=0.05), SGPT (36.9 vs28.9; p<0.05), LDLc (122.9 vs 103.6mg%; p<0.05)
and carotid intima media thickness (794.7µm vs. 730.3 µm; p=0.03). Additionally,
despite similar BMI, the HV group had higher fatness as seen in the total body fat
(41.7%, 38%, p=0.05), % fat in legs (36% vs. 29.9%; p=0.04) and genycoid (41.4
vs. 36.5%; p= 0.06). Following 1 year of intervention, which resulted in weight
reduction in both groups, but no BP lowering, reducted BP variability was seen only
with the HV group.
Conclusions: In MetS, higher BP variability is linked to increased CRP, LDL cholesterol, SGOT (indicative of fatty liver), intima-media thickness and increased body
fatness despite indistinguishable BMI. Increased BP variability in the MetS can be
QRUPDOL]HGWKURXJKDPXOWLGLVFLSOLQDU\LQWHUYHQWLRQLQGHSHQGHQWRI%3
O. Drapkina, E. Zyatenkova.
First Moscow Medical University, Moscow, RUSSIA
Objective: The structure of the vessels wall and myocardium is an independent
predictor of cardiovascular events among patients with hypertension (HTN) and
heart failure. There is a data that metabolic syndrome (MS) accelerates the progression of structural and functional disorders of vessel wall and myocardium.
To investigate the characteristics of vessels wall and myocardium in patients with HTN
and heart failure with preserved ejection fraction (HF-PEF) with and without MS.
Design and method: 59 patients with HTN and HF-PEF were included. First group
– patients without MS (n=29), second group – patients with MS (n=30). Following
FKDUDFWHULVWLFVZHUHHYDOXDWHGDUWHULDOVWLIIQHVV VWLIIQHVVLQGH[6, UHÀHFWLRQLQGH[
(RI), augmentation index (Alp). The function of big vessels was evaluated by phase
VKLIW 36 RIWKHVPDOOYHVVHOV±E\WKHRFFOXVLRQLQGH[ 2, ,QYHVWLJDWLRQV6L]HV
of the heart chambers and the thickness of the myocardium wall were evaluated
echocardiographically.
Results: $PRQJWKHSDWLHQWVIURPERWKJURXSVVLJQL¿FDQWFKDQJHVRIWKHYHVVHOV
wall and myocardial structure were found.
6, DW WKH ¿UVW JURXS ZDV “ PV DW WKH VHFRQG JURXS ± “ PV
QRQVLJQL¿FDQWS 5,DWWKH¿UVWJURXSZDV“DWWKHVHFRQG±
“ QRQVLJQL¿FDQWS $OSDWWKH¿UVWJURXSZDV“
DW WKH VHFRQG ± “ VLJQL¿FDQW S 36 DW WKH ¿UVW JURXS ZDV
“PVDWWKHVHFRQG±“PV QRQVLJQL¿FDQWS 2,DWWKH¿UVW
JURXSZDV“DWWKHVHFRQG±“ QRQVLJQL¿FDQWS Intergroup differences were found in the interventricular septum thickness: 10,3±1,2
4B.07
EFFECTS OF PHENTERMINE AND TOPIRAMATE
EXTENDED-RELEASE ON WEIGHT LOSS AND BLOOD
PRESSURE BY BASELINE HEART RATE
J. Jordan 1, N. Finer 2, W. Day 3. 1 Institute of Clinical Pharmacology, Hannover
Medical School, Hannover, GERMANY, 2 Institute for Cardiovascular Science,
University College, London, London, UNITED KINGDOM, 3 VIVUS, Inc.,
Mountain View, CA, USA
Objective: 3KHQWHUPLQHWRSLUDPDWHH[WHQGHGUHOHDVH 3+(1730(5 GHPRQVWUDWHGVLJQL¿FDQWZHLJKWORVVDQGLPSURYHPHQWVLQFDUGLRPHWDEROLFSDUDPHWHUV
LQ WKH (48,3 DQG &2148(5 VWXGLHV RI REHVHRYHUZHLJKW VXEMHFWV ZLWK RU
without weight-related comorbidities. This post-hoc analysis evaluated percent
weight loss and changes in systolic blood pressure (SBP), diastolic BP (DBP),
heart rate (HR), and antihypertensive medication use from baseline to week 56
after stratifying subjects (safety set) by baseline HR to explore whether HR affects the treatment response.
Design and method: Data from the 56-week, double-blind, placebo-controlled,
UDQGRPL]HG3KDVHVWXGLHV(48,3 ERG\PDVVLQGH[>%0,@X!!X!NJ
P DQG&2148(5 %0,X!!X!WRX!X!NJPZLWKX!!
X!FRPRUELGLWLHV ZHUHSRROHG6XEMHFWVUHFHLYLQJSODFHER Q 3+(1
PJ730(5PJ Q 3+(1PJ730(5PJ Q RU 3+(1 PJ730 (5 PJ Q ZHUH VWUDWL¿HG LQWR
TXDUWLOHV IRU EDVHOLQH +5 ESP X! X! >Q @ ! WR X!X!
e51
Journal of Hypertension Volume 32, e-Supplement 1, 2014
>Q @!WRX!X!>Q @DQG!>Q @ $OOVXEMHFWVUHFHLYHG
OLIHVW\OHPRGL¿FDWLRQFRXQVHOLQJ
Results: $W EDVHOLQH PHDQ ZHLJKW ZDV “NJ %0, “NJP
6%3'%3“PP+J+5“ESPDQGUHSRUWHG
having hypertension, whereas 47.3% were using antihypertensive medications.
$WZHHNVXEMHFWVUHFHLYLQJ3+(1730(5RUH[SHULHQFHGVLJQL¿FDQWO\JUHDWHUPHDQSHUFHQWZHLJKWORVVUHJDUGOHVVRIEDVHOLQH+5 3
YVSODFHERDOOFRPSDULVRQV %3ZDVGHFUHDVHGLQ3+(1730(5±WUHDWHGVXEjects across all baseline HR categories (Table). HR increased in subjects with
ORZHU EDVHOLQH +5 X!X! ESP RU ! WR X! X! ESP EXW GHFUHDVHGLQVXEMHFWVZLWKEDVHOLQH+5!ESP 7DEOH )XUWKHUPRUHVXEMHFWV
UHFHLYLQJKDGDQHWGHFUHDVHLQDQWLK\SHUWHQVLYHPHGLFDWLRQXVHLQDOO+5
categories, whereas net increases occurred in placebo-treated subjects. Common
adverse events across HR categories were constipation, dry mouth, and paraesthesia and were similar to the overall population.
Conclusions: 5HJDUGOHVVRIEDVHOLQH+53+(1730(5ZKHQXVHGLQFRQMXQFWLRQ ZLWK OLIHVW\OH PRGL¿FDWLRQV ZDV DVVRFLDWHG ZLWK VLJQL¿FDQW ZHLJKW
loss and BP improvements vs placebo. This weight loss was accompanied by
GHFUHDVHG DQWLK\SHUWHQVLYH PHGLFDWLRQ XVH ZLWK WKH GRVH7KHVH UHVXOWV
VWURQJO\ VXJJHVW WKDW 3+(1730 (5 PHGLDWHG ZHLJKW ORVV LPSURYHV FDUGLRvascular risk markers.
4B.08
BRAIN NATRIURETIC PEPTIDE PREVENTS THE
DEVELOPMENT OF CARDIAC DYSFUNCTION IN
OBESE AND DIABETIC DB/DB MICE
J. Gutkowska, E. Plante, M. Jankowski, S. Engeli. CR-CHUM, University of
Montreal, Department of Medicine, Montreal, CANADA
Objective: Obesity and diabetes enhance the risk of developing cardiovascular
GLVHDVHVDQGKHDUWIDLOXUH7KHVHPHWDEROLFGLVRUGHUVDUHJHQHUDOO\UHÀHFWHGE\
QDWULXUHWLFSHSWLGHVV\VWHPGH¿FLHQF\6LQFHEUDLQQDWULXUHWLFSHSWLGH %13 LV
NQRZQ WR LQÀXHQFH PHWDEROLVP DQG FDUGLRSURWHFWLRQ ZH LQYHVWLJDWHG WKH HIfect of chronic exogenous BNP treatment on adverse myocardial consequences
related to obesity and diabetes.
Design and method: 7HQZHHNROG&%/.V-GEGEREHVHGLDEHWLFPLFH GE
GE DQGWKHLUOHDQFRQWUROOLWWHUPDWHV GE ZHUHWUHDWHGZLWK%13 —JNJK RUVDOLQHGXULQJZHHNV Q JURXS 6HULDOEORRGDQGWRPRJUDSK\DQDO\VLV
were performed. Cardiac function was determined by echocardiography, and
biochemical and histological heart and fat analysis were also performed.
Results: BNP treatment resulted in an average increase in plasma levels of 70
SJPO$QLPSURYHPHQWLQWKHPHWDEROLFSUR¿OHRIGEGEPLFHZDVREVHUYHG
including a reduction in fat content, increased insulin sensitivity, improved
JOXFRVH WROHUDQFH DQG ORZHU EORRG JOXFRVH GHVSLWH LQFUHDVH IRRG LQWDNH 'E
db mice receiving saline displayed both early systolic and diastolic dysfunction
whereas these functional changes were prevented by BNP treatment. The cardioprotective effects of BNP were attributed to the inhibition of cardiomyocytes
DSRSWRVLVP\RFDUGLDO¿EURVLVFDUGLDFK\SHUWURSK\DQGDGYDQFHGJO\FDWLRQHQG
SURGXFWVUHFHSWRUIRUDGYDQFHGJO\FDWLRQHQGSURGXFWV $*(5$*( DVZHOODV
QRUPDOL]DWLRQRIFDUGLDF¶DGHQRVLQHPRQRSKRVSKDWHDFWLYDWHGSURWHLQNLQDVH
(AMPK) and endothelial nitric oxide synthase (eNOS) activities.
Conclusions: 7KLVVWXG\GHPRQVWUDWHGEHQH¿FLDOHIIHFWRIFKURQLFORZGRVHLQIXVLRQRI%13RQPHWDEROLVPSUR¿OHWRJHWKHUZLWKWKHSUHYHQWLRQRIGLDEHWLF
KHDUW GLVHDVH LQ GEGE PLFH PRGHO &DUGLRSURWHFWLYH PHFKDQLVPV RI %13 LQFOXGHQRUPDOL]DWLRQRIFDUGLDF$03.DQGH126DFWLYLWLHVDVZHOODVDUHGXFHG
cardiac AGE formation. These observations clearly suggest a potential role for
BNP in replacement therapy for the prevention of cardiovascular complications
of diabetes and obesity.
4B.09
LAPAROSCOPIC ROUX-EN-Y GASTRIC BYPASS
(RYGB) INDUCES FAVORABLE CHANGES IN
METABOLOMIC PROFILES IN MORBIDLY OBESE
ADOLESCENTS
Y. Chen 1, (*URQRZLW]2, T. Olbers 3, C. Marcus 4, J. Dahlgren 2, 03HLW]VFK5,
G. Eisenhofer 5, P. Friberg 1. 1 Department of Molecular and Clinical Medicine,
University of Gothenburg, Gothenburg, SWEDEN, 2 Department of Pediatrics,
University of Gothenburg, Gothenburg, SWEDEN, 3 Department of Surgery,
University of Gothenburg, Gothenburg, SWEDEN, 4 Department of Clinical
Science, Intervention and Technology, Karolinska Institute, Stockholm,
SWEDEN, 5 Institute of Clinical Chemistry and Laboratory Medicine,
Technical University Dresden, Dresden, GERMANY
Objective: Recently we reported that RYGB in morbidly obese adolescents
caused a substantial weight loss, reduced fasting insulin, and improved cardiovascular risk factors. The mechanisms involved are less known. High level of
the branch-chained amino acids (BCAA) and aromatic amino acids (AAA) is
associated with adult obesity and insulin resistance (IR). We tested the hypothesis that a targeted metabolomic approach involving a broader spectrum of meWDEROLWHVPD\KHOSWRLGHQWLI\PHFKDQLVPVLQYROYHGLQWKHEHQH¿FLDOHIIHFWVRI
RYGB on morbidly obese adolescents.
Design and method: Fasting plasma samples were obtained from 41 obese
DGROHVFHQWV DJH“\HDUV%0,“NJPJLUOV DWEDVHOLQHDQG
RQH \HDU DIWHU 5<*% IRU GHWHUPLQLQJ PHWDEROLWH SUR¿OHV XVLQJ WKH$EVROXWH
IDQTM p180 kit (Biocrates Life Science). A total 186 metabolites were measured: 21 amino acids, hexose, free carnitine, 39 acylcarnitines, 15 sphingomyolines (SM), 90 phosphatidylcholines (PC) and 19 biogenic amines. HDL, LDL,
triacylglycerol, insulin and glucose were also measured and HOMA-IR was
calculated.
Results: One year after RYGB there was a substantial reduction in BMI, fasting
insulin, triacylglycerol and LDL, and an increase in HDL. Using a BonferroniFRUUHFWHG VLJQL¿FDQFH OHYHO S[ ZH IRXQG WKDW SODVPD OHYHO RI PHWDEROLWHV FKDQJHG VLJQL¿FDQWO\ DIWHU 5<*% 6SHFL¿FDOO\ 5<*% LQGFXHG D
substantial decrease in BCAA isoleucine, leucine and valine and their C3 and
C5 acylcarnitine metabolites, as well as AAA phenylalanine and tyrosine. Furthermore, we found that higher baseline level of BCAA and AAA was associDWHGZLWKVPDOOHUGHFUHDVHLQ%0,DIWHU5<*%:HGLGQRW¿QGDQ\DVVRFLDWLRQ
between baseline level of these metabolites and changes in HOMA-IR after
5<*%5<*%LQGXFHGVLJQL¿FDQWFKDQJHVLQ60VO\VR3&VDQG3&V
Interestingly, 8 PCs that decreased after RYGB are diacyl-PCs, while 3 PCs
that increased after RYGB are acyl-alkyl-PCs. Changes in acyl-alkyl-PCs were
exclusively and positively associated with changes in HDL.
Conclusions: RYGB in morbidly obese adolescents led to favorable changes
LQPHWDEROLWHSUR¿OHVHYLGHQFHGDVGHFUHDVHG%&$$DQG$$$DQGLQFUHDVHG
acyl-alkyl-PCs. In addition, baseline level of BCAA and AAA predicted BMI
change 1 year after RYGB.
4B.10
LEAN MASS LOSS DURING THE METABOLICSYNDROME TREATMENT HAS UNFAVORABLE
CARDIOVASCULAR EFFECTS NEGATING BENEFITS
ATTAINED BY FAT MASS LOSS
Y. Marcus 1, J. Sack 1, E. Segev 2, G. Shefer 1, R. Limor 1, G. Shenkerman 1,
B. Tal 1, M. Yaron 1, E. Carmeli 3, M. Margaliot 1, N. Stern 1. 1 Institute of
Endocrinology, Metabolism and Hypertension, Tel Aviv Medical Center, Tel
Aviv, ISRAEL, 2 Holon Institute of Technology, Faculty of Science, Holon,
ISRAEL, 3 Physical Therapy, University of Haifa, Haifa, ISRAEL
Objective: Intentional weight loss induces favorable cardiovascular (CV) effects secondary to fat mass reduction. However, the CV impact of reduction in
lean body mass, which often accompanies weight loss, has not been explored.
0XVFOHGLVLQWHJUDWLRQFRXOGHOLFLWLQÀDPPDWLRQZLWKDGYHUVHV\VWHPLFHIIHFWV
potentially affecting the vasculature.
7RH[DPLQHWKHUHODWLRQVKLSEHWZHHQOHDQIDWPDVVORVVEORRGSUHVVXUH %3 DQG LQWLPDPHGLD WKLFNQHVV ,07 GXULQJ \HDU RI H[HUFLVHGLHW WUHDWPHQW LQ
patients with the metabolic syndrome (MetS).
Design and method: Thirty eight subjects with MetS participated in a multidisciplinary program targeting all known risk factors with emphasis on diet and
exercise. Carotid intima media thickness (IMT), 24h ambulatory BP monitoring
(ABPM), central BP and body composition by DEXA, were evaluated before the
intervention and 1 year later.
Results: 3UHGLFWDEO\PHQZLWKODUJHUIDWPDVVUHGXFWLRQ ! HQMR\HGVLJQL¿FDQW UHGXFWLRQ LQ$%30 V\VWROLF SUHVVXUH PP+J S +RZHYHU
e52
Journal of Hypertension Volume 32, e-Supplement 1, 2014
compared to men showing good muscle preservation (gain or loss<2.9% in lean
PDVV PHQZLWKQRWDEOHOHDQPDVVGHSOHWLRQ ! VKRZHG QRGHFOLQHLQ
central systolic BP (+2mmHg vs. -21mmHg; p<0.0033); (2) no reduction in IMT
XPYVXPS /LNHZLVHZRPHQZLWKVLJQL¿FDQWOHDQPDVVORVV
showed no decline in mean ABPM diastolic pressure.
Conclusions: The loss of lean body mass during treatment of the MetS is
associated with negative effects on BP and IMT, particularly in men. This
novel association should draw attention to the possibility that muscle preservation may be important for cardiovascular outcome during intentional
weight loss.
Abstracts
e53
ORAL SESSION
ORAL SESSION 4C
CORONARY HEART DISEASE AND HEART
FAILURE
4C.01
PREDICTIVE VALUE OF CIRCULATING ENDOTHELIALDERIVED APOPTOTIC MICROPARTICLES IN
PATIENTS WITH ISCHEMIC SYMPTOMATIC CHRONIC
HEART FAILURE
$%HUH]LQ$.UHP]HUY. Martovitskaya, T. Samura.
State Medical University, Zaporozhye, UKRAINE
Objective: To evaluate the prognostic value of circulating endothelialderived microparticles (EMPs) for cumulative survival in patients with ischemic chronic heart failure (CHF).
Design and method: A total of 154 patients with ischemic symptomatic
moderate-to-severe CHF were enrolled in the study on discharge from the
hospital. Observation period was up to 3 years. Blood samples for biomarkers measurements were collected. Flow cytometry analysis for quantifying
the number of EMPs was used. EMPs number for cumulative survival cases
due to CHF was tested. Additionally, all-cause mortality, and CHF-related
death were examined.
Results: During a median follow-up of 2.18 years, 21 participants died and
VXEMHFWVZHUHKRVSLWDOL]HGUHSHWLWLYHO\0HGLDQVRIFLUFXODWLQJOHYHOVRI
(03VLQVXUYLYHGDQGGLHGSDWLHQWFRKRUWZHUHQP/ FRQ¿GHQFH
LQWHUYDO>&,@ QP/ DQGQP/ &, Q
mL) (P<0.001). Number of circulating EMPs was distributed into Quartiles
4 4 QP/ 4 QP/ 4 QP/ DQG 4 ! QP/ 52& DQDO\VLV KDV EHHQ VKRZQ WKDW FXW RII SRLQW
RI (03V QXPEHU IRU FXPXODWLYH VXUYLYDO IXQFWLRQ ZDV QP/ $UHD
under cure was 0.913 (Std. error = 0.025; 95% CI = 0.863-0.962), sensitivity
DQGVSHFL¿FLW\ZHUHDQGUHVSHFWLYHO\,WKDVEHHQIRXQGDVLJQL¿FDQWO\GLYHUJHQFHRI.DSODQ0HLHUVXUYLYDOFXUYHVLQSDWLHQWVZLWKKLJK
TXDUWLOH (03V QXPEHU ! QP/ RI (03V QXPEHUV ZKHQ FRPSDUHG
with low quartiles. Using a stepwise model selection method for multivariable prediction model we have been investigated that EMPs number alone
and combination of EMPs number with NT-pro-BNP remained statistically
VLJQL¿FDQWSUHGLFWRUVIRUDOOFDXVHPRUWDOLW\&+)UHODWHGGHDWKDQG&+)
related re-hospitalisations, whereas combination of EMPs with both NT-proBNP and LVEF did not.
Conclusions: Increased circulating EMPs associates with increased 3-year
&+)UHODWHG GHDWK DOOFDXVH PRUWDOLW\ DQG ULVN IRU UHFXUUHQW KRVSLWDOL]Dtion due to CHF. New studies with more statistical powerful are required.
Knowledge of the functional properties of EMPs will contribute to a better
understanding of the pathological mechanisms of communication between
cells and CHF progression, because EMPs may be an attractive prognostic
biomarker for CHF.
4C.02
ASSOCIATIONS OF TRYPTOPHAN METABOLISM
WITH SYSTOLIC AND DIASTOLIC LEFT VENTRICULAR
FUNCTION IN PATIENTS WITH PRIMARY
HYPERPARATHYROIDISM
$7RPDVFKLW]1, N. Verheyen 2, M. Gaksch 3, M. Grübler 2, -:HW]HO2,
E. Belyavskiy 2, C. Colantonio 2, E. Kraigher-Krainer 2, :0lU]4,5,6,
T. Grammer 6, $0HLQLW]HU5, J. Rus-Machan 1, A. Fahrleitner-Pammer 3,
B. Pieske 2, 63LO]3,7. 1 Specialist Clinic of Rehabilitation PV Bad Aussee,
Bad Aussee, AUSTRIA, 2 Medical University of Graz, Dept. of Cardiology,
Graz, AUSTRIA, 3 Medical University of Graz, Dept. of Int. Med., Div.
of Endocrinology and Metabolism, Graz, AUSTRIA, 4 Synlab Academy,
Synlab Services LLC, Mannheim, GERMANY, 5 Medical University of Graz,
Clinical Institute of Medical and Chemical Laboratory Diagnostics, Graz,
AUSTRIA, 6 Mannheim Institute of Public Health, Ruperto Carola University
Heidelberg, Medical Faculty Mannheim, Mannheim, GERMANY, 7 Department
of Epidemiology and Biostatistics, EMGO Institute for Health and Care
Research, VU University Medical Centre, Amsterdam, NETHERLANDS
Objective: Accumulating evidence points to a profound role of tryptophan
metabolism for left ventricular function. Circulating parathyroid hormone
(PTH) has been associated with underlying causes of heart failure. We therefore aimed to evaluate the relationship between tryptophan metabolites and
left ventricular (LV) function in patients with primary hyperparathyroidism
(pHPT).
Design and method: $WEDVHOLQHYLWDPLQ'VXI¿FLHQW K\GUR[\YLWDPLQ'!QJP/ S+37SDWLHQWVHQUROOHGLQWKH(IIHFWVRI(SOHUHQRQH
on Parathyroid Hormone Levels in Patients with Primary Hyperparathyroidism trial (EPATH) underwent two-dimensional transthoracic echocardiogUDSK\WLVVXH'RSSOHULPDJLQJ DQGGLDVWROLFIXQFWLRQDVVHVVPHQWZLWK(H¶
FDOFXODWHG DV WKH UDWLR RI HDUO\ GLDVWROLF WUDQVPLWUDO ÀRZ YHORFLW\ WR PLWUDO
annular velocity at the medial wall), 24-hour ambulatory blood pressure
monitoring and serum N-terminal pro-brain natriuretic peptide (NTproBNP)
GHWHUPLQDWLRQ3DUDPHWHUVUHÀHFWLQJWU\SWRSKDQPHWDEROLVPLQFOXGLQJWU\Stophan, kynurenine, kynurenic acid, picolinic acid and quinolinic acid were
measured in serum.
Results: 3+37SDWLHQWV PHDQ“6'RUPHGLDQ>,45@PHDQDJH“\
79.7% females) had mild disease with total serum calcium of 2.63 ± 0.13
PPRO/ DQG 37+ RI >@ SJPO 0HDQ /9 HMHFWLRQ IUDFWLRQ
/9() RIWKHVWXG\SRSXODWLRQZDV“PHDQ(HUDWLRZDV
± 6.2.
Tryptophan, kynurenine and quinolinic acid correlated inversely with LVEF
3HDUVRQ FRUUHODWLRQ FRHI¿FLHQWV U S U S and r=-0.363, p=0.008, respectively). NT-pBNP correlated positively with
knyurenine (r=0.341, p=0.008), kynurenic acid (r=0.369, p=0.004) and quinolinic acid (r=0.401, p=0.002). In addition, quinolinic acid showed a signifLFDQWFRUUHODWLRQZLWK(H U S Multiple linear regression analysis adjusted for age, sex, body mass index,
ongoing antihypertensive medication, estimated GFR (CKD-EPI), HbA1c,
NT-pBNP, smoking status, PTH, 25(OH)D, total serum calcium, 24-hour
DPEXODWRU\ V\VWROLF EORRG SUHVVXUH UHYHDOHG WU\SWRSKDQ EHWD FRHI¿FLHQW ȕ
S DQG TXLQROLQLF DFLG ȕ S DV LQGHSHQGHQW
SUHGLFWRUVRI/9()DQG(HUHVSHFWLYHO\
Conclusions: This investigation indicates that tryptophan metabolism is independently related to systolic and diastolic function in patients with PTH
excess. Studies in broader cardiovascular risk groups are warranted to furWKHUHOXFLGDWHWKHUROHRIWU\SWRSKDQKRPHRVWDVLVIRUSUHGLFWLQJDQGRUPHGLating myocardial function.
4C.03
THE RELATIVE CONTRIBUTION OF DIRECT
DIFFERENTIATION VERSUS PARACINE EFFECT
ON ADIPOSE-DERIVED STEM CELL THERAPY FOR
MYOCARDIAL INFARCTION
W. Wang 1, D. Yang 1, W. Wang 1, L. Li 1, Y. Peng 1, H. Huang 2,
Y. Guo 2, H. Wang 1, C. Zeng 1 1 Department of Cardiology, Daping Hospital,
Third Military Medical University, Chongqing, CHINA, 2 Department of
Ultrasonography, Southwest Hospital, Third Military Medical University,
Chongqing, CHINA
Objective: Recent studies have demonstrated that transplantation of adipose-derived stem cell (ADSC) can improve cardiac function in animal models of myocardial infarction (MI). However, mechanisms underlying this are
QRWIXOO\XQGHUVWRRG,QWKLVVWXG\ZHFKDUDFWHUL]HGWKHSDUDFULQHHIIHFWRI
transplanted ADSC and investigated its relative importance versus direct differentiation in ADSC transplantation mediated cardiac repair.
Design and method: MI was experimentally induced in mice by ligation
of the left anterior descending coronary artery. Either ADSC, ADSC-conditioned medium (CM) or control medium was injected into the peri-infarct re-
S
U
N
D
A
Y
O
R
A
L
S
e54
Journal of Hypertension Volume 32, e-Supplement 1, 2014
gion immediately after MI. Cardiac function, cardiac remodeling and infarct
VL]HZHUHH[DPLQHGDQGGLIIHUHQWLDWLRQFDSDFLW\SDUDFULQHDQWLDSRSWRWLFHIfect and pro-angiogenic effect of ADSC were evaluated in vitro and in vivo.
Results: Compared with the control group, both ADSC and ADSC-CM sigQL¿FDQWO\ UHGXFHG P\RFDUGLDO LQIDUFW VL]H DQG LPSURYHG FDUGLDF IXQFWLRQ
7KH WKHUDSHXWLF HI¿FDF\ RI$'6& ZDV PRGHUDWHO\ VXSHULRU WR$'6&&0
0,'0(0YV0,$'6&YV0,$'6&&0LQIDUFWVL]H“YV
32.2±2.8% vs. 35.7±2.5%; LVEF: 39.8±3.5% vs. 57.6±4.4% vs. 51.1±4.5%,
S $'6&&0 VLJQL¿FDQWO\ UHGXFHG FDUGLRP\RF\WH DSRSWRVLV LQ WKH
LQIDUFWERUGHU]RQHWRDVLPLODUGHJUHHZLWK$'6&WUHDWPHQW 781(/SRVLtive cardiomyocytes per 10^6 nuclei: MI+DMEM: 867.3±67.9; MI+ADSC:
657.4±64.2; MI+ADSC-CM: 646.7±54.1). ADSC enhanced angiogenesis in
WKHLQIDUFWERUGHU]RQHEXWWRDJUHDWHUGHJUHHWKDQWKDWVHHQLQWKH$'6&
&0WUHDWPHQW FDSLOODULHVSHU¿HOGVWDLQHGE\&'0,'0(0“
MI+ADSC: 52.9±4.5; MI+ADSC-CM: 44.4±3.6; p<0.05). ADSC was able
to differentiate to endothelial and smooth muscle cells in post-MI heart;
these ADSC-derived vascular cells amount to about 9% of the enhanced angiogenesis. No cardiomyocyte differentiated from ADSC was found.
Conclusions: $'6&&0 LV VXI¿FLHQW WR LPSURYH FDUGLDF IXQFWLRQ RI LQfarcted hearts. The therapeutic function of ADSC transplantation is mainly
induced by paracrine-mediated cardioprotection and angiogenesis, while
$'6&GLIIHUHQWLDWLRQFRQWULEXWHVDPLQRUEHQH¿WE\EHLQJLQYROYHGLQDQJLogenesis. Paracrine mechanisms are primarily involved in ADSC therapeutic
functions for MI.
4C.04
NOT RESTING BUT MAXIMAL EXERCISE BLOOD
PRESSURE IS AN INDEPENDENT FACTOR OF LEFT
VENTRICULAR MASS IN ELITE PROFESSIONAL
MALE ATHLETES
M. Zdravkovic 1, 60D]LF2, M. Djelic 2, I. Nedeljkovic 4, M. Dekleva 5,
M. Antic 3, T. Acimovic 2. 1 University Hospital Medical Center Bezanijska
Kosa, Faculty of Medicine, University of Belgrade, Belgrade, SERBIA,
2
Institute for Physiology, Faculty of Medicine, University of Belgrade,
Belgrade, SERBIA, 3 Institute of Sport, Belgrade, SERBIA,
4
Institute for Cardiovascular Diseases, Belgrade, SERBIA, 5 University
Clinical Center Zvezdara, Department of Cardiology, Belgrade, SERBIA
Objective: Exaggerated blood pressure (BP) response during exrcise is associated with increased risk of worsening hypertension in normotensives, as
ZHOODVLQDWKOHWHVZLWKKLJKQRUPDOEORRGSUHVVXUH7RGDWHFRQÀLFWLQJGDWD
have been reported concerning the nature (physiologic versus pathologic) of
left ventricular hypertrophy (LVH). Additionally, increased blood pressure
is risk factor for LVH.
7KHDLPRIWKHVWXG\ZDVWRHYDOXDWHWKHLQÀXHQFHRIWKHUHVWLQJDQGPD[LPDO
exercise BP values to the LVH in professional athletes.
Design and method: A total of 585 men professional athletes from a variHW\RIVSRUWVZHUHH[DPLQHG%3OHYHOVZHUHGLYLGHGDFFRUGLQJWRWKH(6+
(6&JLXGHOLQHVLQJURXSV JUXRS,RSWLPDOJURXS,,±QRUPDO
JURXS,,,±KLJKQRUPDODQGJURXS,9K\SHUWHQVLRQ!PP+J 0D[LPDOH[HUFLVHDQGUHFRYHU\FKDUDFWHULVWLFV
were obtained during a graded treadmill test until exhaustion: maximal oxygen uptake (VO2 max), heart rate (HRmax) and blood presure (TA max).
Standard echoacrdiographic measurements were obtained and left ventricular mass index (LVMI) was calculated according to the recommendations.
Results: The players mean age was 21,5 years (13-58), rest heart rate 62 ±
ESPDQGPHDQUHVW%3“PP+J DWKOHWHVKDG
optimal blood presure, 83 (14,2%) had normal BP , while groups III and IV
FRXQWHG DQG DWKOHWHVUHVSHFWLYHO\1RVLJQL¿FDQWFRUUUHODWLRQVEHWZHHQ/90,DQGUHVWYDOXHVRI%3ZHUHGHWHFWHG+RZHYHUVLJQL¿cant correlations were described between LVMI and maximal diastolic BP
S V\VWROLF%3DIWHUWKH¿UVWPLQXWHLQPD[LPDOH[HUFLVH S GLDVWROLF%3DIWHUWKH¿UVWPLQXWHLQPD[LPDOH[HUFLVH S DQGGLDVtolic BP after the third minute in maximal exercise (p=0.041). Multivariante
analysis failed in revealing resting blood pressure as an independent prognostic factor for LVH, but BP in maximal exercise is indeed an independent
prognostic factor for LVH.
Conclusions: 6LJQL¿FDQWO\KLJKHU%3YDOXHVDIWHUH[HUFLVHLQDWKOHWHVZLWK
normal and high normal BP strongly linked to the elevated LVMI. BP in
maximal exercise is an independent prognostic factor for LVH.
4C.05
RISK FACTORS AND THEIR PREDICTIVE VALUE OF
EVENTS IN ACUTE CORONARY SYNDROME
R. Palma Dos Reis 1, R. Rodrigues 2, A. Pereira 2, S. Gomes 2, A. Sousa 2,
G. Guerra 2, E. Henriques 2, S. Borges 2, D. Pereira 2, M. Mendonca 2.
1
Faculty of Medical Sciences, New University of Lisbon, Lisbon, PORTUGAL,
2
Research Unit, Funchal Hospital Centre, Funchal, PORTUGAL
Objective: Although traditional risk factors and some new risk markers are predictive of cardiovascular events, it is still unknown which ones associate with a poor
prognosis in acute coronary syndrome (ACS).
Our aim was to investigate the traditional risk factors and new risk markers associated with an adverse prognosis in ACS.
Design and method: A prospective study was performed between 2006 and 2010
with 583 patients with ACS who underwent a follow-up period of 3 years. For all
LQGLYLGXDOVZHDQDO\]HGWKHWUDGLWLRQDOULVNIDFWRUVDUWHULDOK\SHUWHQVLRQ $+7 diabetes, dyslipidemia, smoking, sedentary life style and new cardiovascular risk
markers such as: high-sensitivity C-reactive protein (hs-CRP), carotid-femoral pulse
ZDYHYHORFLW\ 3:9FI OHXNRF\WRVLV¿EULQRJHQDQGXULFDFLG8QLYDULDWHDQDO\VLV
ZDV SHUIRUPHG WR DQDO\]H GLIIHUHQFHV EHWZHHQ JURXSV ZLWK DQG ZLWKRXW HYHQWV and Cox regression estimated the independent predictors of cardiovascular events.
Results: This study showed that 41% of the ACS patients presented events during the follow-up: acute myocardial infarction, death, stroke, and coronary restenosis. High hs-CRP (p=0.049) and leukocytosis (p=0.008) were the biochemical
PDUNHUVWKDWVKRZHGVWDWLVWLFDOVLJQL¿FDQFHEHWZHHQJURXSV&R[UHJUHVVLRQSHUIRUPHGZLWKWUDGLWLRQDOULVNIDFWRUVKV&53¿EULQRJHQ3:9FIOHXNRF\WRVLV
DQG XULF DFLG VKRZHG WKDW$+7 KV&53 DQG VPRNLQJ ZHUH VLJQL¿FDQWO\ DQG
independently predictive factors of cardiovascular events (see Table).
Conclusions: Similarly to ACCORD BP, this study performed with ACS patients, showed that AHT was an independent predictor of cardiovascular events.
+V&53 DQ LQÀDPPDWRU\ PDUNHU DQG VPRNLQJ KDELWV ZHUH DOVR LQGHSHQGHQW
predictors of prognosis. This work highlights the importance of blood pressure
FRQWURODQGTXLWVPRNLQJDVVLJQL¿FDQWVWHSVWRLPSURYHSURJQRVLVLQ$&6
4C.06
MORBIDITY AND MORTALITY DUE TO
CARDIOVASCULAR DISEASES IN THE KAZAKHSTAN
POPULATION IN THE LATE PERIOD AFTER
RADIATION EXPOSURE
A. Markabayeva 1, T. Belikhina 2, L. Pivina 1, A. Kerimkulova 1, B. Ashimova 1,
$1XU]KDQRYD1, S. Maukayeva 1. 1 Semey State Medical University, Semey,
KAZAKHSTAN, 2 Research Institute for Radiation Medicine and Ecology,
Semey, KAZAKHSTAN
Objective: This study of morbidity and mortality rates due to cardiovascular
GLVHDVHVLQWKH.D]DNKVWDQSRSXODWLRQH[SRVHGWRUDGLDWLRQ
Design and method: :HKDYHDQDO\]HGGDWDEDVHRIWKH6WDWH6FLHQWL¿F5HJLVWHU
RI.D]DNKVWDQSRSXODWLRQH[SRVHGWRUDGLDWLRQ:HVWXGLHGWKHSUHYDOHQFHRI&9'
in the group of radiation risk (total 6,347 persons) which included people directly
exposed to radiation and their offspring (main group). Mortality rates for CVD
ZHUHDQDO\]HGEDVHGRQGHDWKFHUWL¿FDWHVLQWKHSHULRGIURPWR
Comparison group was represented by age matched people non-exposed to radiation which arrived to the studied territories after cessation of nuclear tests in 1990.
Results: For the all studied period the prevalence rates of CVD in the main group
ZHUHLQWKHUDQJH±FDVHVSHUSRSXODWLRQDQGVLJQL¿FDQWO\SUHvailed comparison rates (402.3 - 436.7 cases). In 2010, the prevalence rate of CVD
in the main group was 611.8 per 1,000 population, while in the comparison group
it was 428.7 per 1,000 population (RR =1.43; 95% CI 1.23; 1.65); in 2012 these
rates were 638.2 and 405.8 per 1000 population, respectively (RR=1.58; 95% CI
1.39; 1.79). High relative risks for CVD were found in the age groups 30-39; 4049, and 50-59 of the main group (RR=2.08; 1.94; 1.89 respectively).
In the CVD structure hypertension has leading position (27.4 %) followed by
coronary artery disease (20.3 %), and cerebrovascular disease (19.6%).
e55
Journal of Hypertension Volume 32, e-Supplement 1, 2014
In the main group mortality rates of CVD were in the diapason from 925.9 to
960.3 cases per 100,000 population; in the comparison group – 574.0-618.3
cases (average annual RR=1.57; 95% CI 1.41; 1.71).
Conclusions: Results of study show the possible relation of radiation exposure
DQGVLJQL¿FDQWLQFUHDVLQJRI&9'UDWHVLQWKHSHRSOHH[SRVHGGLUHFWO\ DJH
! DQGWKHLURIIVSULQJ DJH 4C.07
RENAL DENERVATION ATTENUATES CARDIAC
DIASTOLIC DYSFUNCTION THROUGH SPECIFIC
RESTORATION OF SERCA2A
D. Hirohama 1, F. Mori 2, S. Ogura 3, S. Mu 4, Y. Uetake 5, R. Jimbo 6,
L. Reheman 7, C. Wang 7, Y. Yatomi 7, T. Fujita 8, M. Nangaku 1, T. Shimosawa 7.
1
The University of Tokyo Graduate School of Medicine, Department of
Nephrology and Endocrinology, Tokyo, JAPAN, 2 Tokyo Women’s Medical
University, Department of Endocrinology and Hypertension, Tokyo, JAPAN,
3
Nihon University School of Medicine, Department of Pathology and
Microbiology, Division of Laboratory Medicine, Tokyo, JAPAN, 4 University of
Arkansas for Medical Science, Department of Pharmacology and Toxicology,
Fayetteville, AR, USA, 5 The University of Tokyo Graduate School of Medicine
DQG)DFXOW\RI0HGLFLQH2I¿FHIRU5HVHDUFK(WKLFV6XSSRUW7RN\R-$3$16
Odaira Memorial Tokyo Hitachi Hospital, Department of Internal Medicine,
Tokyo, JAPAN, 7 The University of Tokyo Graduate School of Medicine,
Department of Clinical Laboratory, Tokyo, JAPAN, 8 The University of Tokyo,
Reserch Center for Advanced Science and Technology, Division of Clinical
Epigenetics, Tokyo, JAPAN
Objective: Chronic kidney disease (CKD) is an independent risk factor for
cardiovascular disease (CVD) even from early stage of CKD. Clinically,
CKD and heart failure (HF) often worsen each organ concurrently, referred
to as the cardiorenal syndrome (CRS). However, the mechanisms and mediators underlying this interaction are poorly understood. Former studies suggests that sympathetic tone is altered in CKD patients and recently renal
denervation successfully reduced blood pressure and cardiac function in eiWKHUK\SHUWHQVLYHDQG+)SDWLHQWV,QWKLVVWXG\:HK\SRWKHVL]HGWKDWUHQDO
denervation has direct cardioprotective effect on cardiac function in CRS.
Design and method: Three-week-old male Sprague-Dawley rats were
subjected to right uninephrectomy with or without left-side renal denervation, and fed normal-salt diet (0.3% NaCl) or high-salt diet (8% NaCl) for
6 weeks. Left ventricle (LV) diastolic function measured as time constant
at the isovolumic relaxation phase (Tau) were investigated by cardiac cathHWHUL]DWLRQ 3URWHLQ OHYHO RI VDUFRSODVPLF UHWLFXOXP &D$73DVH W\SH D
(SERCA2a) and phospholamban (PLB) were determined, and related gene
H[SUHVVLRQZDVTXDQWL¿HG
Results: +LJKVDOWORDGLQJLQGXFHGDVLJQL¿FDQWHOHYDWLRQRIEORRGSUHVVXUH
(BP) (134.8 ± 1.35 vs 224.7 ± 6.57 mmHg, p<0.01) and impaired LV relaxation (Tau; 11.9 ± 0.21 vs 16.9 ± 0.66 ms, p<0.01), accompanied by reduced
SERCA2a expression in the cardiac tissue. Renal denervation improved LV
relaxation (Tau; 16.9 ± 0.66 vs 14.3 ± 0.82 ms, p<0.05) accompanied by
restoring SERCA2a expression despite neither BP (224.7 ± 6.57 vs 202.2
± 11.7 mmHg, p=0.15) nor urinary protein levels (397.9 ± 51.7 vs 358.9 ±
PJGD\S ZHUHDOWHUHG%3UHGXFWLRQE\K\GUDOD]LQHDWWKHHDUO\
phase (197.5 ± 6.89 vs 164.0 ± 7.09 mmHg, p<0.05) tended to restore LV
relaxation (Tau; 16.9 ± 0.66 vs 14.6 ± 0.67 ms, p=0.08), while SERCA2a
expression remained reduced. PLB-phosphorylation was not altered by renal
denervation.
Conclusions: In this CKD animal model, renal denervation showed the cardioprotective effect on cardiac diastolic dysfunction independent from BP
UHGXFWLRQDVZHOODVUHQDOIXQFWLRQSRVVLEO\WKURXJKVSHFL¿FUHVWRUDWLRQRI
SERCA2a expression, providing new insight into the mechanism of CRS.
Design and method: The study population comprised 7645 ACS patients
enrolled in the Acute Coronary Syndromes Israeli Survey (ACSIS) between
DQG :H DQDO\]HG WKH DVVRFLDWLRQ EHWZHHQ DGPLVVLRQ 6%3 DQG
the rates of 7-day and 1-year all-cause mortality and of 30 days major carGLRYDVFXODUDGYHUVHHYHQWV 0$&( $GPLVVLRQ6%3ZDVFDWHJRUL]HGDVORZ
(<110mmHg), normal (110-140mmHg), high (140-160mmHg) and veryKLJK !PP+J Results: Compared to patients with normal admission SBP (n=3173), those
with low SBP (n=837) had more than a 2.5-fold increased risk for 7-day
mortality (p<0.001), and approximate 2-fold increased risk for 1-year mortality (p<0.001) and a 1.5-fold increased risk for 30 days MACE (P<0.001).
Inversely, compared with the normal admission SBP group, patients with
very-high admission SBP (n=1706) had a 54% lower risk of 7-day and 46%
lower risk for 1-year all-cause mortality (p=0.003, p<0.001, respectively).
The association between SBP levels and mortality was consistent in patients
with ST elevation MI (STEMI) and non-ST elevation MI (NSTEMI).
Conclusions: Among adults with ACS, elevated admission SBP levels is associated with short and long term favorable outcome.
4C.09
3&KULVWR¿GRX1, C. Nelson 1, M. Nikpay 2, L. Qu 3, M. Li 3, P. Braund 1,
M. Denniff 1, R. Roberts 2, H. Schunkert 4, M. Reilly 3, J. Erdmann 4,
R. McPherson 3, I. Konig 4, J. Thompson 1, N. Samani 1, 07RPDV]HZVNL1.
1
University of Leicester, Leicester, UNITED KINGDOM, 2 University of
Ottawa, Ontario, CANADA, 3 University of Pennsylvania, Philadelphia, PA,
USA, 4 University of Lübeck, Lübeck, GERMANY
Objective: 5XQVRIKRPR]\JRVLW\ 52+ ORQJVHJPHQWV W\SLFDOO\!0E RI
XQLQWHUUXSWHGVHTXHQFHVRI!FRQVHFXWLYHKRPR]\JRXV613VDUHUHFRJQLVHG
markers of recessive variants in human DNA. Such variants have been largely
ignored by genome-wide association studies (GWAs) that examined primarily
alleles operating under additive mode of inheritance in complex diseases. We
H[SORUHGGLIIHUHQFHVLQJHQHWLFDUFKLWHFWXUHRIKRPR]\JRVLW\EHWZHHQSDWLHQWV
with coronary artery disease (CAD) and CAD-free controls in a large multicentre CARDIoGRAM Consortium.
Design and method: Approximately 2.5 million single nucleotide polymorphisms (SNPs) from previously conducted GWAs in 10,548 patients with CAD
and 10,273 CAD-free controls were used to identify and characterise ROH and
their distribution across all 22 autosomes in 9 cohorts of white European ancesWU\7KLVZDVIROORZHGE\DQDO\VLVRIDVVRFLDWLRQEHWZHHQPHDVXUHVRIKRPR]\gosity and CAD in 20,821 subjects.
Results: Each individual had on average 32.1±8.7 ROH in their DNA. The
VWUHWFKHVRIKRPR]\JRXV613VKDYHDQDYHUDJHOHQJWKRI“NEDQG
cover an average total length of 44.1±15.0 Mb (approximately 1.6% of the human genome). Compared to CAD-free controls, CAD patients had approximately 0.7 excess of ROH - each additional ROH was associated with approximately
1% increase in the risk of CAD (OR=1.01, 95% CI: 1.006-1.014, P=2.57x10-6).
An average ROH was 5.2 kb longer in CAD patients than in controls. Globally,
the average total length of ROH covering autosomal genome was approximately
1162.0 kb longer in patients with CAD compared to controls (95% CI: 758.41565.7, P=1.70x10-8).
Conclusions: 7KLVVWXG\SURYLGHVWKH¿UVWHYLGHQFHIRUDQH[FHVVRIKRPR]\JRsity in CAD. Our data also suggest that recessive variants may be an important
factor in the genetic architecture of CAD.
4C.10
4C.08
ELEVATED ADMISSION SYSTOLIC BLOOD PRESSURE
IN PATIENTS WITH ACUTE CORONARY SYNDROME IS
ASSOCIATED WITH FAVORABLE SHORT AND LONG
TERM OUTCOMES
E. Grossman 1, G. Shlomai 1, E. Kopel 2, I. Goldenberg 2. 1 Department of
Internal Medicine D and Hypertension Unit, Tel-Hashomer, ISRAEL, 2 Heart
Institute and the Neufeld Cardiac Research Institute Leviev Heart Center, the
Chaim Sheba Medical Center, Tel-Hashomer, ISRAEL
Objective: In patients with acute coronary syndromes (ACS) the predictive value of
admission systolic blood pressure (SBP) on short and long-term outcomes is not entirely clear. We investigated the association between admission SBP in patients hosSLWDOL]HGZLWK$&6DQGVXEVHTXHQWPRUELGLW\DQGPRUWDOLW\LQDUHDOZRUOGVHWWLQJ
SIGNATURES OF RECESSIVE ALLELES AND
SUSCEPTIBILITY TO CORONARY ARTERY DISEASE.
GENOME-WIDE HOMOZYGOSITY ANALYSIS
LINK BETWEEN LEVEL OF CIRCULATING
GALECTIN-3 AND CONCENTRATION OF
PROANGIOGENIC MONONUCLEAR PROGENITOR
CELLS IN CHRONIC HEART FAILURE PATIENTS
$%HUH]LQ$.UHP]HUT. Samura, Y. Martovitskaya.
State Medical University, Zaporozhye, UKRAINE
Objective: To evaluate the interrelationship between galectin-3 (Gal-3) concentrations and proangiogenic mononuclear progenitor cells (MPCs) in ischemic
CHF patients.
Design and method: The study population was structured retrospectively after determining the coronary artery disease (CAD) by contrast-enhanced spiral
computed tomography angiography in 126 subjects (54 male), aged 48 to 62
years, with mild-to-severe ischemic CHF (median of left ventricular ejection
fraction = 42.7%; interquartile range was 39.9 – 47.5 %). Multispiral computed
e56
Journal of Hypertension Volume 32, e-Supplement 1, 2014
WRPRJUDSK\ DQJLRJUDSK\ DQGRU DQJLRJUDSKLF VWXG\ KDYH EHHQ FDUULHG RXW WR
verify the ischemic origin of CHF and have been performed for all patients prior
to their inclusion in the study. When atherosclerotic lesions of the coronary arterLHVZHUHYHUL¿HGSDWLHQWVZHUHVXEMHFWHGWRFRQYHQWLRQDODQJLRJUDSKLFH[DPLQDWLRQSURYLGHGLQGLFDWLRQVIRUUHYDVFXODUL]DWLRQZHUHDYDLODEOH&$'ZDVFRQsidered to be diagnosed upon availability of previous angiographic examinations
carried out not later than 6 months ago provided no new cardiovascular events
occurred for this period, and the procedure are available for assay. The coronary artery wall structure was measured by means of contrast spiral computed
WRPRJUDSK\DQJLRJUDSK\7KHÀRZF\WRPHWULFWHFKQLTXHZDVXVHGIRUSUHGLFWably distinguishing cell subsets that depend on the expression of CD14, CD34,
Tie-2, CD45, and CD309 (VEGFR2). Circulating Gal-3 level was determined by
ELISA method, and NT-pro-BNP level was measured by immunoelectrochemiluminesence method.
Results: Concentrations of Gal-3 were distributed by quartiles (Me; IQR):
4, QJPO4,, QJPO4,,, QJPODQG4,9 QJPO7KHUHZDVDVLJQL¿FDQWFKDQJH
in level of circulating MPCs depended on quartiles of Gal-3 concentration. SubMHFWVZLWKKLJKHU*DOTXDUWLOHKDGVLJQL¿FDQWO\ORZHU03&VFRXQWVZKHQFRPpared with patient with low quartiles. Elevated Gal-3 concentration more 16.7
QJPO DVVRFLDWHG ZLWK GHFOLQHG FLUFXODWLQJ 03&V 6XEVWDQWLDO QHJDWLYH HIIHFW
RI *DO FRQFHQWUDWLRQV PRUH WKDQ QJPO RQ FLUFXODWLQJ &'&'
CD45-CD34+, CD14+CD309+,CD14+CD309+Tie2+ MPCs was preserved
even after adjusted to conventional cardiovascular risk factors (T2DM, eGFR,
and hypertension), and NT-pro-BNP plasma level.
Conclusions: Circulating level MPCs progressively declines depended on quartiles of Gal-3 concentration in CHF subjects.
Abstracts
e57
ORAL SESSION
ORAL SESSION 4D
RENIN-ANGIOTENSIN-ALDOSTERONE
SYSTEM
4D.01
CARDIOPROTECTIVE ACTION OF ALDOSTERONE
RECEPTOR ANTAGONISTS: ROLE OF REDOX
BALANCE
A. Ashton 1, 2, T. Le 2, 3, M. Mardini 1, 2, 3, &*RPH]6DQFKH]4, 5, A. Mihailidou 1, 2.
Kolling Institute for Medical Research, Royal North Shore Hospital, Sydney,
AUSTRALIA, 2 University of Sydney, Sydney, AUSTRALIA, 3 Westmead
Hospital, Sydney, AUSTRALIA, 4 Division of Endocrinology, G.V. (Sonny)
Montgomery VA Medical Center, Jackson, MS, USA, 5 University of Mississippi
Medical Center, Jackson, MS, USA
1
Objective: Increased levels of aldosterone (Aldo) lead to target organ damDJH E\ SURR[LGDQW LQÀDPPDWRU\ DQG SURDSRSWRWLF DFWLRQ GXULQJ K\SHUWHQsion, heart failure and myocardial infarction (MI). We have shown free radical
scavenger Tempol, prevents Ald-induced cardiac damage during experimental
MI to the same extent as mineralocorticoid receptor (MR) or Aldo receptor antagonists, suggesting a role for redox balance. Further, low dose MR antagonists
alone prevented reperfusion injury by preventing apoptosis. Since activation of
oxidative stress triggers apoptosis during hypertension and MI, we examined the
role of redox balance in the cardioprotective action of low dose MR antagonists.
Results: ,5VLJQL¿FDQWO\LQFUHDVHGVXSHUR[LGHOHYHOV>“ ,51 YV“ VKDP,51 3@DQGGHFUHDVHGWKHUDWLRRIUHGXFHG
(GSH) to oxidised (GSSG) glutathione (Fig.1A), indicating accumulation of
GSSG and loss of antioxidant defence. This correlated with activation of apoptosis (Fig. 1B). SPIRO alone restored redox balance (Fig 1A) and prevented
I-R-induced apoptosis, whereas Tempol alone did not prevent I-R induced apoptosis, despite restoring redox balance. Aldo potentiated I-R induced decrease
in GSH levels (Fig. 1A) and aggravated apoptosis (Fig. 1B). Redox state was
PDQLSXODWHG LQ +F FHOOV E\ VHOHFWLQJ D %62 GRVH ȝ0 WKDW QRUPDOLVHG
WKHHIIHFWRI63,52FRQ¿UPHGE\GHFUHDVHG*6+OHYHOV%62LQGXFHGR[LGDQW
stress increased both Sgk-1 and PAI-1 transcription (1.59 ± 0.18 and 1.21 ± 0.04
-fold change) indicating MR activation; SPIRO blocked these increases despite
absence of anti-oxidant action.
Conclusions: 2XU¿QGLQJVVXJJHVWWKDWWKDWWKHFDUGLRSURWHFWLYHDFWLRQVRI05
antagonists involve both maintaining redox balance as well as preventing MR
activation.
4D.02
ACE2 INDEPENDENT PATHWAYS IN ANGIOTENSIN 1-7
FORMATION IN MICE
O. Domenig 1, $0DQ]HO2, J. Stegbauer 3, S. Gurley 4, M. Antlanger 1,
J. Kovarik 1, R. Linker 2, M. Saemann 1, M. Poglitsch 5. 1 Division of Nephrology
and Dialysis, Department of Medicine III, Medical University of Vienna, Vienna,
AUSTRIA, 2 Department of Neurology, University Hospital Erlangen, Erlangen,
GERMANY, 3 Department of Nephrology, Medical Faculty, Heinrich Heine
University, Düsseldorf, GERMANY, 4 Division of Nephrology, Department of
Medicine, Duke University and Durham VA Medical Centers, Durham, NC, USA,
5
Attoquant Diagnostics GmbH, Vienna, AUSTRIA
Objective: The Renin-Angiotensin-System is a peptide hormone cascade involved in the regulation of blood pressure, salt retention and tissue remodeling.
The main effector hormone of the RAS, AngII, has been shown to promote
YDVRFRQVWULFWLRQDQG¿EURVLVZKLOHLWVIXQFWLRQDOFRXQWHUSDUW$QJKDVEHHQ
reported to oppose AngII mediated physiologic effects. ACE2 has been found
to be responsible for the formation of Ang1-7 in vivo. However, recent data
LQGLFDWHG WKDW WKHUH PLJKW EH IXUWKHU LPSRUWDQW HQ]\PHV LQYROYHG LQ$QJ
metabolism. The aim of this study was the investigation of ACE2 independent
Ang1-7 mechanisms regarding their relative contribution to Ang1-7 formation
in vivo and in vitro.
Design and method: 8VLQJ D /&0606 EDVHG DSSURDFK ZH PHDVXUHG WKH
concentration of 10 RAS metabolites in heart, kidney und plasma samples of
:7DQG$&(NQRFNRXWPLFH &%/EDFNJURXQG LQWKHDEVHQFHDQGSUHVence of ACE-Inhibitor (Enalapril) treatment.
7LVVXH5$6HQ]\PHDFWLYLWLHVZHUHDQDO\]HGE\LQYHVWLJDWLQJWKHPHWDEROLVP
of Angiotensin spikes in tissue homogenates. The relative contribution of proWHRO\WLFSDWKZD\VWR$QJIRUPDWLRQZDVTXDQWL¿HGE\XVLQJVSHFL¿FHQ]\PH
inhibitors.
Design and method: We used our ex-vivo model of ischemia-reperfusion (I-R)
in rat hearts with spironolactone (SPIRO, 10 nM) or Tempol (100 mM) perfused 15 mins. prior to ischemia (30 min) and throughout reperfusion (2.5hr) and
apoptosis was measured by in-situ nick end-labeling (TUNEL) assay. In separate studies, cultured rat cardiomyocytes (H9c2) were treated with buthionine
sulfoximine (BSO), an inhibitor of glutathione synthesis, to simulate oxidative
stress (± 10 nM SPIRO) and Sgk-1 and PAI-1 transcripts were used as a measure
of MR activation.
Results: Endogenous Ang1-7 concentrations in heart, kidney and plasma were
VLPLODULQ:7DQG$&(GH¿FLHQWPLFH(QDODSULOWUHDWPHQWUHVXOWHGLQHI¿FLHQW
pharmacologic inhibition of ACE in kidney, heart and plasma, indicated by a
GHFUHDVHG$QJ,,$QJ,UDWLRDQGLQLQFUHDVHG$QJSODVPDOHYHOV+RZHYHU
while AngII was observed being reduced in kidney and heart, circulating AngII
plasma levels remained unaffected by ACE inhibitor treatment.
Neprilyin (NEP) and Prolyl Endopeptidase (PEP) were found to be responsible
IRU$QJIRUPDWLRQIURP$QJ,LQNLGQH\VRI:7DQG$&(GH¿FLHQWPLFH
Additionally, Prolyl Carboxypepdidase (PCP) was found to be main producer of
renal Ang1-7 from AngII in WT and ACE2 KO animals.
Conclusions: 2XU¿QGLQJVLQGLFDWHDPLQRUUROHRI$&(LQ$QJSURGXFWLRQ
suggesting a previously underestimated contribution of NEP, PEP and PCP to
$QJIRUPDWLRQ7KHWLVVXHVSHFL¿FUHGXFWLRQRI$QJ,,DQGSODVPDVSHFL¿F
increase of Ang1-7 following ACE inhibitor administration may both contribute
WREHQH¿FLDOHIIHFWVLQWKHWUHDWPHQWRIFDUGLRYDVFXODUGLVHDVHVLQYLYRZKLFK
needs to be elucidated by further studies.
S
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e58
Journal of Hypertension Volume 32, e-Supplement 1, 2014
4D.03
DETERMINANTS OF PLASMA RENIN ACTIVITY.
ROLE OF A HUMAN RENIN GENE VARIANT AS A
GENETIC FACTOR
T. Konoshita 1, T. Nakaya 1, K. Yamamoto 1, M. Yamada 1, M. Ichikawa 1,
S. Sato 1, M. Imagawa 1, Y. Makino 1, M. Fujii 1, Y. Zenimaru 1, K. Arakawa 1,
-6X]XNL1, 7,VKL]XND1, H. Nakamura 2. 1 University of Fukui Faculty of
Medical Sciences, Fukui, JAPAN, 2 Kanazawa University Graduate School of
Medical Science, Kanazawa, JAPAN
Objective: &RQYHQWLRQDODQGUHFHQWFRKRUWVWXGLHVFRQ¿UPHGWKDWKLJKHUSODVPD
renin level is associated with greater morbidity and mortality. The plasma renin
activity (PRA) is affected by a number of environmental factors. On the other
KDQGVLJQL¿FDQWKHULWDELOLW\KDVEHHQVKRZQIRUWKHDFWLYLW\$K\SRWKHVLVWKDW
DFDQGLGDWHU613&7RIKXPDQUHQLQJHQHVKRXOGKDYHVLJQL¿FDQWHIIHFW
on PRA was elucidated and an updating of independent determinants of PRA
was attempted.
Design and method: We enrolled consecutive 810 subjects who had consulted our hospitals for life-style related diseases. Genotypes were assayed
with genomic DNA for C-5312T. Among the genetic variants, the difference
of PRA was evaluated. Monovariate linear regression analysis was performed
to test the correlation between PRA and clinical variables. Finally, stepwise
multiple regression analysis was performed to evaluate the independent determinants.
Results: &RPSDULVRQEHWZHHQJHQRW\SHJURXSV&&&7DQG7DOOHOHKRPR]\JRWHWKHJHRPHWULFPHDQVRI35$ZHUHDQGQJPOKUUHVSHFWLYHO\
(F=5.992, p=0.015). Monovariate linear regression analysis revealed that a numEHURIYDULDEOHVKDYHVLJQL¿FDQWFRUUHODWLRQZLWKWKHDFWLYLW\LQFOXGLQJXULQDU\
salt excretion. A stepwise multivariate regression analysis revealed that renin
C-5312T variant (TT) is one of the independent determinants of PRA.
Conclusions: 7KXV IRU WKH ¿UVW WLPH LW ZDV VKRZQ WKDW D KXPDQ UHQLQ JHQH
YDULDQWVKRXOGKDYHVLJQL¿FDQWHIIHFWRQ35$DVDJHQHWLFIDFWRUDQGWKHLQGHpendent determinants for the activity was updated including genetic factor. This
result also implies a possibility that the genetic variant might be a determinant
of life span.
4D.04
INHIBITION OF PHOSPHODIESTERASE 5
ATTENUATES ANGIOTENSIN II-DEPENDENT
HYPERTENSION AND RENAL VASCULAR
DYSFUNCTION IN C57BL/6 MICE
M. Thieme 1, S. Sivritas 1, S. Potthoff 1, S. Mende 1, M. Hoffmann 1, S. Stamer 1,
L. Rump 1, E. Mergia 2, J. Stegbauer 1. 1 Department of Nephrology, Heinrich
Heine University, Düsseldorf, GERMANY, 2 Department of Pharmacology and
Toxicology, Ruhr University, Bochum, GERMANY
Objective: The kidney plays an outstanding role in the regulation of blood pressure (BP) and vascular tone.
The renal vasoconstrictor response of angiotensinII (AngII) is balanced by
WKH 12F*03SDWKZD\$QJ,, FDXVHV K\SHUWHQVLRQ DQG UHGXFHV HQGRWKHOLum-dependent relaxation by decreasing NO-bioavailability. Thus, it has been
shown that AngII is able to increase cGMP degradation by activating phosphodiesterase1 (PDE1) and PDE5 in vitro. The role of the PDE1 or PDE5
LQK\SHUWHQVLRQDQGUHQDOEORRGÀRZ 5%) UHJXODWLRQLVXQNQRZQ7KHDLP
RIWKLVVWXG\ZDVWRLQYHVWLJDWHWKHVSHFL¿F3'(UHVSRQVLEOHIRUUHJXODWLQJ
RBF and thereby BP.
Design and method: To examine the dominant PDE in renal vasculature, we
WHVWHGWKHUHQDOYDVRGLODWRUHIIHFWRIVSHFL¿F3'(DQG3'(LQKLELWLRQLQDQ
DFXWH SHUIXVLRQ PRGHO ZKHUH$QJ,, QJNJPLQ ZDV JLYHQ FRQWLQXRXVO\
while BP and RBF were measured invasively. Once Ang II had induced a staEOHHOHYDWHG%3D3'(LQKLELWRU VLOGHQD¿O RUD3'(LQKLELWRU YLQSRFHWLQ were applicated in increased concentrations. Furthermore, we tested the effect of
3'(LQKLELWLRQLQ$QJ,,GHSHQGHQWK\SHUWHQVLRQ QJNJPLQGD\V RQ
BP-reduction and on renal vascular relaxation in the model of isolated perfused
kidney.
Results: ,Q WKH DFXWH SHUIXVLRQ PRGHO VLOGHQD¿O VLJQL¿FDQWO\ GHFUHDVHG V\VWHPLF%3 ȝJNJ6LOGHQD¿O“S DQGLQFUHDVHGUHQDOEORRG
ÀRZ ȝJNJ6LOGHQD¿O“S $GPLQLVWUDWLRQRIYLQSRFHWLQ
showed almost no effect on systemic BP and RBF, suggesting a pivotal role of
the PDE5 in the regulation of renal vascular tone. Based on these results, we
tested the impact of chronic PDE5-inhibition on Ang II-dependent hypertension.
+HUHZHVKRZHGWKDWFKURQLF6LOGHQD¿OWUHDWPHQWVLJQL¿FDQWO\DWWHQXDWHG$QJ,,GHSHQGHQWK\SHUWHQVLRQLQ&%/ ZRYVZVLOGHQD¿O“YV“
S 0RUHRYHU LQ LVRODWHG SHUIXVHG NLGQH\V VLOGHQD¿OWUHDWPHQW VLJQL¿cantly improved NO-dependent vasorelaxation in kidneys of AngII-treated WT.
Conclusions: ,Q &%/ PLFH 3'( LV WKH SUHGRPLQDQW 3'( LQ UHJXODWLQJ
RBF.
,QKLELWLRQRI3'(E\VLOGHQD¿ODPHOLRUDWHVFKURQLF$QJ,,GHSHQGHQWK\SHUWHQsion and improves endothelium-dependent dysfunction in the isolated perfused
kidney through inhibition of cGMP degradation. This study reveals new evidence for the pivotal role of PDE5 in the pathogenesis of AngII-induced hypertension.
4D.05
TORCETRAPIB, DALCETRAPIB, AND ANACETRAPIB
INDUCE ADIPOCYTE-DERIVED ALDOSTERONE
PRODUCTION THROUGH REDOX SENSITIVE
MECHANISMS
F. Rios 1, A. Nguyen Dinh Cat 1, R. Palacios 2, C. Jenkins 1, A. Carswell 1,
$0RQWH]DQR1, 507RX\]1. 1 Institute of Cardiovascular and Medical
Sciences, University of Glasgow, Glasgow, UNITED KINGDOM,
2
Departamento de Bioquímica, Fisiología y Genética Molecular Facultad
de CC. de la Salud, Universidad Rey Juan Carlos, Madrid, SPAIN
Objective: Clinical trials demonstrated that CETP inhibitors, such as torcetrapib
(TORC), which increase HDL levels, had unexpected side effects, such as hyperadosteronism and hypertension. Given that CETP inhibitors may accumulate
in adipose tissue and that adipocytes are a source of aldosterone, we questioned
ZKHWKHU &(73 LQKLELWRUV LQÀXHQFH DOGRVWHURQH SURGXFWLRQ LQ DGLSRF\WHV DQG
evaluated putative mechanisms for this.
Design and method: Human adipocytes (SW872), expressing CETP, were studied and compared to mouse adipocytes (3T3-L1), which lack the CETP gene.
Cells were treated with TORC, dalcetrapib (DALC), or anacetrapib (ANAC).
Aldosterone levels were evaluated by ELISA. Gene expression for mineralocoricoid receptor (MR), StAR, aldosterone synthase (CYP11B2), and Nox en]\PHV ZHUH HYDOXDWHG E\ UHDOWLPH 3&5 3URWHLQ H[SUHVVLRQ ZDV DVVHVVHG E\
western-blot. Reactive oxygen species (ROS) production was evaluated by
lucigenin and Amplex-Red assay. To evaluate the role of ROS and Nox homologues, cells were pre-treated with N-acetylcystein (NAC–ROS scavenger),
0/DQG*.7 12;DQG12;LQKLELWRUUHVSHFWLYHO\ Results: In human adipocytes, TORC, DALC and ANAC increased superoxide
(2-fold) and H2O2 production (1.5-fold)(p<0.05). Aldosterone production was
REVHUYHGDIWHUKVWLPXODWLRQZLWK725& SJP/ '$/& SJP/ DQG
$1$& SJP/ FRPSDUHGWRFRQWURO SJP/ S DQHIIHFWEORFNHG
by NAC. TORC, DALC and ANAC increased mRNA and protein expression
for CYP11B2, CYP11B1, StAR and MR(p<0.05). TORC increased Nox1, 4
and 5 (2-fold,p<0.05); DALC increased Nox4 (2-fold,p<0.05) and, ANAC increased Nox1 and 4 (3-fold,p<0.05). Aldosterone production induced by TORC
and ANAC was inhibited by Nox inhibitors. While ML171 inhibited the effects
of TORC; GKT blocked the effects of both TORC and ANAC on gene expression of CYP11B2, StAR and MR. Aldosterone production or gene expression
induced by DALC were not blocked by Nox inhibitors. In mouse adipocytes,
725&DQG'$/&LQGXFHGDOGRVWHURQHSURGXFWLRQ SJP/DQGSJP/YV
FRQWSJP/S DQGVWLPXODWHG526SURGXFWLRQ IROGS Conclusions: TORC, DALC and ANAC induced aldosterone production in huPDQDQGPRXVHDGLSRF\WHV2XU¿QGLQJVLQGLFDWHWKDW&(73LQKLELWRUVVWLPXODWH DOGRVWHURQH SURGXFWLRQ IURP DGLSRF\WHV SURFHVVHV GHSHQGHQW RQ 1R[
1R[LQGXFHG 526 SURGXFWLRQ 7KHVH QRYHO ¿QGLQJV KDYH LPSRUWDQW FOLQLFDO
VLJQL¿FDQFHDQGPD\H[SODLQLQSDUWWKHK\SHUDOGRVWHURQLVPDQGK\SHUWHQVLRQ
reported in CETP clinical trials.
4D.06
ALISKIREN REDUCES MYOCARDIAL ISCHEMIAREPERFUSION INJURY BY A BRADYKININ B2
RECEPTOR- AND ANGIOTENSIN AT2 RECEPTORMEDIATED MECHANISM
S. Koid 1, J. Ziogas 2, D. Campbell 1, 3. 1 St. Vincent’s Institute of Medical
Research, Fitzroy, AUSTRALIA, 2 Department of Pharmacology and
Therapeutics, The University of Melbourne, Parkville, AUSTRALIA,
3
Department of Medicine, The University of Melbourne, Fitzroy, AUSTRALIA
Objective: $QJLRWHQVLQFRQYHUWLQJHQ]\PHLQKLELWRUVDQGDQJLRWHQVLQ$7UHFHSWRUEORFNHUVUHGXFHP\RFDUGLDOLVFKDHPLDUHSHUIXVLRQ ,5 LQMXU\YLDEUDG\NLQLQ%DQGRUDQJLRWHQVLQ$7UHFHSWRUPHGLDWHGPHFKDQLVPV7KHUHQLQLQhibitor aliskiren increases cardiac tissue kallikrein and bradykinin levels, both of
which are important for cardioprotection. In the present study, we investigated
WKH HIIHFW RI DOLVNLUHQ RQ P\RFDUGLDO ,5 LQMXU\ DQG WKH UROHV RI % DQG$7
receptors in the mechanism of action of aliskiren.
Design and method: Female Sprague-Dawley rats were treated for 4 weeks
ZLWK YHKLFOH DOLVNLUHQ PJNJGD\ YDOVDUWDQ PJNJGD\ RU WKH
e59
Journal of Hypertension Volume 32, e-Supplement 1, 2014
combination of aliskiren and valsartan. We examined the roles of the B2
and AT2 receptors by co-adminsitration of vehicle, the B2 receptor antagoQLVWLFDWLEDQW PJNJGD\ RUWKH$7UHFHSWRUDQWDJRQLVW3' PJNJGD\ 0\RFDUGLDO,5LQMXU\ZDVHOLFLWHGE\PLQRFFOXVLRQRIWKH
left anterior descending coronary artery followed by 120 min reperfusion in
anaesthetised rats.
Results: 4 weeks administration of aliskiren increased cardiac bradykinin
levels and attenuated valsartan-induced increases in plasma angiotensin II
levels. Co-administration of aliskiren and PD123319 did not prevent the
aliskiren-induced increases in cardiac bradykinin levels. In vehicle-treatHG UDWV P\RFDUGLDO LQIDUFW VL]H DUHD DW ULVN PHDQ“6(0 Q ZDV
43±3%. This was reduced to a similar extent by aliskiren, valsartan, and their
combination to 24±3%, 25±3%, 22±2%, respectively. Icatibant reversed the
cardioprotective effects of aliskiren and the combination of aliskiren and
valsartan, but not cardioprotection by valsartan alone, indicating that valsartan induced cardioprotection by a B2 receptor-independent mechanism that
was prevented by aliskiren co-administration. PD123319 reversed the cardioprotective effects of aliskiren, valsartan and the combination of aliskiren
plus valsartan. In a separate series of rats, short-term aliskiren administration
GLGQRWUHGXFHP\RFDUGLDOLQIDUFWVL]HGHVSLWHUHGXFWLRQLQEORRGDQJLRWHQVLQ
peptide levels.
Conclusions: $OLVNLUHQ SURWHFWV WKH KHDUW IURP P\RFDUGLDO ,5 LQMXU\ YLD
a B2 and AT2 receptor-mediated mechanism whereas cardioprotection by
valsartan is mediated via the AT2 receptor. In addition, aliskiren prevents
AT2 receptor-mediated cardioprotection by valsartan by attenuating valsartan-induced increases in angiotensin II levels. Thus the combination of
aliskiren and valsartan does not provide greater cardioprotection than either
drug alone.
4D.07
HIGHER INCIDENCE OF ARTERIAL HYPERTENSION
IN SALT SENSITIVE NORMOTENSIVE OFFSPRING
OF HYPERTENSIVE PARENTS. A 18 YEARS FOLLOWUP. RESPONSE TO ANGIOTENSIN II RECEPTOR
BLOCKADE
$5DPLUH]1, P. Fischer 2, L. Masnatta 2, -6DQFKH]3, 56DQFKH]1.
Hypertension and Metabolic Unit, Fundación Favaloro, Buenos Aires,
ARGENTINA, 2 University RG Favaloro, Buenos Aires, ARGENTINA,
3
Children Hospital Buenos Aires University, Buenos Aires, ARGENTINA
1
Objective: It was previously shown that subjects with a positive family history of hypertension are able to develop hypertension throughout their life span.
Thus, it was valuated the incidence of hypertension in a group of normotensive
subjects with salt sensitive family related hypertension (SSNT) followed for a
PHDQWLPHRI\HDUVDQGDQDO\]HGLIIHUHQWPDUNHUVRIK\SHUWHQVLRQULVN
Design and method: We followed 41 (18-34 years, 18 female) offsprings of
hypertensive parents with normal blood pressure values, for up to 18 years. Each
one of them was controlled every 6 months and a full clinical and laboratory
evaluation was performed once in a year. Blood pressure was measured twice in
WKHRI¿FHDQGWKHPHDQYDOXHFRQVLGHUHGDVWKH%3YDOXHRIWKHSDWLHQW$K
ABPM was performed once every year. Post ischemic minimum forearm vascular resistance (FAVRm), plasma renin activity (PRA), urinary Kallikrein (UK)
and microalbuminuria (mAlb) were measured at baseline.
Results: Blood pressure increased in 26 individuals more than 10mmHg after 7
days of 260mmol of sodium load being thus considered as SSNT. The remaining
15 subjects were considered as salt resistant (SRNT).
Eighteen SSNT, out of 26 (69.23%; 19-32y, 12 females), developed established
K\SHUWHQVLRQ$%30PHDQGD\WLPHYDOXHVLQFUHDVHGIURP““PP+J
WR ““PP+J S ,Q 6517 RQO\ RXW RI \
IHPDOHV GHYHORSHG K\SHUWHQVLRQ $%30 IURP ““PP+J WR
““PP+JS SSNT had at baseline lower UK (2.6±0.4IU) and higher PRA: (4.2±0.8ng.
ml.h) than SRNT (UK: 4.0±0.2IU; PRA: 2.2±0.5ng.ml.h; p<0.05). Furthermore,
SSNT showed higher FAVRm at baseline (2.8±0.7AU; p<0.01) and higher mAlb
(50±4µg.min) than SRNT (1.6±0.3AU, p<0.01 and 10±2µg.min; p<0.005, respectively).
Treatment with Telmisartan (40-80mg for 24 weeks) reduced BP in SSNT from
““PP+J WR ““PP+J S DQG LQ 6517 LQGLYLGXDOV
IURP““PP+JWR““PP+J S Conclusions: SSNT are at higher risk of developing hypertension. This, together with the higher PRA and MA levels, confers to SSNT a higher risk for
developing cardiovascular morbidity and kidney impairment. Telmisartan norPDOL]HG%3LQLQERWKK\SHUWHQVLYHJURXSV7KLVVXSSRUWVWKHLGHDIRUDUHGXFHG
cardiovascular risk in these patients.
4D.08
THE ROLE OF SOX6 TRANSCRIPTION FACTOR IN
RENIN CELL FATE SPECIFICATION
-*RPH]K. Ardhanareeswaran, 9']DXM. Mirotsou.
Duke University, Durham, NC, USA
Objective: Despite the importance of the renin-angiotensin system, the mechaQLVPV WKDW JRYHUQ WKH VSHFL¿FDWLRQ RI UHQLQ SURGXFLQJ FHOOV XQGHU QRUPDO RU
pathophysiological conditions are poorly understood. During development, renin cells are broadly distributed throughout the kidney, whereas in the adult
kidney renin is restricted to few cells in the juxtaglomerular area (JG). When
homeostasis is compromised the number of adult renal cells expressing renin
increase through a process termed JG recruitment. This process involves transdifferentiation of renal smooth muscle cells (VSMCs) as well as differentiation
RISHULF\WHPHVHQFK\PDOOLNHFHOOSRSXODWLRQV 06&V Our objective was to determine new regulators of renin cell fate during kidney
development and JG recruitment.
Design and method: *HQHH[SUHVVLRQSUR¿OHVRI06&VDQG-*FHOOVZHUHDVsessed by microarray and qRT-PCR. In vitro assays were performed in adult
UHQDO06&VRU960&VLVRODWHGIURP&%/5HQF<)3PLFH5HQLQH[SUHVVLRQLQYLWURZDVLQGXFHGE\WUHDWPHQWZLWK,)>,%0; —0 DQG)RUVNROLQ
—0 @IRUGD\V)RUJDLQRIIXQFWLRQDQGORVVRIIXQFWLRQVWXGLHVWKHFHOOV
were transduced with lentivirus carrying vectors for Sox6, Sox6 shRNA expression or appropriate controls. Ex vivo analysis was performed in embryonic kidneys (14.5 dpc) isolated and injected with lentivirus. The kidneys were then
cultured for 4 days in agar blocks containing standard growth media.
Results: Our preliminary data show that the transcription factor Sox6 is expressed in
renin producing cells in the developing kidney and in the adult kidney after stimulation that promotes JG recruitment. Overexpression of Sox6 enhances differentiation
of renal MSCs to renin producing cells in vitro. Moreover, loss of Sox6 reduces
differentiation of renal MSCs to renin producing cells, as well as the re-expression
of renin in renal VSMCs in vitro. Accordingly, knocking down of Sox6 in an ex vivo
model of kidney development results in reduction of renin expression.
Conclusions: These results strongly support a novel role for Sox6 in in renin
FHOOIDWHVSHFL¿FDWLRQDQGWKHUHE\LQUHQDOGHYHORSPHQWDQGSK\VLRORJ\0RUHRver they open new possibilities of addressing questions regarding both developmental and physiological regulation of renin.
4D.09
ASSOCIATION OF URINARY ANGIOTENSINOGEN
EXCRETION WITH BLOOD PRESSURE IN A GROUP
OF AFRICAN ANCESTRY
F. Michel, G. Norton, M. Maseko, M. Badenhorst, A. Woodiwiss. University of
the Witwatersrand, School of Physiology, Johannesburg, SOUTH AFRICA
Objective: Groups of African ancestry have a high prevalence of low-renin hypertension and a poor blood pressure (BP) response to renin-angiotensin system
(RAS) inhibitors. However, we have recently demonstrated an important role of
circulating angiotensinogen (AGT) concentrations in contributing toward salt
intake-BP relations. Whether intrarenal AGT contributes toward BP in this ethnic group is unknown.
Design and method: We therefore evaluated the relationships between 24-hour urinary AGT excretion and BP in 425 randomly recruited, never-treated participants
of African ancestry from a community sample with acceptable 24-hour urine samples in South Africa, 340 of whom had 24-hour ambulatory BP data that met with
SUHVSHFL¿HGTXDOLW\FRQWUROFULWHULD2I¿FH%3ZDVGHWHUPLQHGIURPWKHPHDQRI
high-quality nurse-derived measurements. Plasma and urinary AGT concentrations
were determined using an ELISA assay capable of detecting low concentrations.
Results: In a multivariate model, the log of urinary AGT-to-creatinine ratios
$*7FUHDWLQLQH ZDV DVVRFLDWHG ZLWK SODVPD$*7 FRQFHQWUDWLRQ S EXWQRWZLWKHVWLPDWHGJORPHUXODU¿OWUDWLRQUDWHRUZLWKXULQDU\1D.+RZever, in a multivariate model, plasma AGT concentrations were not independentO\DVVRFLDWHGZLWKRI¿FHV\VWROLF%3 SDUWLDOU S ,QFRQWUDVWXULQDU\
$*7FUHDWLQLQH ZDV LQGHSHQGHQWO\ DVVRFLDWHG ZLWK RI¿FH V\VWROLF %3 SDUWLDO
U S $UHODWLRQVKLSEHWZHHQXULQDU\$*7FUHDWLQLQHDQGKRXU
systolic BP (partial r=0.11, p<0.05) was also noted in the subgroup of participants with high quality 24-hour BP data. Participants with the highest quintile
RI XULQDU\$*7FUHDWLQLQH VKRZHG DQ DSSUR[LPDWHO\ PP +J KLJKHU RI¿FH
V\VWROLF%3WKDQSDUWLFLSDQWVZLWKWKHORZHVWXULQDU\$*7FUHDWLQLQH S Conclusions: In conclusion, in a group of African ancestry, urinary AGT excretion is more closely associated with BP than plasma AGT. The intrarenal RAS
may play a more important role in BP control than the circulating RAS in groups
of African ancestry.
e60
Journal of Hypertension Volume 32, e-Supplement 1, 2014
4C.01
ALDOSTERONE MODULATES THE ASSOCIATION
BETWEEN ASYMPTOMATIC ORGAN DAMAGE AND
SODIUM INTAKE IN ESSENTIAL HYPERTENSIVES
H. Li 1, Y. Shen 3, S. Chu 1,2, S. Chen 1, X. Tang 1, J. Du 1, Y. Kong 1, Y. Hu 1,
J. Zhang 1, P. Gao 1,2. 1 Department of Hypertension, Ruijin Hospital, Shanghai
Jiaotong University School of Medicine, Shanghai, CHINA, 2 Shanghai
Institute of Hypertension, Shanghai, CHINA, 3 Department of Ultrasound,
Renji Hospital, Shanghai Jiaotong University School of Medicine, Shanghai,
CHINA
Objective: High plasma renin activity (PRA), serum aldosterone (SAL) and aldosterone renin ratio (ARR) have been reported to be closely associated with
high cardiovascular risk. We examined the association of asymptomatic target
organ damage (TOD) with PRA, SAL and ARR in essential hypertensives and
tested whether the association varied by levels of sodium intake.
Design and method: A total of 835 essential hypertensives(551 men; age
“ \HDUV UHFHLYLQJ DQWLK\SHUWHQVLYH GUXJV ZLWK OLWWOH LQÀXHQFH RQ WKH
renin-angiotensin-aldosterone system were enrolled. Patients were standing for
at least 2h with blood sampling at 8 am, PRA and SAL were measured by radioimmunoassay. Left ventricular mass measurements (LVMI) measured by echocardiography was used to assess cardiac damage. Subclinical kidney damage
was assessed by estimating GFR (eGFR) by the CKD-EPI creatinine equation
and urine albumin creatinine ratio(ACR). Sodium intake was assessed by measuring 24-h urine sodium excretion (24-h UNa).
Results: After adjustment for age, sex, body mass measurements, serum total
cholesterol, fasting plasma glucose, mean arterial pressure, 24-h urine potasVLXP H[FUHWLRQ DQG K 81D ORJWUDQVIRUPHG 6$/ VLJQL¿FDQWO\ FRUUHODWHG
ZLWK/90, ȕ 3 H*)5 ȕ 3 DQGORJWUDQVIRUPHG
$&5 ȕ 3 7KH FRUUHODWLRQ EHWZHHQ ORJWUDQVIRUPHG 6$/ DQG
ORJWUDQVIRUPHG$&5ZDVVLJQL¿FDQWLQHDFKWHUWLOHRIK81D+RZHYHULW
ZDVVWURQJHULQXSSHUWHUWLOH ȕ 3 WKDQLQPLGGOHWHUWLOH ȕ 3 DQG ORZHU WHUWLOH ȕ 3 6LJQL¿FDQWO\ DVVRFLDWLRQ RI ORJ
WUDQVIRUPHG 6$/ ZLWK /90, ȕ 3 DQG H*)5 ȕ 3 ZDVRQO\REVHUYHGLQXSSHUWHUWLOHRIK81D1RVLJQL¿FDQWUHODWLRQVKLSZDV
observed between log-transformed PRA, log-transformed ARR and measurements of TOD.
Conclusions: It is SAL, but not PRA or ARR, closely associated with asymptomatic TOD in essential hypertensives,especially in those with high sodium intake. The correlation between sodium intake and asymptomatic TOD may partly
attribute to the close association between SAL and asymptomatic TOD.
4D.01
IMPACT AND FUNCTION OF A MINERALOCORTICOID
RECEPTOR NON-CODING VARIANT ON ARTERIAL
STIFFNESS
M. Lenders 1, %6FKPLW]2, %.DVSU]DN3, S. Brand 2, E. Brand 1. 1 University
Hospital Münster, Internal Medicine D, Nephrology, Hypertension and
Rheumatology, Münster, GERMANY, 2 University Hospital Münster, Institute
of Sports Medicine, Molecular Genetics of Cardiovascular Disease, Münster,
GERMANY, 3 University Hospital Münster, Department of Vascular and
Endovascular Surgery, Münster, GERMANY
Objective: Arterial dysfunction is one of the key events in arteriosclerosis development, preceding structural changes. Pulse-wave velocity (PWV) correlates
well with arterial stiffness and is a useful non-invasive tool to assess arteriosclerosis. In the current work, we report on an association of a mineralocorticoid
receptor (NR3C2) variant within the 3’ untranslated region (3’UTR) and arterial
stiffness.
Design and method: PWV measurements were performed using a Mobil-OGraph device (I.E.M., Stolberg) in 81 patients after femoral bypass or vein
stripping procedure to determine arterial stiffness. Patinets were genotyped for
NR3C2 (rs5534). The impact of rs5534 on PWV was tested by a multivariate
approach using SAS9.3. To determine the function of rs5534, full length NR3C2
3’UTR including the rs5534 minor A or major G allele was inserted into a reporter gene vector (pMIR-dual-glow) and transiently transfected into human
endothelial (EA.hy926) and kidney epithelial cells (IHKE). Transcriptional acWLYLW\ZDVDVVHVVHGE\)LUHÀ\DQG5HQLOODOXFLIHUDVHDFWLYLW\
Results: 3DWLHQWV¶ PHGLDQ DJH ZDV >@ \HDUV DQG PHGLDQ 3:9 ZDV
>@ PV 7KH UV$ DOOHOH ZDV DVVRFLDWHG ZLWK LQFUHDVHG 3:9
(p=0.0017). The estimated difference between A and G allele carriers in the
FRKRUW ZDV PV 7UDQVLHQW WUDQVIHFWLRQ RI KXPDQ FHOO OLQHV UHYHDOHG WUDQscriptional activity of the major G allele of ~10-25% of control. Insertion of the
PLQRU$DOOHOHUHVXOWHGLQDVLJQL¿FDQWIROGLQFUHDVHRIOXFLIHUDVHDFWLYLW\LQ
EA.hy926 (p=0.007) and IHKE cells (p=0.001).
Conclusions: 'XHWRWKHREVHUYHGVLJQL¿FDQWLQFUHDVHRIWUDQVFULSWLRQDODFWLYity, the minor A allele may lead to increased NR3C2 expression or decreased
transcript degradation, resulting in an up-regulation of genes involved in arterial
VWLIIQHVVVXFKDVWKHHSLWKHOLDOVRGLXPFKDQQHO (1D& DQGWKH1D.$73DVH
Based on our data, we propose the minor A allele of rs5534 as a potential predictor for increased PWV and potentially increased cardiovascular risk.
4D.02
BENEFICIAL EFFECTS OF COMBINED
ANGIOTENSIN AT2 RECEPTOR STIMULATION AND
PHOSPHODIESTERASE 5 INHIBITION ON CARDIAC
ANTI-REMODELLING
E. Jones, Y. Wang, R. Widdop. Monash University, Department of
Pharmacology, Melbourne, AUSTRALIA
Objective: Angiotensin II has an important role in cardiac remodelling and
acts at multiple receptor subtypes, including AT1 receptors (AT1R) and AT2
receptors (AT2R). Protective AT2R signaling in cardiovascular tissues is primarily via increased levels of nitric oxide (NO) which stimulate cyclic guanosine
monophosphate (cGMP) and downstream targets which are known to activate
DQWL¿EURWLFDQGDQWLLQÀDPPDWRU\HIIHFWV,QWKHKHDUW12F*03VLJQDOOLQJLV
principally terminated by degradation of cGMP by phosphodiesterase type 5
(PDE5), which is expressed at low levels in healthy hearts but upregulated in
many forms of cardiovascular disease. Thus in conditions in which the cardioSURWHFWLYHUROHRI$75VWLPXODWLRQZRXOGEHPRVWEHQH¿FLDOLQFUHDVHG3'(
expression and activity may result in more effective termination of cGMP-dependent signaling. Therefore, we hypothesised that combined treatment with the
$75DJRQLVW&DQGWKH3'(LQKLELWRUVLOGHQD¿OZRXOGSURYLGHVXSHULRU
cardiac anti-remodelling effects than either drug given alone.
Design and method: )9%1PLFHZHUHSODFHGRQDKLJKVDOW +6 GLHWIRU
ZHHNVWRLQGXFHFDUGLDFK\SHUWURSK\DQG¿EURVLV7KH+6GLHWZDVWKHQFRQWLQued for a further 4 weeks, during which time mice were treated with either C21
PJNJGD\VFYLDRVPRWLFPLQLSXPS VLOGHQD¿O PJNJGD\LQGULQNLQJ
ZDWHU RUDFRPELQDWLRQRI&DQGVLOGHQD¿O$WWKHHQGRIWUHDWPHQWKHDUWV
were removed for histological and biochemical analysis.
Results: $OOGUXJWUHDWPHQWVUHYHUVHGFDUGLDF¿EURVLVFRPSDUHGWRPLFHZKLFK
remained on the HS diet without drug intervention. However, biochemical markHUV RI FDUGLDF UHPRGHOLQJ LQFOXGLQJ 7*)EHWD PDFURSKDJH LQ¿OWUDWLRQ DQG
P\R¿EUREODVWGLIIHUHQWLDWLRQZHUHGHFUHDVHGWRORZHVWOHYHOVLQDQLPDOVZKLFK
UHFHLYHG WKH FRPELQHG & DQG VLOGHQD¿O WUHDWPHQW ,QWHUHVWLQJO\ PDUNHUV RI
LQÀDPPDWLRQVXFKDV0&3DQGSKRVSKR,NDSSD%ZHUHUHGXFHGE\VLOGHQD¿OHLWKHUZLWKRUZLWKRXW&VXJJHVWLQJEHQH¿WVRIFRPELQDWLRQWKHUDS\LQ
addition to potentiated AT2R-mediated signaling.
Conclusions: 7KHFXUUHQWVWXG\SURYLGHVWKH¿UVWHYLGHQFHWKDWWKHEHQH¿FLDO
cardiac effects of low-dose C21 may be enhanced by simultaneous PDE5 inhibiWLRQDQGUHSUHVHQWVDQRYHODSSURDFKWRPD[LPL]HLQGLYLGXDOGUXJVHOHFWLYLW\
DQGHI¿FDF\LQWKHRQJRLQJTXHVWIRULPSURYHGFDUGLDFDQWLUHPRGHOLQJWKHUDpies.
Abstracts
e61
ORAL SESSION
ORAL SESSION 5A
BLOOD PRESSURE MEASUREMENT
5A.01
RELATIONSHIP BETWEEN CARDIO-ANKLE
VASCULAR STIFFNESS INDEX (CAVI) AND 24H
BLOOD PRESSURE PARAMETERS IN HYPERTENSIVE
PATIENTS
B. Cuko 1, L. Lonati 1, G. Bilo 1, F. Negri 1, A. Giglio 1, G. Caldara 1,
S. Salerno 1, G. Parati 1,2. 1 Dept. of Cardiology, S. Luca Hospital, IRCCS
Istituto Auxologico Italiano, Milan, ITALY, 2 Dept. of Health Sciences,
University of Milano-Bicocca, Dept. of Cardiovascular, Neural and Metabolic
Sciences, S. Luca Hospital, Milan, ITALY
hypertensive cohorts (323 participants) gave a pooled systolic IAD prevalence
! PP+J RI &, WR , S ¿YH VWXGLHV RI
diabetic cohorts (1363 participants) gave a pooled systolic IAD prevalence
>=10mmHg of 7.0% (5.1 to 9.0; I2 =45%, p=0.12). Six studies (2594 participants) reported simultaneous measurements of IAD in populations considered
likely to represent the general population, giving a pooled systolic IAD prevalence
>=10mmHg of 4.4% (3.6 to 5.2; I2 = 0%, p=0.45). Prevalences for these subJURXSVGLIIHUHGVLJQL¿FDQWO\ ¿JXUH 3UHYDOHQFHVUHSRUWHGE\VWXGLHVXVLQJRWKHU
measurement techniques were higher.
Conclusions: The prevalence of an inter-arm difference rises in relation to the
baseline cardiovascular risk of the population studied, and is over-estimated when
DUREXVWPHWKRGRIPHDVXUHPHQWLVQRWXVHG6XFKSRSXODWLRQVSHFL¿FYDULDWLRQVLQ
prevalences of inter-arm differences should be taken into account in planning future
studies and interventions.
Objective: &DUGLR$QNOH 9DVFXODU VWLIIQHVV ,QGH[ &$9, KDV EHHQ GH¿QHG DV D
blood pressure (BP) independent index of arterial stiffness unlike aortic pulse wave
velocity and augmentation index that are strictly dependent on the BP at the time of
measurement. Arterial stiffness measured with CAVI has been shown to be a comprehensive indicator of arteriosclerosis, and it would thus be important to explore its
relation with daily life BP patterns. Aim of our study was to investigate this issue.
Design and method: 212 treated caucasian essential hypertensive patients (age
18-75yrs) consecutively afferent to our outpatients Hypertension Centre underwent clinical evaluation, 24h ABPM (AND 2430) and CAVI assessment (VaSera
)XNXGD'HQVKL 7KHUHODWLRQRI&$9,ZLWKRI¿FH%3DQGZLWKKGD\DQGQLJKW
ABP mean values and variability was investigated.
Results: 1RUHODWLRQZDVIRXQGEHWZHHQ&$9,DQGDOORI¿FH%3SDUDPHWHUV S16 &RQYHUVHO\&$9,LQXQLYDULDWHDQDO\VLVVKRZHGDVLJQL¿FDQWUHODWLRQZLWKDPEXODtory PP (day R=0,31 p<0,0001-night R=0,25 p<0,001- 24h R=0,28 p<0,0001) but
not with the corresponding ambulatory SBP and DBP. The relation between CAVI
DQGDPEXODWRU\33UHPDLQHGVLJQL¿FDQW S HYHQDIWHUDFFRXQWLQJIRUDJHWKH
strongest predictor of CAVI (r=0,68; p<0,0001). Concerning short term BP variability we observed only a weak relation of CAVI with 24h weighted systolic BP
VWDQGDUGGHYLDWLRQ 5 S ZKLFKORVWVLJQL¿FDQFHDIWHUFRUUHFWLRQIRUDJH
Conclusions: 7KHVHGDWDFRQ¿UPWKHLQGHSHQGHQFHRI&$9,IURP%3YDOXHVREtained at the time of measurement. However, our study provides novel evidence
RQWKHUHODWLRQEHWZHHQ&$9,DQGDPEXODWRU\33LHZLWKDSDUDPHWHUUHÀHFWLQJ
both dynamic BP behavior during cardiac cycle in daily life and the degree of large
arteries stiffness. Our data provides further support to the possible clinical usefulness of CAVI in the evaluation of vascular properties in hypertensive patients.
5A.02
THE INTER-ARM DIFFERENCE IN BLOOD
PRESSURE: PREVALENCE VARIES FOR DIFFERENT
POPULATIONS
C. Clark, A. Shore, R. Taylor, J. Campbell.
University of Exeter Medical School, Exeter, UNITED KINGDOM
Objective: Systolic differences in blood pressure between arms >=10mmHg
are associated with increased cardiovascular mortality and morbidity. A range of
prevalences have been reported for such inter-arm differences (IAD). Variations
may be explained by differing underlying vascular risk and by the method of
PHDVXUHPHQW5HSHDWHGVLPXOWDQHRXVPHDVXUHPHQWVKDYHEHHQLGHQWL¿HGDVWKH
reference standard for IAD measurement. Robust estimates of IAD prevalences
in different cohorts relevant to primary care populations could inform the design
of future studies, and aid the appraisal of existing studies. Therefore a metaanalysis of reference standard studies has been undertaken.
Design and method: A comprehensive continually updated database of studies reporting inter-arm differences has been maintained by the authors based
on searches for previous reviews. Studies from this database that employed a
repeated simultaneous measurement protocol, and examined a cohort likely
to represent general or primary care populations, were eligible for inclusion.
Using study level data, pooled estimates of mean prevalence of systolic IAD
>=10mmHg were calculated and compared using a random effects model.
Results: The database contains 73 IAD cohorts assessed by any method, datLQJIURP)URPWKHVHVWXGLHVPHWWKHLQFOXVLRQFULWHULD'DWDIRUWKUHH
5A.03
EFFECTIVENESS OF A SUPPORT PROGRAM
DESIGNED TO SENSITIZE AND ASSIST
HYPERTENSIVE PATIENTS TO DECREASE THEIR
SALT CONSUMPTION
S. Jain. University of British Columbia, Vancouver, CANADA
Objective: Assess the incremental effect of a salt intake support program in
monitoring dietary salt intake and blood pressure (BP) in patients with mild to
moderate hypertension managed in a real-life clinical setting by Canadian general
practitioners.
Design and method: Open label, prospective cohort, randomized, multi-center
study in patients with hypertension treated with perindopril for 16 weeks. Patients
were randomized into either the control group (routine care) or the group which
received information on salt (such as sources of salt, how to read food labels, how
to reduce salt intake and to follow the Canadian guidelines of not exceeding 1500
mg of salt intake per day).
Results: 12,697 patients with hypertension were recruited. Mean ± SD age at
baseline was 60 ± 13 years. Majority of patients were males (55%) and Caucasian (78%). At baseline, 3.5% of patients were below salt intake target, 8.2%
ZHUHPRGHUDWHO\DERYHDQGZHUHVLJQL¿FDQWO\DERYHWDUJHW$WZHHN
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e62
Journal of Hypertension Volume 32, e-Supplement 1, 2014
10.5% of patients were below salt intake target, 18.4% were moderately above
DQG ZHUH VLJQL¿FDQWO\ DERYH WDUJHW ZLWKRXW DQ\ VLJQL¿FDQW GLIIHUHQFHV
between randomization groups (P=0.449). Two-way ANOVA used to assess the
association between target intake and the absolute change in BP showed that,
upon adjusting for baseline salt intake, patients maintaining stable salt intake
experienced an additional decrease of -13.1 mmHg in SBP compared to patients
increasing their salt intake (P=0.008). Similarly, patients decreasing their salt
consumption experienced an additional -1.3 mmHg decrease in SBP (P=0.054).
+RZHYHUQRVLJQL¿FDQWDVVRFLDWLRQZDVREVHUYHGEHWZHHQVDOWLQWDNHDQGWKH
absolute change in DBP.
Conclusions: Study demonstrated that patients maintaining or reducing their sodium consumption had more favorable BP parameters. The results suggest that intervention at the patient behavior level to decrease the level of sodium consumption
LQDGGLWLRQWRWUHDWPHQWZLWKSHULQGRSULOPD\EHEHQH¿FLDOLQDFKLHYLQJ%3FRQWURO
Salt consumption changesV3-V1
N SBD1/DBP2 Changes V3-V1 (mmHg)
Decrease
1741
-20.6/-10.3
No change
7
-31.7/-25.3
Increase
485
--19.0/-10.1
Between-group P-value was assessed with non-parametric Kruskal Wallis test.
1p=0.001, 2 p=0.711
5A.04
PROGNOSTIC IMPACT OF A GENDER-AMBULATORY
BLOOD PRESSURE INTERACTION IN 10
COHORTS OF 17,312 PATIENTS DIAGNOSED WITH
HYPERTENSION. SYSTEMATIC REVIEW AND METAANALYSIS
G. Roush, A. De La Sierra, R.H. Fagard, G. Salles, S. Pierdomenico, G. Reboldi,
P. Verdecchia, K. Eguchi, K. Kario, J. Polonia, R. Hermida, E. Dolan,
J. Fapohunda. ABC-H Investigators, Terrassa, SPAIN
Objective: We aimed to evaluate whether ambulatory blood pressure (BP) among
hypertensives better predicts cardiovascular events (CVEs) in women versus men.
Design and method: In this review, we searched PUBMED and OVID databases
and contacted lead investigators who provided most data elements. Cohorts were
required to have hypertension, 1+ years of follow up, with stroke and coronary
artery disease as outcomes. Random effects meta-analyses were used to obtain
hazard ratios for CVEs from a 1 standard deviation (SD) increase in SBP and a
10 mmHg increase in SBP. Meta-regression and subgroup analyses were used to
quantify the relative prognostic value of women versus men.
Results: Patients were from Europe, Brazil, and Japan (10 cohorts, N=17,312,
&9(V 2QH FRKRUW ODFNHG JHQGHUVSHFL¿F +5V IURP KRXU DQG FOLQLF
6%3 EXW RWKHUZLVH KDG JHQGHUVSHFL¿F LQIRUPDWLRQ 7KHUH ZDV D WHQGHQF\ IRU
ZRPHQWRKDYHDJUHDWHU6'RI6%3DQGDJUHDWHUFRHI¿FLHQWRIYDULDWLRQDV
compared to men. For women relative to men, a 1 SD increase in nighttime, dayWLPHKRXUDQGFOLQLF6%3JDYH55V FRQ¿GHQFHLQWHUYDOV RI 1.31), 1.23 (1.09-1.40), 1.21 (1.07-1.37), and 0.94 (0.83-1.06), respectively. For
a 10 mmHg increase in SBP, the corresponding RRs were 1.06 (0.99-1.14), 1.13
(1.03-1.23), 1.10 (1.01-1.21), and 0.96 (0.89-1.03), respectively.
5A.05
DIURNAL VARIATION OF CENTRAL BLOOD
PRESSURE IN ADOLESCENTS AND YOUNG ADULTS:
A PILOT STUDY
A. Ntineri 1, A. Kollias 1, A. Vazeou 2, A. Achimastos 1, G.S. Stergiou 1.
Hypertension Center, STRIDE Hellas-7, Third University Department of
Medicine, Sotiria Hospital, Athens, GREECE, 2 First Department of Pediatrics,
P. and A. Kyriakou Children Hospital, Athens, GREECE
1
Objective: There is evidence that in adolescents and young adults with elevated
brachial systolic blood pressure (BP), central aortic BP often is low. Moreover,
DPEXODWRU\%3PRQLWRULQJLVUHJDUGHGDVLQGLVSHQVDEOHIRUWKHFRQ¿UPDWLRQRIK\pertension in young individuals. This study aimed to compare the diurnal variation
of central compared to brachial ambulatory BP in adolescents and young adults.
Design and method: A total of 19 apparently healthy subjects referred for BP
evaluation (15 males; mean age 16.9 years; range 11-25) underwent 24-hour ambulatory brachial and aortic BP monitoring simultaneously using a noninvasive
brachial cuff-based oscillometric device (Mobil-O-Graph 24h PWA).
Results: According to their brachial ambulatory BP, 6 participants had hypertension, 3 high-normal BP and 10 normotension. All subjects presented higher brachial than central systolic ambulatory BP during periods (daytime difference range
9-31 mmHg, nighttime 2-18 mmHg). The average difference between peripheral
and central systolic BP was larger during daytime (mean difference 18.3±5.6 [SD]
mmHg) than nighttime (8.6±3.9 mmHg, P<0.001). The average nocturnal decline
of central BP was lower (6.0±7.8 mmHg or 5.0±7.1%) than that of brachial systolic BP (15.7±6.4 mmHg or 12.0±4.8%, P<0.001 for difference in both average and
percentage BP decline). However, in 5 subjects (3 non-dippers, 1 dipper, 1 riser
according to brachial BP) central BP increased during nighttime sleep, indicating
a potential “reverse dipping” behavior.
Conclusions: These preliminary data suggest that in adolescents and young adults
there is considerable difference between brachial and central systolic BP which
is largely attenuated during nighttime sleep. Thus, central systolic BP exhibited a
lesser nocturnal dip than brachial BP, which is line with previous data in the adults.
Further research is needed to reveal the full spectrum of central BP diurnal patterns
and their relationship with brachial BP in young individuals.
5A.06
EFFECTS OF SMOKING ON CENTRAL BLOOD
PRESSURE AND PRESSURE AMPLIFICATION IN
HYPERTENSION OF THE YOUNG
F. Saladini 1, E. Benetti 1, C. Fania 1, L. Mos 2, A. Mazzer 3, A. Bortolazzi 4,
E. Casiglia 1, P. Palatini 1. 1 Medicine Department, Università degli Studi di
Padova, Padua, ITALY, 2 Town Hospital, San Daniele del Friuli, ITALY, 3 Town
Hospital, Vittorio Veneto, ITALY, 4 Town Hospital, Rovigo, ITALY
Objective: Smoking is a risk factor for cardiovascular disease and arterial stiffness,
but little is known about the effect of smoking on central blood pressure (BP). The
aim of the present study was to investigate the effect of cigarette smoking on peripheral and central BPs in a group of young-to-middle-age stage I hypertensives.
Design and method: We examined 344 untreated subjects from the
HARVEST (mean age 37±10 years, 73.5% males, mean BP at entry
142.1±12.9/90.0±8.1mmHg). Central BP was obtained from radial artery tonometry using the Specaway DAT System. Patients were divided into 3 classes
RIVPRNLQJQRQVPRNHUVPLOGVPRNHUV FLJDUHWWHVGD\ DQGPRGHUDWH
to-heavy smokers (>5 cigarettes/day), and into 3 classes of age (18-29, 30-39,
>=40 years). A 2-way ANCOVA was performed to investigate the interactive
effect of smoking with age, adjusting for several confounders and other lifestyle factors.
Results: Smokers were less active than non smokers and were more frequently
alcohol and coffee drinkers. No smoking-related differences were found for peripheral BP and pulse pressure (PP), whereas central systolic BP was higher in
VPRNHUVFRPSDUHGWRQRQVPRNHUV V\VWROLF%3“PP+JLQQRQVPRNers, 130.0±2.1 mmHg in mild smokers, 130.6±2.4 mmHg in moderate-to-heavy
VPRNHUVS 33“PP+J“PP+JDQG“PP+J
UHVSHFWLYHO\ S $OVR ORZHU V\VWROLF %3 DPSOL¿FDWLRQ S DQG
33 DPSOL¿FDWLRQ S ZHUH REVHUYHG LQ VPRNHUV “ PP+J DQG
10.6±2.2 mmHg, respectively in mild smokers and 13.1±2.7 mmHg and 8.0±2.6
mmHg, respectively in moderate-to-heavy smokers) compared to non smokers
(21.4±0.9 mmHg and 15.0±0.8 mmHg, respectively). In a 2-way ANCOVA,
V\VWROLF %3 DPSOL¿FDWLRQ VKDUSO\ GHFOLQHG DFURVV WKH DJH FODVVHV S and from non smokers to smokers (p =0.0004). The effect of smoking on BP
DPSOL¿FDWLRQZDVFRPSDUDEOHWRWKDWRIEHLQJ\HDUVROGHU
Conclusions: In patients with hypertension, ambulatory SBPs better predict CVEs
in women than in men.
Conclusions: These data show that in young to middle age stage I hypertensives
smoking has a detrimental effect on central BP accelerating the age-related decline
LQ%3DPSOL¿FDWLRQ
Abstracts
e63
ORAL SESSION
ORAL SESSION 5B
COMBINATION TREATMENT AND
ADHERENCE THERAPY
5B.01
PREVENTION OF CORONARY AND STROKE
EVENTS WITH PERINDOPRIL, AMLODIPINE AND
ATORVASTATIN IN COMBINATION: SUB-GROUP
ANALYSIS OF THE ANGLO-SCANDINAVIAN CARDIAC
OUTCOMES TRIAL (ASCOT)
S. Watson, A. Gupta, N.R. Poulter. International Centre for Circulatory Health,
Imperial College London, London, UNITED KINGDOM
Objective: The coexistence of moderate hypertension and moderate dyslipidemia increases the probability of a cardiovascular (CV) event more than in
patients with isolated marked elevations in BP or cholesterol levels alone. Calcium antagonists and ACE inhibitors in combination and the use of statins are
recommended for hypertensive patients in current guidelines based on extensive
trial data. The objective of this analysis was to perform an on-treatment analysis
of the lipid-lowering arm of the ASCOT trial (ASCOT-LLA) to assess whether
patients who concurrently took a calcium antagonist, ACE inhibitor and atorvasWDWLQEHQH¿WHGLQWHUPVRIIHZHU&9RXWFRPHVUHODWLYHWRSDWLHQWVZKRFRQFXUUHQWO\WRRNDGLXUHWLFȕEORFNHUDQGDWRUYDVWDWLQ
Design and method: ASCOT-LLA patients who concurrently took amlodipine, perindopril and atorvastatin (‘APA’, n=1814) were compared to patients
ZKRFRQFXUUHQWO\WRRNDWHQROROEHQGURÀXPHWKLD]LGHDQGDWRUYDVWDWLQ µ$%$¶
n=1978) during a median follow-up period of 3.3 years, including and excluding
those taking other anti-hypertensive medications. When at least one of the three
drugs in either triplet was stopped, the triple therapy period was deemed to have
ended. Only CV events occurring during the triple therapy period were included.
Results: Patients taking the APA combination, irrespective of other anti-hyperWHQVLYHPHGLFDWLRQVGLVSOD\HGDVLJQL¿FDQWUHODWLYHULVNUHGXFWLRQ 555 in the composite of CV mortality, non-fatal myocardial infarction (MI) and
stroke [0.58 (0.40-0.85] compared to those receiving the ABA combination. The
APA combination was also associated with an RRR of 39% in the composite
of non-fatal MI, fatal coronary heart disease (CHD) and coronary revascularization procedures [0.61 (0.38-0.97], 50% [0.50 (0.29-0.86] in stroke and 24%
> @ LQ WRWDO &9 HYHQWV DQG SURFHGXUHV$ QRQVLJQL¿FDQW
RRR [0.62 (0.36-1.08] in the composite of non-fatal MI and fatal CHD was
also apparent. Results were unchanged by excluding patients taking other antihypertensive medications.
Conclusions: 2QWUHDWPHQWDQDO\VLVRI$6&27//$GHPRQVWUDWHGWKHEHQH¿W
in terms of large reductions in major CV events among hypertensive patients
with at least three CV risk factors and cholesterol <=6.5mmol/L for patients on
the APA combination compared with the ABA combination.
5B.02
THE INFLUENCE OF ELECTRONIC VERSION OF
SCORE ON THE TREATMENT ADHERENCE IN
HYPERTENSIVE PATIENTS
D. Nebieridze, A. Safarian, A. Saricheva.
National Research Centre for Prev.Medicine, Moscow, RUSSIA
Objective: In this study we tested the hypothesis that using electronic version of
SCORE (EV SCORE) should improve compliance to treatment in hypertensive
patients (pts) in primary health care. We suggested that vivid demonstration to
the pts their real risk and its favorable changes if achieving goals of therapy
would lead to high motivation to treatment recommendations.
Design and method: 188 hypertensive males aged 40-55 with high risk according to SCORE evaluation (all of them were smokers and had high level of total
cholesterol) and without signs of atherosclerotic disease were included in the
trial. They were randomly divided in two groups by 94 pts in each. In one group
total risk was calculated by using EV SCORE (main group).In the second group
total risk was evaluated by chart version of SCORE (reference group ). In both
groups pts were shown not only initial risk but its change if achieving goals of
therapy. All pts, as high risk ones, were prescribed antihypertensive and lipidlowering drugs as well as healthy life-style recommendations during 9 months
Results: Adherence to both antihypertensive and lipid lowering therapy was
VLJQL¿FDQWO\ KLJKHU LQ WKH JURXS ZKHUH (9 6&25( ZDV XVHG ,Q WKLV JURXS
70 pts out of 94 (74,4%) remained on antihypertensive drugs by the end of the
study, while only 33 pts (35,1%) - in reference group, p< 0,0001. Similarly the
percentage of pts who remained on lipid- lowering drugs by the end of the study
ZDV VLJQL¿FDQWO\KLJKHULQWKHPDLQJURXS FRPSDULQJZLWKUHIHUHQFHJURXS ±
respectively 57 pts (60,6%) and 26 pts (27,6%), p< 0,0001. As a result more pts
in the main group achieved blood pressure and lipid variables goals, then in the
reference group.
Conclusions: Integration of EV SCORE in routine clinical practice allows not
only quick evaluation of total risk but also motivates pts to better adherence to
antihypertensive and lipid-lowering therapy. It is very important because pts
without signs of atherosclerotic disease are weakly motivated to drug treatment.
5B.03
COMBINATION THERAPY WITH LERCANIDIPINE
AND ENALAPRIL IMPROVES WAVE REFLECTION
IN HYPERTENSIVE PATIENTS WITH METABOLIC
SYNDROME
L. Ghiadoni 1, R. Bruno 2, G. Cartoni 1, F. Stea 2, A. Magagna 1, A. Virdis 1,
D. Grassi 3, C. Ferri 3, S. Taddei.. 1 Department of Clinical and Experimental
Medicine, University of Pisa, Pisa, ITALY, 2 Institute of Clinical Physiology,
CNR, Pisa, ITALY, 3 Department of Internal Medicine and Public Health,
University of L’Aquila, L’Aquila, ITALY
Objective: $UWHULDOVWLIIQHVVDQGZDYHUHÀHFWLRQDUHLQGHSHQGHQWSUHGLFWRUVRI
cardiovascular events. In a randomized, open, parallel group study we compared
the effect on these parameters of a combination therapy with an ACE-inhibitor
plus calcium channel blocker or thiazide diuretic in 76 hypertensive patients
with metabolic syndrome uncontrolled by ACE-inhibitor monotherapy.
Design and method: After 4 weeks run-in with enalapril (ENA, 20 mg), patients were randomized to a combination therapy with lercanidipine (LER, 1020 mg) or hydrochlorothiazide (HCT, 12.5-25 mg) for 24 weeks. Aortic stiffness
(carotid to femoral pulse wave velocity, PWV), central blood pressure (BP) and
ZDYH UHÀHFWLRQ DXJPHQWDWLRQ LQGH[$,[ ZHUH PHDVXUHG E\ DSSODQDWLRQ WRnometry.
Results: $IWHU UXQLQ RI¿FH %3 ZDV VLPLODU LQ WKH WZR JURXSV (1$/(5
““ (1$+&7 “ PP+J 2I¿FH (1$/(5 ““
ENA/HCT 133±7/83±5 mmHg), 24-hour (ENA/LER 123±11/75±7; ENA/HCT
122±12/77±7 mmHg) and central BP (ENA/LER 121±13/80±9; ENA/HCT
122±13/79±9 mmHg) were similarly reduced after 24 weeks. PWV was similar
after run-in and equally reduced by the two treatments (ENA/LER from 8.6±1.5
to 8.1±1.3 m/s, p<0.05; ENA/HCT from 8.5±1.2 to 8.2±1.0 m/s, p<0.05). FiQDOO\ ERWK FRPELQDWLRQV UHGXFHG$,[ EXW LWV UHGXFWLRQ UHVXOWHG VLJQL¿FDQWO\
greater (p<0.05) in ENA/LER (from 26.8±10.9 to 20.6±9.1%) than in ENA/
HCT arm (from 28.2±9.0 to 24.7±8.7%).
Conclusions: In conclusion, the combination with LER caused a similar PWV
reduction as compared to HCT, but a greater reduction in AIx in hypertensive
patients with metabolic syndrome not controlled by ENA alone. These results
LQGLFDWHDSRVLWLYHHIIHFWRIWKHFRPELQDWLRQRI(1$/(5RQZDYHUHÀHFWLRQ
suggesting a potential additive role for cardiovascular protection.
5B.04
HIGH RATES OF NON-ADHERENCE TO
ANTIHYPERTENSIVE TREATMENT DEMONSTRATED
BY MASS SPECTROMETRY URINALYSIS: THE
NEGATIVE CORRELATION BETWEEN THE NUMBER
OF DRUGS PRESCRIBED AND THE NUMBER TAKEN
C. White 1, P. Patel 3, N. Masca 1,2, R. Damani 1, J. Hepworth 3, N. Samani 1,2
P. Gupta 1,3, W. Madira 3, A. Stanley 1,3, B. Williams 4, M. Tomaszewski 1,2.
1
Dept. of Cardiovascular Sciences, University of Leicester, Leicester, UNITED
KINGDOM, 2 NIHR Leicester Biomedical Research Unit in Cardiovascular
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Journal of Hypertension Volume 32, e-Supplement 1, 2014
Disease, Leicester, UNITED KINGDOM, 3 University Hospitals of Leicester
NHS Trust, Leicester, UNITED KINGDOM, 4 Institute of Cardiovascular
Science and NIHR University College London Hospitals Biomedical Research
Centre, Leicester, UNITED KINGDOM
Objective: Non-adherence to therapy is an important cause of suboptimal blood
pressure [BP] control and resistant hypertension. Few practical tools exist to
accurately determine its prevalence. In our specialist cardiovascular centre we
used a simple urine-based assay to audit the prevalence of non-adherence to
antihypertensive medication and its impact on BP.
Design and method: 208 hypertensive patients [125 new referrals, 66 followups with inadequate BP control, 17 renal denervation referrals] underwent biochemical screening for non-adherence to antihypertensive treatment. Spot urine
sample analysis was performed at clinic visits, using high-performance liquid
chromatography-tandem mass spectrometry [HPLC-MS/MS] to detect any of
40 of the most commonly prescribed antihypertensive medications, or their metabolites.
Results: Over the whole population, 25% of patients were non-adherent to anWLK\SHUWHQVLYH WUHDWPHQW >WRWDO QRQDGKHUHQFH SDUWLDO QRQDGKHUHQFH
14.9%]. The greatest prevalence of partial and total non-adherence was amongst
follow-up patients with inadequate BP control [28.8%] and those with “resistant
hypertension” referred for Renal Denervation [23.5%]. There was a negative
FRUUHODWLRQEHWZHHQWKHQXPEHURIGUXJVSUHVFULEHGDQGWKHQXPEHUGHWHFWHG
RISDWLHQWV>Q @ZKRZHUHSUHVFULEHG¿YHRUPRUHGUXJVVKRZHGVRPH
degree of non-adherence.
The mean difference between adherent and non-adherent patients’ clinic SBP /
DBP was 9.8mmHg [p*= 0.021] / 9.8 mmHg [p*= 0.001]. The mean difference
between adherent and non-adherent patients ambulatory SBP / DBP was 6.4
[p*0.181] / 7.7 mmHg [p*= 0.029].
7KHUHZDVDVWDWLVWLFDOO\VLJQL¿FDQWOLQHDUUHODWLRQVKLSEHWZHHQEORRGSUHVVXUH
DQGWKHGLIIHUHQFHLQSUHVFULEHGGHWHFWHGDQWLK\SHUWHQVLYHPHGLFDWLRQV±HYHU\
unit increase in this difference was associated with 3.0 mmHg , 3.1 mmHg and
1.9 mmHg increase in clinic SBP, clinic DBP and 24-hour DBP (P=0.0051,
P=8.62x10-6, P=0.0057), respectively.
Conclusions: Non-adherence to anti-hypertensive therapy is much more common than previously recognised, particularly in those with multi-drug regimens
correlating with suboptimal BP control and/or referred for Renal Denervation.
HPLC-MS could be used to exclude non-adherence and stratify further diagnostic and therapeutic needs.
5B.05
THE ASSESSMENT OF SERUM ANTIHYPERTENSIVE
DRUG LEVELS TO EVALUATE ADHERENCE TO
TREATMENT IN PATIENTS WITH RESISTANT
HYPERTENSION
E. Florczak 1, M. Kala 2, B. Tokarczyk 2, E. Warchol-Celinska 1,
E. Szwench-Pietrasz 1, A. Prejbisz 1, M. Kabat 1, K. Narkiewicz 3,
A. Januszewicz 1. 1 Institute of Cardiology, Department of Hypertension,
Warsaw, POLAND, 2 Institute of Forensic Research, Kraków, POLAND,
3
Medical University of Gdansk, Department of Hypertension and Diabetology,
Gdansk, POLAND
Objective: The aim of the study was to evaluate patients’ treatment adherence
by assessing serum antihypertensive drugs levels in selected patients with true
resistant hypertension (RHTN) in the Resist-Pol study.
Design and method: 204 consecutive patients (123M, 81F, mean age 48,4,
UDQJH±\UV ZLWK WUXH 5+71 H*)5 !POPLQP DQG ZLWK QR
history of diabetes were investigated. All patients underwent thorough exDPLQDWLRQLQFOXGLQJSRO\VRPQRJUDSK\HFKRFDUGLRJUDSK\UHQDODUWHU\DGrenal and renal CT scan, hormonal evaluations for primary aldosteronism,
pheochromocytoma and Cushing syndrome. In patients in whom the presence of secondary hypertension was excluded, taking at least 4 antihypertensive drugs and having the most pronounced inadequate BP control, serum
antihypertensive drugs levels using the method of liquid chromatography
coupled with tandem mass spectrometry (LC-MS-MS) were assessed. The
total medical adherence was determined if the serum drug concentration of
DOODQWLK\SHUWHQVLYHGUXJVZDVDERYHWKHOLPLWRITXDQWL¿FDWLRQ3DWLHQWVLQ
ZKRPWKHVHUXPOHYHORIDWOHDVWRQHGUXJZDVEHORZWKHOLPLWRITXDQWL¿FDtion were labeled as non-adherent.
Results: ,QSDWLHQWV 0)PHDQDJHUDQJH\UV DQWLK\SHUtensive drugs levels were assessed. The assessment of serum drug concentration
was possible for 3,7 ±1,2 out of 4,9 ±1,2 antihypertensive drugs prescribed for
HDFKSDWLHQW,QSDWLHQWV WKHFULWHULDRIQRQDGKHUHQFHZHUHIXO¿OOHG
Moreover in 5 patients (13,9%) none of prescribed drugs was detectable and
only 5 patients (13,9%) were fully compliant. The degree of the adherence to
medical recommendations was also assessed by the number of drugs which serum concentration was in therapeutic range. The serum drug concentration of all
prescribed drugs in the therapeutic range was determined in 2 patients (5,6%). In
8 patients (22,2%) the serum drug concentration of more than a half prescribed
drugs in the therapeutic range was determined. None of the prescribed drugs
concentration in the therapeutic range was found in 16 patients (44,4%).
Conclusions: The level of non-adherence in patients with apparently resistant
K\SHUWHQVLRQVKRXOGEHFRQVLGHUGDVKLJK2XU¿QGLQJVLQGLFDWHWKDWWKHSUHYDlence of true resistant hypertension is lower than previously reported.
5B.06
IMPROVEMENT IN BP CONTROL IN HYPERTENSIVE
PARTICIPANTS WHO WERE SWITCHED TO
NIFEDIPINE GITS/CANDESARTAN CILEXETIL FROM
PREVIOUS MONOTHERAPY OR COMBINATION
ANTIHYPERTENSIVE THERAPY
S.E. Kjeldsen 1, D.A. Sica 2, H. Haller 3, G. Cha 4, B. Gil-Extremera 5, P. Harvey 6,
F. Heyvaert 7, A. Lewin 8, G. Villa 9, G. Mancia 10. 1 Oslo University Hospital,
Ullevaal, Oslo, NORWAY, 2 Virginia Commonwealth University, Richmond,
VA, USA, 3 Hannover Medical School, Hannover, GERMANY, 4 KRK Medical
Research Institute, Dallas, TX, USA, 5 Hospital Universitario San Cecilio,
Granada, SPAIN, 6 The Crouch Oak Family Practice, Addlestone, UNITED
KINGDOM, 7 Huisartsenpraktijk De Regenboog, Antwerp, BELGIUM, 8
National Research Institute, Los Angeles, CA, USA, 9 Fondazione S. Maugeri,
IRCCS, Pavia, ITALY, 10 University of Milano-Bicocca, Milan, ITALY
Objective: :HDLPHGWRGRDSRVWKRFDQDO\VLVRIWKH',67,1&7 UH'H¿QLQJ
,QWHUYHQWLRQ ZLWK 6WXGLHV 7HVWLQJ ,QQRYDWLYH 1LIHGLSLQH *,76 ± &DQGHVDUWDQ
Therapy) study, to assess blood pressure (BP) control in hypertensive participants randomised to nifedipine GITS/candesartan cilexetil according to previous
treatment and BP control status.
Design and method: This was a multicentre, double-blind, multifactorial study
LQZKLFKK\SHUWHQVLYHSDUWLFLSDQWV GLDVWROLF%3! ±PP+J ZHUHUDQdomised to nifedipine GITS (N; 20, 30 or 60 mg) and/or candesartan cilexetil
(C; 4, 8, 16 or 32 mg) or placebo for 8 weeks. We performed a post-hoc analysis
of BP control rates (<140/90 mmHg) according to previous antihypertensive
treatment (monotherapy or combination therapy recorded at screening [baseline]
visit) and in non-responders (patients with uncontrolled hypertension under their
previous antihypertensive treatment [baseline BP>=140/90 mmHg]).
Results: Overall, 853 patients were analysed (prior monotherapy [n=385] and
prior combination [n=468]). Baseline BP control (<140/90 mmHg) was low.
However, treatment with nifedipine GITS/candesartan cilexetil (NC) combiQDWLRQ VLJQL¿FDQWO\ LPSURYHG %3 FRQWURO LQ SDUWLFLSDQWV VZLWFKHG IURP HLWKHU
monotherapy or combination therapy (Table; *P<0.0001). Even in previous
monotherapy and combination therapy non-responders, the BP control rates after 8 weeks of NC combination were similarly improved.
Conclusions: 6LJQL¿FDQWLPSURYHPHQWVLQ%3FRQWUROUDWHVZHUHVHHQLQSDUWLFLpants who switched to 8 weeks of randomised treatment with nifedipine GITS/
candesartan combination therapy from previous antihypertensive monotherapy
or combination therapy. Nifedipine GITS/candesartan appears to be a powerful
combination to achieve BP control in hypertensive patients.
e65
Journal of Hypertension Volume 32, e-Supplement 1, 2014
5B.07
ADHERENCE TO TREATMENT AND ASSOCIATED
FACTORS IN UNCONTROLLED HYPERTENSIVE
ADULT MALE AND FEMALE PATIENTS: A FRENCH
STUDY
G. Reach 1, D. Guedj-Meynier 2, A. Tabellion 3, B. Darné 4, D. Herpin 5.
Avicenne Hospital APHP, Department of Endocrinology, Diabetes and
Metabolic Diseases, Bobigny, FRANCE, 2 Cardiologist, Paris, FRANCE,
3
Laboratoires Menarini, Rungis, FRANCE, 40RQLWRULQJ)RUFH6FLHQWL¿F
DQG0HGLFDO'HSDUWPHQW0DLVRQV/DI¿WWH)5$1&(5 CHRU La Milètrie,
University of Poitiers, Department of Cardiology, Poitiers, FRANCE
1
Objective: To assess medical and non medical factors associated with poor adherence to treatment, in males and females with uncontrolled hypertension.
Design and method: A cross-sectional observational study, in which each
JHQHUDOSUDFWLWLRQHU *3 KDGWRLQFOXGHWKH¿UVWPDOHDQGWKH¿UVWIHPDOH
patients with uncontrolled treated hypertension. Adherence to antihypertensive
treatment was estimated using the French League Against High blood pressure
(FLAH) questionnaire, a validated 6-question self-questionnaire) and by the
GPs themselves. A stepwise logistic regression analysis was used to identify
factors associated with poor adherence (self-questionnaire). Analyses were independently performed in males and in females.
Results: Between February and August 2013, 1636 males (61±11 yrs, 160/90
mmHg) and 1613 females (62±11 yrs, 160/90 mmHg) were included by 873
*3V$GKHUHQFH WR WUHDWPHQW ZDV VLJQL¿FDQWO\ EHWWHU LQ IHPDOHV YHUVXV PDOHV
and when estimated by the GPs in comparison with the FLAH questionnaire (see
table). Concordance between the FLAH questionnaire and GPs was poor (Kappa
FRHI¿FLHQWRIDQGLQPDOHVDQGIHPDOHVUHVSHFWLYHO\ /DFNRIPRWLYDWLRQZDVWKH¿UVWIDFWRUDVVRFLDWHGZLWKSRRUDGKHUHQFHLQERWK
sexes. Considering hypertension as a simple anomaly and not a disease that can
lead to cardiac or cerebral disorders was the second common parameter. Other
FRPPRQIDFWRUVLQERWKVH[HVZHUHPRQWKO\SHULRGVRI¿QDQFLDOGLI¿FXOWLHVDQG
absence of regular screening for colon cancer. Factors associated with poor adherence also included obesity, SBP level, number of pills, a history of stroke
in males, number of treatments, lack of motivation for other recommendations
(e.g. diet), no regular smear screening for cervical cancer, a history of or current smoking and cardio-ischemic disorders in females. Females even when not
motivated had a better adherence to treatment when doing regular screening for
cancer.
Conclusions: Adherence to treatment is better in uncontrolled hypertensive females. Poor adherence is mainly associated with non medical factors, with the
lack of motivation being the main factor.
Abstracts
e66
ORAL SESSION
ORAL SESSION 5C
ATHEROSCLEROSIS
5C.01
DIRECT AT2R STIMULATION PREVENTS
ENDOTHELIAL INFLAMMATION AND LEUKOCYTE
ADHESION AND IMPROVES PLAQUE STABILITY
A. Sampson 1, J. Irvine 1, W. Shihata 1, N. Lumsden 1, O. Huet 1, U. Steckelings 2,
R. Widdop 3, J. Chin-Dusting 1. 1 Baker IDI Heart and Diabetes Institute,
Melbourne, AUSTRALIA, 2 University of Southern Denmark, Odense,
DENMARK, 3 Monash University, Clayton, AUSTRALIA
Objective: Activation of the angiotensin II type I receptor (AT1R), induces
cytokine and chemokine expression which promotes the recruitment, rolling
and adhesion of leukocytes to the activated endothelium; critical early events
in plaque formation. Blockade of the angiotensin II type 2 receptor (AT2R) is
reported to exacerbate atherosclerotic plaque deposition suggesting an anti-inÀDPPDWRU\UROHIRUWKH$75:KHWKHUGLUHFW$75DFWLYDWLRQSUHYHQWVWKHLQLtial adhesion of leukocytes to the endothelium remains unknown.
7RH[DPLQHWKHDQWLLQÀDPPDWRU\SRWHQWLDORIFKURQLF$75DFWLYDWLRQRQYDVFXODULQÀDPPDWLRQWKHDGKHVLRQFDVFDGHDQGSODTXHSURJUHVVLRQ
Design and method: :HLQYHVWLJDWHGWKHDQWLLQÀDPPDWRU\FDSDFLW\RI$75
VWLPXODWLRQ RQ YDVFXODU LQÀDPPDWLRQ DQG OHXNRF\WH DGKHVLRQ LQ YLWUR DQG LQ
vivo using a mouse model of diet-induced atherosclerosis.
Results: 6HOHFWLYH$75 VWLPXODWLRQ &RPSRXQG & —0 DWWHQXDWHG 71)Į QJP/ LQGXFHG PRQRF\WH DGKHVLRQ WR FXOWXUHG KXPDQ XPELOLFDO
vascular endothelial cells (HUVECs) by 59±12% but not in the presence of the
$75 DQWDJRQLVW 3' —0 FRQ¿UPLQJ WKDW WKH HIIHFWV RI & DUH
$75PHGLDWHG)XUWKHUPRUH&WUHDWPHQWDWWHQXDWHG71)ĮLQGXFHGXSUHJXODWLRQ RI DGKHVLRQ PROHFXOHV DQG DEROLVKHG71)ĮLQGXFHG 526 SURGXFWLRQ
71)ĮLQGXFHG 1)ț% WUDQVORFDWLRQ IURP WKH F\WRSODVP WR WKH QXFOHXV HVVHQWLDOIRUF\WRNLQHSURGXFWLRQZDVSUHYHQWHGE\& QXFOHDU1)ț%LQ+89(&V
WUHDWHG ZLWK 71)Į “ 71)Į&“ ÀXRUHVFHQFH LQWHQVLW\ XQLWV
p<0.05). In addition, we examined ApoE knockout mice fed for 10 weeks with
either a normal chow diet or a high fat diet (HFD 21%, 0.15% cholesterol), to
LQGXFH LQÀDPPDWLRQ ZLWK HLWKHU VDOLQH RU & QJNJPLQ VF WUHDWPHQW
IRUWKH¿QDOZHHNV:HREVHUYHG+)'LQGXFHGOHXNRF\WHDGKHVLRQDQGF\WRkine gene expression was attenuated in mice treated with C21 (11±1.5 vs 6±1
OHXNRF\WHV¿HOGRIYLHZYHVVHOSQ 3ODTXHVWDELOLW\LQPLFHWUHDWHG
with C21 was improved with increased smooth muscle cell composition and
decreased lipid size compared to HFD-saline mice.
Conclusions: This study demonstrates that direct stimulation of the AT2R preYHQWV 71)ĮLQGXFHG DQG +)'LQGXFHG YDVFXODU LQÀDPPDWLRQ LQ YLWUR DQG LQ
vivo. We provide novel evidence describing the AT2R intracellular signaling
SDWKZD\ WKDW SUHYHQWV HQGRWKHOLDO LQÀDPPDWLRQ LQ YLWUR DQG LPSURYHV SODTXH
stability in vivo.
5C.02
THE MAGNITUDE, BUT NOT THE TIME COURSE, OF
THE FLOW-MEDIATED DILATATION AT BRACHIAL
ARTERY WAS ASSOCIATED WITH CAROTID INTIMAMEDIA THICKNESS
L. Zhang, F. Li, F. Wei, T. Xu, J. Wang, Y. Li. Shanghai Institute of
Hypertension, Ruijin Hospital, Shanghai Jiaotong University School of
Medicine, Shanghai, CHINA
Objective: $OWKRXJKÀRZPHGLDWHGGLODWDWLRQ )0' DWWKHEUDFKLDODUWHU\LV
GHHPHGPHDQLQJIXOIRUFDUGLRYDVFXODUULVNVWUDWL¿FDWLRQLQWHUSUHWDWLRQRIFXUrent literature remains challenging. Previous studies usually did not take into
account the effect of arterial diameter on FMD and the value of the FMD timecourse. We therefore studied the association between carotid intima-media
thickness (IMT) and brachial FMD, while accounting for the pre-ischaemic arterial diameter and both the magnitude and time-course of FMD.
Design and method: We recruited consecutive untreated patients referred for
ambulatory blood pressure monitoring to our hypertension clinic. Brachial FMD
was measured using a dedicated system (UNEXEF18G, Japan). We computed
FRUUHFWHG)0'VWDQGDUGL]HGWRWKHVH[VSHFL¿FDYHUDJHGLDPHWHURIWKHEUDFKLDO
artery. IMT at the left and right common carotid arteries was measured by the
ArtLab echo-tracking system (Esaote, Italy) and averaged for analysis.
Results: The 408 participants included 217 (53.2%) men and 261 (64.3%) hypertensive patients. Stepwise regression analysis revealed that the crude FMD
differed between men and women (P=0.005), and was mainly determined by
baseline brachial diameter ( 1.6% per 0.6 mm [SD] increase; P<0.001). Corrected FMD remained different between men and women (P<0.005), but was also
determined by 24-hour pulse pressure ( 0.32% per 8 mmHg increase; P=0.009)
and fasting blood glucose (-0.24% per quartile increase; P=0.026). Larger body
mass index (1.0 s per 2.8 kg/m2 increase; P=0.002) and baseline brachial diameter (1.0 s per 0.6 mm increase; P=0.004) were associated with longer time to
peak dilatation. Carotid IMT was associated with common risk factors, including age, sex, body mass index, 24-h mean arterial pressure and pulse pressure,
the total-to-HDL cholesterol ratio, current smoking, fasting blood glucose and
the diameter of carotid arteries. After adjustment for these factors, carotid IMT
ZDV VLJQL¿FDQWO\ DVVRFLDWHG ZLWK FRUUHFWHG )0' XP SHU LQFUHDVH
P=0.017) only, but not the crude FMD or the time to peak dilatation (P>=0.18).
Conclusions: The magnitude, but not the time-course of the brachial FMD was
independently associated with carotid IMT. FMD corrected for baseline arterial
diameter is proposed to be used in future research on endothelial function.
5C.03
PREDICTORS FOR THE DEVELOPEMENT OF
MICROALBUMINURIA AND INTERACTION WITH
RENAL FUNCTION
C. Chatzikyrkou 1, J. Izzo 2, J. Menne 1, G. Viberti 3, T. Rabelink 4, E. Ritz 5,
L.M. Ruilope 6, L. Rump 7, H. Haller 1. 1 Nephrology Section, Hannover
Medical School, Hannover, GERMANY, 2 Department of Medicine, Erie
County Medical Center Buffalo, NY, USA, 3 KCL Guys Hospital, London,
UNITED KINGDOM, 4 Department of Nephrology and Hypertension,
Leiden University Medical Center, Leiden, NETHERLANDS, 5 University of
Heidelberg, Department of Nephrology, Heidelberg, GERMANY, 6 Division of
Hypertension, Universidad Autonome, Madrid, SPAIN, 7 University Hospital,
Düsseldorf, GERMANY
Objective: It is important to know which factors predict the development of
microalbuminuria in patients with diabetes mellitus type II.
Design and method: Data from ROADMAP (Randomised Olmesartan And Diabetes MicroAlbuminuria Prevention) study, which included 4447 patients with a
median follow up of 3,2 years were used. Possible predictors for new onset microDOEXPLQXULDZHUHLGHQWL¿HGE\ORJLVWLFUHJUHVVLRQDQDO\VLVZLWKVWHSZLVHVHOHFWLRQ
of baseline and postbaseline parameters. Furthermore, the interaction of baseline
albuminuria and baseline GFR and the effects of olmesartan were investigated.
Results: The most important predictor of MA was the baseline urinary albumincreatinine ratio (UACR). Other well-known cardio-metabolic risk factors such as
age, weight, HbA1c, total cholesterol, systolic blood pressure and number of antihypertensives were also found to be important. The effects of olmesartan were
more pronounced in patients with the highest baseline UACR (>5mg/g, HR=0.69,
p=0.004). Patients belonging to the highest GFR quartile (>=95.3 ml/min/1.73m2)
VKRZHGWKHPRVWVLJQL¿FDQW*)5GHFUHDVH POPLQP ZLWKROPHVDUWDQ
whereas in the lowest quartile the decrease in eGFR in the olmesartan-treated patients was negligible (-0.41ml/min/1.73m2). There was no association between
EDVHOLQHUHQDOIXQFWLRQDQG0$EXWROPHVDUWDQVLJQL¿FDQWO\UHGXFHGWKHULVNDW
lower eGFR levels (10.42% vs. 7.28% and 10.48% vs. 7.57% for the two lowest
GFR categories respectively). In the overall cohort those with the highest UACR
exhibited a faster decline in GFR. In patients who developed MA the greatest
GFR decrease was observed in those with the lowest initial UACR but the GFR
decrease was much higher in the placebo group (8.03 vs. 2.48 ml/min/1.73m2).
Conclusions: Predictors of MA are the classical cardiovascular risk factors. At
lower GFR prevention of MA by olmesartan seems to preserve renal function.
The lowest UACR at baseline is associated with the greatest GFR decrease if
breakthrough MA occurs and this is dampened by olmesartan. At higher UACR
the prevention of albuminuria by olmesartan is associated with a reduction of
*)5SUREDEO\E\FRXQWHUDFWLQJK\SHU¿OWUDWLRQ
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Journal of Hypertension Volume 32, e-Supplement 1, 2014
5C.04
SIGNIFICANT RELATIONSHIP BETWEEN
ARTERIAL STIFFNESS AND RETINAL
ARTERIOLES ABNORMALITY IN PATIENTS WITH
ATHEROSCLEROTIC DISEASE
J. Iwasaki 1, S. Sakuragi 2, K. Enkoh 1, T. Takamura 1, H. Kobayashi 1.
1
Onomichi Municipal Hospital, Onomichi, JAPAN, 2 Iwakuni Medical Center,
Iwakuni, JAPAN
Objective: Retinal arterioles provide important information on cerebral microvascular disease noninvasively because retinal arterioles have similar characteristics to the cerebral arterioles. Arterial stiffening has been reported to be associated with incidence of stroke and impairment of cognitive function; however
there has been little information on the relationship between arterial stiffness
and cerebral microvascular disease. In this study, we evaluated the relationship
between arterial stiffness and impairment of retinal arterioles.
Design and method: We examined 70 patients with atherosclerotic disease.
Pulse wave velocity (PWV), which is an index of arterial stiffness, was measured with form PWV/AVI (Colin/Omron, Japan). Retinal arterioles were evaluated with seven components including arteriolar constriction, arteriolar caliber
LUUHJXODULW\UHWLQDOKHPRUUKDJHDUWHULRYHQRXVFURVVLQJLQFUHDVHLQOLJKWUHÀH[
soft or hard exudates, and arterial silver wiring. The severity of retinal arterioles
disease was determined according to the number of these components. Patients
ZHUHFODVVL¿HGLQWRWKUHHJURXSVDFFRUGLQJWRWKHQXPEHURIUHWLQDODUWHULROHV
DEQRUPDOLW\ *URXSQ *URXSQ *URXSQ Results: Patients with higher number of retinal arterioles abnormality have
higher PWV 13.7±2.0, 15.6±3.3, 18.2±3.3 m/sec, respectively, p=0.013) (Figure). In univariable analysis, number of retinal arterioles abnormality was sigQL¿FDQWO\DVVRFLDWHGZLWK3:9 U S 7KLVVLJQL¿FDQFHZDVVWLOO
held even after adjustment for age, gender, blood pressure, heart rate, HbA1c
and BMI.
Conclusions: It is suggested that retinal arterioles abnormalities is associated
with arterial stiffness independently of age and blood pressure.
5C.05
HIGH INTRALUMINAL PRESSURE PROMOTES
VASCULAR INFLAMMATION AND ATHEROSCLEROTIC
PLAQUE INSTABILITY VIA A CAVEOLAE-DEPENDENT
MECHANISM
J. Chin-Dusting 1, D. Michell 1, K. Andrews 1, A. Sampson 1, K. Woollard 2,
N. Lumsden 1, O. Huet 1, X. Moore 1, K. Jackson 1, M. Parat 3, G.A. Head 1,
R. Parton 4. 1 Baker Idi Heart and Diabetes Institute, Melbourne, AUSTRALIA,
2
Department of Medicine, Imperial College, London, UNITED KINGDOM,
3
School of Pharmacy, University of Queensland, Brisbane, AUSTRALIA,
4
Institute for Molecular Bioscience, University of Queensland, Brisbane,
AUSTRALIA
Objective: Hypertension is a risk factor for coronary artery disease. Whilst
PDQ\ KRUPRQDO VWLPXOL HOHYDWHG LQ K\SHUWHQVLRQ SURPRWH YDVFXODU LQÀDPPDtion, blockade of these stimuli without blood pressure lowering is not always
effective suggesting that high intraluminal pressure may play an important role.
We hypothesised that high intraluminal pressure per se induces the adhesion
FDVFDGHDQGYDVFXODULQÀDPPDWLRQOHDGLQJWRLQFUHDVHGDWKHURVFOHURWLFSODTXH
instability.
Design and method: A customised perfusion vessel chamber was used to assess
leukocyte adhesion to the endothelium of pressurized rat carotid arteries. The
effect of hypertension on plaque stability was also studied in a newly developed
hypertensive atherosclerotic mouse model (hypertensive BPH/2J mice crossed
with Apoe-/- mice (BPHxApoe-/-).
Results: Elevations of intraluminal pressure increased leukocyte adhesion to
the endothelium in harvested vessels (P<0.001) and increased the expression
of adhesion molecules (ICAM-1 and MCP-1) and the number of endothelial
microparticles from pressurised HUVECs (P<0.05). Increased reactive oxygen species (ROS) production was observed in pressurized HUVECs and a
functional role for ROS and was supported via a reduced leukocyte adhesion
in vessels incubated with apocynin or the mitochondrial ROS inhibitor cycloVSRULQ$3UHVVXUHLQGXFHGLQÀDPPDWLRQZDVGHSHQGHQWXSRQWKHWUDQVFULSWLRQ
IDFWRU 1)ț% VLQFH LQFUHDVHV LQ SUHVVXUH DXJPHQWHG QXFOHDU WUDQVORFDWLRQ RI
1)ț%LQ+89(&V&DY &DYHROLQ PLFHDQG&DYNQRFNGRZQFHOOVKDG
reduced leukocyte adhesion and adhesion molecule gene expression in response
WR71)ĮVWLPXODWLRQ)XUWKHUPRUHLQFUHDVHGSUHVVXUH PP+J VLJQL¿FDQWO\UHGXFHGWKHQXPEHURIFDYHRODHSHU—POHQJWKRIPHPEUDQHPHDVXUHGYLD
electron microscopy, when compared to 0 and 80 mmHg. Aortic sinus lesions
from BPHxApoe-/- mice had greater lipid deposition (Oil Red O; P<0.05) and
macrophage content (CD68; P<0.05) compared to Apoe-/- mice, indicative of
UHGXFHGSODTXHVWDELOLW\)XUWKHUPRUHDQWLLQÀDPPDWRU\WKHUDS\LQWKHSUHVHQFH
of hypertension, partially improved plaque stability, increasing plaque collagen
content.
Conclusions: +LJKLQWUDOXPLQDOSUHVVXUHLQGXFHVYDVFXODULQÀDPPDWLRQE\SURPRWLQJ FDYHRODH ÀDWWHQLQJ 1$'3+ R[LGDVH GHSHQGHQW 526 SURGXFWLRQ DQG
1)ț% WUDQVORFDWLRQ ZKLFK DOO FRQWULEXWH WR HQGRWKHOLDO DFWLYDWLRQ DGKHVLRQ
molecule expression and enhanced leukocyte adhesion. Furthermore, chronic
high blood pressure reduces plaque stability, which in the presence of hypertenVLRQLVSDUWLDOO\LPSURYHGE\DQWLLQÀDPPDWRU\WKHUDS\
5C.06
SYNERGISTIC INHIBITORY EFFECT OF
ROSUVASTATIN AND AN AT2 RECEPTOR AGONIST
ON VASCULAR REMODELING
H. Bai 1, M. Mogi 1, H. Nakaoka 1, H. Kan-No 1, K. Tsukuda 1, K. Ohshima 2,
T. Chisaka 3, X. Wang 1, L. Min 1, J. Iwanami 1, M. Horiuchi 1. 1 Ehime
University, Graduate School of Medicine, Department of Molecular
Cardiovascular Biology and Pharmacology, Toon, JAPAN, 2 Ehime University,
Graduate School of Medicine, Department of Cardiology, Pulmonology,
Hypertension and Nephrology, Toon, JAPAN, 3 Ehime University, Graduate
School of Medicine, Department of Pediatrics, Toon, JAPAN
Objective: Accumulating evidence suggest that direct angiotensin II type
2 (AT2) receptor stimulation a role in preventing cardiovascular remodeling.
Here, we investigate the possibility that co-administration of statin and compound 21 (C21), a newly generated selective AT2 receptor agonist, could exert
synergistic preventive effects on vascular injury.
Design and method: Vascular injury was induced by polyethylene cuff-placement on the femoral artery in male nine-week-old C57BL/6J mice. Mice were
treated with rosuvastatin administered orally (0.5 or 5 mg/kg/day), and/or with
&LQMHFWHGLQWUDSHULWRQHDOO\ RUȝJNJGD\ DIWHUFXIISODFHPHQW1HRLQtima formation was determined 14 days after operation by Elastica van Gieson
staining. Cell proliferation, superoxide anion production and mRNA expressions
RILQÀDPPDWRU\F\WRNLQHVGD\VDIWHUFXIISODFHPHQWZHUHHYDOXDWHGE\SURliferating cell nuclear antigen (PCNA) staining, dihydroethidium staining, and
real-time quantitative RT-PCR respectively.
Results: Systolic blood pressure before and after treatment did not differ sigQL¿FDQWO\LQHDFKJURXS1HRLQWLPDIRUPDWLRQZDVVLJQL¿FDQWO\DWWHQXDWHGE\
WKHWUHDWPHQWRIURVXYDVWDWLQ PJNJGD\ RU& ȝJNJGD\ DVVRFLDWHG
with the decreases in PCNA labeling index, superoxide anion production and
H[SUHVVLRQRILQÀDPPDWLRQPDUNHUVVXFKDV0&3H[SUHVVLRQDQGLWVUHFHSWRU&&5,/ȕDQG71)Į7UHDWPHQWZLWKQRQHIIHFWLYHGRVHVRIURVXYDVWDWLQ PJNJGD\ SOXV& ȝJNJGD\ VLJQL¿FDQWO\LQKLELWHGQHRLQWLPD
formation, PCNA labeling index, superoxide anion production and the mRNA
H[SUHVVLRQRILQÀDPPDWLRQPDUNHUV$7UHFHSWRUP51$H[SUHVVLRQGLGQRW
differ in each group, while AT2 receptor mRNA expression was increased by
DGPLQLVWUDWLRQRI&DWWKHGRVHRIȝJNJGD\EXWQRWE\&DWWKHGRVH
RIȝJNJGD\+RZHYHU$7UHFHSWRUP51$H[SUHVVLRQZDVLQFUHDVHGE\
co-administration of rosuvastatin (0.5 mg/kg/day). Vascular protective effects
RIFRPELQDWLRQRIURVXYDVWDWLQDQG&ZHUHEOXQWHGLQ$7UHFHSWRUGH¿FLHQW
mice.
Conclusions: Combination of rosuvastatin and AT2 receptor agonist exerted
synergistic preventive effects on vascular remodeling and could be a powerful
approach to prevent vascular disease.
5C.07
PROGNOSTIC IMPORTANCE OF ATHEROSCLEROSIS
AND ARTERIOSCLEROSIS PREVALENCE IN A
HEALTHY DANISH POPULATION
R. Kruger 1, S. Vikström Greve 2, M. Blicher 2, M. Pareek 2, T. Sehestedt 3,
J. Vishram 4, T. Jørgensen 4, M.H. Olsen 1,2. 1 Hypertension in Africa Research
Team (HART), North-West University, Potchefstroom, SOUTH AFRICA,
2
Cardiovascular Prevention Clinic, Department of Endocrinology, Odense
University Hospital, Odense, DENMARK, 3 Department of Cardiology,
Herlev University Hospital, Copenhagen, DENMARK, 4 Research Centre
for Prevention and Health, Glostrup University Hospital, Copenhagen,
DENMARK
Objective: To explore the independent predictive value of arteriosclerosis assessed as carotid-femoral pulse wave velocity (PWV) and of atherosclerosis assessed as presence of atherosclerotic plaques measured by carotid ultrasound
and investigate whether arteriosclerosis increases the risk associated with atherosclerosis.
Design and method: A group of 2115 apparently healthy subjects, aged 41, 51,
e68
Journal of Hypertension Volume 32, e-Supplement 1, 2014
61 and 71 years, examined in 1993, were included in this study. In 2006 the composite endpoint (CEP) of cardiovascular death, non-fatal myocardial infarction,
non-fatal stroke and hospitalization for ischemic heart disease was recorded.
Results: After adjusting in multiple Cox regression analyses for age, gender,
smoking, waist circumference, systolic blood pressure, heart rate, total cholesterol, high density lipoprotein cholesterol, triglycerides, insulin and gluFRVH ERWK 3:9 +5 ± S DQG DWKHURVFOHURWLF SODTXHV
+5 ± S LQGHSHQGHQWO\SUHGLFWHG&(3ZLWKRXWDQ\LQteraction. After stratifying for age and gender, PWV predicted CEP in men aged
\HDUV +5 ± S DQGZRPHQDJHG\HDUV +5 ± S ZKHUHDV SUHVHQFH RI DWKHURVFOHURWLF SODTXHV SUHGLFWHG
&(3 LQ PHQ DJHG +5 ± S +5 ±
S DQG\HDUV +5 ± S DQGLQZRPHQDJHG
+5 ± S +5 ± S DQG
\HDUV +5 ± S $SURJQRVWLFLQWHUDFWLRQEHWZHHQ3:9
and atherosclerotic plaques was only seen in women aged 71 years (HR=1.06
± S Conclusions: In an apparently healthy Danish population arteriosclerosis measured by PVW and atherosclerosis measured by carotid ultrasound carry additive
SURJQRVWLFLQIRUPDWLRQZLWKRXWVLJQL¿FDQWLQWHUDFWLRQ
Abstracts
e69
ORAL SESSION
ORAL SESSION 5D
ENDOTHELIUM AND MICROCIRCULATION
5D.01
RETINAL MICROPERFUSION ONE YEAR AFTER
RENAL ARTERY DENERVATION IN TREATMENT
RESISTANT HYPERTENSIVE PATIENTS
R.E. Schmieder 1, C. Ott 1, M. Uder 2, A. Schmid 2, A. Jumar 1, G. Michelson 3,
J. Harazny 1, 4. 1 Nephrology and Hypertension, University Hospital,
Erlangen, GERMANY, 2 Diagnostic Radiology, University Hospital, Erlangen,
GERMANY, 3 Ophthalmology, University Hospital, Erlangen, GERMANY,
4
Department of Pathophysiology, Warmia and Masury University, Olsztyn,
POLAND
Objective: 5HWLQDOPLFURSHUIXVLRQRIWHQFRQVLGHUHGWRUHÀHFWFHUHEUDOPLFURS
erfusion can be measured in humans non-invasively. The current analysis aimed
at measuring retinal capillary perfusion before, 6 months, and one year after renal denervation (RDN) in patients with treatment resistant hypertension (TRH).
Design and method: Three retinal capillary perfusion (RCF) images were taken
non-invasively by Heidelberg Retina Flowmetry in the right non-mydriatic eye
RI 0) K\SHUWHQVLYHSDWLHQWV DJH“\HDUV EHIRUH 0 DQG
0 PRQWKVDIWHU5'1$OOSDWLHQWVKDG75+DFFRUGLQJWRWKHGH¿QLWLRQE\
2013 ESH/ESC guidelines. Flow images were analysed by AFFPIA V.4.011 and
mean RCF of 3 images were calculated. RCF in the systole and diastole could
also be determined in 56 patients from the best image of the 3 RCF pulse curves.
3XOVHG5&) V\VWROLF5&)±GLDVWROLF5&) ZDVFDOFXODWHGVLQFHDQLQFUHDVHLQ
systolic RCF and pulsed RCF increases shear stress on the retinal endothelium
leading to endothelial dysfunction. To date, 60 patients were successfully followed up over one year. For comparison, non parametric tests for paired samples
were used (SPSS V.19).
Results: 6\VWROLFDQGGLDVWROLFRI¿FHEORRGSUHVVXUH %3 GHFUHDVHGVLJQL¿FDQWO\
6M after RDN (143±18 / 80±11mmHg, p<0.001) and 12M after RDN (141±19
/ 80±13mmHg, p<0.001) compared to baseline values (155±21 / 85±14mmHg).
+HDUWUDWH +5 GHFUHDVHGVLJQL¿FDQWO\IURP“EPSWR“EPS0DIWHU
RDN (p=0.044) and to 66±14bmp 12M after RDN (p<0.001). 24-h ambulatory
BP was reduced after 6 months (145±15 / 81±9mmHg, p<0.001) and 12 months
(145±15 / 81±11 mmHg, p<0.001) compared to baseline (155±86 / 86±13
mmHg).
The retinal microperfusion data are demonstrated in table 1.
Conclusions: In hypertensive patients with TRH, we observed decrease of systolic and pulsed RCF 6 and 12 months after RDN, in parallel to decreases of BP
and HR. An increase of pulsed RCF is related to less shear stress on the vascular
wall and indicative of impaired microvascular function. Hence, the reduction
of pulsed RCF after RDN suggests an improvement of retinal (and potentially
cerebral) microcirculation.
5D.02
DELETION OF OSTEOGLYCIN GENE PROMOTES
ISCHEMIA-INDUCED BLOOD FLOW RECOVERY VIA
MODULATING REDOX BALANCE
Q. Wu 1, X. Liu 2, P. Gao 3, Y. Ma 4. 1 Shanghai Key Laboratory of
Hypertension and Department of Hypertension, Ruijin Hospital, Shanghai,
CHINA, 2 Laboratory of Vascular Biology and Key Laboratory of Stem Cell
Biology, Institute of Health Sciences, Shanghai, CHINA, 3 Shanghai Institute of
Hypertension, Shanghai Jiao Tong University School of Medicine, Shanghai,
CHINA
Objective: Osteoglycin (OGN) plays important roles in bone formation by os-
teoblasts as a bone anabolic factor. However, the relationship between OGN and
vascular injury remains unknown. We therefore sought to investigate the effect
of the deletion of the OGN gene on ischemia-induced angiogenesis and address
the underlying mechanisms.
Design and method: Limb ischemia model was established in OGN-/- (n=12)
and wild type (n=12) mice. Perfusion recovery was estimated by Laser Doppler imaging, and capillary formation in gastrocnemicus muscle was detected by
&'LPPXQRÀXRUHVFHQFHVWDLQLQJ,QYLWURVWXGLHVWXEHIRUPDWLRQLQPDWULJHO
and transwell assays of human umbilical vein endothelial cells (HUVECs) were
performed when OGN was knocked down by siRNA. Intracellular ROS accuPXODWLRQZDVVWDLQHGE\¶¶GLFKORURÀXRUHVFLQGLDFHWDWHDQGWKHFKDQJHVRI
NADPH oxidases (NOX) family were measured by real-time PCR and western
blot.
Results: 7KH EORRG ÀRZ UHFRYHU\ RI ZLOG W\SH PLFH ZDV DQG
69.6% respectively at day4, day7 and day14 after limb ischemia, while that
of OGN -/- mice was 45.5%, 70.9%, and 80.6%. Capillary density was also
higher in OGN -/- mice in the gastrocnemicus muscle of the ischemia limb.
Tube formation was promoted in OGN knockdown group (41.3±2.906 value),
compared with negative control group (17±2.028 value p<0.01) and migration
was also enhanced in OGN knockdown group (55.33±5.70 cells per scope vs.
16.67±2.72 cells per scope p<0.01). ROS was accumulated and NOX family
(NOX1, NOX2, NOX4 and p22phox) was up-regulated in the OGN knockdown
JURXSEXWRQO\12;DQG12;ZHUHVLJQL¿FDQWO\FKDQJHG3DQLQKLELWLRQRI
NOX family reversed the tube formation induced by OGN knockdown.
Conclusions: This study demonstrates the crucial roles of OGN in the setting
of ischemia-induced angiogenesis through enhancing the tube formation and
migration of endothelial cells. This phenomenon may be correlated with the
up-regulation of oxidative stress and the increased expression of NOX family.
5D.03
INTEGRIN-MEDIATED ADHESION IN ACUTE
MYOCARDIAL INFARCTION PATIENTS
C. Bueno-Beti 1, D. Perez-Cremades 1, A. Mompeon 1, X. Vidal-Gomez 2,
M. Heras 3, J. Sanchis 4, C. Hermenegildo 1,2, S. Novella 1,2. 1 Dept. Physiology,
Univ. Valencia, Valencia, SPAIN, 2 INCLIVA Biomedical Research Institute,
Valencia, SPAIN, 3 IDIBAPS and Inst. Clinic Torax, Barcelona, SPAIN,
4
Cardiology Department, Hospital Clínico of Valencia, Univ. Valencia,
Valencia, SPAIN
Objective: Acute myocardial infarction (AMI) leads to the mobilization of
endothelial progenitor cells (EPCs) from the bone marrow to promote the revascularization of ischemic tissue. EPCs are recruited to sites of ischemia by
a mechanism known as “homing” mainly mediated by integrins, a family of
transmembrane receptors related to the attachment of endothelial cells to extraFHOOXODUPDWUL[7RNQRZWKHVSHFL¿FUROHRILQWHJULQVLQWKHDGKHVLRQRI(3&
FRXOGEHDQLPSRUWDQWVWHSLQWKHHI¿FLHQF\RIUHYDVFXODUL]DWLRQ7KXVRXUDLP
is to study EPC mobilization and the integrin expression related to adhesion in
EPCs from AMI patients after 30 days of infarction.
Design and method: Healthy individuals (n=8) and AMI patients (n=8) were
recruited. EPC mobilization was determined by measuring levels of circulating
(3&E\ÀRZF\WRPHWU\DV&'.'5&'FHOOV)XQFWLRQDOEHKDYLRUZDV
assessed in cultured EPC obtained from peripheral blood mononuclear cells by
Lymphoprep density gradient. Adhesion was determined by seeding 5x104 cells
RQWR¿EURQHFWLQWUHDWHGSODWHVIRUPLQ([SUHVVLRQOHYHOVRISRWHQWLDOO\LQ
YROYHGLQWHJULQVLQKRPLQJSURFHVV ĮĮĮĮ9‰‰‰ ZHUHWHVWHGE\
immunoblotting.
Results: Circulating EPC increased in AMI patients (648.5 cells/mL) compared
to healthy individuals (66.5 cells/mL) up to 9.75-fold (p<0.01). Cultured EPC
from AMI patients showed a 1.5-fold increment (35.46% for AMI patients vs.
IRUFRQWUROV3 LQWKHLUDELOLW\WRDGKHUHWRWKH¿EURQHFWLQPDWUL[
$QLQFUHPHQWLQSURWHLQH[SUHVVLRQZDVIRXQGRQO\IRULQWHJULQVĮĮ9‰DQG
‰
Conclusions: Circulating EPC mobilization and adhesion properties of cultured
EPC are increased and maintained 30 days after suffering an AMI. The increment in the protein expression indicates that the reendothelialization process
FRXOGEHUHODWHGWRLQWHJULQVĮĮ9‰DQG‰LQ$0,SDWLHQWV
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e70
Journal of Hypertension Volume 32, e-Supplement 1, 2014
5D.04
ASSOCIATIONS BETWEEN THE RETINAL
MICROCIRCULATION AND 24-HOUR AMBULATORY
PULSE WAVE VELOCITY: A PILOT STUDY IN
HYPERTENSIVE AND NORMOTENSIVE INDIVIDUALS
E. Aissopou 1, A. Argyris 1, M. Papathanassiou 2, E. Nasothimiou 1,
G. Konstantonis 1, K. Tampakis 1, N. Tentolouris 3, P. Theodosiadis 2,
T. Papaioannou 4, 36¿NDNLV1, A. Protogerou 1. 1 Hypertension Unit and
Cardiovascular Research Laboratory, 1st Department of Propaedeutic
Internal Medicine, Laiko Hospital, Athens, GREECE, 2 2nd Department
of Ophthalmology, Attikon University Hospital, Athens, GREECE, 3 1st
Department of Propaedeutic and Internal Medicine, Athens University Medical
School, Laiko Hospital, Athens, GREECE, 4 Biomedical Engineering Unit,
1st University Department of Cardiology, Hippokration Hospital, Athens,
GREECE
Objective: Early remodeling of the retinal microcirculation can be evaluated
by potential cardiovascular risk biomarkers, namely, central retinal arteriolar
equivalent (CRAE), central retinal venular equivalent (CRVE) and arteriolar to
venular ratio (AVR). Herein, we tested the hypothesis that in normotensive and
hypertensive individuals the early changes in retinal vessels are associated with
arterial stiffness, as assessed by carotid to femoral pulse wave velocity (cfPWV)
DWUHVWDVZHOODVIRUWKH¿UVWWLPHZLWKDPEXODWRU\KRXU3:9
Design and method: In 107 individuals without diabetes, cardiovascular disease, aged 53.7 ± 12.67 years (men 51.4%; hypertension in 79.4%) we obtained
digital retinal images from both eyes (n=214) and the CRAE, CRVE and AVR
were measured with a validated software. Static cfPWV (m/sec) was measured
by tonometry and 24-hour ambulatory PWV was assessed by a novel validated
automatic oscillometric brachial cuff-based device (Mobil-O-Graph, IEM).
Results: All stiffness biomarkers (cfPWV 8.87±1.95; 24-hourPWV 7.90±1.87,
DZDNH3:9 “ DVOHHS3:9 “PVHF SURYLGHG VLJQL¿FDQW DVsociations with CRAE, CRVE and AVR which were even stronger in eyes of
normotensive individuals (Table). After adjusting for age, gender and blood
SUHVVXUHRQO\WKHDPEXODWRU\3:9ZDVDVVRFLDWHGWR&59( ȕ S at the total population.
Conclusions: Increased arterial stiffness is strongly associated with remodeling
of the retinal microcirculation at early stages, even in normotensive individuals,
with no or mild retinopathy. Only the ambulatory PWV provided age and pressure independent associations indicating that it may be useful for investigating
the pathophysiology of hypertensive retinopathy in prospective studies.
5D.05
RETINAL ARTERIOLAR REMODELING AS ASSESSED
BY ADAPTATIVE OPTICS IS LINKED TO LEFT
VENTRICLE REMODELING IN HYPERTENSION
D. Rosenbaum 1, E. Koch 2, N. Kachenoura 3, A. Redheuil 3, P. Cluzel 4,
M. Paques 2, X. Girerd 1. 1 Unité de Prévention des Maladies
Cardiovasculaires, Pitié Salpêtrière Hospital, Paris, FRANCE, 2 Institut de la
Vision, CIC des 15/20, Paris, FRANCE, 3 Laboratoire d’Imagerie Biomédicale,
UPMC INSERM U 678, Paris, FRANCE, 4 Département d’Imagerie
Cardiovasculaire, Pitié Salpêtrière Hospital, Paris, FRANCE
Objective: Hypertension is associated with ventricular and arteriolar remodelling with an increase in wall thickness and a decrease in lumen diameter. The
aim of our study was to show the relationships between these 2 territories using
cardiovascular MRI and retinal imaging by adaptative optics (AO).
Design and method: Left Ventricle Mass/Volume ratio (M/V) was calculated
using telediastolic masses and volumes semi-automatically obtained using the
QMASS ® software on small axis Cine sequences acquired on a 1.5 Tesla MRI
(Siemens®). Retinal images obtained by AO examination were semi-automatically analyzed to obtain the Wall/Lumen ratio (WLR) on the temporal superior
artery. Ascending aortic diameters and strain were calculated using the ARTFUN
software ® and an automated segmentation of SSFP cine acquisitions acquired
in the axial view, during breath-holding, at the level of pulmonary bifurcation
perpendicular to the aorta. Aortic strain was used to calculate aortic distensibility
LQHDFKVXEMHFWGLVWHQVLELOLW\ $' VWUDLQF33ZKHUHF33LVWKHFHQWUDOSXOVH
pressure obtained by tonometry (sphygmocor ®). Home and central blood pressures (BP) levels were recorded.
Results: Population included 55 treated hypertensives patients in primary prevention (mean age 53.4years) and 16 normotensive subjects matched for age/
gender/body mass index/Hba1c and smoking status. Male proportion was 55.5%
and 50% of hypertensives had uncontrolled home BP (122/76 vs. 150/94mmHg
p<.01). Remodeling was present in both territories. WLR was increased with
respectively .335 and .303 vs. 26.7 (p<.001) in uncontrolled hypertensives, controlled hypertensives and untreated normotensives. M/V was higher in uncontrolled hypertensives (4.61) and differed from controlled hypertensives (4.02
p<.05) and untreated normotensives (3.65 p<.001). AD was different in the 3
groups (p<.03) with 33.2, 24.2 and 18.1 10-3kPa-1 in untreated subjects, controlled and uncontrolled hypertensives respectively. In univariate analysis, age,
gender, BMI, central and home BP were linked to M/V whereas only AD and
BP were linked to WLR. The strong correlation between M/V and WLR (R=.51,
p=.01) disappeared after adjustment for blood pressure levels
Conclusions: Arteriolar and ventricular remodelling are associated and linked
through BP levels. Retinal remodelling imaging by AO could represent a quick
and non invasive surrogate for myocardial remodelling.
5D.06
RENAL ARTERIOLAR INJURY BY SALT INTAKE
CAUSES ‘‘SALT MEMORY’’
O. Hideyo, H. Sasamura, K. Shinoda, S. Morita, H. Kono, K. Nakagawa,
K. Ishiguro, K. Hayashi, M. Nakamura, T. Azegami, M. Oya, H. Itoh.
Departments of Internal Medicine and Urology, School of Medicine, Keio
University, Tokyo, JAPAN
Objective: The mechanism of salt-intake in the development of hypertension
has not been fully elucidated. Our aim was to examine the effect of transient saltintake during the prehypertensive period in Dahl salt-sensitive rats (DS rats).
Design and method: (1) DS rats were fed from 6-14 weeks with high-salt and
high-salt with angiotensin-receptor-blocker (ARB), calcium-channel-blocker
(CCB), ARB+CCB, and returned to normal-salt with discontinuation of antihypertensive-agents for 3 months. (2) The kidney of DS rats fed with high-salt
from age 6-14 weeks and returned to normal-salt (salt-treated rats) were transplanted into rats fed with normal-salt (untreated rats) at the same age 14weeks
(n=3). Conversely, the kidney of untreated rats were transplanted into salt-treated rats (n=3).
Results: (1) Rats in the high-salt group caused elevation in blood pressure (BP)
not only during treatment period, but also for 3 months after returning to normalsalt, phenomenon which we named ‘salt memory’ (about 60 mmHg). Renal arteriolar injury and RAS activation were observed in the high-salt group at age
14 weeks and end of experiment. ARB did not induce BP reduction and caused
renal arteriolar damage, and after returning to normal-salt and discontinuation of
ARB, salt memory persisted in similar fashion to the high-salt group. Although
BP was suppressed to control levels by CCB, renal RAS activation and renal
DUWHULRODU LQMXU\ UHPDLQHG DQG VDOW PHPRU\ GLG QRW GLVDSSHDU &&%JURXS
“PP+J YV &RQWUROJURXS “PP+J &&%$5% VXSSUHVVHG UHQDO
arteriolar injury, resulting in loss of salt memory. (2) Kidney cross-transplantations from salt-treated rats to untreated rats caused increase of BP, whereas the
kidneys of untreated rats caused reduction in BP of hypertensive rats, suggesting
FHQWUDOUROHRINLGQH\7RFRQ¿UP%3FKDQJHDFFRPSDQLHGE\GHQHUYDWLRQZLWK
kidney transplantation or transplantation itself, we conducted kidney transplantation between salt-treated rats in which the same levels of salt memory were
FRQ¿UPHGDQGEHWZHHQXQWUHDWHGUDWVDQGQRPDMRUFKDQJHVLQ%3ZHUHVHHQ
Conclusions: Renal arteriolar injury through BP elevation and renal RAS activation play important role in the development of salt memory for hypertension.
.LGQH\ FURVVWUDQVSODQWDWLRQ VWXGLHV FRQ¿UPHG WKDW WKH PHPRU\ ZDV PDLQO\
localized in the kidney.
5D.07
ASSOCIATION OF ENDOTHELIAL DYSFUNCTION
WITH MICRO- AND MACRO-VASCULAR ALTERATIONS
IN ESSENTIAL HYPERTENSION
E. Gavriilaki 1, E. Gkaliagkousi 2, A. Triantafyllou 1, B. Nikolaidou 2,
F. Chatzopoulou 3, P. Anyfanti 2, X. Zabulis 4, S. Douma 1. 1 3rd Department
of Internal Medicine, Aristotle University of Thessaloniki, Thessaloniki,
GREECE, 2 2nd Prop. Department of Internal Medicine, Aristotle University of
Thessaloniki, Thessaloniki, GREECE, 3 Medical School, Aristotle University
of Thessaloniki, Thessaloniki, GREECE, 4 Institute of Computer Science,
Foundation for Research and Technology-Hellas, Heraklion, GREECE
e71
Journal of Hypertension Volume 32, e-Supplement 1, 2014
Objective: Asymmetric dimethylarginine (ADMA), an endogenous inhibitor
of endothelial nitric oxide synthase (NOS3), is a robust marker of endothelial
dysfunction and has been found elevated even in the early stages of essential
hypertension (EH). ADMA levels have been also implicated in micro- and macro-vascular changes observed in EH; however, available data are scant. The purpose of this study was to investigate the possible association between endothelial dysfunction and other markers of micro and macro-vascular damage, namely
indices of arterial stiffness and retinal vessel calibers in grade 1 EH.
Design and method: We enrolled consecutive patients with untreated recently
GLDJQRVHGJUDGH(+DQGQRVLJQL¿FDQWFRPRUELGLWLHV 8+ DQGFRQVHFXWLYH
age- and sex-matched normotensive (NT) individuals. Baseline characteristics
and routine laboratory results were recorded. 24-hour ABPM (Spacelabs 90207)
was applied to all patients. Applanation tonometry (Sphygmocor device) was
used to assess central pulse pressure (cPP) and pulse-wave velocity (PWV) according to a standard protocol. Retinal vascular calibers were estimated using
a computer-based program for retinal photographs taken with a non-mydriatic
digital fundus camera (NIDEK AFC-230/210). Central retinal artery (CRAE)
and vein (CRVE) equivalents, as well as arterio-venous ratio (AVR) were calculated to estimate retinal abnormalities.
Results: A total of 205 (155 UH and 50 NT) individuals aged 46.6±12.7 years
ZHUHVWXGLHG8+H[KLELWHGVLJQL¿FDQWO\LQFUHDVHG$'0$OHYHOV “YV
“ ȝPROO S DV ZHOO DV VLJQL¿FDQWO\ LQFUHDVHG F33 3:9 DQG
GHFUHDVHG&5$($'0$OHYHOVZHUHVLJQL¿FDQWO\FRUUHODWHGZLWKDOOWKHPHDsured markers of early vascular dysfunction such as cPP, PWV, CRVE and AVR.
By contrast, no association was observed with the traditional cardiovascular risk
IDFWRUV DJHJHQGHUVPRNLQJRI¿FHDQGDPEXODWRU\EORRGSUHVVXUHOLSLGSUR¿OH ,QWKHPXOWLYDULDWHDQDO\VLV&59( EHWD S DQGFHQWUDO33
(beta=0.215, p=0.005) proved the only independent predictors of ADMA levels.
Conclusions: 7RRXUNQRZOHGJHWKLVLVWKH¿UVWVWXG\WRGRFXPHQWDQLQGHSHQdent association between ADMA levels and indices of micro- and macro-vascular dysfunction in EH. Thus, endothelial dysfunction may be the common
denominator of micro- and macro-vascular alterations observed from the early
stages of EH.
5D.08
CYCLOOXYGENASE-2-DERIVED PROSTANOIDS
CONTRIBUTES TO ENDOTHELIAL DYSFUNCTION
IN SMALL VESSELS FROM PATIENTS WITH
PHEOCHROMOCYTOMA
A. Virdis 1, E. Duranti 1, U. Dell’Agnello 1, D. Carrara 1, A. Bacca 1,
G. Materazzi 2, G. Bernini 1, S. Taddei 1. 1 Department of Clinical and
Experimental Medicine, University of Pisa, Pisa, ITALY, 2 Department of
Surgery, University of Pisa, Pisa, ITALY
Objective: Peripheral microcirculation of patients with pheochromocytoma
(Pheo) shows an impaired endothelial function. The exact mechanism underlying this alteration remains unknown. In this study we assessed the role of the
two cyclooxygenase (COX) isoforms (COX-1 and COX-2) as determinants of
endothelial dysfunction in isolated small resistance arteries taken from the periadrenal visceral fat from Pheo patients (n=7) vs control subjects (NT, n=6).
Design and method: Each subject underwent a biopsy of the visceral fat during
laparoscopic surgery. Small arteries were investigated on a pressurized micromyograph. Endothelium-dependent vasodilation (VD) was assessed by acetylcholine (ACh)-induced relaxation. ACh was also repeated in the presence of
L-NAME (NO synthase inhibitor), SC-560 (COX-1 inhibitor), DuP 697 (COX-2
inhibitor) or SQ-29548 (TP receptors antagonist). Protein expression of COX
isoforms was determined by Western Blot (WB). Release of COX-derived pros-
WDQRLGVVXFKDVNHWRSURVWDJODQGLQ 3* )ĮDQGLVRSURVWDQH ,3 ZDVGHtermined by immunoenzymatic assay (EIA) either under basal condition or after
incubation with SC-560 or Dup 697.
Results: In NT, maximal VD to ACh (95.1±1.8%) was blunted by L-NAME
“ 3 DQG QRW PRGL¿HG E\ 6& “ RU 'X3 (94.9±0.8%). In Pheo, VD to ACh was blunted vs NT (53.8±1.1%; P<0.001),
resistant to L-NAME (45.6±0.6%; P<0.001 vs NT), not affected by SC-560
“ EXW VLJQL¿FDQWO\ SRWHQWLDWHG 3 E\ 'X3 “ SQ-29548 (75.2±1.6%) or their co-administration (75.0±1.9%). Pheo showed a
VLJQL¿FDQWRYHUH[SUHVVLRQRI&2;DQGJUHDWHUUHOHDVHRI,3WKDWZDVVHQsitive to the effect of Dup 697 but resistant to SC-560. Pheo showed a similar
UHOHDVHRINHWR3*)ĮYV17WKDWZDVQRWPRGL¿HGE\LQKLELWLRQRI&2;
isoforms.
Conclusions: Small resistance vessels from Pheo show a marked endothelial
dysfunction with a reduced availability of NO. COX-2 overexpression plays an
important role in this alteration in a receptor-dependent manner by the production of vasoconstrictor prostanoids, such as 8-IP.
5D.09
EFFECT OF COMBINATION OF TELMISARTAN AND
ATORVASTATIN ON ANGIOGENIC RESPONSIVENESS
IN CORONARY ENDOTHELIAL CELLS OF ISCHEMIA
REPERFUSED RAT HEART
K. Chaudagar 1,2, A. Mehta 2, N. Tribulova 1. 1 Institute for Heart Research,
SAV, Bratislava, SLOVAK REPUBLIC, 2 L. M. College of Pharmacy,
Ahmedabad, INDIA
Objective: It is well known that endothelial dysfunction is associated with diseases, such as hypertension, dislipidemia and diabetes. Clinical trial indicated
that VEGF induced therapeutic angiogenesis in no option patients failed to
promote neovascularization that may be related to endothelial dysfunctioning.
Telmisartan and atorvastatin increased angiogenic responsiveness of disturbed
coronary endothelial cells in our previous study. Therefore, our objective was to
study effect of telmisartan and atorvastatin combined treatment on vascular endothelial growth factor (VEGF) induced angiogenic responsiveness in coronary
endothelial cells (VEGF-ang-r-cEC).
Design and method: Adult, male Wistar rats were divided into following
groups, normal rats, 30 and 60 days STZ-diabetic rats; they were further subgroups into telmisartan or atorvastatin or telmisartan and atorvastatin treated
rats. Each subgroup were underwent either sham injury or ischemia reperfusion
injury. Coronary endothelial cells (cEC) were isolated from each subgroup for
study of angiogenic responsiveness and nitric oxide (NO) releasing properties
using CAM assay and Griess method, respectively.
Results: &RPELQDWLRQWUHDWPHQWRIWHOPLVDUWDQDQGDWRUYDVWDWLQVKRZHGVLJQL¿cant increase in VEGF-ang-r-cEC and VEGF induced NO release as compared
to their respective non-treated or telmisartan or atorvastatin treated groups. The
FRPELQHG HIIHFWV RI WHOPLVDUWDQ DQG DWRUYDVWDWLQ ZHUH VLJQL¿FDQWO\ LQKLELWHG
by pretreatment of cECs with endothelial nitric oxide synthase (eNOS) inhibitor, NG-nitro-l-arginine methylester (l-NAME) and Phosphoinositide-3-kinase
(PI3K) inhibitor, wortmannin. Protein kinase-C (PKC) inhibitor, chelerythrine,
GLGQRWVKRZDQ\VLJQL¿FDQWFKDQJHV
Conclusions: Our data suggest that combination of telmisartan and atorvastatin
improves coronary angiogenic activity in normal and diabetic rats via activation
of VEGF/PI3K/eNOS/NO pathway. Results revealed novel pleiotropic effects
of drugs that are frequently used in patients with metabolic syndrome to treat
hypertension and dyslipidemia.
Abstracts
e72
ORAL SESSION
ORAL SESSION 6A
PREGNANCY, CHILDREN
AND ADOLESCENTS
6A.01
ARTERIAL STIFFNESS IS INCREASED IN YOUNG
SUBJECTS WITH MASKED CENTRAL HYPERTENSION
S. Totaro 1, P. Khoury 2, T. Kimball 2, L. Dolan 2, E. Urbina 2. 1 Department
of Medical Sciences, University of Turin, Turin, ITALY, 2 Cincinnati Children
Hospital and University of Cincinnati, Cincinnati, OH, USA
Objective: Central aortic blood pressure (BP) is predictive of cardiovascular
risk in adults, but there is a paucity of data regarding its relation to arterial stiffness (AS) and target organ damage (TOD) in young. Information on masked
central hypertension (MH) is also lacking.
Aim: To elucidate determinants of MH and to evaluate the relation between high
central BP, AS and measures of TOD.
Design and method: Anthropometrics, lab data, brachial and central BP
(SphygmoCor, AtCor Medical, Sydney, Australia) were obtained on 430 normotensive subjects (NT) (16-24 years, 34% male, 44% Caucasian, 27% type-2 diaEHWHV7'0 17ZDVGH¿QHGDVQRUPDOEUDFKLDO%3 WK5HSRUWRU-1& DQG
QRUPDOFHQWUDO%3 IRURXUOHDQFRQWUROV 0+ZDVGH¿QHGDVHOHYDWHG
central BP, with normal brachial BP.
ANOVA was performed to determine differences in covariates and TOD between NT and MH. General linear models were created to see if central BP was
an independent determinant of TOD.
of Valencia, Valencia, SPAIN, 2 CIBER Fisiopatología Obesidad y Nutrición
(CB06/03), Instituto de Salud Carlos III, Madrid, SPAIN, 3 Hypertension
Clinic, Hospital Clinico, INCLIVA, University of Valencia, Valencia, SPAIN
Objective: 7RDVVHVVWKHLPSDFWRIELUWKZHLJKW %: DQGSRVWQDWDOZHLJKWJDLQ
RQEORRGSUHVVXUH %3 DQGPHWDEROLFSUR¿OHGXULQJWKH¿UVW¿YH\HDUVRIOLIH
Design and method: One hundred and thirty nine newborns (63 females) born
at term after uncomplicated pregnancies and in the absence of perinatal illness
were included. Subjects were divided according to size at birth in small, appropriate, and large for gestational age. After the initial evaluation on the second
day of life, infants were followed up at 6 months, 2 and 5 years. Anthropometric
parameters and BP were measured at each visit and metabolic assessment was
SHUIRUPHGDW¿YH\HDUVRIDJH
Results: In relation to the general characteristics of the mothers, there were no
GLIIHUHQFHV DPRQJ JURXSV UHJDUGLQJ PRWKHU¶V DJH PHDQ DJH “ \HDUV
S VPRNLQJKDELWV QRVPRNHUVDQGKHDY\VPRNHUVS DQG ZHLJKW JDLQ GXULQJ SUHJQDQF\ PHDQ “ NJ S ,Q FKLOGUHQ
RYHUDOOZHLJKWJDLQGXULQJWKH¿UVWPRQWKVDQG\HDUVZHUH“NJ
“NJDQG“NJUHVSHFWLYHO\1RGLIIHUHQFHVLQZHLJKWJDLQZHUH
REVHUYHGDPRQJWKHWKUHH%:FDWHJRULHVDWDQ\WLPHPRQWKVRU\HDUV
Birth weight was a positive determinant of systolic BP at birth, afterwards curUHQWZHLJKWZDVWKHVWURQJHVWGHWHUPLQDQWEHFRPLQJVLJQL¿FDQWDW\HDUVRIDJH
DQGSURJUHVVLYHO\LQFUHDVLQJLWVLQÀXHQFH$W¿YH\HDUVLQVXOLQ+20$LQGH[
DQGWULJO\FHULGHVZHUHGHSHQGHQWRQ%:FXUUHQWZHLJKWDQGSRVWQDWDOZHLJKW
JDLQ7KHFRQFXUUHQWLQÀXHQFHRIERWK%:DQGFXUUHQWZHLJKWRQ+20$LQGH[
LVVKRZQLQWKH¿JXUH,QDGGLWLRQ%:ZDVSRVLWLYHO\DVVRFLDWHGWR+'/FKROHVterol and inversely to uric acid. A positive relationship among insulin, BP values
and uric acid, was observed even early in life.
Results: There were 397 NT (84%) and 77 (16%) MH subjects. MH were more
frequently female, African-American, and had a higher prevalence of obesity
DQG7'0DPRUHDGYHUVHPHWDEROLFSUR¿OHDQGKLJKHUOHYHOVRILQÀDPPDWLRQ
FRPSDUHGWR170+KDGVLJQL¿FDQWO\KLJKHUEUDFKLDO%3 WKRXJKVWLOOLQQRUPDO
range), higher central pulse pressure and heart rate compared to NT.
0+ZDVVLJQL¿FDQWO\DVVRFLDWHGZLWKKLJKHU$6 3:9“YV“P
VHFS DQGORZHUEUDFKLDOGLVWHQVLELOLW\ YVFKDQJHPP+J
S FRPSDUHGWR17 )LJXUH 7KHUHODWLRQUHPDLQHGVLJQL¿FDQWZLWK
higher AS in MH when compared to the control group matched for age, sex,
%0,REHVLW\7'0DQGPHDQDUWHULDO%3 S3:9%UDFK' 7KH
VLJQL¿FDQW GLIIHUHQFH LQ OHIW YHQWULFXODU PDVV S FDURWLG LQWLPD PHGLD
thickness (p=0.02) and Augmentation Index (p<.0001) was lost in the matched
controls analysis.
Conclusions: Female sex, African-American race and the presence of recognized cardiovascular risk-factors including brachial BP in the high-normal
range, identify a group of conventionally normotensive patients who have elevated central BP. This pattern of MH is related to increased AS and a more
adverse TOD pattern.
Conclusions: Acceleration of early infant weight gain may aggravate the effects
RIORZ%:0XOWLSOHLQWHUDFWLRQVEHWZHHQKHPRG\QDPLFDQGPHWDEROLFSDUDPeters foresee the clustering of cardiometabolic risk factors later in life.
6A.03
CARDIOVASCULAR EVENTS IN WOMEN WITH A
HISTORY OF PRE-ECLAMPSIA IN THE GENERATION
SCOTLAND: SCOTTISH FAMILY HEALTH STUDY
D. Carty 1, C. Brown 1, 65RELQVRQ1, M. Schneider 1, S. Kerr 2, P. Linksted 2,
A. Campbell 2, A.F. Dominiczak 1, S. Padmanabhan 1, C. Delles 1, Generation
Scotland 3. 1 Institute of Cardiovascular and Medical Sciences, University of
Glasgow, Glasgow, UNITED KINGDOM, 2 Centre for Molecular Medicine,
University of Edinburgh, Edinburgh, UNITED KINGDOM, 3 A Collaboration
between the University Medical Schools and NHS in Aberdeen, Dundee,
Edinburgh and Glasgow, UNITED KINGDOM
6A.02
ASSOCIATIONS OF BIRTH WEIGHT AND POSTNATAL
WEIGHT GAIN WITH CARDIOMETABOLIC RISK
PARAMETERS AT FIVE YEARS OF AGE
E. Lurbe 1,2, C. Garcia-Vicent 1, M. Torró 1,2, F. Aguilar 1,2, -ÈOYDUH]1,2,
-5HGRQ 2,3. 1 Pediatric Department, Consorcio Hospital General, University
Objective: :RPHQZLWKDKLVWRU\RISUHHFODPSVLDDUHUHSRUWHGWRKDYHDQLQFUHDVHG ULVN RI IXWXUH FDUGLRYDVFXODU &9 GLVHDVH DQG GHDWK PRQLWRULQJ DQG
HDUO\WUHDWPHQWRIDIIHFWHGZRPHQKDYHEHHQSURSRVHG:HDLPHGWRGHWHUPLQH
the frequency of CV events in women with a history of pre-eclampsia from the
Generation Scotland: Scottish Family Health Study (GS:SFHS).
Design and method: Over 24,000 adults were recruited between 2006-11 for
S
U
N
D
A
Y
O
R
A
L
S
e73
Journal of Hypertension Volume 32, e-Supplement 1, 2014
GS:SFHS, a Scotland-wide population-based study. Data on hospital admissions
605 DQGPDWHUQLW\DGPLVVLRQV 605 GDWLQJEDFNWRZHUHREtained from Information Services Division NHS Scotland. ICD-9 and -10 codes
IRUPRGHUDWHDQGVHYHUHK\SHUWHQVLRQZLWKSURWHLQXULDZHUHXVHGWRGH¿QHSUH
HFODPSVLDSULPDU\GLDJQRVLVFRGHVIRULVFKDHPLFKHDUWGLVHDVHFHUHEURYDVFXODU
disease, hypertension, pulmonary vascular and peripheral vascular disease were
used to classify CV outcomes. CV event rates were compared between women
with and without a history of pre-eclampsia.
Results: 5HFRUGOLQNDJHDQDO\VLVZDVDYDLODEOHIRUSUHJQDQFLHVEHWZHHQ
1980 and 2013 (in 6,040 women), of which 364 (3.2% of pregnancies, occurring
in 329 women) were complicated by pre-eclampsia . Of the 329 women with a
KLVWRU\RISUHHFODPSVLD ZHUHSULPLJUDYLGDHWKHLURIIVSULQJZHUHRI
lower birthweight (p<0.001), born at earlier gestation (p=0.015), and were more
likely to be delivered by Caesarean Section (p<0.01).
Of the 6,040 women, 278 had a subsequent CV event. 26 of the 329 women with
a history of pre-eclampsia (7.9%) had a CV event compared to 252 of the 5,711
ZRPHQ ZLWK D KLVWRU\ RI QRUPRWHQVLYH SUHJQDQF\ 25 &,
WR3 7KHUHZDVQRGLIIHUHQFHLQDJHDWWLPHRI¿UVW&9HYHQW
\UV“YV\UV“S QV QRURIWLPHEHWZHHQ¿UVWSUHJQDQF\DQG¿UVW&9
HYHQWEHWZHHQZRPHQZLWKDQGZLWKRXWDKLVWRU\RISUHHFODPSVLD “\UVYV
“\UVS QV Conclusions: In the current study we have seen that even in relatively young
women from an unselected population cohort, those with a history of pre-ecODPSVLDKDYHDQHDUO\IROGLQFUHDVHGULVNRIFDUGLRYDVFXODUGLVHDVH:RPHQ
with pre-eclampsia should be targeted for more intensive cardiovascular risk
reduction measures.
6A.04
CREATININE AND URIC ACID LEVELS
DURING PREGNANCY PREDICT LONG TERM
ATHEROSCLEROTIC MORBIDITY DURING NONPREGNANT LIFE
7:RODN1, I. Shoham-Vardi 2, 56HUJLHQNR2, Y. Henkin 3, E. Paran 1,
E. Sheiner 4. 1 Hypertension Unit, Soroka University Medical Center, Faculty
of Health Sciences Ben-Gurion University of the Negev, Beer Sheva, ISRAEL,
2
Department of Public Health, Faculty of Health Sciences, Ben-Gurion
University of the Negev, Beer Sheva, ISRAEL, 3 Cardiology Department,
Soroka University Medical Center, Faculty of Health Sciences, Ben-Gurion
University of the Neg, Beer Sheva, ISRAEL, 4 Department of Obstetrics and
Gynecology, Soroka University Medical Center, Faculty of Health Sciences,
Ben-Gurion Univ., Beer Sheva, ISRAEL
Conclusions: Uric acid and creatinine levels during pregnancy may predict maternal atherosclerotic morbidity later in non-pregnant life.
6A.05
PULSE WAVE AMPLIFICATION AND VELOCITY
ACROSS BLOOD PRESSURE CATEGORIES IN
YOUTHS
M. Torro 1,2, -$OYDUH]1,2, C. García-Vicent 2, F. Aguilar 1,2, -5HGRQ2,3,
E. Lurbe 1,2. 1 Cardiovascular Risk Unit, Hospital General Universitario,
University of Valencia, Valencia, SPAIN, 2 CIBEROBN, Health Institute Carlos
III, Madrid, SPAIN, 3 Hypertension Unit, Hospital Clinico, University of
Valencia, Valencia, SPAIN
Objective: Over the last several years there has been an increasing interest in
isolated systolic high blood pressure (ISHBP) in youth. This subtype of hypertension (HTN) has a higher prevalence than systo-diastolic high BP (SDHBP) in
this age group. The objective was to analyze 24-hour and central BP, as well as
SXOVHZDYHDPSOL¿FDWLRQDQGYHORFLW\DFURVV%3FDWHJRULHVLQ\RXWKV
Design and method: Seven hundred and nineteen Caucasians of both sexes
(346 females), of European origin, from 8 to 18 years of age (mean age 12.4 2.3)
were included. The subjects were divided into 3 groups: normotensive (NT),
,6+%3 RU6'+%3 DFFRUGLQJWRWKH(6+RI¿FH
%3FULWHULD /XUEHHWDO-+\SHUWHQV 7ZHQW\IRXUKRXU$%30ZDVSHUformed using an oscillometric device (Spacelabs 90217) during a regular school
GD\&DURWLGIHPRUDOSXOVHZDYHYHORFLW\ 3:9 WRJHWKHUZLWKUDGLDODQGFDURWid tonometry and pulse wave analysis were assessed and central BP was derived.
Results: 7KHJHQHUDOFKDUDFWHULVWLFVRI¿FH%3KRXUDPEXODWRU\%3FHQWUDO
%3DQGSXOVHZDYHDPSOL¿FDWLRQDQGYHORFLW\DUHVKRZQLQWKH7DEOH6LJQL¿FDQWGLIIHUHQFHVZHUHSUHVHQWIRU6%3 RI¿FHKRXUVGD\WLPHDQGQLJKWWLPH EHWZHHQ17DQGERWK,6+%3DQG6'+%3JURXSVZKLOHWKHUHZHUHQRVLJQL¿FDQWGLIIHUHQFHVEHWZHHQWKHODVWWZRJURXSV)RU'%3VLJQL¿FDQWGLIIHUHQFHV
ZHUH SUHVHQW DPRQJ WKH WKUHH JURXSV IRU SHULSKHUDO DQG FHQWUDO %3 5DWLR RI
SHULSKHUDOFHQWUDOSXOVHSUHVVXUHDVDQHVWLPDWHRIDPSOL¿FDWLRQSKHQRPHQRQ
ZDVKLJKHULQ,6+%3DVFRPSDUHGWR17DQG6'+%3$VLJQL¿FDQWLQFUHPHQW
LQ3:9ZDVREVHUYHGIURP17WR,6+%3DQG6'+%3ZLWKWKHKLJKHVWYDOXHV
in the latter.
Objective: To examine the association between uric acid (UA) and creatinine
(Cr) levels during pregnancy and the development of future long-term maternal
atherosclerotic morbidity (including cardiovascular, cerebrovascular and renal
disease).
Design and method: A case-control study was conducted. Cases were women
who delivered between the years 2000-2012 and subsequently were hospitalized
during non-pregnant period due to atherosclerotic morbidity (cardiovascular
(CV) procedures, minor events and major events). Controls were women who
delivered between the years 2000-2012 but weren’t hospitalized with atherosclerotic morbidity. Three controls were matched to each one of the cases, according
to maternal year of birth. There were 588 cases and 3645 controls for whom at
least one uric acid test during pregnancy was available and 661 cases and 4373
controls for whom at least one creatinine test during pregnancy was available.
7KHELUWKZLWKWKHKLJKHVWOHYHOVRI8$&UZHUHFKRVHQDVWKHLQGH[SUHJQDQcies. Cox proportional hazards models were used to estimate the adjusted hazard
UDWLRV +5 IRUKRVSLWDOL]DWLRQV
Results: $ VLJQL¿FDQW DVVRFLDWLRQV ZHUH GRFXPHQWHG EHWZHHQ ORQJWHUP PDternal atherosclerotic morbidity and both UA and Cr measured at pregnancy.
0HDQOHYHOVRI8$GXULQJSUHJQDQF\ZHUHORZHVWLQFRQWUROV PJG/“
DQGLQFUHDVHGZLWKVHYHULW\RI&9KRVSLWDOL]DWLRQPJG/“LQZRPHQ
KRVSLWDOL]HG RQO\ IRU &9 SURFHGXUHV PJG/“IRU KRVSLWDOL]DWLRQ IRU
PLQRUHYHQWVDQGPJG/“IRUPDMRUHYHQWV6LPLODUUHVXOWVZHUHREVHUYHGIRUFUHDWLQLQHOHYHOV0HDQOHYHOVRI&5GXULQJSUHJQDQF\ZHUHORZHVW
LQFRQWUROV PJG/“ DQGLQFUHDVHGZLWKVHYHULW\RI&9KRVSLWDOL]DWLRQ
PJG/ “ LQ ZRPHQ KRVSLWDOL]HG RQO\ IRU &9 SURFHGXUHV PJ
G/“IRUKRVSLWDOL]DWLRQIRUPLQRUHYHQWVDQGPJG/“IRUPDMRU
events.
Cox proportional hazard models, adjusting for confounders such as maternal
age, gestational hypertension, gestational diabetes mellitus and obesity showed
WKDWKLJK8$ ! PJGO DVZHOODVKLJK&5OHYHOV ! PJGO GXULQJ
pregnancy remained independently associated with atherosclerotic hospitalizaWLRQV DGMXVWHG +5 &, 3 DQG DGMXVWHG +5 95% CI 1.2.14-5.7, P<0.001 respectively).
Conclusions: Youths, with ISHBP are mainly male, showing a higher pulse
ZDYH DPSOL¿FDWLRQ DQG ORZHU 3:9 DV FRPSDUHG WR 6'+%3 GHVSLWH KDYLQJ
similar peripheral and central BP. Future studies may further contribute to a better understanding of this condition.
6A.06
ROLE OF AMBULATORY BLOOD PRESSURE
MONITORING IN LONG-TERM FOLLOW-UP OF
GESTATIONAL HYPERTENSION
V. Gessi, A. Maresca, C. Mongiardi, L. Merletti, F. Annoni, V. Vacirca,
C. Gadaleta, /5REXVWHOOL7HVWV. Ferrari, E. Ferrario, P. Messina, A. Grandi.
Department of Clinical and Experimental Medicine, University of Insubria,
Varese, ITALY
Objective: Several studies demonstrated that women with gestational hypertension and preeclampsia have an increased risk to develop chronic hypertension
later in life than women who had normotensive pregnancies. In these studies
K\SHUWHQVLRQZDVGLDJQRVHGRQO\E\RI¿FHEORRGSUHVVXUH7KHDLPRIWKHVWXG\
e74
Journal of Hypertension Volume 32, e-Supplement 1, 2014
was to evaluate the incidence of hypertension after a long term follow up in
women with previous gestational hypertension, preeclampsia and normotensive
pregnancy using an ambulatory blood pressure monitoring (ABPM).
Design and method: :H VHOHFWHG ZRPHQ ZKR GHOLYHUHG LQ9DUHVH IURP
2002 to 2005: 50 women with gestational hypertension, 50 with preeclampsia
DQGZLWKQRUPRWHQVLYHSUHJQDQF\:RPHQZLWKDKLVWRU\RIK\SHUWHQVLRQEHfore pregnancy, diabetes mellitus and cardiovascular events were excluded. The
groups had similar age and body mass index at the beginning of pregnancy. At
WKHIROORZXS PHDQ“\HDUV HYHU\ZRPDQKDGERWKRI¿FHEORRGSUHVVXUH
(BP) measurements and performed an ABPM.
Results: :RPHQ ZLWK SUHYLRXV JHVWDWLRQDO K\SHUWHQVLRQ DQG SUHHFODPSVLD
developed more often hypertension than women who had a normotensive
pregnancy (56% and 38% versus 20% respectively, p=0.001): these data
ZHUHFRQ¿UPHGE\.DSODQ0HLHUFXUYHDQDO\VLV /RJ5DQNS +\SHUWHQVLRQSUHYDOHQFHZDVKLJKHUXVLQJ$%30WKDQRI¿FH%3 YHUVXV
12% in the gestational hypertension group, 26% versus 12% in the preecODPSVLDJURXSDQGYHUVXVLQWKHFRQWUROJURXSS :HIRXQG
a higher rate of masked hypertension in women with previous gestational
hypertension and preeclampsia than in the control group (26% and 24% versus 12%, p=0.05).
Design and method: :HH[DPLQHGOHYHOVRIDOGRVWHURQHDQG3O*)DWJHVWDWLRQDO
week 14-16 in stored samples from women who had previously taken part in
WKH3URWHRPLFVLQ3UHHFODPSVLD 3,3 VWXG\DORQJLWXGLQDOVWXG\RISUHJnancies designed to identify early biomarkers to predict later development of
pre-eclampsia. Stored urine and plasma samples were obtained for 48 cases and
48 matched, healthy pregnant controls. Urinary tetrahydroaldosterone (THAldo)
excretion was measured by gas chromatography-mass spectrometry (GC-MS)
and PlGF by enzyme linked immunosorbent assay (ELISA).
Results: 7KHUHZDVQRVLJQL¿FDQWGLIIHUHQFHLQDJHERG\PDVVLQGH[RUERRNLQJV\VWROLFEORRGSUHVVXUHEHWZHHQJURXSV,QOLQHZLWK¿QGLQJVRIWKH3,3
study booking diastolic blood pressure was higher, although still within the
normal range, in women who went on to develop pre-eclampsia (72mmHg,
,45 FI PP+J ,45 E\ 0DQQ:KLWQH\ S 8ULQDU\
7+$OGRFUHDWLQLQH UDWLR ZDV VLJQL¿FDQWO\ ORZHU DPRQJ FDVHV WKDQ FRQWUROV
—JPPRO ,45 FI —JPPRO ,45 E\ WWHVW
S :KLOVWWKHUHZDVQRVLJQL¿FDQWGLIIHUHQFHLQHDUO\SUHJQDQF\3O*)
levels between the groups, we did observe a linear relationship between PlGF
and THAldo in both cases and controls (Spearman’s rank correlation 0.415,
S DVVKRZQLQWKH¿JXUHEHORZ
Conclusions: Ambulatory blood pressure monitoring appears more reliable than
RI¿FH%3WRHYDOXDWHK\SHUWHQVLRQLQZRPHQZLWKSUHYLRXVJHVWDWLRQDOK\SHUtension, given the high incidence of masked hypertension in this setting.
6A.07
CORRELATION BETWEEN PLACENTAL GROWTH
FACTOR AND URINARY TETRAHYDROALDOSTERONE
EXCRETION IN EARLY PREGNANCY
G. Currie 1, N. Eisele 2, H. Small 1, G. Escher 2, C. Gennari-Moser 2,
D. Carty 1, M. Mohaupt 2, C. Delles 1. 1 Institute of Cardiovascular and
Medical Sciences, University of Glasgow, Glasgow, UNITED KINGDOM, 2
Department of Nephrology and Hypertension, Bern University Hospital, Bern,
SWITZERLAND
Objective: Aldosterone levels are known to be elevated in healthy, normotensive pregnancy but fall despite volume contraction in pre-eclampsia. Vascular
endothelial growth factor (VEGF) and soluble fms-like tyrosine kinase 1 (sFlt1) have been implicated in this phenomenon in-vitro and in animal work. Low
levels of placental growth factor (PlGF), which is closely linked to VEGF signalling, appear to identify women at risk of pre-eclampsia between gestational
ZHHNVDQG:HDLPHGWRH[SORUHWKHVHUHODWLRQVKLSVLQKXPDQVXEMHFWVLQ
early pregnancy.
Conclusions: THAldo and PlGF appear closely linked in early pregnancy. Given the critical role of THAldo in pregnancy, these data suggest that in women
destined to develop pre-eclampsia THAldo rather than PlGF may be causal exWHQGLQJWKH¿QGLQJVRISUHYLRXVDQLPDOZRUNWRKXPDQVXEMHFWV
Abstracts
e75
ORAL SESSION
ORAL SESSION 6B
EPIDEMIOLOGY
6B.01
ENDOTHELIAL DYSFUNCTION PLAYS A KEY
ROLE IN INCREASING CARDIOVASCULAR EVENT
RISK IN TYPE 2 DIABETES, IMPAIRED GLUCOSE
METABOLISM AND THE INSULIN RESISTANT STATE:
THE HOORN STUDY
T. Van Sloten 1, 5+HQU\1, -'HNNHU2, G. Nijpels 2, M. Schram 1,
C. Stehouwer 1. 1 Maastricht University Medical Center, Department of
Medicine, Maastricht, NETHERLANDS, 2 VU University Medical Centre,
EMGO Institute for Health and Care Research, Amsterdam, NETHERLANDS
Objective: It has been hypothesized that individuals with type 2 diabetes are
particularly prone to the detrimental effects of endothelial dysfunction on the
development of cardiovascular disease, a key mechanism in the pathogenesis of
atherothrombosis, and that this may explain the increased cardiovascular risk in
W\SHGLDEHWHV(YLGHQFHLQKXPDQVIRUWKLVK\SRWKHVLVLVKRZHYHUOLPLWHG:H
therefore investigated the interaction between endothelial dysfunction and type
2 diabetes, impaired glucose metabolism and insulin resistance with regard to
risk of cardiovascular events.
Design and method: Data were obtained from 1524 participants (67.5% womHQ PHDQ DJH \HDUV ZLWK QR KLVWRU\ RI VWURNH LQ WKH JHQHUDO SRSXODWLRQ
RI 2KDVDPD -DSDQ +RPH K\SHUWHQVLRQ ZDV GH¿QHG DV V\VWROLFGLDVWROLF %3
! PP+JDPEXODWRU\K\SHUWHQVLRQDV%3! PP+JDQGRI¿FH
K\SHUWHQVLRQDV%3! PP+J3DUWLFLSDQWVZHUHFODVVL¿HGLQWRWKHIROORZLQJ VL[ JURXSV QRUPRWHQVLYH 17 WUXH:&+7 LVRODWHG RI¿FH K\SHUWHQVLRQ SDUWLDO:&+7 LQ RWKHU ZRUGV SDUWLDO VXVWDLQHG K\SHUWHQVLRQ 6+7 DW
KRPHRUDPEXODWRU\DQGRI¿FHK\SHUWHQVLRQSDUWLDO0+7 HLWKHUKRPHRUDPEXODWRU\K\SHUWHQVLRQZLWKRXWRI¿FHK\SHUWHQVLRQ WUXH0+7 ERWKKRPHDQG
DPEXODWRU\K\SHUWHQVLRQZLWKRXWRI¿FHK\SHUWHQVLRQ DQG6+7
Results: A total of 225 (14.8%) stroke events occurred over a mean of 15.2
(maximum, 21.6) follow-up years. After adjusting for sex, age, body mass index,
current smoking and drinking habits, history of heart disease, diabetes mellitus,
hyperlipidemia and treatment with antihypertensive drugs, the Cox regression
PRGHOVKRZHGDVLJQL¿FDQWO\KLJKHUULVNIRUVWURNHLQSDUWLFLSDQWVZLWKSDUWLDO
:&+70+7RU6+7WKDQLQ17LQGLYLGXDOV )LJXUH 1RVLJQL¿FDQWGLIIHUHQFH
ZDVREVHUYHGEHWZHHQWKHWUXH:&+7DQG17JURXSVLQVWURNHULVN )LJXUH :KHQSDUWLFLSDQWVZLWKSDUWLDO:&+7ZHUHVXEGLYLGHGLQWRWKRVHZLWKKRPHRU
ambulatory hypertension, both subgroups had a higher risk for stroke than the
17JURXS 3 :KHQWKHIROORZXSGXUDWLRQZDVVKRUWHQHGWRDPD[LPXP
RI\HDUVQRVLJQL¿FDQWGLIIHUHQFHZDVHYLGHQWEHWZHHQWKHSDUWLDO:&+7DQG
NT groups in stroke risk (P=0.2).
Design and method: In a prospective population-based cohort (n=445, 69
\HDUVZRPHQW\SHGLDEHWHVLPSDLUHGJOXFRVHPHWDEROLVP E\
GHVLJQ HQGRWKHOLDOG\VIXQFWLRQ EUDFKLDODUWHU\ÀRZPHGLDWHGGLODWDWLRQ JOXcose tolerance status (oral glucose tolerance test) and insulin sensitivity (homeoVWDVLVPRGHODVVHVVPHQW+20$,5 ZHUHGHWHUPLQHG,QDGGLWLRQDPRUELGLW\
and mortality registration was kept.
Results: After a median follow-up of 7.6 years, 107 participants had had a
cardiovascular event. After adjustment for cardiovascular risk factors, -1 SD
ÀRZPHGLDWHG GLODWDWLRQ ZDV DVVRFLDWHG ZLWK FDUGLRYDVFXODU HYHQWV LQ W\SH GLDEHWHV +5>&,@ DQGLPSDLUHGJOXFRVHPHWDEROLVP > @ DQG DPRQJ WKRVH LQ WKH KLJKHVW +20$,5 WHUWLOH >
@ EXWQRWLQQRUPDOJOXFRVHPHWDEROLVP >@ RUDPRQJWKRVH
LQWKHORZHUWZR+20$,5WHUWLOHVFRPELQHG >@ ,QWHUDFWLRQ
EHWZHHQÀRZPHGLDWHGGLODWDWLRQDQGW\SHGLDEHWHVLPSDLUHGJOXFRVHPHWDERlism or insulin resistance was present on an additive (relative excess risk due to
interactions>0) and a multiplicative scale (P-interactions<.05).
Conclusions: Endothelial dysfunction and type 2 diabetes, impaired glucose
metabolism or insulin resistance synergistically increase cardiovascular risk.
7KLV LGHQWL¿HV HQGRWKHOLDO G\VIXQFWLRQ DV D NH\ WKHUDSHXWLF WDUJHW LQ WKHVH LQdividuals.
6B.02
LONG-TERM STROKE RISK IN THE GENERAL
POPULATION DUE TO TRUE AND PARTIAL WHITECOAT HYPERTENSION BASED ON HOME AND
AMBULATORY BLOOD PRESSURE MEASUREMENTS
M. Satoh 1, M. Kikuya 2, M. Hosaka 3, K. Asayama 3,4, 5,QRXH 5, H. Metoki 2,
M. Utsugi 6, T. Obara 1,2, T. Hirose 7, A. Hara 4, K. Totsune 3,8, H. Hoshi 9,
N. Mano 1, Y. Imai 3, T. Ohkubo 10. 1 Department of Pharmacy, Tohoku
University Hospital, Sendai, JAPAN, 2 Tohoku Medical Megabank
Organization, Sendai, JAPAN, 3 Department of Planning for Drug
Development and Clinical Evaluation, Tohoku University, Sendai, JAPAN,
4
Department of Cardiovascular Diseases, University of Leuven, Leuven,
BELGIUM, 5 Medical Information Technology Center, Tohoku University
Hospital, Sendai, JAPAN, 6 National Institute of Health and Nutrition, Tokyo,
JAPAN, 7 Center for Interdisciplinary Research in Biology, College de France,
Paris, FRANCE, 8 Faculty of Synthetic Welfare, Tohoku Fukushi University,
Sendai, JAPAN, 9 Ohasama Hospital, Iwate, JAPAN, 10 Department of Hygiene
and Public Health, Teikyo University School of Medicine, Tokyo, JAPAN
Objective: 7KHSURJQRVWLFYDOXHRIZKLWHFRDWK\SHUWHQVLRQ :&+7 LVVWLOOGHbated. The objective of the present study was to investigate the long-term stroke
ULVNGXHWR:&+7DQGPDVNHGK\SHUWHQVLRQ 0+7 EDVHGRQKRPHDPEXODWRU\DQGRI¿FHEORRGSUHVVXUH %3 PHDVXUHPHQWV
Conclusions: 3DUWLFLSDQWV ZLWK SDUWLDO:&+7 KDG WZLFH WKH ORQJWHUP VWURNH
risk of NT individuals, which is a risk similar to those with MHT and SHT.
3DUWLDO:&+7LHSDUWLDO6+7VKRXOGEHGHWHFWHGE\PHDVXULQJERWKKRPHDQG
DPEXODWRU\%3LQRUGHUWRLPSURYHVWURNHULVNVWUDWL¿FDWLRQ
6B.03
ANALYSIS OF SOME RECENT DATA THAT COULD
EXPLAIN THE REDUCTION OF STROKE MORTALITY
IN PORTUGAL DURING THE 2003-2011 INTERVAL
-3RORQLD1, L. Martins 2. 1 Department Medicine, Faculdade Medicina
Universidade, Porto, PORTUGAL, 2 Serviço Cardiologia, CHEDV, Epe, Feira,
Porto, PORTUGAL
Objective: Portugal is a peculiar European country showing a higher mortality
E\VWURNHLQFRPSDULVRQZLWKFRURQDU\GLVHDVH &' 5HFHQWGDWDVKRZHGWKDW
in Portugal mortality by stroke was reduced (all ages per 100.000) from 116.9
(2003) to 62.3 deaths (2011) whereas death by CD changed from 56.8 to 43.8.
Design and method: Factors that could theoretically contribute positively or
negatively for such a progress during that period are analyzed from data of representative surveys in Portugal.
Results: There was a clear improvement of health coverage and patients’s access to health care. The percentage of the population effectively included in the
¿OHVRIWKHSULPDU\KHDOWKFDUHLQFUHDVHGIURP WRPRUHWKDQ
6WURNH8QLWV W\SH$% ZHUHSDUWLFXODUO\GHYHORSHGDIWHU6\VWROLFGLDVWROLFEORRGSUHVVXUH %3 RIDOODGXOWSRSXODWLRQZDVLQDYHUDJHUHGXFHG
E\PP+JIURPWR IURPWRPP+J S
U
N
D
A
Y
O
R
A
L
S
e76
Journal of Hypertension Volume 32, e-Supplement 1, 2014
For a similar prevalence of hypertension (HT) found in 2003 and 2011 (42.1%)
the rate of treated hypertensive patients increased from 38.9% to 74.9 % and the
rate of HT control increased from 11.2% to 41.6%. Average sodium intake in the
K\SHUWHQVLYHSRSXODWLRQZDVUHGXFHGLQWKLVLQWHUYDOIURPWRPPROK
UHGXFWLRQRIJGD\RIVDOWLQWDNH ,QWKHVDPHLQWHUYDOSUHVFULSWLRQ QXPEHU
of packages) of anti-hypertensive drugs (AHd) was increased by 61% and of
DQWLWKURPERWLFVE\XVHRI$+GLQ¿[HGGRVHFRPELQDWLRQVZLWKLQWKH
100 most prescribed drugs increased by 702%. In contrast in that interval, averDJHERG\PDVVLQGH[LQFUHDVHGIURPWR.JPSUHYDOHQFHRIREHVLW\
increased from 14.6 to 22.4% and the prevalence of diabetes increased from 6.5
to 12.9%.
Conclusions: Despite the disadvantage of the increase in the prevalence of obesity and diabetes in Portugal, the improvement of the health system, the reduction of salt intake and of the overall BP values and the increase of the hypertension treatment and control may have participate in the striking reduction of
mortality by stroke observed in Portugal in the last decade.
6B.04
ETHNIC DIFFERENCES IN SYSTOLIC BLOOD
PRESSURE IN EUROPE: A SYSTEMATIC REVIEW AND
META-ANALYSIS
P. Modesti 1, C. Agyemang 2, F. Cappuccio 3, E. Perruolo 1, *5HPX]]L4,
G. Parati 5, *5HEROGL6, %(6+:*RQ&95LQ/567. 1 Dept. of Medicine
Sperimentale e Clinica, University of Florence, Florence, ITALY, 2 Dept.
of Public Health, Academic Medical Centre, University of Amsterdam,
Amsterdam, NETHERLANDS, 3 University of Warwick, Warwick Medical
School and University Hospitals Coventry and Warwickshire NHS Trust,
Coventry, UNITED KINGDOM, 4 IRCCS Istituto di Ricerche Farmacologiche
Mario Negri, Bergamo, ITALY, 5 Dept. of Health Sciences, University of
Milano-Bicocca, Dept. of Cardiology, S. Luca Hospital, IRCCS Istituto
Auxologico, Milan, ITALY, 6 Dept. of Internal Medicine, University of Perugia,
Perugia, ITALY, 7 On behalf of ESH WG on CV Risk in Low Resource Settings,
EUROPEAN UNION
Objective: To use a prediction model from other ethnicity may have bad perforPDQFHLQGLVFULPLQDWLQJKLJKULVNLQGLYLGXDOVRIGLVHDVH:HDLPHGWRGHYHORS
a prediction model for incident hypertension using the sample cohort database
from the National Health Insurance Service (NHIS) and to validate it using a
prospective community-based cohort data in Korea.
Design and method: The sample cohort database from NHIS contains both the
national health examination data and medical records, which have prescription
and diagnostic codes from 2006 to 2010. Of 174,625 underwent the national
health examination, 70,421 participants at aged 40-69 without hypertension at
baseline were used to develop a risk prediction model (NHIS model). The operDWLRQDOGH¿QLWLRQRIK\SHUWHQVLRQZDVGH¿QHGDVV\VWROLFEORRGSUHVVXUH 6%3 >=140mmHg, or diastolic blood pressure (DBP) >=90mmHg, or taking antihypertensive medications in the national health examination in 2007-2010 or the
FDVHV KDG GLDJQRVWLF FRGHV IRU K\SHUWHQVLRQ E\ ,QWHUQDWLRQDO &ODVVL¿FDWLRQ RI
Diseases version 10 (ICD-10) from medical records. Logistic regression model
ZDVXVHGWRLGHQWLI\WKHULVNIDFWRUVDQGWRFRQVWUXFWWKHSUHGLFWLRQPRGHO:H
validated the NHIS model in another cohort, the Korean Genome and Epidemiology Study (KoGES). The performance of NHIS model was assessed by both
GLVFULPLQDWLRQ DUHDXQGHUDUHFHLYHURSHUDWLQJFKDUDFWHULVWLFFXUYH$8&52& DQGFDOLEUDWLRQ +RVPHU/DPHVKRZ¶VJRRGQHVVRI¿WWHVW Results: During an approximately 4-year follow-up, the cumulative incidence
of hypertension was 21.7%. In multiple logistic regression analysis, age, sex,
body mass index, SBP, DBP, family history of hypertension, and current smoking status. The interaction between diastolic blood pressure and age was also staWLVWLFDOO\VLJQL¿FDQW1+,6PRGHOKDGJRRGGLVFULPLQDWLRQ $8&52& &, DQG FDOLEUDWLRQ +RVPHU/DPHVKRZ¶V Ȥð 3YDOue=0.0578).
Objective: 7RH[SORUHWKHRFFXUUHQFHRIJHQGHUVSHFL¿FDEVROXWHGLIIHUHQFHVLQ
RI¿FHV\VWROLFEORRGSUHVVXUH 6%3 OHYHOVEHWZHHQ(XURSHDQVDQGLPPLJUDQW
populations of Sub-Saharan African (SSA) and South Asian (SA) descent.
Design and method: :HV\VWHPDWLFDOO\UHYLHZHGDYDLODEOHREVHUYDWLRQDOVWXGLHVFRQGXFWHGDPRQJ(XURSHDQUHVLGHQWVRIGLIIHUHQWHWKQLFRULJLQXVLQJVSHFL¿F
VHDUFKVWUDWHJLHVDQGVHOHFWLRQFULWHULD6WXGLHVZHUHLGHQWL¿HGWKURXJK0HGOLQH
:HERI6FLHQFHDQG6FRSXVGDWDEDVHVHDUFKLQJDQGWKURXJKFLWDWLRQVIURPUHIerences, up to 31st December 2013.
)URPRYHUVWXGLHVZHLGHQWL¿HGFURVVVHFWLRQDOVXUYH\VWKDWPHWSUHGH¿QHGHOLJLELOLW\FULWHULD:HH[WUDFWHG%3GDWDRI66$6$DQG
67603 European subjects.
Main outcome measures were weighted mean differences in SBP between immigrants and native Europeans, using a random effects model and tested for
heterogeneity.
Results: SSA subjects had higher SBP values than native Europeans with an overDOOZHLJKWHGPHDQGLIIHUHQFHRIPP+J>&,WRS@
*HQGHUVSHFL¿FGLIIHUHQFHVZHUHPP+JIRUPHQ>WRS @
DQGPP+J>WRS @IRUZRPHQZLWKQRHYLGHQFHRIJHQGHULQWHUDFWLRQ S ,QFRQWUDVW6%3YDOXHVZHUHVLJQL¿FDQWO\ORZHULQ
SA than in European subjects with an overall weighted mean difference of -4.24
PP+J>WRS@:LWKLQJHQGHUGLIIHUHQFHVZHUH>
WR S@ DQG PP+J > WR S @ IRU PHQ DQG
women respectively, with no evidence of interaction (p=0.3793). HeterogeneLW\ZDVODUJH ,VTXDUHGDQGIRUWKHWZRHWKQLFLWLHVS DQG
unexplained by gender differences.
Conclusions: (WKQLFDOGLIIHUHQFHVLQ(XURSHDUHDVVRFLDWHGZLWKVLJQL¿FDQWPHDQ
GLIIHUHQFHV LQ RI¿FH 6%3 DOWKRXJK VXFK GLIIHUHQFHV DUH DIIHFWHG E\ VLJQL¿FDQW
heterogeneity. SSA descent is associated with SBP values systematically higher
than those of Europeans who, conversely, are characterized by higher SBP than
VXEMHFWVRI6$GHVFHQW7KHLGHQWL¿FDWLRQRIIDFWRUVUHVSRQVLEOHIRUVXFKYDULDELOLW\LVQRZDSULRULW\WRJXLGHWKHLPSOHPHQWDWLRQRIVSHFL¿FSUHYHQWLRQSROLFLHV
6B.05
DEVELOPMENT AND VALIDATION OF PREDICTION
MODEL FOR INCIDENT HYPERTENSION IN KOREAN
POPULATION
N. Lim 1, M. Cho 2, H. Park 1. 1 Korea National Institute of Health, Division of
Cardiovascular and Rare Diseases, Chungcheongbuk-Do, SOUTH KOREA, 2
Chungbuk National University, College of Medicine, Department of Internal
Medicine, Cheongju, SOUTH KOREA
Conclusions: In this study, we constructed a new risk prediction model using
nationwide large health examination data and validated it in prospective community-based cohort. It will be considered as a useful tool to prevent hypertension, which is one of the important public health problems in Korea.
6B.06
CLINIC AND AMBULATORY HYPERTENSION AMONG
HIGH ALTITUDE DWELLERS. HIGHCARE-ANDES
HIGHLANDERS STUDY
G. Bilo 1, F. Villafuerte 2, &$Q]D5DPLUH]2, -0DFDUOXSX2,
G. Vizcardo-Galindo 2, 05HYHUD1, A. Giuliano 1,3, A. Faini 1, S. Caravita 1,3,
F. Gregorini 1, G. Parati 1,3. 1 Dept. of Cardiovascular, Neural and Metabolic
Sciences, Ospedale San Luca, Istituto Auxologico Italiano, Milan, ITALY,
2
Universidad Peruana Cayetano Heredia, Lima, PERU, 3 Dept. of Health
Sciences, University of Milano-Bicocca, Milan, ITALY
Objective: Arterial hypertension is highly prevalent among lowlanders, being
a major risk factor for mortality and disability worldwide. However, little is
known about its prevalence and determinants in high altitude dwellers. MoreoYHUDYDLODEOHLQIRUPDWLRQUHOLHVRQFDVXDORI¿FHEORRGSUHVVXUH %3 PHDVXUH-
e77
Journal of Hypertension Volume 32, e-Supplement 1, 2014
ments, while data obtained with ambulatory BP monitoring are lacking. Aim
RI+,*+&$5($1'(6+LJKODQGHUVVWXG\ZDVWRH[SORUHK\SHUWHQVLRQSUHYDlence and determinants in a sample of high altitude inhabitants.
VRFLDWLRQEHWZHHQ:%& RU&53 FKDQJHGXULQJIROORZXSZDVDOVRDVVHVVHG
in a subset.
Design and method: :HSHUIRUPHGDPEXODWRU\%3PRQLWRULQJ $1'70
-DSDQ DQGFROOHFWHGEDVLFFOLQLFDOLQIRUPDWLRQLQUDQGRPO\VHOHFWHGDGXOWV \HDUV SHUPDQHQWO\ OLYLQJ LQ &HUUR GH 3DVFR 3HUX P 5DWHV RI %3
control according to different BP variables and the relation between presence of
hypertension and several clinical variables were assessed.
Results: &RPSOHWH GDWD ZHUH REWDLQHG LQ VXEMHFWV DJH “\
0) %0, “ NJP 6S2 “ KHPRJORELQ “
J/ 2I¿FH K\SHUWHQVLRQ V\VWROLF 6 %3! DQGRU GLDVWROLF ' %3! PP+J ZDV IRXQG LQ VXEMHFWV 5DWHV RI DPEXODWRU\ K\SHUWHQVLRQ
ZHUH IRU K %3 ! PP+J IRU GD\WLPH ! PP+J IRUQLJKWWLPH ! PP+J 'LDVWROLFK\SHUWHQVLRQZDV
more frequent than systolic hypertension (10.1 vs. 6.3% for 24h BP), the difference depending mainly on nocturnal hypertension (12.9 vs. 6.3%). IndividuDOVZLWKHOHYDWHGK%3VLJQL¿FDQWO\GLIIHUHGIURPQRUPRWHQVLYHVLQWHUPVRI
DJH “ YV “\ %0, “ YV “ NJP 6S2
“YV“ DQGKHPRJORELQ “YV“J/ ,QORJLVtic regression analysis including age, sex, BMI, 24h heart rate, hemoglobin and
SpO2 the factors independently associated with hypertension were: age, SpO2
DQGKHPRJORELQIRUGD\WLPHK\SHUWHQVLRQDJHK+5DQGVH[IRUQLJKWWLPH
hypertension. Independent association with hemoglobin was found for diastolic
but not for systolic hypertension.
Conclusions: Our study suggests that hypertension prevalence is low but not
negligible among Andean high altitude dwellers, being higher when considering
DPEXODWRU\UDWKHUWKDQRI¿FH%3YDOXHV7KHUHDUHUHOHYDQWGLIIHUHQFHVLQIDFWRUV
associated with daytime vs. night-time and diastolic vs. systolic hypertension
and increased blood viscosity due to polycythemia appears to play a relevant
role in hypertension among highlanders.
6B.07
INFLAMMATORY MARKER AND RISK OF INCIDENT
HYPERTENSION, DIABETES AND METABOLIC
SYNDROME IN 96,622 EAST ASIANS
K. Sung, 65\X.
Sungkyunkwan University, School of Medicine, Seoul, SOUTH KOREA
Objective: ,WLVXQFHUWDLQZKHWKHU&53DQG:%& LQÀDPPDWRU\PDUNHUV DUH
robust in biomarkers of metabolic disease in Asians. In this study, we explored
WKH DVVRFLDWLRQ EHWZHHQ &53 :%& DQG LQFLGHQW K\SHUWHQVLRQ RU GLDEHWHV RU
metabolic syndrome in a large population of Koreans.
Design and method: 5HWURVSHFWLYH VWXG\ RI SDWLHQWV HQUROOHG LQ D
health screening program in a large community hospital. Cox proportional
KD]DUGPRGHOVZHUHXVHGWRHVWLPDWHKD]DUGUDWLRV +5V IRULQFLGHQWPHWDEROLF GLVHDVH DVVRFLDWHG ZLWK TXDUWLOHV RI EDVHOLQH :%& DQG &53 7KH DV-
Results: During the follow-up period of a median of 4.49 years, 12,890 participants developed incident diabetes or hypertension or metabolic syndrome. The
LQFLGHQFH UDWHV RI WKHVH WKUHH RXWFRPHV E\ TXDUWLOH RI LQFUHDVLQJ :%& ZHUH
3124, 3641,4006 and 4650 in men (P for trend < 0.01), 697,906,1036 and 1344
in women (P for trend < 0.01). In the multivariate model adjusted for age, smokLQJVWDWXVDOFRKROLQWDNHUHJXODUH[HUFLVHDQG%0,EDVHOLQH:%&UHPDLQHG
VLJQL¿FDQWO\ SUHGLFWLYH RI LQFLGHQW WKUHH RXWFRPHV )LQGLQJV ZHUH VLPLODU LQ
&53TXDUWLOH
Conclusions: 7KHVH ¿QGLQJV LPSOLHG WKDW KLJKHU:%& DQG &53 RU H[LVWHQFH
RIFKURQLFV\VWHPLFLQÀDPPDWLRQSUHFHGHVYDULRXVPHWDEROLFGLVHDVHLQFLGHQFH
independent of traditional risk factors.
Abstracts
e78
ORAL SESSION
ORAL SESSION 6C
NEURAL AND REFLEX MECHANISMS
6C.01
PVN G-ALPHA I2 PROTEIN-MEDIATED RENAL NERVE
DEPENDENT REGULATION OF NOREPINEPHRINE
SECRETION AND NCC ACTIVITY: IMPLICATIONS FOR
SALT-SENSITIVE HYPERTENSION
5:DLQIRUGS. Mahne, -.XZDEDUD.
Boston University, Department of Pharmacology, Boston, MA, USA
Objective: :HH[DPLQHGWKHUROHRI391*ĮLSURWHLQVZKLFKDUHHQGRJHQRXVO\
upregulated by increased dietary salt-intake in Sprague-Dawley (SD) rats, in blood
pressure regulation, sodium homeostasis, renal norepinephrine (NE) content and
renal sodium chloride co-transporter (NCC) activity during high salt-intake.
Design and method: ,QWDFWELODWHUDOUHQDOGHQHUYDWHG 5'1; RUVKDPGHQHUYDWHG 6'1; PDOH6'UDWVUHFHLYHGDELODWHUDO391LQIXVLRQRIDVFUDPEOHG
6 RU *ĮL ROLJRGHR[\QXFOHRWLGH 2'1QJVLGHGD\ DQG D GD\ QRUPDO
0.4% (NS) or high 8% NaCl (HS) diet. On day-7 24h Na+ balance was assessed.
In sub-groups MAP, estimated blood (EBV) and plasma (EPV) volumes, plasma
1( NLGQH\ 1( DQG QDWULXUHVLV WR LY K\GURFKORURWKLD]LGH +&7= PJNJ LQIXVLRQZDVDVVHVVHG 1 JSVWXG\ Results: +6LQWDNHVXSSUHVVHGSODVPD1(NLGQH\1(FRQWHQW 1(>SJPJ@16
“YV+6“3 DQGQDWULXUHVLVWR+&7= 3 ZLWKRXWDOtering MAP, EBV, EPV or Na+ balance in intact PVN S infused rats.
+6LQWDNHLQUDWVUHFHLYLQJD391*ĮLLQIXVLRQHYRNHGHOHYDWHGSODVPD1( 1(
>QPRO/@16“YV+6“3 LQFUHDVHGQDWULXUHVLVWR+&7= SHDN
FKDQJH81D9WR+&7=>ȝHTPLQ@16“YV+6“3 K\SHUWHQVLRQ 0$3>PP+J@16“YV+6“3 VRGLXPUHWHQWLRQ K
1DEDODQFH>PHT@16“YV+6“3 DQGLQFUHDVHGEORRGDQG
SODVPDYROXPH (39>PO@16“YV+6“3(%9>PO@*ĮL
“YV+6“3 6LJQL¿FDQWO\LQ*ĮLLQIXVHGUDWV+6LQWDNH
LQFUHDVHGNLGQH\1(FRQWHQW 1(>SJPJ@16“YV+6“3 DQG
NLGQH\1(WXUQRYHU 1(WXUQRYHU>SJPJKU@16“YV+6“3 5'1;LQ+6PDLQWDLQHG391*ĮLLQIXVHGUDWVSUHYHQWHGK\SHUWHQVLRQ 0$3
>PP+J@6'1;+6*ĮL“YV5'1;+6*ĮL“3 HOHYDWHG
plasma NE, sodium retention and enhanced natriuresis to HCTZ (P<0.05).
Conclusions: ,PSDLUPHQWRI391*ĮLVLJQDOWUDQVGXFWLRQGXULQJKLJKVDOWLQtake results in dysregulation of renal NE content, impaired NCC activity and
UHQDO QHUYH GHSHQGHQW K\SHUWHQVLRQ:H VSHFXODWH WKDW G\VUHJXODWLRQ RI 391
*ĮL SDWKZD\V HYRNHV 1( PHGLDWHG RYHUDFWLYLW\ RI 1&& WR GULYH VRGLXP ÀXLGUHWHQWLRQWULJJHULQJWKHGHYHORSPHQWRIVDOWVHQVLWLYHK\SHUWHQVLRQ
6C.02
AMBULATORY BLOOD PRESSURE VARIABILITY
PREDICTS OUTCOME AFTER RENAL DENERVATION
M. Monge 1, G. Bobrie 2, E. Curis 1, M. Frank 2, M. Sapoval 3, -(O*KR]L4,
M. Azizi 1,2. 1 European Hospital Georges Pompidou, Clinical Investigation
Center, Paris, FRANCE, 2 European Hospital Georges Pompidou, Hypertension
Unit, Paris, FRANCE, 3 European Hospital Georges Pompidou, Radiology Unit,
Paris, FRANCE, 4 Necker Hospital, Nephrology Unit, Paris, FRANCE
Objective: 5HQDO GHQHUYDWLRQ 5'1 LV D GHYLFHEDVHG WUHDWPHQW RI SULPDU\
UHVLVWDQWK\SHUWHQVLRQ 5+ +RZHYHUHI¿FDF\SUHGLFWRUVDUHODFNLQJ2XUDLP
ZDVWRLGHQWLI\DPDUNHURIEORRGSUHVVXUH %3 UHVSRQVHWR5'1XVLQJDPEXODtory BP (ABP) measurements.
Design and method: :HFRPSDUHGSDWLHQWVZLWK5+ GD\WLPH$%3 G$%3 ! DQGRUPP+JGHVSLWHWKUHHIXOOGRVHDQWLK\SHUWHQVLYHPHGLFDWLRQV
LQFOXGLQJ D GLXUHWLF DQG DSSURSULDWH DUWHULDO DQDWRP\ ZKR XQGHUZHQW 5'1
SURFHGXUH 5'1JURXS ZLWKVL[HOLJLEOH5'1XQWUHDWHGSDWLHQWV REVHUYDWLRQ
JURXS %DVHOLQHDQGPRQWKIROORZXSRI¿FH%3 2%3 $%3KHDUWUDWHDQG
BP variability assessed by dABP standard deviation (SD) were recorded.
Results: Baseline clinical, BP and biological characteristics were comparable
LQERWKJURXSV,QWKH5'1JURXSV\VWROLFGLDVWROLF 6' 2%3DQGG$%3GH-
FUHDVHGE\PP+JDQGPP+JUHVSHFWLYHO\ S 16DQGS 16
NS versus observation group). The systolic OBP (SOBP) decrease at 6 months
ZDVVLJQL¿FDQWO\DQGQHJDWLYHO\FRUUHODWHGZLWKWKHEDVHOLQH6'RIWKHV\VWROLF
dABP (SdABP) (r= -0.67, p=0.009). The decrease in both SOBP and SdABP at
PRQWKVZDVQHJDWLYHO\DQGVLJQL¿FDQWO\FRUUHODWHGWRWKHFKDQJHLQWKH6'RI
6G$%3EHWZHHQEDVHOLQHDQGPRQWKV U S DQGU S respectively). No such correlations were observed in the observation group.
Conclusions: Initial BP variability is associated with a greater OBP response
WR5'1VXJJHVWLQJWKDWSUHSURFHGXUH%3YDULDELOLW\PD\EHXVHIXOWRSUHGLFW
WKHVXFFHVVRI5'1)XUWKHUPRUHGHFUHDVHLQ%3YDULDELOLW\DIWHU5'1LVDVsociated with OBP and ABP changes. BP variability as a marker of sympathetic
activity, should be tested in larger scale studies to assess its value with good
VHQVLWLYLW\DQGVSHFL¿FLW\
6C.03
LOW-INTENSITY AEROBIC TRAINING AVOIDS
AGE-RELATED LOSS OF CARDIAC VAGAL
PREGANGLIONIC NEURONS IN SPONTANEOUSLY
HYPERTENSIVE RATS
$5XJJHULC. Santos, 53LQKHLURS. Aguiar, A. Ceroni, L. Michelini. Dept.
Physiology and Biophysics, Biomedical Sciences Institute, University of São
Paulo, São Paulo, BRAZIL
Objective: 6LQFH6+5H[KLELWVDJHUHODWHGLPSDLUPHQWRIYDJDOFRQWURORIWKH
heart, we investigate the sequential effects of training (T) on hemodynamic
SDUDPHWHUVEDURUHÀH[FRQWURORIKHDUWUDWH +5 DQGGHQVLW\RIFDUGLDFYDJDO
preganglionic neurons in autonomic brainstem areas during the establishment
of hypertension.
Design and method: 0DOH6+5 GD\V ZHUHVXEPLWWHGWRWUHDGPLOO7 RIPD[LPDOFDSDFLW\KGD\GZHHN RUNHSWVHGHQWDU\ 6 IRUZHHNV$W
weeks 0, 1, 2, 4 and 8, chronic catheters were implanted for resting pressure
$3 DQG+5UHFRUGLQJVDQGWHVWLQJRIEDURUHÀH[VHQVLWLYLW\ %U6SKHQ\OHSKULQH
DQGVRGLXPQLWURSUXVVLGHLY 5DWVZHUHHXWKDQL]HGDQGSHUIXVHG '0(03)$
EUDLQVZHUHSRVW¿[HGDQGFU\RSURWHFWHG6HTXHQWLDOEUDLQVWHPVOLFHV —P ZHUHSURFHVVHGIRUFKROLQHDFHW\OWUDQVIHUDVH &+$7LPPXQRUHDFWLYLW\ LPDJHV ZHUH DFTXLUHG DQG DQDO\]HG ,PDJH - $JHPDWFKHG :.< VHUYHG DV
time-control.
Results: 7LQFUHDVHGWUHDGPLOOSHUIRUPDQFH YV6+56 DQGUHGXFHG$3
“PP+JDW7YV“PP+JLQ6+56JURXS 7DXJPHQWHGDJHUHODWHG+5IDOO 6 “6 “EPLQ FDXVLQJFRPSOHWHQRUPDOL]DWLRQRI
UHVWLQJ+5 “EPLQDW77YDOXHVLPLODUWRDJHPDWFKHG:.< (YHQ
LQWKHSHUVLVWHQFHRIK\SHUWHQVLRQ7QRUPDOL]HGEDURUHÀH[FRQWURORI+5 +5
UDQJH “EPLQ%U6 “EPLQPP+JDW77DQGLQFUHDVHVYV6+56 DQGEORFNHGLWVDJHGHSHQGHQWZRUVHQLQJ +5UDQJH “
EPLQDQG%U6 “EPLQPP+JDW6 7KHVHHIIHFWVZHUHDFFRPSDQLHG
by a prompt increase in integrated density of CHAT-positive neurons in the inWHUPHGLDWHSRUWLRQRIWKHGRUVDOPRWRUQXFOHXVRIWKHYDJXV “DW77YV
“DW6FDODPXVVFULSWRULXPWR—P DQGE\LQFUHDVHGLQWHQVLW\DW7
(+18%) associated with blockade of age-related reduction in CHAT neurons in
WKHQXFOHXVDPELJXXVFRPSDFWSDUW “DW6DQG7YV“QHXURQVDW6 Conclusions: ,QDGGLWLRQWRUHGXFHSUHVVXUHRIWKH\RXQJ6+57QRUPDOL]HVERWK
UHVWLQJ+5DQGEDURUHFHSWRUUHÀH[FRQWURORI+52XUGDWDVXJJHVWWKDW7LQGXFHG
preservation of cardiac vagal preganglionic neurons is the main determinant of imSURYHGDXWRQRPLFFRQWURORIWKHKHDUWLQWUDLQHG6+5
6C.04
RENAL SYMPATHETIC REGULATION IN A
CONSCIOUS RABBIT MODEL OF CHRONIC KIDNEY
DISEASE
G.A. Head, S. Burke, P. Davern, /9DQ5HQVFKM. Schlaich. Baker IDI Heart
and Diabetes Institute, Melbourne, AUSTRALIA
Objective: Chronic kidney disease is an increasing disease burden affecting
nearly 1 in 20 Australians (AusDiab 2012). Impairment of renal function is associated with neuro-humoral disturbances and strongly predicts mortality. A feature of the disease is activation of the sympathetic nervous system and elevated
EORRGSUHVVXUH:HLQYHVWLJDWHGDQRYHOFRQVFLRXVUDEELWPRGHORIFKURQLFLP-
S
U
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A
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e79
Journal of Hypertension Volume 32, e-Supplement 1, 2014
paired renal function in which quantitative comparisons can be made of symSDWKHWLF DFWLYLW\ :H DLPHG WR FKDUDFWHULVH WKH VWDELOLW\ RI WKH LPSDLUHG UHQDO
IXQFWLRQRYHUWKH¿UVWIHZZHHNVDQGGHWHUPLQHWKHHIIHFWRQDXWRQRPLFUHÀH[
function and the response to stress and hypoxia.
Design and method: &KURQLFUHQDOIDLOXUHZDVLQGXFHGE\OHVLRQLQJRIWKRI
the glomerular layer of the renal cortex in one kidney and after 2 weeks recovery
removing the contralateral kidney.
Results: In 4 rabbits, plasma creatinine was elevated the following day and rePDLQHGKLJKHUIRUWKHHQWLUHZHHNVWXG\SHULRG%RG\ZHLJKWDQGÀXLG
intake were well maintained in 3 of the 4 rabbits but in all cases had recovered by
2-3 weeks. After 3 weeks, a renal nerve electrode was implanted on the remaining
kidney and at 4 weeks the experiment was performed while the rabbit was conscious. Blood pressure, heart rate and renal sympathetic nerve activity were 9%,
15% and 98% greater than that observed in the sham group. The increase in the
response to a 10 minute airject stress was also 50-70% greater in the renal failure
group compared to sham. The sympathetic response to hypoxia was over 300%
greater in the renal failure group but the slope and range of renal sympathetic and
FDUGLDF EDURUHÀH[ FXUYHV ZHUH VLPLODU LQ ERWK JURXSV 7KH RQO\ FKDQJH LQ WKH
EDURUHÀH[V\PSDWKHWLFFXUYHZDVDQXSZDUGVKLIWRIERWKWKHXSSHUDQGORZHUSODteaus indicating a “baro-independent” activation of sympathetic nervous activity.
Conclusions: 7KHVH¿QGLQJVVXJJHVWWKDWVKRUWWHUPLPSDLUHGUHQDOIXQFWLRQFDQ
lead relatively quickly to a baroreceptor independent activation of central sympathetic pathways and hyper-responsivity to stress and chemoreceptor activation. These factors may explain the poor prognosis of renally impaired patients.
6C.05
DECREASED CAROTID DISTENSIBILITY IS PRESENT
BUT DOES NOT EXPLAIN THE IMPAIRMENT OF
BAROREFLEX-FUNCTION IN SCHIZOPHRENIC
PATIENTS
A. Sárközi 1, B. Mersich 2, D. Cseh 1, M. Kollai 1, A. Pintér 1. 1 Semmelweis
University, Institute of Human Physiology and Clinical Experimental Research,
Budapest, HUNGARY, 2 Semmelweis University, Department of Psychiatry and
Psychotherapy, Budapest, HUNGARY
Objective: Increased cardiovascular mortality was reported in schizophrenic
patients, most frequently due to arrhythmia-related sudden cardiac death. It was
shown that impaired short-term blood pressure regulation, indicated by reduced
EDURUHÀH[VHQVLWLYLW\ %56 ZDVDULVNIDFWRUIRUVXGGHQFDUGLDFGHDWKLQYDULRXVGLVHDVHGVWDWHV5HGXFHG%56ZDVIRXQGLQVFKL]RSKUHQLFSDWLHQWVEXWWKH
XQGHUO\LQJPHFKDQLVPZDVQRWFODUL¿HG6WLIIHQLQJRIEDURUHFHSWRUYHVVHOZDOO
PD\UHVXOWLQGHFUHDVHGDFWLYLW\RIWKHEDURUHFHSWRUVDQGEOXQWWKHEDURUHÀH[,Q
this study, we investigated the distensibility of a baroreceptor vessel wall – such
DVWKHFRPPRQFDURWLGDUWHU\±DQGWHVWHGWKHK\SRWKHVLVWKDWUHGXFHG%56LV
associated with increased carotid artery stiffness in schizophrenic patients.
Design and method: ¿UVWHSLVRGHVFKL]RSKUHQLFSDWLHQWV “\HDUV DQG
28 healthy, age- and gender-matched control subjects were examined. Diastolic
diameter and pulsatile distension of the common carotid artery were measured
by echo wall-tracking, carotid pulse pressure was registered by tonometry.
%DVHG RQ WKHVH GDWD GLVWHQVLELOLW\ FRHI¿FLHQW '& ZDV FDOFXODWHG 7KH %56
was determined by analysing 10-minute-long, simultaneous ECG and beat-tobeat blood pressure recordings.
Results: DC showed marked reduction in schizophrenic patients compared to
FRQWUROVXEMHFWV “‚YV“ ñ[PP+J $VH[SHFWHG%56ZDV
VLJQL¿FDQWO\ GHFUHDVHG LQ SDWLHQWV “‚ YV “ PVPP+J 1R UHODWLRQ ZDV IRXQG EHWZHHQ WKH '& DQG WKH %56 LQ SDWLHQWV ZKHUHDV WKH WZR
SDUDPHWHUVVKRZHGVLJQL¿FDQWSRVLWLYHFRUUHODWLRQLQFRQWUROVXEMHFWV U ‚ PHDQ“6'XQSDLUHGWWHVW3HDUVRQ¶VFRUUHODWLRQWHVW‚S Conclusions: In schizophrenic patients, carotid artery distensibility was markHGO\ UHGXFHG EXW LW ZDV QRW UHODWHG WR GLPLQLVKHG EDURUHÀH[VHQVLWLYLW\ 7KH
underlying mechanism for increased carotid artery stiffness is yet unclear. In
schizophrenic patients, elevated plasma homocysteine level and increased oxidative stress may contribute to the decrement of carotid distensibility. Our results suggest that decreased carotid elasticity does not contribute to the impairPHQWRIEDURUHÀH[IXQFWLRQVXEVWDQWLDOO\:HSUHVXPHWKDWUHGXFHG%56PD\EH
UHODWHGWRDQHXURQDOGDPDJHZLWKLQWKHEDURUHÀH[DUFK
6C.06
THE EFFECTS OF POSITIVE ALLOSTERIC
MODULATION OF GABAA RECEPTORS UPON
STRESS AND HYPERTENSION IN SCHLAGER
HYPERTENSIVE MICE
E. Stevenson, .-DFNVRQB. Abegaz, -0RUHWWLC. Gueguen, P. Davern. Baker
IDI Heart and Diabetes Institute, Neuropharmacology, Melbourne, AUSTRALIA
Objective: An exaggerated pressor response to stress has been shown to be a predictor
RIWKHVXEVHTXHQWGHYHORSPHQWRIK\SHUWHQVLRQ+\SHUWHQVLYH6FKODJHUPLFH %3+- have neurogenic hypertension associated with abnormal reactivity of neurons in the
IRUHEUDLQLQWHJUDWLQJWKHUHVSRQVHWRDYHUVLYHVWUHVV5HFHQWVWXGLHVVXJJHVWWKH\DOVR
have functional and molecular differences in GABAA receptors compared to their norPRWHQVLYH FRXQWHUSDUWV %31- $OORSUHJQDQRORQH LV DQ HQGRJHQRXV QHXURVWHURLG
reduced by chronic stress and when administered, decreases anxiety by positive alORVWHULFPRGXODWLRQRI*$%$$UHFHSWRUV:HDLPHGWRGHWHUPLQHLIDOORSUHJQDQRORQH
UHGXFHVWKHSUHVVRUHIIHFWVRIVWUHVVDQGEDVDO0$3LQ%3+-PLFH
Design and method: 0DOH%31- Q DQG%3+- Q PLFHUHFHLYHGYHKLFOH
RUDOORSUHJQDQRORQH —JKRXU YLDVXEFXWDQHRXVPLQLSXPSVIRUDSHULRGRIWZR
weeks. Prior implantation of telemetric probes enabled recording of mean arteULDOSUHVVXUH 0$3 KHDUWUDWH +5 DQGDFWLYLW\EHIRUHDQGDQGGD\VDIWHU
minipump implantation. The cardiovascular response to aversive and non-aversive
VWUHVVWHVWVDVZHOODVJDQJOLRQLFEORFNDGHZLWKPJNJSHQWROLQLXPZHUHUHFRUGHG
before and 7-14 days after minipump implantation. Mice were perfused following
stress and brains were removed for immunohistochemistry.
Results: Two weeks of allopregnanolone reduced systolic arterial pressure
(-8.8mmHg, P=0.01) and attenuated the depressor response to pentolinium in
%3+-PLFHZKHUHDVQRHIIHFWXSRQ0$3RU+5ZHUHREVHUYHGLQ%31-PLFH
Allopregnanolone produced marked reductions in the pressor response to both
FDJHVZLWFKDQGIHHGLQJVWUHVV 3 LQ%3+-PLFHZKLOVWLQFUHDVLQJ
WKHSUHVVRUUHVSRQVHWRDYHUVLYHVWUHVVLQ%31-PLFH 3 6WUHVV
induced Fos counts within the medial amygdala and paraventricular nucleus were
KLJKHULQXQWUHDWHG%3+-FRPSDUHGWR%31-$OORSUHJQDQRORQHUHGXFHG)RV
expression and treatment abolished the difference between strains.
Conclusions: The selective antihypertensive and stress inhibitory effects of alORSUHJQDQRORQHLQ%3+-K\SHUWHQVLYHPLFHVXJJHVWVWKDWDOORVWHULFPRGXODWLRQ
of GABAA receptors at the level of the hypothalamus and amygdala may be a
major cause of hypertension in this model and may offer a possible new area for
the development of therapy.
6C.07
BEYOND PRESSURE-NATRIURESIS: INSIGHTS
INTO THE RENAL NERVE MEDIATED MECHANISMS
RESPONSIBLE FOR MAINTAINING SODIUM AND
VOLUME HOMEOSTASIS DURING AN ACUTE SODIUM
CHALLENGE
5:DLQIRUG-.XZDEDUDS. Mahne.
Boston University, Department of Pharmacology, Boston, MA, USA
Objective: :HUHFHQWO\UHSRUWHGWKDWGXULQJQRQSUHVVRULVRYROXPHWULFVRGLXP
ORDGLQJ&16*ĮLVXEXQLWSURWHLQJDWHGVLJQDOWUDQVGXFWLRQSDWKZD\VSOD\DQ
essential role in mediating renal nerve dependent natriuresis in conscious rats.
The aim of this study was to investigate the role(s) of the renal sympathetic
QHUYHVLQWKHVXSSUHVVLRQRIUHQDOĮ ȕDGUHQHUJLFUHFHSWRUPHGLDWHGVRGLXP
reabsorption, to facilitate natriuresis, during an acute sodium load.
Design and method: An isovolumetric sodium load (1M NaCl) was adminisWHUHGRYHUKYLDLYLQIXVLRQ ȝOPLQ LQFRQVFLRXVVKDPRUDFXWHELODWHUDO
UHQDOGHQHUYDWHG 5'1; PDOH6SUDJXH'DZOH\UDWV 1 JS ,QVHSDUDWHFRKRUWVRIDQLPDOV 1 JS 01D&OZDVDGPLQLVWHUHGLYZLWKHLWKHUYHKLFOH
VDOLQH DQĮDQWDJRQLVW WHUD]RVLQȝJNJPLQ RUDȕDQWDJRQLVW SURSUDQROROȝJNJPLQ 0$3+5DQGXULQDU\VRGLXPH[FUHWLRQ 81D9 ZHUH
continuously recorded during a 1hr control, 2h NaCl load, and a 2h recovery
period. Plasma and hematocrit were collected - estimated plasma volume (EPV),
estimated blood volume (EBV), and plasma sodium was determined.
Results: $FXWH5'1;EOXQWHGWKHSHDNQDWULXUHWLFUHVSRQVH SHDNFKDQJH81D9
>ȝHTȝO@6KDP“YV5'1;“3 WRDQLVRYROXPHWULFVRGLXPORDGWKDWGLGQRWDOWHU0$3RU+5,QKLELWLRQRIĮDGUHQRFHSWRUVEOXQWHGWKH
FXPXODWLYHQDWULXUHWLFUHVSRQVHWRDQRQSUHVVRUVRGLXPORDGWRDVLJQL¿FDQWO\
JUHDWHUPDJQLWXGHWKDQWKDWREVHUYHGGXULQJȕDGUHQRFHSWRUDQWDJRQLVP FXPXODWLYH81D9>ȝHTȝO@9HKLFOH“YV7HUD]RVLQ“YV3URSUDQRORO
“3 1HLWKHUĮRUȕUHFHSWRUDQWDJRQLVPUHVXOWHGLQDOWHUHGSODVma sodium content. However, terazosin, but not propranolol, infusion resulted
LQ DVLJQL¿FDQWLQFUHDVHLQ(39GXULQJWKHVRGLXPORDGDQGUHFRYHU\SHULRGV
(39>PO@7HUD]RVLQFRQWURO“YVVRGLXPORDG“YVUHFRYHU\
“3 DQG DVLJQL¿FDQWUHGXFWLRQLQIUHH+2FOHDUDQFH7KLV
LPSOLHV YDVRSUHVVLQ PHGLDWHG ZDWHU UHWHQWLRQ RFFXUUHG GXULQJ ĮDGUHQRFHSWRU
antagonism to maintain plasma sodium homeostasis.
Conclusions: Our data demonstrate a critical role of the renal sympathetic
nerves in maintaining sodium homeostasis during an acute sodium challenge
independently from the traditional pressure-natriuresis response. Moreover, we
FDQLQIHUWKDWWKHVHSURFHVVHVDUHIXQFWLRQLQJWKURXJKDSUHGRPLQDQWO\ĮUDWKHU
WKDQȕUHFHSWRUPHGLDWHGSDWKZD\WRIDFLOLWDWHQDWULXUHVLV
Abstracts
e80
ORAL SESSION
ORAL SESSION 6D
NEW THERAPEUTIC DEVELOPMENTS
AND PERIPHERAL VASCULAR DISEASE
6D.01
PDE3 INHIBITOR, CILOSTAZOL IMPROVES BLOOD
FLOW IN HIND LIMB ISCHEMIA THROUGH PPARȖ/
HGF/ENOS PATHWAY
Y. Kanbara 1, F. Sanada 1, Y. Taniyama 1,2, M. Iwabayashi 1, Y. Ikeda-Iwabe 1,
-$]XPD1, +5DNXJL2, 50RULVKLWD1. 1 Department of Clinical Gene
Therapy, Osaka University Graduate School of Medicine, Suita, JAPAN,
2
Department of Geriatric and Nephrology, Osaka University Graduate School
of Medicine, Suita, JAPAN
Objective: Cilostazol is the only drug that has been shown in multiple randomized clinical trials to decreased intermittent claudication and improved ability to
walk in patients with peripheral arterial disease (PAD). Additionally, it improves
EORRGÀRZWRWKHLVFKHPLFOLPEZLWKSKDUPDFRORJLFDOHIIHFWVWKDWLQFOXGHYDVRdilation, inhibition of platelet activation and aggregation, inhibition of thrombosis. However, its mechanism remains unclear.
were measured non-invasively with validated devices. Left ventricular mass
index (LVMI) was measured by cardiac ultrasonography using the Devereux
IRUPXOD&UHDFWLYHSURWHLQ &53 ZDVPHDVXUHGDVDQLQGH[RILQÀDPPDWRU\
status. Chronic kidney disease stage was determined according to estimated
JORPHUXODU ¿OWUDWLRQ UDWH YDOXHV 7KH \HDU ULVN IRU FDUGLRYDVFXODU GLVHDVH
&9' ZDV FDOFXODWHG XVLQJ WKH )UDPLQJKDP 5LVN 6FRUH &RUUHODWLRQ FRHI¿FLHQWV DQDO\VLV RI YDULDQFH DQG UHJUHVVLRQ DIWHU FRQWUROOLQJ IRU FRQIRXQGHUV
were calculated.
Results: 7KHFRKRUWZDV\RXQJ DJH“\HDUVROG ZLWKPLOGPRGHUDWHK\SHUWHQVLRQ V\VWROLF%3“PP+JGLDVWROLF%3“PP+J DQGPHDQ
$%,YDOXH“ZHUHPHQVPRNHGDQGZHUHGLDEHWics. Left ventricular hypertrophy was detected in 42.2% of the population and
WKH\HDU&9'ULVNZDV“$%,FRUUHODWHGZLWKFI3:9FHQWUDOV\VWROLF%3$,[/90,DQG&53 3HDUVRQ¶VU
respectively, p<0.01 for all). The 10-year risk for CVD increased with lower
ABI values (r=-0.077, p<0.01). After adjusting for confounders, patients with
/9+KDGKLJKHUOHYHOVRI$%,ORZHU$%,YDOXHVZHUHREVHUYHGZLWKZRUVHQLQJ
renal function (Figure).
Design and method: Mice at 3 months of age were fed with either Cilostazol
or Aspirin, starting from one week before the generation of hind limb ischemia
model through the experiment. Neutralizing antibody against hepatocyte growth
factor (HGF) was injected intra peritoneum for the analysis of the mechanism
underlying the effectiveness of Cilostazol on limb ischemia. Local level of HGF
expression was evaluated by immunocytochemistry and ELISA. Human as well
DV5DWDRUWLFVPRRWKPXVFOHFHOOVZHUHXVHGLQYLWURWRHOXFLGDWHWKHGRZQVWUHDP
target of Cilostazol. Akt, eNOS, c-Met phosphorylation were evaluated by western blotting.
Results: Administration of Cilostazol (0.3% chow), but not Aspirin (0.1%
FKRZ VLJQL¿FDQWO\ UHVWRUHG EORRG ÀRZ ZHHNV DIWHU PRXVH KLQG OLPE LVFKemia. Interestingly, HGF protein expression was 1.5 times higher in Cilostazol
treatment group compare to control or aspirin treatment group, and secreted
PDLQO\IURP60&LQWKHDUWHU\&RQVLVWHQWZLWKWKLV¿QGLQJLWVEHQH¿FLDOHIIHFW
RQEORRGÀRZZDVFDQFHOOHGE\WKHLQMHFWLRQRIQHXWUDOL]LQJDQWLERG\DJDLQVW
HGF. Theas observations suggest that Cilostazol ameliorates tissue oxygenation
through the increase in the expression of HGF in the artery.
)XUWKHU ZH IRXQG WKDW &LORVWD]RO XSUHJXODWHV 33$5Ȗ DFWLYLW\ ZKLFK VXEVHquently enhances HGF transcripts by binding its promoter. Consequently, endothelial cells co-cultured with medium in which SMC was stimulated with
&LORVWD]ROIRUKRXUVVKRZHGVLJQL¿FDQWLQFUHDVHLQWKHS$NWSH126H[pression through HGF receptor, c-Met.
Conclusions: &LORVWD]ROHQKDQFHVEORRGÀRZLQLVFKHPLFOLPEWKURXJK33$5Ȗ
+*)F0HW SDWKZD\7KLV PHFKDQLVP PLJKW FRQWULEXWHV WR IDYRUDEOH HIIHFW RI
cilostazol observed in clinical trials of patients with PAD.
6D.02
ARE INTERMEDIATE ANKLE-BRACHIAL INDEX
VALUES IMPORTANT IN HYPERTENSION? INSIGHTS
FROM A LARGE COHORT OF NEVER-TREATED
HYPERTENSIVES
3;DSODQWHULVA. Aggelakas, M. Abdelrasoul, N. Ioakeimidis, A. Synodinos,
G. Vyssoulis, C. Stefanadis. 1st Department of Cardiology, Hippokration
Hospital, Athens Medical School, Athens, GREECE
Objective: Ankle brachial index (ABI) is a diagnostic tool for peripheral arteULDOGLVHDVHPRUHRYHULWKDVDSURJQRVWLFYDOXHIRUIXWXUHFDUGLRYDVFXODUHYHQWV
+RZHYHU WKH UROH RI LQWHUPHGLDWH$%, YDOXHV WR LV VWLOO XQFOHDU:H
investigated the interplay of intermediate ABI values with indices of subclinical
organ damage in a large cohort of newly diagnosed, never treated hypertensives.
Design and method: 1,127 newly diagnosed, never-treated hypertensives were
recruited. ABI was measured with the oscillometric method and subjects with
ABI <0.9 or >1.3 were not included in the study. Carotid-femoral pulse wave veORFLW\ FI3:9 FHQWUDO DRUWLF EORRGSUHVVXUHVDQGDXJPHQWDWLRQLQGH[ $,[ Conclusions: Intermediate ABI values carry prognostic information in nevertreated hypertensives, as they are related to large artery stiffness, impaired central hemodynamic indices, LVH, renal function impairment and 10-year risk of
CVD. ABI measurements should be part of an integrated approach to hypertensive patients for both diagnostic and prognostic reasons.
6D.03
SAFETY AND PERFORMANCE OF THE ENLIGHTN
RENAL DENERVATION SYSTEM IN PATIENTS WITH
UNCONTROLLED HYPERTENSION: 1 MONTH
RESULTS OF THE FIRST 100 PATIENTS IN THE
ENLIGHTN II STUDY
6:RUWKOH\1, -0RQWDUHOOR1, M. Saxena 2, $-DLQ2, ':DOWHUV3,
M. Pincus 3, M. Lobo 2. 1 Cardiovascular Research Centre, Royal Adelaide
Hospital, Adelaide, AUSTRALIA, 2 William Harvey Heart Centre, Queen
Mary University of London, London, UNITED KINGDOM, 3 Prince Charles
Hospital, Brisbane, AUSTRALIA
Objective: 5HDOZRUOGUHVXOWVIURP5HQDO'HQHUYDWLRQWULDOVZLWKODUJHUQXPEHU
of patients and sites including moderate HTN and medication intolerant patients
KDYHQRWEHHQUHSRUWHG:HIXUWKHULQYHVWLJDWHGWKHVDIHW\DQGHI¿FDF\RIDPXOti-electrode catheter ablation system.
Design and method: 3DWLHQWVZHUHDVVLJQHGWRRQHRIWKUHHJURXSV*URXS$
RI¿FH6%3!PP+JDQGH*)5!P/PLQ*URXS%RI¿FH6%3
PP+JDQGH*)5!P/PLQDQG*URXS&RI¿FH6%3!PP+JDQGH*)5
!P/PLQ)RUDOOWKUHHJURXSVVXEMHFWVZHUHUHTXLUHGWREHRQDWOHDVWDQWL
hypertensive medications (including 1 diuretic), or to have documented drug
intolerances and to be unable to take 3 anti-hypertensive drugs.
Results: 7KHUHVXOWVRIWKH¿UVWSDWLHQWVZLWKPRQWKIROORZXSZLOOEHSUHVHQWHG$WRWDORISDWLHQWV DYHUDJHDJH“\UVWDNLQJDQDYHUDJHRI
“PHGLFDWLRQV ZHUHLQFOXGHGLQWKLVVXEDQDO\VLV2IWKHVHSDWLHQWV
were female, 32.3% had Coronary Artery Disease, 43% had hyperlipidemia, 20%
had type II Diabetes Mellitus, and 11% had history of sleep apnea. Bilateral renal
nerve ablation was performed using a percutaneous femoral approach. The mean
DEODWLRQWLPHZDV“PLQXWHV%DVHOLQHDYHUDJHRI¿FHV\VWROLFEORRGSUHV-
S
U
N
D
A
Y
O
R
A
L
S
e81
Journal of Hypertension Volume 32, e-Supplement 1, 2014
VXUHZDV“PP+JDQGDYHUDJHKRXUDPEXODWRU\EORRGSUHVVXUHZDV
“PP+J$VRIWKHUHZHUHPRQWKIROORZXSYLVLWV
FRPSOHWHG7KHDYHUDJHUHGXFWLRQLQRI¿FH%3 2%3 ZDVPP+J2XWRI
these 89 subjects, 75 subjects were able assigned to one of the 3 groups accordLQJWKHSURWRFRO7KHDYHUDJHUHGXFWLRQLQ2%3SHUJURXSLVDVIROORZV*URXS$
Q PP+J*URXS% Q PP+JDQG*URXS& Q PP+J
The data will be refreshed prior to the meeting to include patients with 1 month of
follow-up data and safety data will also be presented.
Conclusions: In this study, we conclude that data demonstrates that the EnligHTN ablation system is safe and effective in the treatment of patients with
uncontrolled hypertension.
6D.04
LCZ696, A NOVEL ANGIOTENSIN RECEPTOR
NEPRILYSIN INHIBITOR: THE FIRST TRIAL IN
PATIENTS WITH SEVERE HYPERTENSION
K. Kario 1, Y. Tamaki 2, H. Kim 2, H. Gotou 2, M. Zhu 3, -=KDQJ4. 1 Division of
Cardiovascular Medicine, Department of Medicine, Jichi Medical University
School of Medicine, Tochigi, JAPAN, 2 Clinical Development, Novartis Pharma
KK, Tokyo, JAPAN, 3 Beijing Novartis Pharma Co. Ltd, Beijing, CHINA,
4
Novartis Pharmaceuticals Corporation, East Hanover, NJ, USA
Objective: Severe hypertension is associated with high cardiovascular risk and
EORRGSUHVVXUH %3 FRQWUROLVGLI¿FXOWWRDFKLHYH/&= -DSDQHVH$GRSWHG
1DPH>-$1@6XFDELWULO9DOVDUWDQ6RGLXP+\GUDWH@LVD¿UVWLQFODVVDQJLRWHQVLQ
UHFHSWRUQHSULO\VLQLQKLELWRU $51, 7KLVVWXG\HYDOXDWHGIRUWKH¿UVWWLPHWKH
VDIHW\WROHUDELOLW\DQGHI¿FDF\RI/&=LQ$VLDQSDWLHQWVZLWKVHYHUH *UDGH
3) hypertension.
Design and method: This was an 8-week, multi-center, open-label study. After
ZHHNVRIUXQLQSHULRGHOLJLEOHSDWLHQWV ZLWKHLWKHURI¿FHV\VWROLFEORRG
SUHVVXUH>6%3@! PP+JRURI¿FHGLDVWROLFEORRGSUHVVXUH>'%3@! mmHg) received LCZ696 200 mg. The dose was up-titrated to 400 mg at or
DIWHU:HHNLQSDWLHQWVZLWKLQDGHTXDWH%3FRQWURODQGZLWKRXWVDIHW\FRQFHUQV
followed by addition of another antihypertensive drug (except angiotensin reFHSWRUEORFNHU>$5%@DQJLRWHQVLQFRQYHUWLQJHQ]\PHLQKLELWRU>$&(,@RU¿[HG
FRPELQDWLRQFRQWDLQLQJ$5%RU$&(, DWRUDIWHU:HHNLI%3UHPDLQHGLQDGequately controlled and no safety concerns were observed. Safety was assessed
E\UHFRUGLQJDOODGYHUVHHYHQWV $(V DQGHI¿FDF\ZDVDVVHVVHGDVPHDQFKDQJH
LQ%3IURPEDVHOLQHWR:HHNHQGSRLQW
Results: A total of 35 patients received study treatment and all of them comSOHWHGWKHVWXG\ PHDQDJH\HDUVPHDQ>VWDQGDUGGHYLDWLRQ6'@EDVHOLQH
%3>@>@PP+JDQGPDOHV $WWKHVWXG\HQGRI
the 35 patients, 3 (8.6%), 11 (31.4%) and 21 (60%) patients received LCZ696
200mg, LCZ696 400mg and LCZ696 400mg with add-on antihypertensives, respectively. Seventeen patients (48.6%) reported AEs, the most common being
nasopharyngitis (n=6, 17.1%), increased blood creatine phosphokinase (n=3,
8.6%), and hyperuricemia (n=2, 5.7%). There were no cases of dizziness, hypotension, or angioedema. One patient experienced a serious AE of abnormal liver
function test with LCZ696 200 mg that was not suspected to be drug related and
ZDVUHVROYHG&OLQLFDOO\VLJQL¿FDQW%3UHGXFWLRQVZHUHREVHUYHGDW:HHNV
4, 6 and 8 with an LCZ696 based regimen (Table).
Objective: Previous studies in normotensive anesthetized rats (Lapi Arch.Ital.
Biol 151:11-23,2013) showed that peripheral stimulation of the trigeminal nerve
induced by submaximal mouth opening (mandibular extension, ME) caused prolonged (at least 80min) bradycardia, hypotension and cerebral hemodynamic
changes (pial arterioles showed a characteristic response pattern consisting in a
VLJQL¿FDQWFRQVWULFWLRQGXULQJ0(IROORZHGE\DGLODWDWLRQIRUWKHHQWLUHUHPDLQing observation time).
Design and method: In this study we assessed the in vivo effects of ME on
+5 0$%3 DQG SLDO PLFURFLUFXODWLRQ LQ K\SHUWHQVLYH UDWV ([SHULPHQWV ZHUH
SHUIRUPHGLQPDOH:LVWDUUDWVZHLJKLQJJ Q +\SHUWHQVLRQZDVLQGXFHGE\LQWUDSHULWRQHDOGDLO\LQMHFWLRQRIGH[DPHWKDVRQH PJNJGD\ IRU
10 days. ME was obtained by inserting an ad hoc developed retractor between
WKHGHQWDODUFKHV+5DQG0$%3ZHUHUHFRUGHGE\(&*DQGDFDWKHWHUSODFHG
in the left femoral artery and measured by a computer-assisted system. Pial arterioles were observed through a closed cranial window implanted above the left
SDULHWDOFRUWH[DQGYLVXDOL]HGE\DQLQYLYRÀXRUHVFHQFHPLFURVFRS\WHFKQLTXH
to assess vessel diameter changes before (baseline), during 10min ME and thereafter until 160min. Arteriolar diameters were measured with a computer-assisted
method (MIP Image program, frame by frame).
Results: ,QVKDPWUHDWHG QR0( K\SHUWHQVLYHUDWV Q +50$%3DQGSLDO
microcirculation did not change during whole observation period. Hypertensive
UDWVVXEMHFWHGWR0( Q VKRZHGDVLJQL¿FDQWGHFUHDVHRI+5DQG0$%3+5
declined by 42bpm, (p<0.01) starting from 60 min after ME up to 160min, while
MABP by 18mmHg (p<0.05) starting from 20min after ME up to 100min, compared with baseline. Pial arterioles exhibited a biphasic response: the arteriolar
GLDPHWHUGHFUHDVHGE\ȝP S GXULQJ0(DIWHUZDUGVLWVLJQL¿FDQWO\
LQFUHDVHGE\ȝP S VWDUWLQJIURPPLQDIWHU0(WKLVYDVRGLODWDWLRQ
lasted for the whole observation period.
Conclusions: Our results suggest that ME is able to exert profound and prolonged regulatory effects on systemic arterial blood pressure and pial arteriolar
tone in hypertensive rats.
6D.06
COMPARATIVE EFFICACY OF VALSARTAN AND
LCZ696, AN ANGIOTENSIN RECEPTOR NEPRILYSIN
INHIBITOR (ARNI), IN HYPERTENSIVE INDIVIDUALS
OVER AGE 65
-,]]R-U1, /05XLORSH2, L. Conde 3, D. Zappe 4, Y. Zhang 4, -=KDQJ4.
State University of New York at Buffalo and Erie County Medical Center,
Department of Medicine, Buffalo, NY, USA, 2 Instituto de Investigación,
Unidad de Hipertensión, Hospital 12 de Octubre, Madrid, SPAIN, 3 Novartis
Pharma AG, Global Medical Affairs, Basel, SWITZERLAND, 4 Novartis
Pharmaceuticals, Clinical Development, East Hanover, NJ, USA
1
Objective: After middle age, patients with hypertension (HTN) are characterized
by increasing stiffness of large arteries, elevated systolic blood pressure (SBP) and
pulse pressure (PP), and reduced responsiveness to antihypertensive drugs, espeFLDOO\ZKHQJLYHQDVPRQRWKHUDS\:HKDYHSUHYLRXVO\UHSRUWHGWKDWLQLQGLYLGXDOV
RYHUDJHWKHHI¿FDF\RIYDOVDUWDQLVORZHUWKDQK\GURFKORURWKLD]LGH7KHSUHVHQW
DQDO\VLVDGGUHVVHVWKHTXHVWLRQZKHWKHUDJLQJLQÀXHQFHVWKHHI¿FDF\RI/&=
-DSDQHVH$GRSWHG1DPH>-$1@6XFDELWULO9DOVDUWDQ6RGLXP+\GUDWH D¿UVWLQ
FODVVDQJLRWHQVLQUHFHSWRUQHSULO\VLQLQKLELWRU $51, FRPSDUHGWRYDOVDUWDQ
Design and method: Data were pooled from two 8-week, multicenter, randomized, double-blind, placebo- and active-controlled studies in patients with
HTN to evaluate reductions in mean sitting (ms)BP and msPP in response to
daily therapy with either LCZ696 400 mg, valsartan 320 mg, or placebo. Patients were also dichotomized by age (>=65 yrs).
Conclusions: 7KH QRYHO $51, /&= EDVHG UHJLPHQ ZDV JHQHUDOO\ VDIH
well tolerated, and effective for the treatment of severe hypertension in Asian
patients.
6D.05
THE HYPOTENSIVE AND BRADYCARDIC EFFECTS OF
MOUTH OPENING: EVIDENCE IN AN ANIMAL MODEL
D. Lapi 1,2, C. Del Seppia 3, S. Ghione 3,4, A. Colantuoni 1, 56FXUL2.
Department of Clinical Medicine and Surgery, Federico II University
Medical School, Naples, ITALY, 2 Department of Translational Research on
New Technologies in Medicine and Surgery, University of Pisa, Pisa, ITALY,
3
Institute of Clinical Physiology, CNR, Pisa, ITALY, 4 Fondazione Toscana
Gabriele Monasterio, Pisa, ITALY
1
Results: Overall, 231 (27%) elderly and 617 (73%) non-elderly patients were
randomized. In the elderly patients treated with LCZ696 (mean age 70.5 yrs, 19%
! \UVPDOH&DXFDVLDQPHDQERG\ZHLJKWNJPHDQERG\
PDVVLQGH[NJPðPHDQGXUDWLRQRI+71\UV EDVHOLQHPVV\VWROLF 6
BP, ms diastolic (D)BP, and msPP were 160.7, 89.9, and 70.8 mmHg, respectively. In non-elderly (<65 yrs) patients, baseline msSBP, msDBP, and msPP were
156.8, 98.3, and 58.5 mmHg, respectively. After 8 weeks of treatment, in elderly
HTN patients, LCZ696 lowered msSBP by 5.1 mmHg (p<0.0001) and msPP by
4.5 mmHg (p<0.01) more than valsartan (Table). Treatment with LCZ696 was
safe and well tolerated with low adverse event rates in all groups.
e82
Journal of Hypertension Volume 32, e-Supplement 1, 2014
Conclusions: LCZ696 was superior to valsartan in reducing SBP and PP in oldHUDGXOWVHVSHFLDOO\LQWKRVHRYHUDJH7KXV$51,LVDQDWWUDFWLYHVWUDWHJ\
for the treatment of HTN in older patients. Further investigation is required to
identify whether LCZ696 has a direct effect on arterial stiffness.
6D.07
A NOVEL ANTI-HYPERTENSIVE THERAPY:
EVIDENCE FOR FLAXSEED AS A SOLUBLE EPOXIDE
HYDROLASE INHIBITOR IN A RANDOMIZED,
DOUBLE-BLINDED, PLACEBO CONTROLLED
CLINICAL TRIAL
S. Caligiuri 1,2,5, H. Aukema 2,4, $5DYDQGL1,5,6, 5*X]PDQ3, G. Pierce 1,2,5.
1
St. Boniface Hospital Research Centre, Institute of Cardiovascular Sciences,
Winnipeg, CANADA, 2 St. Boniface Hospital Research Centre, Canadian
Centre for Agri-Food Research in Health and Medicine, Winnipeg, CANADA,
3
St. Boniface Hospital Research Centre, Asper Institute of Clinical Research,
Winnipeg, CANADA, 4 University of Manitoba, Human Nutritional Sciences,
Winnipeg, CANADA, 5 University of Manitoba, Physiology, Winnipeg,
CANADA, 6 University of Manitoba, Internal Medicine, Winnipeg, CANADA
Objective: Previously, in the FlaxPAD trial, participants with peripheral arterial
GLVHDVHDQGK\SHUWHQVLRQFRQVXPHGJRIPLOOHGÀD[VHHGGD\DQGH[KLELWHG
VLJQL¿FDQW UHGXFWLRQV LQ V\VWROLF PP+J DQG GLDVWROLF PP+J EORRG
SUHVVXUHDIWHUPRQWKV$SURPLQHQWFRPSRQHQWRIÀD[VHHGLVWKHQIDWW\DFLG
DOSKDOLQROHQLFDFLG $/$ $VDUHVXOWSODVPD$/$LQFUHDVHGVLJQL¿FDQWO\LQ
WKHÀD[JURXSDQGZDVLQYHUVHO\DVVRFLDWHGZLWKEORRGSUHVVXUH'HVSLWHWKLVUHlationship, the mechanism of action remained unclear. Polyunsaturated fatty acids can be metabolized to oxylipins. Some oxylipins can regulate vascular tone.
7KHUHIRUHLWZDVK\SRWKHVL]HGWKDWÀD[VHHGFRQVXPSWLRQUHGXFHGYDVRFRQVWULFWLYH R[\OLSLQV7KH VWXG\ REMHFWLYH ZDV WR GHWHUPLQH LI ÀD[VHHG FRQVXPSWLRQ
FKDQJHGWKHSODVPDR[\OLSLQSUR¿OHLQDPDQQHUWKDWLQÀXHQFHGEORRGSUHVVXUH
Design and method: FlaxPAD is a randomized, double-blinded, placebo controlled clinical trial. Plasma of FlaxPAD participants (n=76) underwent solid
SKDVHH[WUDFWLRQPXOWLSOHUHDFWLRQPRQLWRULQJDQG+3/&0606DQDO\VLV2[\OLSLQVZHUHTXDQWL¿HGZLWKWKHVWDEOHLVRWRSHGLOXWLRQPHWKRG
Results: $IWHU PRQWKV WKH ÀD[ JURXS H[KLELWHG D VLJQL¿FDQW GHFUHDVH LQ plasma oxylipins versus control (p<0.05). Six of these oxylipins were associDWHGZLWKLQÀDPPDWLRQDQGORVVRIYDVRGLODWLRQ GLK\droxyeicosatrienoic acid, 9,10- and 12,13-dihydroxyoctadecenoic acid). These
six oxylipins were products of the enzyme soluble epoxide hydrolase (sEH), a
pharmacological target for anti-hypertensive treatment. This suggested a bioDFWLYH RI ÀD[VHHG PD\ KDYH LQKLELWHG V(+ 8VLQJ DQ V(+ LQKLELWRU VFUHHQLQJ
DVVD\LQFUHDVLQJSK\VLRORJLFDOFRQFHQWUDWLRQVRIWKHÀD[VHHGELRDFWLYH$/$
GHFUHDVHGV(+DFWLYLW\ S ȡ 6(+PD\EHDQHIIHFWLYHDQWLK\pertensive target because individuals that exhibited a decrease in total plasma
V(+GHULYHGR[\OLSLQVH[KLELWHGDVLJQL¿FDQWGHFUHDVHLQV\VWROLFEORRGSUHVVXUH
>PP+J @YHUVXVWKRVHZKRH[KLELWHGLQFUHDVHGSODVPDV(+
GHULYHGR[\OLSLQV>PP+J @6SHFL¿FDOO\RQO\DUHGXFWLRQLQ
plasma 9,10-dihydroxyoctadecenoic acid and 8,9-dihydroxyeicosatrienoic acid
ZHUHVLJQL¿FDQWO\DVVRFLDWHGZLWKEORRGSUHVVXUHUHGXFWLRQ
Conclusions: 7KHVH ¿QGLQJV GHPRQVWUDWH WKDW WKH$/$ LQ ÀD[VHHG PD\ EH D
novel anti-hypertensive therapy by inhibiting sEH and reducing plasma oxylipLQVDVVRFLDWHGZLWKLQÀDPPDWLRQDQGORVVRIYDVRGLODWLRQ
6D.08
SAFETY, TOLERABILITY, PHARMACOKINETICS AND
PHARMACODYNAMICS OF MULTIPLE ASCENDING
DOSES OF QGC001, A CENTRALLY-ACTING
AMINOPEPTIDASE A INHIBITOR, IN HEALTHY
VOLUNTEERS
F. Balavoine 1, M. Azizi 2, D. Bergerot 2, N. De Mota 3, 53DWRXUHW4, %5RTXHV4,
C. Llorens-Cortes 3. 1 Quantum Genomics, Massy, FRANCE, 2 Clinical
Investigation Centre 9201, Hôpital Européen Georges Pompidou, Université
Paris-Descartes, Paris, FRANCE, 3 INSERM U1050, CIRB, Collège de
France, Paris, FRANCE, 4 INSERM U1022, Université Paris-Descartes, Paris,
FRANCE
Objective: Inhibition of brain aminopeptidase A (APA), the enzyme generating brain angiotensin-III, has emerged as a novel antihypertensive treatment,
DV GHPRQVWUDWHG LQ DQLPDO PRGHOV 4*& SUHYLRXVO\ QDPHG 5% LV D
prodrug converted in the brain in its active metabolite EC33, a selective APA
inhibitor. Single oral dose administration of QGC001 is safe up to 1250 mg in
KXPDQV:HWKXVHYDOXDWHGLWVVDIHW\DQGLWVSKDUPDFRNLQHWLFDQGSKDUPDFRG\QDPLFSUR¿OHVDIWHUUHSHDWHGGRVLQJ
Design and method: 36 normotensive male volunteers were randomly assigned
to receive in double-blind and fasted conditions, 500, 750, and 1000 mg b.i.d. of
4*& Q GRVH RUSODFHER Q GRVH IRUGD\V:HPHDVXUHGSODVPDDQG
XULQHOHYHOVRIERWK4*&DQG(&E\/&0606SODVPDUHQLQFRQFHQWUDWLRQV 35& SODVPDDOGRVWHURQH 3$OGR DQGSODVPDFRUWLVRO 3&RUW FRQFHQWUDWLRQVDQG6%3'%3DQGKHDUWUDWH +5 DWYDULRXVWLPHSRLQWV
Results: QGC001 up to 750 mg b.i.d. was well-tolerated. At the 1000 mg b.i.d.
dose, 4 subjects had liquid stools and 6 a rash. All QGC001 doses were rapidly
absorbed (tmax range: 1-5 h) and converted to EC33 within 3.5 to 5h. Peak
plasma concentrations (Cmax) and area under the curve (AUC) of QGC001 and
EC33 increased linearly with the dose and time. The median AUC accumulation ratio of QGC001 was 1.3, 1.6, 2.7 and that of EC33 was 1.6, 1.5, 2.1 for
the 500, 750 and 1000 mg b.i.d. dose. The median plasma elimination half-life
W RI 4*& LQFUHDVHG IURP K RQ 'D\ WR !K RQ 'D\ DQG WKDW RI
(&LQFUHDVHGIURPWR!KUHVSHFWLYHO\:KHQFRPSDUHGWRSODFHER
4*&GLGQRWVLJQL¿FDQWO\FKDQJH35&3$OGR3&RUW+56%3DQG'%3LQ
any treatment group.
Conclusions: 4*&KDGDJRRGVDIHW\SUR¿OHXSWRPJELG7KHUHZDV
DPLOGDFFXPXODWLRQRI4*&DQG(&DQGLQFUHDVHLQWZLWKWLPH$V
shown in animal experiments, QGC001 had no effect (i) on the systemic reninDQJLRWHQVLQDOGRVWHURQHSDUDPHWHUVDQG LL RQ%3RU+5LQQRUPRWHQVLYHVXEMHFWV7KHVHGDWDVXSSRUWIXUWKHUHYDOXDWLRQRILWVFOLQLFDOHI¿FDF\LQK\SHUWHQsive patients.
6D.09
ACTIVATED PROTEIN C-PROTEIN C INHIBITOR
COMPLEX FOR DETECTION OF ABDOMINAL AORTIC
ANEURYSM IN 65 YEAR OLD MEN
M. Zarrouk, A. Gottsäter, -+ROVWB. Lindblad, M. Sterner.
Lund University, Malmö, SWEDEN
Objective: $EGRPLQDO DRUWLF DQHXU\VP $$$ GH¿QHG DV DRUWLF GLDPHWHU
>=30 mm, is a lethal cardiovascular disease in case of growth and rupture, and
$$$SDWLHQWV KDYH KLJK SUHYDOHQFH RI FDUGLRYDVFXODU GLVHDVHV K\SHUWHQVLRQ
ischemic heart disease and stroke. Screening for AAA therefore enables both
adequate treatment of cardiovascular risk factors, and surgical interventions to
reduce rupture and mortality. Our department annually invites 4300 65-year-old
men to AAA-screening.
Ultrasound is the standard screening method. However, it is operator dependent, more expensive than blood sampling, and sometimes inconclusive. AAApatients have increased levels of cardiovascular biomarkers, and we therefore
evaluated one, the activated protein C-protein C inhibitor (APC-PCI) complex,
in men undergoing ultrasound AAA-screening.
Design and method: In a cross-sectional cohort study, APC-PCI levels were
evaluated in 47 men with ultrasound detected AAA and 48 men with normal
aortic diameter. APC-PCI complex samples were drawn in conjunction with ultrasound screening and analyzed by investigators blinded to ultrasound results.
Results: PHGLDQ>UDQJH@ $RUWLFGLDPHWHUFRUUHODWHG U S ZLWK
APC-PCI complex levels.Men with AAA showed higher APC-PCI complex
>@ YV >@ —J/S %0, >
@YV>@S WULJO\FHULGHV >@YV>@
PPROO S DQG :%& >@ YV >@S EXW
ORZHU DQNOH EUDFKLDO LQGH[ >@ YV >@S DQG
+'/FKROHVWHURO >@ YV > @ PPROOS WKDQ PHQ
with normal aortic diameter. Men with AAA also more often were smokers,
>@YV>@S XVHGDQWLK\SHUWHQVLYHV >@YV
>@S DQGVWDWLQV >@YV>@S ,QPXOtivariate analysis this difference persisted (p=0.025) only for APC-PCI complex
OHYHOV$WKUHVKROGYDOXHRI$3&3&,FRPSOH[RI—J/VKRZHGDVSHFL¿Fity of 62.5% and a sensitivity of 81% for the presence of an AAA. Area under a
5HFHLYHURSHUDWLQJFKDUDFWHULVWLF 52& FXUYHZDV
Conclusions: APC-PCI complex levels are higher in AAA-patients, and show
KLJKHQRXJKVHQVLWLYLW\DQGDUHDXQGHUWKHFXUYHLQ52&DQDO\VLVWREHIXUWKHU
studied as alternative to ultrasound for the detection of AAA in a screening setting. However, the sensitivity of the marker is still too weak to be used as the
only diagnostic tool in 65-year-old men.
Abstracts
e83
ORAL SESSION
ORAL SESSION
ISH AUSTIN DOYLE AWARD
AD.01
AMBULATORY RECORDING OF WAVE REFLECTIONS
AND ARTERIAL STIFFNESS DURING INTRA- AND
INTERDIALYTIC PERIODS IN END-STAGE RENAL
DISEASE PATIENTS UNDER HEMODIALYSIS
P. Georgianos 1, 36DUD¿GLV1,3, A. Karpetas 1, G. Koutroumpas 2,
V. Sgouropoulou 1, G. Tzanis 1, K. Raptopoulou 1, A. Protogerou 4,
V. Liakopoulos 1, P. Zebekakis 1, $/DVDULGLV1. 1 Section of Nephrology and
Hypertension, 1st Department of Medicine, AHEPA University Hospital,
Thessaloniki, GREECE, 2 Department of Nephrology, Achillopouleion
General Hospital, Volos, GREECE, 3 Therapeutiki Dialysis Unit, Thessaloniki,
GREECE, 4 Hypertension Unit and Cardiovascular Research Laboratory, Laiko
Hospital, Medical School, National and Kapodistrian U, Athens, GREECE
Objective: (OHYDWHGZDYHUHÀHFWLRQVDQGDUWHULDOVWLIIHQLQJDUHVWURQJSUHGLFWRUVRIFDUGLRYDVFXODUPRUELGLW\DQGPRUWDOLW\LQKHPRGLDO\VLVSDWLHQWV
3UHYLRXVVWXGLHVLQYHVWLJDWLQJDUWHULDOFXVKLRQLQJIXQFWLRQLQWKHVHLQGLYLGXDOVZHUHEDVHGRQO\RQRI¿FHPHDVXUHPHQWVREWDLQHGVKRUWO\EHIRUHRUDIWHU
WKHKHPRGLDO\VLVSURFHGXUH7KHDLPRIWKLVVWXG\ZDVWRLQYHVWLJDWHSRWHQWLDOYDULDWLRQVLQZDYHUHÀHFWLRQDQGDUWHULDOVWLIIQHVVSDUDPHWHUVGXULQJWKH
LQWUD DQG LQWHUGLDO\WLF SHULRGV RYHU D KRXU SHULRG LQ FKURQLF KHPRGLDO\VLVSDWLHQWV
Design and method: $ WRWDO RI KHPRGLDO\VLV SDWLHQWV XQGHUZHQW D KRXU EUDFKLDO DQG DRUWLF DPEXODWRU\ EORRG SUHVVXUH PRQLWRULQJ $%30 ZLWK WKH XVH RI WKH QHZO\ FRPPHUFLDOO\ DYDLODEOH 0RELO2*UDSK GHYLFH
,(0 6WROEHUJ *HUPDQ\ $%30 LQFOXGHG D ZKROH KRXU KHPRGLDO\VLV
VHVVLRQDQGWKHVXEVHTXHQWKRXULQWHUGLDO\WLFLQWHUYDO0RELO2*UDSKLV
DQRYHOYDOLGDWHGEUDFKLDOFXIIEDVHGDXWRPDWLFRVFLOORPHWULFGHYLFHZKLFK
DGGLWLRQDOO\ UHFRUGV LQ DPEXODWRU\ FRQGLWLRQV SXOVH ZDYHIRUPV DW EUDFKLDO
DUWHU\DQGDVVHVVHVZDYHUHÀHFWLRQDQGDUWHULDOVWLIIQHVV 3XOVH:DYH9HORFLW\3:9 YLDPDWKHPDWLFDOWUDQVIRUPDWLRQ
VWLIIQHVV&DURWLGVWLIIQHVVKDVEHHQDVVRFLDWHGZLWKLQFLGHQWFDUGLRYDVFXODU
GLVHDVH &9' DQGPD\WKHUHIRUHEHDXVHIXOLQWHUPHGLDWHPDUNHUIRU&9'
WREHXVHGDVRXWFRPHLQREVHUYDWLRQDOFRKRUWDQGLQWHUYHQWLRQVWXGLHV6R
IDUWKHLQWHUSUHWDWLRQRIFDURWLGVWLIIQHVVYDOXHVKDVEHHQKDPSHUHGE\WKH
DEVHQFHRIUHIHUHQFHYDOXHVKRZHYHU:HWKHUHIRUHDLPHGWRHVWDEOLVKDJH
DQGVH[VSHFL¿FUHIHUHQFHLQWHUYDOVIRUFDURWLGVWLIIQHVVWRKHOSLQWHUSUHWDWLRQ
RIWKHVHPHDVXUHV
Design and method: :HFRPELQHGGDWDREWDLQHGE\HFKRWUDFNLQJRQ
LQGLYLGXDOV PHQDJHUDQJH IURPUHVHDUFKFHQWUHVDFURVV
FRXQWULHVZRUOGZLGH,QGLYLGXDOVZLWKRXW&9'FDUGLRYDVFXODUULVNIDFWRUV
&95)VLHVPRNLQJK\SHUWHQVLRQGLDEHWHVG\VOLSLGDHPLDREHVLW\ DQG
ZKR ZHUH QRW RQ EORRGSUHVVXUH OLSLG DQGRU JOXFRVHORZHULQJ PHGLFDWLRQFRQVWLWXWHGDKHDOWK\VXESRSXODWLRQ Q PHQ XVHGWRHVWDEOLVKVH[VSHFL¿FHTXDWLRQVIRUSHUFHQWLOHVRIFDURWLG'&DFURVVDJH
Results: 7KHVH[VSHFL¿FSHUFHQWLOHVRIFDURWLG'&LQWKHKHDOWK\VXESRSXODWLRQDUHVKRZQLQWKH)LJXUH,QWKHVXESRSXODWLRQZLWKRXW&9'DQGWUHDWPHQW Q PHQ FDURWLG'&=VFRUHVEDVHGRQWKHHTXDWLRQVIRU
WKHVHSHUFHQWLOHVZHUHLQGHSHQGHQWO\DQGQHJDWLYHO\DVVRFLDWHGZLWKGLDEHWHVPHDQDUWHULDOSUHVVXUH 0$3 WRWDOWR+'/FKROHVWHUROUDWLRDQGERG\
PDVVLQGH[ %0, ZKHUHDVWKHVHZHUHSRVLWLYHO\DVVRFLDWHGZLWKVPRNLQJ
6WDQGDUGL]HGȕVUHÀHFWLQJWKHGHYLDWLRQIURPWKHKHDOWK\SRSXODWLRQPHDQ
RU WK SHUFHQWLOH ZHUH LQ PHQ DQG ZRPHQ UHVSHFWLYHO\ &,
DQG IRUGLDEHWHV DQG
IRU0$3 DQG IRU
WRWDOWR+'/FKROHVWHUROUDWLR DQG IRU%0,DQG DQG IRUVPRNLQJ
Conclusions: :HHVWLPDWHGDJHDQGVH[VSHFL¿FSHUFHQWLOHVRIFDURWLGVWLIIQHVVLQDKHDOWK\SRSXODWLRQDQGDVVHVVHGWKHDVVRFLDWLRQEHWZHHQ&95)V
DQGFDURWLG'&=VFRUHVZKLFKHQDEOHVFRPSDULVRQRIFDURWLGVWLIIQHVVYDOXHVIRU SDWLHQW JURXSVZLWKGLIIHUHQWFDUGLRYDVFXODUULVNSUR¿OHVKHOSLQJ
LQWHUSUHWDWLRQRIVXFKPHDVXUHVREWDLQHGLQUHVHDUFKDQGFOLQLFDOVHWWLQJV
Results: ,QKHPRGLDO\VLVRQGD\ 'D\ PHDQKHDUWUDWHDGMXVWHGDXJPHQWDWLRQLQGH[ $,[ ZDVVLJQL¿FDQWO\ORZHUGXULQJWKHLQWUDGLDO\WLFSHULRG
WKDQ GXULQJ WKH RXWRIGLDO\VLV SHULRG “ YV “ 3 ,Q FRQWUDVW 3:9 GLG QRW VLJQL¿FDQWO\ GLIIHU EHWZHHQ WKH LQWUDGLDO\WLF DQG
RXWRIGLDO\VLV LQWHUYDOV RI WKH KHPRGLDO\VLVRQ GD\ “ YV “
PVHF3 %RWK$,[ DQG3:9ZHUHVLJQL¿FDQWO\HOHYDWHGGXULQJ
WKHKRXUSHULRGRIWKHKHPRGLDO\VLVRIIGD\ 'D\ DVFRPSDUHGWRWKH
RXWRIGLDO\VLVSHULRGRIWKHKHPRGLDO\VLVRQGD\ “YV“
3 DQG “ YV “ PVHF 3 IRU $,[ DQG 3:9
UHVSHFWLYHO\ Conclusions: 7KLV VWXG\ VKRZV D JUDGXDO LQWHUGLDO\WLF LQFUHDVH LQ DUWHULDO
ZDYHUHÀHFWLRQVDORQJZLWKDVOLJKWDQGSRWHQWLDOO\%3GHSHQGHQWHOHYDWLRQ
LQDUWHULDOVWLIIQHVVGXULQJWKHLQWHUGLDO\WLFSHULRGLQKHPRGLDO\VLVSDWLHQWV
AD.02
REFERENCE INTERVALS FOR LOCAL ARTERIAL
STIFFNESS: THE CAROTID ARTERY
L. Engelen 1, -%RVVX\W2, ,)HUUHLUD3, /09DQ%RUWHO2, &6WHKRXZHU1,
K. Reesink 4, P. Segers 2, S. Laurent , 3%RXWRX\ULH. 1 Maastricht
University Medical Centre, Department of Internal Medicine, Maastricht,
NETHERLANDS, 2 Ghent University, Heymans Institute of Pharmacology,
Ghent, BELGIUM, 3 Maastricht University Medical Centre, Department of
Epidemiology, Maastricht, NETHERLANDS, 4 Maastricht University Medical
Centre, Department of Biomedical Engineering Medicine, Maastricht,
NETHERLANDS, 5 Hôpital Européen Georges Pompidou, Department of
Pharmacology, Paris, FRANCE
Objective: 1RQLQYDVLYHPHDVXUHVRIFDURWLGDUWHU\SURSHUWLHVVXFKDVGLDPHWHUDQGGLVWHQVLRQDQGEUDFKLDOSXOVHSUHVVXUHKDYHEHHQZLGHO\XVHG
WR GHWHUPLQH FDURWLG GLVWHQVLELOLW\ FRHI¿FLHQW '& D PHDVXUH RI FDURWLG
AD.03
ENDOSTATIN: A NOVEL MARKER FOR
HYPERTENSIVE TARGET ORGAN DAMAGE?
A. Carlsson 1, T. Ruge 2, J. Ärnlöv 1. 1 Uppsala University, Uppsala, SWEDEN,
Umeå University, Umeå, SWEDEN
2
Objective: (QGRVWDWLQ LV D FOHDYHG IUDJPHQW RI FROODJHQ ;9,,, LQ WKH H[WUDFHOOXODU PDWUL[ DQG D SRWHQW HQGRJHQRXV LQKLELWRU RI DQJLRJHQHVLV (QGRVWDWLQKDVEHHQVXJJHVWHGWREHDPDUNHURI(&0UHPRGHOOLQJLQWKHGHYHORSPHQWRIFDUGLRYDVFXODUGLVHDVHV+\SHUWHQVLYHWDUJHWRUJDQGDPDJHLV
PDLQO\DVVRFLDWHGZLWKDQDIIHFWHGRUJDQFLUFXODWLRQDQGUHODWHGWRLQFUHDVHG
PRUWDOLW\DQGWKHUHVXOWRISURORQJHGH[SRVXUHWRK\SHUWHQVLRQ<HWOHVVLV
NQRZQDERXWWKHUROHRIKLJKHUOHYHOVRIHQGRVWDWLQDPRQJLQGLYLGXDOVZLWK
K\SHUWHQVLRQ LQ UHODWLRQ WR RWKHU FOLQLFDOO\ XVHG K\SHUWHQVLYH WDUJHW RUJDQ
GDPDJH OHIWYHQWULFXODUK\SHUWURSK\ /9+DQGPLFURDOEXPLQXULD DQGFRPSHOOLQJLQGLFDWLRQVLQK\SHUWHQVLRQ JORPHUXOHDU¿OWUDWLRQUDWH H*)5 GLDEHWHVDQGSUHYDOHQWFDUGLRYDVFXODUGLDVHDVH &9' DEEUHYLDWHG72'LQ
WKHSUHVHQWSDSHU:HK\SRWKHVL]HWKDWHQGRVWDWLQLVFDXVDOO\DVVRFLDWHGZLWK
DQLQFUHDVHGULVNRIFDUGLRYDVFXODUPRUWDOLW\LQOHYHOZLWKRWKHUHVWDEOLVKHG
72'V+HUHLQZHDLPHGWRVWXG\WKHLPSDFWRIHOHYDWHGOHYHOVRIHQGRVWDWLQ
RQFDUGLRYDVFXODUPRUWDOLW\UDWHDORQHDGMXVWHGIRU72'VDVZHOODVLQDGGLWLRQWRRWKHUHVWDEOLVKHGFDUGLRYDVFXODUULVNIDFWRUV
S
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A
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Journal of Hypertension Volume 32, e-Supplement 1, 2014
AD.05
Design and method: 7KH8SSVDOD/RQJLWXGLQDO6WXG\RI$GXOW0HQ 8/6$0 VWXG\ ZDV LQLWLDWHG LQ GHVFULEHG LQ GHWDLO RQ KWWSZZZSXEFDUHXXVH
8/6$0 7KHVH SUHVHQW DQDO\VHV DUH EDVHG RQ WKH IRXUWK H[DPLQDWLRQ F\FOH
ZKHQSDUWLFLSDQWVZHUHDSSUR[LPDWHO\\HDUVROG 2ILQYLWHGPHQSDUWLFLSDWHG2IWKHVHZHUHH[FOXGHGGXHWRPLVVLQJGDWDRQ
HQGRVWDWLQOHDYLQJSDUWLFLSDQWVDVWKHSUHVHQWVWXG\VDPSOH$IWHUH[FOXVLRQ
RISDUWLFLSDQWVZLWKRXWK\SHUWHQVLRQUHPDLQHG
6HUXPOHYHOVRIHQGRVWDWLQZHUHDQDO\]HGXVLQJDFRPPHUFLDOO\DYDLODEOH(/,6$NLWIRUHQGRVWDWLQ '<5 '6\VWHPV0LQQHDSROLV01 Results: &R[ UHJUHVVLRQ PRGHOV LQ LQGLYLGXDOV ZLWK K\SHUWHQVLRQ DUH VKRZQ LQ
7DEOH,QGLYLGXDOVZLWKHQGRVWDWLQOHYHOVLQWKHIRXUWKTXDUWLOHKDGDPRUHWKDQ
GRXEOHGPRUWDOLW\UDWHWKDQLQGLYLGXDOVZLWKORZHUHQGRVWDWLQOHYHOV7KHUHVXOWV
UHPDLQHGHVVHQWLDOO\XQDOWHUHGZKHQDGMXVWHGIRURWKHU&9'ULVNIDFWRUVEXWZHUH
VRPHZKDW DWWHQXDWHG ZKHQ ZH WKH DGMXVWHG IRU DOO RWKHU72'V<HW DGGLWLRQDO
DGMXVWPHQWVIRUFDUGLRYDVFXODUULVNIDFWRUVGLGQRWDWWHQXDWHEH\RQG72'V
Conclusions: &LUFXODWLQJHQGRVWDWLQLVDVVRFLDWHGZLWKFDUGLRYDVFXODUPRUWDOLW\LQGHSHQGHQWO\RI72'V
AD.04
ANGIOTENSIN II TYPE2 RECEPTOR ACTIVATION
PLAYS A ROLE IN BINGE EATING DISORDER
DOES RENAL DENERVATION AFFECT NEUROHORMONAL AND HEMODYNAMIC RESPONSE
TO ORTHOSTATIC STRESS IN PATIENTS WITH
RESISTANT HYPERTENSION?
<9XLJQLHU 1, 19DNLO]DGHK1, 20XOOHU2, E. Grouzmann 3, 00DLOODUG1,
64DQDGOL4, 0%XUQLHU1, *:XHU]QHU1. 1 Service of Nephrology, Lausanne
University Hospital, Lausanne, SWITZERLAND, 2 Service of Cardiology,
Lausanne University Hospital, Lausanne, SWITZERLAND, 3 Clinical
Pharmacology, Lausanne University Hospital, Lausanne, SWITZERLAND,
4
Departement of Radiology, Lausanne University Hospital, Lausanne,
SWITZERLAND
Objective: 7KHV\PSDWKHWLFQHUYRXVV\VWHPDIIHFWNLGQH\IXQFWLRQDWWKUHH
OHYHOV UHQLQ UHOHDVH VRGLXP H[FUHWLRQ DQG UHQDO SODVPD ÀRZ ,Q SDWLHQWV
ZLWK UHVLVWDQW K\SHUWHQVLRQ FDWKHWHUEDVHG UHQDO V\PSDWKHWLF GHQHUYDWLRQ
5'1 KDVEHHQVKRZQWRGHFUHDVHRI¿FHEORRGSUHVVXUH7KHREMHFWLYHRI
WKHVWXG\ZDVWRGHWHUPLQHZKHWKHU5'1ZRXOGDIIHFWUHQDOUHVSRQVHWRDQ
RUWKRVWDWLFVWUHVVLQGXFHGE\ORZHUERG\QHJDWLYHSUHVVXUH /%13
Design and method: 7KLVZDVDRSHQVLQJOHFHQWHUSURVSHFWLYHVWXG\3DWLHQWVFRXOGEHLQFOXGHGLIWKH\ZHUHUHIHUUHGIRU5'1DQGERWKZKLWHFRDW
K\SHUWHQVLRQ DQG VHFRQGDU\ K\SHUWHQVLRQ KDG EHHQ H[FOXGHG %ORRG SUHVVXUH KHDUW UDWH SODVPD UHQLQ DFWLYLW\ 35$ SODVPD DOGRVWHURQH QRUHSLQHSKULQH HSLQHSKULQH VRGLXP DQG FUHDWLQLQH H[FUHWLRQ ZHUH PHDVXUHG DW
EDVHOLQHDQGDIWHURQHKRXUPEDU/%13EHIRUH5'1DQGPRQWKDIWHU
5'1'LXUHWLFVZHUHZLWKKHOGRQWKHGD\RILQYHVWLJDWLRQ$SDLUHGWWHVWRU
D:LOFR[RQPDWFKHGSDLUVVLJQHGUDQNWHVWZDVSHUIRUPHGEHWZHHQEDVHOLQH
YDOXHVDQG/%13YDOXHVDQGEDVHOLQHYDOXHVEHIRUHDQGDIWHU5'1
Results: (OHYHQSDWLHQWV PHQZRPHQ SDUWLFLSDWHGLQWKLVVWXG\0HDQ
DJHZDV“\HDUVDQGERG\PDVVLQGH[ZDV“NJP7DEOH
GLVSOD\VWKHKHPRG\QDPLFUHQDODQGKRUPRQDOUHVSRQVHVWR/%13EHIRUH
DQGDIWHU5'1
+1DNDRND1, 00RJL 1, +.DQ1R1, .7VXNXGD1, .2KVKLPD2,
7&KLVDND3, ;:DQJ1, +%DL1, /0LQ1, -,ZDQDPL1, 0+RULXFKL1.
1
Ehime University, Graduate School of Medicine, Department of Molecular
Cardiovascular Biology and Pharmacology, Toon, JAPAN, 2 Ehime University,
Graduate School of Medicine, Department of Cardiology, Pulmonology,
Hypertension and Nephrology, Toon, JAPAN, 3 Ehime University, Graduate
School of Medicine, Department of Pediatrics, Toon, JAPAN
Objective: %LQJH HDWLQJ GLVRUGHU %(' LV DVVRFLDWHG ZLWK GRSDPLQHUJLF
DFWLYDWLRQLQIRRGUHZDUGDQGFRQWULEXWHVWRWKHSDWKRJHQHVLVRIPHWDEROLVP
UHODWHGGLVRUGHUVVXFKDVREHVLW\DQGGLDEHWHV5HFHQWVWXGLHVKDYHGHPRQVWUDWHGWKDWVWLPXODWLRQRIDQJLRWHQVLQ,,W\SH $7 UHFHSWRULQKLELWVGRSDPLQH '$ V\QWKHVLV,QWKLVVWXG\ZHLQYHVWLJDWHGWKHUHODWLRQVKLSEHWZHHQ
'$VLJQDOLQJDQG%('DIWHUIDVWLQJFRQGLWLRQDQGWKHHIIHFWRI$7UHFHSWRU
VWLPXODWLRQRQ%('DQGERG\ZHLJKW
Design and method: 0DOHZLOGW\SHPLFH :7&%/VWUDLQ W\SHGLDEHWLFPLFH ..$\ DQG$7UHFHSWRUQXOOPLFH $7.2 DWZHHNVRIDJH
ZHUHWUHDWHGZLWKDQLQWUDSHULWRQHDOLQMHFWLRQRI$7UHFHSWRUDJRQLVWFRPSRXQG & DWWKHGRVHRIȝJNJGD\RUVDOLQHIRUZHHNV7ZRGD\V
DIWHUIDVWLQJIRRGDQGZDWHULQWDNHDQGUHERXQGZHLJKWJDLQZHUHPHDVXUHG
XQGHUUHIHHGLQJFRQGLWLRQIRUGD\V'$OHYHOLQWKHVWULDWXPZDVPHDVXUHGE\PLFURGLDO\VLV$IWHUWKHVHWHVWVEUDLQVDPSOHVZHUHREWDLQHGDQGWKH
H[SUHVVLRQV RI '$ UHFHSWRU ' '5' '$ UHFHSWRU ' '5' DQG '$
WUDQVSRUWHU '$7 LQ WKH VXEVWDQWLD QLJUD ZHUH HYDOXDWHG E\ LPPXQRKLVWRFKHPLFDOVWDLQLQJ
Results: )RRGDQGZDWHULQWDNHDQG'$OHYHOLQWKHVWULDWXPZHUHVLJQLILFDQWO\ LQFUHDVHG KRXUV DIWHU IDVWLQJ FRPSDUHG ZLWK QRQIDVWLQJ ..$\
DQG$7.2$GPLQLVWUDWLRQRI&VLJQLILFDQWO\DWWHQXDWHGWKHVHLQFUHDVHV
ZLWKRXW DIIHFWLQJ V\VWROLF EORRG SUHVVXUH LQ ..$\ EXW GLGQ¶W LQIOXHQFH
WKHVHFKDQJHVLQ$7.20RUHRYHU&WUHDWPHQWVLJQLILFDQWO\LQKLELWHG
UHERXQGZHLJKWJDLQDIWHUUHIHHGLQJFRPSDUHGZLWKYHKLFOHWUHDWHGJURXS
EXWGLGQ¶WLQKLELWWKLVLQ$7.2,Q..$\WKHH[SUHVVLRQVRI'5''5'
DQG '$7 LQ WKH VXEVWDQWLD QLJUD ZHUH PDUNHGO\ GHFUHDVHG FRPSDUHG ZLWK
:7ZKHUHDVWKHVHUHGXFWLRQVZHUHEOXQWHGE\DGPLQLVWUDWLRQRI&,QWHUHVWLQJO\UHERXQGZHLJKWJDLQDIWHUUHIHHGLQJLQ$7.2ZDVVLJQLILFDQWO\
LQFUHDVHGFRPSDUHGZLWK:7KRZHYHUWKLVLQFUHDVHZDVQRWLQKLELWHGE\
C21.
Conclusions: $FWLYDWLRQRI$7UHFHSWRUFRXOGFRQWULEXWHWRWKHLQKLELWLRQ
RI %(' DQG UHERXQG ZHLJKW JDLQ ZLWK PRGXODWLRQ RI GRSDPLQH VLJQDOLQJ
7KHVHUHVXOWVLQGLFDWHWKDWVWLPXODWLRQRI$7UHFHSWRUFRXOGEHDQHZWKHUDSHXWLF DSSURDFK WR LPSURYH WKH HDWLQJ GLVRUGHU DVVRFLDWHG ZLWK GRSDPLQH
UHVLVWDQFH
0HDQ EORRG SUHVVXUH QRUHSLQHSKULQH LQFUHDVHG DQG FUHDWLQLQH FOHDUDQFH XULQDU\VRGLXPH[FUHWLRQGHFUHDVHGGXULQJWKH/%13SHULRGEHIRUH5'1%DVHOLQH
YDOXHVDQGUHVSRQVHWR/%13GLGQRWFKDQJHDIWHU5'1H[FHSWIRUDVOLJKWEXW
QRWVLJQL¿FDQWGHFUHDVHLQ35$DQGSODVPDDOGRVWHURQH
Conclusions: 7KH KHPRG\QDPLF UHQDO DQG KRUPRQDO UHVSRQVH WR RUWKRVWDWLF
VWUHVVGRHVQRWVHHPWREHDIIHFWHGE\5'1
AD.06
RENAL EXPRESSION AND CIRCULATING LEVELS OF
MICRORNA MIR-181A IN REGULATION OF RENIN AND
BLOOD PRESSURE
)0DUTXHV1,2, 0'HQQLII2,3, ,*DUUHOGV 4, C. Nelson 2,3, /:RMQDU,
.0XVLDOLN, N. Samani 2,3, 3%RJGDQVNL, (=XNRZVND6]F]HFKRZVND,
$+-'DQVHU4, )-&KDUFKDU1, 07RPDV]HZVNL2,3. 1 Faculty of Health,
Federation University Australia, Ballarat, AUSTRALIA, 2 Department
of Cardiovascular Sciences, University of Leicester, Leicester, UNITED
KINGDOM, 3 Leicester National Institute for Health Research, Biomedical
5HVHDUFK8QLWLQ&DUGLRYDVFXODU'LVHDVH*OHQ¿HOG+RVSLWDO/HLFHVWHU
UNITED KINGDOM, 4 Division of Pharmacology and Vascular Medicine,
Department of Internal Medicine, Erasmus Medical Centre, Rotterdam,
NETHERLANDS, 5 Department of Urology and Oncological Urology, Medical
University of Poznan, Poznan, POLAND, 6 Department of Internal Medicine,
Metabolic Disorders and Hypertension, Medical University of Poznan, Poznan,
POLAND, 7 Department of Internal Medicine, Diabetology and Nephrology,
Medical University of Silesia, Zabrze, POLAND
Objective: 0LFUR51$VDUHVPDOOQRQFRGLQJ51$VZKLFKELQGWRXQWUDQVODWHG
UHJLRQVRIPDQ\JHQHVLQFOXGLQJWKRVHUHVSRQVLEOHIRUFDUGLRYDVFXODUGLVHDVH
:HSUHYLRXVO\IRXQGWKDWWKHPLFUR51$PL5DELQGVWRDQGUHJXODWHVWKH
OHYHOV RI UHQLQ P51$ LQ YLWUR DQG DVVRFLDWHV ZLWK WKH H[SUHVVLRQ RI UHQLQ LQ
KXPDQNLGQH\,QWKLVVWXG\ZHH[SORUHGWKHUROHRIERWKUHQDOH[SUHVVLRQDQG
FLUFXODWLQJFRQFHQWUDWLRQVRIPL5DDVDGHWHUPLQDQWRIEORRGSUHVVXUH %3 UHJXODWLRQXVLQJDODUJHFROOHFWLRQRIKXPDQWLVVXHVFROOHFWHGLQWKH3ROLVK.LGQH\3URMHFW
e85
Journal of Hypertension Volume 32, e-Supplement 1, 2014
Design and method: 51$ZDVH[WUDFWHGIURPVHUXPDQGNLGQH\VRIZKLWH
(XURSHDQVXEMHFWVZKRXQGHUZHQWHOHFWLYHXQLODWHUDOQHSKUHFWRPLHVEHFDXVHRI
QRQLQYDVLYH UHQDO FDQFHU 7KH WLVVXH VDPSOHV ZHUH FROOHFWHG IURP D KHDOWK\
XQDIIHFWHGE\FDQFHU SROHRIWKHNLGQH\5HQDOH[SUHVVLRQRIUHQLQP51$DQG
PL5DDVZHOODVPL5DLQVHUXPZHUHPHDVXUHGE\TXDQWLWDWLYHUHDO
WLPH 3&5 T3&5 &LUFXODWLQJ VHUXP OHYHOV RI UHQLQ ZHUH PHDVXUHG E\ UHQLQ
LPPXQRUDGLRPHWULFDVVD\
Results: 7KHUH ZDV D QHJDWLYH FRUUHODWLRQ LQ H[SUHVVLRQ RI PL5D DQG UHQLQLQKXPDQNLGQH\V ȕ ±6( 3 6HUXPOHYHOVRIPL5D
ZHUHVWURQJO\FRUUHODWHGZLWKLWVH[SUHVVLRQLQKXPDQNLGQH\V ȕ 6( 3 %RWKUHQDODQGVHUXPH[SUHVVLRQRIPL5DZHUHDVVRFLDWHGZLWK
%3LQERWKSDWLHQWVZKRZHUHRQDQWLK\SHUWHQVLYHWUHDWPHQWDQGWKRVHQRWPDQDJHGSKDUPDFRORJLFDOO\ 3IRUDOODQDO\VHV 7KHPRVWVLJQL¿FDQWDVVRFLDWLRQZDVLGHQWL¿HGEHWZHHQVHUXPOHYHOVRIPL5DDQGGLDVWROLF%3LQWKRVH
QRWRQ%3ORZHULQJWKHUDS\±HDFKXQLWLQFUHDVHLQPLFUR51$OHYHOLQFUHDVHG
GLDVWROLF%3E\DSSUR[LPDWHO\PP+J ȕ 6( 3 7KHDVVRFLDWLRQEHWZHHQVHUXPPL5DDQG%3ZDVLQGHSHQGHQWRINLGQH\H[SUHVVLRQ
RIUHQLQRULWVVHUXPOHYHOV&LUFXODWLQJUHQLQZDVDVVRFLDWHGZLWKK\SHUWHQVLRQ
25 &, 3 DQG V\VWROLF %3 ȕ 6( 3 DQGLWZDVSRVLWLYHO\FRUUHODWHGZLWKUHQDOUHQLQ ȕ 6( 3 Conclusions: 7KHVHGDWDVKRZWKDWPL5DLVDQHJDWLYHUHJXODWRURIUHQLQ
H[SUHVVLRQLQWKHKXPDQNLGQH\5HQLQLQGHSHQGHQWHIIHFWRIPL5DRQ%3
VXJJHVWVWKDWWKLVPLFUR51$PXVWDIIHFWWUDQVFULSWLRQRIRWKHUPROHFXOH V WKDW
FRQWULEXWHWR%3UHJXODWLRQDQGWKHQHWHIIHFWRIWKHVHLQWHUDFWLRQVWUDQVODWHVLQWR
%3HOHYDWLRQ
AD.07
SHORTER STATURE AND HIGH PREVALENCE
OF LOW BMD AND FRACTURES AMONG
HYPERTENSIVES SUGGEST A FORM OF
ACCELERATED AGEING
5(O%LNDL1, -7UHPEOD\1, 57DKLU1, 0-RIIUHV2, 26HGD1, /6HGRYD1,
3$ZDGDOOD3, C. Laberge 4, %.QRSSHUV , 3'XPDV1, '*DXGHW,
/6WH0DULH1, 3+DPHW1. 1 Centre Hospitalier de l’Université de Montreal,
Université de Montreal, Montreal, CANADA, 2 Simon Fraser University,
British Columbia, CANADA, 3 CHU Ste-Justine, Université de Montreal,
Montreal, CANADA, 4 Médecine Génétique, Université Laval, Ste-Foy,
CANADA, 5 Centre of Genomics and Policy, McGill University, Montreal,
CANADA, 6 Ecogene-21 Clinical Research and Department of Medicine,
Université de Montreal, Montreal, CANADA
Objective: +\SHUWHQVLRQDQGRVWHRSRURVLVDUHWZRGLVHDVHVWKDWDUHSUHYDOHQW
LQDJHLQJSRSXODWLRQV2XUDLPZDVWRXQYHLOWKHSRVVLEOHUHODWLRQVKLSEHWZHHQ
WKHVHWZRFRPRUELGLWLHV
Design and method: &$57D*(1(FRKRUWLQFOXGHVUDQGRPO\VHOHFWHG
VXEMHFWVDJHGEHWZHHQDQG\HDUV$OOVXEMHFWVZHQWWKURXJKDWKUHHKRXU
GHWDLOHG SKHQRW\SLQJ VHVVLRQ WKDW LQFOXGHG SHULSKHUDO DQG FHQWUDO EORRG SUHVVXUH KHLJKW DQG ERQH PLQHUDO GHQVLW\ %0' 4XDQWLWDWLYH XOWUDVRXQG RI WKH
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1 DQGDIDPLO\FRKRUWRIWKH6DJXHQD\/DF6W-HDQSRSXODWLRQ 1 IURPIDPLOLHV Results: ,Q WKH WKUHH FRKRUWV ZH REVHUYHG WKDW K\SHUWHQVLYHV DUH WDOOHU DW D
\RXQJHU DJH \HDUV ROG DQG VKRUWHU WKDQ QRUPRWHQVLYHV DW DQ ROGHU DJH
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U S DQGWKLVFRUUHODWLRQZDVVWURQJHUDPRQJK\SHUWHQVLYHVXEMHFWV U S FRPSDUHG WR QRUPRWHQVLYHV U S 7KH
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&, :KHUHDVLQK\SHUWHQVLYHVIRUHYHU\XQLWLQFUHDVHLQKHLJKWZH
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Conclusions: +\SHUWHQVLRQLVDULVNIDFWRUIRUORZ%0'DQGIUDFWXUHVDQGPRUH
VRLQ\RXQJHUK\SHUWHQVLYHZRPHQ:HSURSRVHWKDWK\SHUWHQVLRQPD\EHDIRUP
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AD.08
THE PROGNOSTIC ROLE OF NON-DIPPING BLOOD
PRESSURE PROFILE IN SLEEP APNEA PATIENTS
L. Korostovtseva, <6YLU\DHYN. Zvartau, 25RWDU$2.RQUDGL(6KO\DNKWR.
Federal Almazov Medical Research Centre, Saint-Petersburg, RUSSIA
Objective: 7KHUHFHQWGDWDVXJJHVWWKDWQRQGLSSLQJEORRGSUHVVXUH %3 SUR¿OHLVDVVRFLDWHGZLWKSRRUVXUYLYDOLQJHQHUDOSRSXODWLRQ$WWKHVDPHWLPH
WKHDEVHQFHRIQRFWXUQDO%3IDOOLVFRPPRQIRUREVWUXFWLYHVOHHSDSQHD 26$ EHLQJDQLQGHSHQGHQWFDUGLRYDVFXODUULVNIDFWRU%HVLGHVWKHUHLVQRHYLGHQFH
ZKHWKHUWKHQHJDWLYHSURJQRVLVLQVOHHSGLVRUGHUHGEUHDWKLQJLVUHODWHGWR
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VWXG\WKHUROHRIQRQGLSSLQJ%3SUR¿OHIRUWKHGHYHORSPHQWRIFDUGLRYDVFXODU
HYHQWVLQK\SHUWHQVLYHSDWLHQWVZLWKREVWUXFWLYHVOHHSDSQHD 26$ Design and method: 6LQFHWLOORXWRIVFUHHQHGSDWLHQWVZHVHOHFWHG
VXEMHFWV> PDOHV@ZLWKFRQWUROOHGK\SHUWHQVLRQDQGZLWKRXWNQRZQ
RWKHUFDUGLRYDVFXODUGLVHDVHVDQGGLDEHWHVPHOOLWXV$OOVXEMHFWVZHUHRYHUZHLJKW
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VOHHS VWXG\ (PEOHWWD ,FHODQG WKH VXEMHFWV ZHUH GLYLGHG LQWR DJH DQG VH[
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FDPHIRUDQRI¿FHYLVLWIRUSK\VLFDODQGLQVWUXPHQWDOH[DPLQDWLRQ7KHFRPELQHG
SULPDU\HQGSRLQWLQFOXGHGIDWDODQGQRQIDWDOFDUGLRYDVFXODUHYHQWV&R[UHJUHVVLRQPRGHOLQFOXGHGDSQHDK\SRSQHDLQGH[ $+, %3OHYHOQRQGLSSLQJ%3SUR¿OH ELQDU\YDULDEOH VWDQGDUGULVNIDFWRUV%0,FDUGLRYDVFXODUWKHUDS\FKDQJHV
Results: 7KH PHGLDQ IROORZXS SHULRG ZDV PRQWKV $IWHU
\HDUV VLQFH WKH ¿UVW HQUROOHG SDWLHQW VHYHQWHHQ VXEMHFWV GLHG DQG
SDWLHQWVDFKLHYHGSULPDU\HQGSRLQW7KHPXOWLSOH&R[UHJUHVVLRQ
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ZHUHDVVRFLDWHGZLWKSRRUVXUYLYDO$+, S ORZGHQVLW\OLSRSURWHLQOHYHO S IDVWLQJSODVPDJOXFRVH S DQGKHUHGLW\ S :KHQ
QRQGLSSLQJ%3SUR¿OHZDVLQFOXGHGLQWKHPRGHO FKLVTXDUH S LWVKRZHGWREHDVLJQL¿FDQWSUHGLFWRURIWKHZRUVHRXWFRPH S ZKLOH
$+,EHFDPHQRQVLJQL¿FDQW S Conclusions: 2XUGDWDVXJJHVWWKDWQRQGLSSLQJ%3SUR¿OHFDQEHDVVRFLDWHG
ZLWKWKHSRRUSURJQRVLVLQK\SHUWHQVLYHSDWLHQWVZLWK26$DQGWKHZRUVHRXWFRPHPLJKWEHPHGLDWHGE\WKHLPSDFWRIVOHHSGLVRUGHUHGEUHDWKLQJRQKRXU
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AD.09
N-TERMINAL PRO-BRAIN NATRIURETIC PEPTIDE,
BLOOD PRESSURE AND COGNITIVE DECLINE IN THE
OLDEST OLD: THE LEIDEN 85-PLUS STUDY
P. Van Vliet 1,2, %6DED\DQ2, /:LMVPDQ2, R. Poortvliet 3, 60RRLMDDUW2,
:'H5XLMWHU3, J. Gussekloo 3, $'H&UDHQ2, 5:HVWHQGRUS2.
1
Department of Neurology, Leiden University Medical Center, Leiden,
NETHERLANDS, 2 Department of Gerontology and Geriatrics, Leiden
University Medical Center, Leiden, NETHERLANDS, 3 Department of
Public Health and Primary Care, Leiden University Medical Center, Leiden,
NETHERLANDS
Objective: +\SHUWHQVLRQLQPLGGOHDJHLVDULVNIDFWRUIRUGHPHQWLDZKHUHDV
LQROGDJHFRJQLWLYHLPSDLUPHQWLVDVVRFLDWHGZLWKORZEORRGSUHVVXUH,QFUHDVLQJSUHYDOHQFHRIKHDUWIDLOXUHPD\SOD\DUROHLQWKLVUHYHUVDORIDVVRFLDWLRQV
+HUHZHVWXGLHGWKHUHODWLRQEHWZHHQ1WHUPLQDOSUREUDLQQDWULXUHWLFSHSWLGH
17SUR%13 OHYHOVDVDVHUXPPDUNHURIOHIWYHQWULFXODUG\VIXQFWLRQEORRG
SUHVVXUHDQGFRJQLWLYHGHFOLQHLQWKHROGHVWROG
Design and method: ,QDSURVSHFWLYHFRKRUWVWXG\SDUWLFLSDQWVDOO\HDUV
ROGZHUHLQFOXGHGIURPWKHSRSXODWLRQEDVHG/HLGHQSOXV6WXG\6HUXP17
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PXOWLYDULDEOHOLQHDUUHJUHVVLRQPRGHOV
Results: 6XEMHFWVLQWKHKLJKHVWWHUWLOHRI17SUR%13OHYHOVVFRUHGSRLQWV
ORZHURQWKH006(WKDQVXEMHFWVLQWKHORZHVWWHUWLOH S DQGKDGD
SRLQWVWHHSHUGHFOLQHLQ006(VFRUHSHU\HDU S 6XEMHFWVLQWKHFDWHJRU\KLJKHVWWHUWLOHRI17SUR%13DQGWKHORZHVWWHUWLOHRIV\VWROLF%3KDGD
SRLQWORZHU006(VFRUHDWEDVHOLQH S DQGDSRLQWVWHHSHUGHFOLQH
LQ006(VFRUHSHU\HDU S FRPSDUHGWRVXEMHFWVLQWKHRWKHUFDWHJRULHV
Conclusions: ,QWKHROGHVWROGKLJK17SUR%13OHYHOVDUHDVVRFLDWHGZLWKORZHU006(VFRUHVDQGZLWKVWHHSHUGHFOLQHVLQ006(VFRUH7KHFRPELQDWLRQ
RIKLJK17SUR%13OHYHOVDQGORZV\VWROLF%3LVPRVWGHWULPHQWDOIRUJOREDO
FRJQLWLYHIXQFWLRQ3RVVLEO\DIDLOLQJSXPSIXQFWLRQRIWKHKHDUWUHVXOWVLQORZHU
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e86
Journal of Hypertension Volume 32, e-Supplement 1, 2014
AD.10
DIETARY NITRATE TO REDUCE BLOOD PRESSURE
IN HYPERTENSIVE PATIENTS (DINA-HTN): A
RANDOMIZED, DOUBLE-BLIND, PLACEBOCONTROLLED CLINICAL TRIAL
V. Kapil, 5.KDPEDWD0-&DXO¿HOG$$KOXZDOLD. William Harvey Research
Institute, Clinical Pharmacology, Queen Mary University London, London,
UNITED KINGDOM
Objective: $VLQJOHRUDOGRVHRILQRUJDQLFQLWUDWHDVDVXSSOHPHQWRUYLDGLHWDU\LQWDNHVXEVWDQWLDOO\UHGXFHVEORRGSUHVVXUH %3 LQKXPDQVRYHUKRXUV
7KLVHIIHFWLVFDXVHGE\WKHLQYLYRFRQYHUVLRQRIQLWUDWHWRQLWULWHDQGWKHQRI
QLWULWHWRWKHSRWHQWYDVRGLODWRUQLWULFR[LGH,QWKLVVWXG\ZHDVVHVVHGZKHWKHUD
RQFHGDLO\LQJHVWLRQRIGLHWDU\QLWUDWHPLJKWH[HUWDVXVWDLQHGHIIHFWXSRQ%3LQ
K\SHUWHQVLYHSDWLHQWV
Design and method: $ WRWDO RI K\SHUWHQVLYH SDWLHQWV ZHUH HQUROOHG LQ
D UDQGRPL]HG GRXEOHEOLQG SODFHERFRQWUROOHG WULDO ZLWK VWUDWL¿FDWLRQ DFFRUGLQJ WR ZKHWKHU WKH\ ZHUH DQWLK\SHUWHQVLYH WUHDWPHQWQDwYH Q RU
WUHDWHG Q )ROORZLQJDZHHNUXQLQSHULRGSDWLHQWVZHUHSURYLGHGGDLO\GLHWDU\VXSSOHPHQWDWLRQIRUZHHNVZLWKHLWKHUGLHWDU\QLWUDWH PPRO
QLWUDWHDVP/EHHWURRWMXLFH RUSODFHER P/QLWUDWHGHSOHWHGEHHWURRW
MXLFH IROORZHGE\DZHHNZDVKRXW7KHSULPDU\HQGSRLQWZDVFKDQJH
LQ FOLQLF DPEXODWRU\ DQG KRPH %3 FRPSDUHG WR SODFHER 6HFRQGDU\ RXWFRPH PHDVXUHV LQFOXGHG SXOVH ZDYH YHORFLW\ 3:9 HQGRWKHOLDO IXQFWLRQ
DVVHVVHGE\PHDVXUHPHQWRIÀRZPHGLDWHGGLODWDWLRQ )0' DQGSODVPDQLWULWHDQGQLWUDWHFRQFHQWUDWLRQ7KHUHZHUHGURSRXWVIURPHDFKOLPEDQGVR
Q FRPSOHWHGWKHWULDOLQHDFKJURXS7KLVVWXG\LVUHJLVWHUHGZLWK&OLQLFDOWULDOVJRY 1&7 'DWDDUHH[SUHVVHGDVPHDQ &, Results: 'DLO\ VXSSOHPHQWDWLRQ ZLWK GLHWDU\ QLWUDWH FDXVHG LQFUHDVHV LQ
SODVPD>QLWULWH@RIXPRO/ S DQGSODVPD>F*03@RI
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PP+J S IRU ERWK ZLWK VLJQL¿FDQW UHGXFWLRQV VHSDUDWHO\ LQ ERWK GD\ DQG QLJKW SHULRGV +RPH %3 ZDV UHGXFHG E\
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1
Oslo University Hospital Ullevaal, Department of Internal Medicine,
Oslo, NORWAY, 2 University of Bergen, Department of Global Public
Health and Primary Care, Bergen, NORWAY, 3 Oslo University Hospital
Ullevaal, Department of Neurology, Oslo, NORWAY, 4 Uppsala University,
Department of Medical Sciences, Uppsala, SWEDEN, 5 Bispebjerg
Hospital, Department of Neurology, and University of Copenhagen,
Copenhagen, DENMARK
Objective: 7KH 6FDQGLQDYLDQ &DQGHVDUWDQ $FXWH 6WURNH 7ULDO 6&$67 VKRZHGQREHQHILFLDOHIIHFWDWPRQWKVRIEORRGSUHVVXUHORZHULQJWUHDWPHQW ZLWK FDQGHVDUWDQ LQ WKH DFXWH SKDVH RI VWURNH $V D SUHVSHFLILHG
VHFRQGDU\ DQDO\VLV ZH LQYHVWLJDWHG ZKHWKHU WKH UHVXOWV ZHUH FRQVLVWHQW
RYHUWLPHRUZKHWKHUDGLIIHUHQWHIIHFWFRXOGEHREVHUYHGGXULQJORQJWHUP
IROORZXS
Design and method: 6&$67ZDVDQLQWHUQDWLRQDOPXOWLFHQWUHUDQGRPLVHG
DQGSODFHERFRQWUROOHGWULDORIFDQGHVDUWDQLQSDWLHQWVZLWKDFXWHLVFKDHPLFRUKDHPRUUKDJLFVWURNH)RUWKH6ZHGLVKDQG'DQLVKSDWLHQWV
LQFOXGHGLQWKHWULDOZHFROOHFWHGGDWDIURPWKHQDWLRQDOKRVSLWDOUHJLVWULHV
DQGGHDWKUHJLVWULHVXSWR\HDUVDIWHUUDQGRPLVDWLRQ:HDVVHVVHGWKHHIIHFW
RIWUHDWPHQWRQWKHFRPSRVLWHHQGSRLQWRIYDVFXODUGHDWKP\RFDUGLDOLQIDUFWLRQRUVWURNHDQGRQDOOFDXVHGHDWK:HXVHG&R[UHJUHVVLRQIRUDQDO\VLV
DQG DGMXVWHG IRU DJH JHQGHU FDXVH RI VWURNH V\VWROLF EORRG SUHVVXUH DQG
6FDQGLQDYLDQ6WURNH6FDOHVFRUHDWEDVHOLQH
Results: 2IWKHSDWLHQWVHQUROOHGGDWDZHUHDYDLODEOHIRUSDWLHQWV
)LJXUH VKRZV VXUYLYDO FXUYHV IRU ERWK HIIHFW YDULDEOHV 'XULQJ \HDUVCIROORZXSWKHULVNRIWKHFRPSRVLWHHQGSRLQWGLGQRWGLIIHUEHWZHHQ
WUHDWPHQW JURXSV FDQGHVDUWDQ HYHQWV YV SODFHER HYHQWV DGMXVWHG
KD]DUG UDWLR &, S 7KH GLIIHUHQFH ZDV VLPLODU
IRU DOOFDXVH GHDWK FDQGHVDUWDQ HYHQWV YV SODFHER HYHQWV DGMXVWHG
KD]DUGUDWLR&,S Conclusions: 7KLVLVWKH¿UVWHYLGHQFHRIVXVWDLQHG%3UHGXFWLRQZLWKGLHWDU\
QLWUDWHVXSSOHPHQWDWLRQLQDUHOHYDQWSDWLHQWJURXSVXJJHVWLQJDUROHIRUGLHWDU\
QLWUDWHDVDFKHDSUHDGLO\DYDLODEOHDGMXQFWLYHWUHDWPHQWLQPDQDJHPHQWRIK\pertensive patients.
AD.11
EFFECTS OF BLOOD PRESSURE LOWERING
TREATMENT WITH CANDESARTAN IN ACUTE
STROKE ON VASCULAR EVENTS DURING LONGTERM FOLLOW-UP
$+RUQVOLHQ1, -,JODQG2, (6DQGVHW3, A. Terent 4, *%R\VHQ, (%HUJH1.
Conclusions: 7UHDWPHQWZLWKFDQGHVDUWDQLQWKHDFXWHSKDVHRIVWURNHZDVQRW
DVVRFLDWHG ZLWK D UHGXFHG ULVN RI YDVFXODU HYHQWV RU GHDWK GXULQJ ORQJWHUP
IROORZXS7KHUHVXOWVIRUDOO6FDQGLQDYLDQSDWLHQWVZLOOEHSUHVHQWHGDW
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Abstracts
e87
ORAL SESSION
LATE-BREAKERS SESSION 2
LB02.01
RENAL DENERVATION VERSUS INTENSIFIED
MEDICAL TREATMENT INCLUDING
SPIRONOLACTONE IN PATIENTS WITH TRUE
RESISTANT HYPERTENSION: 6-MONTHS RESULTS
OF MULTICENTER RANDOMIZED PRAGUE
J. Widimsky 1, J. Rosa 1,2, P. Tousek 2, K. Curila 2, M. Taborsky 3, J. Vaclavik 3,
M. Branny 4, I. Nykl 4, O. Jiravsky 4, O. Petrak 1, P. Waldauf 5, T. Zelinka 1,
R. Holaj 1, P. Widimsky 2. 1 3rd Department of Medicine, Center for
Hypertension, General University Hospital and First Faculty of Medicine,
Prague, CZECH REPUBLIC, 2 Cardiocenter, University Hospital Kralovske
Vinohrady and Third Faculty of Medicine, Charles University, Prague,
CZECH REPUBLIC, 3 Department of Internal Medicine I, University Hospital,
Olomouc, CZECH REPUBLIC, 4 Cardiocenter, Nemocnice Podlesí, Trinec,
CZECH REPUBLIC, 5 Department of Anesthesiology, University Hospital
Kralovske Vinohrady and Third Faculty of Medicine, Charles University,
Prague, CZECH REPUBLIC
7
Kangbuk Samsung Hospital, Seoul, SOUTH KOREA, 8 Gil Hospital, Incheon,
SOUTH KOREA, 9 Wonju Severans Hospital, Wonju, SOUTH KOREA,
10
Catholic University Hospital, Seoul, SOUTH KOREA, 11 Jeju National
University Hospital, Jeju, SOUTH KOREA, 12 Chungbook National University
Hospital, Chunju, SOUTH KOREA
Objective: The presence of hypertension in patients with metabolic syndrome
(MetS) was known to the high prevalence of organ damage and cardiovascular
(CV) risk. However, few are known about the effects of the correction of MetS
after hypertension treatment. In this study, we evaluated whether the early correction of MetS improves abnormal albuminuria, a marker of organ damage, in a year.
Objective: 7RHYDOXDWHWKHHIIHFWRIUHQDOGHQHUYDWLRQ 5'1 YHUVXVLQWHQVL¿HG
antihypertensive therapy including spironolactone on 24 hour blood pressure
in patients with true resistant hypertension.
Design and method: The PRAGUE-15 trial was designed as an open, prospective, randomized multicenter trial comparing RDN (Symplicity, Medtronic) with
LQWHQVL¿HGSKDUPDFRORJLFDOWUHDWPHQWLQFOXGLQJVSLURQRODFWRQHLQSDWLHQWVZLWK
true-resistant hypertension. The primary endpoint were changes in blood pressure during ambulatory blood pressure monitoring (ABPM) from baseline to 6
PRQWKV7UXHUHVLVWDQFHZDVFRQ¿UPHGE\$%30DIWHUWKHH[FOXVLRQRIVHFRQGDU\K\SHUWHQVLRQDQGFRQ¿UPDWLRQRIDGKHUHQFHWRWKHUDS\E\WKHPHDVXUHPHQW
of plasma antihypertensive drug levels.
2QHKXQGUHGDQGVL[SDWLHQWV SWV PHQZRPHQPHDQ%0, were randomized to RDN (n-52, 56 ±12 years), or to pharmacological (PHAR)
treatment group (n-54, 59± 9 years) . In the RDN group the mean number of
succesfull RF ablations was 5 ±1.2 on right renal arteries, 4.8 ±1.4 resp. on left
renal arteries. In the PHAR group spironolactone was added if tolerated. There
were no substantial differences in the number of antihypertensives between
PHAR and RDN group (5,4 ±1,2 vs. 5,1 ±1,2).
Results: :H QRWHG VLJQL¿FDQW UHGXFWLRQ LQ K 6%3 DIWHU PRQWKV PP+J LQ 5'1 S YV PP+J LQ 3+$5 S ZKLFK ZDV
FRPSDUDEOHLQERWKJURXSV S 6LJQL¿FDQWGHFUHDVHRIK'%3 PP+JLQ5'1SYVPP+JGHFOLQHLQ3+$5S ZDVDOVR
FRPSDUDEOHLQERWKJURXSV S &OLQLFDO%3GHFUHDVHGVLJQL¿FDQWO\DIWHU
6 months in both groups , but the differences between two groups were not
VLJQL¿FDQW S S UHVS :HREVHUYHGQRQVLJQL¿FDQWFKDQJHVRI
h pulse rate (-1/min in RDN, p=0.31 vs. -2/min in PHAR, p=0.06) with no
VLJQL¿FDQWEHWZHHQJURXSGLIIHUHQFHV S *)5PHDVXUHGE\0'5'ZDV
QRWVLJQL¿FDQWO\DIIHFWHGGXULQJPRQWKVLQERWKJURXSVZLWKQRGLIIHUHQFHV
between PHAR and RDN pts. RDN procedure was safe a no serious complications were recorded.
Conclusions: 5'1LVQRWVXSHULRUWRLQWHQVL¿HGSKDUPDFRORJLFDOWKHUDS\LQ
patients with true resistant hypertension.
LB02.02
THE EARLY CORRECTION OF METABOLIC
SYNDROME IMPROVES ORGAN DAMAGE,
IRRESPECTIVELY OF BLOOD PRESSURE
REDUCTION IN PATIENTS WITH HYPERTENSION:
K-METS STUDY
J. Park 1, S. Kang 2, K. Kim 3, K. Kim 4, D. Kim 5, D. Shin 6, K. Sung ,
M. Shin 8, S. Lee 9, E. Cho 10, S. Joo 11, G. Hong 2, K. Hwang 12. 1 Cheil
General Hospital, Kwandong University, Seoul, SOUTH KOREA, 2 Severans
Hospital, Yonsei University, Seoul, SOUTH KOREA, 3 Chonnam University
Hospital, Kwnagju, SOUTH KOREA, 4 Bundang Seoul National University
Hospital, Sungnam, SOUTH KOREA, 5 Inje Baik University Hospital, Busan,
SOUTH KOREA, 6 Youngnam University Hospital, Daegu, SOUTH KOREA,
Design and method: Among a total of 10,601 patients of the K-MetS study,
5481 patients who had complete data of 5 metabolic components in before (B)
DQGDIWHUPRQWK 0 ZHUHDQDO\]HG7KHGH¿QLWLRQRIPHWDEROLFV\QGURPH
ZDVEDVHGRQWKHKDUPRQL]HGGH¿QLWLRQIRUPHWDEROLFV\QGURPH7KHSDWLHQWV
ZHUHJURXSHGDVJURXS%0HW6 DQG00HW6 JURXS%0HW6 DQG00HW6 JURXS%0HW6 DQG00HW6 DQGJURXS%0HW6 DQG00HW6 $OOSDWLHQWVUHFHLYHGDQJLRWHQVLQUHFHSWRUEORFNHU¿PDVDUWDQ
with or without other antihypertensive drug through the study.
Results: 7KH GLVWULEXWLRQ RI DJH ZDV VLPLODU EHWZHHQ PHQ \HDUV DQG ZRPHQ \HDUV 7KH SUHYDOHQFH RI 0HW6 LQ EDVHOLQH PRQWK DQG \HDU ZDV DQG UHVSHFWLYHO\ VKRZLQJ VLJQL¿FDQW LPSURYHPHQW LQ PRQWK$Q DYHUDJH “VWDQGDUG GHYLDWLRQ RI
clinic systolic/diastolic BP (SBP/DBP) in baseline, 3-month and 1-year was
““ PP+J ““ PP+J DQG
““PP+JUHVSHFWLYHO\$OEXPLQFUHDWLQLQHUDWLR $&5 VKRZHG D VLPLODU SDWWHUQ RI %3V DQG 0HW6 FKDQJHV VKRZLQJ VLJQL¿FDQW LPSURYHPHQWIURPEDVHOLQH “PJJ WRPRQWK “PJJ ZLWKRXWIXUWKHULPSURYHPHQWLQ\HDU$&5LQ\HDUZHUHVLJQL¿FDQWO\KLJKHU
LQ*URXSWKDQRWKHUJURXSV YHUVXVSYDOXH )LJXUH The changes of BPs, MetS and ACR were similar between men and women.
Conclusions: Early correction of MetS in hypertensive patients, who are treated
with angiotensin receptor blocker for 1-year, normalized albumin creatinine ratio irrespectively of the blood pressure reduction.
LB02.03
NON-INVASIVE HEMODYNAMIC MONITORING AS A
GUIDE TO DRUG TREATMENT: RELATION BETWEEN
CHANGES IN HEMODYNAMIC PARAMETERS AND IN
BLOOD PRESSURE VALUES. THE BEAUTY STUDY
T. Comotti 1,2, P. Rebora 2, F. Fadl Elmula 3, A. Talvik 4, S. Salerno 1,2,
E. Miszkowska-Nagórna 5, X. Liu 1,2, M. Heinpalu-Kuum 4, A.C. Larstorp 3,
M. Rostrup 6, M.G. Valsecchi 2, S.E. Kjeldsen 3, M. Viigimaa 4, K. Narkiewicz 5,
G. Parati 1,2, S. Laurent . 1 Istituto Auxologico Italiano, Department of
Cardiology, S. Luca Hospital, IRCCS, Milan, ITALY, 2 University of MilanBicocca, Department of Health Sciences, Milan, ITALY, 3 University of
Oslo, Ullevaal Hospital, Section for Cardiovascular and Renal Research,
Department of Cardiology, Oslo, NORWAY, 4 Tallinn University of Technology,
North Estonia Medical Centre, Tallinn, ESTONIA, 5 Medical University,
Department of Hypertension and Diabetology, Gdansk, POLAND, 6 University
of Oslo, Ullevaal Hospital, Section for Cardiovascular and Renal Research,
S
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e88
Journal of Hypertension Volume 32, e-Supplement 1, 2014
Department of Acute Medicine, Oslo, NORWAY, 7 Hôpital Européen Georges
Pompidou, Department of Pharmacology and INSERM U970, Paris, FRANCE
Objective: In the BEtter control of blood pressure (BP) in hypertensive
pAtients monitored Using the HOTMAN® sYstem (BEAUTY) Study, we
H[SORUHG ZKHWKHU GUXJ VHOHFWLRQ EDVHG RQ QRQLQYDVLYH LQWHJUDWHG KHPRdynamic management (IHM) improves hemodynamic status in patients with
uncontrolled hypertension (UCH) during a 6-month follow-up as compared
to conventional drug selection (control), and 2) whether treatment-induced
changes in hemodynamic parameters are related to changes in BP.
Design and method: 8&+ RI¿FH6\VWROLF 6 %3!PP+JDQGDPEXODWRU\GD\WLPH6%3!PP+JZLWK! DQWLK\SHUWHQVLYHGUXJV SDWLHQWVZHUH
randomized to IHM-guided (n=83) vs. conventional (control, n=84) management in an investigator-initiated multicenter prospective randomized parallel
groups controlled study. The comprehensive change in hemodynamic status
ZRUVHQHG VWDEOH RU LPSURYHG EHWZHHQ ¿QDO YLVLW DQG EDVHOLQH EDVHG RQ
integrated changes in different hemodynamic parameters, was independently
HYDOXDWHG E\ WZR H[SHULHQFHG LQYHVWLJDWRUV 7& DQG 66 EOLQG WR SDWLHQWV¶
UDQGRPL]DWLRQZLWKKLJKDJUHHPHQW :HLJKWHG.DSSD FRQ¿GHQFH
LQWHUYDO 6%3FKDQJHZDVFODVVL¿HGDVZRUVHQHGIRU6%3LQFUHDVHV
! PP+JLPSURYHGIRU6%3UHGXFWLRQV! PP+JDQGVWDEOHRWKHUZLVH
Results: While hemodymanic parameters, evaluated separately, did not display a different trend between groups, comprehensive hemodynamic status
LPSURYHG PRUH LQ ,+0 DQG WKDQ LQ FRQWURO JURXS DQG according to both TC and SS (p=0.038 and p=0.008 respectively). Improvement in hemodynamics and in BP control agreed with Weighted Kappa=0.18
(and 0.26) in IHM vs 0.18 (and 0.21) in control group. Coherently, the joint
improvement of hemodynamic status and BP control was greater in IHM (42
DQG WKDQLQFRQWUROJURXS DQG S DQG)LQDOO\
DGYHUVH HYHQWV ZHUH OHVV IUHTXHQW LQ ,+0 WKDQ LQ FRQWURO JURXS S EXWWKHLURFFXUUHQFH ZDV QRWVLJQL¿FDQWO\ DVVRFLDWHGZLWKFKDQJHV LQKHPRdynamic parameters.
Conclusions: Easy-to-do non-invasive monitoring of hemodynamic parameWHUVFRPELQHGZLWKDSUHGH¿QHGDOJRULWKPRIGUXJVHOHFWLRQLQGXFHVPRUHIDvorable hemodynamic changes in UCH and guarantees greater joint improvement in hemodynamic status and BP control than conventional drug selection,
ZLWKIHZHUVLGHHIIHFWV7KHVH¿QGLQJVPD\KDYHSUDFWLFDOLPSOLFDWLRQVIRUD
better control of hypertension.
LB02.04
EFFECTS OF THE LERCANIDIPINE-ENALAPRIL
COMBINATION ON HOME BLOOD PRESSURE AND
ITS DAY-BY-DAY VARIABILITY
S. Omboni 1, A. Coca 2, I. Chazova 3, X. Girerd 4, H. Haller 5, P. Pauletto 6,
D. Pupek-Musialik , Y. Svyshchenko 8, G. Parati 9, G. Mancia 10. 1 Clinical
Research Unit, Italian Institute of Telemedicine, Varese, ITALY, 2 Hospital
Clinic of Barcelona, University of Barcelona, Barcelona, SPAIN, 3 Institute of
Clinical Cardiology, Department of Systemic Hypertension, Moscow, RUSSIA,
4
Cardiovascular Prevention Unit, Hôpital de la Pitié Salpétrière, Paris,
FRANCE, 5 Hannover Medical School, Dept. of Nephrology and Hypertension,
Hannover, GERMANY, 6 Department of Internal Medicine, University
Hospital of Treviso and University of Padua, Padua, ITALY, 7 Department
of Biochemistry and Molecular Biology, Karol Marcinkowski University of
Medical Sciences, Poznan, POLAND, 8 Strazhesko Institute of Cardiology,
Kiev, UKRAINE, 9 Department of Cardiology, IRCCS, Ospedale San Luca,
Istituto Auxologico Italiano and Department of Health Sciences, Univ. of
Milano-Bicocca, Milan, ITALY, 10 University of Milano-Bicocca and IRCCS,
Istituto Auxologico Italiano, Milan, ITALY
Objective: To assess the impact of drug treatment with an ACE-inhibitor,
a dihydropyridine calcium-channel blocker or their combination on home
blood pressure (HBP) and its day-by-day variability in a post-hoc analysis
of the FELT Study.
Design and method: After a 2-week placebo wash-out, patients with an elHYDWHGRI¿FH%3 GLDVWROLFDQGV\VWROLFPP+J DQG+%3 GLDVWROLF! PP+J ZHUHUDQGRPL]HGGRXEOHEOLQGWRDZHHNWUHDWPHQW
with placebo, lercanidipine (L) 10 or 20 mg daily, enalapril (E) 10 or 20 mg
daily, or the four possible combinations. HBP was measured semiautomatically in the morning and the evening during the week before randomization
and at the end of treatment. Baseline and treatment HBP values were sepaUDWHO\DYHUDJHGIRUWKHZKROHZHHNH[FOXGLQJWKH¿UVWGD\RIWKHUHFRUGLQJ
'D\E\GD\+%3YDULDELOLW\ZDVGH¿QHGDVWKHVWDQGDUGGHYLDWLRQ 6' RU
WKHYDULDWLRQFRHI¿FLHQW 9& RIWKHGDLO\%3DYHUDJHV
Results: 854 patients with valid HBP recordings at baseline and at the end of
treatment were analyzed (intention-to-treat population). From the baseline valXH “ PP+J V\VWROLF +%3 PHDQ VKRZHG D VPDOO UHGXFWLRQ >DYHUDJH
EDVHOLQHDGMXVWHGUHGXFWLRQ FRQ¿GHQFHLQWHUYDO PP+J@ZLWK
SODFHERDQGDPRUHPDUNHGVLJQL¿FDQWIDOOZLWKDOODFWLYHWUHDWPHQWVWKHPD[LPDOHIIHFWEHLQJREVHUYHGZLWKWKH/(FRPELQDWLRQ> YV
DQG PP+JZLWK(DQG/UHVSHFWLYHO\ S/(
YV / DQG S DFWLYH WUHDWPHQW YV SODFHER @ 6\VWROLF %3 6' ZDV UHGXFHG
E\ FRPELQDWLRQ WUHDWPHQW >DYHUDJH EDVHOLQHDGMXVWHG UHGXFWLRQ PP+J SHUFHQWDJH FKDQJH S YV SODFHER@ ( PRQRWKHUDS\ >
PP+JSYVSODFHER@DQGWRDOHVVHUH[WHQWE\/PRQRWKHUDS\> PP+J@ZKHUHDV9&ZDVQRWVLJQL¿FDQWO\DIIHFWHG
E\DQ\LQWHUYHQWLRQ6LPLODU¿QGLQJVZHUHREWDLQHGIRUGLDVWROLF+%3
Conclusions: 7KLV ODUJH +%3 GDWDEDVH VKRZV WKDW WKH /( FRPELQDWLRQ
lowers HBP more effectively than the corresponding monotherapies. It also
shows that the combination, and more in general active treatment, can reduce
the day-by-day BP variability. This appears to be largely attributable to the
reduction in HBP absolute level.
LB02.05
THE PROGRESSION FROM NORMAL BLOOD
PRESSURE TO RESISTANT HYPERTENSION IS
ATTENUATED BY FITNESS
P. Kokkinos 1, M. Doumas 1, C. Faselis 1, A. Tsimploulis 1, A. Pittaras 1,
A.J. Manolis 2, P. Narayan 3. 1 Veteran Affairs Medical Center, Dept. of
Cardiology, Washington, DC, USA, 2 Asklepeion Hospital, Dept. of Medicine,
Thessaloniki, GREECE, 3 Hippokration Hospital, Dept. of Medicine, Athens,
GREECE
Objective: Resistant hypertension (HTN) is associated with increased mortalLW\ULVN&DUGLRUHVSLUDWRU\¿WQHVVDVUHÀHFWHGE\H[HUFLVHFDSDFLW\LVLQYHUVHO\
associated with progression from normotension to hypertension. The impact
RIFDUGLRUHVSLUDWRU\¿WQHVVRQWKHUDWHRISURJUHVVLRQWRUHVLVWDQW+71KDVQRW
been studied. The objective of the study was to assess the association between
H[HUFLVH FDSDFLW\ DQG WKH SURJUHVVLRQ WR UHVLVWDQW +71 LQ LQGLYLGXDOV ZLWK
normal blood pressure (BP) at baseline.
Design and method: From 1986 to 2013, 11,335 apparently healthy individuals unGHUZHQWDQH[HUFLVHVWUHVVWHVWDWWKH9HWHUDQV$IIDLUV0HGLFDO&HQWHU:DVKLQJWRQ
'&:HLGHQWL¿HGLQGLYLGXDOV PHDQDJH“ ZLWKQRUPDOEORRGSUHVVXUH
SULRUWRH[HUFLVHWHVWLQJ:HHVWDEOLVKHG¿YH¿WQHVVFDWHJRULHVEDVHGRQWKH0(7
OHYHODFKLHYHG,QGLYLGXDOVZLWKDSHDN0(7OHYHO 0(7 FRPSULVHGWKH
/HDVW)LWFDWHJRU\ Q 7KRVHZKRDFKLHYHGD0(7OHYHOEHWZHHQWKH
DQG 0(7 FRPSULVHGWKH/RZ)LWFDWHJRU\ Q WKRVHZLWKD
SHDN0(7OHYHOEHWZHHQDQG 0(7 FRPSULVHGWKH0RGHUDWH)LW
Q WKRVHZLWK0(7OHYHOVRI FRPSULVHGWKH)LWJURXS
Q DQGWKRVHZLWKD0(7OHYHO! ! FRPSULVHGWKH+LJK)LWFDWHJRU\
Q 5HVLVWDQWK\SHUWHQVLRQ +71 LVGH¿QHGDV%3!PP+JGHVSLWH
the concurrent use of 3 antihypertensive agents of different classes prescribed at
optimal dose amounts, preferably one of them diuretic.
Results: 'XULQJWKHIROORZXSWLPHRI“\HDUVLQGLYLGXDOV GHYHORSHG UHVLVWDQW +71$IWHU DGMXVWLQJ IRU DJH ERG\ PDVV LQGH[ %0, cardiovascular (CV) disease, CV risk factors, muscle-wasting disease, lipid-lowering agents, and cardiac medications, the rate of progression to resisWDQWK\SHUWHQVLRQZDVORZHU KD]DUGUDWLR &,S in High-Fit compared with Least-Fit individuals.
Conclusions: ([HUFLVHFDSDFLW\!0(7VDWWHQXDWHGWKHUDWHRISURJUHVVLRQ
to resistant HTN in veterans. The association is independent of age, BMI and
other comorbidities.
LB02.06
EFFECTS OF BLOOD PRESSURE LOWERING IN
PATIENTS WITH ACUTE ISCHEMIC STROKE AND
CAROTID ARTERY STENOSIS
M. Jusufovic 1, E.C. Sandset 1, P.M.W. Bath 2, B.W. Karlson 3, E. Berge 4,
on behalf of the Scandinavian Candesartan Acute Stroke Trial (SCAST)
Study Group. 1 Department of Neurology, Oslo University Hospital, Oslo,
NORWAY, 2 Stroke Trials Unit, Division of Clinical Neuroscience, University
of Nottingham, Nottingham, UNITED KINGDOM, 3 AstraZeneca R&D
and Department of Molecular and Clinical Medicine, Institute of Medicine,
Sahlgrenska Academy, Gothenburg, SWEDEN, 4 Department of Internal
Medicine, Oslo University Hospital, Oslo, NORWAY
Objective: The Scandinavian Candesartan Acute Stroke Trial (SCAST)
VKRZHGQREHQH¿FLDOFOLQLFDOHIIHFWVRIEORRGSUHVVXUHORZHULQJZLWKFDQGH-
e89
Journal of Hypertension Volume 32, e-Supplement 1, 2014
sartan in the acute phase of stroke. We wanted to see if the effects of blood
pressure lowering are harmful in the subgroup of patients with carotid artery
stenosis.
Design and method: SCAST was a randomized- and placebo-controlled trial
RISDWLHQWVZLWKDFXWHVWURNHDQGKLJKV\VWROLFEORRGSUHVVXUH !PP
+J 2ISDWLHQWVZLWKLVFKHPLFVWURNHXQGHUZHQWFDURWLGDUWHU\LPDJLQJDQGWKHGHJUHHRIVWHQRVLVZDVFDWHJRUL]HGDVQRLQVLJQL¿FDQW Q PRGHUDWH Q RU VHYHUH ! Q 7KH WULDO¶V WZR
co-primary effect variables were the composite end-point of vascular death,
stroke or myocardial infarction, and functional outcome according to the modL¿HG5DQNLQ6FDOH
Results: Among patients with moderate or severe carotid stenosis the vascular
HQGSRLQW RFFXUUHG LQ RI SDWLHQWV WUHDWHG ZLWK FDQGHVDUWDQ DQG
LQRIFRQWUROV DQGWKHUHZDVQRHYLGHQFHRIDGLIIHUHQWULVN
LQSDWLHQWVZLWKVHYHUHVWHQRVLV DGMXVWHGKD]DUGUDWLRFRQ¿GHQFH
interval 0.28-1.96, p=0.54, Fig. 1). For functional outcome there was also no
clear difference, although in patients with severe stenosis the risk of a poor
outcome was somewhat higher than in any of the other groups (adjusted odds
UDWLR FRQ¿GHQFH LQWHUYDO S )LJ 3URJUHVVLYH
stroke also occurred more often in patients with carotid artery stenosis treated
ZLWKFDQGHVDUWDQ RISDWLHQWV YVRISDWLHQWV ZLWK
a trend towards an increased risk with increasing severity of stenosis (p-value
for linear trend=0.04).
Conclusions: There is no clear evidence that the effect of candesartan is qualitatively different in patients with carotid artery stenosis, but there are signals
that patients with severe stenosis are at particularly high risk of stroke progression and poor functional outcome.
Design and method: 3DWLHQWVZHUHUHTXLUHGWRKDYHDQRI¿FHV\VWROLFEORRG
SUHVVXUH 6%3 ! PP+JDQGDQDPEXODWRU\KRXU6%3! PP+J
RQDVWDEOHDQWLK\SHUWHQVLYHGUXJUHJLPHQRIGUXJVLQFOXGLQJDGLXUHWLFDW
PD[LPDOO\WROHUDWHGGRVHV3DWLHQWGLDULHVGRFXPHQWHGPHGLFDWLRQXVHGXULQJ
the 2 week screening period before randomization and for 2 weeks before the
6-month primary endpoint. There were 8 patient visits between enrolment and
6-month follow-up. Other analyses include assessment of medication changes,
and response in medication subgroups and according to geographic region.
Results: SDWLHQWVUHFHLYHGGHQHUYDWLRQDQGSDWLHQWVZHUHLQWKHVKDP
JURXS2I¿FHDQGDPEXODWRU\6%3GURSSHGVLJQL¿FDQWO\IURPEDVHOLQHLQERWK
JURXSV“PP+JLQWKHGHQHUYDWLRQJURXSDQG“PP+J
LQWKHVKDPJURXSIRURI¿FHDQG“PP+JLQWKHGHQHUYDWLRQJURXS
DQG “ PP +J LQ WKH VKDP JURXS IRU DPEXODWRU\ KRXU PHDVXUHPHQWV DOOS EXWWKHGLIIHUHQFHVEHWZHHQWKHJURXSVZHUHQRWVLJQL¿FDQW0HGLFDWLRQVFKDQJHVIROORZLQJUDQGRPL]DWLRQZHUHFRPPRQ WKH
PDMRULW\UHODWHGWRFKDQJHVLQPD[LPDOO\WROHUDWHGGRVHGUXJV6%3FKDQJHV
varied widely by geographic region for sham (-16.1 mmHg in the Southeast,
-15.6 mmHg in the South, -10.0 mmHg in the Midwest, -8.4 mmHg in the
West and -4.5 mmHg in the Northeast) but not denervation patients.
Conclusions: 7KHXQH[SHFWHGEORRGSUHVVXUHGURSLQWKHVKDPJURXSSRVVLEO\
attributed to increased patient follow-up and medication adherence, combined
with the unique features of the trial design such as the sham procedure and
RYHUQLJKW KRVSLWDOL]DWLRQ WKDW GR QRW UHÀHFW XVXDO FOLQLFDO SUDFWLFH VXJJHVW
factors that could have impacted results. Detailed medication use analysis is
underway to further aid in understanding these observations.
LB02.08
THE FRENCH DENER-HTN TRIAL:
RENAL DENERVATION + STANDARDIZED
ANTIHYPERTENSIVE TREATMENT VS.
STANDARDIZED ANTIHYPERTENSIVE TREATMENT
ALONE IN PATIENTS WITH RESISTANT
HYPERTENSION
M. Azizi 1, M. Monge 1, H. Pereira 1, M. Sapoval 1, on behalf of DENER-HTN
Investigators 2. 1 Hôpital Européen Georges Pompidou, Paris, FRANCE, 2 The
French network of ESH Excellence Centers, FRANCE
Objective: The DENER-HTN trial is a multicenter, prospective, randomized,
RSHQ FRQWUROOHG VWXG\ ZLWK EOLQG HQGSRLQW HYDOXDWLRQ RI WKH HI¿FDF\ DQG
safety of renal denervation (Symplicity® catheter) in addition to standardized
optimal antihypertensive treatment compared to standardized optimal antihypertensive treatment alone in patients with resistant hypertension (RH).
Design and method: (OLJLEOH SDWLHQWV ZHUH PHQ RU ZRPHQ DJHG \HDUVZLWK5+WR! DQWLK\SHUWHQVLYHGUXJVLQFOXGLQJDGLXUHWLF VXSLQH
RI¿FH%3! PP+J DQGVXLWDEOHUHQDODUWHU\DQDWRP\H*)5! ml/min and absence of secondary hypertension. Included patients were given
a 4-week standardised triple therapy (STT) with indapamide 1.5mg/d, ramipril 10mg/d (or irbesartan 300mg/d if cough), and amlodipine 10mg/d. After
ZHHNVRIWKH677RQO\SDWLHQWVZLWKFRQ¿UPHG5+DVGH¿QHGE\DGD\WLPH
DPEXODWRU\6%3'%3! PP+JZHUHUDQGRPLVHGWRWKHGHQHUYDWLRQ
or the control group. At follow-up visits on month 2, 3, 4 and 5, the antihypertensive treatment was similarly reinforced in each group if home BP
ZDV! PP+JE\VHTXHQWLDOO\DGGLQJVSLURQRODFWRQH PJG ELsoprolol (10mg/d), prazosin (5mg/d), and rilmenidine (1mg/d), respectively.
The primary outcome is the change in daytime ambulatory SBP at 6 months.
LB02.07
FACTORS IMPACTING BLOOD PRESSURE
RESPONSE TO A SHAM PROCEDURE: AN ANALYSIS
FROM THE SYMPLICITY HTN-3 RANDOMIZED
CLINICAL TRIAL
G.L. Bakris 1, D. Bhatt 2. 1 University of Chicago Medicine, Chicago, IL, USA,
Brigham and Women Hospital Heart and Vascular Center and Harvard
Medical School, Boston, MA, USA
2
Objective: Controlled trials of hypertension treatment report minimal placebo
responses and SYMPLICITY HTN-2 showed no response in unblinded control
patients not receiving renal denervation. In SYMPLICITY HTN-3, a randomL]HGEOLQGHGVKDPFRQWUROOHGWULDOWKHUHZDVDJUHDWHUWKDQH[SHFWHGUHVSRQVH
in the sham arm that may partially account for the failure of the trial to meet
WKH SULPDU\ HI¿FDF\ HQGSRLQW 3RVVLEOH IDFWRUV DIIHFWLQJ WKH VKDP UHVSRQVH
were investigated.
Results: From 01/06/2012 to 15/10/2013, 1416 patients with RH were
VFUHHQHGDPRQJZKLFKFRXOGQRWVDWLVI\DOOLQFOXVLRQH[FOXVLRQFULWHULDLQFOXGLQJVHFRQGDU\K\SHUWHQVLRQ Q XQVXLWDEOHUHQDODUWHU\DQDWRP\ Q DJH Q H*)5 Q DQGRWKHUH[FOXVLRQFULWHULD Q $PRQJWKHSDWLHQWVZLWK5+ZKRIXO¿OOHGDOOLQFOXVLRQH[FOXVLRQFULWHULD UHIXVHGWRSDUWLFLSDWHWRWKHVWXG\)LQDOO\SDWLHQWVZHUH
LQFOXGHGLQWKHVWXG\DPRQJZKLFKKDGFRQ¿UPHG5+E\$%30DIWHU
4-week STT and were randomized to the denervation (n=53) or the control
JURXS Q 3DWLHQWVFKDUDFWHULVWLFVDWUDQGRPLVDWLRQZHUHDJH\UV
PHQ &DXFDVLDQ RI¿FH %3 PP+J KRPH %3
PP+J GD\WLPH DPEXODWRU\ %3 PP+J %0, NJPH*)5POPLQ
Conclusions: 2QRIWKHSDWLHQWVKDGPRQWKIROORZXS7KH
last patient-last visit at 6 months is scheduled on 05/15/2014. The 6-month BP
and safety results will be presented at the ESH meeting.
e90
Journal of Hypertension Volume 32, e-Supplement 1, 2014
LB02.09
RELATIONSHIPS BETWEEN PHARMACOKINETICS
OF ANTIANGIOGENIC DRUGS, LARGE ARTERIES
PROPERTIES AND CANCER PROGRESSION
M. Alivon 1, B. Blanchet 2, -*LURX[3, M. Vidal 2, F. Goldwasser 3, S. Laurent 1,
P. Boutouyrie 1. 1 INSERM U970, PARCC, Pharmacology Department HEGP,
Paris, FRANCE, 2 Pharmacology Department Cochin, Paris, FRANCE, 3
Oncology Department Cochin, Paris, FRANCE
S H[SODLQLQJ DQG RI WKH YDULDQFH 6LPLODU UHVXOWV ZHUH REWDLQHG EHWDFRHI¿FLHQWIRU6'PVDQGPVUHVSHFWLYHO\S
High concentration of TKI during follow-up was associated with a lessHU FDQFHU SURJUHVVLRQ IRU 6' LQFUHDVH 55 &, >@
p=0.035). Concentrations above -0.5 SD discriminates patients with lower
SURJUHVVLRQIURPWKHRWKHUV55>@ ¿JXUH Objective: Tyrosine kinase inhibitors (TKI) which are targeting the VEGF pathway
are used for metastatic cancer treatment. TKI induced hypertension is frequent, interHVWLQJRISDWLHQWV:HSUHYLRXVO\UHSRUWHGDSUHVVXUHLQGHSHQGHQWODUJHDUteries stiffening under TKI. We hypothesized that stiffening of large arteries could be
UHODWHGWRWKHLQWHQVLW\RIH[SRVXUHWR7.,DVPHDVXUHGIURPVHULDOGRVDJHVLQEORRG
:HIXUWKHUK\SRWKHVL]HGWKDWH[SRVXUHWR7.,ZDVUHODWHGWRFDQFHUSURJUHVVLRQ
Design and method: In this prospective, single center observational study,
61 patients with metastatic cancer receiving TKI treatment by sorafenib or
VXQLWLQLE ZHUH LQFOXGHG 3DWLHQWV ZHUH H[SORUHG EHIRUH WKH LQWURGXFWLRQ RI
the treatment, then every two week for two months (V0 to V4). Peripheral
DQG FHQWUDO EORRG SUHVVXUH ZDYH UHÀHFWLRQ DQG DRUWLF SXOVH ZDYH YHORFity (PWV) were measured. Blood samples were obtained from V1 to V4
for the pharmacokinetic study. Concentrations were determined by HPLC.
Since concentrations were different between sorafenib and sunitinib, Z-score
standardization (mean=0, SD=1) was used to combine both drugs. Robust
stepwise regression analysis was performed for studying the determinants
RI3:9LQFUHDVH&R[UHJUHVVLRQZDVXVHGWRHVWDEOLVKWKHUHODWLRQVKLSEHtween TKI concentrations and cancer progression.
Results: 0HDQ DJH ZDV PHDQ 6%3 PP+J $W 9 PHDQ
blood pressure increased by 5(14) mmHg and by 5(13) at V4. Determinants
of PWV increase were high ITK blood concentration and mean blood presVXUHLQFUHDVH EHWDFRHI¿FLHQWIRU6'PVDQGPVUHVSHFWLYHO\
Conclusions: In conclusion, large arteries stiffening observed under TKI
LVSURSRUWLRQDOWRWKHLQWHQVLW\RIH[SRVXUHWR7.,LQGHSHQGHQWO\RIEORRG
SUHVVXUHLQFUHDVH3DWLHQWVXQGHUH[SRVHGWR7.,DUHDWKLJKHUULVNRIGLVHDVH
progression.
Abstracts
e91
ORAL SESSION
ORAL SESSION 7A
THERAPEUTIC ASPECTS
7A.01
EFFECTS OF BETA-BLOCKERS WITH OR WITHOUT
VASODILATING PROPERTIES ON CENTRAL BLOOD
PRESSURE: A NETWORK META-ANALYSIS OF
RANDOMIZED TRIALS IN HYPERTENSION
G. Pucci 1, M. Ranalli 2, F. Battista 1, F. Anastasio 1, M. Crapa 1, G. Schillaci 1.
Department of Medicine, University of Perugia, Internal Medicine, Santa
Maria Hospital, Terni, ITALY, 2 Department of Political Sciences, University of
Perugia, Perugia, ITALY
1
Objective: 7UHDWPHQWZLWKȕEORFNHUVLVHIIHFWLYHLQUHGXFLQJSHULSKHUDOEORRG
SUHVVXUH S%3 EXW OHVV HIIHFWLYH WKDQ RWKHU DQWLK\SHUWHQVLYHGUXJ FODVVHV LQ
UHGXFLQJFHQWUDOEORRGSUHVVXUH F%3 ,WLVFRQWURYHUVLDOZKHWKHUYDVRGLODWLQJ
ȕEORFNHUV 9%FDUYHGLOROQHELYROROODEHWDORO PD\EHPRUHHIIHFWLYHLQUHGXF
LQJF%3FRPSDUHGWRQRQYDVRGLODWLQJȕEORFNHUV 19%DWHQROROPHWRSURORO
ELVRSUROROSURSUDQRORO Design and method: $QHWZRUNPHWDDQDO\VLVZDVFRQGXFWHGE\VHOHFWLQJUDQ
GRPL]HGWULDOVH[SORULQJWKHHIIHFWVRIȕEORFNHUVRQF%3:HVHDUFKHG3XEPHG
(PEDVH DQG 0HGOLQH HOHFWURQLF GDWDEDVHV EHIRUH -DQXDU\ 7ZHQW\WZR
VWXGLHVZHUHVHOHFWHGDQGFRPSDULVRQVZHUHPDGHEHWZHHQWULDODUPV Q IRU19%DQGQ IRU9% 7KHGLIIHUHQFHEHWZHHQS6%3DQGF6%3ZDVHYDO
XDWHG ERWK DW EDVHOLQH DQG DIWHU WUHDWPHQW $ UDQGRPHIIHFW PHWDUHJUHVVLRQ
PRGHOZDVXVHGWRFRPSXWHZHLJKWHGHVWLPDWHV7KHIROORZLQJFRYDULDWHVZHUH
LQWURGXFHGLQWKHPRGHOWUHDWPHQW IRUEDVHOLQHDQGDIWHUWUHDWPHQW GUXJ
FODVV 9%YV19% LQWHUDFWLRQWHUP WUHDWPHQW[GUXJFODVV PHDQDJHGXUD
WLRQRIWKHVWXG\DQGGHVLJQRIWKHVWXG\ SDUDOOHOYVFURVVRYHU Results: VXEMHFWV 19% 9% ZHUH LQFOXGHG LQ WKH DQDO\VLV
0HDQS6%3ZDVPP+JIRU19%DQGPP+JIRU9%DWEDVHOLQHDQG
PP+J IRU 19% DQG PP+J IRU 9% DIWHU WUHDWPHQW 7KH GLIIHUHQFH
EHWZHHQS6%3DQGF6%3DWEDVHOLQH S6%3F6%3 ZDVPP+JIRU19%
DQGPP+JIRU9%7UHDWPHQWZLWKHLWKHU9% RU19% ZDV IROORZHGE\
D UHGXFWLRQ RI WKH DERYH GLIIHUHQFH WR PP+J IRU 19% DQG PP+J
IRU9%,QWKH¿QDOPRGHOWKHHIIHFWRIGUXJFODVVRQWKHGLIIHUHQFHEHWZHHQ
S6%3DQGF6%3 DIWHUWUHDWPHQW±EDVHOLQH ZDVPDUJLQDOO\EXWQRWVLJQL¿FDQWO\
VPDOOHUIRU9% PP+J WKDQIRU19% PP+JWYDOXHS Conclusions: 9%KDYHDPDUJLQDOO\DOWKRXJKQRWVLJQL¿FDQWO\OHVVXQIDYRXU
DEOHHIIHFWVRQF6%3FRPSDUHGWR19%7KHEORRGSUHVVXUHORZHULQJHIIHFWRI
ȕEORFNHUVLVPRUHSURQRXQFHGIRUS6%3WKDQIRUF6%3
7A.02
DARK CHOCOLATE INTAKE IMPROVES
ENDOTHELIAL FUNCTION AND CENTRAL ARTERIAL
HEMODYNAMICS IN YOUNG HEALTHY PEOPLE: A
RANDOMIZED AND CONTROLLED TRIAL
T. Pereira 1, -0DOGRQDGR2. 1 Instituto Politécnico de Coimbra, ESTESC,
DCPL, Coimbra, PORTUGAL, 2 Instituto de Investigação e Formação
Cardiovascular, Coimbra, PORTUGAL
Objective: 7KHDLPRIWKLVVWXG\ZDVWRDVVHVVWKHYDVFXODUEHQH¿WVRIDGDUN
FKRFRODWHLQWDNHSURJUDPSDUWLFXODUO\RYHUWKHHQGRWKHOLDOIXQFWLRQDQGWKHFHQ
WUDODUWHULDOKHPRG\QDPLFVLQKHDOWK\DQG\RXQJLQGLYLGXDOV
Design and method: $UDQGRPL]HGDQGFRQWUROOHGWULDOZDVFDUULHGRXWLQYROY
LQJKHDOWK\\RXQJLQGLYLGXDOVUDQGRPL]HGLQWRWZRJURXSVFRQWUROJURXS
&*Q DQGLQWHUYHQWLRQJURXS ,*Q 7KH,*LQJHVWHGDGDLO\GRVDJH
RIJRIGDUNFKRFRODWH !FRFRD IRUDPRQWK$OOWKHLQGLYLGXDOVZHUH
VXEPLWWHGWRWZRFOLQLFDOHYDOXDWLRQVEDVDODQGDIWHURQHPRQWKRILQWHUYHQWLRQ
LQZKLFKWKHLUZHLJKWKHLJKWERG\PDVVLQGH[ %0, V\VWROLFEORRGSUHVVXUH
6%3 GLDVWROLFEORRGSUHVVXUH '%3 KHDUWUDWH +5 ÀRZPHGLDWHGGLODWLRQ
)0' DUWHULDO VWLIIQHVV LQGH[ $6, DRUWLF SXOVH ZDYH YHORFLW\ 3:9 DQG
SXOVHZDYHDQDO\VLVRYHUWKHFDURWLGDUWHU\ 3:$ ZHUHDVVHVVHG
Results: &* DQG ,* JURXSV KDG VLPLODU EDVHOLQH FOLQLFDO DQG GHPRJUDSKLF
FKDUDFWHULVWLFV$IWHUWKHLQWHUYHQWLRQ%0,+5DQGEUDFKLDO%3GLGQ¶WVXIIHU
VLJQL¿FDQWYDULDWLRQVLQHLWKHUJURXS7KHEDVHOLQH3:9DQG3:$SDUDPHWHUV
ZHUHVLPLODULQERWKJURXSVEXWZHUHVLJQL¿FDQWO\GLIIHUHQWLQWKHVHFRQGHYDOX
DWLRQZLWKWKH,*VKRZLQJORZHU3:9ORZHU$6,DQGORZHUDXJPHQWDWLRQLQ
GH[HV $L; $UWHULDOIXQFWLRQLPSURYHGDIWHULQWHUYHQWLRQLQWKH,*ZLWK3:9
GHFUHDVLQJ IURP “PV EDVHOLQH WR “ PV SRVWLQWHUYHQWLRQ
S ZLWKQRVLJQL¿FDQWGLIIHUHQFHVREVHUYHGLQWKH&*$VLJQL¿FDQWGH
FUHDVHLQ$6, “DWEDVHOLQHDQG“SRVWLQWHUYHQWLRQS DQG$L; DWEDVHOLQH“DQGSRVWLQWHUYHQWLRQ“S ZHUHDOVRGHSLFWHGIRUWKH,*EXWQRWIRUWKH&*(QGRWKHOLDOIXQFWLRQLPSURYHG
LQWKH,*DIWHUWKHPRQWKLQWHUYHQWLRQZLWKWKH)0'LQFUHDVLQJIURP“
EDVHOLQH WR “ SRVWLQWHUYHQWLRQ S ZLWK QR VLJQL¿FDQW GLIIHU
ences in the CG.
Conclusions: 7KHGDLO\LQJHVWLRQRIJGDUNFKRFRODWH !FRFRD GXULQJD
PRQWKLPSURYHVWKHYDVFXODUIXQFWLRQLQ\RXQJDQGKHDOWK\LQGLYLGXDOVSURED
EO\UHÀHFWLQJDSRVLWLYHPRGXODWLRQRIWKHHQGRWKHOLXPGHSHQGHQWYDVRGLODWLRQ
7A.03
EFFECTS OF THIAZIDE-TYPE AND THIAZIDE-LIKE
DIURETICS ON CARDIOVASCULAR EVENTS AND
MORTALITY. A SYSTEMATIC REVIEW AND METAANALYSIS
52OGH(QJEHULQN1, :)UHQNHO2, %9DQ'HQ%RJDDUG2, L. Brewster 2,
/9RJW1, %9DQ'HQ%RUQ2. 1 Academic Medical Center, Department of
Nephrology, Amsterdam, NETHERLANDS, 2 Academic Medical Center,
Department of Vascular Medicine, Amsterdam, NETHERLANDS
Objective: 7KLD]LGHGLXUHWLFVFDQEHGLYLGHGDFFRUGLQJWRWKHLUPROHFXODUVWUXF
WXUH LQ WKLD]LGHOLNH DQG WKLD]LGHW\SH GLXUHWLFV 5HFHQW VWXGLHV VXJJHVW WKDW
FKORUWKDOLGRQHDWKLD]LGHOLNHGLXUHWLFDQGK\GURFKORURWKLD]LGHDWKLD]LGHW\SH
GLXUHWLF PD\ GLIIHU LQ WKHLU FDSDFLW\ WR UHGXFH FDUGLRYDVFXODU PRUELGLW\ DQG
PRUWDOLW\:HK\SRWKHVL]HGWKDWWKLVGLIIHUHQWLDOHIIHFWRQFDUGLRYDVFXODUHYHQWV
PD\EHUHODWHGWRWKHGLIIHUHQWSKDUPDFRORJLFDOSURSHUWLHVRIWKLD]LGHW\SHDQG
WKLD]LGHOLNHGLXUHWLFVDQGQRWWRK\GURFKORURWKLD]LGHDQGFKORUWKDOLGRQHDORQH
,QWKLVVWXG\ZHFRPSDUHGWKHHIIHFWVRIWKLD]LGHW\SHDQGWKLD]LGHOLNHGLXUHWLFV
RQFDUGLRYDVFXODUPRUELGLW\DQGPRUWDOLW\
Design and method: 0HGOLQH (PEDVH DQG &RFKUDQH OLEUDU\ ZHUH VHDUFKHG
XQWLO6HSWHPEHU IRUFOLQLFDOWULDOVLQZKLFKWKLD]LGHGLXUHWLFVZHUHJLYHQ
DV ¿UVWOLQH DQWLK\SHUWHQVLYH WUHDWPHQW 6WXGLHV WKDW FRPSDUHG WKH HIIHFWV RI
WKLD]LGHW\SH RU WKLD]LGHOLNH GLXUHWLFV ZLWK SODFHER RU RWKHU DQWLK\SHUWHQVLYH
GUXJVRQFDUGLRYDVFXODUHYHQWVRUPRUWDOLW\ZHUHVHOHFWHG5DQGRPL]HGVWXGLHV
LQDGXOWK\SHUWHQVLYHSDWLHQWVZLWKDWOHDVWRQH\HDUIROORZXSZHUHLQFOXGHG
7KLD]LGHW\SHDQGWKLD]LGHOLNHZHUHFRPSDUHGLQGLUHFWO\EHFDXVHGLUHFWFRP
SDULVRQV DUH ODFNLQJ$Q DQDO\VLV RI FRYDULDQFH ZDV SHUIRUPHG WR FRUUHFW IRU
DFKLHYHGEORRGSUHVVXUHUHGXFWLRQVDPRQJVWXGLHV7KHDQDO\VLVZDVZHLJKWHG
E\WKHLQYHUVHYDULDQFHRIWKHQDWXUDOORJDULWKPRIWKHULVNUDWLRV%RWK\LQWHU
FHSWDQGVORSHRIWKHVHUHJUHVVLRQOLQHVZHUHFDOFXODWHGDQGFRPSDUHG
Results: 7ZHQW\RQHVWXGLHVWRWDOOLQJFRPSDULVRQVZHUHLQFOXGHG,QGL
UHFWFRPSDULVRQRIWKLD]LGHW\SHDQGWKLD]LGHOLNHGLXUHWLFVDQGGUXJDGMXVWHG
DQDO\VHV FDOFLXPDQWDJRQLVWVDQG$&(LQKLELWRUV VKRZHGQRGLIIHUHQFHLQWKH
FRPSRVLWHRIFDUGLRYDVFXODUHYHQWVDQGWKHVHSDUDWHHQGSRLQWVFRQVLVWLQJRI
FHUHEURYDVFXODUHYHQWVFRURQDU\HYHQWVKHDUWIDLOXUHDQGDOOFDXVHPRUWDOLW\
ZLWKSODFHERDQGRWKHUDQWLK\SHUWHQVLYHWKHUDS\DVFRPSDUDWRUJURXS)RUD
JLYHQ UHGXFWLRQ LQ EORRG SUHVVXUH WKLD]LGHOLNH GLXUHWLFV VKRZHG VLJQL¿FDQW
PRUHULVNUHGXFWLRQWKDQWKLD]LGHW\SHGLXUHWLFVIRUWKHFRPSRVLWHRIFDUGLR
YDVFXODUHYHQWV )LJXUHRQOHIROORZLQJSDJH DQGKHDUWIDLOXUH S M
O
N
D
A
Y
O
R
A
L
S
e92
Journal of Hypertension Volume 32, e-Supplement 1, 2014
UNITED KINGDOM, 4 Department of Nephrology and Hypertension,
Leiden University Medical Center, Leiden, NETHERLANDS, 5 University of
Heidelberg, Department of Nephrology, Heidelberg, GERMANY, 6 Division of
Hypertension, Universidad Autonome, Madrid, SPAIN, 7 University Hospital,
Düsseldorf, GERMANY
Objective: $OWKRXJKWKHUHLVDVWURQJFRUUHODWLRQEHWZHHQSUHWUHDWPHQWEORRG
SUHVVXUH %3 OHYHOVDQGUHVSRQVHWRWKHUDS\WKHHIIHFWVRIDZLGHUDQJHRISUH
WUHDWPHQW%3YDOXHVKDYHQRWEHHQZHOOVWXGLHG
Design and method: 'LDEHWLFVZLWKRXWPLFURDOEXPLQXULD Q HQWHUHGWKH
5DQGRPLVHG2OPHVDUWDQ$QG'LDEHWHV0LFUR$OEXPLQXULD3UHYHQWLRQ 52$'
0$3 VWXG\WRWHVWWKHK\SRWKHVLVWKDWRQVHWRIPLFURDOEXPLQXULDFDQEHSUH
YHQWHGE\ROPHVDUWDQPJGDLO\$WRQH\HDUVXEMHFWVZHUHHOLJLEOHIRU
%3UHVSRQVHDQDO\VLV
Conclusions: 7KLD]LGHOLNHGLXUHWLFVDUHPRUHHIIHFWLYHLQUHGXFLQJFDUGLRYDV
FXODUHYHQWVDQGKHDUWIDLOXUHFRPSDUHGWRWKLD]LGHW\SHGLXUHWLFVZKHQFRPSD
UDEOHEORRGSUHVVXUHUHGXFWLRQVDUHDFKLHYHG
7A.04
EFFECT OF ANTI-VEGF AGENTS FOR
DIABETIC RETINOPATHY AND SUB-CLINICAL
ATHEROSCLEROSIS IN HYPERTENSIVE PATIENTS
WITH DIABETIC NEPHROPATHY IN EARLY STAGES
*'LPDV1, *%DODQLNDV2, ),OLDGLV1, &6DYRSRXORV1, $$OH[DQGULGLV2,
9.DUDPSDWDNLV, $+DW]LWROLRV1, '*UHNDV1. 1 First Propaedeutic
Medical Department, Ahepa University Hospital, Aristotle University of
Thessaloniki, Thessaloniki, GREECE, 2 First Department of Opthalmology
Ahepa University Hospital Aristotle University of Thessaloniki, Thessaloniki,
GREECE, 3 Laboratory of Experimental Opthalmology, Aristotle University of
Thessaloniki, Thessaloniki, GREECE
Objective: ,W UHPDLQV FRQWURYHUVLDO WKH PHFKDQLVP E\ ZKLFK YDVFXODU HQ
GRWKHOLDOJURZWKIDFWRU 9(*) ZRUNVLQWKHNLGQH\DVZHOODVLQWKHYHVVHOV
DWOHDVWLQWKHHDUO\VWDJHVRIGLDEHWLFQHSKURSDWK\ '1 DQGFKURQLFNLGQH\
GLVHDVH &.' 5HFHQWO\DQXPHURXVHDUO\VWXGLHVVXJJHVWDQLPSRUWDQWSR
WHQWLDOUROHIRUDQWL9(*)DJHQWVLQWKHPDQDJHPHQWRIGLDEHWLFUHWLQRSDWK\
'5 ,QWUDYLWUHDO XVH DOVR KDV EHHQ VKRZQ WR KDYHEHQH¿FLDO VKRUWWHUP HI
IHFWVRQGLDEHWLFPDFXODUHGHPD '0( YLVXDODFXLW\DQGUHWLQDOWKLFNQHVV
Design and method: '1 W\SH SDWLHQWV ZHUH LQFOXGHG 7KH\ UHFHLYHG
DUHFRPELQDQWKXPDQL]HGPRQRFORQDODQWLERG\RIDQWL9(*)E\VLQJOHXVH
RIPJLQWUDYLWUHDOLQMHFWLRQHYHU\GD\VIRUPRQWKVRWKHU
SDWLHQWVUHFHLYHGFRQWUROVKDPWUHDWPHQW
Results: :LWK ÀXRUHVFHLQ DQJLRJUDSK\ ZDV EHHQ GHPRQVWUDWHG D OHDNDJH RI
VHURXVÀXLGIURPYHVVHOVDQGWKHUHIRUHDFFXPXODWLRQWRPDFXODUHGHPD:LWK
RFXODU FRKHUHQFH WRPRJUDSK\ 2&7 SDWLHQWV H[KLELWHG D GHFUHDVH RI '0(
RI PP PRUH WKDQ LQ FRQWUROV D VLJQL¿FDQW GHFUHDVH RI FHQWUDO
UHWLQDODUWHU\WKLFNQHVVDQGLPSURYHPHQWRIYLVXDODFXLW\,QWLPDPHGLDWKLFN
QHVV ,07 RIFDURWLGVDVDVXEFOLQLFDODWKHURVFOHURWLFPDUNHUUDQJHGIURP
WRPP
Conclusions: 'HVSLWHSURPLVLQJHDUO\HIIHFWVRIWKLVPHGLFDWLRQZHHDJHUO\
DZDLWWKHUHVXOWVRIODUJHFRQWUROOHGWULDOVWRVXEVWDQWLDWHWKHVDIHW\HI¿FDF\
DQG HI¿FLHQF\ RI DQWL9(*) GUXJV IRU '5 DQG VXEFOLQLFDO DWKHURVFOHURVLV
HVSHFLDOO\LQHDUO\VWDJHVRI'1DWWKHVWDJHRIK\SHUSHUIXVLRQZLWKUHYHUV
LEOHOHVLRQV
7A.05
INFLUENCE OF PRETREATMENT BLOOD PRESSURE
LEVELS ON ANTIHYPERTENSIVE DRUG BENEFITS
IN DIABETICS: THE ROADMAP EXPERIENCE AT ONE
YEAR
&&KDW]LN\UNRX1, -,]]R2, -0HQQH1, *9LEHUWL, 75DEHOLQN, (5LW] 5,
L.M. Ruilope , L. Rump , ++DOOHU1. 1 Nephrology Section, Hannover
Medical School, Hannover, GERMANY, 2 Department of Medicine, Erie
County Medical Center Buffalo, NY, USA, 3 KCL Guys Hospital, London,
Results: %3 DW UDQGRPL]DWLRQ ZDV >PHDQ 6' @ PP+J
ZLWKD%3UDQJHRIPP+J$W\HDUPHDQ%3ZDV PP+JDQGWKHRYHUDOOFRQWUROUDWH PP+J H[FHHGHG7KH
PHDQ UHGXFWLRQV LQ V\VWROLF > PP+J@ DQG GLDVWROLF %3 > PP+J@ZHUHKLJKO\GHSHQGHQWRQWKH%3OHYHO DFFRUGLQJWR-1& DW9LVLW
$W\HDUWUHDWPHQWGHFUHDVHGWKHSUHYDOHQFHRI6WDJHK\SHUWHQVLRQIURP
WR>PHDQ%3FKDQJH PP+J@DQG6WDJHK\SHUWHQVLRQ
IURPWR>PHDQ%3FKDQJH PP+J@ZLWKFRUUHVSRQG
LQJLQFUHDVHVLQWKHSUHYDOHQFHRISUHK\SHUWHQVLRQIURPWR>PHDQ%3
FKDQJH PP+J@DQGQRUPRWHQVLRQIURPWR>PHDQ
%3 FKDQJH PP+J@7KHVH HIIHFWV UHPDLQHG XQFKDQJHG
XSWR\HDU
Conclusions: 7KXV DQ DV\PPHWULF ORZHULQJ RI %3 ZDV REVHUYHG GXULQJ
52$'0$3ZLWKPRUH%3ORZHULQJHIIHFWVLQSDWLHQWVZLWKKLJKHUEDVHOLQH%3
7A.06
ASSOCIATION BETWEEN INSOMNIA AND USE OF
BP-LOWERING DRUGS IN HYPERTENSIVE PATIENTS:
A CROSS-SECTIONAL COHORT STUDY
R. Bruno 1, /3DODJLQL2, 90DQFXVR2, 0&DUJLROOL2, $*HPLJQDQL 1,
M. Mauri 2, /*KLDGRQL2, 67DGGHL2. 1 Institute of Clinical Physiology, CNR,
Pisa, ITALY, 2 Department of Clinical and Experimental Medicine, University
of Pisa, Pisa, ITALY
Objective: ,QVRPQLD DQG VKRUW VOHHS GXUDWLRQ KDYH EHHQ DVVRFLDWHG ZLWK LQ
FUHDVHG SUHYDOHQFH LQFLGHQFH DQG VHYHULW\ RI K\SHUWHQVLRQ +RZHYHU WKH UH
ODWLRQVKLSEHWZHHQLQVRPQLDDQGXVHRIGLIIHUHQWDQWLK\SHUWHQVLYHGUXJFODVVHV
KDVQRWEHHQDVFHUWDLQHG\HW
Design and method: K\SHUWHQVLYHSDWLHQWVDWWKHLU¿UVWYLVLWLQDWHUWLDU\
+\SHUWHQVLRQ2XWSDWLHQW8QLWZHUHHQUROOHGLQDFURVVVHFWLRQDOVWXG\,QVRPQLD
6HYHULW\,QGH[ ,6, %HFN'HSUHVVLRQ,QYHQWRU\ %', DQG6WDWH7UDLW$Q[L
HW\ ,QYHQWRU\ 67$<< ZHUH DGPLQLVWHUHG ,QVRPQLD ZDV GH¿QHG DV ,6,!
GHSUHVVLYHV\PSWRPVDV%',!WUDLWDQ[LHW\DV67$,<!3DWLHQWVZLWK
VHOIUHSRUWHG VOHHS DSQHDV RU VQRULQJ Q RU ZLWK LQFRPSOHWH GDWD Q ZHUHH[FOXGHG
Results: 'DWDIURPSDWLHQWVZHUHDQDO\]HG PDOHVPHDQDJH“
\HDUV DQWLK\SHUWHQVLYH WUHDWPHQW SUHYLRXV &9 HYHQWV GLDEHWHV REHVLW\ VPRNLQJ K\SHUFKROHVWHUROHPLD ,QVRPQLDFV Q ZHUHROGHUWKDQQRQLQVRPQLDFV “YV“\HDUVS IHPDOH
JHQGHU YV S DQ[LHW\ YV S DQG GHSUHVVLYH
V\PSWRPV YVS ZHUHPRUHSUHYDOHQWLQLQVRPQLDFV,QVRPQLDFV
ZHUHWUHDWHGZLWKKLJKHUQXPEHURIDQWLK\SHUWHQVLYHGUXJV “YV“
S DQGPRUHIUHTXHQWO\ZLWKDQJLRWHQVLQUHFHSWRUEORFNHUV $5%VYV
S DQGGLXUHWLFV YVS ZKHUHDVWKHXVHRIRWKHU
GUXJFODVVHVZDVVLPLODU
,QDPXOWLSOHORJLVWLFUHJUHVVLRQDQDO\VLVDGMXVWHGIRUFDUGLRYDVFXODUDQGSV\
FKLDWULFYDULDEOHV$5%VXVH 25&/ WRJHWKHUZLWKGHSUHVVLYH
V\PSWRPV 25&/ DQGDQ[LHW\ 25&/ ZDV
DVVRFLDWHGZLWKDVLJQL¿FDQWO\KLJKHUSUREDELOLW\RILQVRPQLD
Conclusions: 7KLVFURVVVHFWLRQDODQDO\VLVVXJJHVWVWKDW$5%VXVHPD\EHDV
VRFLDWHGZLWKLQVRPQLDLQDFRKRUWRIK\SHUWHQVLYHSDWLHQWV
7A.07
QUALITY OF LIFE IN PATIENTS WITH CAROTID
BAROREFLEX ACTIVATION THERAPY
T. Alnima, -6PLWV3:GH/HHXZ$.URRQ.
Maastricht University Medical Centre, Maastricht, NETHERLANDS
Objective: &DURWLGEDURUHÀH[DFWLYDWLRQWKHUDS\ %$7 LVDGHYLFHEDVHGWKHU
DS\ZLWKORQJWHUPEORRGSUHVVXUHIDOOLQSDWLHQWVZLWKUHVLVWDQWK\SHUWHQVLRQ
e93
Journal of Hypertension Volume 32, e-Supplement 1, 2014
1HYHUWKHOHVVTXDOLW\RIOLIHUHPDLQVXQFOHDULQSDWLHQWVZHDULQJWKLVGHYLFH
7KH DLP RI WKLV VWXG\ LV WR HYDOXDWH WKH TXDOLW\ RI OLIH LQ SDWLHQWV UHFHLYLQJ
BAT.
Design and method: SDWLHQWVZHUHHQUROOHGLQWKHGRXEOHEOLQG5KHRV3LY
RWDO7ULDO*URXSFRQVLVWHGRISDWLHQWVZKRUHFHLYHG%$7RQHPRQWKDIWHU
GHYLFHLPSODQWDWLRQ7KHVXEMHFWVFRPSULVLQJ*URXSUHFHLYHGRSWLPDOGUXJ
WUHDWPHQWDQGVWDUWHG%$7PRQWKVDIWHULPSODQWDWLRQ'DWDRI6KRUW)RUPDW
6) DQG)ORULGD3DWLHQW$FFHSWDQFH6XUYH\ )3$6 ZHUHFROOHFWHGDWVFUHHQ
LQJ EHIRUHGHYLFHDFWLYDWLRQ PRQWKVDQG0XOWLOHYHOVWDWLVWLFDODQDO\VHV
ZHUHSHUIRUPHGDQGDGMXVWHGIRUSDWLHQWFKDUDFWHULVWLFVFKDQJHVLQEORRGSUHV
VXUHDQGDQWLK\SHUWHQVLYHWKHUDSHXWLFLQGH[GXULQJIROORZXS
Results: 0HDQ SK\VLFDO 6) VFRUH GLG QRW FKDQJH GXULQJ IROORZXS QHLWKHU
LQJURXS ““DQG“DWVFUHHQLQJPRQWKVDQGUHVSHFWLYHO\ QRUJURXS ““DQG“DWVFUHHQLQJPRQWKVDQGUHVSHFWLYHO\ $GGLWLRQDOO\QRFKDQJHZDVREVHUYHGLQWKHPHQWDO6)VFRUHLQERWKJURXSV
JURXS “ “ DQG “ DQG JURXS “ “ DQG “ DW
VFUHHQLQJPRQWKVDQGUHVSHFWLYHO\ 0HGLDQ)3$6ZDVZLWKLQWHUTXDU
WLOHUDQJHLQERWKJURXSVDWPRQWKVDQG
Conclusions: +DYLQJD%$7GHYLFHGLGQRWGHWHULRUDWHWKHTXDOLW\RIOLIHLQSD
WLHQWV ZLWK UHVLVWDQW K\SHUWHQVLRQ7KH UDWH RI GHYLFH DFFHSWDQFH ZDV DOVR ID
YRXUDEOHLQWKLVSDWLHQWJURXS
7A.08
THE COMMON CONTROL OF HYPERTENSION
AND THERAPEUTIC ATTITUDES IN BELGIUM AND
LUXEMBOURG STUDY (COME STAI)
3YDQGH%RUQH1, L. Missault 2, A. Persu , :9DQ0LHJKHP. 1 Hôpital
Erasme, Université Libre de Bruxelles, Brussels, BELGIUM, 2 AZ Sint, Jan
Brugge, Oostende, Brugge, BELGIUM, 3 Cliniques Universitaires Saint-Luc,
Brussels, BELGIUM, 4 Ziekenhuis Oost-Limburg, Genk, BELGIUM
Objective: 'HVSLWHRYHUZKHOPLQJHYLGHQFHWKDWK\SHUWHQVLRQ +7 LVDPDMRU
FDUGLRYDVFXODU ULVN &95 IDFWRU D QRWLFHDEOH SURSRUWLRQ RI SDWLHQWV UHPDLQ
XQDZDUH RI WKLV FRQGLWLRQ DQG QRUPDO EORRG SUHVVXUH %3 OHYHOV DUH VHOGRP
DFKLHYHG$VDUHVXOWK\SHUWHQVLRQUHPDLQVDOHDGLQJFDXVHRIFDUGLRYDVFXODU
GHDWKLQ(XURSHDQGHOVHZKHUHLQWKHZRUOG7KHDLPRIWKH&20(67$,VWXG\
ZDVWRFKDUDFWHULVHK\SHUWHQVLRQFRQWURODPRQJJHQHUDOSUDFWLWLRQHUVLQ%HOJLXP
DQG/X[HPERXUJGXULQJWKH\HDU
Design and method: JHQHUDOSK\VLFLDQVZHUHDVNHGWRHQUROFRQVHFXWLYH
+7SDWLHQWV$OOSK\VLFLDQVXVHGWKHVDPHGH¿QLWLRQVIRUWKHDVVHVVPHQWRIJOREDO
&95
Results: 2I¿FHV\VWROLF%3GLDVWROLF%3DQGKHDUWUDWHZHUHUHVSHFWLYHO\
PP+J PHDQ6' Q PP+J Q DQG ESP Q $JHZDV\HDUVDQGERG\PDVVLQGH[NJPð
RI WKH FRQVXOWDWLRQV GLG QRW UHVXOW LQ FKDQJHV LQ DQWLK\SHUWHQVLYH WKHUDS\ DO
WKRXJKRIWKHVHSDWLHQWVKDGD6%3!PP+JZHUHRQQR
PHGLFDWLRQRQPRQRWKHUDS\DQGRQ!PHGLFDWLRQV Q RIWKHSDWLHQWVZHUHDWKLJK&95UHFHLYHGPRUHIUHTXHQWO\!DQWL+7PHGLFD
WLRQV YVLQWKRVHDWORZHUULVNS&KLð EXWXQGHUZHQWOHVV
WUHDWPHQWLQWHQVL¿FDWLRQ YVLQWKRVHDWORZHUULVNS&KLð %3 ZDV KLJKHU ZKHQ WUHDWPHQW ZDV LQWHQVL¿HG PP+J YV
PP+J3 ,QWKRVHZLWKD6%3!PP+JWKHUDS\
ZDV LQWHQVL¿HG LQ DIWHU \HDUV Q YV LQ EHIRUH \HDUV
Q S&KLð $IWHU\HDUV%3ZDVPP+J
WUHDWPHQW LQWHQVL¿FDWLRQ RFFXUUHG LQ ZKHQ 6%3 ZDV EHWZHHQ DQG
PP+J Q EXWRFFXUHGLQVWHDGLQZKHQ6%3ZDV!PP+J
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LQ DQWLK\SHUWHQVLYH WKHUDS\ FKDQJHV GHVSLWH ZHUH VWLOO K\SHUWHQVLYH DQG UHFHLYHGDQWLK\SHUWHQVLYHPHGLFDWLRQV+LJKHU%3DQG&95ZLWK
PHGLFDWLRQVUHVXOWHGLQWKHUDS\LQWHQVL¿FDWLRQV3DUWRIWKLVWKHUDS\LQHUWLDZDV
H[SODLQHGE\DKLJKHUWKUHVKROGIRU%3FRQWURODIWHU\HDUV
7A.09
EFFECTS OF SINGLE LOW DOSE OF BISOPROLOL
IN PATIENTS WITH ARTERIAL HYPERTENSION AND
CHRONIC OBSTRUCTIVE PULMONARY DISEASE
/5DWRYD1, 2$JDSRYD2, .=\NRY2, %1D]DURY1, <'ROJXVKHYD1,
,&KD]RYD 1. 1 Russian Cardiology Research and Production Complex,
Moscow, RUSSIA, 2 Moscow State Medico-Stomatological University, Moscow,
RUSSIA
Objective: 7KHDLPRIRXUVWXG\LVWRGHWHUPLQHWKHHIIHFWVRIVLQJOHGRVHFDU
GLRVHOHFWLYHEHWDEORFNHUELVRSUROROPJRQIRUFHGH[SLUDWRU\YROXPHLQ
VHFRQG )(9 IRUFHGYLWDOFDSDFLW\ )9& DQGDFXWHEURQFKRGLODWRUUHVSRQVH
WRVDOEXWDPROPFJLQSDWLHQWVZLWKDUWHULDOK\SHUWHQVLRQ $+ DQGFKURQLF
REVWUXFWLYHSXOPRQDU\GLVHDVH &23' Design and method: SDWLHQWV DJHG “ \HDUV ZLWK$+ DQG &23'
ZHUH LQFOXGHG LQ WKH VWXG\ DQG UHFHLYHG VLQJOH GRVH ELVRSURORO PJ7KH
)(9DQG)9&ZHUHDVVHVVHGLQLWLDOO\DIWHUPLQDQGDIWHUXSWR
PLQVDOEXWDPROPFJ6WDWLVWLFDODQDO\VLVZDVSHUIRUPHGXVLQJ:LOFR[RQ
PDWFKHGSDLUVWHVW5HVXOWVDUHSUHVHQWHGDV0HDQ“VWG
Results: ,QLWLDOO\WKH)(9ZDV“)9&ZDV“DQGERWK
GLGQ¶WFKDQJHVLJQL¿FDQWO\,QDQGPLQ)(9ZDV“
“ “ DQG “ UHVSHFWLYHO\ SDWLHQWV GLGQ¶W KDYH
DQ\UHGXFWLRQRI)(9RWKHUSDWLHQWVVKRZHGDGHFOLQHRI)(9LQPLQ
XWHVIRUPOLQPLQXWHVIRUPOLQPLQXWHVIRUPODQGLQ
PLQXWHV IRU PO DFFRUGLQJO\ )RU WKHVH SDWLHQWV WKH GLIIHUHQFH EH
WZHHQLQLWLDO)(9DQGLWVPLQLPDOYDOXHZDVVLJQL¿FDQW į)(9“
S 7KH)9&GLGQRWFKDQJHVLJQL¿FDQWO\$IWHUDGPLQLVWUDWLRQRIVDOEX
WDPROLQFUHDVHRI)(9XSWR“ZDVUHJLVWHUHG7KHEURQFKRGLODWLQJ
HIIHFWRIVDOEXWDPRORQį)(9ZDV S 7KH)9&DOVRLQFUHDVHG
VLJQL¿FDQWO\XSWR“ S Conclusions: 3DWLHQWVZLWK$+DQG&23'GLGQRWVKRZDQ\VLJQL¿FDQWFKDQJH
RI)(9DIWHUDGPLQLVWUDWLRQRIDVLQJOHGRVHRIELVRSUROROPJ+RZHYHU
GHVSLWHWKHDERYHDVLJQL¿FDQWUHGXFWLRQRI)(9ZDVUHYHDOHGLQPRVWSDWLHQWV
DIWHUWKH\WRRNPJRIELVRSURORO7KHEURQFKRGLODWLQJHIIHFWRIVDOEXWDPRO
ZDVQRWDOWHUHG
Abstracts
e94
ORAL SESSION
ORAL SESSION 7B
HEART AND HAEMODYNAMICS
7B.01
LIPOCALIN-2 IS A NOVEL DETERMINANT OF
CARDIAC HYPERTROPHY
)0DUTXHV1, P. Prestes 1, ,5DQD1, E. Porrello 2, 3/HZDQGRZVNL,
/'HOEULGJH, 6%+DUUDS, )-&KDUFKDU1. 1 Faculty of Health, Federation
University Australia, Ballarat, AUSTRALIA, 2 School of Biomedical Sciences,
University of Queensland, Brisbane, AUSTRALIA, 3 School of Medicine,
Deakin University, Geelong, AUSTRALIA, 4 Department of Physiology,
University of Melbourne, Melbourne, AUSTRALIA
Objective: 7KHPROHFXODUSURFHVVHVOHDGLQJWRFDUGLDFK\SHUWURSK\LQGHSHQG
HQW RI EORRG SUHVVXUH DUH VWLOO XQNQRZQ 7KH +\SHUWURSKLF +HDUW 5DW ++5 LVDXQLTXHQRUPRWHQVLYHPRGHORIKXPDQSRO\JHQLFFDUGLDFK\SHUWURSK\ZLWK
UHGXFHGFRPSOHPHQWRIFDUGLRP\RF\WHVIURPELUWKWKDWSUHGLVSRVHVWRFDUGLDF
IDLOXUHDQGSUHPDWXUHGHDWK7KHDLPRIWKHVWXG\ZDVWRLQYHVWLJDWHWKHPROHFX
ODUPHFKDQLVPVWKDWOHDGWRK\SHUWURSK\LQWKLVPRGHO
Design and method: FRQVHFXWLYHSDWLHQWVZLWKFOLQLFDOLQGLFDWLRQWRFRUR
QDU\DQJLRJUDSK\SURVSHFWLYHO\XQGHUZHQWVWDQGDUGXOWUDVRXQGH[DPLQDWLRQIRU
WKHHYDOXDWLRQRI/9PDVVLQGH[ /90LJP UHODWLYHZDOOWKLFNQHVV 5:7 GLVWDODQWHULRUGHVFHQGLQJFRURQDU\DUWHU\ÀRZYHORFLW\ /$'GBYHO FDURWLGXO
WUDVRXQGZLWKUHDOWLPHHFKRWUDFNLQJV\VWHPIRUPHDVXUHPHQWRIFHQWUDOEORRG
SUHVVXUH F6%3 F'%3 FRPPRQ FDURWLG LQWLPD PHGLD WKLFNQHVV F,07 DQG
FDURWLG SXOVH ZDYH YHORFLW\ F3:9 (VDRWH 0\/DE 7KH QRQLQYDVLYH
HYDOXDWLRQV ZHUH SHUIRUPHG EOLQGO\ WR FOLQLFDO LQIRUPDWLRQ EHIRUH FRURQDU\
DQJLRJUDSK\
Resultus: F,07 DQG F3:9 ZHUH KLJKHU LQ SDWLHQWV ZLWK FRQFHQWULF /9+
/90,! JK LQ PHQ DQG ! JK LQ ZRPHQ DQG 5:7! DV
FRPSDUHGWR1 QRUPDO/9PDVVDQGJHRPHWU\ DQG&5 FRQFHQWULFUHPRGHOLQJ
QRUPDO/90LDQG5:7! /$'GBYHOZDVJUHDWHULQSDWLHQWVZLWKFRQFHQ
WULF/9+WKDQLQRWKHUVJURXSV7KHSUHYDOHQFHRIFRURQDU\VWHQRVLV ! ZDV
JUHDWHULQSDWLHQWVZLWKFRQFHQWULF/9+DQG&5DVFRPSDUHGWR13DWLHQWVZLWK
FRQFHQWULFJHRPHWU\ 5:7! VKRZHGKLJKHUYDOXHVRIF,07F3:9DQG
/$'GBYHODQGDJUHDWHUSUHYDOHQFHRIFRURQDU\VWHQRVLV ! WKDQSDWLHQWV
ZLWK5:7
Design and method: 7RGHWHUPLQHGLIIHUHQWLDOO\H[SUHVVHGJHQHVEHWZHHQWKH
++5DQGLWVFRQWUROVWUDLQWKH1RUPDO+HDUW5DW 1+5 ZKROHJHQRPHJHQH
H[SUHVVLRQZDVPHDVXUHGE\$II\PHWUL[5DW*HQH67$UUD\VIURPWKHOHIWYHQ
WULFOHRIQHRQDWDODQLPDOV Q DQGJHQHVIRXQGGLIIHUHQWLDOO\H[SUHVVHGZHUH
YDOLGDWHG E\ T3&5 7R GHWHUPLQH ZKHWKHU PROHFXODU FKDQJHV ZHUH OLQNHG WR
KHDUW VL]H ZH SHUIRUPHG DQ ) FURVVEUHHGLQJ VWXG\ EHWZHHQ ++5 DQG 1+5
Q :HDOVRRYHUH[SUHVVHG/FQLQDFDUGLDFFHOOOLQHLQYLWURWRGHWHUPLQH
/FQIXQFWLRQ
Results: 6WDWLVWLFDODQDO\VLVLGHQWL¿HGGLIIHUHQWLDOO\H[SUHVVHGJHQHVLQWKH
OHIWYHQWULFOHRIWKH++5 )'5DQGIROGFKDQJH! 7KHJHQHIRUOLSRFD
OLQ /FQ ZDVWKHPRVWVLJQL¿FDQWO\GLIIHUHQWLDOO\H[SUHVVHGJHQHZLWKIROG
KLJKHUH[SUHVVLRQLQWKH++5ZKLFKZDVIXUWKHUYDOLGDWHGE\T3&5IURPQHR
QDWDOWRZHHNROGDQLPDOV DOO3 /FQLVORFDWHGLQTXDQWLWDWLYHWUDLW
ORFLSUHYLRXVO\DVVRFLDWHGZLWKFDUGLDFPDVVLQGHSHQGHQWRIEORRGSUHVVXUHLQ
UDWV ,Q WKH FURVVEUHHGLQJ VWXG\ ZH LGHQWL¿HG LW DV D UHFHVVLYH WUDQVPLVVLRQ
+LJKHU/FQH[SUHVVLRQZDVDVVRFLDWHGZLWKVPDOOHUKHDUWVLQQHRQDWDOVIURP
WKH) U 3 DQGZLWKELJJHUKHDUWVLQDGXOWVIURPWKH) U 3 3ODVPD /FQ LQYHVWLJDWHG E\ HQ]\PHOLQNHG LPPXQRVRUEHQW DVVD\V
(/,6$ ZDV KLJKHU LQ ++5 DQLPDOV Q DOO DJHV 3 7KH RYHUH[
SUHVVLRQRI/FQLQFDUGLRP\RF\WHVLQYLWUROHDGWRDGHFUHDVHLQWKHQXPEHURI
FHOOV 3 DQGDGHFUHDVHLQSKRVSKRKLVWRQH 3 LQGLFDWLQJJURZWK
DUUHVW7KHUHZDVDOVRDQLQFUHDVHLQDSRSWRVLVPHDVXUHGE\FDVSDVHDFWLYLW\
DQGÀRZF\WRPHWU\ 3 Conclusions: 7RJHWKHUWKHVH¿QGLQJVVXJJHVWWKDWG\VUHJXODWLRQRI/FQLQWKH
++5LVDQLPSRUWDQWUHJXODWRU\PHFKDQLVPJRYHUQLQJFDUGLRP\RF\WHSUROLIHUD
WLRQOHDGLQJWRWKHGHYHORSPHQWRIFDUGLDFK\SHUWURSK\
7B.02
RELATIONSHIP BETWEEN VASCULAR DAMAGE
AND LEFT VENTRICULAR GEOMETRY IN PATIENTS
UNDERGOING CORONARY ANGIOGRAPHY
06DOYHWWL1, A. Paini 1, M. Cesana 2, A. Moreo , R. Facchetti 2, 3)DJJLDQR1,
6&DUHUM, *0XUHGGX5, 1*DLED]]L, )5LJR, C. Giannattasio ,
M.L. Muiesan 1. 1 Internal Medicine, University of Brescia, Brescia, ITALY,
2
Dipartimento di Scienze della Salute, Bicocca University, Milan, ITALY,
3
Bicocca University, Ospedale Niguarda Ca’ Granda, Dipartimento
Cardiotoracovascolare De Gasperis, Milan, ITALY, 4 Department of
Cardiology, Messina University, Messina, ITALY, 5 Ospedale San Giovanni
Addolorata, Rome, ITALY, 6 University of Parma, Parma, ITALY, 7 Department
of Cardiology, Ospedale dell’Angelo, Mestre-Venezia, ITALY
Objective: 9DVFXODU VWUXFWXUDO LQWLPDPHGLD WKLFNQHVV ,07 DQG IXQFWLRQDO
FDURWLGVWLIIQHVVF3:9 DOWHUDWLRQVDUHUHODWHGWRGLIIHUHQWSDWWHUQRIOHIWYHQ
WULFXODU /9 JHRPHWU\ LQ JHQHUDO SRSXODWLRQV DQG LQ K\SHUWHQVLYHV7KH UHOD
WLRQVKLSEHWZHHQYDVFXODUGDPDJHDQG/9JHRPHWU\KDVQRWEHHQDQDO\]HGSUR
VSHFWLYHO\LQSDWLHQWVXQGHUJRLQJFRURQDU\DQJLRJUDSK\
Conclusions: 2XUUHVXOWVFRQ¿UPWKDWLQSDWLHQWVXQGHUJRLQJFRURQDU\DQJLRJ
UDSK\FRQFHQWULFJHRPHWU\LQDVVRFLDWHGZLWKVWUXFWXUDODQGIXQFWLRQDOFDURWLG
DOWHUDWLRQVZLWKLQFUHDVHGFHQWUDOEORRGSUHVVXUHDQGDQWHULRUGHVFHQGLQJFRUR
QDU\DUWHU\ÀRZYHORFLW\
,QWKLVODUJHJURXSRISDWLHQWVFRQFHQWULFJHRPHWU\LVDVVRFLDWHGZLWKDJUHDWHU
SUHYDOHQFHRIFRURQDU\VVWHQRVLVDVDVVHVVHGE\FRURQDU\DQJLRJUDSK\
7B.03
PROGNOSTIC VALUE OF LEFT VENTRICULAR
DIASTOLIC DYSFUNCTION IN A GENERAL
POPULATION
7.X]QHWVRYD/7KLMV-.QH]/+HUERWV-6WDHVVHQ. KU Leuven, Research
Unit of Hypertension and Cardiovascular Epidemiology, Department of
Cardiovascular Sciences, Leuven, BELGIUM
Objective: 1HZWHFKQLTXHVRI7LVVXH'RSSOHU,PDJLQJ 7', HQDEOHWKHPHDV
XUHPHQW RI P\RFDUGLDO YHORFLWLHV DQG SURYLGH YDOXDEOH LQIRUPDWLRQ DERXW OHIW
YHQWULFXODU /9 GLDVWROLFIXQFWLRQ5HFHQWVWXGLHVH[SORUHGWKHSURJQRVWLFUROH
RI 7',GHULYHG LQGH[HV +RZHYHU PRVW RI WKHVH VWXGLHV FRQVLGHUHG RQO\ WR
WDOPRUWDOLW\DQGGLGQRWSURYLGHLQIRUPDWLRQRQFDUGLRYDVFXODUPRUWDOLW\DQG
PRUELGLW\ 7KHUHIRUH ZH LQYHVWLJDWHG LQ FRQWLQXRXV DQG FDWHJRULFDO DQDO\VHV
ZKHWKHU 'RSSOHU GLDVWROLF LQGH[HV FRQWDLQHG DQ\ SURJQRVWLF LQIRUPDWLRQ RYHU
DQGEH\RQGWUDGLWLRQDOFDUGLRYDVFXODUULVNIDFWRUVLQDJHQHUDOSRSXODWLRQ
Design and method: :HPHDVXUHGHDUO\DQGODWHGLDVWROLFSHDNYHORFLWLHVRI
PLWUDOLQÀRZ (DQG$ E\FRQYHQWLRQDO'RSSOHUDQGWKHPLWUDODQQXODUYHORFL
WLHV H¶DQGD¶ E\7',LQSDUWLFLSDQWV PHDQDJH\HDUVZRPHQ ZLWKLQWKHIUDPHZRUNRIWKH)OHPLVK6WXG\RQ(QYLURQPHQW*HQHVDQG+HDOWK
2XWFRPHV )/(0(1*+2 :HFDOFXODWHGPXOWLYDULDEOHDGMXVWHGKD]DUGUDWLRV
IRUFRQYHQWLRQDODQG7','RSSOHULQGH[HVZKLOHDFFRXQWLQJIRUIDPLO\FOXVWHU
DQGFDUGLRYDVFXODUULVNIDFWRUV
Results: 0HGLDQ IROORZXS ZDV \HDUV WK WR WK SHUFHQWLOH ² :LWKDGMXVWPHQWVDSSOLHGIRUFRYDULDEOHV7',H¶YHORFLW\ZDVDVLJQL¿FDQWSUH
GLFWRURIIDWDODQGQRQIDWDOFDUGLRYDVFXODU Q 3 DQGFDUGLDFHYHQWV
Q 3 (H¶ZDVERUGHUOLQHDVVRFLDWHGZLWKLQFUHDVHGULVNRIFRPELQHG
FDUGLDFHYHQWV 3 +D]DUGUDWLRVRIDOOFDUGLRYDVFXODU 3 DQG
M
O
N
D
A
Y
O
R
A
L
S
e95
Journal of Hypertension Volume 32, e-Supplement 1, 2014
FDUGLDF 3 HYHQWVZHUHVLJQL¿FDQWO\HOHYDWHGLQSDUWLFLSDQWVZLWK
LQFUHDVHG/9¿OOLQJSUHVVXUHFRPSDUHGZLWKVXEMHFWVZLWKQRUPDOGLDVWROLFIXQF
tion.
Conclusions: /RZHDUO\GLDVWROLFPLWUDODQQXOXVYHORFLW\PHDVXUHGE\7',LQ
GHSHQGHQWO\ SUHGLFWHG KLJKHU IDWDO DQG QRQIDWDO FDUGLRYDVFXODU HYHQWV7', H¶
UHSUHVHQWVDVLPSOHHFKRFDUGLRJUDSKLFPHDVXUHZKLFKPLJKWEHXVHGIRUDVVHVV
LQJ FDUGLRYDVFXODU ULVN LQ D JHQHUDO SRSXODWLRQ )XUWKHUPRUH ZH REVHUYHG DQ
LQFUHDVHLQDOOFDUGLRYDVFXODUHYHQWVLQWKHGLDVWROLFG\VIXQFWLRQJURXSFKDUDF
WHUL]HGE\HOHYDWHG/9¿OOLQJSUHVVXUH
7B.04
VASOCONSTRICTOR EFFECT OF MRS2159, A
PURINORECEPTOR P2X1 ANTAGONIST, ON RENAL
MEDULLARY CIRCULATION IS REVERSED IN ANGIIINDUCED HYPERTENSIVE RATS
0.XF]HULV]ND$:DONRZVND/'REURZROVNL. Mossakowski Medical
Research Centre Poish Academy of Sciences, Warsaw, POLAND
Objective: 7KH H[SUHVVLRQ RI SXULQHUJLF 3 UHFHSWRUV 35 LQ WKH NLGQH\ LV
PRGL¿HGE\K\SHUWHQVLRQ+HUHWRIRUHWKHLPSDFWRQUHQDOIXQFWLRQRI3;5
RQHRIWKHWZR35IDPLOLHVORFDWHGLQUHQDOYHVVHOVDQGWXEXOHVZDVVWXGLHG
PRVWO\LQLVRODWHGSUHSDUDWLRQV7KHSUHVHQWZKROHNLGQH\VWXG\H[SORUHGUHQDO
IXQFWLRQ DV DIIHFWHG E\ 056 6LJPD D VHOHFWLYH 3;5 DQWDJRQLVW LQ
QRUPRWHQVLYHUDWVDQGLQUDWVUHQGHUHGK\SHUWHQVLYHE\WZRZHHNV¶LQIXVLRQRI
DQJLRWHQVLQ,, $QJ,, DWQJPLQGHOLYHUHGE\RVPRWLFPLQLSXPSV
Design and method: ,QDFXWHH[SHULPHQWVZLWKDGXOWPDOH6SUDJXH'DZOH\UDWV
DQDHVWKHWL]HGZLWKXUHWKDQJNJLSHIIHFWVRI056RULWVVDOLQHVROYHQW
RQDUWHULDOSUHVVXUHKHDUWUDWHDQGUHQDOIXQFWLRQZHUHPHDVXUHGVLPXOWDQHRXVO\
$IWHUFRQWUROSHULRGHIIHFWVRIWKUHHVXEVHTXHQWGRVHVRI056 PJNJK RURIDVLQJOHLYLQIXVLRQ PJNJK ZHUHGHWHUPLQHGIROORZHGE\
UHFRYHU\SHULRGV7KHZKROHNLGQH\EORRGÀRZ 5%) ZDVPHDVXUHGXVLQJUH
QDODUWHU\7UDQVRQLFSUREH,QWUDUHQDOUHJLRQDOEORRGSHUIXVLRQZDVGHWHUPLQHG
XVLQJODVHU'RSSOHUSUREHVLQVHUWHGLQWRWKHRXWHUDQGLQQHUPHGXOOD 20%)
,0%) 8ULQHÀRZ 9 VRGLXPH[FUHWLRQ 81D9 DQGXULQHRVPRODOLW\ 8RVP ZHUHDOVRPHDVXUHG
Results: 7KH056HIIHFWVZHUHQRWGRVHGHSHQGHQW5%)GHFUHDVHGUHYHUV
LEO\LQQRUPRWHQVLYH “WR“POPLQJS WHQGHGWRLQFUHDVH
LQK\SHUWHQVLYHUDWV6XUSULVLQJO\,0%)GHFUHDVHGUHYHUVLEO\E\“ S LQQRUPRWHQVLYHDQGLQFUHDVHGLUUHYHUVLEO\E\“ S LQK\SHUWHQVLYH
UDWV9DQG81D9ZHUHQRWDIIHFWHGE\WKHGUXJKRZHYHU8RVPLQFUHDVHGE\
PRVPRONJ+2 S ERWKLQQRUPRWHQVLYHDQGK\SHUWHQVLYHJURXS
Conclusions: 7KHVHZKROHNLGQH\VWXGLHVLQGLFDWHWKDWWKHGHYHORSPHQWRI$Q
J,,LQGXFHGK\SHUWHQVLRQFDQUHYHUVHWKHXVXDO3;5PHGLDWHGHIIHFWVRQWKH
UHQDOKDHPRG\QDPLFV7KLVZDVEHVWYLVLEOHLQWKHLQQHUPHGXOODZKHUHEDVHOLQH
3;5DFWLYLW\VHHPHGWRKDYHHQKDQFHGWKHWRQHRIYHVVHOVFRQWUROOLQJPHGXO
ODU\SHUIXVLRQ±LQFRQWUDVWWRWKHUHVSRQVHLQQRUPRWHQVLYHUDWV5HPDUNDEO\
UHGXFHGEORRGSHUIXVLRQRIWKHUHQDOPHGXOODLVRIWHQSRVWXODWHGWRSURPRWHWKH
GHYHORSPHQWRIK\SHUWHQVLRQ3;5PHGLDWHGHIIHFWVRQUHQDOWXEXODUWUDQV
SRUW SURFHVVHV LQYROYHG LQ XULQH FRQFHQWUDFWLRQ ZHUH QRW PRGL¿HG LQ$QJ,,
LQGXFHGK\SHUWHQVLRQ
7B.05
ANGIOTENSINERGIC INNERVATION OF THE HUMAN
RIGHT ATRIUM, ATRIAL ANGIOTENSINS AND
IMPLICATIONS FOR BARORECEPTOR FUNCTION
-%RKOHQGHU1, -1XVVEHUJHU2, +7HYDHDUDL, +,PERGHQ1. 1 Institute of Cell
Biology, University of Bern, Bern, SWITZERLAND, 2 Department of Medicine,
Centre Hospitalier Universitaire Vaudois (CHUV), Lausanne, SWITZERLAND,
3
Department of Cardiovascular Surgery, Inselspital, University of Bern, Bern,
SWITZERLAND
Objective: 7KHKXPDQDWULDDUHGHQVO\LQQHUYDWHGE\DXWRQRPLF¿EUHVDQGWKH
JDQJOLRQDWHG SOH[XV FRQWUROOLQJ FDUGLDF IXQFWLRQ YROXPH KRPHRVWDVLV DQG
DUWHULDO EORRG SUHVVXUH E\ DXWRQRPLF UHÀH[HV$QJLRWHQVLQ $QJ LV D NQRZQ
QHXURSHSWLGHRIWKHV\PSDWKHWLFQHUYRXVV\VWHPDQGPD\PRGXODWHSHULSKHUDO
DQG FHQWUDO QHUYRXV V\VWHP QHXURWUDQVPLVVLRQ YLD SUH DQG SRVWV\QDSWLF$QJ
UHFHSWRUV:HUHFHQWO\GHWHFWHGDQJLRWHQVLQHUJLF¿EHUVZLWKLQWKHKHDUWEXWLQ
WKH KXPDQ DWULXP WKHLU SUHVHQFH DQDWRPLF GLVWLEXWLRQ DQG UHODWLRQVKLS ZLWK
FDWHFKRODPLQHUJLF¿EHUVDUHVWLOOQRWNQRZQ
Design and method: +XPDQULJKWDWULDOWLVVXHVSHFLPHQV Q REWDLQHGGXU
LQJFDUGLDFVXUJHU\ZHUHLPPHUVLRQ¿[HGLQIRUPDOGHK\GHVWDLQHGIRU$QJ
,, PRQRFORQDODQWLERG\% DQGFRVWDLQHGIRUW\URVLQHK\GUR[\ODVH 7+ WR
GHWHFW FDWHFKRODPLQHUJLF ¿EHUV RU V\QDSWRSK\VLQ 6<1 D V\QDSWLF YHVLFXODU
SURWHLQ,PDJHDQDO\VLVZDVE\GLWLDOÀRXUHVFHQWOLJKWDQGODVHUVFDQQLQJPLFUR
VRS\$WULDO$QJ,9FRQFHQWUDWLRQVZHUHGHWHUPLQHGDIWHUWLVVXHH[WUDFWLRQDQG
+3/&VHSDUDWLRQIROORZHGE\UDGLRLPPXQRDVVD\
Results: $WULDODXWRQRPLFQHUYH¿EHUVDQGJDQJOLRQLFFHOOVVWDLQHGHLWKHUIRU7+
RU$QJ,,RUIRUERWK(SLFDUGLDO$QJSRVLWLYH¿EHUVZHUHPDLQO\SUHVHQWLQODUJH
QHUYHV DQG PRVWO\ QRQYDULFRVH RU FRORFDOL]LQJ7+ ,Q WKH P\RFDUGLDO OD\HU
$QJSRVLWLYH¿EHUVZHUHOHVVIUHTXHQWDQGPDLQO\QRQYDULFRVHFRPSDUHGWRWKH
QXPHURXVYDULFRVH7+SRVLWLYH¿EHUV$QJSRVLWLYH¿EHUVZLWKODUJHYDULFRVL
WLHVRFFDVLRQDOO\FRORFDOL]HG7+,QWKHSHULDUWHULDOSOH[XVDGHQVHQHWZRUNRI
YDULFRVHDQGQRQYDULFRVH$QJSRVLWLYHDQGRIYDULFRVH7+SRVLWLYH¿EHUVZDV
SUHVHQW VRPH$QJSRVLWLYH YDULFRVH ¿EHUV DOVR FRORFDOL]HG7+ (QGRFDUGLDO
$QJSRVLWLYH¿EHUVZHUHPDLQO\QRQYDULFRVHDQGSDUDOOHOLQJWKHVXUIDFH6RPH
HQGRFDUGLDODUHDVVKRZHG FOXVWHUVRIKLJKO\YDULFRVHWRUWXRXVRUVSURXWLQJ
$QJSRVLWLYH¿EHUVH[WHQGLQJDPRQJHQGRWKHOLDOFHOOVDQG JURXSLQJVRIWKLQ
UHFWDQJXODU SDOLVDGHOLNH YDULFRVHQHUYHWHUPLQDOV7+FRORFDOL]DWLRQZDVUDUH
6<1DQG7+VWDLQLQJUHVXOWVZHUHFRPSDUDEOH$WULDO$QJ,DQG,,FRQFHQWUD
WLRQVZHUH“DQG“DQG$QJ,,,9FRQFHQWUDWLRQVIPROJ
ZZUHVSHFWLYHO\
Conclusions: $QJLRWHQVLQHUJLF¿EHUVLQQHUYDWHWKHKXPDQULJKWDWULXPDQGDUH
FDWHFKRODPLQHUJLFRUQRQFDWHFKRODPLQHUJLF SUREDEO\DIIHUHQWRUSDUDV\PSD
WKHWLF $QJ,,DVDQHXURSHSWLGHWUDQVPLWWHUPD\PRGXODWHDWULDOEDURUHFHSWRU
IXQFWLRQ DQG UHVHW DXWRQRPLF UHÀH[HV FRQWUROOLQJ FDUGLRYDVFXODU IXQFWLRQ DQG
EORRGSUHVVXUHYLDLWV$QJUHFHSWRUV
7B.06
ESTROGEN REGULATES ANGIOTENSIN II RECEPTOR
EXPRESSION PATTERNS AND PROTECTS THE
HEART FROM ISCHEMIC INJURY IN FEMALE RATS
/=KDQJ1, 4;XH1, ';LDR1, 6<DQJ2. 1 Loma Linda University School
of Medicine, Loma Linda, CA, USA, 2 California State University San
Bernardino, San Bernardino, CA, USA
Objective: 7KH SUHVHQW VWXG\ WHVWV WKH K\SRWKHVLV WKDW HVWURJHQ SOD\V DQ LP
SRUWDQWUROHLQSURWHFWLQJIHPDOHVIURPWKHKHLJKWHQHGFDUGLDFYXOQHUDELOLW\WR
LVFKHPLFLQMXU\DIWHUDQWHQDWDOK\SR[LFH[SRVXUH
Design and method: 7LPHGDWHGSUHJQDQWUDWVZHUHGLYLGHGEHWZHHQQRUPR[LF
DQGK\SR[LF 2IURPGD\WRRIJHVWDWLRQ JURXSV2YDULHFWRP\
29; DQG HVWURJHQ ( UHSODFHPHQW ZHUH SHUIRUPHG LQ ZHHNROG IHPDOH
RIIVSULQJ7KHUHZHUHJURXSVRIDQLPDOVFRQWUROLQWDFWK\SR[LDLQWDFWFRQ
WURO29; K\SR[LD29; FRQWURO29;( DQG K\SR[LD29;( +HDUWV RI
PRQWKROG IHPDOH SURJHQ\ ZHUH VXEMHFWHG WR PLQ LVFKHPLD DQG PLQ
UHSHUIXVLRQ ,5 LQMXU\LQD/DQJHQGRUIISUHSDUDWLRQ
Results: 3UHLVFKHPLFYDOXHVRIOHIWYHQWULFOH /9 IXQFWLRQZHUHWKHVDPHLQDOO
VL[JURXSV,Q29;DQLPDOVWKHUHZHUHQRVLJQL¿FDQWGLIIHUHQFHVLQSRVWLVFK
HPLFUHFRYHU\RI/9IXQFWLRQFDUGLDFHQ]\PHUHOHDVHDQGLQIDUFWVL]HEHWZHHQ
FRQWURODQGIHWDOK\SR[LFJURXSV,QERWKFRQWURODQGK\SR[LFJURXSV29;VLJ
QL¿FDQWO\GHFUHDVHGSRVWLVFKHPLFUHFRYHU\RI/9IXQFWLRQDQGLQFUHDVHGFDU
GLDFHQ]\PHUHOHDVHDQGLQIDUFWVL]H(UHSODFHPHQWVLJQL¿FDQWO\LPSURYHGWKH
SRVWLVFKHPLFUHFRYHU\29;VLJQL¿FDQWO\GHFUHDVHGERWKP51$DQGSURWHLQ
DEXQGDQFHRI3.&İEXWQRW3.&įDQGGHFUHDVHGSKRVSKR3.&İ$GGLWLRQDOO\
29;UHVXOWHGLQDGHFUHDVHLQ$75EXWDQLQFUHDVHLQ$7529;FDXVHGD
GHFUHDVHLQERWKHVWURJHQUHFHSWRUĮDQGȕ29;KDGQRHIIHFWRQJOXFRFRUWL
FRLGUHFHSWRUV *5V EXWGHFUHDVHGWKHDI¿QLW\RI*5ELQGLQJWRJOXFRFRUWLFRLG
UHVSRQVH HOHPHQWV *5(V DW WKH SURPRWHU RI$7D5 DQG$75 UHVXOWLQJ LQ
GHFUHDVHG *5V ELQGLQJ WR *5(V 7KH 29;LQGXFHG FKDQJHV ZHUH UHFRYHUHG
E\(UHSODFHPHQW
Conclusions: 7KH UHVXOWV LQGLFDWH WKDW WKH UHVLVWDQFH RI IHPDOH RIIVSULQJ WR
IHWDOK\SR[LDLQGXFHGFDUGLDFYXOQHUDELOLW\WRLVFKHPLFLQMXU\REVHUYHGSUH
YLRXVO\ LV QRW PHGLDWHG E\ WKH VH[ VWHURLG KRUPRQH GHYHORSHG SRVWQDWDOO\
DQGVXJJHVWDQRYHOPHFKDQLVPLQWKHHDUO\GHYHORSPHQWSURWHFWLQJIHPDOHV
DJDLQVWIHWDOSURJUDPPLQJRIFDUGLDFG\VIXQFWLRQLQGXFHGE\K\SR[LD1RQH
WKHOHVV HVWURJHQ SOD\V DQ LPSRUWDQW UROH LQ SURWHFWLQJ IHPDOH KHDUWV DJDLQVW
LVFKHPLF LQMXU\ YLD HVWURJHQ UHFHSWRUV LQ UHJXODWLQJ HQGRJHQRXV SURWHFWLYH
mechanisms in the heart.
7B.07
DETERMINANTS OF EARLY CHANGES IN LEFT
VENTRICULAR SYSTOLIC FUNCTION IN PATIENTS
WITH ESSENTIAL HYPERTENSION AND NORMAL
EJECTION FRACTION
'(YDQJHORX1, .1DND1, 5.DODLW]LGLV2, //DNNDV1, A. Bechlioulis 1,
,*NLUGLV1, *1DNDV1, )=DU]RXODV2, $.RWVLD1, 2%DODID2, *7]HOW]HV1,
.3DSSDV1, &.DWVRXUDV 1, ('RXQRXVL2, L. Michalis 1, .6LDPRSRXORV2.
1
University of Ioannina, Department of Cardiology, Ioannina, GREECE,
2
University of Ioannina, Department of Nephrology, Ioannina, GREECE
e96
Journal of Hypertension Volume 32, e-Supplement 1, 2014
Objective: +\SHUWHQVLRQLVDVVRFLDWHGZLWKHDUO\UHGXFWLRQLQP\RFDUGLDOV\V
WROLF IXQFWLRQ DV DVVHVVHG E\ QRYHO ' VSHFNOH WUDFNLQJ '67 HFKRFDUGLRJ
UDSK\ HYHQ LQ WKH SUHVHQFH RI QRUPDO HMHFWLRQ IUDFWLRQ () 7KH DLP RI WKH
VWXG\ZDVWRLQYHVWLJDWHWKHDVVRFLDWLRQRI'67(LQGLFHVRIORQJLWXGLQDODQG
URWDWLRQDOP\RFDUGLDOIXQFWLRQZLWKULVNIDFWRUVDUWHULDOVWLIIQHVVDQGFRURQDU\
PLFURYDVFXODUIXQFWLRQLQK\SHUWHQVLYHSDWLHQWVZLWKQRUPDO()
Design and method: )RUW\RQH PDOH SDWLHQWV PHDQ DJH “ \HDUV ZLWK
QRUPDO()DQGZLWKRXWOHIWYHQWULFXODU /9 K\SHUWURSK\ZHUHHQUROOHG&RQ
YHQWLRQDOWLVVXH'RSSOHU 7' DQG'67HFKRFDUGLRJUDSK\ZDVXVHGWRDVVHVV
FDUGLDFIXQFWLRQ&RURQDU\ÀRZUHVHUYH &)5 LQWKHOHIWDQWHULRUGHVFHQGLQJDU
WHU\XVLQJGLS\ULGDPROHDQGDUWHULDOVWLIIQHVVE\PHDVXUHPHQWRIFDURWLGIHPRUDO
SXOVHZDYHYHORFLW\DQGFHQWUDODXJPHQWDWLRQLQGH[ZHUHDVVHVVHG
Results: *OREDOFLUFXPIHUHQWLDOVWUDLQZDVQRWDVVRFLDWHGZLWKDQ\RIWKHVWXGLHGSD
UDPHWHUV*OREDOORQJLWXGLQDOVWUDLQ */6 ZDVDVVRFLDWHGZLWKFRQYHQWLRQDOHFKR
FDUGLRJUDSKLFLQGLFHVRIV\VWROLFIXQFWLRQYHORFLW\WLPHLQWHJUDORI/9RXWÀRZWUDFW
U S DQG0$36( U S DVZHOODVV\VWROLF U S DQGGLDVWROLF U S EORRGSUHVVXUH %3 KHDUWUDWH U S JORPHUXODU¿OWUDWLRQUDWH U S DQG/9PDVVLQGH[ U S 6\VWROLF %3 % S ZDV WKH VROH LQGHSHQGHQW SUHGLFWRU RI
*/6LQPXOWLYDULDWHDQDO\VLV 5ð $SLFDOWZLVWZDVDVVRFLDWHGZLWK/9()
U S YHORFLW\WLPHLQWHJUDORI/9RXWÀRZWUDFW U S DQG/9PDVVLQGH[ U S ,QGLFHVRIDUWHULDOVWLIIQHVVDQG&)5GLGQRW
FRUUHODWHZLWKJOREDOFLUFXPIHUHQWLDOVWUDLQRU*/6RUDSLFDOWZLVW
Conclusions: ,QFRQFOXVLRQLQKHDOWK\K\SHUWHQVLYHSDWLHQWVZLWKQRUPDO()
ORQJLWXGLQDODQGURWDWLRQDOP\RFDUGLDOIXQFWLRQZHUHLQYHUVHO\DVVRFLDWHGZLWK
V\VWROLF%3DQG/9PDVVUHVSHFWLYHO\EXWQRWZLWKLQGLFHVRIDUWHULDOVWLIIQHVVRU
FRURQDU\PLFURYDVFXODUIXQFWLRQ)XUWKHUUHVHDUFKLVQHHGHGWRDVVHVVWKHSRWHQ
WLDOSDWKRSK\VLRORJLFDODQGSURJQRVWLFUROHRIWKHVHHFKRFDUGLRJUDSKLFLQGLFHV
LQSDWLHQWVZLWKK\SHUWHQVLRQ
7B.08
ECHOCARDIOGRAPHY ESTIMATION OF RIGHT
ATRIAL PRESSURE: COMPARISON AND CLINICAL
VALIDATION AMONG SEVERAL MODELS
&0DJQLQR1, 32PHGp2, :*URVVR0DUUD2, $5DYHUD1, /6DELD1,
'3UHVXWWL2, C. Bucca , C. Moretti 2, F. Gaita 2, )9HJOLR1, A. Milan 1. 1 Città
della Salute e della Scienza, Department of Medical Science, Turin, ITALY, 2
Città della Salute e della Scienza, Department of Cardiology, Turin, ITALY, 3
Città della Salute e della Scienza, Department of Clinical Physiopathology,
Turin, ITALY
Objective: 7KHHVWLPDWLRQRIULJKWDWULDOSUHVVXUH 5$3 KDVDJUHDWLPSDFWRQ
WKHQRQLQYDVLYHHYDOXDWLRQRISXOPRQDU\KHPRG\QDPLFV6HYHUDOPRGHOVKDYH
EHHQGHYHORSHGWRHVWLPDWH5$3EDVHGRQWKHLQIHULRUYHQDFDYD ,9& GLDPHWHU
DQGFROODSVLELOLW\7KHDLPRIRXUVWXG\ZDVWRFRPSDUHYDULRXVPRGHOVIRUWKH
HFKRFDUGLRJUDSKLF HVWLPDWLRQ RI 5$3 LQ D QRQVHOHFWHG SRSXODWLRQ WU\LQJ WR
¿QGWKHRQHZLWKWKHEHVWFOLQLFDOUHOHYDQFHLQWHUPVRIUHOLDELOLW\DQGDFFXUDF\
Design and method: (FKRFDUGLRJUDSK\ ZDV SHUIRUPHG RQ SDWLHQWV ZLWKLQ
PLQXWHVIURPFDUGLDFFDWKHWHUL]DWLRQ,9&ZDVPHDVXUHGDWHQGH[SLUDWLRQDQG
HQGLQVSLUDWLRQERWKLQORQJDQGVKRUWD[LVYLHZ5$3ZDVHVWLPDWHGXVLQJGLIIHU
HQWNQRZQPRGHOVEDVHGRQ,9&HYDOXDWLRQ .LUFKHU3HSL/DQJ
%UHQQDQ5XGVNL )RUWKHPRGHOSURSRVHGE\WKHODVWJXLGHOLQHVERWKWKH
VLPSOHRQH 5XGVNL DQGWKHRQHLQFRUSRUDWLQJVLJQVRIULJKWYHQWULFXODUGLDVWROLF
GLVIXQFWLRQ 5XGVNL ZHUHHYDOXDWHG$OO5$3PRGHOVZHUHFRPSDUHGWRLQYDVLYH
5$3E\FRUUHODWLRQUHJUHVVLRQ%ODQG$OWPDQDQDO\VLVDQGDFFXUDF\DQDO\VLV GH
¿QHGDVQXPEHURIHVWLPDWLRQZLWKLQPP+JGLIIHUHQFHWRWKHLQYDVLYHPHDVXUH Results: SDWLHQWVZHUHVXLWDEOHIRUDQDO\VLV DJH>@L5$3
>@UDQJHPP+J ,9&PHDVXUHVPDGHLQORQJD[LVYLHZ
E\00RGHVKRZHGWKHVWURQJHVWDVVRFLDWLRQZLWKLQYDVLYH5$3 UVTXDUHG
S DQGZHUHFKRVHQIRUWKH5$3HVWLPDWLRQ$OOWKHPRGHOVVKRZHGD
VLJQL¿FDQWFRUUHODWLRQWRL5$3EXWZLWKSRRUYDOXHRIUVTXDUHG PD[LPXPU
VTXDUHGYDOXHIRUWKH%UHQQDQPRGHO 7KH%ODQG$OWPDQDQDO\VLVVKRZHG
DZLGHGLVWULEXWLRQRIWKHHUURUIRUDOOPRGHOVDQGWKHJHQHUDODFFXUDF\ZDVSRRU
PD[LPXPYDOXHIRUWKH/DQJPRGHO VHH7DEOH Conclusions: 2XUVWXG\GHPRQVWUDWHGWKDWWKH5$3HVWLPDWLRQEDVHGRQ,9&
HYDOXDWLRQLVKLJKO\LQDFFXUDWH1RPRGHOVKRZHGDFOHDUVXSHULRULW\RYHUWKH
RWKHUVLQHVWLPDWLQJ5$31HZDSSURDFKHVKDYHWREHIRXQGLQRUGHUWRLPSURYH
5$3HVWLPDWLRQDQGFRQVHTXHQWO\DOVRSXOPRQDU\SUHVVXUHHVWLPDWLRQV
7B.09
HIGHER PULSE PRESSURE AS PREDICTOR OF
LOWER INTRAHOSPITAL MORTALITY IN NYHA II/III
PATIENTS
9,ULF&XSLF1, *'DYLGRYLF1, 60LODQRY2, 03DYORYLF2, 03HWURYLF2.
Clinic of Cardiology, Clinical Center Kragujevac, Kragujevac, SERBIA,
2
Faculty of Medical Sciences, University in Kragujevac, Kragujevac, SERBIA
1
Objective: 3XOVHSUHVVXUHDVDSXOVDWLOHFRPSRQHQWRIEORRGSUHVVXUHLVEORRG
SUHVVXUHYDULDWLRQDIIHFWHGPRVWO\E\OHIWYHQWULFXODUHMHFWLRQIUDFWLRQ /9() DQGKHDUWUDWH/9()LVWKHSHUFHQWDJHRIEORRGSXPSHGRXWRIWKHOHIWYHQWULFOH
ZKLFK FDQ EH QRUPDO RU QHDU QRUPDO LQ DSSUR[LPDWHO\ RI SDWLHQWV ZLWK
KHDUWIDLOXUH5HODWLRQVKLSRISXOVHSUHVVXUHWRKHDUWIDLOXUHGLIIHUVDFURVV1HZ
<RUN +HDUW$VVRFLDWLRQ 1<+$ FODVVHV ZLWK LQYHUVH FRUUHODWLRQ EHWZHHQ 33
OHYHODQGKHDUWIDLOXUHGHJUHH$LPZDVWRDVVHVVWKHOHYHOVRISXOVHSUHVVXUHDQG
/9()DQGUHODWLYHULVNIRULQWUDKRVSLWDOPRUWDOLW\LQSDWLHQWVZLWKKHDUWIDLOXUH
Design and method: 7KLVSURVSHFWLYHUHVHDUFKLQFOXGHGSDWLHQWVZLWKKHDUW
IDLOXUHRILVFKHPLFHWRORJ\1<+$FODVV,,DQG,,,DGPLWWHGWR&OLQLFRI&DUGLRO
RJ\8QLYHUVLW\&OLQLFDO&HQWHU.UDJXMHYDFIURP-XQH-XQH%ORRG
SUHVVXUHZDVPHDVXUHGRQDGPLVVLRQDIWHUPLQXWHVRIUHVWLQDVXSLQHSRVLWLRQ
DQGSXOVHSUHVVXUHZDVFDOFXODWHGDVGLIIHUHQFHEHWZHHQV\VWROLFDQGGLDVWROLF
SUHVVXUH(FKRFDUGLRJUDSK\ZDVXVHGWRDVVHVVSHUFHQWRIHMHFWLRQIUDFWLRQ$OO
GDWDZHUHVWRUHGLQGDWDEDVHDQGVWDWLVWLFDOO\DQDO\]HGXVLQJ6366IRU:LQ
GRZV
Results: 6XEMHFWV KDG PHDQ DJH RI “ \HDUV 3XOVH SUHVVXUH ZDV
!PP+J LQ RI SDWLHQWV [ WHVWS ZLWK D PHDQ YDOXH RI
“PP+J7KHUHZDVVLPLODUGLVWULEXWLRQRISDWLHQWVZLWK1<+$,,,,,
1<+$,,DQG1<+$,,, ZLWKPRUHSDWLHQWVZLWKKLJKHUSXOVH
SUHVVXUHLQ1<+$,,ZLWKQRVLJQL¿FDQWGLIIHUHQFH/9()ZDVQRUPDOLQ
DQGQHDUQRUPDOLQRISDWLHQWVZLWKDPHDQYDOXH“3XOVHSUHV
VXUH KDG SRVLWLYH OLQHDU FRUUHODWLRQ ZLWK /9() 3HDUVRQ¶V FRH¿FLHQWV ,QWUDKRVSLWDOPRUWDOLW\ZDVORZ SDWLHQWVGLHGDQGDFFRUGLQJWRKLJKHU
33UHODWLYHULVNIRULQWUDKRVSLWDOPRUWDOLW\ZDV
Conclusions: +LJKHU SXOVH SUHVVXUH ZDV H[SHFWHG FRQVLGHULQJ WKDW PHDQ DJH
ZDV!\HDUV7KHUHZDVVLJQL¿FDQWFRQQHFWLRQEHWZHHQKLJKHU33DQGORZHU
LQWUDKRVSLWDOPRUWDOLW\LQ1<+$,,,,,SDWLHQWVLQGLFDWLQJWKDW33FRXOGEHFRQ
VLGHUHGDVSRVLWLYHSURJQRVWLFIDFWRULQPRGHUDWHDGYDQFHGKHDUWIDLOXUHGXHWR
SUHVHUYHGVWURNHYROXPHZKLFKFDQWDNHSUHFHGHQFHRYHUVWLIIQHVV
7B.10
EFFECTS OF ACUTE, SYMPATHETIC-INDEPENDENT
INCREASES IN HEART RATE ON ARTERIAL
STIFFNESS, CENTRAL HAEMODYNAMICS AND
CARDIAC FUNCTION
,7DQ1, M. Butlin 1, +.LDW1,2, E. Barin , $$YROLR1. 1 Macquarie University,
Sydney, AUSTRALIA, 2 Cardiac Health Institute, Sydney, AUSTRALIA,
3
Macquarie Heart, Sydney, AUSTRALIA
Objective: $UWHULDOVWLIIQHVVLQFUHDVHVZLWKDJHDQGEORRGSUHVVXUHEXWLWVUHOD
WLRQVKLSZLWKKHDUWUDWH +5 KDVQRWEHHQZHOOHVWDEOLVKHG:KLOVWVWXGLHVKDYH
VKRZQLQFUHDVHGDUWHULDOVWLIIQHVVZLWKLQFUHDVHG+5QRWDOOVWXGLHVVKRZHGD
SUHVVXUHLQGHSHQGHQW DVVRFLDWLRQ )XUWKHUPRUH WKLV UHODWLRQVKLS KDV QRW EHHQ
VWXGLHGLQFRQMXQFWLRQZLWKFRUUHVSRQGLQJFKDQJHVLQFHQWUDOKDHPRG\QDPLFV
DQGFDUGLDFIXQFWLRQ7KLVVWXG\DLPVWRLQYHVWLJDWHWKHHIIHFWVRIDFXWHV\P
SDWKHWLFLQGHSHQGHQWFKDQJHVLQ+5RQDUWHULDOVWLIIQHVVFHQWUDOSUHVVXUHVDQG
FDUGLDFSDUDPHWHUVLQFOXGLQJHMHFWLRQGXUDWLRQ (' DQGFDUGLDFRXWSXW &2 Design and method: 6WXGLHVZHUHFRQGXFWHGLQVXEMHFWV IHPDOHVDJHG
“\HDUVPHDQ“6' ZLWKLQVLWXFDUGLDFSDFHPDNHUVRULPSODQWHGFDUGLRYHUW
HUGH¿EULOODWRUV$UWHULDOVWLIIQHVVZDVDVVHVVHGE\FDURWLGIHPRUDOSXOVHZDYH
YHORFLW\ 3:9 PHDVXUHG XVLQJ D WKLJK FXII DQG FDURWLG WRQRPHWU\ 6SK\J
PR&RUŠ;&(/ DWUDQGRPO\SDFHG+5VRI±EHDWVSHUPLQXWH ESP %UDFKLDO FXIIEDVHG SXOVH ZDYH DQDO\VLV 6SK\JPR&RUŠ ;&(/ ZDV XVHG WR
PHDVXUHFHQWUDOV\VWROLF F6%3 GLDVWROLF F'%3 DQGPHDQSUHVVXUHV 0%3 DVZHOODVDXJPHQWDWLRQLQGH[ $,[ DQG('7RWDOSHULSKHUDOUHVLVWDQFH 735 DQG VWURNH YROXPH 69 ZHUH GHULYHG IURP PHDVXUHG ¿QJHU DUWHULDO SUHVVXUH
ZDYHIRUP )LQRPHWHUŠ DQG&2ZDVFDOFXODWHGDVWKHSURGXFWRI69DQG+5
Results: $OO PHDVXUHG SDUDPHWHUV FKDQJHG VLJQL¿FDQWO\ ZLWK +5 7DEOH
PHDQ“6(0 $,[735 (' DQG 69 GHFUHDVHG ZLWK LQFUHDVH LQ +5 ZKHUHDV
3:9F'%30%3DQG&2LQFUHDVHG+RZHYHUWKHVLJQL¿FDQFHIRU3:9ZDV
e97
Journal of Hypertension Volume 32, e-Supplement 1, 2014
ORVWRQFHLWZDVFRUUHFWHGIRUFKDQJHVLQ0%3F6%3VWD\HGUHODWLYHO\FRQVWDQW
ZLWK+5H[FHSWDWESP
Conclusions: $FXWHV\PSDWKHWLFLQGHSHQGHQWLQFUHDVHVLQ+5UDLVHV&2DQG
F'%3ZKLFKLQWXUQLQFUHDVHV0%3GHVSLWHGHFUHDVHVLQ69DQG735DQGUH
VXOWVLQLQFUHDVHGDUWHULDOVWLIIQHVV7KLVPD\LQSDUWH[SODLQWKH¿QGLQJVLQVWXG
LHVZKHUHSUHVVXUHFKDQJHVZHUHREVHUYHGLQFRQMXQFWLRQZLWKFKDQJHVLQDUWH
ULDOVWLIIQHVVZLWK+5LQSDFHGSDWLHQWV6LQFHWKHVH¿QGLQJVSHUWDLQHVVHQWLDOO\
WRDQHOGHUO\PDOHFRKRUWRIVXEMHFWVIXUWKHUVWXGLHVZLOODVVHVVWKHHIIHFWVRI
DJHDQGJHQGHURQDVVRFLDWLRQVEHWZHHQ+5DQGDUWHULDOVWLIIQHVV
7B.11
COMPUTATIONAL MODELLING OF THE AORTIC
PULSE WAVEFORM IN THE CLINICAL SETTING
WRMXVWWKH¿UVWJHQHUDWLRQRIELIXUFDWLRQVGLGZHVHHDPRUHVXEVWDQWLDOFKDQJHLQ
WKHSUHVVXUHZDYHIRUP\HWWKHHUURUVRIGLDVWROLFDQGV\VWROLFSUHVVXUHUHODWLYH
WRWKHFRPSOHWHDUWHU\PRGHOZHUHVWLOO
Conclusions: $UHGXFHGPRGHORISXOVHZDYHSURSDJDWLRQLQWKHDRUWDFDQEH
GHULYHGIURPUHODWLYHO\IHZPHDVXUHPHQWV
7B.12
THE ASSOCIATION OF DIASTOLIC DYSFUNCTION
WITH LEFT VENTRICULAR MASS INDEX ACCORDING
TO GLUCOMETABOLIC STATUS: A CROSSSECTIONAL STUDY
03DUHHN1, 01LHOVHQ 1, 0/HyVGyWWLU2, 5.UXJHU, 6*UHYH1, M. Blicher 1,
76HKHVWHGW, .:DFKWHOO5, 301LOVVRQ, 0+2OVHQ. 1 Cardiovascular
and Metabolic Preventive Clinic, Department of Endocrinology, CIMA,
Odense, DENMARK, 2 Department of Cardiology, Skåne University Hospital,
Malmö, SWEDEN, 3 Hypertension in Africa Research Team (HART), NorthWest University, Potchefstroom, SOUTH AFRICA, 4 Department of Cardiology,
Herlev University Hospital, Herlev, DENMARK, 5 Department of Internal
Medicine, Glostrup University Hospital, Glostrup, DENMARK, 6 Department
of Clinical Sciences, Lund University, Skåne University Hospital, Malmö,
SWEDEN
S. Epstein 1, +)RN2, 3&KRZLHQF]\N2, -$ODVWUXH\1. 1 Department
of Biomedical Engineering, King’s College London, London, UNITED
KINGDOM, 2 Department of Clinical Pharmacology, St.Thomas Hospital,
London, UNITED KINGDOM
Objective: 7RH[DPLQHZKHWKHUZRUVHQLQJRIJOXFRPHWDEROLFVWDWXVLVDVVRFL
DWHGZLWKDQLQFUHDVHGSUHYDOHQFHRIOHIWYHQWULFXODUGLDVWROLFG\VIXQFWLRQLQGH
SHQGHQWO\RIKLJKHUOHIWYHQWULFXODUPDVVLQGH[ /90, LQPLGGOHDJHGRUROGHU
DSSDUHQWO\KHDOWK\VXEMHFWV
Objective: :LWKLQ WKH FDUGLRYDVFXODU PRGHOOLQJ FRPPXQLW\ WKHUH LV D GULYH
WRZDUGV EXLOGLQJ LQFUHDVLQJO\ HODERUDWH PRGHOV RI WKH FDUGLRYDVFXODU V\VWHP
9DULRXVFRPELQDWLRQVRIWKUHHGLPHQVLRQDO ' WZRGLPHQVLRQDO ' RQH
GLPHQVLRQDO ' DQGOXPSHGSDUDPHWHU ' PRGHOVKDYHEHHQSURSRVHGWR
PRGHOEORRGÀRZLQYHVVHOV+RZHYHUDVZHLQFUHDVHWKHVSDWLDOGLPHQVLRQVRI
RXUPRGHOVZHUHTXLUHODUJHUDPRXQWVRIFOLQLFDOGDWDWRGHWHUPLQHDOOWKHPRGHO
SDUDPHWHUVIRUSDWLHQWVSHFL¿FVLPXODWLRQVLQWKHFOLQLFDOVHWWLQJ
Design and method: :H H[DPLQHG FURVVVHFWLRQDO DVVRFLDWLRQV EHWZHHQ WKH
SUHVHQFHRIJUDGHRUGLDVWROLFG\VIXQFWLRQ/90,DQGIDVWLQJSODVPDJOX
FRVH )3* FDWHJRUL]HG DV QRUPDO IDVWLQJ JOXFRVH 1)* )3* PPRO/ LPSDLUHGIDVWLQJJOXFRVH ,)*)3*PPRO/ DQGGLDEHWHVPHOOLWXV '0
)3*! PPRO/ LQPHQDQGZRPHQDJHG\HDUVZLWKRXWRYHUW
FDUGLRYDVFXODUGLVHDVHZKRUHFHLYHGQRFDUGLRYDVFXODUDQWLGLDEHWLFRUOLSLGORZ
HULQJGUXJV&RUUHODWLRQVZHUHDVVHVVHGXVLQJ3HDUVRQSURGXFWPRPHQWFRUUHOD
WLRQDQGWKHDVVRFLDWLRQVZHUHIXUWKHUHYDOXDWHGXVLQJELQDU\ORJLVWLFUHJUHVVLRQ
DQDO\VLV
Design and method: 8VLQJDYHUL¿HGYHVVHOQRQOLQHDU'PRGHORISXOVH
ZDYH SURSDJDWLRQ LQ HODVWLF YHVVHOV ZH V\VWHPDWLFDOO\ UHGXFHG WKH QXPEHU
RI JHQHUDWLRQV RI ELIXUFDWLRQV ZKLOH SUHVHUYLQJ WKH WRWDO FRPSOLDQFH DQG QHW
SHULSKHUDO UHVLVWDQFH RI WKH V\VWHP WR EHWWHU XQGHUVWDQG WKH FRQWULEXWLRQV RI
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D ' PRGHO YHVVHO WR WKDW RI D WZRHOHPHQW ' PRGHO WKDW DFFRXQWV IRU WKH
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Results: :KHQWHVWHGRQDVLPSOHELIXUFDWLRQPRGHOWKHFKDQJHLQSXOVHSUHV
VXUHIURPWKDWRIDWKUHHVHJPHQWELIXUFDWLRQPRGHOWRWKDWRIDOXPSHGVLQJOH
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WKH GLPHQVLRQDOLW\ RI WKH ' YHVVHO WKDW ZH KDYH D VPDOO XQGHUHVWLPDWLRQ LQ
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WLRQVZDVLPSO\LQJWKDWRXUPHWKRGRORJ\LVDGHTXDWHDWFDSWXULQJWKH
resistance.
:KHQDSSOLHGWRWKHDUWHU\PRGHOZHREVHUYHGWKDWDUHGXFWLRQLQWKHJHQ
HUDWLRQVRIELIXUFDWLRQVIURPWRUHVXOWHGLQDURRWPHDQVTXDUHGLIIHUHQFHRI
SUHVVXUHZDYHIRUPVKDSHRI2QO\ZKHQWKHDUWHU\PRGHOZDVUHGXFHG
Results: 'LDVWROLF G\VIXQFWLRQ U S DV ZHOO DV /90, U S VLJQL¿FDQWO\ FRUUHODWHG ZLWK )3* FDWHJRU\7KH VWUHQJWK RI WKH FRU
UHODWLRQEHWZHHQGLDVWROLFG\VIXQFWLRQDQG/90,LQFUHDVHGZLWKZRUVHQLQJJOX
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DQG/90,$IWHUDGMXVWLQJIRUDJHJHQGHUVPRNLQJVWDWXVV\VWROLFEORRGSUHV
VXUH KHDUW UDWH WRWDO FKROHVWHURO KLJKGHQVLW\ OLSRSURWHLQ FKROHVWHURO ERG\
PDVVLQGH[DQGZDLVWFLUFXPIHUHQFHERWK)3*FDWHJRU\ H[S EHWD FRQ¿GHQFHLQWHUYDO &, S DQG/90, H[S EHWD &, S LQGHSHQGHQWO\SUHGLFWHGGLDVWROLFG\VIXQFWLRQ
Conclusions: :RUVHQLQJ )3* FDWHJRU\ DQG LQFUHDVLQJ /90, SUHGLFWHG WKH
SUHVHQFHRIJUDGHRUGLDVWROLFG\VIXQFWLRQLQGHSHQGHQWO\RIHDFKRWKHU7KH
FRUUHODWLRQ RI /90, ZLWK GLDVWROLF G\VIXQFWLRQ LQFUHDVHG LQVLJQL¿FDQWO\ ZLWK
ZRUVHQLQJ)3*FDWHJRU\7KHUHIRUHWKHLQFUHDVHGSUHYDOHQFHRIGLDVWROLFG\V
IXQFWLRQZLWKZRUVHQLQJJOXFRPHWDEROLFVWDWXVZDVRQO\SDUWLDOO\H[SODLQHGE\
LQFUHDVHG/90,
Abstracts
e98
ORAL SESSION
ORAL SESSION 7C
CARDIOVASCULAR RISK FACTORS
7C.01
PROGNOSTIC IMPORTANCE OF VASCULAR AGE
ESTIMATED FROM PULSE WAVE VELOCITY
M. Blicher 1, 6*UHYH1, 5.UXJHU2, 03DUHHN1, 76HKHVWHGW, -9LVKUDP,
7-RHUJHQVHQ, 0+2OVHQ1. 1 Odense University Hospital, Department of
Endocrinology, Odense, DENMARK, 2 North-West University, Hypertension of
Africa Research Team, Potchefstroom, SOUTH AFRICA, 3 Herlev University
Hospital, Department of Cardiology, Copenhagen, DENMARK, 4 Glostrup
University Hospital, Research Centre for Prevention and Health, Copenhagen,
DENMARK
Objective: 9DVFXODU DJH HVWLPDWHG IURP FDURWLGIHPRUDO SXOVH ZDYH YHORFLW\
FI3:9 XVLQJWKHFORVHDVVRFLDWLRQEHWZHHQFI3:9DJHDQGPHDQEORRGSUHV
VXUH 0%3 FDQLGHQWLI\VXEMHFWVGHYHORSLQJHDUO\YDVFXODUDJLQJ (9$ DVVRFL
DWHGZLWKDGYHUVHSURJQRVLV
Design and method: VXEMHFWV RI ZKLFK KDG NQRZQ FDUGLRYDVFXODU
GLVHDVH &9' DJHGDQG\HDUVZHUHH[DPLQHGLQ,Q
WKH FRPSRVLWH HQGSRLQW &(3 RI FDUGLRYDVFXODU GHDWK QRQIDWDO P\RFDUGLDO
LQIDUFWLRQ QRQIDWDO VWURNH DQG KRVSLWDOL]DWLRQIRU LVFKHPLF KHDUW GLVHDVH ZDV
UHFRUGHG %DVHG RQ WKH HTXDWLRQ GHVFULELQJ WKH UHODWLRQVKLS EHWZHHQ FI3:9
DJHDQG0%3GHULYHGIURPWKHODUJH(XURSHDQGDWDVHWIURPWKH$UWHULDO6WLII
QHVV&ROODERUDWLRQSUHGLFWHGFI3:9ZDVFDOFXODWHGDQGYDVFXODUDJHHVWLPDWHG
6&25(ZDVXVHGWRDVVHVULVNRIFDUGLRYDVFXODUGHDWK
Results: ,QPXOWLSOH&R[UHJUHVVLRQDQDO\VHVHVWLPDWHGYDVFXODUDJHSUHGLFWHG
&(3LQGHSHQGHQWO\RIDJHDQGJHQGHULQSDWLHQWVZLWKNQRZQ&9' +5 3 EXWQRWVLJQL¿FDQWO\LQKHDOWK\VXEMHFWV +5 3 DQGQRW
LQGHSHQGHQWO\ RI FI3:9 9DVFXODU DJH WHQGHG WR SUHGLFW &(3 LQGHSHQGHQWO\
RI NQRZQ &9' JHQGHU DQG VPRNLQJ LQ VXEMHFWV DJHG \HDUV +5 3 DQG \HDUV +5 3 EXW QRW \HDUV +5 3 QRU\HDUV +5 3 FI3:9SUHGLFWHG&(3LQGHSHQGHQW
O\RINQRZQ&9'JHQGHUDQGVPRNLQJLQVXEMHFWVDJHG\HDUV +5 3 \HDUV +5 3 DQGLQVLJQL¿FDQWO\LQVXEMHFWVDJHG
\HDUV +5 3 EXWQRW\HDUV +5 3 %RWKYDVFX
ODUDJHDQGFI3:9SUHGLFWHG&(3LQVXEMHFWVZLWKKLJKRUYHU\KLJK6&25(
ULVN +5 DQG +5 3 ,Q VXEMHFWV ZLWK ORZ RU PRGHUDWH
6&25( ULVN FI3:9 +5 3 EXW QRW YDVFXODU DJH +5 3 SUHGLFWHG&(3
Conclusions: 9DVFXODU DJH HVWLPDWHG IURP FI3:9 SUHGLFWHG &(3 LQ SDWLHQWV
ZLWK NQRZQ &9' ROG VXEMHFWV RU VXEMHFWV ZLWK KLJK 6&25( ULVN +RZHYHU
3:9E\LWVHOISUHGLFWHGRXWFRPHEHWWHUWKDQYDVFXODUDJH
7C.02
MAGNESIUM IN 24-HOUR URINE IS INVERSELY
RELATED WITH CARDIOVASCULAR RISKS IN MIDDLE
AGED SUBJECTS IN 50 POPULATIONS IN THE
WORLD
<<DPRUL, 06DJDUD, 60L]XVKLPD, L. Liu , .,NHGD, <1DUD.
Institute for World Health Development, Mukogawa Womens University,
Nishinomiya, JAPAN, 2 Laboratory of Preventive Nutritional Medicine,
Research Institute for Production Development, Kyoto, JAPAN, 3 International
(Former WHO-Collaborating) Center for Research on Primary Prevention
of Cardiovascular Diseases, Kyoto, JAPAN, 4 Department of Epidemiology
and Public Health, Yokohama City University Graduate School of Medicine,
Yokohama, JAPAN, 5 Department of Epidemiology and Biostatistics, Drexel
University School of Public Health, Philadelphia, PA, USA, 6 School of
Pharmacy and Pharmaceutical Sciences, Mukogawa Womens University,
Nishinomiya, JAPAN
1
Objective: 6HUXPSODVPDDQGGLHWDU\PDJQHVLXPKDVEHHQUHSRUWHGWREHLQ
YHUVHO\DVVRFLDWHGZLWKFDUGLRYDVFXODUGLVHDVHULVNIDFWRUV7KHDLPRIWKLVVWXG\
ZDVWRH[DPLQHWKHDVVRFLDWLRQVEHWZHHQKRXUXULQDU\PDJQHVLXPFUHDWLQLQH
UDWLR 0J&UH DQGFDUGLRYDVFXODUGLVHDVHULVNIDFWRUVVXFKDVERG\PDVVLQGH[
%0, EORRGSUHVVXUH %3 VHUXPWRWDOFKROHVWHURO 7& DQGSUHYDOHQFHRIREH
VLW\K\SHUWHQVLRQDQGK\SHUFKROHVWHUROHPLD
Design and method: :HFRQGXFWHGDFURVVVHFWLRQDODQDO\VLVDPRQJSDU
WLFLSDQWV PHQDQGZRPHQ DJHGWR ZLWKDQDYHUDJHDJHDW
\HDUVROG IURPSRSXODWLRQVDPSOHVRIFRXQWULHVLQWKH:RUOG+HDOWK2U
JDQL]DWLRQ :+2 FRRUGLQDWHG&DUGLRYDVFXODU'LVHDVHVDQG$OLPHQWDU\&RP
SDULVRQ &$5',$& 6WXG\ Results: ,Q OLQHDU UHJUHVVLRQ DQDO\VHV 0J&UH ZDV LQYHUVHO\ DVVRFLDWHG ZLWK
%0,V\VWROLF%3GLDVWROLF%3DQGVHUXP7& SIRUDOOOLQHDUWUHQGV 7KH SUHYDOHQFH RI REHVLW\ K\SHUWHQVLRQ DQG K\SHUFKROHVWHUROHPLD DPRQJ WKH
VXEMHFWVZLWKLQWKHORZHVWTXLQWLOHRI0J&UHZDVDQGWLPHVKLJKHU
UHVSHFWLYHO\ S IRU DOO OLQHDU WUHQGV WKDQ LQ WKH VXEMHFWV ZLWKLQ WKH
KLJKHVWTXLQWLOHRI0J&UH7KHVHDVVRFLDWLRQVZHUHQRWDSSUHFLDEO\DOWHUHGE\
IXUWKHUDGMXVWPHQWIRURWKHUSRWHQWLDOFRQIRXQGLQJYDULDEOHVLQFOXGLQJWUDGLWLRQ
DOULVNIDFWRUVRWKHUXULQDU\PDUNHUVDQGFRKRUWHIIHFWV7KHDVVRFLDWLRQEHWZHHQ
K\SHUWHQVLRQDQG0J&UHZDVQRWGRVHGHSHQGHQWDQGRQO\WKHVXEMHFWVZLWKLQ
WKH ORZHVW TXLQWLOH RI 0J&UH KDG VLJQL¿FDQWO\ KLJKHU ULVN WKDQ WKH VXEMHFWV
ZLWKLQWKHKLJKHVWTXLQWLOH
Conclusions: +LJKHUKRXUXULQDU\0J&UHZDVDVVRFLDWHGZLWKORZHUFDU
GLRYDVFXODUGLVHDVHULVNIDFWRUVLQFOXGLQJ%0,V\VWROLFDQGGLDVWROLF%37&
REHVLW\K\SHUWHQVLRQDQGK\SHUFKROHVWHUROHPLD
7C.03
MORBIDITY AND MORTALITY RISK AMONG
SUBJECTS WITH SCREENING-DETECTED SEVERE
HYPERTENSION IN THE MALMÖ PREVENTIVE
PROJECT
&:HVWHUGDKO1, %=|OOHU1, E. Arslan 2, 6(UGLQH2, 301LOVVRQ1. 1 Lund
University, Lund, SWEDEN, 2 Istanbul University, Istanbul, TURKEY
Objective: 6FUHHQLQJRIK\SHUWHQVLRQ +7 KDVEHHQDGYRFDWHGIRUHDUO\GHWHF
WLRQDQGWUHDWPHQW6HYHUHK\SHUWHQVLRQ 6+JUDGH+7 LVDVWURQJSUHGLFWRU
IRUFDUGLRYDVFXODUGLVHDVH7KLVVWXG\DLPHGWRHYDOXDWHULVNIDFWRUVIRUGHYHORS
LQJ6+EXWDOVRWKHSURVSHFWLYHPRUELGLW\DQGPRUWDOLW\ULVNDVVRFLDWHGZLWK6+
LQDSRSXODWLRQEDVHGVFUHHQLQJDQGLQWHUYHQWLRQSURJUDPPH
Design and method: ,Q DOO VXEMHFWV IURP D SRSXODWLRQEDVHG FRKRUW
XQGHUZHQWDEDVHOLQHH[DPLQDWLRQLQDQGZHUHUHH[DPLQHGLQ
LQ0DOP|6ZHGHQ7RWDOO\ VXEMHFWVZLWK6+ZHUHLGHQWL¿HGDW
UHH[DPLQDWLRQDQGSUHGLFWLYHULVNIDFWRUVIURPEDVHOLQHFDOFXODWHG7RWDODQG
FDXVHVSHFL¿F PRUELGLW\ DQG PRUWDOLW\ ZHUH IROORZHG LQ QDWLRQDO UHJLVWHUV LQ
DOO6+VXEMHFWVDVZHOODVLQDJHDQGVH[PDWFKHGQRUPRWHQVLYHFRQWUROV&R[
DQDO\VHVIRUKD]DUGUDWLRV +5 ZHUHXVHG
Results: 0DOHVXEMHFWVGHYHORSLQJ6+GLIIHUHGIURPPDWFKHGFRQWUROVLQEDVH
OLQHYDULDEOHVDVVRFLDWHGZLWKWKHPHWDEROLFV\QGURPHDVZHOODVSDWHUQDOKLV
WRU\ RI K\SHUWHQVLRQ S )HPDOHV ZLWK ODWHU 6+ ZHUH FKDUDFWHUL]HG E\
HOHYDWHG %0, DQG D SRVLWLYH PDWHUQDO KLVWRU\ IRU +7 DW EDVHOLQH7KH ULVN RI
PRUWDOLW\ FRURQDU\ HYHQWV VWURNH DQG GLDEHWHV GXULQJ IROORZXS ZDV KLJKHU
DPRQJ6+VXEMHFWVFRPSDUHGWRFRQWUROV)RUFRURQDU\HYHQWVWKHULVNUHPDLQHG
HOHYDWHGDGMXVWHGIRURWKHUULVNIDFWRUV+5 FRQ¿GHQFHLQWHUYDO
S Conclusions: )DPLO\KLVWRU\DQGYDULDEOHVDVVRFLDWHGZLWKPHWDEROLFV\QGURPH
DUHSUHGLFWRUVIRU6+DIWHUORQJWHUPIROORZXS
6+ LV DVVRFLDWHG ZLWK LQFUHDVHG PRUWDOLW\ FDUGLRYDVFXODU PRUELGLW\ DQG LQFL
GHQWGLDEHWHVLQVSLWHRIWUHDWPHQW7KLVFDOOVIRULPSURYHGULVNIDFWRUFRQWURO
LQVXEMHFWVZLWK6+
7C.04
RECLASSIFICATION IMPROVEMENT AND
DISCRIMINATION BY TESTOSTERONE IN
HYPERTENSIVE MALES
1,RDNHLPLGLV&9ODFKRSRXORV$$JJHOLVP. Pietri, '7HUHQWHV3ULQW]LRV
0$EGHOUDVRXO,*RXUJRXOL,$QGURXWVRVC. 6WHIDQDGLV. 1st Department of
Cardiology, Athens, GREECE
Objective: $QGURJHQGH¿FLHQF\FRQIHUVDQLQGHSHQGHQWULVNIRUFDUGLRYDVFXODU
HYHQWVDQGWRWDOPRUWDOLW\+\SHUWHQVLRQKDVDOVREHHQDVVRFLDWHGZLWKLQFUHDVHG
M
O
N
D
A
Y
O
R
A
L
S
e99
Journal of Hypertension Volume 32, e-Supplement 1, 2014
SUHYDOHQFHRIORZWHVWRVWHURQH7KHSXUSRVHRIWKLVVWXG\ZDVWRGHWHUPLQHQHW
UHFODVVL¿FDWLRQLPSURYHPHQW 15, DQGLPSURYHGULVNSUHGLFWLRQEDVHGRQWR
WDOWHVWRVWHURQH 77 LQFRPSDULVRQZLWKWUDGLWLRQDOULVNIDFWRUVLQPLGGOHDJHG
K\SHUWHQVLYHPHQ
LQWRWKHYHQWURPHGLDOK\SRWKDODPXV/HSWLQDQWDJRQLVWLQMHFWLRQLQWRYHQWUR
PHGLDOK\SRWKDODPXVGHFUHDVHGEORRGSUHVVXUH DYHUDJH3 EXWQR
FKDQJHVZHUHREVHUYHGZKHQJLYHQWRGRUVRPHGLDOK\SRWKDODPXVLQKLJKIDW
GLHWUDEELWV1HXURSHSWLGH<LQMHFWLRQKDGQRHIIHFWRQEORRGSUHVVXUHRUUHQDO
V\PSDWKHWLFQHUYHDFWLYLW\LQHLWKHUQXFOHL
Conclusions: (OHYDWHGEORRGSUHVVXUHDQGV\PSDWKHWLFQHUYHDFWLYLW\LQKLJK
IDW GLHW UDEELWV PD\ EH GXH WR DQ LQFUHDVHG VHQVLWLYLW\ RI WKH OHSWLQ VLJQDO
OLQJSDWKZD\ZKLFKLQYROYHVWKHGRUVRPHGLDODQGYHQWURPHGLDOK\SRWKDODPLF
SURMHFWLRQRI$OSKDPHODQRF\WHVWLPXODWLQJKRUPRQHDFWLYDWHGVHFRQGRUGHU
neurons.
7C.06
A GOOD LEFT VENTRICULAR DIASTOLIC
PERFORMANCE IS PREDICTIVE OF BETTER
OUTCOME IN YOUNG SUBJECTS IN THE EARLY
STAGE OF HYPERTENSION
29UL]1, 39LVHQWLQ2, )6DODGLQL2, C. Fania 2, S. Martina 1, L. Mos 1,
$0D]]HU2, )'RULJDWWL2, $%RUWOROD]]L2, P. Palatini 2. 1 San Antonio
Hospital, Department of Cardiology and Emergency Medicine, San Daniele del
Friuli, ITALY, 2 University of Padua, Department of Internal Medicine, Padua,
ITALY
Design and method: 0DMRUDGYHUVHFDUGLRYDVFXODUHYHQWV 0$&( LQUHODWLRQ
WR77ZHUHDQDO\]HGLQSDWLHQWV PHDQDJH\HDUV 7KHUHFODVVL¿FDWLRQRI
0$&(ULVNDVVRFLDWHGZLWK77
ZDVDVVHVVHGXVLQJDPHWKRGWKDWTXDQWL¿HV15,7KHGLVFULPLQDWRU\FDSDELOLW\
RI77ZDVH[DPLQHGXVLQJ&VWDWLVWLFV
Results: 'XULQJ D PHDQ IROORZXS RI PRQWKV SDUWLFLSDQWV H[SHUL
HQFHGD0$&(&RPSDUHGWRSDWLHQWVZKRGLGQRWH[SHULHQFH0$&(K\SHUWHQ
VLYHVXEMHFWVZKRGHYHORSHG0$&(KDGORZHU77FRQFHQWUDWLRQ 3 DQGD
KLJKHUSUHYDOHQFHRIK\SRJRQDGLVP 3 7KHRYHUDOOQHWUHFODVVL¿FDWLRQ
LQGH[ 15, ZDV ] 3 7KH&VWDWLVWLFIRUWKHPXOWLYDULDWH
PRGHOLQFOXGLQJ)56IDFWRUVZDV$GGLWLRQRI77WRWKLVPRGHORIIHUHGD
VWDWLVWLFDOO\VLJQL¿FDQWLPSURYHPHQWLQWKHUHVXOWLQJ&VWDWLVWLFWR 3
IRUFRPSDULVRQEHWZHHQWKHDUHDXQGHUWKHFXUYH LQGLFDWLQJWKHDELOLW\RI77
IRU0$&(GLVFULPLQDWLRQEH\RQGWKHFODVVLFDOULVNIDFWRUVLQRXUSRSXODWLRQ
Conclusions: 7HVWRVWHURQH LPSURYHV ULVN SUHGLFWLRQ ZKHQ DGGHG WR VWDQGDUG
ULVNSUHGLFWLRQPRGHOVDQGPD\UHSUHVHQWDYDOXDEOHELRPDUNHURISUHGLFWLRQRI
0$&(ULVNLQPLGGOHDJHGK\SHUWHQVLYHSDWLHQWV
7C.05
OBESITY RELATED HYPERTENSION: ALTERED
DOWNSTREAM REGULATION OF LEPTIN ON
HAEMODYNAMIC AND RENAL SYMPATHETIC NERVE
ACTIVITY IN HIGH FAT FED RABBITS
./LP%%DU]HO6%XUNH*$+HDG.
Baker IDI Heart and Diabetes Institute, Melbourne, AUSTRALIA
Objective: 2XUIRFXVKDVEHHQRQWKHPHFKDQLVPXQGHUO\LQJWKHLQFUHDVHLQ
EORRGSUHVVXUHDQGLQSDUWLFXODUWKHUROHRIWKHV\PSDWKHWLFQHUYRXVV\VWHPLQ
WKHGHYHORSPHQWRIWKHK\SHUWHQVLYHVWDWH/HSWLQLVDQDGLSRNLQHWKDWSOD\V
DQLPSRUWDQWUROHLQUHJXODWLQJHQHUJ\LQWDNHDQGHQHUJ\H[SHQGLWXUHLQFOXG
LQJDSSHWLWHDQGPHWDEROLVPDQGDFWVDVDNH\SHULSKHUDOKRUPRQHLQGLVWLQFW
QHXURQVLQWKHK\SRWKDODPXV,QWKHSUHVHQWVWXG\RXUDLPZDVWRGHWHUPLQH
ZKHWKHU WKHUH DUH DOWHUHG GRZQVWUHDP VLJQDOOLQJ SDWKZD\V RI OHSWLQ $OSKD
PHODQRF\WHVWLPXODWLQJKRUPRQHDQG1HXURSHSWLGH< LQWKHVSHFL¿FUHJLRQV
RIFHQWUDOQHUYRXVV\VWHPLQUHVSRQVHWRDKLJKIDWGLHWLQFRQVFLRXVUDEELWV
Design and method: 1HZ=HDODQG:KLWH5DEELWVZHUHIHGZLWKDQRUPDORUD
KLJKIDWGLHWIRUZHHNV$ELODWHUDOJXLGHFDQQXODLQWRWKHGRUVRPHGLDO
RUYHQWURPHGLDOK\SRWKDODPXVDQGDUHQDOV\PSDWKHWLFQHUYHDFWLYLW\UHFRUG
LQJ HOHFWURGH ZDV LPSODQWHG$IWHU ZHHNV RQ WKH GLHW$OSKDPHODQRF\WH
VWLPXODWLQJKRUPRQH QPRO 1HXURSHSWLGH < QPRO OHSWLQ
DQWDJRQLVW —J RUYHKLFOHZHUHLQMHFWHG
Results: 5DEELWV H[KLELWHG KLJKHU EORRG SUHVVXUH KHDUW UDWH DQG UHQDO V\P
SDWKHWLF QHUYH DFWLYLW\ ZKHQ IHG D KLJK IDW GLHW FRPSDUHG WR FRQWUROV Q $OSKDPHODQRF\WHVWLPXODWLQJ KRUPRQH LQMHFWLRQ LQWR WKH GRUVRPHGLDO
K\SRWKDODPXV LQFUHDVHG EORRG SUHVVXUH DYHUDJH RI 3 DQG UHQDO
V\PSDWKHWLFQHUYHDFWLYLW\ DYHUDJHRI3 LQKLJKIDWGLHWUDEELWV
%\FRQWUDVWQRFKDQJHVZHUHREVHUYHGLQEORRGSUHVVXUHRUUHQDOV\PSDWKHWLF
QHUYH DFWLYLW\ IROORZLQJ DOSKDPHODQRF\WHVWLPXODWLQJ KRUPRQH LQMHFWLRQV
Objective: (FKRFDUGLRJUDSKLFGDWDDUHLPSRUWDQWSUHGLFWRUVRIRXWFRPHLQK\
SHUWHQVLRQ+RZHYHULWLVQRWFOHDUZKLFKHFKRFDUGLRJUDSKLFSDUDPHWHUVKDYH
EHWWHUSURJQRVWLFFDSDFLW\FKLHÀ\LQ\RXQJVXEMHFWVLQWKHHDUO\VWDJHRIK\SHU
WHQVLRQ,QWKHSUHVHQWVWXG\ZHDVVHVVHGWKHSUHGLFWLYHYDOXHRIVWUXFWXUDODQG
IXQFWLRQDOHFKRFDUGLRJUDSKLFSDUDPHWHUVIRUWKHGHYHORSPHQWRIK\SHUWHQVLRQ
LQDFRKRUWRI\RXQJWRPLGGOHDJHVXEMHFWVIURPWKH+$59(67VWXG\
Design and method: 3DUWLFLSDQWV ZHUH DGXOWV PHQ DJH “
\HDUV VFUHHQHG IRU VWDJH K\SHUWHQVLRQ 3DWLHQWV ZHUH VHHQ HYHU\ VL[
PRQWKVWRGHWHUPLQHZKLFKVXEMHFWVGHYHORSHGK\SHUWHQVLRQQHHGLQJWKHUD
S\DFFRUGLQJWRFXUUHQWJXLGHOLQHV +7 (FKRFDUGLRJUDSK\DQGDPEXODWRU\
EORRG SUHVVXUH %3 PRQLWRULQJ ZHUH SHUIRUPHG DW HQWU\ /HIW YHQWULFXODU
/9 PDVVLQGH[UHODWLYHZDOOWKLFNQHVV/9VWUHVV/9HMHFWLRQIUDFWLRQDQG
WKH($UDWLRDVDPHDVXUHRI/9GLDVWROLFIXQFWLRQZHUHFDOFXODWHG7KHSUH
GLFWLYHYDOXHRIHFKRFDUGLRJUDSKLFGDWDZDVDVVHVVHGLQPXOWLYDULDEOH&R[
DQDO\VHV DGMXVWLQJ IRU DJH JHQGHU ERG\ PDVV LQGH[ KRXU V\VWROLF RU
GLDVWROLF%3DQGOLIHVW\OHIDFWRUV
Results: 'XULQJ D PHGLDQ IROORZXS RI \HDUV RI WKH VXEMHFWV
GHYHORSHG+7,QDPXOWLYDULDEOH&R[DQDO\VLVKV\VWROLF%3 S K GLDVWROLF %3 S FRIIHH FRQVXPSWLRQ S DQG WKH ($
UDWLR LQYHUVHDVVRFLDWLRQS ZHUHLQGHSHQGHQWSUHGLFWRUVRIRXWFRPH
1RQH RI WKH RWKHU HFKRFDUGLRJUDSKLF SDUDPHWHUV ZHUH DVVRFLDWHG ZLWK WKH
ULVN RI +7 ,Q WKH VXEMHFWV GLYLGHG LQWR TXLQWLOHV RI ($ UDWLR DQ LQFUHDVH
LQWKHUDWHRI+7ZDVREVHUYHGRQJRLQJIURPWKHWRS WRWKHERWWRP
S IRU WUHQG ($ TXLQWLOH ZLWK D WHQGHQF\ WR DQ LQYHUWHG /
VKDSHGUHODWLRQVKLS+DYLQJDQ($UDWLR! ORZHUOLPLWRIWKHWRSTXLQ
WLOH VKRZHGDSURWHFWLYHHIIHFWRQWKHULVNRI+7FRPSDUHGWRWKHVXEMHFWV
RIWKHERWWRPTXLQWLOH KD]DUGUDWLR &, ±S Conclusions: 7KHVH GDWD VKRZ WKDW D JRRG /9 GLDVWROLF SHUIRUPDQFH LV D
KDUELQJHURIEHWWHURXWFRPHLQ\RXQJVXEMHFWVVFUHHQHGIRUVWDJHK\SHUWHQ
VLRQZKHUHDVVWUXFWXUDOHFKRFDUGLRJUDSKLFGDWDRU/9SXPSIXQFWLRQDUHQRW
SUHGLFWLYHRIRXWFRPHLQWKLVVHWWLQJ
7C.07
INCREASED AORTIC WAVE REFLECTION AND
SMALLER PULSE PRESSURE AMPLIFICATION IN
SMOKERS AND PASSIVE SMOKERS CONFIRMED
BY URINARY COTININE LEVELS: THE NAGAHAMA
STUDY
<7DEDUD1, <7DNDKDVKL2, .6HWRK1, S. Muro , 7.DZDJXFKL 1, C. Terao 1,
6.RVXJL, $6HNLQH5, 5<DPDGD1, M. Mishima , 71DND\DPD2,
)0DVXGD1. 1 Center for Genomic Medicine, Kyoto University Graduate
School of Medicine, Kyoto, JAPAN, 2 Department of Health Informatics,
Kyoto University School of Public Health, Kyoto, JAPAN, 3 Department
of Respiratory Medicine, Kyoto University Graduate School of Medicine,
Kyoto, JAPAN, 4 Department of Medical Ethics and Medical Genetics, Kyoto
University School of Public Health, Kyoto, JAPAN, 5 EBM Research Center,
Kyoto University Graduate School of Medicine, Kyoto, JAPAN
Objective: &HQWUDO EORRG SUHVVXUH F6%3 LV VXJJHVWHG WR EH D EHWWHU SUH
GLFWRURIFDUGLRYDVFXODUULVNWKDQEUDFKLDO%3$OWKRXJKEUDFKLDO%3OHYHOV
DPRQJVPRNHUVKDYHEHHQUHSRUWHGWREHWKHVDPHRUVRPHZKDWORZHUWKDQ
WKRVHLQQRQVPRNHUVLWLVVXJJHVWHGWKDWVPRNLQJPLJKWKDYHDVXEVWDQWLDO
impact on cSBP.
e100
Journal of Hypertension Volume 32, e-Supplement 1, 2014
Design and method: :H FRQGXFWHG D FURVVVHFWLRQDO VWXG\ WR FODULI\ WKH
DVVRFLDWLRQRIVPRNLQJKDELWZLWKDUWHULDOWRQHDQGF6%3LQDJHQHUDOSRSXOD
WLRQRISDUWLFLSDQWVXVLQJXULQDU\FRWLQLQHOHYHOVDVDQREMHFWLYHPDUN
HURIVPRNLQJLQWHQVLW\$EVROXWHSUHVVXUHRIWKHODWHV\VWROLFSHDN 6%3 ZDV REWDLQHG E\ FDOLEUDWLQJ WKH UDGLDO ZDYHIRUP ZLWK EUDFKLDO V\VWROLF %3
E6%3 DQGFRQVLGHUHGWREHWKHF6%3
Results: &RQIRXQGLQJ IDFWRUDGMXVWHG PHDQ SXOVH SUHVVXUH DPSOL¿FDWLRQ
33D E6%3F6%3 ZDV VLJQL¿FDQWO\ VPDOOHU LQ KDELWXDO VPRNHUV FXU
UHQW“SDVW“QHYHU“PP+JS )XUWKHU
DPRQJ VPRNHUV 33D ZDV OLQHDUO\ GHFUHDVHG ZLWK LQFUHDVLQJ XULQDU\ FRWL
QLQHTXDUWLOH 4“4“4“4“
PP+JS 0XOWLSOHOLQHDUUHJUHVVLRQDQDO\VLVLGHQWL¿HGERWKVPRN
LQJ KDELW S DQG XULQDU\ FRWLQLQH OHYHOV S DV LQGHSHQGHQW
GHWHUPLQDQWVRI33D8ULQDU\FRWLQLQHZDVDOVRGHWHFWHGLQDVPDOOIUDFWLRQ
RI QHYHU VPRNHUV 7KHVH SDVVLYH VPRNHUV VKRZHG D VPDOOHU 33D
SDVVLYHVPRNHU“QHYHUVPRNHU“PP+JS EXWQRW
E6%3 ““PP+JS SHUVRQ\HDUV LQ WKH VPRNHUQRWKDYLQJ 5+7 JURXS FDVHV SHU
SHUVRQ\HDUV LQ WKH QRQVPRNHUKDYLQJ 5+7 JURXS DQG FDVHV
SHUSHUVRQ\HDUVLQWKHVPRNHUKDYLQJ5+7JURXS8QDGMXVWHGDQDO\
VLVVKRZHGWKDWQRQVPRNHUVKDYLQJ5+7KDGFRPSDUDEOHULVNWRVPRNHUV
QRWKDYLQJ 5+7 +5 &, YV +5 &, S IRU
ERWK ZKLOH WKH VPRNHUKDYLQJ 5+7 JURXS H[KLELWHG WKH ZRUVH SURJQRVLV
+5&,S $IWHUDGMXVWLQJIRUHVWDEOLVKHGULVNIDFWRUVWKH
VLJQL¿FDQW ULVN RI WKH QRQVPRNHUVKDYLQJ 5+7 JURXS ZDV PDLQWDLQHG \HW
DWWHQXDWHGZKLOHWKHVPRNHUQRWKDYLQJ5+7JURXSH[KLELWHGQRZWKHZRUVH
SURJQRVLV
Conclusions: 6PRNLQJDQG5+7H[KLELWDVLPLODUO\VLJQL¿FDQWFDUGLRYDVFX
ODUULVNZKLOHDIWHUFRQWUROOLQJIRUHVWDEOLVKHGULVNIDFWRUVWKHVPRNHUVWDWXV
UHPDLQVDVWKHPRVWSRWHQWSUHGLFWRUDPRQJWKHWZR&RQFXUUHQWULVNIDFWRUV
VWUHQJWKHQ WKH FDUGLRYDVFXODU ULVN RI 5+7 WR D JUHDWHU H[WHQW FRPSDUHG WR
WKDWRIVPRNLQJ
7C.09
DO DIETARY SUGARS RAISE BLOOD PRESSURE
AND BLOOD LIPIDS?
/7H0RUHQJD1, $+RZDWVRQ1,2, 5-RQHV1,2, -0DQQ. 1 Department of
Human Nutrition, University of Otago, Dunedin, NEW ZEALAND, 2 Riddet
Institute, University of Otago, Dunedin, NEW ZEALAND, 3 Edgar National
Centre for Diabetes and Obesity Research, University of Otago, Dunedin,
NEW ZEALAND, 4 Department of Medicine, University of Otago, Dunedin,
NEW ZEALAND
Objective: 7KHH[WHQWWRZKLFKVXJDUVLQÀXHQFHKHDOWKLVFXUUHQWO\RQHRI
WKH WRSLFDO LVVXHV LQ SXEOLF KHDOWK QXWULWLRQ 'LHWDU\ VXJDUV KDYH EHHQ LP
SOLFDWHGDVDFDXVHRIREHVLW\VHYHUDOFKURQLFGLVHDVHVDQGDUDQJHRIFDU
GLRPHWDEROLF ULVN IDFWRUV EXW WKHUH LV QR FRQYLQFLQJ HYLGHQFH RI D FDXVDO
UHODWLRQVKLSRWKHUWKDQEHWZHHQVXJDUVDQGERG\ZHLJKW7KHUHIRUHWKHRE
MHFWLYHRIWKLVUHVHDUFKZDVWRTXDQWLI\WKHHIIHFWVRIGLHWDU\VXJDUVRQEORRG
SUHVVXUHDQGOLSLGV
Conclusions: 1RWRQO\KDELWXDOVPRNLQJEXWDOVRSDVVLYHVPRNLQJKDGKDUPIXO
HIIHFWVRQ$,[DQGFHQWUDO%32XUUHVXOWVVWURQJO\HPSKDVL]HWKHLPSRUWDQFHRI
DYRLGLQJSDVVLYHVPRNLQJWRWKHSUHYHQWLRQRIFDUGLRYDVFXODUULVNVRIZKLFKWKH
VXEMHFWLVOLNHO\XQDZDUH
7C.08
COMPARISON OF CARDIOVASCULAR RISK OF
RESISTANT HYPERTENSION AGAINST THAT OF
SMOKING: A 3.6 YEAR FOLLOW-UP STUDY
$.DVLDNRJLDV&7VLRX¿V$.RUGDOLV.'LPLWULDGLV')OHVVDV
$0D]DUDNL..LQWLV/1LNRORSRXORX(.RXWUD$$ERXVKDPDOD
'7RXVRXOLV&6WHIDQDGLV. First Cardiology Clinic, University of Athens,
Hippokration Hospital, Athens, GREECE
Objective: 5HVLVWDQWK\SHUWHQVLRQ 5+7 KDVJDLQHGJUHDWLQWHUHVWLQWKHUHFHQW
\HDUVGXHWRLWVVLJQL¿FDQWSUHYDOHQFHDQGQHHGIRUFDUHIXOGLDJQRVWLFDQGWKHUD
SHXWLFDSSURDFK7KHSURJQRVWLFVLJQL¿FDQFHRI5+7DJDLQVWRWKHUHVWDEOLVKHG
ULVNIDFWRUVVXFKDVVPRNLQJKDVQRWEHHQLQYHVWLJDWHG
Design and method: :HSURVSHFWLYHO\IROORZHGWUHDWHGK\SHUWHQVLYH
SDWLHQWV ZLWKRXW D KLVWRU\ RI FDUGLRYDVFXODU GLVHDVH IRU D PHDQ SHULRG RI
“ \HDUV$W WKH EDVHOLQH YLVLW D WKRURXJK FOLQLFDO DQG ODERUDWRU\ H[
DPLQDWLRQZDVSHUIRUPHG&XUUHQWVPRNLQJZDVUHFRUGHGDVVPRNLQJRIDW
OHDVW RQH FLJDUHWWH GDLO\ DQG 5+7 DV RI¿FHEDVHG XQFRQWUROOHG K\SHUWHQ
VLRQ XQGHU DW OHDVW GUXJV LQFOXGLQJ D GLXUHWLF RU FRQWUROOHG K\SHUWHQVLRQ
XQGHURUPRUHGUXJV%DVHGRQWKHVPRNLQJKDELWVDQG5+7VWDWXVIRXU
JURXSVZHUHLGHQWL¿HGQRQVPRNHUVQRWKDYLQJ5+7 Q RIWKH
WRWDO SRSXODWLRQ VPRNHUVQRWKDYLQJ 5+7 Q QRQVPRNHUV
KDYLQJ5+7 Q DQGVPRNHUVKDYLQJ5+7 Q (QGSRLQW
RILQWHUHVWZDVFDUGLRYDVFXODUPRUELGLW\GH¿QHGDVWKHFRPSRVLWHRIFRUR
QDU\ KHDUW GLVHDVH DQG VWURNH DQG QRQVPRNHUVQRW KDYLQJ 5+7 VHUYHG DV
WKHUHIHUHQFHJURXS
Results: 'XULQJIROORZXSHYHQWVRFFXUUHG FDVHVSHUSHUVRQ
\HDUV ,QFLGHQFH UDWHV RI FDUGLRYDVFXODU HYHQWV ZHUH FDVHV SHU SHUVRQ\HDUV LQ WKH QRQVPRNHUQRW KDYLQJ 5+7 JURXS FDVHV SHU
Design and method: :HFRQGXFWHGDV\VWHPDWLFUHYLHZDQGPHWDDQDO\VLV
RIUDQGRPLVHGFRQWUROOHGGLHWDU\LQWHUYHQWLRQVWXGLHVFRPSDULQJWKHHIIHFWV
RIPRGL¿FDWLRQRIGLHWDU\IUHHVXJDUVRQEORRGSUHVVXUHDQGOLSLGV6FLHQWL¿F
GDWDEDVHVZHUHVHDUFKHGWKURXJKWR$XJXVWWRLGHQWLI\VWXGLHVODVWLQJ
! ZHHNVDQGUHSRUWLQJWUHDWPHQWGLIIHUHQFHVLQLQWDNHVRIVXJDUVDQGDW
OHDVWRQHRXWFRPHPHDVXUHIRUEORRGSUHVVXUHRUOLSLGV:HH[FOXGHGWULDOV
FRQIRXQGHGE\DGGLWLRQDOPHGLFDORUOLIHVW\OHLQWHUYHQWLRQV
Results: 2IWKHWULDOVLGHQWLILHGZHUHLQFOXGHGUHSRUWHGEORRG
SUHVVXUHDQGUHSRUWHGOLSLGRXWFRPHV7KHUHZDVVLJQLILFDQWKHWHURJHQH
LW\ 3 , IRUV\VWROLFEORRGSUHVVXUH 6%3 ZLWKDVLJQLILFDQW
LQWHUDFWLRQZLWKVWXG\GXUDWLRQ 3 IRUERWK6%3DQGGLDVWROLFEORRG
SUHVVXUH '%3 7KHUHZDVQRHIIHFWRIVXJDUVRQ6%3RU'%3DPRQJVWWUL
DOVZHHNV,QWKHWULDOV!ZHHNVGXUDWLRQKLJKHUVXJDUVLQWDNHZDV
DVVRFLDWHGZLWKKLJKHU6%3RIPP+J>&,@DQG'%3
RI PP+J > &, @ +LJKHU VXJDUV LQWDNH ZDV DOVR DVVR
FLDWHG ZLWK VWDWLVWLFDOO\ VLJQLILFDQW LQFUHDVHV LQ WULJO\FHULGHV PPRO/
>&, +'/FKROHVWHURO PPRO/>&,@ /'/ FKROHVWHURO PPRO/ > &, @ DQG WRWDO FKROHVWHURO
PPRO/ > &, @ &KDQJHV LQ ERG\ ZHLJKW H[SODLQHG
VRPHEXWQRWDOORIWKHFDUGLRPHWDEROLFHIIHFWRIVXJDUV:HIRXQGQRHI
IHFWRIW\SHRIVXJDU
Conclusions: 'LHWDU\ VXJDUV FRQWULEXWH WR UDLVHG EORRG SUHVVXUH DQG LQ
FUHDVHGFDUGLRYDVFXODUULVN
7C.10
CARDIOVASCULAR RISK MARKERS PREDICT
INSULIN SENSITIVITY IN YOUNG MEN AFTER 17
YEARS
66NnUQ1, M. Rostrup 1, 6(.MHOGVHQ2, A. Flaa 2, 7$NVQHV. 1 Section
for Cardiovascular and Renal Research, Dept. of Acute Medicine, Medical
Clinic, Oslo University Hospital, Ullevål, Oslo, NORWAY, 2 Section for
Cardiovascular and Renal Research, Dept. of Cardiology, Medical Clinic, Oslo
University Hospital, Ullevål, Oslo, NORWAY, 3 Section for Cardiovascular
and Renal Research, Ullevål and Dept. of Cardiology, Akershus University
Hospital, Oslo, NORWAY
Objective: :HKDYHSUHYLRXVO\VKRZQWKDWV\PSDWKRDGUHQDOUHDFWLYLW\SUH
GLFWVIXWXUHLQVXOLQUHVLVWDQFH GHWHUPLQHGE\KRPHRVWDVLVPRGHODVVHVVPHQW
RILQVXOLQUHVLVWDQFH+20$,5 LQ\RXQJPHQ\HDUVODWHU:HQRZIRU
WKH¿UVWWLPHDLPHGWRLQYHVWLJDWHWKHLQÀXHQFHRIRWKHUFDUGLRYDVFXODUULVN
PDUNHUVRQLQVXOLQVHQVLWLYLW\LQVLPLODU\RXQJPHQDIWHU\HDUVRIIROORZ
e101
Journal of Hypertension Volume 32, e-Supplement 1, 2014
XS WKLV WLPH PHDVXUHG E\ WKH ³JROGVWDQGDUG´ PHWKRG K\SHULQVXOLQDHPLF
LVRJO\FDHPLFJOXFRVHFODPS
Design and method: KHDOWK\\RXQJPHQZHUHGXULQJH[DP
LQHGIRUFDUGLRYDVFXODUULVNPDUNHUVLQFOXGLQJLQVXOLQVHQVLWLYLW\PHDVXUHG
E\ K\SHULQVXOLQDHPLF LVRJO\FDHPLF JOXFRVH FODPS JOXFRVH GLVSRVDO UDWH
*'5 ,QZHUHH[DPLQHGPHQZLWKWKHIXOOFODPSSUR
FHGXUH
Results: 7KH WDEOH VKRZV FKDUDFWHULVWLFV DW EDVHOLQH DQG IROORZXS $IWHU
PHDQ “ \HDUV RI IROORZXS LQVXOLQ VHQVLWLYLW\ PHDVXUHG DV *'5
ZDVSUHGLFWHGE\EDVHOLQHERG\PDVVLQGH[ %0, U S WR
WDO FKROHVWHURO U S DQG WULJO\FHULGHV 7*V U S LQXQLYDULDWHDQDO\VHV*'5DWEDVHOLQHGLGQRWUHDFKWKHOHYHORI
VLJQL¿FDQFH U S 2QO\7*VUHPDLQHGVLJQL¿FDQWLQPXOWLYDUL
DWHVWHSZLVHUHJUHVVLRQDQDO\VHV
+5 RI$+ RYHU \HDUV RI IROORZXS LQ ZRPHQ ZLWK KLJK IDPLO\VWUHVV ZDV
IROG KLJKHU &, S +5 RI 0, ZDV IROG
KLJKHU &,S FRPSDUHGWRWKRVHZLWKORZHUOHYHOVRI
IDPLO\VWUHVV7KHUHZHUHWHQGHQFLHVRILQFUHDVLQJ$+DQG0,UDWHVLQPDUULHG
ZRPHQH[SHULHQFHGVWUHVVLQIDPLO\FRPSDUHGWRXQPDUULHGGLYRUFHGDQGZLG
RZHGZLWKWKHVDPHVWUHVVOHYHO$+GHYHORSHGVLJQL¿FDQWO\KLJKHULQZRPHQ
ZLWKXQLYHUVLW\DQGVSHFLDOL]HGVHFRQGDU\HGXFDWLRQFRPSDUHGWRWKRVHKDYLQJ
HOHPHQWDU\VFKRROZLWK [ GI S[ GI SIRUXQLYHU
VLW\DQGVSHFLDOL]HGVHFRQGDU\UHVSHFWLYHO\ RUZLWKRXWVWUHVVDWKRPH [ GI S [ GI S UHVSHFWLYHO\ ,Q UHODWLRQ WR RFFXSDWLRQDO
FODVV$+UDWHVZHUHKLJKHULQJURXSV¿UVWOLQHPDQDJHU [ GI S DQG SK\VLFDO ZRUNHU [ GI S H[SHULHQFHG VWUHVV LQ IDPLO\ 0,
UDWHVZHUHWHQGLQJWREHKLJKHULQPDQDJHUVDQGHQJLQHHUVZLWKIDPLO\VWUHVV
Conclusions: 7KHSUHYDOHQFHRIKLJKVWUHVVLQIDPLO\LQIHPDOHSRSXODWLRQDJHG
\HDUVLVPRUHWKDQLQ5XVVLD:RPHQZLWKKLJKIDPLO\VWUHVVKDG
VLJQL¿FDQWO\KLJKHUUHODWLYHULVNRI$+DQG0,RYHUWK\HDUVRIIROORZXS
5DWHVRI$+0,GHYHORSPHQWZHUHPRUHOLNHO\LQPDUULHGZRPHQZLWKKLJKHU
HGXFDWLRQDO OHYHO DQG KLJK IDPLO\ VWUHVV LQ SURIHVVLRQDO FODVV PDQDJHUV DQG
SK\VLFDOODERUHUV
7C.12
IMPACT OF THE METABOLIC SYNDROME ON
STRUCTURAL AND FUNCTIONAL ARTERIAL
CHANGES: GENDER DIFFERENCES
'DWDDUHSUHVHQWHGDVPHDQV“6'VH[FHSWIRUGDLO\VPRNHUV
1$QRWDYDLODEOH
SYDOXH SYDOXH
0/RER]5XGQLFND1, --DURFK1, =%RFLDJD1, (.UXV]\QVND1,
%5]\F]NRZVND1, :5\FKDUG1, .'XGHN2, ,8FKPDQRZLF],
./RER]*UXG]LHQ. 1 T. Marciniak Hospital, Department of Cardiology,
Wroclaw, POLAND, 2 Karkonosze College, Faculty of Natural Sciences and
Technology, Jelenia Gora, POLAND, 3 Wroclaw Medical University, Faculty of
Health Science, Wroclaw, POLAND
Conclusions: &DUGLRYDVFXODUULVNPDUNHUVVXFKDVLQVXOLQUHVLVWDQFH LQYHUVHRI
JOXFRVHGLVSRVDOUDWH %0,IDVWLQJJOXFRVHDQGOLSLGVLQFUHDVHGLQ\RXQJPHQ
DIWHU\HDUV7KHUHZDVDVLJQL¿FDQWQHJDWLYHFRUUHODWLRQEHWZHHQ%0,WRWDO
FKROHVWHURODQG7*VDQGIXWXUHLQVXOLQVHQVLWLYLW\
Objective: 7KHDLPRIWKLVVWXG\ZDVWRH[DPLQHWKHLQÀXHQFHRIWKHPHWDEROLF
V\QGURPH 06 RQIXQFWLRQDO H[SUHVVHGE\FDURWLGVWLIIQHVV&6 DQGVWUXFWXUDO
H[SUHVVHG E\ FDURWLG LQWLPD PHGLD WKLFNQHVV ± &,07 DUWHULDO FKDQJHV ZLWK
UHJDUGWRJHQGHUGLIIHUHQFHV
7C.11
FAMILY STRESS IN WOMEN LEAD TO ARTERIAL
HYPERTENSION AND MYOCARDIAL INFARCTION
OVER 16 YEARS IN RUSSIA (BASED ON WHO
EPIDEMIOLOGICAL PROGRAM MONICAPSYCHOSOCIAL)
9*DIDURY1, '3DQRY2, (*URPRYD2, ,*DJXOLQ1, $*DIDURYD 1.
Collaborative Laboratory of Cardiovascular Diseases Epidemiology SB
RAMS, Novosibirsk, RUSSIA, 2 FSBI Institute of Internal and Preventive
Medicine SB RAMS, Novosibirsk, RUSSIA
1
Design and method: 7KH VWXG\ JURXS FRQVLVWHG RI DV\PSWRPDWLF VXE
MHFWVPHQ 0 DQGZRPHQ : ZLWKFDUGLRYDVFXODU &9 ULVNIDFWRUV
H[FOXGLQJ GLDEHWHV PHOOLWXV DQG ZLWKRXW PDQLIHVW &9 GLVHDVH 06 GH¿QHG
DFFRUGLQJWRWKH,')GH¿QLWLRQZDVIRXQGLQ0DQG:&,07ZDVRE
WDLQHGXVLQJ'XOWUDVRXQGDQG&6SDUDPHWHUVEHWDVWLIIQHVVLQGH[SUHVVXUH
VWUDLQ HODVWLF PRGXOXV (S DUWHULDO FRPSOLDQFH $& DQG ORFDO SXOVH ZDYH
YHORFLW\ 3:9EHWD ZHUHGHWHUPLQHGZLWKWKHXVHRIWKHKLJKUHVROXWLRQHFKR
WUDFNLQJV\VWHP
Design and method: 8QGHU WKH WKLUG VFUHHQLQJ RI WKH :+2 021,&$SV\
FKRVRFLDOSURJUDPUDQGRPUHSUHVHQWDWLYHVDPSOHRIZRPHQDJHG\HDUV
Q ZHUHVXUYH\HGLQ1RYRVLELUVN4XHVWLRQQDLUH $ZDUHQHVVDQGDWWLWXGH
WRZDUGVWKHKHDOWK ZDVXVHGWRHVWLPDWHOHYHOVRIIDPLO\VWUHVV)URPWR
ZRPHQZHUHIROORZHGIRUWKHLQFLGHQFHRI$+DQG0,ZLWKXVLQJ³0\R
FDUGLDO,QIDUFWLRQ5HJLVWU\´GDWD&R[UHJUHVVLRQPRGHOZDVXVHGIRU$+0,
UHODWLYHULVNDVVHVVPHQW +5 Results: 1RLPSDFWRI06RQ&,07ZDVIRXQG,QWKHZKROHSRSXODWLRQKLJKHU
YDOXHVRI(SDQG3:9EHWDZHUHREVHUYHGLQLQGLYLGXDOVZLWK06WKDQZLWKRXW
06 “YV“S“YV“S ,Q:KLJKHUYDOXHV
RI3:9EHWDDQGORZHUYDOXHVRI$&ZHUHIRXQG “YV“S
“YV“S LQWKHVXEJURXSZLWK06,Q0QRVLJQL¿FDQW
GLIIHUHQFHVLQ&6SDUDPHWHUVEHWZHHQWKHVXEJURXSZLWK06DQGZLWKRXW06
ZHUHREVHUYHG8QLYDULDWHUHJUHVVLRQDQDO\VLVUHYHDOHGWKDWLQWKHZKROHSRSXOD
WLRQ06ZDVDVVRFLDWHGZLWK(S EHWDFRHI¿FLHQWS DQG3:9EHWD
EHWDFRHI¿FLHQWS 6HSDUDWHDQDO\VLVRI:DQG0VKRZHGWKDWDV
VRFLDWLRQEHWZHHQ06DQG&6ZDVVLJQL¿FDQWRQO\LQ:ZLWK$& EHWDFRHI¿
FLHQW±S DQG3:9EHWD EHWDFRHI¿FLHQWS 6WHSZLVH
OLQHDUUHJUHVVLRQDQDO\VLVLQ:UHYHDOHGWKDWDIWHUDGMXVWPHQWIRUDJHRQO\DVVR
FLDWLRQZLWK$&UHPDLQHGVLJQL¿FDQW EHWDFRHI¿FLHQWS Results: 7KHSUHYDOHQFHRIKLJKIDPLO\VWUHVVOHYHOLQZRPHQDJHG\HDUV
ZDV
Conclusions: 0HWDEROLFV\QGURPHKDVDQLPSDFWRQIXQFWLRQDODUWHULDOFKDQJHV
H[SUHVVHGE\FDURWLGVWLIIQHVVRQO\LQZRPHQEXWQRWLQPHQ
Objective: :HVWXGLHGWKHLQÀXHQFHRIIDPLO\VWUHVVRQUHODWLYHULVNRIDQDUWH
ULDOK\SHUWHQVLRQDQGP\RFDUGLDOLQIDUFWLRQ 0, LQIHPDOHSRSXODWLRQDJHGRI
\HDUVLQ5XVVLDRYHU\HDUVRIIROORZXS
Abstracts
e102
ORAL SESSION
ORAL SESSION 7D
ENDOCRINE HYPERTENSION
7D.01
COMMON SOMATIC MUTATIONS IN CAV1.3, ADRENAL
IMMUNOHISTOCHEMISTRY, AND INHIBITION OF
ALDOSTERONE SECRETION BY CAV1.3 BLOCKADE,
INDICATE A ZONA GLOMERULOSA-LIKE SUBSET OF
ALDOSTERONE
($]L]DQ1, A. Teo 1, &;LH1, /+DULV6KDLNK1, -=KRX1, 6*DUJ1,
:=KRX2, 6.DQJ, 56LOYHUPDQ, M. Brown 1. 1 Clinical Pharmacology
Unit, Centre for Clinical Investigation, Addenbrookes Hospital, University of
Cambridge, Cambridge, UNITED KINGDOM, 2 Human Research Tissue Bank,
Cambridge University Hospitals National Health Service (NHS) Foundation
Trust, Addenbrookes, Cambridge, UNITED KINGDOM, 3 Department
of Chemistry, Center for Molecular Innovation and Drug Discovery,
Northwestern University, Evanston, IL, USA
Objective: =RQD JORPHUXORVD =* OLNH DOGRVWHURQHSURGXFLQJ DGHQRPDV
$3$V KDYHJDLQRIIXQFWLRQPXWDWLRQVRIDQ/W\SHFDOFLXPFKDQQHO /7&& &D9 :HLQYHVWLJDWHGZKHWKHU&D9LVD=*VHOHFWLYH/7&&DQGLWV
UROHRQVWHURLGRJHQHVLV
Design and method: :H XVHG D QRYHO !IROG VHOHFWLYH DQWDJRQLVW RI
&D9 &RPSRXQG & ZKLFK ZH FRPSDUHG WR WKH DQWLK\SHUWHQVLYH
GUXJQLIHGLSLQHDGLK\GURS\ULGLQH '+3 ZLWKVHOHFWLYLW\IRUWKHYDVFXODU
/7&&&D9/RFDOL]DWLRQRI&D9LQKXPDQDGUHQDOVZDVGHWHUPLQHGXV
LQJLPPXQRKLVWRFKHPLVWU\ ,+& 'UXJHIIHFWVZHUHWHVWHGLQWKHKXPDQDGUH
QRFRUWLFDOFHOOOLQH+5DQGERWK$3$DQGDGMDFHQWQRUPDODGUHQDO 1$ FHOOVIURPSDWLHQWVZLWK$3$V7KHVHZHUHWUHDWHGIRUKZLWK&QLIHGLSLQH
RUSUHJDEDOLQ DQDQWDJRQLVWRIWKHĮįVXEXQLWRIDOO/7&&V &RQFHQWUDWLRQRI
FRUWLFRVWHURLGVDQGH[SUHVVLRQRIVWHURLGRJHQLFJHQHVZHUHPHDVXUHG
$OWKRXJKDGUHQDO]RQDJORPHUXORVD =* LVWKHSULQFLSDOVLWHRISK\VLRORJLFDO
DOGRVWHURQHSURGXFWLRQFODVVLFDO$3$VSDUDGR[LFDOO\UHVHPEOHFHOOVRIWKHFRUWL
VROVHFUHWLQJ]RQDIDVFLFXODWD =) 7KH¿QGLQJRIJDLQRIIXQFWLRQPXWDWLRQVLQ
DGLVWLQFWJURXSRIVPDOOHU$3$VUHVHPEOLQJ=*FHOOV $]L]DQ SURPSWHG
WKHTXHVWLRQVZKHWKHUWKHVHWXPRXUVRULJLQDWHIURPQRUPDODGUHQDO=*DQGLI
WKHSURFHVVRIWXPRULJHQHVLVGLIIHUVEHWZHHQ=*DQG=)OLNH$3$V
Design and method: 0LFURDUUD\ FRPSDULVRQ RI QRUPDO DGUHQDO =* DQG =)
FHOOV XVLQJ ODVHU FDSWXUH PLFURGLVVHFWLRQ /&0 VKRZHG VHYHUDO SXWDWLYH =*
JHQHV XSUHJXODWHG PDQ\IROG LQ =* YV =)$ VHFRQG PLFURDUUD\ ZDV WKHUH
IRUHSHUIRUPHGFRPSDULQJ¿YH=*OLNH$3$VZLWKPXWDWLRQVLQ&$&1$'RU
$73$WRHLJKW=)OLNH$3$VZLWKPXWDWLRQVLQ.&1-)RUSURRIRIFRQFHSW
WKDW WKH JHQHV XSUHJXODWHG LQ =*±OLNH$3$V LQGLFDWH D =* RULJLQ H[SUHVVLRQ
ZDVYDOLGDWHGE\TXDQWLWDWLYH3&5 T3&5 DQGLPPXQRKLVWRFKHPLVWU\
Results: 0LFURDUUD\ DQDO\VHV LGHQWL¿HG JHQHV GLIIHUHQWLDOO\ H[SUHVVHG LQ
WKH=*OLNH$3$ZLWK!IROGJUHDWHUH[SUHVVLRQWKDQ=)OLNH$3$VDQGIDOVH
GLVFRYHU\UDWH )'5 RI7KHOLVWZDVKHDGHGE\1HSKURQHFWLQ 1317 [S ( 7KLVLVDVHFUHWHGH[WUDFHOOXODUPDWUL[SURWHLQUHFHQWO\UH
SRUWHGWRUHJXODWHFHOOPLJUDWLRQDQGLQYDVLRQLQPDOLJQDQWPHODQRPD .XSKDO
T3&5FRQ¿UPHGWKDW1317ZDVIROGPRUHKLJKO\H[SUHVVHGLQQRU
PDO=*YV=) 3 DQGIROGXSUHJXODWHGLQ=*OLNHYV=)OLNH$3$V
3 $WSURWHLQOHYHOLPPXQRKLVWRFKHPLVWU\VKRZHGKLJKO\VHOHFWLYH
VWDLQLQJRI=* )LJ DQGFRQ¿UPHGWKDW1317ZDVPRUHDEXQGDQWLQ=*
OLNH )LJ D WKDQ =)OLNH WXPRXUV )LJ E 1317 VWDLQLQJ RXWOLQHG JURXSV
µJORPHUXOL¶ RIFHOOVLQDOOFDVHV
Results: ,+&ORFDOL]HG&D9WRWKH=*,Q1$FHOOVRQO\&LQKLELWHGVWHURLG
SURGXFWLRQDOGRVWHURQHWRDQGRIEDVDODWDQGX0FRUWLVRO
WRDQGRIEDVDOS1LIHGLSLQHX0LQFUHDVHGDOGRVWHURQHE\
S DQGGHFUHDVHGDOGRVWHURQHRQO\WRDWX0S QLIHGLSLQHX0LQFUHDVHGFRUWLVROE\S %\FRQWUDVWLQ$3$FHOOV
ERWK&DQGQLIHGLSLQHX0GHFUHDVHGDOGRVWHURQHWRDPD[RIDQG
UHVSHFWLYHO\S6LPLODUO\LQ+5FHOOVERWK&DQGQLIHGLSLQH
X0GHFUHDVHGDOGRVWHURQHVHFUHWLRQ S 7KHUHGXFWLRQVLQVHFUHWLRQZHUHQRW
GXHWRUHGXFHGWUDQVFULSWLRQRI&<3%RU&<3%3UHJDEDOLQQ0GLG
QRWDIIHFWDOGRVWHURQHRUFRUWLVROVHFUHWLRQIURP1$EXWDWDQGQ0LQFUHDVHG
DOGRVWHURQHVHFUHWLRQIURP+5FHOOVE\DQGUHVSHFWLYHO\ S Conclusions: 7KLVVWXG\VKRZVWKDWVHOHFWLYH&D9EORFNDGHGHFUHDVHVVWH
URLGVHFUHWLRQIURPERWK1$DQG$3$FHOOVZKHUHDVEORFNDGHRIRWKHU/7&&
VXEXQLWVKDVQRHIIHFWRQRULQFUHDVHVVHFUHWLRQIURP1$FHOOV$FWLYDWLRQRU
PXWDWLRQRI&D9LQ$3$VPD\LQFUHDVHLWVVHQVLWLYLW\WRQLIHGLSLQH6HOHFWLYH
&D9 EORFNDGH PD\ RIIHU D QRYHO ZD\ RI WUHDWLQJ SULPDU\ K\SHUDOGRVWHUR
QLVPZKLFKDYRLGVWKHFRPPRQ&D9PHGLDWHGDQNOHHGHPDRIQRQVHOHF
WLYH'+3FDOFLXPEORFNHUV
Conclusions: 3KHQRW\SLFDOO\ DQG JHQRW\SLFDOO\GLVWLQFW IURP =)OLNH $3$V
VPDOO1317ULFK$3$VSUREDEO\UHVROYHWKHSDUDGR[RIWKHµPLVVLQJ¶$3$VRI
=*RULJLQ1317PD\KDYHDUROHLQFHOOFOXVWHULQJWRIRUPIXQFWLRQDOXQLWVIRU
DOGRVWHURQHVHFUHWLRQRULQUHJXODWLQJWKHORQJSRVWXODWHGFHQWULSHWDOFHOOPLJUD
WLRQIURP=*WR=)/RVVRI1317DGMDFHQWWRDQ$3$PD\IDFLOLWDWHPLJUDWLRQ
DQGKHQFHGRZQUHJXODWLRQRIDOGRVWHURQHSURGXFWLRQ
7D.03
7D.02
HIGHLY SELECTIVE EXPRESSION OF
NEPHRONECTIN DELINEATES A COMMON SUBTYPE
OF ALDOSTERONE-PRODUCING ADENOMAS OF
ZONA GLOMERULOSA ORIGIN AND A PUTATIVE
ROLE IN ALDOSTERONE PRODUCTION
A. Teo 1, ($]L]DQ1, /6KDLNK1, -=KRX1, ':DOWHUV2, 61HRJL,
,0F)DUODQH, M. Brown 1. 1 Clinical Pharmacology Unit, Centre for Clinical
Investigation, Addenbrookes Hospital, University of Cambridge, Cambridge,
UNITED KINGDOM, 2 Tissue Bank, Department of Histopathology,
Addenbrookes Hospital, Cambridge, UNITED KINGDOM, 3 National Institute
for Health Research (NIHR) Biomedical Research Centre (BRC), Department
of Clinical Biochemistry, Cambridge, UNITED KINGDOM
Objective: 2YHU RI K\SHUWHQVLRQ LV GXH WR DGUHQDO DOGRVWHURQHSURGXFLQJ
DGHQRPDV $3$V ZKLFKDUHSRWHQWLDOO\FXUDEOHE\XQLODWHUDODGUHQDOHFWRP\
PREVALENCE AND CLINICAL CHARACTERISTICS OF
SOMATIC MUTATIONS IN CHINESE PATIENTS WITH
ALDOSTERONE-PRODUCING ADENOMA
)=KHQJ1, /=KX1, $1LH2, ;/L2, .=KDQJ, -&KHQ1, :=KRX, =6KHQ,
<=KX5, '=KX1, P. Gao . 1 Shanghai Institute of Hypertension, Shanghai,
CHINA, 2 Shanghai Institute of Endocrinology and Metabolism, Shanghai,
CHINA, 3 Institute of Health Sciences, Laboratory of Vascular Biology and
Key Laboratory of Stem Cell Biology, Shanghai, CHINA, 4 Ruijin Hospital,
Department of Urology, Shanghai, CHINA, 5 Fudan University Shanghai
Medical College, Department of Physiology and Pathophysiology, Shanghai,
CHINA
Objective: ,WKDVEHHQHVWDEOLVKHGWKDWWKHVRPDWLFPXWDWLRQVLQWKH.&1-JHQH
ZKLFKHQFRGHVWKH*SURWHLQDFWLYDWHGLQZDUGUHFWL¿HU.FKDQQHO *,5. DV
ZHOODVLQWKH$73$$73%DQG&$&1$'JHQHVDUHDVVRFLDWHGZLWKWKH
SDWKRJHQHVLVRIDOGRVWHURQHSURGXFLQJDGHQRPD $3$ ZLWKYDULHGRFFXUUHQFH
M
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A
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e103
Journal of Hypertension Volume 32, e-Supplement 1, 2014
SUR¿OHVLQGLIIHUHQWHWKQLFJURXSV7KHSUHYDOHQFHDQGFOLQLFDOSUR¿OHRIWKHPX
WDWLRQVLQ&KLQHVHSDWLHQWVZLWK$3$UHPDLQXQNQRZQ
Design and method: :H VHTXHQFHG .&1- $73$ $73% DQG &$&
1$'LQ&KLQHVHSDWLHQWVZLWK$3$
Results: :H IRXQG D FRQVLGHUDEOH KLJK IUHTXHQF\ RI .&1- PXWD
WLRQV3DUWLFXODUO\ZHLGHQWL¿HGDQHZVRPDWLF.&1-PXWDWLRQ FLQ
V*$$S77LQV5 ZKLFKOHGWRD.FXUUHQWUHGXFWLRQDQGD1DFXU
UHQW LQFUHDVH LQ HOHFWURSK\VLRORJLFDO H[SHULPHQWV7KH H[SUHVVLRQ LQWHQVLW\ RI
*,5. SURWHLQ ZDV PXFK ORZHU LQ$3$V ZLWK .&1- PXWDWLRQV WKDQ WKRVH
ZLWKRXWPXWDWLRQV.&1-PXWDWLRQFDUULHUVKDGQRWRQO\KLJKHUXULQDU\DOGRV
WHURQH DQG ODUJHU WXPRU VL]H EXW DOVR ORZHU SODVPD UHQLQ DFWLYLW\ DQG VHUXP
.OHYHO)XUWKHUPRUHWKHZKROHSUHYDOHQFHRIVRPDWLF$73$$73%DQG
&$&1$'PXWDWLRQVZDVLQFOXGLQJDQRYHO$73$PXWDWLRQ F
GHO$7*77$ S0/GHO DQG D QRYHO $73% PXWDWLRQ F
GHO*7&$&7*7*&7**7&LQV$*&$&$&7&SGHO99LQV67/ Conclusions: 6RPDWLF.&1-PXWDWLRQVDUHFRQVSLFXRXVO\PRUHSRSXODUWKDQ
RWKHUJHQHV¶PXWDWLRQVLQ$3$IRU&KLQHVHSDWLHQWVZKLFKFRXOGEHUHVSRQVLEOH
IRUDPRUHUHPDUNDEOHSKHQRW\SH$QHZPXWDWLRQLQ.&1-LVLGHQWL¿HGDQG
FRQ¿UPHGWRUHVXOWLQDQRQVHOHFWLYHFKDQQHO
7D.04
ANGIOTENSIN 1-7 IS A NOVEL REGULATOR OF
ALDOSTERTONE SECRETION AND A MODULATOR
OF THE ALDOSTERONE RESPONSE TO SALT
RESTRICTION
<0DUFXV1, *6KHIHU1, R. Limor 1, (.QROO1, S. Braun 2, 3=DGLFDULR2,
16WHUQ1. 1 Institute of Endocrinology, Metabolism and Hypertension, Tel Aviv
Medical Center, Tel Aviv, ISRAEL, 2 Tel Aviv University, Tel Aviv, ISRAEL
Objective: $QJLRWHQVLQ $QJ DQWDJRQL]HGPDQ\RIWKHFDUGLRYDVFXODU
HIIHFWV RI $QJLRWHQVLQ ,, $QJ,, :H UHFHQWO\ UHSRUWHG WKDW $QJ DWWHQX
DWHVWKHLQFUHDVHLQFLUFXODWLQJUHQLQDQGDOGRVWHURQHLQGXFHGLQDUDWPRGHORI
PHWDEROLFV\QGURPH:KHWKHURUQRWWKHUHGXFWLRQLQDOGRVWHURQHZDVLQGLUHFW
RSHUDWLQJWKURXJKDGHFUHDVHLQUHQLQUHPDLQHGXQFOHDU
7RVWXG\WKHHIIHFWRI$QJDGPLQLVWUDWLRQLQYLYRRQWKHUHQLQDQGDOGRVWHU
one response to salt restriction in rats.
Design and method: 5DWV ZHUH IHG RQ HLWKHU QRUPDO FKRZ RU ORZ VDOW GLHW
7HNODG 5DW 'LHW +DUODQ IRU RQH ZHHN GXULQJ ZKLFK HLWKHU YHKLFOH RU
$QJ ZDV FRQWLQXRXVO\ LQIXVHG WKURXJK$O]HW SXPSV —JNJGD\ VF
Q JURXS %ORRGZDVGUDZQIRUSODVPDUHQLQFRQFHQWUDWLRQDQGDOGRVWHURQH
SULRUWRWKHVXEGLYLVLRQWRGLHWDU\LQWHUYHQWLRQDQGE\WKHHQGRIWKHH[SHULPHQW
IROORZLQJ ZKLFK DQLPDOV ZHUH WKHQ HXWKDQL]HG WR KDUYHVW WKH NLGQH\V 5HQDO
VOLFHVZHUHSUHSDUHGWRDVVHVVH[YLYRUHQLQUHOHDVH6LQFHURGHQWVKDYHORZFLU
FXODWLQJDQJLRWHQVLQRJHQDOOUHQLQDVVD\VZHUHFDUULHGLQPHGLDHQULFKHGZLWK
SODVPDIURPKQHSKHUFWRPL]HGUDWV
Results: ,QUDWVIHGRQUHJXODUFKRZ$QJLQIXVLRQKDGQRHIIHFWRQHLWKHU
SODVPDDOGRVWHURQHRUSODVPDUHQLQDFWLYLW\ 35$ ,QUDWVIHGRQDORZVDOWGLHW
DOGRVWHURQHLQFUHDVHGIURP“WR“QJGO S EXWWKLVLQFUHDVHZDV
DWWHQXDWHGE\$QJLQIXVLRQ “QJGOS 35$URVHE\LQ
VDOWUHVWULFWHGUDWVZKLFKZDVQRWPRGL¿HGE\$QJLQIXVLRQ5HQLQVHFUHWLRQ
ZDVKLJKHULQUHQDOVOLFHVSUHSDUHGIURPVDOWGHSULYHGUDWVFRPSDUHGZLWKUDWV
IHGRQQRUPDOFKRZ S DQGZDVLQFUHDVHGLQUHQDOVOLFHVIURP$QJ
WUHDWHGUDWV S )LQDOO\0DV$QJUHFHSWRUZDVH[SUHVVHGLQWKHDGUH
QDOFRUWH[EXWQRWLQWKHPHGXOODDQG$QJUHGXFHGWKHDOGRVWHURQHUHVSRQVH
WR$QJ,,LQ]RQDJORPHUXORVDFHOOVIURPQRUPDOUDWV
Conclusions: 7KLVLVWKH¿UVWUHSRUWVKRZLQJWKDW$QJLVDQHJDWLYHPRGXODWRU
RIWKHDOGRVWHURQHUHVSRQVHWRVDOWGHSULYDWLRQDFWLQJLQGHSHQGHQWRIWKHUHQLQ
5DWKHUWKLVHIIHFWLVDSSDUHQWO\H[HUWHGYLD0DVUHFHSWRUVH[SUHVVHGLQWKHDGUHQDO
FRUWH[WKURXJKZKLFK$QJUHGXFHVWKHVWLPXODWRU\HIIHFWRI$QJ,,RQDOGRV
terone secretion.
7D.05
PRIMARY ALDOSTERONISM IS MAJOR CAUSE OF
HYPERTENSION IN PATIENTS WITH SUBCLINICAL
CUSHING’S SYNDROME
-6DLWR1, M. Omura 1, .0DNLWD2, S. Matsui , 01DJDWD, 77RNL1,
<0DWVX]DZD1, 71LVKLNDZD1. 1 Endocrinology and Diabetes Center,
Yokohama Rosai Hospital, Yokohama, JAPAN, 2 Department of Radiology,
Nerima Hikarigaoka Hospital, Tokyo, JAPAN, 3 Department of Radiology,
Yokohama Rosai Hospital, Yokohama, JAPAN, 4 Department of Urology,
Yokohama Rosai Hospital, Yokohama, JAPAN
Objective: 3DWLHQWV ZLWK VXEFOLQLFDO &XVKLQJ¶V V\QGURPH 6&6 GXH WR FRUWL
VROSURGXFLQJ DGUHQDO DGHQRPD &3$ KDYH D KLJKHU SUHYDOHQFH RI K\SHUWHQ
VLRQGLDEHWHVPHOOLWXVDQGG\VOLSLGHPLDWKDQWKHJHQHUDOSRSXODWLRQZKLOHLWLV
REVFXUHZKHWKHURUQRWPLOGH[FHVVRIFRUWLVROLQYROYHVSDWKRJHQHVLVRIK\SHU
WHQVLRQ6&6KDGUHFHQWO\EHHQUHSRUWHGWRFRPSOLFDWHSULPDU\DOGRVWHURQLVP
3$ 7KHUHIRUHZHWULHGWRSURVSHFWLYHO\VWXG\WKHSUHYDOHQFHRI3$DQGK\SHU
tension in cases with CPA.
Design and method: FRQVHFXWLYHSDWLHQWVZLWKDGUHQDO6&6RU&XVKLQJ¶VV\Q
GURPH &6 HVWLPDWHGE\RYHUQLJKWGH[DPHWKDVRQHVXSSUHVVLRQWHVWZHUHHQUROOHG
LQWRWKLVVWXG\IURPWR3$ZDVVXVSHFWHGZKHQPD[LPDODOGRVWHURQH
FRQFHQWUDWLRQZDVPRUHWKDQQJGODIWHUȝJRI$&7+VWLPXODWLRQ+\SHUDO
GRVWHURQLVPZDVGLDJQRVHGZKHQFRQFHQWUDWLRQRIDOGRVWHURQHZDV!QJGOLQ
HIÀXHQWVDPSOHGDWYDULRXVLQWUDDGUHQDOWULEXWDU\YHLQVDIWHU$&7+VWLPXODWLRQ
66$96 5HPLVVLRQRIK\SHUWHQVLRQZDVLQYHVWLJDWHGRQH\HDUDIWHUXQLODWHUDO
SDUWLDODGUHQDOHFWRP\IRU&3$RUDOGRVWHURQHSURGXFLQJDGHQRPD $3$ Results: $OGRVWHURQHUHQLQUDWLRZDVOHVVWKDQQJGOSHUQJPOKLQDPRQJ
FDVHVZLWK&3$KRZHYHUFDVHVDPRQJZLWK6&6DQGDPRQJZLWK
&6 ZHUH VXVSHFWHG WR FRPSOLFDWH 3$ DIWHU$&7+VWLPXODWLRQ WHVW$PRQJ ZLWK6&6FRPSOLFDWLQJ3$FDVHVZHUHK\SHUWHQVLYHDQG66$96GH¿QLWH
O\GHWHFWHGFRUWLVROSOXVDOGRVWHURQHSURGXFLQJDGHQRPDV &$3$ &3$V
FRPSOLFDWLQJ$3$LQRSSRVLWHVLGHRIDGUHQDOJODQG &3$$3$ DQG&3$V
ZLWK,+$ &3$,+$ $OOFDVHVZLWK&6 EHFDPHK\SRWHQVLYHGXHWRDGUHQDO
LQVXI¿FLHQF\DIWHUXQLODWHUDODGUHQDOHFWRP\$OOFDVHVZLWK&$3$DQGFDV
HV ZLWK &3$$3$ WUHDWHG E\ XQLODWHUDO DGUHQDOHFWRP\ IRU$3$ EHFDPH QRU
PRWHQVLYH:KLOHFDVHVDPRQJZLWK&3$$3$DQGFDVHVDPRQJZLWK
&3$,+$VWLOOKDGK\SHUWHQVLRQHYHQWKRXJKK\SHUFRUWLVROLVPZDVFXUHGRQH
\HDUDIWHUXQLODWHUDODGUHQDOHFWRP\IRU&3$
Conclusions: 3UHYDOHQFHRI3$DPRQJSDWLHQWVZLWK6&6ZDV8QLODWHUDO
DGUHQDOHFWRP\IRUWUHDWLQJWKHLUK\SHUWHQVLRQVKRZHGUHPLVVLRQHIIHFWLQ
FDVHVSHUIRUPHGIRU$3$EXWRQO\FXUDWLYHHIIHFWLQFDVHVSHUIRUPHGIRU
&3$7KHUHIRUHZHVKRXOGSUHFLVHO\GLDJQRVH3$DQGWUHDW3$LQRUGHUWRLP
SURYHDQGFXUHK\SHUWHQVLRQLQFDVHVZLWK6&6
7D.06
PATHOLOGICAL SUBCLASSIFICATION AND
STEROIDOGENIC PATHOPHYSIOLOGY OF PRIMARY
ALDOSTERONISM
F. Satoh 1, <2QR1, R. Morimoto 1, 0.XGR1, <,ZNXUD 1, .2PDWD1,
.6HLML2, .7DNDVH2, <1DNDPXUD, 0'RL, +2NDPXUD, &*RPH]
6DQFKH]5, +6DVDQR, 6,WR1. 1 Division of Nephrology, Endocrinology
and Vascular Medicine, Tohoku University Hospital, Sendai, JAPAN,
2
Department of Diagnostic Radiology, Tohoku University Hospital, Sendai,
JAPAN, 3 Department of Pathology, Tohoku University Hospital, Sendai,
JAPAN, 4 Department of Systems Biology, Graduate School of Pharmaceutical
Sciences, Kyoto University, Kyoto, JAPAN, 5 Division of Endocrinology, G.V.
Montgomery VA Medical Center, and the University of Mississippi Medical
Center, Jackson, MS, USA
Objective: 7KHUDSHXWLF PDQDJHPHQW RI SULPDU\ DOGRVWHURQLVP 3$ UHTXLUHV DF
FXUDWH GLIIHUHQWLDWLRQ EHWZHHQ DOGRVWHURQHSURGXFLQJ DGHQRPD $3$ DQG LGL
RSDWKLF K\SHUDOGRVWHURQLVP ,+$ $GUHQDO YHQRXV VDPSOLQJ $96 LV WKH RQO\
UHOLDEOH VXEFODVVL¿FDWLRQ PHWKRG 3DWKRORJLFDO FRQ¿UPDWLRQ IRU $3$ LV FULWLFDO
DIWHU VXUJHU\ 7KH H[SUHVVLRQV RI VWHURLGRJHQLF HQ]\PHV WR SURGXFH DOGRVWHURQH
OLNH&<3%&<3%%+6'DQG%+6'UHPDLQWREHFODUL¿HGWRFRQ¿UP
SDWKRORJLFDOVXEFODVVL¿FDWLRQEHWZHHQ$3$DQG,+$0RURYHUZHH[DPLQHGWKH
FRUUHODWLRQ EHWZHHQ$3$ WXPRU VL]H DQG WKH VWDWXV RI LQWUDWXPRUDO VWHURLGRJHQLF
HQ]\PHVLQYROYHGLQDOGRVWHURQHELRV\QWKHVLVXVLQJLPPXQRKLVWRFKHPLVWU\
Design and method: 6XUJLFDOO\ SURYHQ IRUW\$3$ SDWLHQWV DQG WHQ ,+$ SDWLHQWV
ZHUHUHWURVSHFWLYHO\VWXGLHG0XOWLGHWHFWRUFRPSXWHGWRPRJUDSK\$96DQGODSD
URVFRSLFDGUHQDOHFWRP\ZHUHSHUIRUPHGLQDOORIWKHSDWLHQWVVWXGLHG7KHWXPRU
DUHDRI$3$DWWKHPD[LPXPGLDPHWHURIWKHVHFWLRQVZDVSUHFLVHO\PHDVXUHGE\
,PDJH-VRIWZDUH7KHVWDWXVRIVWHURLGRJHQLFHQ]\PHVZDVLPPXQRKLVWRFKHPLFDOO\
DQDO\]HG XVLQJ PRQRFORQDO DQWLERGLHV IRU &<3% &<3% %+6' DQG
%+6'DQGWKH¿QGLQJVZHUHHYDOXDWHGDFFRUGLQJWRWKH+VFRUHV\VWHPEDVHG
RQERWKWKHQXPEHURILPPXQRSRVLWLYHFHOOVDQGUHODWLYHLPPXQRLQWHQVLW\$GUHQDO
PDVVHVZHUHQRWGHWHFWHGE\FRPSXWHGWRPRJUDSK\LQ$3$SDWLHQWV
Results: ,QDOORI,+$SDWLHQWVK\SHUSODVWLF]RQDJORPHUXORVDZDVDFFRPSDQLHG
E\DUREXVWH[SUHVVLRQRI+6'%,QFRQWUDVWWXPRUFHOOVLQDOO$3$SDWLHQWV
ZHUH QRW LPPXQRSRVLWLYH WR +6'% EXW VWURQJO\ DQG GRPLQDQW\ H[SUHVVHG +6
'%3HUKDSV GXH WR FRPSHQVDWRU\ UHVSRQVHV WR H[FHVV DOGRVWHURQH$3$ KDG DQ
DGMDFHQW]RQDJORPHUXORVDZKRVHLPPXQRUHDFWLYLWLHVWR+6'%DQG+6'%ZHUH
SURIRXQGO\ UHGXFHG LQ DOO $3$ SDWLHQWV 0D[LPXP WXPRU DUHD REWDLQHG LQ WKH
VSHFLPHQVZDVVLJQL¿FDQWO\FRUUHODWHGZLWKSUHRSHUDWLYHSODVPDDOGRVWHURQHFRQFHQ
WUDWLRQXULQDU\DOGRVWHURQHH[FUHWLRQWKH+VFRUHRI&<3%DQGZDVLQYHUVHO\
FRUUHODWHGZLWKWKH+VFRUHRI&<3%7KHVHUHVXOWVGHPRQVWUDWHGWKDWVPDOODG
HQRPDVFRXOGSURGXFHVXI¿FLHQWDOGRVWHURQHWRFDXVHFOLQLFDOO\RYHUWSULPDU\DOGR
VWHURQLVPEHFDXVHRIWKHVLJQL¿FDQWO\KLJKHU&<3%H[SUHVVLRQSHUWXPRUDUHD
e104
Journal of Hypertension Volume 32, e-Supplement 1, 2014
Conclusions: 0RQRFORQDODQWLERGLHVDJDLQVW+6'%DQG+6'%FRXOGEHXVH
IXO IRU LPPXQRKLVWRFKHPLFDO GLIIHUHQWLDWLRQ EHWZHHQ$3$ DQG ,+$ ,Q DGGLWLRQ
WKHUHODWLYHO\KLJKHU&<3%H[SUHVVLRQSHUDUHDLQVPDOOHU$3$FRXOGFOLQLFDOO\
FDXVH3$GHVSLWHWKHLU&7XQGHWHFWDEOHWXPRUVL]H
7D.07
GLFWLYHPDUNHUVRIFDUGLRYDVFXODUGLVHDVH7KHLQÀXHQFHRIDQGURJHQOHYHORQ
WKHDJHDQGEORRGSUHVVXUHUHODWHGLQFUHDVHLQDRUWLFVWLIIQHVVLVXQNQRZQ
STEM CELL MARKER, LGR5 AND ITS LIGAND
RSPO3 ARE SELECTIVELY EXPRESSED IN ZONA
GLOMERULOSA OF THE HUMAN ADRENAL AND
MAY EXPLAIN HIGH PREVALENCE OF SMALL
ALDOSTERONE-PRODUCING ADENOMAS
/+DULV6KDLNK1, A. Teo 1, -=KRX1, ($]L]DQ1, 6*XKD1HRJL2,
,0F)DUODQH2, 1)LJJ , $'DYHQSRUW1, M. Brown 1. 1 Clinical Pharmacology
Unit, Department of Medicine, University of Cambridge, Cambridge, UNITED
KINGDOM, 2 Genomics CoreLab, NIHR, Cambridge BioMedical Research
Centre, Cambridge, UNITED KINGDOM, 3 Divison of Cardiovascular
Medicine, Department of Medicine, University of Cambridge, Cambridge,
UNITED KINGDOM
Objective: 6PDOO ]RQD JORPHUXORVD =* OLNH DOGRVWHURQHSURGXFLQJ DGHQR
PDV $3$V ZLWKFRPPRQVRPDWLFPXWDWLRQVLQ&$&1$'RU$73$PD\
EHDFRQVHTXHQFHRIKLJKWXUQRYHURIDGUHQRFRUWLFDOFHOOVDQGORQJSUHVXPHG
SURFHVVRIFHQWULSHWDOPLJUDWLRQ,QRUGHUWRLGHQWLI\WKHJHQHVGULYLQJWKLVSUR
FHVVZHDLPHG>L@WRFRPSDUHE\PLFURDUUD\WKHWUDQVFULSWRPHRI=*YV]RQD
IDVFLFXODWD =) >LL@WRFRPSDUHFHOOWXUQRYHULQWKHVH]RQHV>LLL@WRH[DPLQH
HIIHFWV RQ DOGRVWHURQH SURGXFWLRQ RI JHQHV LQ WKH :17ȕFDWHQLQ VLJQDOOLQJ
SDWKZD\ZKLFKPLFURDUUD\IRXQGWREHXSUHJXODWHG
Design and method: 51$ IURP =* DQG =) RI KXPDQ DGUHQDOV ZDV LVR
ODWHG E\ /DVHU FDSWXUH PLFURGLVVHFWLRQ /&0 7KH 51$ ZDV DQDO\VHG LQ DQ
$II\PHWUL[PLFURDUUD\FRPSDULVRQRIWKHWZR]RQHV6LJQL¿FDQW¿QGLQJVZHUH
YDOLGDWHG E\ T3&5 DQG LPPXQRKLVWRFKHPLVWU\ ,+& 7KH FRJQDWH OLJDQG RI
/*55VSRQGLQ 5632 ZDVXVHGWRDVVHVVWKHHIIHFWRIUHFHSWRUDFWLYDWLRQ
RQ DOGRVWHURQH VHFUHWLRQ XVLQJ UDGLRLPPXQRDVVD\ 3KDUPDFRORJLFDO DQDO\VLV
ZDVSHUIRUPHGRQSULPDU\DGUHQDODQGLPPRUWDOLVHG+5RU+$&DGUH
nocortical cell lines.
Results: 7KH SXWDWLYH VWHP FHOO PDUNHU DQG D NH\ JHQH IRU :17 VLJQDOOLQJ
/*5ZDVWKHPRVWXSUHJXODWHGJHQHLQ=* [3 YVSDLUHG=)
,WVFRJQDWHOLJDQG5632 [3 DQG:17 [3 ZHUH
DOVRKLJKO\H[SUHVVHGLQ=*0LFURDUUD\UHVXOWVZHUHFRQ¿UPHGXVLQJT3&5
,+&FRQ¿UPHGVHOHFWLYHORFDOLVDWLRQRI/*5LQ=*781(/VWDLQLQJVKRZHG
DKLJKUDWHRIDSRSWRVLVLQWKH=*,QERWKSULPDU\KXPDQDGUHQDODQG+5
DGUHQRFRUWLFDOFHOOV5632FDXVHGGRVHUHODWHGLQKLELWLRQRIDOGRVWHURQHVHFUH
WLRQ )LJ 6LOHQFLQJ/*5LQFUHDVHGDOGRVWHURQHSURGXFWLRQ
Design and method: 7RWDOWHVWRVWHURQH 77 OHYHOVZHUHPHDVXUHGLQPHQ
ZLWKQRHYLGHQFHRIFOLQLFDODWKHURVFOHURVLV&DURWLGIHPRUDO3XOVH:DYH9HORF
LW\ 3:9FI ZDVPHDVXUHGDVDQLQGH[RIDRUWLFVWLIIQHVV
Results: ,QPXOWLYDULDWHDQDO\VLV3:9FIZDVLQYHUVHO\FRUUHODWHGWR77DIWHU
DGMXVWPHQWIRUFRQIRXQGHUV E 3 ,Q\RXQJHUFDWHJRULHV \UVDQG\UV SDWLHQWVZLWK7'KDGKLJKHUEORRGSUHVVXUHDGMXVWHG3:9F
I 3 DQG 3 UHVSHFWLYHO\ FRPSDUHG WR VXEMHFWV ZLWK QRUPDO 77
ZKHUHDV LQ ROGHU DJH FDWHJRULHV 3:9FI EHWZHHQ7' SDWLHQWV DQG PHQ ZLWK
QRUPDO77GLGQRWGLIIHU OHIWSORW )XUWKHUPRUHLQPHQZLWKDKLJKHUPHDQSUHVVXUH PP+JDQG!
PP+J SDWLHQWV ZLWK 7' KDG KLJKHU DJHDGMXVWHG 3:9FI 3 FRP
SDUHG WR VXEMHFWV ZLWK QRUPDO 77 ZKHUHDV LQ PHQ ZLWK ORZHU PHDQ SUHVVXUH
OHYHO7'SDWLHQWVDQGPHQZLWKQRUPDOKDGFRPSDUDEOH3:9FIYDOXHV ULJKW
plot).
Conclusions: 77 OHYHOV DUH LQGHSHQGHQWO\ DVVRFLDWHG ZLWK DRUWLF VWLIIHQLQJ
7KHHIIHFWRIORZWHVWRVWHURQHFRQFHQWUDWLRQRQDRUWLFVWLIIQHVVLVHPSKDVL]HGLQ
\RXQJPHQDQGVXEMHFWVZLWKKLJKHUEORRGSUHVVXUHOHYHO7KHVH¿QGLQJVXQGHU
OLQHWKHLPSRUWDQWUROHRIWHVWRVWHURQHDVDPDUNHURIDUWHULDOGDPDJH
7D.09
THE OVARIAN CYCLE AS A SOURCE OF VARIABILITY
IN THE SCREENING FOR HYPERALDOSTERONISM
AND IN THE ASSESSMENT OF INSULIN RESISTANCE
IN HYPERTENSIVE WOMEN IN FERTILE AGE
.&KDW]LDQDJQRVWRX1, S. Ghione 1,2, E. Fommei . 1 Fondazione Toscana
Gabriele Monasterio, Pisa, ITALY, 2 Institute of Clinical Physiology, CNR,
Pisa, ITALY, 3 Dept. of Clinical and Experimental Medicine, University of Pisa,
Pisa, ITALY
Objective: :HUHSRUWHG )RPPHL-+XP+\SHUWHQV WKDWLQORZ
UHQLQK\SHUWHQVLYHZRPHQWKHLQFUHPHQWRISODVPDDOGRVWHURQHWKDWRFFXUVLQ
WKHOXWHDO / FRPSDUHGWRWKHIROOLFXODU ) SKDVHPDUNHGO\LQFUHDVHVWKHSRVL
WLYLW\IRUVXVSHFWHGSULPDU\K\SHUDOGRVWHURQLVPLQWKHVDPHSDWLHQWVDQGIRUWKH
VDPHFULWHULDWKHSRVLWLYLW\YDULHGIURP ) DQGIURP / :H
KHUHUHSRUWWKHSUHOLPLQDU\UHVXOWVRIDQRQJRLQJVWXG\RQ XSWRQRZ ZRPHQ
HYDOXDWHGEHFDXVHRIDUWHULDOK\SHUWHQVLRQ6LQFHLWKDVEHHQUHSRUWHGWKDWDOGR
VWHURQLVPLVDVVRFLDWHGWRLQVXOLQUHVLVWDQFH ,5 *DUJ-&OLQ(QGRFULQRO0HWDE
DQGWKDW,5VOLJKWO\EXWVLJQL¿FDQWO\LQFUHDVHVLQWKH/SKDVH
LQQRUPRWHQVLYHZRPHQ <HXQJ-&OLQ(QGRFULQRO0HWDE ZH
KDYHDOVRDQDO\]HGWKH+20$,5 JOLF[LQV LQGH[
Conclusions: /*5 LV WKH PRVW =*VHOHFWLYH JHQH LQ KXPDQ DGUHQDO ZKRVH
DFWLYDWLRQE\5632PD\EHWKHGULYHUWRKLJK=*FHOOWXUQRYHU:HSRVWXODWH
WKDWLQUHVSRQVHWRW\SLFDOO\KLJKVDOWLQWDNHWKHUROHRIXSUHJXODWHG=*JHQHV
LQKXPDQVLVWRLQKLELWDOGRVWHURQHSURGXFWLRQLQSDUWWKURXJKDSRSWRVLVRUPL
JUDWLRQ+LJK=*FHOOWXUQRYHUZRXOGWKHQFRQIHUDVHOHFWLYHDGYDQWDJHWRFHOOV
ZLWKFRQVWLWXWLYHDOGRVWHURQHSURGXFWLRQHJIROORZLQJVRPDWLFPXWDWLRQRYHU
FHOOVSURJUDPPHGWRGLYLGHDQGGLH7KLVPD\H[SODLQWKHVPDOOVL]HDQGKLJK
IUHTXHQF\RI$3$VDULVLQJLQ=*
7D.08
TESTOSTERONE DEFICIENCY: A DETERMINANT OF
AORTIC STIFFNESS IN MEN
1,RDNHLPLGLV&9ODFKRSRXORV$$JJHOLV'7HUHQWHV3ULQW]LRVP. Pietri,
0$EGHOUDVRXO,*RXUJRXOL,$QGURXWVRV.$]QDRXULGLV&6WHIDQDGLV.
1st Department of Cardiology, Athens, GREECE
Objective: 7HVWRVWHURQHGH¿FLHQF\ 7' DQGLQFUHDVHGDRUWLFVWLIIQHVVDUHSUH
Design and method: $OOPHDVXUHVZHUHGRQHLQWKHVXSLQHSRVLWLRQDWWKHWK
) DQGQG / GD\RIWKHRYDULDQF\FOHZLWKRXWK\SRWHQVLYHWKHUDS\RUZLWK
GR[D]RVLQPJSHUGD\$OOZRPHQUHSRUWHGDUHJXODUF\FOHDJH“
\HDUV%0,“ NJP
Results:
3ODVPD SURJHVWHURQH 35 FRUUHODWHG SRVLWLYHO\ ZLWK SODVPD DOGRVWHURQH
S LQVXOLQ S DQG +20$,5 S 0XOWLSOH UHJUHVVLRQ
DQDO\VLVGHPRQVWUDWHGWKDW35EXWQRWDOGRVWHURQHDQG%0,ZHUHVWURQJDQG
VLJQL¿FDQW SRVLWLYH LQGHSHQGHQW SUHGLFWRUV RI SODVPD LQVXOLQ DQG +20$,5
XQLYDULDWH DQDO\VLV LQVXOLQ YV 35 S YV %0, S +2
0$,5 YV 35 S YV %0, S PXOWLYDULDWH DQDO\VLV LQVXOLQ
YV35 S %0, S +20$,5YV35 S %0,
S Conclusions: 7KHVH GDWD LQ K\SHUWHQVLYH ZRPHQ FRQ¿UP WKDW SODVPD DOGRV
WHURQHPD\JUHDWO\LQFUHDVHGXULQJWKHRYDULDQF\FOHXQGHUSURJHVWHURQHVWLP
e105
Journal of Hypertension Volume 32, e-Supplement 1, 2014
XODWLRQ DQG DOVR VXJJHVW WKDW SURJHVWHURQH PD\ LQFUHDVH LQVXOLQ UHVLVWDQFH WR
DJUHDWHUH[WHQWWKDQLQQRUPRWHQVLYHZRPHQ 7KHRYDULDQF\FOHLVWKXVD
VRXUFHRIYDULDELOLW\RISODVPDDOGRVWHURQHDQGRILQVXOLQUHVLVWDQFHLQK\SHUWHQ
VLYHZRPHQLQIHUWLOHDJHZLWKSRWHQWLDOUHOHYDQFHLQWKHGLDJQRVWLFZRUNXSDQG
LQHQGRFULQRPHWDEROLFSDWKRSK\VLRORJ\RIK\SHUWHQVLRQ
7D.10
GENETIC SPECTRUM AND CLINICAL CORRELATES
OF SOMATIC MUTATIONS IN ALDOSTERONEPRODUCING ADENOMA
))HUQDQGHV5RVD , 7$:LOOLDPV , F. Beuschlein , A. Riester ,
6%RXONURXQ1,2, S. Monticone , L. Amar , T. Meatchi , F. Mantero ,
04XLQNOHU, F. Fallo , B. Allolio , ;-HXQHPDLWUH, P. Mulatero ,
05HLQFNH5, 0=HQQDUR. 1 INSERM, UMRS 970, Paris Cardiovascular
Research Center, Paris, FRANCE, 2 University Paris Descartes, Paris Cité
Sorbonne, Faculty of Medicine, Paris, FRANCE, 3 Assistance Publique,
Hôpitaux de Paris, Hôpital Européen Georges Pompidou, Paris, FRANCE,
4
Division of Internal Medicine and Hypertension, Department of Medicine
and Experimental Oncology, University of Turin, Turin, ITALY, 5 Medizinische
Klinik Innenstadt, Ludwig Maximilians University, Munich, GERMANY,
6
Endocrine Unit, Dept. of Medical and Surgical Sciences, University of Padua,
Padua, ITALY, 7 Clinical Endocrinology, Campus Mitte, University Hospital
Charité, Berlin, GERMANY, 8 Dept. of Medicine, University of Padua, Padua,
ITALY, 9 Department of Medicine I, Endocrine and Diabetes Unit, University
Hospital Würzburg, Wurzburg, GERMANY
5
5
Objective: 3ULPDU\DOGRVWHURQLVP 3$ LVWKHPRVWFRPPRQIRUPRIVHFRQGDU\
K\SHUWHQVLRQ6RPDWLFPXWDWLRQVLQWKH.&1-$73$$73%DQG&$&
1$'JHQHVKDYHUHFHQWO\EHHQGHVFULEHGLQDOGRVWHURQHSURGXFLQJDGHQRPDV
$3$ 7KHDLPRIWKLVVWXG\ZDVWRLQYHVWLJDWHWKHSUHYDOHQFHRIVRPDWLFPXWD
WLRQVLQWKHVHJHQHVLQXQVHOHFWHGSDWLHQWVZLWK$3$DQGWRDQDO\]HFOLQLFDODQG
ELRFKHPLFDOFRUUHODWHVRIWKHPXWDWLRQVWDWXV
Design and method: 6HTXHQFLQJRIWKH.&1-$73$$73%DQG&$&
1$'ZDVSHUIRUPHGRQVRPDWLF'1$RISDWLHQWVZLWK$3$ Q FROOHFWHG
WKURXJKWKH(16#7 (XURSHDQ1HWZRUNIRUWKH6WXG\RI$GUHQDO7XPRUV QHW
ZRUN&RUUHODWLRQVZLWKFOLQLFDODQGELRFKHPLFDOSDUDPHWHUVZHUH¿UVWDQDO\]HG
LQDVXEVHWRISDWLHQWVIURPDVLQJOHFHQWHUDQGWKHQUHSOLFDWHGLQWZRDG
GLWLRQDOFHQWHUV
Results: 6RPDWLFKHWHUR]\JRXV.&1-PXWDWLRQV S*O\$UJ3/HX$UJ
S7US$UJ DQG S7KU$OD ZHUH IRXQG LQ RI RI $3$
:H IRXQG RI RI VRPDWLF $73$ PXWDWLRQV S*O\$UJ
S/HX$UJ S3KHB/HXGHO DQG S9DOJO\ DQG RI RI $73% PXWDWLRQV S9DOB/HXGHO RU S/HXB9DOGHO $O
UHDG\ UHSRUWHG VRPDWLF &$&1$' PXWDWLRQV S9DO$VS S*O\$UJ
S3KH/HXS,OH0HWS3UR$UJS9DO0HWRUS0HW,OH DQG
DOVRQRYHO&$&1$'PXWDWLRQV S6HU/HXS/HX3URS7\U&\V
S,OH3KH S9DO$VS S/\V$VQ S$OD,OH S$OD9DO DQG
S9DO3KH ZHUHLGHQWL¿HGLQRI $3$$VDOUHDG\REVHUYHG
.&1-PXWDWLRQVZHUHVLJQL¿FDQWO\PRUHIUHTXHQWLQIHPDOHV 3 WKDQ
LQPDOHVDQGLQ\RXQJHUSDWLHQWV “\V3 ZKHQFRPSDUHGWRFDU
ULHUVRIRWKHUPXWDWLRQVRUQRQFDUULHUV&$&1$'PXWDWLRQVZHUHDVVRFLDWHG
WRVPDOOHUDGHQRPDV S ZKHUHDV$73DVHPXWDWLRQVZHUHDVVRFLDWHGWR
KLJKHUSUHRSHUDWLYHSODVPDDOGRVWHURQHOHYHOV S 7KHUHZDVQRGLIIHU
HQFHLQWKHFHOOXODUFRPSRVLWLRQRI$3$QRULQ&<3%.&1-$73$RU
$73%H[SUHVVLRQLQ$3$DFURVVJHQRW\SHVññ
Conclusions: ,QFRQFOXVLRQLQWKH(16#7FRKRUWWKHSUHYDOHQFHRIVRPDWLF
PXWDWLRQVLQ$3$LV7KH\DUHSUHGRPLQDQWO\IRXQGLQWKH.&1-JHQHLQ
\RXQJZRPHQ7KHPXWDWLRQVWDWXVRI$3$LVDVVRFLDWHGWRVSHFL¿FFOLQLFDODQG
ELRFKHPLFDOFKDUDFWHULVWLFVRI3$
7D.11
AMBULATORY BLOOD PRESSURE MONITORING
AND KYNURENIC ACID IN FEMALE PATIENTS WITH
PRIMARY HYPERPARATHYROIDISM
$7RPDVFKLW]1, 19HUKH\HQ2, 0*DNVFK, 0*UEOHU2, -:HW]HO2,
(%HO\DYVNL\2, C. Colantonio 2, (.UDLJKHU.UDLQHU2, :0lU],
T. Grammer , $0HLQLW]HU 5, -5XV0DFKDQ1, $)DKUOHLWQHU3DPPHU,
%3LHVNH2, 63LO]. 1 Specialist Clinic of Rehabilitation PV Bad Aussee, Bad
Aussee, AUSTRIA, 2 Medical University of Graz, Department of Cardiology,
Graz, AUSTRIA, 3 Medical University of Graz, Department of Internal
Medicine, Division of Endocrinology, Graz, AUSTRIA, 4 Synlab Academy,
Synlab Services LLC, Mannheim, GERMANY, 5 Medical University of Graz,
Clinical Institute of Medical and Chemical Laboratory Diagnostics, Graz,
AUSTRIA, 6 Mannheim Institute of Public Health, Ruperto Carola University
Heidelberg, Medical Faculty Mannheim, Mannheim, GERMANY, 7 Department
of Epidemiology and Biostatistics, EMGO Institute for Health and Care
Research, VU University Medical Centre, Amsterdam, NETHERLANDS
Objective: .\QXUHQLFDFLG .<1$ LVDQHXURWR[LFHQGSURGXFWRIWU\SWRSKDQ
FDWDEROLVP.<1$LVLQFUHDVLQJO\VXJJHVWHGWRFRQWULEXWHWRFRJQLWLYHLPSDLU
PHQWREVHUYHGLQGHSUHVVLRQDQGK\SHUWHQVLRQ7KHUHODWLRQVKLSEHWZHHQFLUFX
ODWLQJ.<1$DQGDPEXODWRU\EORRGSUHVVXUH $%3 LQIHPDOHSDWLHQWVZLWKSUL
PDU\K\SHUSDUDWK\URLGLVP S+37 ZKLFKLVUHODWHGWRLPSDLUHGPHQWDOKHDOWK
VWDWXVLVKRZHYHUXQNQRZQ
Design and method: :HDLPHGWRHYDOXDWHWKHFURVVVHFWLRQDOUHODWLRQVKLSEH
WZHHQ.<1$DQGKRXU$%3LQQRQRSHUDWHGIHPDOHS+37SDWLHQWVHQUROOHG
LQWKH(IIHFWVRI(SOHUHQRQHRQ3DUDWK\URLG+RUPRQH/HYHOVLQ3DWLHQWVZLWK
3ULPDU\ +\SHUSDUDWK\URLGLVP WULDO (3$7+ $W EDVHOLQH YLWDPLQ ' VXI¿
FLHQW K\GUR[\YLWDPLQ'!QJP/ IHPDOHSDWLHQWVZLWKS+37XQGHU
ZHQWKRXU$%3PRQLWRULQJDQGPHDVXUHPHQWRI.<1$LQVHUXP
Results: 3+37 SDWLHQWV PHDQ“6' RU PHGLDQ>,45@ PHDQ DJH “ \ KDGPLOGGLVHDVHZLWKWRWDOVHUXPFDOFLXPRI“PPRO/DQG37+RI
>@SJPO0HDQGD\WLPHDQGQLJKWWLPHKRXUV\VWROLF 6%3 DQGGLDVWROLF '%3 SUHVVXUHRIWKHVWXG\SRSXODWLRQZHUH““
“DQG“““PP+JUHVSHFWLYHO\
0XOWLSOH UHJUHVVLRQ DQDO\VHV LQFOXGLQJ DJH VH[ ERG\ PDVV LQGH[ HVWLPDWHG
*)5 &.'(3, +E$F17S%13VPRNLQJVWDWXV37+ 2+ 'WRWDOVH
UXPFDOFLXPDVSRWHQWLDOFRQIRXQGHUVUHYHDOHG.<1$DVVWURQJHVWSUHGLFWRURI
PHDQKRXU6%3 5EHWDFRHI¿FLHQWȕ S DQGGD\WLPH
6%3 5ȕ S $ERUGHUOLQHVLJQL¿FDQWDVVRFLDWLRQZDVRE
VHUYHGEHWZHHQ.<1$DQGQLJKWWLPH6%3 5ȕ S :HGLG
QRWGHWHFWDVLJQL¿FDQWDVVRFLDWLRQEHWZHHQ'%3DQG.<1$
Conclusions: 7KLVLQYHVWLJDWLRQVXJJHVWVDVWURQJSRVLWLYHDVVRFLDWLRQEHWZHHQ
.<1$DQGKRXUDPEXODWRU\6%3LQIHPDOHS+37SDWLHQWVSHUKDSVPHGLDWHG
WKURXJKQHXURWR[LFPHFKDQLVPV
7D.12
NEW GERM-LINE MUTATIONS AND A RARE
CODING SINGLE NUCLEOTIDE POLYMORPHISM
WITHIN KCNJ5 IN “APPARENTLY SPORADIC”
PRIMARY ALDOSTERONISM: A POSSIBLE ROLE IN
PATHOGENESIS
6;X1, 00XUWK\2, G. Massimo 2, 5*RUGRQ1, M. Stowasser 1,
.2¶6KDXJKQHVV\2. 1 Endocrine Hypertension Research Centre, Univ.
Queensland School of Medicine, Greenslopes And Princess Alexandra
Hospitals, Brisbane, AUSTRALIA, 2 Clinical Pharmacology Unit, Department
of Medicine, University of Cambridge, Addenbrookes Hospital, Cambridge,
UNITED KINGDOM
Objective: 3ULPDU\ DOGRVWHURQLVP 3$ LV WKH FRPPRQHVW VSHFL¿FDOO\ WUHDWDEOH
FDXVHRIK\SHUWHQVLRQ7KH.&1-SRWDVVLXPFKDQQHOLVRIJUHDWLQWHUHVWEHFDXVH
ERWKJHUPOLQHPXWDWLRQV )DPLOLDO+\SHUDOGRVWHURQLVP7\SH DQGVRPDWLFPX
WDWLRQVZLWKLQDOGRVWHURQHSURGXFLQJDGHQRPDVKDYHUHFHQWO\EHHQGHVFULEHG3$
XVXDOO\DSSHDUVWREHVSRUDGLFUDWKHUWKDQIDPLOLDO7KLVVWXG\DLPVWRVHHNJHUPOLQH
YDULDQWVZKLFKPLJKWFRQWULEXWHWRWKHSDWKRSK\VLRORJ\RIWKHFRPPRQVSRUDGLF3$
Design and method: 7KHFRGLQJVHTXHQFHDQGÀDQNLQJUHJLRQVRI.&1-ZHUH
UHVHTXHQFHG LQ &DXFDVLDQ VXEMHFWV ZLWK ³DSSDUHQWO\ VSRUDGLF´ 3$ )XQF
WLRQDOFKDQJHLQPXWDWHGFKDQQHOVZDVVWXGLHGLQYLWURE\H[SUHVVLQJWKHPLQ
;HQRSXVRRF\WHVDQGKXPDQDGUHQRFRUWLFDOFDUFLQRPDFHOOV5HVWLQJPHPEUDQH
SRWHQWLDOVDQGFXUUHQWYROWDJH ,9 SORWVIRUFODPSHG;HQRSXVRRF\WHVH[SUHVV
LQJHLWKHUZLOGW\SH :7 RUPXWDQW.&1-FKDQQHOVZHUHUHFRUGHG%DVDODQG
DQJLRWHQVLQ,,LQGXFHGDOGRVWHURQHUHOHDVHIURP+5FHOOVWUDQVLHQWO\WUDQV
IHFWHGZLWKHLWKHUWKHFRQWURO HPSW\*)3YHFWRU RURQHRIWKHPXWDQW.&1-
FKDQQHOVZDVREVHUYHG&OLQLFDOIHDWXUHVRISDWLHQWVDIIHFWHGDQGXQDIIHFWHGE\
PXWDWLRQVZHUHFRPSDUHG
Results: 7KUHH³QHZ´KHWHUR]\JRXVPLVVHQVHPXWDWLRQV 5+(.DQG
*5 ZHUHLGHQWL¿HGDQGSDWLHQWV RIWKHFRKRUW ZHUHFDUULHUVIRU
WKHUDUHQRQV\QRQ\PRXVVLQJOHQXFOHRWLGHSRO\PRUSKLVP 613 UV
ZLWK(4VXEVWLWXWLRQRI.&1-2QH[SUHVVLRQRIWKHFKDQQHOVLQ;HQR
SXVRRF\WHVDQGKXPDQDGUHQDO+5FHOOVWKH5+(.DQG(4
VXEVWLWXWLRQVZHUHIXQFWLRQDOEXWWKH*5PXWDWLRQZDVLQGLVWLQJXLVKDEOH
IURP:7$OWKRXJKWKHIXQFWLRQDOVXEVWLWXWLRQVDUHUHPRWHIURPWKHVHOHFWLYLW\
¿OWHUWKH\DIIHFWHG LQZDUGUHFWL¿FDWLRQ DELOLW\RIWKH.&1-FKDQQHOV
WR FRQGXFW 1D FXUUHQWV DQG $7,,LQGXFHG DOGRVWHURQH UHOHDVH IURP WKH
+5FHOOOLQH&OLQLFDOO\SDWLHQWVFDUU\LQJUVZHUHDVVRFLDWHGZLWK
OHVVÀRULG3$
Conclusions: 7KHVHGDWDVXJJHVWWKDWJHUPOLQHYDULDWLRQVLQWKH.&1-JHQH
SOD\DUROHLQWKHFRPPRQVSRUDGLFDVZHOODVLQWKHUDUHV\QGURPLFIRUPVRI3$
)XUWKHUVWXGLHVDUHQHHGHGWRFRQ¿UPWKHVH¿QGLQJVDQGH[SORUHUROHVRIRWKHU
JHUPOLQHYDULDQWVLQ.&1-LQYDULRXVIRUPVRI3$
Abstracts
e106
ORAL SESSION
ORAL SESSION 8A
LIFESTYLE CHANGES AND SPORT
8A.01
FIVE RANDOM CASUAL URINES ARE SUFFICIENT
TO ESTIMATE DAILY URINARY SODIUM/POTASSIUM
RATIO IN HYPERTENSIVES
T. Iwahori 1, H. Ueshima 2, S. Torii 2, Y. Saito 2, T. Ohkubo 2, K. Miura 2.
Omron Healthcare Co., Ltd., Muko, JAPAN, 2 Shiga University of Medical
Science, Otsu, JAPAN
1
Objective: High dietary sodium and low dietary potassium intakes are associated with adverse blood pressure (BP) levels and excess risks of cardiovascular
diseases. For effective dietary improvement, a convenient, cheap and appropriate monitoring system for supporting salt reduction and potassium increase is
needed. Recently, we found mean sodium-to-potassium ratio of casual urine is
useful for estimating 24-hr urinary sodium-to-potassium ratio in participants,
mostly normotensives. Our aim was to clarify the optimal number and type of
casual-urine required to estimate an individual’s urinary sodium-to-potassium
ratio in individuals with hypertension or high-normal BP.
Design and method: A total of 21 participants with hypertension or with highnormal BP (systolic/diastolic BP >=130/80 mmHg), 9 with anti-hypertensive
medication and 12 without anti-hypertensive medication, aged 40 to 69 were
recruited from volunteers. Sodium-to-potassium ratio in each casual urine and
GD\ KU XULQH VDPSOHV ZHUH PHDVXUHG 3HDUVRQ¶V FRUUHODWLRQ FRHI¿FLHQWV
and agreement quality analysis by the Bland-Altman method were computed for
sodium-to-potassium ratio of casual urine against 7-day 24-hr urinary sodiumto-potassium ratio.
Results: Overall mean value of 24-hr sodium-to-potassium ratio was 3.72,
whereas Na excretion and K excretion were 202 mmol/24h and 57 mmol/24h,
respectively. 5-days of random casual urine sodium-to-potassium ratio was
strongly correlated with 7-day 24-hr urinary sodium-to-potassium ratio in both
participant with and without antihypertensive-medication (r=0.88 and r=0.86,
UHVSHFWLYHO\ 7KHELDVHVWLPDWHZLWKWKH%ODQG$OWPDQPHWKRGGH¿QHGDVWKH
difference between sodium-to-potassium ratio of 7-day 24-hr urine and 5-days
of random casual-urine were small in both participant with and without medication (-0.23 and 0.15). The mean difference and the limits of agreement (mean 2
standard-deviation) estimate between sodium-to-potassium ratio of 7-day 24-hr
XULQH DQG ¿YH UDQGRP FDVXDO XULQH VSHFLPHQV ZHUH VPDOO LQ ERWK SDUWLFLSDQW
with and without medication (2.15 and 2.21), and also similar to that of 2-day
24-hr urinary sodium-to-potassium ratio in both participant with and without
medication (2.98 and 2.23).
Conclusions: Our new method using mean sodium-to-potassium ratio of 5-days
of random casual urine was a good substitute for 2-day 24-hr urinary sodium-topotassium ratio in individuals with hypertension or high-normal BP, irrespective
of the use of antihypertensive-medication.
8A.02
PERSONALIZED WORKPLACE WALKING PROGRAM
IMPROVES BLOOD GLUCOSE LEVELS
P. Veerabhadrappa 1, H. Weiss 1, S. Bhat 2, R. Alweis 2. 1 Shippensburg University,
Shippensburg, PA, USA, 2 Reading Health System, Reading, PA, USA
Objective: The extent to which short-term changes in physical activity pattern
can modify the blood glucose levels in healthy individuals is unknown. We investigated the effects of workplace ambulatory activity assessed by pedometer
on blood glucose levels among healthy University employees.
Design and method: Participants were recruited via campus-wide email sent
to all employees. A health history questionnaire and physical activity questionnaire was used to exclude participants with any self-reported chronic illnesses,
including any form of cardiovascular disease, diabetes, lung, liver or renal disease. Forty-one (11Males/30Females, 50±6yrs) apparently healthy but sedentary
non-smokers were included. Omron HJ-323U (USB pedometer with web-based
solution) setting was personalized based on the participant’s body mass index
and walking stride length. Maintaining their regular diet, participants completed wellness walks around campus (step-goal: 10,000-steps/day, 5-days/week,
ZHHNV ([HUFLVH UHPLQGHUV ZLWK ZHHNO\ PRWLYDWLRQDO ÀLHUV ZHUH VHQW YLD
emails. Web-based walking data were retrieved at the end of each week. Fasting
EORRGJOXFRVHDQGOLSLGSUR¿OHZHUHDQDO\VHGXVLQJ&KROHVWHFK/';DQDO\]HU
before and after the physical activity intervention.
Results: There was 8.3% increase in step-count to 10129 steps/day at the
HQG RI ZHHN LQWHUYHQWLRQ %HIRUH YV SRVWLQWHUYHQWLRQ 0HDQ“6' IRU WRtal cholesterol (200.3±40.2 vs. 191.3±41.0mg/dl; p=0.01), blood glucose
(98.9±9.0 vs. 96.3±9.1g/dl; p=0.04) and low density lipoprotein (124.6±39.8 vs.
“PJGO S ZHUH VWDWLVWLFDOO\ VLJQL¿FDQW &KDQJH LQ EORRG JOXFRVHZDVDVVRFLDWHGZLWKFKDQJHLQWRWDOFKROHVWHURO U S &KDQJHLQ
blood glucose was not associated with change in BMI. There was a statistically
VLJQL¿FDQWGHFUHDVHLQWKHUDWHRISUHGLDEHWLFV; 1 S
post intervention from 46.3% (19/41) to 36.6% (15/41).
Conclusions: In our preliminary study, four-week walking intervention modestly reduced blood glucose by 2.6%. There was a ~10% reduction in the number
of participants with prediabetes. This suggests that short-term physical activity
improves blood glucose levels and reverses the prediabetes risk among University employees independent of changes in BMI. It is incumbent that healthcare
develop innovative worksite physical activity and wellness programs to improve
employee health and wellness. A pedometer monitored walking program maybe
one such way how workplace wellness could curb healthcare costs.
8A.03
BLOOD PRESSURE RECOVERY AFTER
MAXIMAL EXERCISE AT HIGH ALTITUDE IN MILD
HYPERTENSIVE SUBJECTS AND EFFECTS OF
ANTIHYPERTENSIVE COMBINATION TREATMENT
A. Faini 1, 6&DUDYLWD1,2, 0/DQJ1,3, J. Macarlupu 4, &$Q]D4, E. Salvioni 5,
M. Revera 1, A. Giuliano 1,2, F. Gregorini 1, J. Rossi 1, &/RPEDUGL1,
G. Bilo 1, F. Villafuerte 4, G. Mancia 1, P. Agostoni 5,6,7, G. Parati 1,2. 1 Dept.
of Cardiovascular, Neural and Metabolic Sciences, S. Luca Hospital, IRCCS
Istituto Auxologico Italiano, Milan, ITALY, 2 Dept. of Health Sciences,
University of Milano-Bicocca, Milan, ITALY, 3 Dept. of Kinesiology,
Universidad de Antofagasta, Antofagasta, CHILE, 4 Laboratorio de Fisiologia
Comparada, Universidad Cayetano Heredia, Lima, PERU, 5 Centro
Cardiologico Monzino, IRCCS, Milan, ITALY, 6 Department of Clinical
Sciences and Community Health, University of Milan, Milan, ITALY,
7
Division of Pulmonary and Critical Care and Medicine, Department of
Medicine, University of Washington, Seattle, WA, USA
Objective: Exposure to high-altitude(HA) hypoxia induces an increase in resting and ambulatory blood pressures(BP) in humans. No data are available on the
behavior of systolic BP (SBP) both at peak exercise and during recovery from
exercise in hypertensive subjects acutely exposed to HA.
Design and method: PLOGK\SHUWHQVLYHVXEMHFWVIURP+,*+&$5($1'(6
study (age 57.5±8.9; 29M/26F) performed an incremental cardiopulmonary exHUFLVHWHVWWRH[KDXVWLRQLQFRQGLWLRQVDWVHDOHYHO 6/ RIIWUHDWPHQW 6/EDV DQGZHHNVDIWHUGRXEOHEOLQGUDQGRPL]DWLRQ 6/W[ WRWHOPLVDUWDQ 7 1LIHGLSLQH
1 *,76 Q RUSODFHER 3/Q DQGRQWKHVWIXOOGD\RISHUPDQHQFHDW
3260m a.s.l.(Huancayo-Perù) under randomized treatment. For all of them SBP
values were available at rest, at peak exercise, and at 1-3-5-7-10 min of recovery.
BP was measured with the auscultatory technique always by the same operator.
Results: $W6/EDVWKHUHZHUHQRGLIIHUHQFHVDPRQJWKHWZRWUHDWPHQWJURXSV
+$H[SRVXUHLQFUHDVHG6%3DWUHVWLQERWKJURXSVDOWKRXJK6%3ZDVVLJQL¿FDQWO\ORZHULQ71JURXS$WSHDNH[HUFLVH6%3ZDVVLPLODUEHWZHHQ6/W[DQG
HA, but peak exercise at HA corresponded to a 13% lower (p<0.001) oxygen
consumption. T/N-GITS reduced SBP not only at rest, but also at peak exercise
DQGGXULQJWKHZKROHUHFRYHU\SHULRGERWKDW6/W[DQGDW+$
)RU WKH ¿UVW PLQXWHV LPPHGLDWHO\ DIWHU H[HUFLVH 6%3 ZDV VLPLODU EHWZHHQ
6/W[DQG+$HLWKHURQ71*,76RURQ3/&RQYHUVHO\DWWKHWKWKDQGWK
PLQXWHVRIUHFRYHU\6%3ZDVKLJKHUDW+$WKDQDW6/W[HLWKHURQ71*,76RU
RQ3/ VHH¿JXUHRQWKHIROORZLQJSDJH M
O
N
D
A
Y
O
R
A
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e107
Journal of Hypertension Volume 32, e-Supplement 1, 2014
effective in M and F as shown in the reduced prevalence of hypertension and
diabetes. Improvements of nutritional markers in 24-hour urine such as salt,
1D.DQGLVRÀDYRQHVZHUHPRUHPDUNHGLQ)DQGUHODWHGZLWKWKHLUVLJQL¿FDQW
risk reduction of hypertension, dyslipidemia and diabetes.
8A.05
POST-EXERCISE THROMBOTIC AND FIBRINOLYTIC
CHANGES IN PATIENTS WITH ESSENTIAL
HYPERTENSION: THE EFFECT OF TREATMENT WITH
AN ANGIOTENSIN II RECEPTOR BLOCKER
G. Triantafyllou 1, E. Gkaliagkousi 2, E. Gavriilaki 1, B. Nikolaidou 2,
)&KDW]RSRXORX3, P. Anyfanti 2, A. Triantafyllou 1, 6'RXPD1. 1 Aristotle
University of Thessaloniki, 3rd Department of Internal Medicine, Papageorgiou
Hospital, Thessaloniki, GREECE, 2 Aristotle University of Thessaloniki, 2nd
Propedeutic Department of Internal Medicine, Thessaloniki, GREECE, 3
Aristotle University of Thessaloniki, Medical School, Thessaloniki, GREECE
Objective: Essential hypertension (EH) is characterized by increased thromERWLF WHQGHQF\ DQG LPSDLUHG ¿EULQRO\WLF DFWLYLW\ +RZHYHU H[HUFLVHLQGXFHG
FKDQJHV LQ FRDJXODWLRQ DQG ¿EULQRO\VLV KDYH QRW \HW EHHQ FODUL¿HG7KXV WKH
REMHFWLYHVRIRXUVWXG\ZHUH¿UVWO\WRHVWLPDWHWKHHIIHFWRIDFXWHKLJKLQWHQVLW\
exercise on the levels of two of the most representative markers of coagulation
DQG¿EULQRO\VLV7$7DQG3$,LQVXEMHFWVZLWKXQWUHDWHG(+DVFRPSDUHGWR
normotensive individuals; and secondly to investigate the effects of treatment
with an Angiotensin II Receptor Blocker (ARB).
Conclusions: Our data show that, in hypertensive subjects:
LQVSLWHRIVLPLODUSHDN6%3EHWZHHQ6/DQG+$UHFRYHU\RI6%3WRZDUGV
resting values after maximal exercise is slower at HA, possibly due to an impairment of the autonomic cardiovascular regulation in hypoxic conditions leading
to persistently increased sympathetic activity;
71*,76HIIHFWLYHO\UHGXFHV6%3ERWKDW6/DQGDW+$QRWRQO\DWUHVWDQG
at peak exercise, but also throughout the whole recovery period.
7KHVH¿QGLQJVVKRXOGEHFRQVLGHUHGZKHQPDQDJLQJSK\VLFDOO\DFWLYHK\SHUWHQsive subjects planning an acute exposure to HA for leisure or work.
8A.04
TEN-YEAR CAMPAIGN FOR EATING SOY AND SEAFOOD RICH TRADITIONAL JAPANESE DIETS WITH
LESS SALT REDUCED CARDIOVASCULAR RISKS
IN HYOGO PREFECTURE, ONE TWENTIETH OF
JAPANESE POPULATION
Y. Yamori 1,2,3, S. Sagara 2, M. Mori 3, Y. Arai 1, H. Kobayashi 1, I. Hayashi 1,
S. Onishi 1, S. Nagata 1. 1 Hyogo Prefecture Health Promotion Association,
Kobe, JAPAN, 2 Research Institute for Production Development, Kyoto, JAPAN,
3
Institute for World Health Development, Mukogawa Womens University,
Nishinomiya, JAPAN
Objective: To test the health effect of soy and seafood-rich Japanese diets, regisWHUHGDV81(6&2¶VLQWDQJLEOHFXOWXUDOKHULWDJHZLWKOHVVVDOWE\SRSXODWLRQDSproach.
Design and method: Ten-year health promotion campaign for eating wellbalanced diets consisting of rice, soy, seafood and vegetables with less salt was
intensively carried out by 2000 health promoters educated every year since 2001
in Hyogo Prefecture, where were living 5.6 million people, 1/20th of Japanese
population. To the health examination for measuring body weight, height, blood
pressure and collecting fasting blood and 24-hour urine samples were randomly
UHFUXLWHGWRPDOHV 0 DQGIHPDOHV ) DJHGWKWRWKIRUWKH¿UVW
years and 500 in the 10th year.
Results: The distribution of daily urinary salt excretions sifted to the left with the
VLJQL¿FDQWUHGXFWLRQRIWKHPHDQV!JLQWKH¿UVW\HDUV&RQFRPLtantly the prevalence of mild hypertensions with 140 to 160 mmHg in systolic
VLJQL¿FDQWO\GHFUHDVHGIURPWR7KHHIIHFWRI\HDUKHDOWKSURPRWLRQ
campaign was evaluated by the reduction of cardiovascular risks, among which
hypertension (40.8 -> 23.2%**in M, 35.5 -> 11.7%*** in F) and diabetes (22.9
! LQ0! LQ) GHFUHDVHGVLJQL¿FDQWO\ S
7HQ\HDUVLJQL¿FDQWLPSURYHPHQWVZHUHQRWHGPRUHLQ)DVVKRZQ
LQWKHVLJQL¿FDQWFKDQJHVRIWKHPHDQVLQV\VWROLFGLDVWROLFEORRGSUHVVXUH ! ! PP+J WULJO\FHULGHV ! PJGO +'/
(62.8 -> 65.9*mg/dl), fasting blood glucoses (98.2 -> 93.2**mg/dl), urinary salt
H[FUHWLRQ ! JGD\ XULQDU\1D. ! DQGXULQDU\LVRÀDvones as the marker of soy intakes (13.8 -> 24.0**µmol/day).
Conclusions: Population approach to reduce cardiovascular risks was proven
Design and method: Study 1 consisted of consecutive patients with untreated
UHFHQWO\ GLDJQRVHG (+ 8+ DQG QR VLJQL¿FDQW FRPRUELGLWLHV DQG FRQVHFXtive age- and sex-matched normotensive (NT) individuals on a 2:1 ratio. UH
who received treatment were included in Study 2 and were followed-up after
a 3-month treatment period with an ARB (valsartan 160 mg). All participants
underwent a treadmill exercise test (according to the Bruce protocol) and 24hour ABPM. Thrombin-antithrombin (TAT) complexes and Human Plasminogen Activator Inhibitor-1 (PAI-1) were measured at baseline, immediately
after a treadmill exercise test and 30 minutes later.
Results: :HUHFUXLWHG8+DQG17LQGLYLGXDOVZLWKQRVLJQL¿FDQWGLIIHUHQFHV LQ EDVHOLQH FKDUDFWHULVWLFV RWKHU WKDQ RI¿FH DQG DPEXODWRU\ EORRG
SUHVVXUHOHYHOV,Q8+7$7DQG3$,OHYHOVZHUHVLJQL¿FDQWO\LQFUHDVHGLPmediately after peak exercise and decreased 30 minutes later, as compared to
EDVHOLQHOHYHOV$WDOOWLPHSRLQWV8+H[KLELWHGVLJQL¿FDQWO\KLJKHU7$7DQG
3$,OHYHOVFRPSDUHGWR171RVLJQL¿FDQWFKDQJHVRI7$7DQG3$,OHYHOV
ZHUHREVHUYHGLQ173RVWWUHDWPHQW7$7DQG3$,YDOXHVZHUHVLJQL¿FDQWO\
reduced at all time-points and were similar to those of the NT group.
e108
Journal of Hypertension Volume 32, e-Supplement 1, 2014
Conclusions: 7RRXUNQRZOHGJHWKLVLVWKH¿UVWVWXG\WRGRFXPHQWSUHDQG
SRVWWUHDWPHQW H[HUFLVHLQGXFHG FKDQJHV LQ FRDJXODWLRQ DQG ¿EULQRO\VLV LQ
EH. A 3-month treatment period with an ARB greatly improved the response
to exercise in hypertensive patients. Whether this effect depends purely on
BP lowering or on the pleiotropic effects of an ARB remains to be further
investigated.
8A.06
DETECTING SODIUM SENSITIVITY RISK FROM
AMBULATORY BLOOD PRESSURE MONITORING.
DATA FROM THE CROATIAN REGISTRY ON ABPM
(HRKMAT)
S. Karanovic 1, T. Zeljkovic Vrkic 1, 0/DJDQRYLF1, J. Josipovic 2, V. Premuzic 1,
I. Pecin 3, J. Kos 1, B. Bozic 4, M. Fistrek Prlic 1, M. Vrsalovic 5, /)RGRU1,
A. Vrdoljak 1, /6LPLFHYLF 6, ,9XNRYLF/HOD1, B. Jelakovic 1. 1 Department
for Nephrology, Hypertension, Dialysis and Transplantation, UHC Zagreb,
School of Medicine University of Zag, Zagreb, CROATIA, 2 Department for
Nephrology, UHC Sisters of Mercy, Zagreb, CROATIA, 3 Department for
Metabolic Diseases, UHC Zagreb, School of Medicine University of Zag,
Zagreb, CROATIA, 4 Department for Nephrology, UH Dubrava, Zagreb,
CROATIA, 5 Department for Cardiology, UHC Sisters of Mercy, Zagreb,
CROATIA, 6 Department for Laboratory Diagnostics UHC Zagreb, Zagreb,
CROATIA
Objective: High daily sodium intake is associated with various deteriorating
HIIHFWV RQ FDUGLRYDVFXODU &9 V\VWHP 6RGLXP VHQVLWLYLW\ 66 RI EORRG SUHVVXUH %3 LQFUHDVHV &9 DQG RYHUDOO PRUWDOLW\ 5HFHQWO\ HVWLPDWLRQ RI 66 ULVN
from the ABPM data in regular every-day conditions and habitual diet was proposed. Our aim was to analyse prevalence and characteristics of subjects with
high SS risk in cohort of subjects from our ABPM database.
Design and method: In this retrospective study we analysed data on 485
subjects(64.9% men). ABPM was performed on regular working day using
6SDFH/DEGHYLFH6XEMHFWVZHUHGLYLGHGLQWRFODVVHVRI66ORZULVNLIGLSSHUV
DQGDKKHDUWUDWH +5 ESP /66 KLJKULVNLIQRQGLSSHUVDQGDK
HR of >70 bpm (HSS); intermediate risk with the remaining combinations(dippers with HR>70 bpm or non-dippers with HR <= 70 bpm). Patients were clasVL¿HG DV ³GLSSHUV´ ZKHQ QRFWXUQDO PHDQ DUWHULDO SUHVVXUH IDOO ZDV ! DQG
ÄQRQGLSSHUV³RWKHUZLVH
Results: Prevalence of HSS subjects was 22.6% with no gender difference. We
failed to observe an increase in SS by ageing. No difference in age (48.5 (20-87)
vs.53(19-88);p>0.05) and eGFR (92.9± 9.4 vs.95.9±12; p>0.05) was observed
EHWZHHQ+66DQG/66VXEMHFWV+66VXEMHFWVKDGORZHU%0, vs.27.5(24.8-29.9);p=0.03) and waist circumference (89.5(78-104) vs.92(83 S WKDQ /66 ,QWHUHVWLQJO\ ZH IDLOHG WR GHWHUPLQH GLIIHUHQFH LQ
systolic BP (127.5(120-139)vs. 126(119-133);p=0,3171) and pulse pressure
YV S YDOXHVEHWZHHQ+66DQG/66+RZHYHUWKHUH
were more masked hypertension in HSS, and more white coat hypertension in
/66JURXSV Ȥ S Conclusions: Prevalence of HSS in this study was lower than expected probably our cohort was younger than others(33.8% were younger than 40 yr). HSS
subjects did not differ in age, kidney function and indices of arterial stiffness
IURPWKRVHZLWK/66ULVN,QWHUHVWLQJO\PDVNHGK\SHUWHQVLRQZDVPRUHSUHYDOHQWLQ+66DQGZKLWHFRDWK\SHUWHQVLRQLQ/66VXEMHFWV3URSRVHGPHWKRG
for SS estimation could be useful in everyday practice particularly when more
VSHFL¿FFXWRIIYDOXHVZRXOGEHGHWHUPLQHG5HWURVSHFWLYHDQDO\VHVRIH[LVWing database could provide interesting and valuable information. However,
in such analyses one should take into account characteristics of group and of
each subject.
8A.07
AWARENESS OF SALT RESTRICTION AND ACTUAL
SALT INTAKE IN TREATED HYPERTENSIVE PATIENTS
AT A HYPERTENSION CLINIC AND A GENERAL
CLINIC
Y. Ohta 1, K. Ohta 2, A. Ishizuka 1, S. Hayashi 1, M. Kishida 1, Y. Iwashima 1,
F. Yoshihara 1, S. Nakamura 1, Y. Kawano 1. 1 Division of Hypertension and
Nephrology, National Cerebral and Cardiovascular Center, Osaka, JAPAN,
2
Ohta Internal Medicine and Gastroenterology Clinic, Fukuoka, JAPAN
Objective: The amount of salt consumption is still high in Japan, although it
has been decreasing. The aim of this study is to investigate awareness of salt
restriction and actual salt intake in hypertensive patients at a hypertension
clinic and a general clinic.
Design and method: Subjects included 330 patients (mean age 69±12 years)
who were treated at a hypertension clinic and 200 patients (mean age 67±11
years) who were treated at a general clinic. We estimated 24-hour salt excretion using spot urine sample and checked the awareness of salt intake using
self-description questionnaire.
Results: 7KHUHZDVQRGLIIHUHQFHLQRI¿FHV\VWROLFEORRGSUHVVXUHEHWZHHQ
the two groups (130±16 vs. 129±16 mmHg). The number of antihypertensive drugs at the hypertension clinic was higher than that at the general
clinic (2.2±1.1 vs. 1.6±0.9, p<0.01). Urinary salt excretion at the hypertenVLRQ FOLQLF ZDV VLJQL¿FDQWO\ ORZHU WKDQ WKDW DW WKH JHQHUDO FOLQLF “
vs. 9.3±2.5 g/day, p<0.01). The rate of achievement of salt intake <6 g/day
was 15% at the hypertension clinic and 6% at the general clinic. The score
regarding the awareness of salt intake at the hypertension clinic was better than that at the general clinic (10±4 vs. 11±4, p<0.01). In patients with
excessive salt intake (>=10g/day), 28% of patients at the hypertensive clinic
and 23% at the general clinic thought that their salt intake was low.
Conclusions: Urinary salt excretion at a hypertensive clinic was lower than
that at a general clinic, however, the rate of achievement of salt intake <6 g/
day was still low and most patients could not comply with the guidelines.
The awareness of salt restriction in patients with excessive salt intake was
low. Repeated guidance and monitoring of urinary salt excretion may be
required for the achievement of salt restriction.
Abstracts
e109
ORAL SESSION
ORAL SESSION 8B
PUBLIC HEALTH
AND PHARMACOECONOMICS
8B.01
IS IT TIME TO TREAT POPULATIONS VERSUS
PATIENTS TO CONTROL HYPERTENSION?
5/HZDQF]XN. University of Alberta, Edmonton, CANADA
Objective: In order to close care gaps in the treatment and control of hypertension it is necessary to understand what contributes to these gaps. In hypertension, we have traditionally focused on practitioners and, to a lesser extent,
on patients. Very little activity has taken place at system levels to facilitate the
closing of care gaps. Our objective was to understand the source care gaps in
the control of hypertension in order to achieve a higher degree of blood pressure
FRQWUROZLWKLQWKHSRSXODWLRQRIWKHSURYLQFHRI$OEHUWD&DQDGD
Design and method: &DQDGDKDVDWRWDOO\SXEOLFKHDOWKFDUHV\VWHPDQGWKXV
medical administrative data on entire population is increasingly available. We
accessed provincial databases as well as selected primary care groups to differentiate provider, patient and system factors that could contribute to hypertension
care gaps.
Results: The prevalence of hypertension in the population of 3.6 million was
15.7% based on administrative data, but based on data from practices, was closer
to the national average of 23%, immediately demonstrating a system care gap
in terms of diagnosis. At an individual practice level, the proportion of hypertensive patients achieving blood pressure targets ranged from about 70-90% depending on the practice. In diabetic hypertensives, about 61% were at the lower
target of 130/80, yet 97% were below 140/90. Overall, within practices, there
was a correlation between continuity of care as well as attendance at follow-up
visits which determined achievement of blood pressure goals. Issues such as
drug cost and resistant hypertension were much less of an issue compared with
not having a primary care provider and/or not seeing a primary care provider for
regular follow-up.
Conclusions: In Alberta, the primary cause of the hypertension (and other
chronic disease) care gap is a) not having a primary care provider and b) of
JUHDWHUVLJQL¿FDQFHQRWVHHLQJWKHSULPDU\FDUHSURYLGHULQUHJXODUIROORZXS
We conclude that achieving population blood pressure control is much more
dependent on attaching individuals to a primary care provider and ensuring proactive access to that provider than focusing on provider behavior.
8B.02
ECONOMIC EVALUATION OF COMBINED THERAPY
OF ARTERIAL HYPERTENSION WITH MARKOV’S
MODELING
E. Tarlovskaya, N. Maksimchuk-Kolobova, S. Malchicova.
Kirov State Medical Academy, Kirov, RUSSIA
Objective: To evaluate by modeling the economic effectiveness of combined
two-antihypertensive therapy in patients with arterial hypertension (HT) and
high cardiovascular risk.
Design and method: 65 patients (19 males, 46 females) with HT and metabolic
disorders, history of previous ineffective therapy were studied. Group V/A was
WUHDWHG ZLWK YDOVDUWDQDPORGLSLQH LQ D ¿[HG FRPELQDWLRQ DW D GRVH RI PJGHSHQGLQJRQEORRGSUHVVXUHOHYHO/$ZLWKORVDUWDQDWDGRVHRI
PJDPORGLSLQHDWGRVHVRIPJ7UHDWPHQWGXUDWLRQZHHNV&KDQJHVRI
%3OHYHO/9+UHJUHVVLRQZHUHDVVHVVHG(FRQRPLFHYDOXDWLRQZDVSHUIRUPHG
RQWKHEDVLVRIPRGHOLQJZLWKVSHFLDOL]HGVRIWZDUH'HFLVLRQ7UHH[OD
Results: (IIHFWRIFRPELQDWLRQWKHUDS\RQ/9+ZDVXVHGWRHVWLPDWHHIIHFWLYHQHVVWREXLOGWKHPRGHO3DWLHQWVZHUHGLVWULEXWHGRQWKHOHIWYHQWULFXODU /9 PDVV DWEDVHOLQHDQGDIWHUZHHNVWKHUDS\ 6LJQL¿FDQWGHFUHDVHLQ/9PDVV
in V/A from 225,1 ± 71,7 to 186,3 ± 44,5 g (p <0.05), there was no dynamics in
/$7KHPRGHOWRRNLQWRDFFRXQWHFRQRPLFDQGIUHTXHQF\IDFWRUVIRU\HDUV
prognosis: V/A prevents 94 deaths, 22 strokes, 64 myocardial infarction (MI)
per 1000 patients. Absence of need in treatment of these prevented events can
save about 5.5 million RUR for every 1000 patients. It would reduce the total
costs per patient during 10 years. V/A saves maximum quality years of life in the
UHVXOWVRI/9PDVVUHJUHVVLRQ \HDUV /$LVWKHPRVWHFRQRPLFDOWKHUDS\
variant due to low cost. It will be need to spend additionaly 286 698.7 RUR for
one quality year of life in V/A. It will be a good investment.
Conclusions: V/A therapy single pill combination has not only clinical advanWDJHVSKDUPDFRHFRQRPLFEHQH¿WVEXWDEHWWHUK\SRWHQVLYHDQGFDUGLRSURWHFtive effects. V/A reduces risk of acute MI, stroke and death more effectively.
/$LVWKHPRVWFRVWHIIHFWLYHSKDUPDFRWKHUDS\YDULDQWLQWHUPVRIWKHFRVWRI
saved year of life with and without quality of life. V/A saves the maximum years
RIOLIHDQGTXDOLW\\HDUVRIOLIHE\UHJUHVVLRQ/9PDVV
8B.03
THE MANAGEMENT OF THE HYPERTENSIVE
PATIENT: FROM PREVENTION TO MANAGEMENT OF
THE COMPLICATIONS
0'H5RVD1, A. Esposito 1, M. Melissa 1, /&HULQL2. 1 University Federico II,
School of Medicine, Naples, ITALY, 2 Bocconi University, Milan, ITALY
Objective: Hypertension is responsible for more deaths worldwide than any
other cardiovascular risk factor. Guidelines based on blood pressure level for
initiation of treatment of hypertension may be too costly compared with an
DSSURDFK EDVHG RQ DEVROXWH FDUGLRYDVFXODU GLVHDVH &9' ULVN HVSHFLDOO\ LQ
developing countries.
Design and method: 8VLQJD0DUNRY&9'PRGHOZHFRPSDUHGVWUDWHJLHV
for initiation of drug treatment—2 different blood pressure levels (165/95 and
PP+J DQGGLIIHUHQWOHYHOVRIDEVROXWH&9'ULVNRYHU\HDUV 35%, 25%, and 15%)—with one of no treatment. We modeled a hypothetical
FRKRUWRIDOODGXOWVZLWKRXW&9'LQ,WDO\QRZDPXOWLHWKQLFGHYHORSLQJFRXQWU\
over 10 years.
Results: The incremental cost-effectiveness ratios for treating those with 10\HDUDEVROXWHULVNIRU&9'!DQGZHUH(XUR
2800, and 6 000 ,respectively per quality-adjusted life-year gained, respectively. Strategies based on a target blood pressure level were both more expensive
and less effective than treatment decisions based on the strategy that used abVROXWH&9'ULVNRI!6HQVLWLYLW\DQDO\VLVRIFRVWRIWUHDWPHQWVSUHYDOHQFH
HVWLPDWHVRIULVNIDFWRUVDQGEHQH¿WVH[SHFWHGIURPWUHDWPHQWGLGQRWFKDQJH
the ranking of the strategies. National inpatient hospital costs for hypertensive
patient with complications were nearly Euro 2.8 billion in 2012. The risk of hospitalization from cardiovascular disease is two to four times higher for women
with diabetes and hypertension compared to women without diabetes.
Conclusions: Hypertension-associated morbidity and mortality is a major
heath concern, however with appropriate treatment, hypertension can be managed and the associated sequelae, reduced. The key to controlling this disease
depends on proper and timely, prevention, detection, evaluation and treatment.
In Italy , current guidelines based on blood pressure levels are both more expensive and less effective than guidelines based on absolute risk of cardiovascular
disease. The use of quantitative risk-based guidelines for treatment of hypertension could free up major resources for other pressing needs, especially in
developping countries.
8B.04
VALIDITY OF EQUATIONS USED TO ESTIMATE
POPULATION SALT CONSUMPTION FROM SPOT
URINE SAMPLES
0&ULQR1, /+XDQJ1, P. Jeffery 2, M. Woodward 1, F. Barzi 1, 50F/HDQ3,
0/DQG1, B. Neal 1. 1 George Institute for Global Health, Sydney Medical
School, University of Sydney, Sydney, AUSTRALIA, 2 School of Exercise and
Nutrition Sciences, Deakin University, Melbourne, AUSTRALIA,
3
Departments of Preventive and Social Medicine, Human Nutrition, University
of Otago, Dunedin, NEW ZEALAND
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Journal of Hypertension Volume 32, e-Supplement 1, 2014
Objective: To determine which estimating equation based upon spot urine samples provides the closest approximation of mean population salt consumption
levels determined from single 24-hour urine collections.
Design and method: We systematically identified all studies done in human
populations that provided estimates of mean population salt intake based
upon 24-hour urine samples and spot urine samples. The method by which
the spot urine sample was used to derive an estimated mean population salt
intake was recorded and results were group accordingly. Scatter plots and
weighted linear regressions were done for each equation to investigate the
association between mean population 24-hour salt intake values estimated
from spot urine samples compared to 24-hour urine samples. Bland Altman
plots were used to check whether the agreement between methods drifted
with increasing absolute values.
Results: 'DWDZHUHDYDLODEOHIRUVWXGLHVLQFOXGLQJSDUWLFLSDQWVDQG
comparisons between mean population 24-hour salt intake values based upon
24-hour urine samples and spot urine samples. There were 6 different equation
types that used spot urine samples to make an estimate; 4 were developed using statistical modelling techniques and 2 were simple calculations that used
HLWKHUUDWHVRUFRQFHQWUDWLRQVWRGHULYHDQHVWLPDWH7KH,17(56$/7HTXDWLRQ
provided the closest approximation to the 24-hour samples with a mean difference of +0.2g/salt/day (95% limits of agreement -0.7g to +1.1g) in the 41
comparisons made. The equations based on rate (0.3g/salt/day, -2.7g to +3.3g)
and concentration (-0.6g/salt/day, -1.5g to +0.3g) provided estimates that were
on average slightly more different and/or more variable between comparisons,
The Tanaka, Kawasaki and Mage equations performed poorly by comparisons.
Conclusions: 7KH,17(56$/7HTXDWLRQEDVHGXSRQVSRWXULQHVDPSOHVSURvided a good prediction of mean population salt consumption levels estimated
from 24-hour urine samples. Equations based upon spot urine samples appear to
provide a real alternate to 24-hour urine samples for estimating average population salt consumption.
8B.05
DIRECT MEDICAL COSTS OF HYPERTENSION AND
ASSOCIATED CO-MORBIDITIES IN SOUTH KOREA.
A RETROSPECTIVE ANALYSIS
S. Ong 1, B. Yang 2, J. Min 2, K. Min 3, S. Seo 2, H. Kim 2, Y. Kim 2, E. Kim 2,
E. Yu 2, G. Machnicki 4. 1 Novartis Pharma AG, Basel, SWITZERLAND,
2
Seoul National University, Seoul, SOUTH KOREA, 3 Ajou University School
of Medicine, Suwon, SOUTH KOREA, 4 Novartis Argentina SA, Buenos Aires,
ARGENTINA
Objective: Hypertension is a primary risk factor for cardiovascular disease.
&RVWVIROORZLQJFDUGLRYDVFXODUHYHQWVLQK\SHUWHQVLYHSDWLHQWVDUHUHSRUWHGly substantial. Hypertension treatment costs in South Korea have increased
considerably by 64.3% over a 4-year period: from $1.4 billion in 2005 to
$2.3 billion in 2009. The cost burden of hypertension and co-morbid conditions in South Korea will be profound with the aging population. This study
aimed to calculate the direct medical costs for treatment of hypertension
and associated comorbidities in South Korea.
Design and method: This was a retrospective database analysis with 2009
South Korean Health Insurance Review and Assessment Service-National
Patients Sample data. Included hypertensive patients were >19 years old,
with at least two outpatient diagnosis codes or one hospital based diagnosis
and at least 6 months of follow-up during the study period. Total medical
cost per patient (sum of inpatient and outpatient costs) known as ‘State
costs’ for a period of 1 year and direct medical costs over a 6-month period
after the ‘first’ event in patients with hypertension known as ‘Event costs’
were calculated. HTN associated comorbidities included coronary heart disHDVH &+' VWURNHKHDUWIDLOXUH +) GLDEHWHVDQGGLDEHWLFQHSKURSDWK\
Results: Overall direct medical costs were higher for the elderly than
adults (19-64 years). Hypertensive patients with associated comorbidities
had higher direct costs per patient than patients with only hypertension in
both elderly and adults. Patients with HF (9.5million KRW for adults and
6.9 million KRW for elderly) or diabetic nephropathy (9.1million KRW for
adults and 8.9 million KRW for elderly) had relatively higher ‘State costs’
SHUSDWLHQWWKDQRWKHUFRPRUELGLWLHVµ(YHQWFRVWV¶RISDWLHQWVZLWK&+' million KRW for adults and 3.4 million KRW for elderly) or HF (4.4 million
KRW for adults and 3.3 million KRW for elderly) were relatively higher
compared to other associated diseases.
Conclusions: Increases in total costs were observed for patients with hypertension and comorbidities. Therefore comorbidities associated with hypertension impose a substantial burden in South Korea. Treatment and prevention strategies for hypertension are important to reduce risk factors and its
associated comorbidities.
8B.06
CAN SPOT URINE BE USED TO REPLACE 24-HOUR
URINE FOR MONITORING POPULATION SALT
INTAKE?
/+XDQJ1, 0&ULQR1, P. Jeffery 2, W. Woodward 1, F. Barzi 1, 50F/HDQ 3,
0/DQG1, N. Bruce 1. 1 George Institute for Global Health, Sydney Medical
School, University of Sydney, Sydney, AUSTRALIA, 2 School of Exercise and
Nutrition Sciences, Deakin University, Melbourne, AUSTRALIA,
3
Departments of Preventive and Social Medicine, Human Nutrition, University
of Otago, Dunedin, NEW ZEALAND
Objective: To investigate whether spot urine is a reliable alternative for prediction of 24-hour population salt intake and to test whether population intake
HVWLPDWHVEDVHGRQVSRWXULQHFDQFRUUHFWO\GH¿QHPHDQVDOWLQWDNHDVDERYHRU
below the WHO recommended daily intake target of 5 g/day/person.
Design and method: :H V\VWHPDWLFDOO\ LGHQWL¿HG DOO VWXGLHV GRQH LQ KXPDQ
populations that reported estimates of mean population salt intake based upon
24-hour urine samples and spot urine samples. The association of population
mean values based upon estimates made using 24-hour urine samples compared
to spot-urine samples was explored with linear regression and Bland Altman
analysis with weighting by study sample size.
Results: A total of 19 studies, 56 comparisons between 24-hour urine samples
and spot urine samples, and 6,803 participants were included. The mean difference between the estimates based upon the two approaches was 0.044 gram sodium chloride with the estimates based upon spot urine samples resulting on average in a slight overestimation. There was moderate variation in the magnitude
of the difference for the various studies included (95% limits of agreement -2.1g
WR J 'HVSLWH WKH VRPHWLPHV ODUJH GLIIHUHQFHV EHWZHHQ HVWLPDWHV EDVHG
upon 24 hour samples and spot urine samples there were only 2 comparisons
where the use of an estimate based upon spot urine samples resulted in misclasVL¿FDWLRQRIDSRSXODWLRQDVDERYHRUEHORZWKH:+2WDUJHWRIJGD\SHUVRQ
For most included comparisons the mean salt intake estimated from 24 hour
urine collections was substantially above this, and on average was 9.0 g/day.
Conclusions: Mean population salt consumption levels based upon estimates
made using spot urine samples appear to provide a valid alternate to 24 hour
urine collections. Estimates based upon pot urine samples appear unlikely to
misinform policy makers about the need for population salt reduction.
8B.07
COST-UTILITY ANALYSIS OF A SINGLE PILL TRIPLE
ANTIHYPERTENSIVE THERAPY WITH VALSARTAN,
AMLODIPINE, AND HYDROCHLOROTHIAZIDE
AGAINST ITS DUAL COMPONENTS
P. Stafylas 1, G. Kourlaba 2, A. Mavrodi 3, M. Hatzikou 4, '*HRUJLRSRXORV4,
36DUD¿GLV1, N. Maniadakis 2. 1 Hypertension Unit, AHEPA University Hospital,
Thessaloniki, GREECE, 2 National School of Public Health, Thessaloniki,
GREECE, 3 Department of Business Administration, University of Macedonia,
Thessaloniki, GREECE, 4 Novartis (Hellas) S.A.C.I., Athens, GREECE
Objective: The objective of the study was to compare the cost-utility of the
¿UVWVLQJOHSLOOWULSOHFRPELQDWLRQDQWLK\SHUWHQVLYHWKHUDS\ZLWKYDOVDUWDQ 9 amlodipine (A) and hydrochlorothiazide (H) with each of the dual combinations deriving from the same components in patients with moderate to severe
hypertension.
Design and method: A Markov model with eight health states was constructed.
The short-term effect of antihypertensive treatment on blood pressure was exWUDSRODWHGWKURXJKWKH+HOOHQLF6&25(DQG)UDPLQJKDPULVNHTXDWLRQVLQRUGHUWRHVWLPDWHWKHORQJWHUPVXUYLYDODQGTXDOLW\DGMXVWHGOLIH\HDUV 4$/<V VDYHG &RVWV DQG RXWFRPHV ZHUH HYDOXDWHG RYHU OLIHWLPH GLYLGHG LQWR DQQXDO
cycles and were discounted at 3.0% with 2013 as reference year. The analysis
was conducted by the Greek third-party-payer (EOPYY) perspective covering
more than 90% of the Greek population.
Results: The cost of treatment with triple combination was estimated at €16,525
in comparison to €15,480 for V/A, €14,125 for V/H and €11,690 for A/H. The
4$/<VVDYHGZLWKWKHWULSOHFRPELQDWLRQZHUHYVDQG
of double combinations respectively. The incremental cost-effectiveness ratio
,&(5 SHU4$/<VDYHGZLWKWKHWULSOHFRPELQDWLRQYHUVXV9$DQG$+ZDV
IDUORZHUWKDQWKH*UHHN*'3SHUFDSLWD ¼4$/<DQG¼4$/<UHVSHFWLYHO\ ZKLOHLWZDVUHDOO\FORVHLQFRPSDULVRQZLWK9+ ¼4$/< ([WHQVLYH VHQVLWLYLW\ DQDO\VHV FRQ¿UPHG WKH UREXVWQHVV RI WKH UHVXOWV 7KH
probability that the triple combination is cost effective was more than 90% at a
ZLOOLQJQHVVWRSD\WKUHVKROGRI¼4$/<
Conclusions: The triple single pill combination therapy with V/A/H is a costeffective antihypertensive choice in comparison to double combinations of V/A,
V/H and A/H for the treatment of moderate to severe hypertension.
Abstracts
e111
ORAL SESSION
ORAL SESSION 8C
MOLECULAR BIOLOGY AND PEPTIDES
8C.01
OXYTOCIN REDUCES CARDIOMYOCYTE
HYPERTROPHY
M. Jankowski, A. Menouar, J. Gutkowska. CR-CHUM, University of Montreal,
Department of Medicine, Montreal, CANADA
Objective: Oxytocin (OT) and OT receptor (OTR) are expressed in the heart
DQGDUHLQYROYHGLQFDUGLRSURWHFWLRQ'XULQJ27V\QWKHVLVLWVSUHFXUVRUWHUPHG
27*O\/\V$UJ 27*.5 LV DEXQGDQWO\ DFFXPXODWHG LQ WKH GHYHORSLQJ UDW
heart. Because the OTR is primarily associated with Gq/11protein subunit that
DFWLYDWHVSKRVSKROLSDVH&PHGLDWHGLQFUHDVHLQLQWUDFHOOXODU&DDQGSURWHLQ
synthesis, we speculated that OT can cause cardiomyocyte hypertrophy. However, in the heart, OTR signalling is associated with anti-hypertrophic atrial
QDWULXUHWLFSHSWLGH $13 UHOHDVHDQGQLWULFR[LGH 12 DFWLYDWLRQ&RQVHTXHQWly, we plan to clarify whether OT treatment promotes or inhibits hypertrophy in
cardiomyocytes.
Design and method: The experiments were carried out in newborn and adult rat
cardiomyocyte cultures. The enhanced protein synthesis and increased cardiomyocyte volume were stimulated by a 24-h treatment with endothelin-1 (ET-1)
or angiotensin II (Ang II).
Results: Treatment with OT or OT-GKR did not increased [35S]-methionine
incorporation by cardiomyocytes and not changed cell volume during 24-72 h.
The treatment of newborn rat cardiomyocytes with OT or its abundant cardiac
precursor, OT-GKR, revealed ANP protein in the cell peri-nuclear region and
LQFUHDVHG LQWUDFHOOXODU F*03 DFFXPXODWLRQ &RQVHTXHQWO\ WKH FDUGLRP\RF\WH
hypertrophy related to ET-1 and Ang II was abolished by the treatment of 10 nM
OT or 10 nM OT-GKR. The ANP receptor blockade by anantin and NO synthasHV E\ /1$0( LQKLELWHG F*03 HQKDQFHPHQW LQ FDUGLRP\RF\WHV H[SRVHG WR
27,QWKHSUHVHQFHRILQKLELWRUV672DQGFRPSRXQG&WKHDQWLK\SHUWURSKic OT effects in cardiomyocytes was reduced which suggest that OT signalling
includes activation of calcium-calmodulin kinase kinase and AMP-activated
protein kinase pathways. Time-course experiments demonstrated that OT alone
activates other signaling pathways, including Akt and the extracellular-regulated
kinase (ERK) with a maximum effect at 24hrs. Moreover, in ET-1 stimulated
cells, OT treatment normalized reduced Akt phosphorylation, prevented abundant accumulation of ANP and blocked ET-1-mediated translocation of nuclear
factor of activated T-cells (NFAT) into the cell nuclei.
Conclusions: cGMP/protein kinase G mediates OT-induced anti-hypertrophic
response with the contribution of ANP and NO. OT treatment represents a novel
approach in attenuation of cardiac hypertrophy during development and cardiac
pathology.
8C.02
INCREASE OF ALDOSTERONE-INDUCED C-SRC
PHOSPHORYLATION IN SHR VASCULAR SMOOTH
MUSCLE CELLS IS ASSOCIATED WITH C-TERMINAL
SRC KINASE (CSK) AND CSK-BINDING PROTEIN
(CBP) DOWN REGULATION
*&DOOHUD1, A. Montezano 2, T. Bruder-Nascimento 1, R.M. Touyz 2.
University of Ottawa, Ottawa, CANADA, 2 University of Glasgow, Glasgow,
UNITED KINGDOM
1
Objective: c-Src phosphorylation is controlled by the recruitment of enzyme regulaWRUVVXFKDV&WHUPLQDO6UFNLQDVH &VN ZKLFKLQKLELWV6UFDFWLYLW\DQGLQWHUDFWLRQV
with transmembrane adaptors. These complex regulatory mechanisms coordinate
activity of c-Src at multiple levels. We previously showed that in aldosterone-stimXODWHG6+5YDVFXODUVPRRWKPXVFOHFHOOV 960&V F6UFSKRVSKRU\ODWLRQDQGLWV
downstream signaling are upregulated. Here we hypothesized that mechanisms unGHUO\LQJYDVFXODUF6UFK\SHUDFWLYDWLRQLQ6+5DUHUHODWHGWRG\VUHJXODWHG&6.DQG
altered autophosphorylation at Tyr416 and Tyr527 in aldosterone-stimulated SHR
FHOOV6WXGLHVZHUHSHUIRUPHGLQFXOWXUHG960&VIURP:.<DQG6+5
Design and method: 7KH VWXG\ ZDV SHUIRUPHG LQ PHVHQWHULF 960& &WHUPLQDO 6UF NLQDVH &VN F\WRVROPHPEUDQH WUDQVORFDWLRQ &VNELQGLQJ SURWHLQ
&%3 DQGF6UFSKRVSKRU\ODWLRQZHUHHYDOXDWHGE\ZHVWHUQEORW&KROHVWHURO
enriched fractions were obtained by sucrose-gradient centrifugation.
Results: Aldosterone (100 nM) induced Tyr527 c-Src phosphorylation
(153.5 ± 13.6 %) which locks the kinase in an inactive conformation. This
ZDV EOXQWHG LQ 6+5 FHOOV &VN LV D F\WRVROLF NLQDVH WKDW FDWDO\]HV F6UF
7\U SKRVSKRU\ODWLRQ$61 X0 D &VN LQKLELWRU SUHYHQWHG WKH NLnase translocation to the membrane and inhibited Tyr527 c-Src phosphoU\ODWLRQLQGXFHGE\DOGRVWHURQHLQ:.<FHOOV,QKLELWLRQRI&VNLQGXFHGDQ
increase in Tyr416 c-Src (180 ± 21%) under basal conditions. In SHR cells,
&VN WUDQVORFDWLRQ WR WKH PHPEUDQH ZDV UHGXFHG E\ DOGRVWHURQH FRPSDUHG
with WKY cells. Aldosterone induced an increase in expression (180.3 ± 39
DQGSKRVSKRU\ODWLRQ “ RIWKHDGDSWRUSURWHLQ&%3LQ:.<
EXWQRWLQ6+5FHOOV$OGRVWHURQHVWLPXODWLRQLQFUHDVHG&VNWUDI¿FNLQJLQWR
lipid rafts/caveolae in WKY cells, without affecting the kinase content in the
cholesterol-enriched fractions from SHR.
Conclusions: 2XU¿QGLQJVGHPRQVWUDWHWKDW NH\UHJXODWRUVRIF6UFDFWLYDWLRQ
E\DOGRVWHURQHVSHFL¿FDOO\&VNDQG&%3DUHDOWHUHGLQ6+5960&V F6UF
UHJXODWLRQ E\ DOGRVWHURQH LQYROYHV OLSLG UDIWVFDYHRODH 7KHVH QRYHO ¿QGLQJV
VXJJHVWWKDWPRGXODWLRQRI&VNFRXOGEHDQLPSRUWDQWVWUDWHJ\WREOXQWF6UF
dependent aldosterone vascular effects.
8C.03
A CROSS-SECTIONAL INVESTIGATION AND GENETIC
VARIATION STUDY OF METABOLIC SYNDROME
AMONG UYGUR POPULATION IN XINJIANG
=/LQJ'=KDQJ/:DQJT. Yin, J. Zhang, /&DLJ. Meng, 1/L
The Center of Hypertension of the People’s Hospital of Xinjiang Uygur
Autonomous Region, Urumqi, CHINA
Objective: To explore distribution characteristics of metabolic syndrome and
the relationship between polymorphism of Suppressor of cytokine signalLQJJHQHDQGPHWDEROLFV\QGURPHRI8\JXUSRSXODWLRQLQ;LQMLDQJ
'HVLJQ DQG PHWKRG 7KH HSLGHPLRORJLFDO UHVHDUFK ZDV SHUIRUPHG
between January and February 2007 among Uygur population in Hetian
GLVWULFWLQ;LQMLDQJ8\JXU$XWRQRPRXV5HJLRQE\FOXVWHUVDPSOLQJDQGEORRG
samples from 1371 Uygur subjects including 582 males and 789 females were
collected.
(2) Representative variations of Suppressor of cytokine signaling-3 gene were
genotyped by TaqMan polymerase chain reaction in 1371 Uygur subjects.
(3)The distribution characteristics of genotypes, or the allele frequency of
rs4969168, rs9914220, and rs12953258 between case and control groups
were analyzed using 2 analyses. All genotype distributions were tested
for deviations from the Hardy-Weinberg equilibrium. (4)The diagnosis of
metabolic syndrome based on criteria of International diabetes federation.
Results: (1) A total of 1371 subjects were analyzed, including 672 individuals
with metabolic syndrome and 699 subjects of non- metabolic syndrome. The
morbidity of metabolic syndrome among Uygur population >30 years-age is
48.5%. Of which, morbidity of each components of metabolic syndrome such
as dyslipidemia, central obesity, hyperglycemia and hypertension is 78%,
57%, 39%, and 36% ,respectively. (2) The highest prevalence of metabolic
syndrome was at 50-60 years olds and the prevalence of metabolic syndrome
in female population is greater than in males. (3) The gender and drinking
contributed to the development of metabolic syndrome greatly. (4) rs9914220
mutation of Suppressor of cytokine signaling-3 gene is associated with essential hypertension of Uygur population and overweight and obesity of Uygur
females. (5) rs12953258 mutation of Suppressor of cytokine signaling-3 gene
is related to hyperlipidemia, pre-diabetes and diabetes mellitus in Uygur population. (6) rs4969168 mutation of Suppressor of cytokine signaling-3 gene
is in association with insulin resistance of Uygur population, overweight and
obesity in Uygur males.
Conclusions: 8\JKXU LQ ;LQMLDQJ LV D SRSXODWLRQ ZLWK KLJK SUHYDOHQFH RI
metabolic syndrome, and polymorphism of Suppressor of cytokine signalLQJJHQHLVDVVRFLDWHGZLWKPHWDEROLFV\QGURPHRI8\JKXULQ;LQMLDQJ
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8C.04
Journal of Hypertension Volume 32, e-Supplement 1, 2014
INCREASED CIRCULATING SERUM LEVELS
OF MATRIX METALLOPROTEINASE-2 ARE
ASSOCIATED WITH HYPERHOMOCYSTEINAEMIA
IN HYPERTENSIVE PATIENTS IN EARLY STAGES OF
CKD AND GLOMERULONEPHRITIS
*'LPDV1, T. Tegos 2, I. Kanellos 1, S. Spiroglou 3, I. Karamouzis 1,
S. Fotiadis 1, A. Frydas 1, S. Veneti 1, G. Konstantinidis 1, &6DYRSRXORV1,
G. Efstratiadis 4, A. Hatzitolios 1, '*UHNDV1. 1 First Propaedeutic Medical
Department, Ahepa University Hospital, Aristotle University of Thessaloniki,
GREECE, 2 First Neurology Medical Department, Ahepa University Hospital,
Aristotle University of Thessaloniki, GREECE, 3 Biochemistry Laboratory,
Ahepa University Hospital, Aristotle University of Thessaloniki, GREECE,
4
Department of Nephrology, Hippokration University Hospital, Aristotle
University of Thessaloniki, GREECE
Objective: Hyperhomocysteinaemia is involved in endothelial injury, which
OHDGVWRYDVFXODULQÀDPPDWLRQZKLFKLQWXUQPD\OHDGWRDWKHURJHQHVLVUHVXOWing in inschemic injury. Hyperhomocysteinaemia is therefore a risk factor for
DUWHU\GLVHDVH'LDEHWLFVXVXDOO\KDYHHOHYDWHGKPFWOHYHOVDQGDKLJKHUULVNIRU
heart attacks and strokes, so they make ideal population to study hmct effects
in human health. Hyperhomocysteinaemia may increase the production and enjymatic activity of matrix metalloproteinase-2 (MMP-2), the effect being more
pronounced in hypertensive patients. Hmct might activate MMPs and induce
collagen synthesis, causes imbalances of elastin/ collagen ratio which compromise vascular elastance, leading to vascular dysfunction and hypertension.
003KDVEHHQLPSOLFDWHGLQFKURQLFNLGQH\GLVHDVH &.' DQGFDUGLRYDVFXODUGLVHDVH &9' 7KHDLPRIWKLVVWXG\ZDVWRLQYHVWLJDWHWKHVHUXPOHYHOVRI
MMP-2 and hmct and the potential correlation with systolic blood pressure (sbp)
DQGGLDVWROLFEORRGSUHVVXUH GES LQHDUO\VWDJHVRI&.'DQGSULPDU\FKURQLF
JORPHUXORQHSKULWLV &*1 Design and method: 3DWLHQWVRIVWDJHVDQGRI&.'ZLWK&*1 Q ZHUH
LQFOXGHG$VFRQWUROVWKHUHZHUHKHDOWK\LQGLYLGXDOV Q &OHDUDQFHRIFUHDWLQLQH &OFU DQGDOEXPLQH[FUHWLRQZHUHH[DPLQHGLQWKHKXULQH003
OHYHOVZHUHGHWHUPLQHGE\DQHQ]\PHOLQNHGLPPXQRVRUEHQWDVVD\ (/,6$ NLW
Hmct levels were measured using a biochemical available laboratory method.
Blood pressure was taken using a manual sphygmomanometer. Intima media
thickness (IMT) of carotid arteries were evaluated by a high resolution ultrasonography.
Results: 7KH GLIIHUHQFH RI 003 VHUXP OHYHOV LQ &*1 JURXS DQG WKH FRQWURO JURXS ZDV S +PFW OHYHOV ZHUH DOVR VLJQL¿FDQWO\ KLJKHU
in patients than in the control groups and their difference was 30.7 (p<0.0001).
Further, MMP-2 levels were independent correlates of IMT (p<0.0001), albuminuria (p<0.0001), hmct (p<0.0001), sbp (p<0.0001) and dbp (p<0.0001).
Conclusions: This study suggests that serum levels of MMP-2 were strongly
correlated with hmct as well as with albuminuria, atherosclerosis and blood
pressure attributing a role for hmct and MMP-2 in blood pressure of early stages
RI&.'DQG&*1003DQGKPFWPLJKWSUHVHQWLQGHSHQGHQWFRUUHODWHVRI
EORRGSUHVVXUHLQHDUO\VWDJHVRI&.'
8C.05
BK CHANNEL ON DIFFERENTIATION OF VASCULAR
SMOOTH MUSCLE CELLS INDUCED BY MECHANICAL
STRETCH
Y. Qi 1, ;:DQ1, H. Zhao 2, Z. Jiang 1. 1 School of Life Sciences and
Biotechnology, Shanghai Jiao Tong University, Shanghai, CHINA,
2
Department of Engineering Mechanics, Tsinghua University, Beijing, CHINA
Objective: /DUJH FRQGXFWDQFH FDOFLXP DQG YROWDJHDFWLYDWHG SRWDVVLXP %. FKDQQHOSOD\VLPSRUWDQWUROHLQK\SHUWHQVLRQ'XULQJK\SHUWHQVLRQWKHGHGLIIHUHQWLDWLRQRIYDVFXODUVPRRWKPXVFOHFHOOV 960&V LQGXFHGE\SDWKRORJLFDO
stretch are involved in vascular remodeling. However, the role of BK channel
LQWKHSDWKRORJLFDOVWUHWFKLQGXFHGGHGLIIHUHQWLDWLRQRI960&VLVVWLOOXQFOHDU
Design and method: 960&VZHUHVXEMHFWHGWR SK\VLRORJLFDO VWUHWFKDQG
15% (pathological) stretch respectively. The effects of different stretch on the
%. FKDQQHO ĮVXEXQLW H[SUHVVLRQ DQG DFWLYLW\ 960& GLIIHUHQWLDWLRQ DQG LQWUDFHOOXODUFDOFLXPLQ960&VZHUHH[DPLQHG)XUWKHUPRUHWKHPHFKDQLVPRI
alternative splicing in response to the pathological stretch was studied.
Results: 7KH H[SUHVVLRQV RI %. FKDQQHO ĮVXEXQLW DQG 960& GLIIHUHQWLDWLRQ
PDUNHUV LH ĮDFWLQ &DOSRQLQ DQG 60 ZHUH H[DPLQHG E\ ZHVWHUQ EORWWLQJ
&RPSDUHGZLWKWKHVWUHWFK SK\VLRORJLFDO WKHH[SUHVVLRQVRI%.ĮVXEXQLW
DQG960&GLIIHUHQWLDWLRQPDUNHUVZHUHVLJQL¿FDQWO\GHFUHDVHGE\VWUHWFK
(pathological). Activity of BK channel, assessed by patch recording, was sigQL¿FDQWO\ LQFUHDVHG E\ WKH VWUHWFK DSSOLFDWLRQ 7KH DOWHUQDWLYH VSOLFLQJ RI
%.ĮVXEXQLWDVDVVHVVHGE\P51$H[SUHVVLRQRIVWUHVVD[LV±UHJXODWHGH[RQV
675(; ZDV DOVR HQKDQFHG E\ VWUHWFK )XUWKHUPRUH WKH SODVPLGV ZLWK
ZKROH %. DQG 675(; GHOHWHG %. UHVSHFWLYHO\ ZHUH WUDQVIHFWHG LQWR +(.
cells, and then subjected to different stretch. Endoplasmic reticulum stress (ERs)
detected by increased xbp1 expression was associated with alternative splicing
XQGHUVWUHWFKDSSOLFDWLRQ%\XVLQJWKDSVLJDUJLQ 7* WKHVSHFL¿F(5VLQGXFHU
WKH675(;P51$ZDVXSUHJXODWHGZKLOHH[SUHVVLRQVRI%.FKDQQHOĮVXEXQLW
DQGGLIIHUHQWLDWLRQPDUNHUVZHUHGRZQUHJXODWHG;ESWDUJHWVL51$WUDQVIHFWLRQ
which blocks ERs, reversed the effects of TG under static and stretch applications.
Conclusions: Our present results suggested that during hypertension, the pathoORJLFDOO\LQFUHDVHGVWUHWFKPD\LQGXFHWKH(5VLQ960&VZKLFKDIIHFWWKHDOternative splicing and activity of BK channel, and then subsequently modulate
960&GHGLIIHUHQWLDWLRQ
8C.06
INDUCTION OF THE EXPRESSION OF ENDOTHELIN-1
IN THE ENDOTHELIAL CELLS INCREASES BLOOD
PRESSURE IN AN ENDOTHELIN TYPE A RECEPTORDEPENDENT MANNER
P. Paradis 1, Y. Rautureau 1, 6&RHOKR1, A. Rehman 1, S. Offermanns 3,4,
(/6FKLIIULQ1,2. 1 Lady Davis Institute for Medical Research, SMBD, Jewish
General Hospital, McGill University, Montreal, CANADA, 2 Department of
Medecine, SMBD, Jewish General Hospital, McGill University, Montreal,
CANADA, 3 Max Planck Institute for Heart and Lung Research, Department
of Pharmacology, Bad Nauheim, GERMANY, 4 Goethe University Frankfurt,
Medical Faculty, Frankfurt, GERMANY
Objective: The mechanisms of blood pressure (BP) regulation by endothelin-1 proGXFHGE\HQGRWKHOLDOFHOOV (& DUHFRPSOH[DQGVWLOOXQFOHDU7UDQVJHQLFPLFHZLWK
(&VSHFL¿FKXPDQHQGRWKHOLQ ('1 RYHUH[SUHVVLRQSUHVHQWHGYDVFXODUGDPDJH
but no change in BP. The latter could be due to adaptation to life-long exposure to
high endothelin-1 levels. To demonstrate the mechanisms of endothelin-1 BP reguODWLRQ ZH JHQHUDWHG DQ LQGXFLEOH (&UHVWULFWHG ('1 RYHUH[SUHVVLQJ WUDQVJHQLF
mouse (ieET-1).
Design and method: 7ZRWUDQVJHQLFPRXVHOLQHV &DQG& H[SUHVVLQJ
FKORUDPSKHQLFRO DFHW\OWUDQVIHUDVH FDW DQG ('1 EHIRUH DQG DIWHU &UHPHGLDWHG
excision, respectively, were created. ieET-1 mice were generated by crossing cat('1 ZLWK PLFH H[SUHVVLQJ D &UH UHFRPELQDVH IXVHG WR D WDPR[LIHQLQGXFLEOH
PRGL¿HGHVWURJHQUHFHSWRUOLJDQGELQGLQJGRPDLQ &UH(57 XQGHUWKHFRQWURORI
(&VSHFL¿FUHFHSWRUW\URVLQHNLQDVH 7LH SURPRWHU526$P7P*P7P*PLFH
H[SUHVVLQJPHPEUDQHWDUJHWHGJUHHQÀXRUHVFHQWSURWHLQ P* DIWHU&UHPHGLDWHG
H[FLVLRQZHUHXVHGWRLQYHVWLJDWHWKHH[WHQWRI&UH(57WDPR[LIHQDFWLYDWLRQDQGWLVVXHVSHFL¿FLW\%3ZDVGHWHUPLQHGE\WHOHPHWU\GD\VEHIRUHWUHDWPHQWGXULQJWKH
GD\VRIWDPR[LIHQ PJNJGD\VF RUYHKLFOH 0LJO\RO—/GD\VF WUHDWments, and the 16 following days. Two groups of ieET-1 mice were treated with 5 or
10 mg/kg/day p.o. of the ET type A receptor blocker atrasentan from day 10 to the
HQGRIWKHVWXG\P*H[SUHVVLRQE\LPPXQRÀXRUHVFHQFHDQGSODVPDHQGRWKHOLQ
E\(/,6$ZHUHGHWHUPLQHG
Results: ,PPXQRÀXRUHFHQFHGHPRQVWUDWHGWKDWWDPR[LIHQWUDQVDFWLYDWHG&UH(57
VSHFL¿FDOO\LQ(&LQWKHKHDUWNLGQH\OXQJVDRUWDDQGPHVHQWHULFDUWHULHVLQZKLFK
“RI(&ZHUHSRVLWLYH7DPR[LIHQLQFUHDVHGE\DQGWLPHVSODVPDHQdothelin-1 in ieET-1-c-134 and ieET-1-c-170 mice, respectively (P<0.01), but not in
vehicle-treated iET-1-c-134 and iET-1-c-170 mice. Tamoxifen elevated night systolLF%3LQLH(7FDQGL(7FE\aPP+J 3 EXWQRWLQ7LH&UHERT2 compared to vehicle-treated ieET-mice. Increase in systolic BP was reversed
partially or completely with 5 or 10 mg/kg/day of atrasentan respectively (P<0.01).
Conclusions: Our results demonstrate that this new mouse model with inducible
(&UHVWULFWHG('1H[SUHVVLRQH[KLELWVHQGRWKHOLQGHSHQGHQWHOHYDWHG%3PHGLated by endothelin type A receptors.
8C.07
ENHANCED EXPRESSION OF GQ ALPHA AND PLC
BETA 1 PROTEINS CONTRIBUTE TO VASCULAR
SMOOTH MUSCLE CELL HYPERTROPHY IN
SPONTANEOUSLY HYPERTENSIVE RATS:
MOLECULAR MECHANISM
M. Atef, M. Anand-Srivastava.
Department of Physiology, Université de Montreal, Montreal, CANADA
Objective: 9DVFXODU*TĮVLJQDOLQJKDVEHHQVKRZQWRFRQWULEXWHWRFDUGLDFK\SHUWURSK\,QDGGLWLRQDQJLRWHQVLQ,, $QJ,, ZDVVKRZQWRLQGXFH960&K\SHUWURSK\
WKURXJK*TĮVLJQDOLQJKRZHYHUWKHVWXGLHVRQWKHUROHRI*TĮDQG3/&ȕSURWHLQV
LQ960&K\SHUWURSK\LQDQLPDOPRGHODUHODFNLQJ7KHSUHVHQWVWXG\ZDVWKHUHIRUH
XQGHUWDNHQWRH[DPLQHWKHUROHRI*TĮ3/&ȕSURWHLQVDQGWKHVLJQDOLQJSDWKZD\V
LQ960&K\SHUWURSK\XVLQJVSRQWDQHRXVO\K\SHUWHQVLYHUDWV 6+5 e113
Journal of Hypertension Volume 32, e-Supplement 1, 2014
Design and method: Protein expression and phosphorylation were determined by
Western blotting and protein synthesis was determined by 3[H]-leucine incorporation.
OXFLJHQLQDQGFHOOSUROLIHUDWLRQE\FRORULPHWULFDVVD\V 077 'DWDZHUHDQDO\]HG
by ANOVA and Bonferroni’s post test.
Results: 960&IURPZHHNROG6+5DQGQRWIURPZHHNROG6+5H[KLELWHG
HQKDQFHGOHYHOVRI*TĮ3/&ȕSURWHLQVDVFRPSDUHGWRDJHPDWFKHG:LVWDU.\RWR
:.< UDWV+RZHYHUSURWHLQV\QWKHVLVZDVVLJQL¿FDQWO\HQKDQFHGLQ960&IURP
ERWKDQGZHHNROG6+5DVFRPSDUHGWR960&IURPDJHPDWFKHG:.<UDWV
)XUWKHUPRUHWKHNQRFNGRZQRI*TĮ3/&ȕLQ960&IURPZHHNROG6+5E\
antisense and siRNA resulted in attenuation of protein synthesis. In addition, the
HQKDQFHGH[SUHVVLRQRI*TĮ3/&ȕSURWHLQVHQKDQFHGSKRVSKRU\ODWLRQRI(5.
DQGHQKDQFHGSURWHLQV\QWKHVLVLQ960&IURP6+5ZHUHDWWHQXDWHGE\$QJ,,$7
and endothelin-1 (ET-1) ETA receptor antagonists, losartan and BQ123 respectiveO\EXWQRWE\(7%UHFHSWRUDQWDJRQLVW%40RUHRYHU3'GHFUHDVHGWKH
HQKDQFHGH[SUHVVLRQRI*TĮ3/&ȕDQGSURWHLQV\QWKHVLVLQ960&IURP6+5
Results: :H¿UVWIRXQGWKDW1R[DQGSSKR[1R[FRPSOH[VXEXQLWVZHUHXS
UHJXODWHGLQPHVHQWHULF960&IURP6+5FRPSDUHGZLWK960&IURPQRUPRWHQVLYHUDWV$IWHUWKHWUHDWPHQWZLWK$,,PHVHQWHULF960&VKRZHGDQLQFUHDVHLQ526
SURGXFWLRQLQKLELWHGE\1R[GVWDW7KH1$'3+R[LGDVHDFWLYLW\VWLPXODWHGE\$,,
ZDVGHFUHDVHGE\1R[GVWDW7KHSHSWLGHDOVRVLJQL¿FDQWO\LQKLELWHG$,,LQGXFHG
proliferation of mesenteric smooth muscle cells from genetically hypertensive rats.
Conclusions: These results suggest that the enhanced levels of endogenous Ang II
and ET-1 through the activation of AT1 and ETA receptors respectively and MAP
NLQDVHVLJQDOLQJHQKDQFHGWKHH[SUHVVLRQRI*TĮ3/&ȕSURWHLQVLQ960&IURP
ZHHNROG6+5DQGUHVXOWLQ960&K\SHUWURSK\
8C.08
SPECIFIC NOX-2 INHIBITION DECREASES OXIDATIVE
STRESS AND IMPAIRS VASCULAR SMOOTH MUSCLE
CELL PROLIFERATION
J. Martinez-Pereira 1, A. Redondo 1, I. Quesada 1, 0&LIXHQWHV2, P. Pagano 2,
&&DVWUR1. 1 School of Medical Science, UNCuyo IMBECU -CONICET,
Mendoza, ARGENTINA, 2 Dept. of Pharmacology and Chemical Biology
and Vascular Medicine Institute University of Pittsburgh School of Medicine,
Pittsburgh, PA, USA
Objective: Oxidative stress has been discussed as a key mechanism of endothelial dysfunction and cardiovascular disease. Reactive Oxygen Species
526 QRWRQO\DOWHUYDVFXODUFRQWUDFWLOLW\EXWDOVRLQÀXHQFHYDVFXODUUHPRGHOLQJ DQRWKHU SKHQRPHQRQ DVVRFLDWHG ZLWK K\SHUWHQVLRQ 1$'3+ R[LGDVH
1R[ LV SUHVHQW LQ WKH YDVFXODU ZDOO DV D SUHFXUVRU DQG LQLWLDWRU RI LQÀDPmation and remodeling suggesting a direct and/or paracrine role in vascular
dysfunction We proposed to examine the molecular mechanisms of Nox-2
subunit inactivation, using an inhibitor peptide Nox2ds-tat designed to speFL¿FDOO\LQKLELWLQWHUDFWLRQVEHWZHHQ1R[R[LGDVHDQGSSKR[LQYDVFXODU
VPRRWKPXVFOHFHOOV 960& REWDLQHGIURPPHVHQWHULFUHVLVWDQFHDUWHULHVRI
spontaneously hypertensive rats (SHR).
Design and method: 0HVHQWHULF960&ZHUHLQFXEDWHGZLWKP01R[GVWDW
a competitive peptide antagonist of p47phox-Nox2 interaction that suppresses the
LQGXFWLRQ RI 2 E\$QJLRWHQVLQ ,, $,, &HOOV ZHUH WUHDWHG ZLWK 1R[GVWDW RU
scrambled 1 hour prior 4 hours treatment with AII (10-7 M). Noxs subunits expresVLRQZDVHYDOXDWHGE\UHDOWLPH3&5526SURGXFWLRQZDVHYDOXDWHGE\LQFXEDWLRQ
ZLWKDÀXRUHVFHQWSUREH +'&)'$ 1R[DFWLYLW\E\FKHPLOXPLQHVFHQFHZLWK
Conclusions: Our results suggest that the inhibitory peptide Nox2 has a potent effect
RQYDVFXODUG\VIXQFWLRQ,WLVDWWUDFWLYHWRVSHFXODWHWKDWVPDOOPROHFXOHVSHFL¿FVHOHFWLYHLQKLELWRUVIRUGLIIHUHQW1R[VFRXOGH[HUWDEHQH¿FLDOHIIHFWRQYDVFXODUSDWKRORJ\
8C.09
SERUM CYSTATIN C AND BRAIN NATRIURETIC
PEPTIDE AS MARKERS FOR HYPERTENSIVE LEFT
VENTRICULAR HYPERTROPHY
6&KDUIHGGLQH1, /$ELG1, M. Turki 2, /&KDU¿2, S. Ben Kahla 1,
S. Kammoun 1. 1 Hédi Chaker Hospital, Department of Cardiology, Sfax, TUNISIA,
2
Habib Bourguiba Hospital, Department of Biochemistry, Sfax, TUNISIA
Objective: 6HUXPF\VWDWLQ&DQGEUDLQQDWULXUHWLFSHSWLGH %13 OHYHOVFDQEHXVHG
to predict morbidity and mortality in patients with cardiovascular disease. However,
the clinical relevance of the two markers levels in patients with hypertensive left
YHQWULFXODUK\SHUWURSK\ /9+ KDVUDUHO\EHHQLQYHVWLJDWHG
7KHDLPRIWKLVVWXG\ZDVWRLQYHVWLJDWHZKHWKHUVHUXPF\VWDWLQ&DQG%13FRQcentrations are associated with cardiac structural and functional alterations in hypertensive patients.
Design and method: This prospective observational study comprised 52 hypertensive patients admitted in a tertiary Tunisian center of cardiology between
0D\DQG'HFHPEHU:HFODVVL¿HGWKHPLQWRWZRJURXSVWKRVHZLWK
/9+ Q DQGWKRVHZLWKRXW/9+ Q $OOSDWLHQWVXQGHUZHQWHFKRFDUGLRJUDSK\VHUXPF\VWDWLQ&DQG%13WHVWLQJ:HDQDO\]HGWKHUHODWLRQVKLS
EHWZHHQVHUXPF\VWDWLQ&%13OHYHOVDQG/9+
Results: 6HUXPF\VWDWLQ&DQG%13OHYHOVZHUHKLJKHULQK\SHUWHQVLYHSDWLHQWVZLWK
/9+WKDQLQWKRVHZLWKRXW/9+ 3 DQG3 :HIRXQGDSRVLWLYHFRUUHODWLRQEHWZHHQVHUXPF\VWDWLQ&OHYHOVDQGLQWHUYHQWULFXODUVHSWDOWKLFNQHVV ,967 (r = 0.267, P = 0.02), posterior wall thickness (PWT) (r = 0.304, P <0.01), and left
YHQWULFXODUZHLJKWLQGH[ /9:, U 3 7KLVVWXG\VKRZHGDOVRD
positive correlation between BNP concentrations, IVST and PWT (P = 0.02 and
P = 0.03). When analyzed by multiple linear regression, the correlations remained
SRVLWLYHEHWZHHQVHUXPF\VWDWLQ&%13OHYHOVDQG,967 ȕ 3 DQGȕ
3 DQG3:7 ȕ 3 DQGȕ 3 Conclusions: 6HUXPF\VWDWLQ&DQG%13FRQFHQWUDWLRQVDUHLQGHSHQGHQWPDUNHUVIRUK\SHUWHQVLYH/9+
Abstracts
e114
ORAL SESSION
ORAL SESSION 8D
WLDOO\ZLWKLQFUHDVLQJDJHXSWRWKHWKGHFDGH2XUGDWDFRQ¿UPWKDW&95)V
related to metabolic disease are associated with femoral artery stiffness.
LARGE ARTERIES
8D.02
8D.01
REFERENCE INTERVALS FOR FEMORAL ARTERY
STIFFNESS, OBTAINED FROM 5,069 SUBJECTS
J. Bossuyt 1, /(QJHOHQ2, I. Ferreira 2,3, &6WHKRXZHU2, P. Boutouyrie 4,
6/DXUHQW4, P. Segers 5, K. Reesink 6, /09DQ%RUWHO1. 1 Heymans Institute of
Pharmacology, Clinical Pharmacology, Ghent University, Ghent, BELGIUM,
2
Department of Internal Medicine and CARIM School for Cardiovascular
Diseases, Maastricht University Medical Centre, Maastricht, NETHERLANDS,
3
Department of Clinical Epidemiology and Medical Technology Assessment,
Maastricht University Medical Centre, Maastricht, NETHERLANDS, 4
Department of Pharmacology and INSERM U970, Hôpital Européen Georges
Pompidou, Paris, FRANCE, 5 Institute Biomedical Technology (IBiTech),
Ghent University, Ghent, BELGIUM, 6 Department of Biomedical Engineering,
CARIM School for Cardiovascular Diseases Maastricht University, Maastricht,
NETHERLANDS
Objective: &DURWLGIHPRUDO SXOVH ZDYH YHORFLW\ LV WKH JROG VWDQGDUG PHDsure of arterial stiffness, representing mainly aortic stiffness. In contrast to
the elastic carotid and aorta, the more muscular femoral artery (FA) is differHQWO\DVVRFLDWHGZLWKFDUGLRYDVFXODUULVNIDFWRUV &95)V ,QWKHHDUO\VWDJes of metabolic disease, such as diabetes and mild non-familiar hypercholesterolemia, FA stiffness was reported to be increased whereas aortic and carotid stiffness were not. Still, clinical application of FA stiffness is hampered
by the absence of reference values across the lifespan. Therefore, our aim
ZDV WRHVWDEOLVKDJHDQGVH[VSHFL¿FUHIHUHQFHYDOXHVIRU)$VWLIIQHVVLQ
KHDOWK\VXEMHFWVDQG LQYHVWLJDWHWKHDVVRFLDWLRQVZLWK&95)V
PULSE WAVE VELOCITY. BIOLOGICAL BEHAVIOR
AND CHARACTERISTICS IN HEALTHY SUBJECTS. A
PROSPECTIVE STUDY OF 3243 SUBJECTS
'/RYLF1, M.S. Kallistratos 2, A. Skyrlas 2, /(3RXOLPHQRV2, V. Stojanov 3,
M. Zdravkovic 4, G. Koracevic 5, (&KDPRGUDND2, N. Kouremenos 2,
I. Zacharopoulou 2, P. Tsinivizov 2, K. Kyfnidis 2, A. Pittaras 2,
2'LDNRXPDNRX2, A.J. Manolis 2. 1 Clinic for Internal Disease Intermedica,
Niš, SERBIA, 2 Asklepeion General Hospital, Cardiology Department, Athens,
GREECE, 3 Clinical Center Serbia, University Belgrade Medical School,
Belgrade, SERBIA, 4 Clinical Hospital Bezanijska Kosa, University Belgrade
Medical School, Belgrade, SERBIA, 5 Clinical Center Niš, University Niš
Medical School, Niš, SERBIA
Objective: &DURWLGIHPRUDOSXOVHZDYHYHORFLW\UHSUHVHQWVWKHJROGVWDQGDUGIRU
aortic stiffness measurement. Aortic stiffness presents an independent predictive
YDOXHIRUIDWDODQGQRQIDWDOFDUGLRYDVFXODUHYHQWVDQGUHSUHVHQWVDVLJQL¿FDQW
tool for total cardiovascular risk assessment. This study had the purpose to assess the biological behavior and characteristics of PWV in healthy subjects.
Design and method: /RFDO DUWHULDO VWLIIQHVV GH¿QHG DV WKH GLVWHQVLELOLW\
FRHI¿FLHQW '&IHP LQ N3D ZDV FDOFXODWHG DV WKH UDWLR RI UHODWLYH
distension (obtained from ultrasound echo-tracking) and local pulse pressure. The reference values database consisted of 5,069 individuals (49.5%
men, age range: 15-87), obtained from 8 different cohorts across 3 counWULHV1RUPDOYDOXHVZHUHHVWDEOLVKHGLQDKHDOWK\VXESRSXODWLRQGH¿QHGDV
WKRVHZLWKRXWHVWDEOLVKHG&9'&95)V LHVPRNLQJK\SHUWHQVLRQGLDEHtes, dyslipidaemia, obesity) and blood-pressure-, lipid-, or glucose-lowering
medication use (n=1,489; 43% men).
Results: 6H[VSHFL¿F HTXDWLRQV LQ WKH KHDOWK\ VXESRSXODWLRQ UHYHDOHG D
FRPSOH[QRQOLQHDUUHODWLRQVKLSZLWKDJH>PHQ'&IHP DJH
ð DJH ð OQ DJH ZRPHQ'&IHP DJH ñ D
JH ñ OQ DJH @,QWKHUHIHUHQFHSRSXODWLRQLQFOXGLQJLQGLYLGXDOVZLWK
DQGZLWKRXW&95)V'&IHP=VFRUHVEDVHGRQWKHVHHTXDWLRQVZHUHLQGHpendently associated with body mass index (BMI), mean arterial pressure
0$3 DQG WRWDOWR+'/ FKROHVWHURO UDWLR LQ GHFUHDVLQJ RUGHU RI LPSRUWDQFH6WDQGDUGL]HGȕVUHÀHFWLQJWKHGHYLDWLRQIURPWKHKHDOWK\SRSXODWLRQ
mean (or 50th percentile) were, in men and women respectively: -0.19 (95%
&, DQG IRU %0, DQG
-0.04 (-0.09; -0.00) for MAP; and -0.03 (-0.09; 0.02) and -0.16 (-0.20; -0.11)
IRUWRWDOWR+'/FKROHVWHUROUDWLR
Conclusions: Reference values for FA stiffness have been established. In young
and middle-aged men and women, normal FA stiffness does not change substan-
Design and method: :HSURVSHFWLYHO\VWXGLHGKHDOWK\VXEMHFWVIURP¿YH
outpatient hypertensive clinics (in Serbia and Greece). In all patients anthropometric characteristics as well as medical history and antihypertensive regiment
was recorded. The statistical behavior of PWV was tested with respect to qualitative parameters such us Gender and Smoking, as well as quantitative variables
such us Age, BMI, systolic BP, diastolic BP and heart rate. Pearson’s correlation
test was used to asses the statistical behavior of PWV compared to the patient’s
M
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N
D
A
Y
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R
A
L
S
e115
Journal of Hypertension Volume 32, e-Supplement 1, 2014
baseline characteristics. ANOVA was utilized in order to identify the distribution
RI3:9EHWZHHQGLIIHUHQFHVGH¿QHGE\DQWKURSRPHWULFSDUDPHWHUV
,07 DWKHURVFOHURWLFSODTXHVDQGHQGRWKHOLDOIXQFWLRQ )0' 7KHDUJHQWLQian and Eur populations were matched using similar criteria.
Results: The magnitude of PWV increase, was related to BP category classi¿FDWLRQ IURP RSWLPDO WR KLJK QRUPDO VWDJH S 3HDUVRQ¶V FRUUHODWLRQ
UHYHDOHG D VLJQL¿FDQW SRVLWLYH DVVRFLDWLRQ RI 3:9 SUDFWLFDOO\ ZLWK DOO PDMRU
baseline characteristics of healthy subjects (BMI, Age, Gender, Systolic BP,
'LDVWROLF %3 6PRNLQJ VWDWXV DQG KHDUW UDWH S &ODVVL¿FDWLRQ RI WKH
KHDOWK\VXEMHFWZLWKUHVSHFWWRWKHLU%0,UHYHDOHGVLJQL¿FDQWVWDWLVWLFDOFKDQJHV
in PWV between normal weights, overweight’s and obese (p<0.004 and p<0.001
respectively).
Results: $IWHUDSSO\LQJWKHH[FOXVLRQFULWHULDRI(XU GLDEHWHV&9HYHQWVDQG
&9 PHGLFDWLRQ D ¿QDO SRSXODWLRQ RI VXEMHFWV ZDV LQFOXGHG +7
and 502 healthy control group). The table shows PWV values distribution according to age and BP. When compared our data with Eur we observed in average higher PWV from 30 to 50 years, while lower values in those elder than 60
years (p <0.05) but the whole part of boths samples showed concordant values.
Conclusions: PWV present a linear correlation with all major biological and
anhtropometirc characteristics of healthy subjects. The degree of PWV increase
is associated with baseline blood pressure levels.
8D.03
A COMPARISON OF PULSE WAVE VELOCITY IN
COHORTS FROM EUROPE AND ARGENTINA. AN
EFFORT TO SETTLE REFERENCE VALUES
P. Forcada, S. Gonzalez, -&KLDEDXW6YDQHS. Obregon, &&DVWHOODUR
F. Inserra, &.RWOLDU. Hospital Universitario Austral, Hypertension Center,
Pilar, Argentina
Objective: Pulse Wave Velocity (PWV) is an indicator of arterial stiffness and
LQGLFDWRU DQG LQFUHDVHG &9 ULVN$Q LPSRUWDQW (XURSHDQ 'DWDEDVH (XU ZLWK
more than 11.000 patients was published settling reference values for Europe.
'DWD UHSRUWHGIURP 8UXJXD\ DQG %UD]LOVKRZHG KLJKHUYDOXHV DQG QRQH KDYH
been described yet in Argentina.
To explore PWV in a large regional sample of Argentina and compare it with Eur.
Conclusions: This study provided a wide range of PWV values in a large Argentinean cohort. The comparison with Eur set a basis for further analysis of
HWKQLFLW\VRFLRHFRQRPLFYDULDEOHVDQGFDUGLRYDVFXODUULVNIDFWRUVLQÀXHQFing similarities and disparities in arterial stiffness between both populations.
The differences between our results and those from our colleagues from UruJXD\DQG%UD]LOSRLQWRXWWKHQHHGRIFRPPRQHIIRUWVWR¿QGRXWWKHUHIHUHQFH
YDOXHVRI3:9LQ/DWLQ$PHULFD
To obtain reference values in large popultions from different regions is of paramount importance for a widespread use of PWV as parameter of vascular disHDVH$V3:9LVUHFRJQL]HGDVDQLPSRUWDQWPDUNHURI&9ULVNZHFRQVLGHUWKDW
obtaining reference values may be also a useful tool for research and clinical
practice.
8D.04
NON-HEMODYNAMIC PREDICTORS OF VARIATION IN
ARTERIAL STIFFNESS AFTER 17 YEARS
M. Gottsäter, G. Östling, M. Persson, G. Engström, O. Melander,
P.M. Nilsson. Lund University, Department of Clinical Sciences, Lund,
SWEDEN
Objective: Arterial stiffness is a risk marker for cardiovascular events and
mortality. The development of the arterial stiffening process associated with
ageing is affected by a number of risk factors but the relative importance of
these individual risk factors for vascular ageing is only partially understood.
A number of different factors have been shown to be associated with arterial
stiffness in cross-sectional studies. The aim of this observational study was to
determine which cardiovascular risk factors and markers could predict arterial
stiffness after a long follow-up time.
Design and method: The study population consists of 3056 individuals
(mean age 56 years at baseline, 39.5% men) from a population-based cohort
study in Malmö, Sweden. Baseline examination took place between 1991
and 1995 and follow-up examination between 2007 and 2012, after a mean
of 17.4 years. At follow-up, carotid-femoral Pulse Wave Velocity (c-f PWV),
a marker of arterial stiffness, was measured with Sphygmocor® and adjusted
for heart rate (HR) and mean arterial pressure (MAP) at the time of the
measurement.
Results: Mean c-f PWV was 10.5 m/s. Baseline waist circumference, fasting
JOXFRVH WULJO\FHULGHV +'/ FKROHVWHURO /'/ FKROHVWHURO DQG DJH ZHUH DOO
associated with c-f PWV at follow up after adjustment for age, sex, ongoing
antihypertensive and lipid-lowering drug therapy, HR and MAP. Baseline
FXUUHQWRUIRUPHUVPRNLQJRUF\VWDWLQ&ZHUHQRWLQGHSHQGHQWO\DVVRFLDWHG
ZLWK FI 3:9 DIWHU IXOO DGMXVWPHQW /'/ FKROHVWHURO ZDV QRW VLJQL¿FDQWO\
associated with c-f PWV in the male subgroup and, in contrast to the other
SUHGLFWRUVORVWLWVVLJQL¿FDQFHDIWHUIXUWKHUDGMXVWPHQWIRUZDLVWFLUFXPIHUence.
Design and method: We evaluated 8219 subjects who consecutively assisted to our Primary Prevention Program (2009-2012). We determined PWV
+HPRG\Q 'LQDS ZLWK &RPSOLRU PHWKRGRORJ\ LQWLPD PHGLD WKLFNQHVV
Conclusions: Both for men and women, waist circumference, fasting glucose,
WULJO\FHULGHVDQG+'/FKROHVWHUROZHUHDOOLQGHSHQGHQWSUHGLFWRUVRIWKHYDULation in c-f PWV (arterial stiffness) after a mean follow-up time of 17 years.
7KLVGHPRQVWUDWHVORQJWHUPLQÀXHQFHVRIULVNPDUNHUVIRUYDVFXODUDJHLQJ
e116
8D.05
Journal of Hypertension Volume 32, e-Supplement 1, 2014
DIASTOLIC BLOOD FLOW REVERSAL IN THE
DESCENDING AORTA DETERMINES RENAL
FUNCTION: POTENTIAL EXPLANATION FOR RENAL
DYSFUNCTION DUE TO AORTIC STIFFENING
J. Hashimoto, S. Ito.
Tohoku University Graduate School of Medicine, Sendai, JAPAN
Objective: $RUWLFVWLIIQHVVLVNQRZQDVDGHWHUPLQDQWRIJORPHUXODU¿OWUDWLRQ
rate (GFR) and as a potential predictor of progressive decline in renal function.
However, the pathophysiological mechanisms linking aortic stiffening with renal dysfunction are not fully understood. It has been recently demonstrated that
DRUWLFVWLIIQHVVUHODWHVWRWKHELGLUHFWLRQDOEORRGÀRZFKDUDFWHULVWLFVRIWKHGHVFHQGLQJWKRUDFLFDRUWDDQGDRUWLFVWLIIHQLQJLQFUHDVHVWKHÀRZUHYHUVDOLQHDUO\
diastole. In the present study, we hypothesized that aortic stiffening-induced reQDOG\VIXQFWLRQLVDWWULEXWDEOHWRDOWHUHGFHQWUDODRUWLFÀRZG\QDPLFV
Design and method: The subject group consisted of 222 patients with hypertension (mean age, 53±13 years). Flow velocity pulse waveforms were recorded
noninvasively with duplex ultrasonography at the proximal descending aorta
WKURXJKWKHVXSUDVWHUQDOZLQGRZWRFDOFXODWHWKHUHYHUVHIRUZDUGÀRZUDWLR7Rnometry was recorded to estimate the aortic pressure waveforms from radial
pressure waveforms and to measure the carotid-femoral (aortic) and carotidradial (peripheral) pulse wave velocities (PWVs) and aortic characteristic impedance. The estimated GFR (eGFR) was calculated from serum creatinine, age
DQGJHQGHU,QWUDUHQDOÀRZG\QDPLFVZDVDOVRHYDOXDWHGXOWUDVRQRJUDSKLFDOO\DW
the segmental arteries.
Results: 7KH PHDQ H*)5 ZDV “POPLQPð 7KH H*)5 ZDV VLJQL¿FDQWO\ 3 FRUUHODWHGZLWKWKHDRUWLFUHYHUVHIRUZDUGÀRZUDWLR U as well as with the aortic PWV (r=-0.40), characteristic impedance (r=-0.25) and
pulse pressure (r=-0.30), whereas it was not correlated with peripheral PWV (r=0.06) or mean arterial pressure (r=-0.10). The association between aortic PWV
and eGFR was independent of covariates including age, diabetes mellitus, and
renin-angiotensin system inhibitor treatment (P=0.04). However, further adjustPHQWIRUWKHDRUWLFUHYHUVHÀRZUDWLRDQGSXOVHSUHVVXUHUHQGHUHGWKLVDVVRFLDWLRQ
LQVLJQL¿FDQWDQGWKHDRUWLFUHYHUVHÀRZUDWLRHPHUJHGDVWKHVWURQJHVWGHWHUPLQDQW RI H*)5 3 &RUUHODWLRQ DQDO\VLV EHWZHHQ WKH DRUWLF DQG UHQDO
KHPRG\QDPLFVUHYHDOHGWKDWKLJKHUDRUWLFUHYHUVHÀRZUDWLRZDVUHODWHGWRORZHU
LQWUDUHQDOV\VWROLFDQGGLDVWROLFIRUZDUGÀRZYHORFLWLHV 3 Conclusions: 7KHVH GDWD VXJJHVW WKDW DQ LQFUHDVH LQ DRUWLF ÀRZ UHYHUVDO LH
UHWURJUDGHÀRZIURPWKHORZHUVXSUDUHQDODRUWDWRZDUGWKHXSSHUDRUWLFDUFK GXHWRDRUWLFVWLIIHQLQJUHGXFHVDQWHJUDGHÀRZLQWRWKHNLGQH\DQGWKHUHE\GHteriorates renal function.
8D.06
GREATER CENTRAL-TO-PERIPHERAL PULSE
PRESSURE AMPLIFICATION IN DIABETES AND
OBESITY: THE RELATIVE MEDIATING ROLE OF
ARTERIAL STIFFNESS, HEART RATE AND WAVE
REFLECTION. THE CODAM STUDY
P. Vaidya, 59DQ'H/DDU , M. Van Greevenbroek, &9DQ'HU.DOOHQ
&6FKDONZLMNM. Prins, &6WHKRXZHUI. Ferreira. Maastricht University
Medical Centre, Maastricht, NETHERLANDS
Objective: 7KH LPSDFW RI PHWDEROLF GLVHDVHV RQ FHQWUDO & WRSHULSKHUDO 3 SXOVH SUHVVXUH DPSOL¿FDWLRQ 33$ LV QRW FOHDU :H WKHUHIRUH LQYHVWLJDWHG WKH
H[WHQWWRZKLFK 33$ 333&33 GLIIHUVDFURVVGLIIHUHQWJOXFRVHPHWDEROLVP
(GM) and body weight states; 2) any such differences could be ascribed to the
primary determinants of PPA: arterial stiffness (carotid-femoral PWV), wave
UHÀHFWLRQ DXJPHQWDWLRQLQGH[$,[ DQGKHDUWUDWH +5 Design and method: Brachial-BP was assessed by automatic oscillometry, and
central-BP derived from radial applanation tonometry in 390 participants of the
&2'$06WXG\VWIROORZXSH[DPLQDWLRQ PHDQDJH“\UVPHQ &RPSDULVRQVRI33VDQG33$EHWZHHQLQGLYLGXDOVZLWKLPSDLUHG ,*0Q RUW\SHGLDEHWHV '0Q YVQRUPDO*0 1*0Q DQGZLWKRYHUweight (n=217) or obesity (n=99) vs. normal-weight (n=74) were conducted
with multiple linear regression models, all adjusted for age, sex, anti-hyperten-
sive treatment and mutually for GM or weight status. Multiple mediation analyses were used to quantify the portion (in %) of the difference in PPA between
JURXSVGXHWR'0RUREHVLW\UHODWHGHIIHFWVRQFI3:9$,[DQGRU+5
Results: $GMXVWHG PHDQ“6( PP+J 333 DQG &33 ZHUH “ DQG
53.7±1.1 in NGM, and respectively, +1.9 and +0.7 in IGM, and +5.9 and +4.1
LQ'0 SWUHQGV 7KHUHIRUH33$ LQPP+J ZDVDQGJUHDWHU
LQ ,*0 DQG '0 SWUHQG $GMXVWHG PHDQ“6( 333 DQG &33 ZHUH
“ DQG “ LQ QRUPDOZHLJKW EXW RQO\ 333 QRW &33 LQFUHDVHG
in overweight (+0.2 and -0.8) and obesity (+2.4 and -0.2). Still, PPA was 1.0
DQG JUHDWHU LQ RYHUZHLJKW DQG REHVLW\ SWUHQG /RZHU $,[ E\
35.5%&52.7%), higher HR (18.0%&21.0%) and higher cfPWV (9.3%&6.5%)
H[SODLQHGDVLJQL¿FDQWDQGLQGHSHQGHQWSRUWLRQRIWKHJUHDWHU33$DVVRFLDWHG
ZLWK'0 LQWRWDO RUREHVLW\ ,QDOOPRGHOVDJHDQGIHPDOH
sex were inversely associated with PPA; the differences reported were similar
in men and women and were not affected by additional adjustment for other
risk factors.
Conclusions: Type-2 diabetes and obesity are independently associated with
greater, not lower PPA, and this can be explained, to a great extent, by increased
DUWHULDOVWLIIQHVVDQG+5EXWSUHGRPLQDWHO\GHFUHDVHGZDYHUHÀHFWLRQDVVRFLDWHG
with these states.
8D.07
NON-INVASIVE ASSESSMENT OF CAROTID PULSE
WAVE VELOCITY BY MEANS OF ACCELEROMETRIC
SENSORS: VALIDATION OF A NEW DEVICE
1'L/DVFLR1, F. Stea 1,2, R.M. Bruno 1, E. Bianchini 1, V. Gemignani 1,
/*KLDGRQL2, F. Faita 1. 1 Institute of Clinical Physiology, National Council of
Research, Pisa, ITALY, 2 Department of Internal Medicine, University of Pisa,
Pisa, ITALY
Objective: &DURWLGSXOVHZDYHYHORFLW\ F3:9 LVFRQVLGHUHGDVXUURJDWHPDUNer for carotid stiffness evaluation and its assessment is increasingly used in cliniFDOSUDFWLFH+RZHYHUDWWKHPRPHQWLWVHVWLPDWLRQQHHGVVSHFL¿FHTXLSPHQW
and a moderate level of technical expertise; moreover, it is based on a mathematical model. Aim of this study was to validate a new easy-to-use system for
non-invasive and model-free cPWV assessment based on accelerometric sensors. For this purpose, accelerometric PWV values (accPWV) were compared
ZLWKXOWUDVRXQGFDURWLGVWLIIQHVV &6 PHDVXUHPHQWVUHODWLYHGLVWHQVLRQ UHO' DQGGLVWHQVLELOLW\ '& YDOXHVLQDGGLWLRQWKHV\VWHPVXFFHVVUDWHZDVFDOFXlated and variability analysis was performed.
Design and method: Ninety-seven presumed healthy volunteers (50.5±19.6
\HDUV PDOHV %0, “ .JP KDYH EHHQ UHFUXLWHG UHO' YDOXHV
were obtained by a contour tracking technique applied to ultrasound B-mode
LPDJHVVHTXHQFHVZKLOH&6DQG'&RQHVZHUHGHULYHGIURPUHO'PHDVXUHPHQWV
combined with tonometric local pulse pressure estimation and Bramwell-Hill
equation. A small device with two percutaneous accelerometers (distance: 2.4
cm) placed on a soft bracket and allowed to freely vibrate was put on the neck of
each subject. Beat-to-beat temporal shifts between the two accelerometric signals were assessed with an optimized cross-correlation technique and accPWV
values were calculated dividing the distance between the sensors for the average
temporal shift.
Results: DFF3:9HYDOXDWLRQV “PV VKRZHGDVLJQL¿FDQWFRUUHODWLRQZLWK&6PHDVXUHPHQWV “PV 5 3 UHO'YDOXHV
“ 5 3 DQG '& DVVHVVPHQWV “ 03D 5 3 &RPSDULVRQEHWZHHQDFF3:9HYDOXDWLRQVDQG&6YDOXHV
showed a mean difference of 0.33 m/s with a standard deviation of the difference
of 1.34 m/s. The system success rate was equal to 87.9% while the variability
DQDO\VLVSURYLGHGFRHI¿FLHQWVRIYDULDWLRQHTXDOWRDQGIRU
intra-operator, inter-operator and inter-session repeatability, respectively.
Conclusions: The accelerometric system allows a simple and quick local carotid
VWLIIQHVV HYDOXDWLRQ DQG WKH YDOXHV REWDLQHG ZLWK WKLV V\VWHP DUH VLJQL¿FDQWO\
correlated with known carotid stiffness biomarkers. Therefore, the presented device could provide a concrete opportunity for an easy carotid stiffness evaluation
even in clinical practice.
Abstracts
e117
ORAL SESSION
ORAL SESSION 9A
RESISTANT HYPERTENSION
9A.01
ENDOCARDIAL ABLATION SYSTEM FOR RENAL
DENERVATION: LESS DEMAND TO ANATOMY OF
RENAL ARTERIES
S. Pekarskiy, A. Baev, V. Mordovin, T. Ripp, G. Semke, E. Sitkova,
V. Lichikaki, A. Krylov, S. Popov, R. Karpov. Research Institute of Cardiology,
Tomsk, RUSSIA
Objective: Current consensus on renal denervation (RD) limits its use to the
cases of a single renal artery (RA) at least 2 cm length and 4 mm diameter.
This excludes patients with multiple arteries, short trunks and other nonobstructive abnormalities representing around 50% of all cases of resistant
hypertension (RH). These limitations paradoxically results from small size
of renal electrodes that creates small contact area resulting in high current
density and risk to overheat arteries <4 mm in diameter. At the same time
parental endocardial ablation systems have larger electrodes creating less
current density yet thin enough for easy manipulation in small arteries, e.g.
) PP7RDVVHVVWKHVDIHW\DQGHI¿FDF\RI5'GRQHE\HQGRFDUGLDO
ablation system in RH patients with high prevalence of non-obstructive abnormalities of RA
Design and method: We performed RD using endocardial ablation catheter
5F, 4 mm length in 53 patients (aged 53,8±9,6 years, 28 male) with drugresistant essential hypertension (NCT01499810 at ClinicalTrials.gov). Series of 4-10 point ablations in RA and segmental branches (in cases of short
WUXQN ZHUHGRQHLQWHPSHUDWXUHFRQWUROPRGHZLWKWDUJHW7 &(I¿FDF\
ZDVHYDOXDWHGE\FKDQJHVLQRI¿FHDQGDPEXODWRU\%3DWDQGPRQWKV
after RD. Safety endpoints included adverse events, changes in renal blood
ÀRZDQGUHQDOIXQFWLRQ
Results: Only 22 (41.5%) met the current anatomical requirements for RD.
However, no damage of RA including segmental branches and accessory
arteries was detected. There were no serious perioperative adverse events.
)RUW\¿YHDQGSDWLHQWVFRPSOHWHGUHVSHFWLYHO\DQGPRQWKV)81R
VLJQL¿FDQWFKDQJHVLQUHQDOEORRGÀRZUHQDOIXQFWLRQZHUHIRXQGGXULQJ)8
$WPRQWKVDIWHU5'WKHUHZDVSRZHUIXOGHFUHDVHRIRI¿FH%3
S PP+JV\VWROLFGLDVWROLF EXWRQO\PRGHUDWHORZHULQJRI
PHDQK%3 S %RWKHIIHFWVVOLJKWO\IXUWKHUJUHZ
XSWR SS DQG S UHVSHFtively at 12 months after RD.
Conclusions: RD done by endocardial ablation system is safe and effective
in RH patients including those with abnormal anatomy of renal arteries who
currently is not eligible for treatment by renal denervation devices.
9A.02
RENAL DENERVATION STOPS THE DECLINE OF
RENAL FUNCTION IN PATIENTS WITH CHRONIC
KIDNEY DISEASE AND RESISTANT HYPERTENSION
C. Ott 1, F. Mahfoud 2, A. Schmid 3, T. Ditting 1, R. Veelken 1, 08GHU3,
M. Böhm 2, R.E. Schmieder 1. 1 Department of Nephrology and Hypertension,
University of Erlangen-Nuremberg, Erlangen, GERMANY, 2 Klinik für Innere
Medizin III, Universitätsklinikum des Saarlandes, Homburg/Saar, GERMANY,
3
University of Radiology, University of Erlangen-Nuremberg, Erlangen,
GERMANY
Objective: Renal denervation (RDN) emerged as an innovative antihypertensive therapy in patients with treatment resistant hypertension. Arterial hypertension is a predominant risk factor of renal function decline over time and its
control preserves renal function. We analyzed whether reducing blood pressure
(BP) by RDN preserves renal function.
Design and method: In an observational prospective uncontrolled study, we
WUHDWHGSDWLHQWVZLWKFKURQLFNLGQH\GLVHDVH &.' VWDJHDQGDQGWUHDWPHQWUHVLVWDQWK\SHUWHQVLRQ RI¿FH%3! PP+JZKLOHRQDWOHDVWDQWLK\SHUWHQVLYHDJHQWVDQGGLDJQRVLVFRQ¿UPHGE\K$%30! PP+J with catheter-based RDN using the Symplicity FlexTM catheter (Medtronic
Inc., Palo Alto, CA). The study was registered at www.clinicaltrials.gov (ID:
NCT01442883). Renal function was evaluated up to 3 years prior and 1 year
DIWHU 5'1 (VWLPDWHG JORPHUXODU ¿OWUDWLRQ UDWH H*)5 ZDV FDOFXODWHG XVLQJ
MDRD formula and the change in eGFR over time was calculated by regression
slope individually for each patient.
Results: Patients (63 ± 10 years) were treated with 5.8 ± 1.6 antihypertensive
drugs on average, and 56 % had type-2 diabetes. One year after RDN, braFKLDORI¿FH%3ZDVUHGXFHGE\PP+J V\VWROLF“YHUVXV“
PP+JSGLDVWROLF“YHUVXV“PP+JS DQG
average systolic 24-h ambulatory BP by 9 mmHg (152 ± 12 versus 143 ± 12
PP+J S 2Q DYHUDJH PHDQ H*)5 GHFOLQH EHIRUH 5'1 ZDV PO
PLQPSHU\HDU,QFRQWUDVWH*)5UHPDLQHGVWDEOH POPLQP DIWHU5'1 EDVHOLQH“YHUVXV\HDU“POPLQP 7KH
FKDQJHRIH*)5SHU\HDUZDVVLJQL¿FDQWO\GLIIHUHQWEHIRUHDQGDIWHU5'1 YHUVXVPOPLQPSHU\HDUS 1RQHRIWKHSDWLHQWVGHYHORSHGD
doubling of serum creatinine or required dialysis after RDN at any point of time.
Conclusions: 2XUREVHUYDWLRQDOSLORWVWXG\LQSDWLHQWVZLWK&.'LQGLFDWH
that treatment of hypertension with RDN slows or even halts the decline of renal, which may be related to the better controlled BP, decrease of sympathetic
activity or both.
9A.03
PRELIMINARY EXPERIENCE WITH AN IRRIGATED
BALLOON-BASED RADIOFREQUENCY DEVICE FOR
RENAL DENERVATION
A. Sticchi 1, A. Latib 1, D. Regazzoli 1, F. Figini 1, V. Panoulas 1, A. Mailhac 1,
G. Pizzetti 1, A. Cappelletti 1, C. Godino 1, C. Lanzani 2, P. Manunta 2,
A. Margonato 1, P. Camici 1, A. Colombo 1. 16DQ5DIIDHOH6FLHQWL¿F,QVWLWXWH
Department of Cardio-Thoracic-Vascular Medicine, Milan, ITALY, 2 San
5DIIDHOH6FLHQWL¿F,QVWLWXWH'LYLVLRQRI1HSKURORJ\DQG'LDO\VLV0LODQ,7$/<
Objective: Several recent studies have shown that renal denervation is a safe
and effective treatment for drug-resistant hypertension. We report our 12-month
experience with the Covidien One-Shot irrigated balloon-based system.
Design and method: 3DUWLFLSDQWVZHUHEHWZHHQ\HDUVRIDJHZLWKRI¿FH
V\VWROLF%3! PP+J ! PP+JIRUSDWLHQWVZLWK7\SHGLDEHWHV RQ
! DQWLK\SHUWHQVLYHDJHQWV LQFOXGLQJDGLXUHWLF 8VLQJWKHVHFULWHULDSDWLHQWVZHUHLGHQWL¿HGDQGWUHDWHGZLWKWKH&RYLGLHQ2QH6KRWDQLUULJDWHGUDGLRfrequency-based balloon catheter. Patients were followed up at 1-3-6-12 months
after the ablation treatment. Follow-up included patient review by a hypertension specialist, blood pressure measurement at the time of the review as well as
blood and urinary sampling for glucose, urea electrolytes, microalbuninuria and
brain natriuretic peptide. 24-hour Ambulatory Blood Pressure Monitoring was
also undertaken prior to clinic review.
Results: All 20 patients underwent post procedure 1-month follow-up with 24hour Ambulatory Blood Pressure Monitoring. This demonstrated an average
systolic drop of 21±23 mmHg and an average diastolic drop of 6±4 mmHg.
Thirteen patients completed 6-month follow-up. 24-hour Ambulatory Blood
Pressure Monitoring at that point showed an average systolic drop of 39±19
mmHg and an average diastolic drop of 18±13 mmHg. Echocolour Doppler imaging of renal arteries at 6 months showed no evidence of renal artery stenosis.
7KHUHZDVQRVLJQL¿FDQFHGLIIHUHQFHLQUHQDOIXQFWLRQDWPRQWKVDVDVVHVVHG
E\FUHDWLQLQHFOHDUDQFH PHDQ&RFNFURIW*DXOWH*)5“P/PLQS Conclusions: This small study suggests that renal denervation using the CoviGLHQ2QHVKRWUHQDOGHQHUYDWLRQV\VWHPDSSHDUVWREHHI¿FDFLRXVIRUWKHWUHDWment of resistant hypertension in this real-world population. Larger studies and
ORQJHUIROORZXSDUHUHTXLUHGWRFRQ¿UPWKHVH¿QGLQJV
M
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e118
9A.04
Journal of Hypertension Volume 32, e-Supplement 1, 2014
SHOULD HOME BP MEASUREMENTS BE A
STANDARD END POINT IN RENAL DENERVATION
STUDIES? RESULTS FROM ENLIGHTN I FIRST-INHUMANS STUDY
V. Papademetriou 2,5, &7VLRX¿V2, M. Worthley 1, A. Sinhal 3, D. Chew 3,
I. Meredith 4, Y. Malaiapan 4, S. Worthley 1. 1 Cardiovascular Research Centre,
c/o the Cardiovascular Investigational Unit, Level 6 Theatre Block, Univ. of
Adelaide, Adelaide, AUSTRALIA, 2 First Cardiology Clinic, University of
Athens, Hippokration Hospital, Athens, GREECE, 3 Department of Cardiology,
Flinders University, Bedford Park, AUSTRALIA, 4 Monash Heart and Monash
University, Melbourne, AUSTRALIA, 5 VA and Georgetown University Medical
Centers, Washington, DC, USA
Objective: Emerging evidence suggest that home BP measurements provide
DGGLWLRQDOLQIRUPDWLRQUHJDUGLQJ%3FRQWURO0RVWVWXGLHVUHSRUWHGRI¿FHDQG
some ambulatory BP changes in renal denervation studies.. Home BP data are
scarce
Design and method: 7KH(QOLJ+71,¿UVWLQKXPDQVWXG\ZDVGHVLJQHGWRDVVHVVWKHVDIHW\DQGHI¿FDF\RIDPXOWLHOHFWURGHDEODWLRQV\VWHPLQSDWLHQWVZLWK
GUXJUHVLVWDQWK\SHUWHQVLRQ7KHSULPDU\HQGSRLQWZDVFKDQJHLQRI¿FH%3EXW
24 hr ambulatory and home BPs were also collected. A total of 46 pts (av. age
“\UVRQ“PHGV ZHUHHQUROOHG2IWKHVHSWVZHUHIHPDOH
were white, 20% had Coronary Artery Disease, 59% had hyperlipidemia, 33%
had type II Diabetes Mellitus, and 30% had history of sleep apnea. Home BP
measurements were in the morning and evening assessed (in triplicates) for at
least 14 days prior to procedure.
Results: %DVHOLQHDYHUDJHRI¿FH%3ZDVPP+JDQGDYHUDJHKUDPEXODWRU\%3PP+J$YHUDJHUHGXFWLRQV PP+J RIRI¿FH%3DW
DQGPRQWKVZHUHDQGPP+J S UHVSHFWLYHO\DQGIRUKUDPEXODWRU\%3DQGIRUPRQWK
(p<0.001). Average home BPs were as follows. Baseline at weeks -3,-2,-1 prior
WRWKHSURFHGXUHDWPRQWK ZHHNV ZHUH
DWPRQWKV ZNV DWPRQWKV
DQGDWPRQWKVDQGPP+* 3IRUDOO Conclusions: Although electrical stimulation of the renal arterial autonomic
nerves has been reported as an end point of effective RDN in dogs, different
settings of electrical stimulation of the renal arterial autonomic nerves in farm
pigs failed to affect either BP or heart rate.
9A.06
PROGNOSTIC IMPACT OF TREATMENT RESISTANT
HYPERTENSION ON CLINICAL EVENTS DURING
2 YEAR FOLLOW-UP IN ELDERLY PATIENTS.
RESULTS OF THE 3 A REGISTRY
I. Kistner 1, 8=H\PHU2, R. Dechend 3, T. Riemer 4, I. Hagedorn 5,
R.E. Schmieder 1. 1 Universitätsklinikum Erlangen, Nephrologie und
Hypertensiologie, Erlangen, GERMANY, 2 Medizinische Klinik B, Klinikum der
Stadt Ludwigshafen, Ludwigshafen, GERMANY, 3 Experimental and Clinical
Research Center, Charité-Campus Buch und Helios Klinikum Berlin Buch,
Berlin, GERMANY, 4 Novartis Pharma GmbH, Nürnberg, GERMANY, 5 IHF
GmbH Institut für Herzinfarktforschung, Ludwigshafen, GERMANY
Objective: Aim of this study was to determine the prognostic value of treatment
resistant hypertension (TRH) on mortality and cardiovascular events during 2
year follow up in a large number of hypertensive elderly patients in Germany.
Design and method: ,QWKLVSURVSHFWLYHREVHUYDWLRQDOUHJLVWU\SDWLHQWVZHUH
included who had TRH according to European society of hypertension guidelines.
Patients were recruited by primary care physicians in Germany. Physicians deFLGHGXSRQWKHPRGL¿FDWLRQRIWKHGUXJUHJLPHRQHVHOIWRDFKLHYHEORRGSUHVVXUH
FRQWURO'XULQJ\HDUVIROORZXSPHGLFDWLRQZDVKHOGVWDEOH$W )8 DQG
)8 \HDUIROORZXSRI¿FHEORRGSUHVVXUHDQGHYHQWVZHUHGHWHUPLQHG
Results: 2XW RI SDWLHQWV ZLWK 75+ VXEMHFWV DJHG ! \HDUV
(61.3%). Systolic blood pressure drop was 23.3±21 mmHg after 2 years in all
SDWLHQWVDQGWKHUHZDVQRVLJQL¿FDQWGLIIHUHQFHLQHOGHUO\DQG\RXQJHUVXEMHFWV
“! \“\S 7KHHOGHUO\ZLWK75+KDGDVLJQL¿FDQWKLJKHUPRUWDOLW\UDWH ! \\S DQGVLJQL¿FDQW
PRUH0$&&(HYHQWV ! \\S DIWHU\HDUV
Conclusions: Data up to 12 months indicate that renal denervation using the
EnligHTN multi-electrode catheter is effective in lowering home BP. Although
the reduction in home BP is less in magnitude it is still clinically meaningful at
all time points. Home BP measurements parallel the 24 hr measurements and
they can be a standard measurement in renal denervation studies.
9A.05
UNMASKING THE DISRUPTION OF THE RENAL
NERVES AT THE CATHETER BASED RENAL
DENERVATION PROCEDURE. DOES ELECTRICAL
STIMULATION ON RENAL ARTERIAL AUTONOMIC
NERVES REALLY WORK?
D. Tsiachris, &7VLRX¿VK. Dimitriadis, A. Kordalis, A. Kefala, K. Kintis,
K. Manakos, I. Kallikazaros, D. Tousoulis, C. Stefanadis. First Cardiology
Clinic, University of Athens, Hippokration Hospital, Athens, GREECE
Objective: Transluminal renal sympathetic denervation (RDN) reduces blood
pressure (BP) in patients with treatment-resistant hypertension but it remains a
blind procedure in the cath lab. Electrical stimulation of the renal arterial autoQRPLFQHUYHVKDVEHHQLGHQWL¿HGDVDQHQGSRLQWRIHQVXULQJUHQDO¿EHUGLVUXStion.We experimentally assessed the effect of electrical stimulation on renal arterial autonomic nerves before and after RDN by catheter based radiofrequency
renal ablation system.
Design and method: An appropriate introducer was inserted into each femoral artery in 10 juvenile farm swines under deep general anesthesia. RDN was
performed using established renal catheter based radiofrequency renal ablation
system inserted from the right femoral artery. BP was continuously monitored
from the left femoral artery. Electrical autonomic nerve stimulation at 20-Hz
frequency, 5-ms pulse duration, and 15-mA output was applied for 60 s to 3 minutes via the distal pair of a quadripolar catheter introduced via the right femoral
artery and placed successively in the ostium, proximal, middle and distal part of
each renal artery before and after RDN.
Results: Renal angiograms performed before and after RDN were normal in
all cases showing no apparent injury. Electrical stimulation was also applied
using different settings (frequency of 20 Hz, with an amplitude of 15 V and
pulse duration of 10 ms) as well as an open irrigation catheter. BP and heart
rate remained unchanged after electrical stimulation of either 1, 2 or 3 minutes
duration applied in the ostium, proximal, middle and distal part of each renal
artery. There was also no response to electrical stimulation of either renal artery after RDN.
,QWHUHVWLQJO\ EHWZHHQ WKH ¿UVW DQG VHFRQG \HDU PRUWDOLW\ UDWH IHOO E\ )8)8 DQG0$&&(HYHQWUDWHE\ )8)8 in elderly patients.
Conclusions: :HGRFXPHQWHGIRUWKH¿UVWWLPHWKDWWKHLQFLGHQFHRIFDUGLRYDVcular events and mortality rate is higher in elderly than in younger patients with
75+7KLVVWXG\DOVRVKRZHGPRGL¿FDWLRQRIGUXJWUHDWPHQWUHVXOWHGLQDFKLHYing blood pressure target in nearly 50%. In parallel mortality rate and MACCE
HYHQWVGHFUHDVHGIURP¿UVWWRVHFRQG\HDU
9A.07
HYPER-RESPONDER VS. NON-RESPONDER
PATIENTS AFTER RENAL DENERVATION: DO THEY
DIFFER?
A. Persu 1, M. Azizi 2, Y. Jin 3, S. Volz 4, J. Rosa 5, F. Fadl Elmula 6,
M. Burnier , P. Mark 8, A. Elvan 9, J. Renkin 1, M. Sapoval 2, T. Kahan 10,
S.E. Kjeldsen 6, J. Staessen 3. 1 Pole of Cardiovascular Research, Institut
de Recherche Expérimentale et Clinique, Université Catholique de Leuven,
Brussels, BELGIUM, 2 Faculté de Médecine, Université Paris Descartes,
Paris, FRANCE, 3 Studies Coordinating Centre, Division of Hypertension
and Cardiovascular Rehabilitation, Leuven, BELGIUM, 4 Department of
Cardiology, Sahlgrenska University Hospital, Gothenburg, SWEDEN,
5
Centre for Hypertension, General University Hospital, First Faculty of
Medicine, Charles University, Prague, CZECH REPUBLIC, 6 Department of
Cardiology, Ullevaal University Hospital, University of Oslo, Oslo, NORWAY,
7
Department of Nephrology, Lausanne University Hospital, Lausanne,
SWITZERLAND, 8 BHF Glasgow Cardiovascular Research Centre, University
of Glasgow, Glasgow, UNITED KINGDOM, 9 Department of Cardiology, Isala
Klinieken, Zwolle, NETHERLANDS, 10 Karolinska Institutet, Department of
Clinical Sciences, Danderyd Hospital, Division of Cardiovascular Medicine,
Stockholm, SWEDEN
e119
Journal of Hypertension Volume 32, e-Supplement 1, 2014
Objective: Blood pressure (BP) response after renal denervation (RDN) is highly variable. Besides baseline BP, no reliable predictors of response have been
FRQVLVWHQWO\LGHQWL¿HG7KHREMHFWLYHRIWKHVWXG\ZDVWRFRPSDUHWKHFKDUDFWHUistics of resistant hypertensive patients showing a major blood pressure decrease
after RDN to those of non-responders to the technique.
Design and method: We compared the main characteristics of extreme BP -responders (ER, 5th quintile) versus non-responders (NR, 1st quintile) included
in the ENCOReD (European Network COordinating research on REnal DenHUYDWLRQ GDWDEDVH Q SDWLHQWV GH¿QHGRQWKHǻRI¿FHRUKDPEXODWRU\
systolic BP 6 months after RDN.
Results: 0HDQǻRI¿FHV\VWROLF%3ZDVPP+JLQ15 Q DQG
PP+JLQ(5 Q &RPSDUHGWR15(5ZHUHPRUHIUHTXHQWO\ZRPHQ YVUHVSHFWLYHO\S KDGKLJKHUEDVHOLQHRI¿FH YV
mmHg, respectively, p<0.001) - but not ambulatory - systolic BP and higher esWLPDWHGJORPHUXODU¿OWUDWLRQUDWH H*)5YVPOPLQPUHVSHFWLYHO\S :KHQFRQVLGHULQJWKHǻKDPEXODWRU\V\VWROLF%3WRGH¿QH
(5DQG15WKHRQO\VLJQL¿FDQWGLIIHUHQFHEHWZHHQ(5DQG15ZDVEDVHOLQH
KDPEXODWRU\EXWQRWRI¿FHV\VWROLF%3 (5PP+JYV15
mmHg, p=0.033). Neither age, nor body mass index or type 2 diabetes appeared
as predictors of response in either analysis.
Conclusions: Clinical situations associated with sympathetic overactivity were
not over-represented in ER vs. NR to RDN. Furthermore, in agreement with
our previous report (Persu A, Jin Y et al., J Hum Hypertens. 2013), eGFR was
VLJQL¿FDQWO\ ORZHU LQ 15 WKDQ LQ (5 ,I FRQ¿UPHG WKH KLJKHU SUHYDOHQFH RI
ZRPHQLQ(5DFFRUGLQJWRRI¿FHEXWQRWDPEXODWRU\%3PLJKWUHÀHFWDGLIIHUence in drug adherence patterns between men and women. The lack of relevant
GLIIHUHQFHVEHWZHHQ(5DQG15GH¿QHGDFFRUGLQJWRDPEXODWRU\%3UDLVHVIXUWKHUTXHVWLRQVDERXWWKHQDWXUHDQGVSHFL¿FLW\RIWKHPHFKDQLVPVXQGHUO\LQJ%3
changes after RDN.
9A.08
NON-INVASIVE HEMODYNAMIC MONITORING AS
A GUIDE TO DRUG TREATMENT IN PATIENTS WITH
UNCONTROLLED HYPERTENSION: THE BEAUTY
STUDY
G. Parati 1, F. Fadl Elmula 2, A. Talvik 3, S. Salerno 1, E. Miszkowska-Nagórna 4,
P. Rebora 5, X. Liu 1, M. Heinpalu-Kuum 3, T. Comotti 1, A. Larstorp 2,
M. Rostrup 6, M. Valsecchi 5, S.E. Kjeldsen 2, M. Viigimaa 3, K. Narkiewicz 4,
S. Laurent . 1 Dept. of Cardiology, S. Luca Hospital, Istituto Auxologico
Italiano and Dept. of Health Sciences University of Milano-Bicocca, Milan,
ITALY, 2 University of Oslo, Ullevaal Hospital, Section for Cardiovascular
and Renal Research, Department of Cardiology, Oslo, NORWAY, 3 Tallinn
University of Technology, North Estonia Medical Centre, Tallinn, ESTONIA,
4
Medical University, Department of Hypertension and Diabetology, Gdansk,
POLAND, 5 Dept. of Health Sciences, University of Milano-Bicocca, Milan,
ITALY, 6 University of Oslo, Ullevaal Hospital, Section for Cardiovascular and
Renal Research, Dept. of Acute Medicine, Oslo, NORWAY, 7 Hôpital Européen
Georges Pompidou, Department of Pharmacology and INSERM U970, Paris,
FRANCE
ZLWK8&+ZHUHUDQGRPL]HGWR,+0JXLGHGGUXJDGMXVWHGWUHDWPHQW Q YV
classical clinically adjusted drug treatment (control, n=81) in an investigatorinitiated multicenter prospective randomized parallel groups controlled study.
Results: Ambulatory daytime SBP decreased on average to the same extent
from baseline to 6 months in IHM (-15±2 mmHg) and control (-16±2 mmHg,
3 JURXSV6LPLODUUHVXOWVZHUHREWDLQHGZKHQRI¿FH6%3FKDQJHVLQWKH
two groups were compared over the 4 study visits (P=0.63). Conversely, home
6%3YDOXHV DYDLODEOHLQ,+0DQGFRQWUROSDWLHQWV GLVSOD\HGDWPRQWKV
VLJQL¿FDQWO\ JUHDWHU UHGXFWLRQ LQ ,+0 “ PP+J WKDQ LQ FRQWURO JURXS
“PP+J3 $YHUDJHQXPEHURIVLGHHIIHFWVZDVVLJQL¿FDQWO\ORZHULQ,+0WKDQLQFRQWUROJURXS 3 Conclusions: 2XU¿QGLQJVVXJJHVWWKDWHDV\WRGRQRQLQYDVLYHPRQLWRULQJRI
KHPRG\QDPLFSDUDPHWHUVDVVRFLDWHGZLWKDSUHGH¿QHGDOJRULWKPRIGUXJVHOHFWLRQLQGXFHVVLPLODUUHGXFWLRQVLQDPEXODWRU\DQGRI¿FH6%3EXWVLJQL¿FDQWO\
greater reductions in home SBP, compared to classical clinical drug selection
in patients with uncontrolled hypertension referred to Hypertension Excellence
Centers. Finally, IHM-guided hypertension management is associated with fewer side effects than conventional management, which may favor better compliDQFHZLWKSUHVFULEHGWUHDWPHQW:HEHOLHYHWKHVH¿QGLQJVPD\JXLGHFOLQLFLDQV
in providing better quality BP control in the population.
9A.09
DIFFERENT PROFILE OF NEUROADRENERGIC
ACTIVATION AND BAROREFLEX FUNCTION
IN RESISTANT HYPERTENSION AND
PSEUDORESISTANT HYPERTENSION: A
MICRONEUROGRAPHIC STUDY
G. Seravalle 1, S. Buzzi 2, L. Magni 2, C. Ciuffarella 2, M. Macchiarulo 2,
M. Bombelli 2, G. Brambilla 2, R. Dell’Oro 2, G. Mancia 1,3, G. Grassi 2,3.
1
Istituto Auxologico Italiano, Milan, ITALY, 2 Clinica Medica, Università
Milano-Bicocca, Ospedale San Gerardo, Monza, ITALY, 3 Dipartimento di
Scienze della Salute, Università Milano-Bicocca, Milan, ITALY
Objective: We have recently shown that resistant hypertension (RHT) is characterized by a marked neuroadrenergic activation coupled with metabolic alterations compared to the non-resistant hypertensive state. It is unknown, however,
ZKHWKHUWKHVHFKDQJHVDUHVSHFL¿FIRUWKH5+7VWDWHRUDUHDOVRGHWHFWDEOHLQ
pseudoresistant hypertension (PRHT).
Design and method: In 11 treated RHT patients, 14 treated essential hypertensives with controlled blood pressure (HT) and 12 normotensive controls (C),
we evaluated sphygmomanometric blood pressure (BP), 24-hour BP (Spacelab),
EHDWWREHDW%3 )LQDSUHV KHDUWUDWHDQGV\PSDWKHWLFQHUYHWUDI¿F 061$PLcroneurography). The assessments, which included plasma aldosterone, HOMA
LQGH[ DQG VSRQWDQHRXV EDURUHÀH[ FRQWURO RI 061$ XVLQJ OLQHDU UHJUHVVLRQ
DQDO\VLV ZHUH DOVR FDUULHG RXW LQ WUHDWHG 35+7 ZKLWHFRDW DQG QRQ
compliant).
Objective: 'UXJWUHDWHGEXWXQFRQWUROOHGK\SHUWHQVLRQ 8&+ LVDZRUOGZLGH
problem. In the BEtter control of blood pressure in hypertensive pAtients moniWRUHG 8VLQJ WKH +270$1Š V<VWHP %($87< 6WXG\ ZH DLPHG DW LQYHVWLgating whether non-invasive monitoring of hemodynamic parameters combined
ZLWK D SUHGH¿QHG DOJRULWKP RI GUXJ VHOHFWLRQ LH LQWHJUDWHG KHPRG\QDPLF
management - IHM) improves the control of systolic blood pressure (SBP) at
ambulatory(A) BP monitoring as compared to classical drug selection (i.e. withRXW,+0 GXULQJDPRQWKLQWHQVLYHWUHDWPHQWSURJUDPLQSDWLHQWVZLWK8&+
Results: The three groups of hypertensive patients had clinic BP and MSNA
VLJQL¿FDQWO\ JUHDWHU WKDQ & :KHQ PDWFKHG IRU DJH ERG\ PDVV LQGH[ FOLQLF
DQGDPEXODWRU\SUHVVXUHWKH5+7KDGDVLJQL¿FDQWO\KLJKHU061$FRPSDUHG
WR+7 “YV“EVPLQ3 DQG& “EVPLQ3
IRUERWK 7KH35+7VKRZHGFOLQLF%3YDOXHVVLPLODUWR5+7EXWVLJQL¿FDQWO\
ORZHUYDOXHVRIKRXU%3DQG061$ “EVPLQ3 ,QDGGLWLRQ
LQWKH5+7JURXSWKHSODVPDDOGRVWHURQHDQG+20$LQGH[ZHUHVLJQL¿FDQWO\
JUHDWHUWKDQLQ+7DQG35+7 DOGRVWHURQH“YV“DQG“QJ
dl, P<0.05, HOMA: 2.3±0.3 vs 1.2±0.2 and 1.5±0.3 au). Finally, the modulation
RIVSRQWDQHRXVEDURUHÀH[FRQWURORI061$ZDVUHGXFHGLQ5+7DVFRPSDUHG
to C and HT (slope:-2.2±0.35 vs -2.9±0.4 and -2.8±0.4, P=NS) and to PRHT
(slope:-2.8±0.28).
Design and method: 8&+SDWLHQWVZHUHUHIHUUHGWR(XURSHDQ+\SHUWHQVLRQ
([FHOOHQFH&HQWHUVIRUWKRURXJKFOLQLFDODQGODERUDWRU\ZRUNXS8&+ZDVGH¿QHGDVHVVHQWLDOK\SHUWHQVLRQZLWKRI¿FH6%3!PP+JDQGDPEXODWRU\GD\WLPH6%3!PP+JZKHQWDNLQJRUPRUHDQWLK\SHUWHQVLYHGUXJV3DWLHQWV
Conclusions: These data provide evidence that the neuroadrenergic overdrive
GHWHFWHGLQ5+7LVVSHFL¿FIRUWKLVFRQGLWLRQDQGLWLVQRWIRXQGLQ35+77KLV
VSHFL¿FLW\PLJKWEHUHODWHGWRWKHDOWHUDWLRQVLQWKHQHXURKXPRUDOSUR¿OHDVZHOO
DVWRDQHDUO\LPSDLUPHQWRIEDURUHÀH[061$PRGXODWLRQ
Abstracts
e120
ORAL SESSION
ORAL SESSION 9B
KIDNEY
9B.01
EVALUATION OF SUBCLINICAL CARDIAC DAMAGE
AND ITS DETERMINANTS IN A COHORT OF KIDNEY
TRANSPLANTED PATIENTS
&$O¿HUL1, R. Floreani 1, M. Meneghini 1, A. Regalia 1, )=DQRQL1, M. Croci 1,2,
M. Rastaldi 1,2, P. Messa 1. 1 Department of Nephrology, Dialysis and Renal
Transplant, Fondazione IRCCS Ca’ Granda Osp. Maggiore Policlinico, Milan,
ITALY, 2 Research Laboratory of Nephrology, Fondazione IRCCS Ca’ Granda
Osp. Maggiore Policlinico, Milan, ITALY
Objective: Chronic kidney disease (CKD) is a condition with a relevant
cardiovascular(CV) risk. Left ventricular hypertrophy(LVH) is mostly responsible of it and is relevant also after kidney transplantation(KTx). In our study,
by means of echocardiography we explored at 1 and 12 months after KTx: 1)
the prevalence of LVH; 2) the factors related with left ventricular mass index
(LVMI) 3) the factors implicated with the development of LVH during the 1st
year of KTx.
Design and method: ,QSDWLHQWV 0 PHDQDJH“\HDUV WUDQVSODQWed in our unit between April 2004 and July 2013, clinical parameters, blood and
urinary samples were collected after an overnight fast at 1, 6 and 12 months
after KTx. In addition, at the same time, plasmatic levels of FGF-23, FetuinA, 25OH-Vitamin D, PTH, Ca, phosphorus and Osteoprotegerin were assessed.
Left ventricular hypertrophy(LVH) was determined by echocardiography, calFXODWLQJOHIWYHQWULFXODUPDVVLQGH[HGDWWKHKHLJKW /90, DWVWDQGWK
PRQWKDQGGH¿QHGDV/90,!JP
or on anti-hypertensive medications, excluding diuretics) subjects underwent
assessment of leg oedema, bioelectrical impedance measurement of total body
ZDWHU 7%: DQGOHJÀXLGYROXPHV /)9 DWQLJKWDQGWKHIROORZLQJPRUQLQJ
same-day 24 hour urine collection divided into day and night-time samples and
automated BP measurement.
Results: +\SHUWHQVLYHV Q %3 ““ KDG KLJKHU KRXU “ YV “ PPRO S DQG QLJKWWLPH 81D9
“ YV “ PPROKRXU S EXW ORZHU GD\WLPH 81D9
“ YV “ PPROKRXU S WKDQ QRUPRWHQVLYHV Q %3““ +\SHUWHQVLYHVKDGPRUHOHJRHGHPDORZHUHYHQLQJOHJLQWUDFHOOXODUÀXLGYROXPH ,&9“YV“/S DQGKLJKHU(&9,&9UDWLR “YV“S WKDQQRUPRtensives.
In normotensives, but not hypertensives, overnight leg ECV change inversely
FRUUHODWHG ZLWK KRXU 81D9 DQG ZDV PRVW VWURQJO\ FRUUHODWHG ZLWK QLJKW
81D9 )LJXUH 2Q VWHSZLVH OLQHDU UHJUHVVLRQ LQFOXGLQJ DJH VH[ %0, V\Vtolic (S)BP and overnight leg ECV change, overnight leg ECV change was the
RQO\LQGHSHQGHQWSUHGLFWRURIKRXU81D9 Uð S GD\81D9
Uð S DQG QLJKW 81D9 Uð S LQ QRUPRWHQVLYHV
,Q K\SHUWHQVLYHV 6%3 ZDV WKH RQO\ LQGHSHQGHQW SUHGLFWRU RI QLJKW 81D9
Uð S ZLWKQRLQGHSHQGHQWUHODWLRQVKLSVEHWZHHQKRXURUGD\
81D9DQGDQ\RIWKHYDULDEOHV
Conclusions: ,QQRUPRWHQVLYHLQGLYLGXDOVWKHFRUUHODWLRQEHWZHHQ81D9DQG
overnight change in leg ECV suggests a normal renal response to increased
ECV. However, in hypertensive patients, the kidneys may be unable to normally
regulate ECV via sodium excretion, resulting in elevated BP in order to excrete
excess sodium overnight.
Results: Fifty-nine and 53% of patients had LVH at 1st (LVHpos1) and 12th
mth (LVHpos12) resp. At univariate regression, at 1st mth, LVMI correlated directly with baseline serum albumin (p=0.008), FGF-23 (p=0.01), sistolic blood
SUHVVXUH S 83URWK S DQGERG\PDVVLQGH[ S /90,DW
12th mth was directly correlated with age (p=0.005), baseline albumin (p=0.01),
OPG (p=0.01), FGF-23 (p=0.05) and with LVMI at 1th mth (p=0.001). DurLQJ WKH ¿UVW \HDU RI .7[ RI SDWLHQWV GHYHORSHG /9+ ZKHUHDV KDG
its regression. Once those variables were analyzed in a logistic regression only
/90,DWEDVHOLQHUHVXOWHGWKHRQO\PRGL¿DEOHULVNIDFWRUDVVRFLDWHGZLWK/9+
GHYHORS1RLQÀXHQFHLQ/9+GHYHORSZDVIRXQGIRU,PPXQRVXSSUHVVLYHDQG
DQWLK\SHUWHQVLYH WKHUDS\ ERWK LQ JHQHUDO DQG FODVVVSHFL¿FDOO\ 1R UHODWLRQV
were found with Hb levels and mineral metabolism parameters.
Conclusions: The prevalence of LVH is relatively high in KTx patients. Nevertheless, in a small portion of them, we observed an improvement of cardiac abnormalities. Albumin, FGF-23 and BMI seem to be directly related with LVMI.
,QDQ\FDVH/90,DWEDVHOLQHLVWKHRQO\PRGL¿DEOHULVNIDFWRUDEOHLQSUHGLFWLQJ
developing of LVH.
9B.02
RELATIONSHIP BETWEEN EXTRACELLULAR FLUID
MOVEMENT DURING SLEEP AND URINE SODIUM
EXCRETION IN NORMOTENSIVE AND HYPERTENSIVE
SUBJECTS
L. White 1, T. Bradley 1, A.G. Logan 2. 1 Sleep Research Laboratory, Toronto
Rehabilitation Institute, University Health Network, Toronto, CANADA,
2
Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto,
CANADA
Objective: ([WUDFHOOXODU ÀXLG YROXPH (&9 LV FORVHO\ UHODWHG WR WKH UHJXODtion of sodium balance. In normal subjects a high salt diet increases ECV and
XULQHVRGLXPH[FUHWLRQ 81D9 'XULQJWKHGD\JUDYLWDWLRQDOIRUFHVLQFUHDVHOHJ
ECV that is reabsorbed overnight during sleep and excreted by the kidneys. In
hypertensive patients, however, defective renal sodium handling may alter such
a relationship. We hypothesized that unlike normotensives, overnight reduction
LQOHJ(&9ZRXOGQRWEHDVVRFLDWHGZLWK81D9LQK\SHUWHQVLYHVZKLFKZRXOG
result in increased intravascular volume and blood pressure (BP).
Design and method: 1RUPRWHQVLYH %3 DQGK\SHUWHQVLYH %3!
9B.03
PRENATAL LIPOPOLYSACCHARIDE EXPOSURE
RESULTS IN DYSFUNCTION OF RENAL DOPAMINE D1
RECEPTOR IN OFFSPRING RATS
X. Wang 1, H. Luo 1, J. Wang 2, C. Chen 1, Y. Cai 1, 6=KHQJ1, /=KRX1,
&=HQJ1. 1 Department of Cardiology, Daping Hospital, Third Military
Medical University, Chongqing, CHINA, 2 Department of Cardiology, First
$I¿OLWDWHG+RVSLWDO6KDQWRX8QLYHUVLW\0HGLFDO&ROOHJH6KDQWRX&+,1$
Objective: Adverse environment in early life can modulate adult phenotype,
including hypertension. Lipopolysaccharide (LPS) exposure in utero results in
increased blood pressure in offspring, but the exact mechanisms are not clear.
Studies have shown that dysfunction of renal D1 receptor(D1R) are linked to hypertension, which associated with oxidative stress. In this study, we test whether
dysfunction of renal D1R is involved in the fetal programmed hypertension, and
whether oxidative stress contribute to this process.
M
O
N
D
A
Y
O
R
A
L
S
e121
Journal of Hypertension Volume 32, e-Supplement 1, 2014
Design and method: Pregnant Sprague–Dawley (SD) rats were intraperitonealO\LQMHFWHGZLWK/36 PJNJ RUVDOLQH PO DWJHVWDWLRQGD\DQG
12. After birth, the blood pressure of offspring rats was measured, and renal D1R
function was anlasysed when treated with or without antioxidant tempol in tap
water for 3 weeks at postnatal12 week.
Results: As compared with control rats, the LPS-treated offspring rats showed
higher blood pressure, decreased renal sodium excretion with increased plasma
ROS activity. After tempol treatment, the increased blood pressure, decreased
sodium excretion were reversed to normal levels in LPS rats. Our further study
found LPS rats had lower renal D1R expression, higher D1R phosphorylation,
and D1R-mediated natriuresis and diuresis were lost. As an important kinase
of D1R phosphorylation, G coupled receptor protein kinase 4 (GRK4) expression was increased in LPS rats. Tempol treatment reversed the decreased D1R
expression, increased D1R phosphorylation and GRK4 expression. Moreover,
the impaired D1R-mediated natriuresis and diuresis were restored to the control
levels in LPS rats after tempol treatment.
Conclusions: Prenatal LPS exposure, via impairment of ROS on renal D1R
function, leads to hypertension in offspring. Reversion of renal D1R function
by alleviation of ROS might be a target for therapy of fetal programming hypertension.
9B.04
ACSDKP-NH2 AS A NEW NON-RADIOACTIVE
PEPTIDIC MARKER OF GLOMERULAR FILTRATION
RATE (GFR) IN HUMANS
A. Blanchard 1, E. Curis 1,2, 9=K\JDOLQD1,2, C. Gauci 3, D. Prie 1,4, E. Ezan 5,
M. Azizi 1,2. 1 Université Paris Descartes, Paris, FRANCE, 2 Centre
d’Investigation Clinique, HEGP, Paris, FRANCE, 3 Département de
Physiologie, HEGP, Paris, FRANCE, 4 Département de Physiologie, Necker,
Paris, FRANCE, 5 CEA, Service de Biochimie et Toxicologie Nucléaire,
Marcoule, FRANCE
Objective: AcSDKP-NH2 is the amidated form of AcSDKP, a natural
hemoregulatory tetrapeptide. We have shown that urinary clearance of AcSDKP-NH2 and of tritiated inulin in rats give identical results. We performed
DQRSHQODEHOHTXLYDOHQFHSKDVH,,,DVWXG\WRYDOLGDWH$F6'.31+DVD
GFR marker in humans.
Design and method: GFR was measured in two groups (G1 and G2) of 25
healthy male subjects and one group (G3) of 15 patients with chronic kidney
disease, using AcSDKP-NH2 and either inulin or 51Cr EDTA as gold standard GFR markers. G1 received simultaneously AcSDKP-NH2 (IV bolus inMHFWLRQRI—JNJIROORZHGE\DFRQWLQXRXVLQIXVLRQRI—JPLQP/
H*)5IRUPLQWRWDOGRVH —J DQGLQXOLQH ,9EROXVRIPJ
NJWKHQFRQWLQXRXVLQIXVLRQRIPJPLQP/H*)5IRUPLQ *
received simultaneously AcSDKP-NH2 (IV bolus 100µg) and 51Cr EDTA
0%T,9EROXV *UHFHLYHGVLPXOWDQHRXVO\$F6'.31+ ,9EROXV
—J DQGLQXOLQ VDPHDV* $F6'.31+ZDVPHDVXUHGE\/&06
MS. GFR was (i) estimated by the MDRD equation (eGFR), (ii) calculated
from urinary clearance or (iii) estimated by two-compartment pharmacokinetics model for single IV administration.
Results: $F6'.31+LQMHFWLRQZDVZHOOWROHUDWHG7KHUHZDVQRVLJQL¿cant bias between GFR Inuline or GFR AcSDKP-NH2 in G1 and G3 (1.1
>,& @ POPLQP S DQG >,& @ PO
PLQPS UHVSHFWLYHO\ :KHQFRPELQLQJWKH*)5YDOXHVRI*
and G3, there was a good concordance between both markers (Lin coef¿FLHQW *)5$F6'.31+LQ* LQIXVLRQ DQG* VLQJOH,9ERlus) were similar. In contrast, GFR 51Cr EDTA (G2) was much lower than
*)5 ,QXOLQH * HYHQ WKRXJK H*)5 YDOXHV ZHUH VLPLODU FRQ¿UPLQJ WKH
known underestimation of GFR by 51Cr-EDTA. Therefore, the bias between
*)5$F6'.31+DQG*)5&U('7$ZDV>,&@PO
PLQPS Conclusions: 7KLV VWXG\ YDOLGDWHV IRU WKH ¿UVW WLPH WKDW$F6'.31+ DV D
new and peptidic marker for GFR measurement in humans, that could be used
in single administration.
9B.05
ENDOTHELIN-1 CAN INDUCE EPITHELIALMESENCHYMAL TRANSITION (EMT) IN THE HUMAN
KIDNEY PROXIMAL TUBULE CELLS
T.M. Seccia 1, B. Caroccia 1, F. Gioco 1, A. Gonzales-Campos 1, V. Buccella 1,
M. Piazza 1, B. Montini 2, L. Calo 1, D. Guidolin 3, A. Belloni 3, G. Rossi 1.
1
Internal Medicine 4, Dept. Medicine-DIMED, University of Padua, Padua,
ITALY, 2 Haematology and Immunology, Dept. Medicine-DIMED, University
of Padua, Padua, ITALY, 3 Human Anatomy, Dept. Molecular Medicine,
University of Padua, Padua, ITALY
Objective: As the mechanisms by which epithelial-mesenchymal transition
(07 FRQWULEXWHV WR UHQDO ¿EURVLV DUH XQNQRZQ ZH LQYHVWLJDWHG WKH UROH RI
endothelin-1 (ET-1) in human renal tubular cells and the ET-1 receptor subtypes
that mediate EMT.
Design and method: The human renal tubular cells HK2 were stimulated in
YLWURZLWK(7LQWKHDEVHQFHRULQWKHSUHVHQFHRIWKH(7$(7%UHFHSWRUDQtagonist macitentan, the selective ETA antagonist ambrisentan, or the selective
(7%DQWDJRQLVW%47*)EHWDVWLPXODWLRQZDVXVHGDVDSRVLWLYHFRQWURO
Changes of expression of the epithelial marker E-cadherin (ECAD) and of the
mesenchymal markers alphaSMA and vimentin (VIM) were used as surrogate
markers for EMT.
Results: Gene expression of ECAD decreased whereas the protein expression
of alphaSMA and VIM increased (all p<.05) after cell stimulation with ET-1.
More marked changes were found for markers (ECAD (by -40%); alphaSMA
S 'RXEOHLPPXQRÀXRUHVFHQFHDQGFRQIRFDOPLFURVFRS\UHYHDOHG
co-expression of epithelial and mesenchymal markers after ET-1 challenge.
These changes were associated with an increased gene expression of collagen
&2// DOSKD&2//DOSKD ERWK &2//DOSKD DQGPHWDOORSURWHDVH 003 DQGZLWKLQFUHDVHG003DFWLYLW\7UDQVLWLRQRI
ET-1-treated HK2 cells into mesenchymal cells and extracellular matrix invaVLRQZDVFRQ¿UPHGE\WKHVFDWWHUWHVW 5HDO7LPH&HOO$QDO\]HU7HFKQRORJ\ Selective ETA receptor blockade prevented changes in ECAD and alphaSMA
expression, nonselective antagonism being ineffective.
Conclusions: In the human renal proximal tubular cells, ET-1 induces EMT
that is characterized by coexpression of epithelial and mesenchymal markers,
collagen deposition and activation of metalloproteases by acting via ETA recepWRU VXEW\SH7KH LGHQWL¿FDWLRQ RI WKLV LQYROYHPHQW RI (7 DQG (7$ LQ (07
could have important therapeutic implications for all conditions leading to renal
¿EURVLV
9B.06
AMBULATORY RECORDING OF WAVE REFLECTION
AND ARTERIAL STIFFNESS PARAMETERS DURING
THE LONG INTERDIALYTIC INTERVAL IN PATIENTS
RECEIVING CONVENTIONAL HEMODIALYSIS
G. Koutroumpas 1, 36DUD¿GLV2, P. Georgianos 2, A. Karpetas 2, A. Protogerou 3,
P. Malindretos 1, C. Syrganis 1, S. Panagoutsos 4, P. Pasadakis 4. 1 Department
of Nephrology, Achillopouleion General Hospital, Volos, GREECE, 2 Section of
Nephrology and Hypertension, 1st Department of Medicine, AHEPA University
Hospital, Thessaloniki, GREECE, 3 Hypertension Unit and Cardiovascular
Research Laboratory, Laiko Hospital, Medical School, National and
Kapodistrian Univ., Athens, GREECE, 4 Department of Nephrology,
Alexandroupolis University Hospital, Alexandroupolis, GREECE
Objective: Vascular remodeling in hemodialysis (HD) patients is characterized
by accelerated arterial stiffening, which represents strong and independent predictor of mortality. Recent cohort studies have demonstrated that long interdialytic interval is associated with heightened risk of cardiovascular death in
patients receiving conventional thrice weekly HD. The aim of this study was to
LQYHVWLJDWHIRU¿UVWWLPHSRWHQWLDOYDULDWLRQVEHWZHHQ'D\'D\DQG'D\RI
DKRXULQWHUGLDO\WLFSHULRGLQ+'SDWLHQWV
Design and method: A total of 32 end-stage renal disease patients receiving
conventional HD underwent a brachial and aortic Ambulatory Blood Pressure
Monitoring (ABPM) with the newly-introduced Mobil-O-Graph device (IEM,
6WROEHUJ*HUPDQ\ $%30FRYHUHGDZKROHKRXULQWHUGLDO\WLFSHULRGSULRUWRWKH¿UVW+'VHVVLRQRIWKHZHHN0RELO2*UDSKLVDYDOLGDWHGEUDFKLDO
cuff-based automatic oscillometric device that records blood pressure (BP) and
pulse waveforms at brachial artery and calculates augmentation index (AIx),
total vascular resistance (TVR) and pulse wave velocity (PWV) in ambulatory
conditions. Mean day-time and night-time values of the above parameters were
compared between Day 1, 2 and 3 of the long interdialytic interval.
Results: 1RVLJQL¿FDQWGLIIHUHQFHVLQGD\WLPH$,[ZHUHHYLGHQWEHWZHHQ'D\
1, Day 2 and Day 3 of the long interdialytic interval, whereas night-time AIx
e122
Journal of Hypertension Volume 32, e-Supplement 1, 2014
DW 'D\ ZDV VLJQL¿FDQWO\ ORZHU WKDQ QLJKWWLPH$,[ DW 'D\ “ YV
32±9.5%, P<0.05). In contrast, a gradual increase in TVR was observed beWZHHQ 'D\ DQG 'D\ DW ERWK GD\WLPH “ YV “ YV “
V PP+JPO3 DQGQLJKWWLPHSHULRGV “YV“YV“
V PP+JPO3 6LPLODUO\3:9ZDVDOVRHOHYDWHGIURP'D\WR'D\
DWUHQGWKDWZDVFRQVLVWHQWLQERWKGD\WLPH “YV“YV“PV
3 DQGQLJKWWLPHSHULRGV “YV“YV“PV3 (P<0.001). A total of 94% (n=33) and 90% (n=18) with the higher resistive index
UHDFKHGWKHFRPELQHGHQGSRLQWDVFRPSDUHGWR Q RIWKRVHZLWKORZHU
UHVLVWLYHLQGH[ PXOWLYDULDWHUHODWLYHULVN&,WR3 Conclusions: 7KLV VWXG\ VKRZHG IRU ¿UVW WLPH D JUDGXDO LQFUHDVH LQ DUWHULDO
VWLIIQHVV SDUDPHWHUV GXULQJ WKH KRXU LQWHUGLDO\WLF SHULRG 7KH VLJQL¿FDQWO\
higher TVR and PWV at Day 3 of the long interdialytic interval may represent
a mechanism possibly involved in the increased risk of death of HD patients at
this time-period.
9B.07
PODOCYTE MICROPARTICLES INDUCE P38
ACTIVATION AND REACTIVE OXYGEN SPECIES
PRODUCTION IN HUMAN CULTURED PROXIMAL
TUBULE CELLS
D. Burger, S. Akbari, M. Turner.
Ottawa Hospital Research Institute, Ottawa, CANADA
Objective: Microparticles (MPs) are small (0.1-1.0), membranous vesicles shed
IURPWKHFHOOVXUIDFHIROORZLQJVWUHVVLQMXU\5HFHQWO\ZHUHSRUWHGWKDW03VDUH
produced by podocytes following mechanical stretch (a mimic of intraglomerular hypertension. However whether podocyte MPs interact with the proximal
WXEXOH DQG LQÀXHQFH IXQFWLRQ LV XQNQRZQ 7KH SXUSRVH RI WKLV VWXG\ ZDV WR
assess the effects of podocyte MPs on proximal tubule cells.
Design and method: Cultured human proximal tubule cells were exposed to
SRGRF\WH03V PO DQGSKRVSKRU\ODWLRQRIS(5.DQG-1.ZHUH
examined by Western blot analysis. Reactive oxygen species (ROS) production
was assessed by lucigenin chemiluminescence.
Results: p38 phosphorylation was increased (~3 fold) after 30 minutes exposure
to podocyte microparticles. By contrast, JNK and ERK phosphorylation levels
were unchaged over 24 hours. In addition, ROS production was shown increased
E\SRGRF\WH03WUHDWPHQWDWKRXUV FRQWURO“YVWUHDWHG“$8
mg protein). Fluorescence microscopy revealed cell surface binding of podocyte
MPs to proximal tubule cells suggesting a paracrine effect.
Conclusions: Our results suggest that podocyte MP interact with proximal
tubule epithelial cells and induce intracellular signaling and ROS production.
Such effects may play a role in the development of tubular injury in hypertensive
and diabetic nephropathy.
9B.08
LONG-TERM OUTCOME AFTER ANGIOPLASTY IN
PATIENTS WITH RENAL ARTERY STENOSIS AND
HIGH RESISTIVE INDEX: A PROSPECTIVE COHORT
STUDY
Conclusions: Patients with renal artery stenosis and a renal resistive index value
RI! GRQRWEHQH¿WIURPDQJLRSODVW\UHJDUGLQJUHQDORUSDWLHQWVXUYLYDO
9B.09
PREDICTIVE VALUE OF MARKERS OF VASCULAR
DAMAGE FOR RENAL OUTCOME IN TYPE 2
DIABETES AND ESSENTIAL HYPERTENSION
R. Bruno 1, A. Salvati 2, M. Barzacchi 2, K. Raimo 2, L. Ghiadoni 2, A. Solini 2.
Institute of Clinical Physiology, CNR, Pisa, ITALY, 2 Department of Clinical
and Experimental Medicine, University of Pisa, Pisa, ITALY
1
Objective: We have recently shown that renal vasodilating response to nitrates
(dynamic renal resistive index, DRIN) is an early vascular alteration, already
present in normoalbuminuric individuals. The aim of the present study is to
evaluate prospectively if this parameter, as well as other markers of systemic
vascular damage, is able to predict microalbuminuria onset.
Design and method: We studied 60 individuals (25 with type 2 diabetes, 35
with essential hypertension) following them prospectively. The following parameters were assessed: renal resistive index (RI), DRIN (% change in RI after
JO\FHU\O WULQLWUDWH *71 ȝJ VO HQGRWKHOLXPGHSHQGHQW ÀRZPHGLDWHGGLlation - FMD) and independent (response to GTN) vasodilation in the brachial
artery, carotid-femoral pulse wave velocity (PWV), and augmentation index
$,[ $WWKHIROORZXSYLVLWPLFURDOEXPLQXULDRQVHWZDVGH¿QHGZLWKXULQDU\
DOEXPLQHFUHDWLQLQHUDWLR 8$&5 !PJJ
Design and method: We measured the renal resistive index with Color Doppler ultrasonography in segmental arteries of both kidneys. 131 patients with
XQLODWHUDORUELODWHUDOUHQDODUWHU\VWHQRVLV !SHUFHQWQDUURZLQJ XQGHUZHQW
UHQDODQJLRSODVW\ SHUFHQW RIWKHVHKDGUHQDOUHQDOUHVLVWLYHLQGH[YDOXHV
!$IXUWKHUJURXSRISDWLHQWVZLWKUHVLVWLYHLQGH[!DQGUHQDODUWHU\
VWHQRVLV ! GLG QRW XQGHUJR DQJLRSODVW\7KH FRPELQHG HQGSRLQW ZDV !
percent decrease in eGFR, end stage renal failure, or death. Mean±SD follow-up
was 8.8±4.0 years.
Results: $IWHU D IROORZXS SHULRG RI “ \HDUV 8$&5 LQFUHDVHG IURP
WR PJJ LQGLYLGXDOV GHYHORSHG PLFURDOEXPLQXULD$W
enrollment, patients who would develop microalbuminuria tended to be older
“ YV “\HDUV S DQG PRUH RIWHQ GLDEHWLF YV
P=0.06). Among vascular parameters, RI (0.63±0.05 vs 0.59±0.06, P=0.04),
'5,1 “ YV “ 3 DQG 3:9 “ YV “PV
P= 0.005), were worse at baseline in those who would develop microalbuminXULD GXULQJ IROORZXS &RQYHUVHO\$,[ “ YV “ S )0'
“ YV “ S DQG *71 “ YV “ S were similar in the two groups.
&RQVLGHULQJ RQO\ GLDEHWLF SDWLHQWV DW HQUROOPHQW '5,1 “ YV
“ S EXW QRW 5, “ YV “ S RU 3:9
“YV“PVS ZDVVLJQL¿FDQWO\ZRUVHLQSDWLHQWVZKRZRXOG
develop microalbuminuria, whereas in the hypertensive group RI (0.61±0.04
YV“S DQG3:9 “PVYV“PVS EXWQRW
'5,1 “YV“S ZHUHDOWHUHGLQSDWLHQWVGHYHORSLQJ
microalbuminuria.
Results: ,QWKRVHSDWLHQWVZLWKUHQDOUHVLVWLYHLQGH[YDOXHV!D!SHUFHQW
GHFUHDVHLQUHQDOIXQFWLRQRFFXUUHGLQ SDWLHQWVZLWKDQJLRSODVW\DQG
ZLWKRXWLQWHUYHQWLRQFRPSDUHGWR RIWKRVHZLWKDQJLRSODVW\DQGORZHUUHVLVWLYHLQGH[ DQG SDWLHQWVFRPSDUHGWR
UHTXLUHGGLDO\VLVDQG DQG FRPSDUHGWR GLHG
Conclusions: These preliminary results suggest that some parameters of vascular damage, such as RI, PWV and DRIN are able to predict microalbuminuria
onset in essential hypertension and type 2 diabetes. These markers might be
useful in elucidating pathophysiology and predicting the development of renal
damage.
N. Scherer 1, F. Limbourg 2, F. Rauch 1, M. Hiss 2, H. Haller 1, J. Radermacher 2.
1
Dept. of Nephrology and Hypertension, Johannes Wesling Klinikum, Minden,
GERMANY, 2 Dept. of Nephrology and Hypertension, Hannover Medical
School, Hannover, GERMANY
Objective: ,GHQWLI\LQJSDWLHQWVZKREHQH¿WIURPUHYDVFXODUL]DWLRQRIUHQDODUtery stenosis has not been possible. We studied whether a high renal resistive
index predicted inferior long-term outcome after revascularization.
Abstracts
e123
ORAL SESSION
ORAL SESSION 9C
BLOOD PRESSURE VARIABILITY
9C.01
ARTERIAL STIFFNESS AND AUTONOMIC NERVOUS
FUNCTION IN ORTHOSTATIC BLOOD PRESSURE
CHANGES
M. Yamamoto, M. Oka, M. Takahashi, N. Miyai, 08WVXPL<8FKLNDZD
S. Hattori, M. Arita. Graduate School of Health and Nursing Science,
Wakayama Medical University, Wakayama, JAPAN
Objective: Emerging evidences suggest that orthostatic blood pressure (BP)
changes are associated with the risk of cardiovascular disease. In this study, we
carried out a simple standing-up test and evaluated the relationships between
orthostatic BP changes, autonomic nervous function and arterial stiffness in a
Japanese general population.
Design and method: $ WRWDO RI VXEMHFWV PHQ DQG ZRPHQ ZHUH
selected from the participants in a Wakayama population-based health study.
They underwent a simple standing-up test, and during the test brachial BP was
measured every min and the R-R intervals of ECG were continuously evaluated. Peripheral pressure waveforms were recorded from the radial artery using tonometry method. Orthostatic hypotension (OH) was assessed with blood
pressure measurements in sitting and standing position. The brachial-ankle (ba)
pulse wave velocity was an index of arterial stiffness. Comparison examination
was carried out among 2 groups of an orthostatic hypotension group and a normal group.
XHV IRU GLIIHUHQW %3 YDULDELOLW\ LQGLFHV ZHUH GH¿QHG ZLWK<RXGHQ PHWKRG E\
DQDO\]LQJWKHLUVHQVLWLYLW\DQGVSHFL¿FLW\LQUHODWLRQWRFDUGLRYDVFXODUPRUWDOLW\
Diastolic BP variability indices previously shown to independently predict outcome in this population were considered (no systolic BP variability estimate was
independently predictive): daytime standard deviation (daySD), weighted 24 h
SD (wSD, time-weighted average of day and night BP SD), average real variability (ARV, average of absolute differences between consecutive BP measures)
and residual BP variability (rBPV, BP variability unexplained by two principal
circadian cyclic components).
Results: All assessed variables had similar areas under receiver operating
characteristics (ROC) curves for cardiovascular mortality (0.61-0.63). Optimal
WKUHVKROGYDOXHVGH¿QHGE\<RXGHQ,QGH[ZHUHPP+JIRUGD\6'
PP+J IRU Z6' PP+J IRU$59 DQG PP+J IRU U%39 %DVHG RQ
these results we propose, as more convenient, a common cut-off of 10 mmHg for
daySD and wSD, 9 mmHg for ARV and 8 mmHg for rBPV, values roughly corUHVSRQGLQJWRWKSHUFHQWLOHVRIGLVWULEXWLRQRIWKHVHYDULDEOHVLQVWXG\SRSXODtion. Kaplan-Mayer curves for survival free of cardiovascular death and hazard
ratios associated with the above thresholds (both unadjusted and adjusted for
major confounders, including average BP) are shown in Figure.
Results: OH was present in 31 subjects with a mean age±standard deviation
RI“DQGDEVHQWLQVXEMHFWVDJHG“6LJQL¿FDQWFRUUHODWLRQV
were found between ba pulse wave velocity and resting systolic blood presVXUH Uð S DQGV\PSDWKHWLFĮIXQFWLRQ Uð 3 6\VWROLFEORRGSUHVVXUHZDVVLJQL¿FDQWO\KLJKHU YVPP+JS įV\PSDWKHWLFĮIXQFWLRQ YVS DQG&&9+) YV
S ZHUHVLJQL¿FDQWO\ORZHULQ2+WKDQZLWKRXW3XOVHZDYHYHORFLW\ZDV
VLJQL¿FDQWO\KLJKHULQ2+WKDQWKRVHZLWKRXW YVPPVS 7KHUHDUHQRVLJQL¿FDQWGLIIHUHQFHVRIPHDQ,07LQERWKJURXS,QPXOWLYDULDWH
UHJUHVVLRQDQDO\VHV6%3FKDQJHVDIWHUVWDQGLQJUHVXOWHGWREHVLJQL¿FDQWO\DVVRFLDWHGWRįĮIXQFWLRQED3:9&955 SDUDV\PSDWKHWLFQHUYHIXQFWLRQ /+
at standing.
Conclusions: ,Q 2+ &&9+) DQG į Į IXQFWLRQ ZHUH VLJQL¿FDQWO\ ORZHU DQG
DUWHULDOZDOOVWLIIQHVVZDVVLJQL¿FDQWO\JUHDWHUWKDQZLWKRXW2+%ORRGSUHVVXUH
FKDQJHVDIWHUVWDQGLQJZDVVLJQL¿FDQWO\UHODWHGWRįĮIXQFWLRQED3:9&955 SDUDV\PSDWKHWLFQHUYHIXQFWLRQ /+DWVWDQGLQJ
These results highlight the possible role of changes in the arterial tree and autonomic nervous function in the hemodynamic response to orthostatic challenges.
9C.02
OUTCOME BASED THRESHOLD VALUES FOR
INCREASED BLOOD PRESSURE VARIABILITY. DATA
FROM DUBLIN OUTCOME STUDY
G. Bilo 1, E. Dolan 2, R. Facchetti 3, E. O’Brien 4, G. Mancia 3, G. Parati 1,3.
Dept. of Cardiovascular, Neural and Metabolic Sciences, Ospedale San
Luca, Istituto Auxologico Italiano, Milan, ITALY, 2 Connolly Hospital, Dublin,
IRELAND, 3 Dept. of Health Sciences, University of Milano-Bicocca, Milan,
ITALY, 4 Conway Institute, University College, Dublin, IRELAND
1
Conclusions: We propose outcome-based threshold values for diastolic BP variability estimates. Further studies are needed in order to validate these thresholds
in other populations.
9C.03
PREDICTIVE VALUE OF DIFFERENT INDICES
OF BLOOD PRESSURE VARIABILITY ON
CARDIOVASCULAR MORTALITY AND ORGAN
DAMAGE: DATA FROM THE PAMELA STUDY
G. Brambilla 1, M. Bombelli 1, R. Facchetti 1, F. Nicoli 1, D. Fodri 1, E. Toso 1,
F. Ganz 1, R. Dell’Oro 1, G. Seravalle 2, G. Grassi 1,3, G. Mancia 2,3. 1 Clinica
Medica, Univesità Milano-Bicocca, Ospedale San Gerardo, Monza, ITALY,
2
Istituto Auxologico Italiano, Milan, ITALY, 3 Dipartimento di Scienze della
Salute, Università Milano-Bicocca, Milan, ITALY
Objective: Blood pressure (BP) variability has been repeatedly shown to have
independent prognostic relevance. However, so far outcome-based threshold BP
variability values for identifying subjects at higher risk because of increased
BP variability are lacking. Aim of this analysis of Dublin Outcome Study data
was to propose such thresholds for several measures of short-term (24 hour)
BP variability, including new indices, devoid of interference from circadian BP
variation.
Objective: Whether and to what extent blood pressure variability may provide
information on cardiovascular prognosis and organ damage remains controversial. This may depend, among other factors, on the different variability indices
used in the studies published so far. The present study was aimed at providing
a vis-a-vis comparison of the value of different variability indices in predicting
cardiovascular events as well as development of target organ damage.
Design and method: The study included 10,500 untreated subjects (age
“ PDOH DVVHVVHG IRU K\SHUWHQVLRQ DQG VXEVHTXHQWO\ IROORZHG
over 5.8 years, in whom 24h ABPM was obtained at baseline. Threshold val-
Design and method: In the PAMELA study was evaluated the variability
(standard deviation, SD) among systolic blood pressure values measured during
a single visit (IT), between visits (IF) and between home measurements (H).
M
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N
D
A
Y
O
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A
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e124
Journal of Hypertension Volume 32, e-Supplement 1, 2014
Weighted SD of 24-hour blood pressure (wSD) was also evaluated. These indices were then related with cardiovascular (CV) and all-cause mortality as well
as with new-onset cardiac organ damage (LVH), diabetes mellitus (DM) and
hypertension.
Results: With the exception of IT all the indices were associated with a
greater risk of CV mortality (IF:HR=1.036, P=0.01; H:HR=1.029, P=0.01;
wSD:HR=1.229, P<0.001). After adjustment for age and gender, however, only
Z6' UHPDLQHG D VLJQL¿FDQW SUHGLFWRU RI &9 PRUWDOLW\ +5 3 Similar results were observed for all-cause mortality. The multivariable analysis performed by stepwise selection showed that CV mortality was indepenGHQWO\ SUHGLFWHG E\ DJH JHQGHU PDOHV DQG V\VWROLF RI¿FH EORRG SUHVVXUH
while all-cause mortality by age, gender (males) and wSD. After adjustment for
FRQIRXQGHUVWKHLQFUHDVHRIZ6'VLJQL¿FDQWO\DXJPHQWHGWKH\HDUULVNRI
developing DM (HR=1.105, P <0.05), while the increase of wSD and IT (but not
IF or H) was associated with an increased risk of developing a new onset LVH
,7+5 3Z6'+5 3 7KHDGMXVWHGULVNRIGHYHORSLQJ DQ RXWRIRI¿FH K\SHUWHQVLRQ ZDV VLJQL¿FDQWO\ LQFUHDVHG E\ Z6' DQG ,7
ZKLOHRQO\WKHLQFUHDVHRIZ6'ZDVVLJQL¿FDQWO\DVVRFLDWHGZLWKDQLQFUHDVHG
ULVNRIGHYHORSLQJRI¿FHK\SHUWHQVLRQ +5 3 pathetic activation and vagal wihtdrawal. By contrast, the increased heart rate rapidly declines after cessation of exercise. Several lines of evidence have suggested that
vagal reactivation plays an important role in heart rate recovery. The aim of the present study was to compare the autonomic nervous system activity indexes obtained
from treadmill exercise stress testing in dipper and non-dipper hypertensive patients.
Conclusions: In the PAMELA study, only the wSD, among the various markers
of blood pressure variability, appears to be predictive of all-cause mortality. This
index also displayed the closest relationship with the development of DM, LVH
and hypertension.
9C.04
PREFERABLE EFFECTS OF OLMESARTAN/CALCIUM
CHANNEL BLOCKER TO OLMESARTAN/DIURETIC ON
BLOOD PRESSURE VARIABILITY IN VERY ELDERLY
HYPERTENSION: A SUB-ANALYSIS OF THE COLM
STUDY
H. Rakugi 1, T. Ogihara 2, I. Saito 3, S. Teramukai 4, T. Saruta 3. 1 Osaka
University, Suita, JAPAN, 2 Morinomiya University of Medical Sciences,
Osaka, JAPAN, 3 Keio University, Tokyo, JAPAN, 4 Kanazawa University
Hospital, Kanazawa, JAPAN
Objective: Lower blood pressure (BP) and lower visit-to-visit variability
(VVV) of BP are reported to be associated with lower incidence of cardiovascuODUHYHQWV7KHDLPRIWKLVVXEDQDO\VLVRIWKH&2/0WULDO>1&7@ZDV
to compare VVV of systolic BP between age groups and between two treatment
combinations, i.e., the ARB olmesartan (OLM) combined with a dihydropyridine CCB or a diuretic in Japanese high-risk hypertensive patients. Furthermore,
we investigated whether these effects on BP variability were associated with
preferable effect of the combination of OLM-CCB versus OLM-diuretic on carGLRYDVFXODUHYHQWVLQYHU\HOGHUO\SDWLHQWV \HDUV Design and method: Hypertensive patients aged 65-84 years with a history of
DQGRUULVNIDFWRUVIRUFDUGLRYDVFXODUGLVHDVHZHUHUDQGRPL]HGWRUHFHLYH2/0
with either a CCB (amlodipine or azelnidipine) or a low-dose thiazide for at
OHDVW\HDUV Q 7KHWDUJHW%3ZDVPP+J7KHSULPDU\HQGSRLQW
was a composite of fatal and non-fatal cardiovascular events. This sub-analysis
FRPSULVHG SDWLHQWV ZKR KDG WKHLU RI¿FH %3 PHDVXUHG RQ WKUHH RU PRUH
GLIIHUHQWRFFDVLRQVGXULQJWKHIROORZXSSHULRG999RI6%3ZDVGH¿QHGDVWKH
FRHI¿FLHQWRIYDULDWLRQ &9 VWDQGDUGGHYLDWLRQPHDQ Results: CV SBP was larger in the very elderly group than the young elderly
\HDUV JURXS YV3 'LIIHUHQFHRI&96%3EHWZHHQWKH
WZRDJHJURXSVZDVDOVRVWDWLVWLFDOO\VLJQL¿FDQWLQWKHDQDO\VLVRIHDFKWUHDWPHQW
group. CV SBP in the OLM-CCB group was smaller than that in the OLMGLXUHWLFJURXSHVSHFLDOO\LQWKHYHU\HOGHUO\JURXS YV3 ,QFLdence rate of primary endpoint increased in association with increases in VVV
of SBP, but there was no statistical difference between the two treatment groups.
Conclusions: Large VVV in the very elderly patients may be associated with an
increase in cardiovascular events compared with young elderly patients. Smaller CV SBP in the OLM-CCB treatment group than those in the OLM-diuretic
group suggests that CCB is preferable to diuretic as a combination with ARB in
the very elderly patients.
9C.05
CARDIAC AUTONOMIC IMPAIRMENT AND
CHRONOTROPIC INCOMPETENCE IN DIPPER AND
NONDIPPER HYPERTENSION
C. Yildiz 1, A. Yildiz 2, F. Tekiner 2, Y. Gunes 3. 1 Ekotom Medical Center,
Istanbul, TURKEY, 2 Medical Park Hospital, Istanbul, TURKEY, 3 Hisar
Intercontinental Hospital, Istanbul, TURKEY
Objective: During exercise, heart rate increases through a combined effect of sym-
Design and method: This study included 214 hypertensive patients under antihypertensive medication. Twenty-four-hour ambulatory blood pressure monitoring
(ABPM) was performed for each patient. Thereafter patients were divided into two
JURXSVGLSSHUK\SHUWHQVLYHV PHDQDJH“ DQGQRQGLSSHUK\SHUtensives (mean age; 55,2±11,4 years). All subjects underwent a maximal exercise
testing according to Bruce protocol. Heart-rate (HR) response during exercise was
HYDOXDWHGE\WKHFKURQRWURSLFLQGH[ &, +5UHFRYHU\ +55 ZDVGH¿QHGDVWKH
GLIIHUHQFHEHWZHHQ+5DWSHDNH[HUFLVHDQG¿UVWPLQXWHDIWHUWKHH[HUFLVHWHVW
Results: Daytime systolic and diastolic BP measurements were similar,
KRZHYHU QLJKWWLPH PHDVXUHPHQWV ZHUH VLJQL¿FDQWO\ ORZHU DPRQJ GLSSHUV
than non-dippers (night-time systolic BP: 114,1±11,4 vs 126,3±15,0 mmHg,
S QLJKWWLPH GLDVWROLF %3 “ YV “ PP+J S &KURQRWURSLF LQGH[ ZDV ORZHU WKDQ QRUPDO LQ ERWK JURXSV “ YV
“S 16 'LSSHUVKDGKLJKHU+55YDOXHVWKDQQRQGLSSHUV “
vs 29,1±4,6 p<0,001). HRR was positively correlated with the percentage decline of systolic and diastolic BP from day to night (r=0,255 p<0.001 and
r=0,228 p=0,001, respectively). There were no correlation between CI and
SHUFHQWDJHRIV\VWROLFDQGGLDVWROLF%3UHGXFWLRQIURPGD\WRQLJKW U S!DQGU S!UHVSHFWLYHO\ Conclusions: Hypertensive patients have abnormal HR response to exercise,
suggesting autonomic impairment and higher risk of cardiac events ang mortality. Nondippers had lower HRR values than dippers. This may due to a relative
general decrease of parasympathetic reactivation after exercise that is linked
to the failure of nighttime fall of BP, both of which might contribute to targetorgans deterioration.
e125
9C.06
Journal of Hypertension Volume 32, e-Supplement 1, 2014
VISIT-TO-VISIT VARIABILITY OF SYSTOLIC BLOOD
PRESSURE IN HYPERTENSIVE PATIENTS TREATED
EXCLUSIVELY WITH A COMBINATION TREATMENT IN
THE ANGLO-SCANDINAVIAN CARDIAC OUTCOMES
TRIAL-BPLA
%3 SRVWSUDQGLDOK\SRWHQVLRQ“QRUPRWHQVLRQ“K\SHUWHQVLRQ
0.83±0.01).
S. Watson, A. Gupta, N.R. Poulter. International Centre for Circulatory Health,
Imperial College London, London, UNITED KINGDOM
Objective: Visit-to-visit variability of systolic blood pressure (SBP) was demonstrated to be a strong predictor of stroke and coronary events in ASCOT-BPLA. This analysis investigates the differences in SBP variability between groups
of patients treated exclusively with combination therapy in order to eliminate the
LQÀXHQFHRIRWKHUDQWLK\SHUWHQVLYHPHGLFDWLRQV
Design and method: ASCOT-BPLA patients treated exclusively with either
DPORGLSLQHSHULQGRSULO Q RU DWHQROROEHQGURÀXPHWKLD]LGH Q for at least six months without other anti-hypertensive medication and with a
PLQLPXPRIWKUHH6%3UHDGLQJVZHUHVHOHFWHGIRULQFOXVLRQ,QLWLDO¿QDODQG
PD[LPXP 6%3 DQG LQGLFDWRUV RI YDULDELOLW\ 6' DQG FRHI¿FLHQW RI YDULDWLRQ
>&R9 6'PHDQ@ ZHUHFROOHFWHG
Results: For both groups, the median follow-up period was approximately 4.5
years with a median of 10 SBP measurements per patient. Mean initial SBP
ZDVVLPLODU DOEHLWVWDWLVWLFDOO\VLJQL¿FDQWO\GLIIHUHQW EHWZHHQWKHWZRJURXSV
7KHDYHUDJH6'DQG&R9RI6%3ZHUHVLJQL¿FDQWO\ORZHULQWKHDPORGLSLQH
SHULQGRSULOJURXSDQGWKHPD[LPXP6%3ZDVKLJKHULQWKHDWHQROROEHQGURÀXmethiazide group.
Conclusions: +\SHUWHQVLYHSDWLHQWVWUHDWHGH[FOXVLYHO\ZLWKDPORGLSLQHSHULQdopril displayed a lower visit-to-visit SBP variability and a lower maximum
SBP, two proven predictors of cardiovascular morbidity. These results add adGLWLRQDOHYLGHQFHDVWRWKHPHFKDQLVPRIEHQH¿WRQPRUWDOLW\DQGFDUGLRYDVFXODU
HYHQWVREVHUYHGZLWKDPORGLSLQHSHULQGRSULOLQWKH$6&27WULDO
9C.07
POSTPRANDIAL HYPERTENSION, AN OVERLOOKED
RISK MARKER FOR ARTERIOSCLEROSIS
Y. Tabara 1, (8HWDQL2, M. Igase 2, G. Haiyan 2, T. Kido 2, N. Ochi 2, R. Takita 2,
K. Kohara 2, T. Miki 2. 1 Center for Genomic Medicine, Kyoto University
Graduate School of Medicine, Kyoto, JAPAN, 2 Department of Geriatric
Medicine, Ehime University Graduate School of Medicine, Toon, JAPAN
Objective: Increased blood pressure (BP) variability is suggested to be a risk
factor for cardiovascular disease. Although a postprandial decline in BP is a
frequently observed phenomenon in the elderly, little attention has been paid
WRWKHFOLQLFDODQGGLDJQRVWLFVLJQL¿FDQFHRISRVWSUDQGLDO%3FKDQJH+HUHZH
aimed to clarify the possible association between postprandial BP dysregulation
and arteriosclerosis.
Design and method: The study subjects were 1,339 apparently healthy middle-aged to elderly persons (66±9 years old). Postprandial changes in BP were
calculated by two readings on the same day, one just before lunch with a standardized Japanese meal and the second 30 min after lunch. Arteriosclerosis was
assessed by carotid intima-media thickness (IMT) and brachial-to-ankle pulse
wave velocity.
Results: 0HDQ SUHSUDQGLDO DQG SRVWSUDQGLDO V\VWROLF %3 ZDV “ DQG
123±18 mmHg respectively. One hundred and twelve subjects (8.4%) showed
a greater than 20-mmHg postprandial decline in systolic BP, while 129 (9.6%)
VKRZHGDJUHDWHUWKDQPP+JLQFUHDVH&DURWLG,07ZDVVLJQL¿FDQWO\KLJKHU
in both postprandial hypotensive (0.83±0.16 mm) and hypertensive (0.82±0.15)
VXEMHFWV WKDQ SRVWSUDQGLDO QRUPRWHQVLYH SHUVRQV “ 7KH SRVWSUDQdial changes in systolic BP was strongly associated with preprandial systolic
BP (r=0.335, p<0.001). The association between postprandial BP change and
carotid IMT was therefore changed to linear after adjustment for basal systoic
Multiple linear regression analysis adjusted for possible covariates, includLQJEDVDO%3LGHQWL¿HGDSRVWSUDQGLDOLQFUHDVHLQ%3DVDQLQGHSHQGHQWGHWHUPLQDQWRILQVXOLQUHVLVWDQFHDVDVVHVVHGE\+20$,5 ȕ S FDURWLG WKLFNQHVV ȕ S DQG SXOVH ZDYH YHORFLW\ ȕ p<0.001).
Conclusions: Postprandial increase in BP is a novel risk marker for arteriosclerosis.
9C.08
PREDICTORS OF VISIT-TO-VISIT VARIABILITY OF
SYSTOLIC BLOOD PRESSURE IN THE “REAL LIFE”:
RESULTS OF THE VOLTAGE STUDY
J.J. Mourad 1, D. Agnoletti 1, J. Kerihuel 2, J. Blacher 3. 1 Avicenne University
Hospital, Bobigny, FRANCE, 2 VERTICAL, Paris, FRANCE, 3 Hôtel-Dieu
Hospital, Paris, FRANCE
Objective: Recent studies suggest that systolic blood pressure (BP) visit-to-visit
YDULDELOLW\ 999 LQÀXHQFHVWKHULVNRIYDVFXODUHYHQWVDQGPRUWDOLW\+RZHYer, it remains uncertain whether factors associated with increased VVV in randomized controlled trials are similar to those observed in clinical practice. The
VOLTAGE study evaluated the association between VVV and patients characteristics and antihypertensive drug treatments in a clinical, “real-world” setting.
Design and method: We included 4151 hypertensive outpatients who had at
least 4 visits with BP readings. Clinical observational data were extracted (mean
age 63±11; 60.5% males, 26.5%diabetes mellitus) and analysed. VVV of systolLF%3 6%3 ZDVGH¿QHGDVWKHVWDQGDUGGHYLDWLRQ 6' DURXQGWKHPHDQ6%3RI
the 4 recordings. The cohort was then divided in tertiles of VVV.
Results: %DVHOLQH FKDUDFWHULVWLFV ZHUH DV IROORZHG 6%3'%3 ““
PP+J%0,“NJPðRISDWLHQWVZHUHWUHDWHGZLWKDPRQRWKHUDS\ZLWKGUXJVDQGZLWK!PROHFXOHV
Age (p<0.0001) and SBP (p<0.0001), but neither gender nor heart rate were
positively associated with an increased VVV. Among collected risk factors
and comorbidities, left ventricular hypertrophy (p<0.01) and renal failure
(p<0.0001) were associated with an increased VVV. Considering ongoing treat-
e126
Journal of Hypertension Volume 32, e-Supplement 1, 2014
ments at time of inclusion, diuretics (p<0.0001) and beta-blockers (p<0.0001)
ZHUHVLJQL¿FDQWO\PRUHIUHTXHQWLQWKHKLJKHVWWHUWLOHRI6%3999,QPXOWLSOH
regression analysis, the remaining independent predictors of VVV were: Age
ȕ 3 UHQDO IDLOXUH ȕ 3 WUHDWPHQW ZLWK GLXUHWLFV
ȕ 3 DQGWUHDWPHQWZLWKEHWDEORFNHUV ȕ 3 Conclusions: The current study provides insight into VVV in a database of reDOZRUOG REVHUYDWLRQV 7KH REVHUYHG UHVXOWV FRQ¿UP WKDW WKH RQO\ PRGL¿DEOH
factors affecting VVV are the nature of pharmacological treatment, with an apSDUHQWGHOHWHULRXVLQÀXHQFHRIEHWDEORFNHUVDQGGLXUHWLFVRQYLVLWWRYLVLWYDULability of systolic blood pressure.
9C.09
THE CORRELATION BETWEEN BEAT-TO-BEAT
HEART RATE VARIABILITY/CIRCADIAN BLOOD
PRESSURE VARIABILITY AND ATHEROSCLEROTIC
CHANGE OR HEMODYNAMIC STATUS
T. Kawai, K. Yamamoto, Y. Takeya, N. Ito, K. Sugimoto, H. Rakugi.
Department of Geriatric Medicine and Nephrology, Osaka University
Graduate School of Medicine, Osaka, JAPAN
Objective: High blood pressure variability and low short term heart rate variability are indicated to be correlated with higher incidence of cardiovascular
HYHQWV+RZHYHUWKHFOLQLFDOVLJQL¿FDQFHVRIGD\WLPHEORRGSUHVVXUHYDULDELOLW\
night-time blood pressure variability, and beat-to-beat heart rate variability are
not well established. In this study, we investigated the correlation between 24-h
GD\WLPHQLJKWWLPHEORRGSUHVVXUHYDULDELOLW\DQGEHDWWREHDWKHDUWUDWHYDULability and renal function or systemic atherosclerotic changes.
Design and method: We analyzed data from 120 patients who underwent reQDO'RSSOHUXOWUDVRQRJUDSK\ 5'8 DQGDPEXODWRU\EORRGSUHVVXUHPRQLWRULQJ
(ABPM) at our hospital ward, and investigated the correlation between circadian blood pressure variability or beat-to-beat heart rate variability, which was
evaluated with Lorenz plot (x-axis: RR interval of beat N, y-axis: RR interval of
EHDW1 REWDLQHGIURP$%30UHVXOWVDQGV\VWHPLFDWKHURVFOHURWLFFKDQJHRU
hemodynamic status, including carotid atherosclerosis and resistive index (RI)
HYDOXDWHGZLWK5'8ZKLFKZDVWKRXJKWWREHDJRRGLQGLFDWRURIUHQDOYDVFXODU
resistance.
Results: Subjects with higher circadian variability in systolic blood presVXUH 6%3 KDG VLJQL¿FDQWO\ KLJKHU 5, 'D\WLPH YDULDELOLW\ LQ 6%3 FRUUHlated more strongly with RI than night-time variability. Meanwhile, only
night-time variability, but not day-time variability, in SBP was related to
carotid atherosclerosis. Subjects with higher 24-hour mean heart rate were
VLJQL¿FDQWO\\RXQJHUDQGVKRZHGVLJQL¿FDQWO\ORZHU5,LQFRPSDULVRQZLWK
subjects with lower 24-hour mean heart rate. Subjects with higher beat-toEHDWKHDUWUDWHYDULDELOLW\ZHUHVLJQL¿FDQWO\ROGHUDQGVKRZHGVLJQL¿FDQWO\
higher RI and plaque score.
Conclusions: Circadian variability in SBP and beat-to-beat heart rate variability
ZHUHVLJQL¿FDQWO\FRUUHODWHGZLWKUHQDOIXQFWLRQ'D\WLPH6%3VWDQGDUGGHYLDtion (SD) was especially more strongly correlated with renal vascular resistance,
DQGQLJKWWLPH6%36'ZDVVLJQL¿FDQWO\FRUUHODWHGZLWKLQWLPDPHGLDWKLFNQHVV
(IMT) and plaque score. Low 24-hour mean heart rate and high beat-to-beat
KHDUW UDWH YDULDELOLW\ ZHUH DOVR VLJQL¿FDQWO\ FRUUHODWHG ZLWK UHQDO YDVFXODU UHsistance. Evaluating circadian blood pressure variability and beat-to-beat heart
rate variability enables an assessment of pathological conditions in hypertensive
patients in order to prevent cardiovascular diseases.
Abstracts
e127
ORAL SESSION
ORAL SESSION 9D
EPIDEMIOLOGY
9D.01
24-HOUR CALCIUM EXCRETION IS ASSOCIATED
WITH DIASTOLIC BLOOD PRESSURE: THE STYRIAN
HYPERTENSION STUDY
DOUHDG\UHFUXLWHGSDUWLFLSDQWV IHPDOHV DQGPDOHV DJHG\HDUV$OOVXEMHFWVVLJQHGLQIRUPHGFRQVHQWDQG¿OOHGYDOLGDWHGTXHVtionnaires regarding lifestyle, concomitant disease and medication. Anthropometry,
IDVWLQJEORRGVDPSOLQJEORRGSUHVVXUH %3 PHDVXUHPHQWZHUHSHUIRUPHG2I¿FH
BP was registered by OMRON (Japan) twice on right hand in sitting position with
calculation of mean BP.
Results: 7KH SUHYDOHQFH RI K\SHUWHQVLRQ DFFRUGLQJ WR +%3 %3! PP
Hg), and antihypertensive treatment (AHT) as well as BP control are presented
in the table. They are age-adjusted according euro-standard.
M. Gaksch 1, K. Kienreich 1, N. Verheyen 2, M. Grübler 2, J. Grogorenz 1,
B.Ó. Hartaigh 3, T.R. Pieber 1, A. Tomaschitz 2,4, S. Pilz 1,5. 1 Department
of Internal Medicine, Division of Endocrinology and Metabolism, Medical
University of Graz, Graz, AUSTRIA, 2 Department of Cardiology, Medical
University of Graz, Graz, AUSTRIA, 3 Department of Internal Medicine/
Section of Geriatrics, Yale School of Medicine, New Haven, CT, USA,
4
Specialist Clinic of Rehabilitation PV Bad Aussee, Bad Aussee, AUSTRIA,
5
Department of Epidemiology and Biostatistics, EMGO Institute for Health and
Care Research, VU University Medical Centre, Amsterdam, NETHERLANDS
Objective: Epidemiological evidence indicates an association between increased
XULQDU\FDOFLXPH[FUHWLRQ 8&D DQGHOHYDWHGEORRGSUHVVXUH %3 1HYHUWKHOHVV
PRVWSULRUVWXGLHVDGGUHVVLQJWKLVWRSLFZHUHOLPLWHGE\XWLOL]LQJRI¿FH%3PHDVXUHments and mid-stream urine samples. Thus, to further understand the relationship
EHWZHHQ%3DQG8&DZHSHUIRUPHGKDPEXODWRU\%3PRQLWRULQJ $%30 DQG
24-h urinary sampling in a cohort of patients diagnosed with hypertension.
Design and method: Patients were derived from a tertiary care centre at the
0HGLFDO8QLYHUVLW\RI*UD]$%30ZDVDVVHVVHGXVLQJD6SDFHODEVPRQLWRU$URXWLQHODERUDWRU\5RFKH+LWDFKL&REDVDQDO\]HUZDVHPSOR\HGWR
determine patients’ total calcium from 24-h urine samples.
Results: We included 240 men and women (median age 62.6 years [interquartile
UDQJH@IHPDOHV ZLWKDKLVWRU\RIDUWHULDOK\SHUWHQVLRQ0HDQ “
VWDQGDUGGHYLDWLRQ KV\VWROLFDQGGLDVWROLF%3ZHUH“PP+JDQG“
PP+JUHVSHFWLYHO\$IWHUVWUDWLI\LQJSDWLHQWVDFFRUGLQJWR8&DTXDUWLOHVDQDO\VLV
RIYDULDQFHGHPRQVWUDWHGDVLJQL¿FDQWYDULDWLRQLQDJH VWYVWKTXDUWLOHYV
\HDUVS ERG\PDVVLQGH[ %0, YVNJPS HVWLPDWHGJORPHUXODU¿OWUDWLRQUDWH H*)5DFFRUGLQJWR&.'(3,IRUPXODYV
POPLQPS LQWDNHRIWKLD]LGHGLXUHWLFV YVS DQGGLDVWROLF%3OHYHOV YVPP+JS $FFRUGLQJWR8&DTXDUWLOHVZHIRXQGQR
VLJQL¿FDQWGLIIHUHQFHVIRUVH[XVHRIEHWDEORFNHUV$&(LQKLELWRUV$7,,EORFNHUV
calcium antagonists, calcium supplementation, diagnosis of hyperparathyroidism,
systolic BP, mean heart rate, and 24-h urinary sodium and potassium concentrations.
2YHUDOOWKHUHZDVDVLJQL¿FDQWFRUUHODWLRQEHWZHHQ8&DDQGGLDVWROLF%3 3HDUVRQ
FRUUHODWLRQFRHI¿FLHQWU S EXWQRWZLWKV\VWROLF%3 U S 7KH UHODWLRQVKLS EHWZHHQ 8&D DQG GLDVWROLF %3 DWWHQXDWHG VOLJKWO\ EHWD p=.040) after adjusting for numerous covariates in multivariable linear regression.
7KHDGMXVWHGDVVRFLDWLRQEHWZHHQ8&DDQGV\VWROLF%3UHPDLQHGQRQVLJQL¿FDQW
Conclusions: ,QWKLVFURVVVHFWLRQDOLQYHVWLJDWLRQZHREVHUYHGDVLJQL¿FDQWDVVRFLDWLRQ EHWZHHQ LQFUHDVLQJ 8&D FRQFHQWUDWLRQV DQG HOHYDWHG K GLDVWROLF
BP. These data support a role for altered calcium homeostasis in the pathogenesis of arterial hypertension.
9D.02
HYPERTENSION PREVALENCE AND CONTROL
IN RUSSIA: AN UP-DATE FROM NEW RUSSIAN
EPIDEMIOLOGY SURVEY ESSE-RF
A.O. Konradi 1, S. Shalnova 2, Y. Balanova 2, A. Deev 2, O. Rotar 1,
E. Oschepkova 3, S. Boitsov 2, Y. Karpov 3, E. Shlyakhto 1. 1 Federal Almazov
Medical Research Centre, Saint-Petersburg, RUSSIA, 2 National Research
Center for Preventive Medicine, Moscow, RUSSIA, 3 Russian Cardiology
Research and Production Complex, Moscow, RUSSIA
Objective: The study estimates current of hypertension (HTN) prevalence,
awareness and control in regions of Russian Federation with different climatic,
socioeconomic and demographic characteristics.
Design and method: A novel epidemiology survey of cardiovascular risk in differHQWUHJLRQVRI5XVVLD (66(5) ZDVSHUIRUPHGLQDPXOWLVWHSVWUDWL¿HGUDQGRP
sample of 1600 participants in 12 selected regions. At the moment 8 regions have
Conclusions: The overall HTN prevalence in Russia still appears to be over
LQWKHVHOHFWHGDJHJURXSZKLOHVLJQL¿FDQWGLVFUHSDQFLHVEHWZHHQUHJLRQV
exists. BP control remains to be poor, however it improved compared to previous periods, especially in selected regions with possible effective healthcare
measures for HTN evaluation and treatment.
9D.03
BLOOD PRESSURE VARIABILITY, METABOLIC
PROFILE AND CARDIOVASCULAR RISK IN CENTRAL
AND EASTERN EUROPE: DATA FROM THE BP-CARE
STUDY
G. Brambilla 1, M. Bombelli 1, G. Seravalle 2, M. Volpe 1, R. Facchetti 1,
S. Buzzi 1, R. Dell’Oro 1, S. Laurent 3, J. Redon 4, G. Mancia 2,5, G. Grassi 1,5.
1
Clinica Medica, Università Milano-Bicocca, Ospedale San Gerardo, Monza,
ITALY, 2 Istituto Auxologico Italiano, Milan, ITALY, 3 Pharmacology Dept. and
INSERM U970 Hosp. Europeen G. Pompidou, Assistance-Publique Hopitaux
de Paris, Descartes Univ., Paris, FRANCE, 4 Internal Medicine, Hospital
Clinico, University of Valencia, Valencia, SPAIN, 5 Dipartimento di Scienze
della Salute, Università Milano-Bicocca, Milan, ITALY
Objective: Previous studies suggest that blood pressure (BP) variability may exert a
predictive role in determining cardiovascular risk. Aim of the present analysis of the
BP-CARE study was to evaluate the relationships between BP variability and cardiovascular risk factors in a hypertensive population of Central and Eastern Europe.
Design and method: In each subject of the BP-CARE study was calculated the
FRHI¿FLHQWRIYDULDWLRQ &9 RIRI¿FHV\VWROLF%37KHSRSXODWLRQZDVWKHQGLYLGHG
LQWRTXDUWLOHVRI&9DQGWKHGLIIHUHQFHVDPRQJTXDUWLOHVLQJOXFRVHDQGOLSLGSUR¿OHV
prevalence of previous cardiovascular events, target organ damage (TOD) and BP
control were analyzed.
Results: The mean age of the 6425 hypertensive patients was 59.2±11.4 years, the
prevalence of males being 49.4%. Individuals in the highest quartile of CV were older
(Q1:58.5±11.4 yrs vs Q4:60.3±11.3 yrs, P<0.001), with a predominance of males
compared to the lowest quartile. Values of body mass index, waist circumference,
prevalence of metabolic syndrome, obesity and dyslipidemia did not differ among
quartiles, while there was a higher prevalence of diabetes, previous cardiovascular
HYHQWVDQGUHVLVWDQWK\SHUWHQVLRQLQVXEMHFWVLQWKH¿UVWDVFRPSDUHGWRIRXUWKTXDUWLOH 4YV44YV4DQG4YV4
respectively, P<0.05). The 24-hour BP control was lower in hypertensives with
greater variability (Q1:31.9% vs Q4:15.8%, P<0.01). Subjects in the highest quartile of CV showed higher total cholesterol and glycaemia than those in the lowest
RQH 4“ PJGO YV 4“ PJGO DQG 4“ PJGO YV
M
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Y
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e128
Journal of Hypertension Volume 32, e-Supplement 1, 2014
4“PJGOUHVSHFWLYHO\3 *ORPHUXODU¿OWUDWLRQUDWHZDVKLJKHULQ
VXEMHFWVLQWKHORZHVWTXDUWLOHRI&9WKDQLQWKRVHLQWKHKLJKHVWRQH 4“P/
PLQPYV4“P/PLQP3 7KHSUHYDOHQFHRI72'ZDV
similar among quartiles of CV, while the cardiovascular risk progressively increased
IURPWKHORZHVWWRWKHKLJKHVWTXDUWLOHRI&9 4YV4 Conclusions: In the hypertensive population of the BP-CARE study the increase in BP variability is associated with an increase in cardiovascular risk, an
XQIDYRUDEOHJOXFRVHDQGOLSLGSUR¿OHDQGDSRRUHUKRXU%3FRQWURO
9D.04
HYPERTENSION IS AN INDEPENDENT RISK FACTOR
FOR TYPE 2 DIABETES
N. Lim 1, H. Park 1, S. Choi 1, M. Cho 2. 1 Korea National Institute of Health,
Division of Cardiovascular and Rare Diseases, Chungcheongbuk-Do, SOUTH
KOREA, 2 Chungbuk National University, College of Medicine, Department of
Internal Medicine, Cheongju, SOUTH KOREA
Objective: We investigated the relationship between blood pressure and development of type 2 diabetes mellitus in the prospective community-based
epidemiologic cohort aged 40-69, which has been followed up for 4 years.
Design and method: A total of 10,038 participants were enrolled in the Korean
Genome Epidemiology Study (KoGES). Among them, 6,211 (2948 men and 3,263
women) without diabetes at baseline examination, were analyzed. Participants
ZHUHFODVVL¿HGLQWRWKUHHFDWHJRULHVDFFRUGLQJWRV\VWROLFDQGGLDVWROLFEORRGSUHVVXUH 6%3'%3 QRUPRWHQVLYH PP+J DQG PP+J SUHK\SHUWHQVLRQ PP+J RU PP+J DQG K\SHUWHQVLRQ ! PP+J RU
! PP+J RU WDNLQJ DQWLK\SHUWHQVLYH PHGLFDWLRQV 0XOWLSOH ORJLVWLF UHJUHVVLRQ
analysis adjusting for risk factors was used to examine the relationship between hySHUWHQVLRQDQGGLDEHWHVZLWKRGGVUDWLRV 25V DQGFRQ¿GHQFHLQWHUYDOV &,V Results: The cumulative incidence of diabetes during 4 years in normotensive,
prehypertension, and hypertension at baseline were 5.5%, 8.0%, and 12.1%, respectively. After adjusting age, sex, high-density lipoprotein cholesterol (HDL-C),
low-density lipoprotein cholesterol (LDL-C), triglycerides (TG), body mass index
(BMI), waist circumference (WC), family history of diabetes, education attainment,
alcohol use, and smoking status, hypertension was independently associated with
increased risk of diabetes compared with normotensive (OR=1.53; 95%CI, 1.181.98). In the prediabetic group at baseline, the prehypertension and hypertension
groups had ORs (95% CIs) for incident diabetes of 1.52 (1.80-2.14) and 1.48 (1.052.10), respectively (P for linear trend=0.028). In the normal glucose tolerance group
(NGT), after adjusting for age and sex, hypertension at baseline, was shown to be
VLJQL¿FDQWO\DVVRFLDWHGZLWKLQFLGHQWGLDEHWHV 25 &, +RZever, after adjusting for entire potential risk factors, the association was attenuated
DQGQRORQJHUVLJQL¿FDQW 25 &, Conclusions: In the present study, we found that blood pressure was an independent risk factor for the development of diabetes. The present data also indicated that
the risk of developing diabetes is higher with hypertension in prediabetic subjects,
suggesting that more intensive blood pressure control is needed in prediabetic status.
9D.05
THE HYPERTENSIVE ROMA PATIENT. PERSPECTIVES
FROM THE LARGEST HYPERTENSION STUDY ON THE
ROMA POPULATION. DATA FROM THE ROMA STUDY
S. Frunza, E. Tintea, A.M. Daraban, C. Grigore, M. Hostiuc, N. Dumitru,
A.L. Oprea, G. Oprea, D. Bartos, E. Badila. Emergency Clinical Hospital,
Department of Internal Medicine, Bucharest, ROMANIA
Objective: As a continuation of our previous studies on the Roma population
ZHHYDOXDWHGWKHFOLQLFDOSUR¿OHRIWKH5RPDSDWLHQWZLWKK\SHUWHQVLRQ +71 known or newly diagnosed.
Design and method: Eight hundred and six adult subjects (age range 18-82
years) from two urban Roma communities were included, between 2012 and
2013, regardless of medical history, and screened for major cardiovascuODU &9 ULVN IDFWRUV )XUWKHU ZH VHOHFWHG DQG VWXGLHG VXEMHFWV ZLWK
HTN (known or newly diagnosed). We performed routine evaluation of the
hypertensive patient as recommended in the ESH guidelines. We recorded:
demographic and anthropometric data, presence of major CV risk factors and
blood pressure measurements with appropriately sized cuffs, presence of left
ventricle hypertrophy (LVH) on echocardiography studies using left ventricle mass index (Devereaux formula), peripheral arterial disease (anklebrachial index < 0.9 in either limb), increased arterial stiffness (pulse wave
YHORFLW\ !PV PLFURDOEXPLQXULD RQ GLSVWLFN DQG JORPHUXODU ¿OWUDWLRQ
rate estimated using CKD-EPI study equation. Associated conditions such
DVGLDEHWHVPHOOLWXV NQRZQRUQHZO\GLDJQRVHG K\SHUXULFHPLD !PJGO
LQIHPDOHV!PJGOLQPDOHV ZHUHQRWHG9LVFHUDOREHVLW\ZDVGH¿QHGDV
ZDLVWFLUFXPIHUHQFH!FPLQPDOHVDQG!FPLQIHPDOHV
Results: The prevalence of HTN was lower than that of the general population
in Romania (33.6% vs 40.5% in the SEPHAR II Study, p<0.01). However, the
5RPDK\SHUWHQVLYHSDWLHQWGLVSOD\VDSUR¿OHZLWKDQLPSUHVVLYH&9EXUGHQ)RU
other results see table.
Conclusions: In a population with a very low level of education, life style related risk factors reach a prevalence over two times that of the general population. Half of the patients are smokers, and over two thirds of them are physically
inactive which translates into a very high prevalence of obesity, women being
VLJQL¿FDQWO\PRUHDIIHFWHG$VVKRZQLQSUHYLRXVVWXGLHVWKHSUHYDOHQFHRIG\Vlipidemia, hyperuricemia and diabetes is much higher, major risk factors that
PDNHXSDKHDY\PHWDEROLFSUR¿OH$VDSURRIRIYDVFXODULQMXU\XQGHUWKHVH
circumstances, peripheral artery disease is found in more than half of the hypertensive Roma patients.
9D.06
PREVALENCE OF HYPERTENSION IN SOUTH ASIA:
SYSTEMATIC REVIEW AND META-ANALYSIS
D. Neupane 1, P. Kallestrup 1, B. Christensen 3, V. Khanal 5, B. Gyawali 2,
S. Mishra 4, C. McLachlan 6. 1 Center for Global Health, Department of Public
Health, Aarhus University, Aarhus, DENMARK, 2 Unit of Health Promotion,
University of Southern Denmark, Esbjerg, DENMARK, 3 Section for General
Medical Practice, Department of Public Health, Aarhus University, Aarhus,
DENMARK, 4 People Health Movement Nepal, Kathmandu, NEPAL, 5 School
of Public Health, Curtin University, Perth, AUSTRALIA, 6 Rural Clinical
School, University of New South Wales, Sydney, AUSTRALIA
Objective: Hypertension is a leading attributable risk factor for global mortality.
Information on both the prevalence of hypertension and associated risk factors
is not always captured in developing and middle-income countries. A systematic review on evidence concerning prevalence and risk factors for hypertension from the region of The South Asian Association for Regional Cooperation
(SAARC) has not previously been carried out.
Design and method: A literature search of MEDLINE was performed with
D FRPELQDWLRQ RI 0H6+ WHUPV µK\SHUWHQVLRQ¶ DQG (SLGHPLRORJ\(3 7KH
e129
Journal of Hypertension Volume 32, e-Supplement 1, 2014
search was supplemented by a manual search of bibliographies of retrieved
articles and WHO publications. The search was restricted to populationbased studies on hypertension in South Asia published between 01 January
2000 and 30 September 2013. Data were extracted following a standard protocol and using structured data collection forms. Out of 240 articles identi¿HGWKLUW\WKUHHSXEOLFDWLRQVPHWWKHLQFOXVLRQFULWHULDDQGZHUHLQFOXGHGLQ
V\QWKHVLVDQGPHWDDQDO\VHV+\SHUWHQVLRQZDVGH¿QHGZKHQDQLQGLYLGXDO
KDGDV\VWROLFEORRGSUHVVXUH! PP+JDQGRUGLDVWROLFEORRGSUHVVXUH
! PP+JRUZDVWDNLQJDQWLK\SHUWHQVLYHGUXJVRUSUHYLRXVO\KDGEHHQ
diagnosed hypertensive by health care professionals.
Results: The average prevalence of hypertension from the studies was found
WR EH 7KH SUHYDOHQFH RI K\SHUWHQVLRQ YDULHG H[WHQVLYHO\ EHWZHHQ
the studies in terms of country, published year and area of data collection,
ZKLFK UDQJHG IURP WR 6WXGLHV IURP XUEDQ DUHDV KDG KLJKHU
prevalence (31.28%) than rural areas (24.04%). The most recent reported
prevalence of hypertension in South Asian countries were: Bangladesh:
%KXWDQ,QGLD0DOGLYHV1HSDO3Dkistan:25% and Sri Lanka:20.9%. Meta-analyses showed that sex (men: OR
&, REHVLW\ 25&, DQGFHQWUDO
REHVLW\ 25 &, ZHUH DVVRFLDWHG ZLWK KLJKHU SUHYDlence of hypertension.
Conclusions: Our study found that hypertension prevalence is high in the
SAARC countries. We also note that studies are not consistent in their data
collection and do not always include the complete range of risk factors.
9D.07
GENDER DIFFERENCES OF HYPERTENSION
INCIDENCE ACCORDING TO SOCIOECONOMIC
STATUS
N. Lim 1, M. Cho 2, H. Park 1. 1 Korea National Institute of Health, Division of
Cardiovascular and Rare Diseases, Chungcheongbuk-Do, SOUTH KOREA,
2
Chungbuk National University, College of Medicine, Department of Internal
Medicine, Cheongju, SOUTH KOREA
Objective: Hypertension is a leading cause of cardiovascular events and
it has been constituted as a large burden on vulnerable classes of people in
the health-care system. We examined whether there is gender difference in
association between socioeconomic status (SES), measured by education attainment and monthly household income, and hypertension incidence using
the community-based cohort data.
Design and method: 'DWDIRUPHQDQGZRPHQDJHGWR
without hypertension at baseline from the Korean Genome and Epidemiology Study (KoGES), were analyzed. Participants were examined approxiPDWHO\HYHU\WZR\HDUVIRU\HDUVDQGZHUHFODVVL¿HGLQWRIRXUFDWHJRULHV
by self-reported education attainment: highest (more than 13 years); midKLJKHVW \HDUV PLGORZHVW \HDUV DQGORZHVW OHVVWKDQ\HDUV and monthly household income (×10,000 Korean Won): highest (more than
400); mid-highest (200-399); mid-lowest (100-199); and lowest (less than
100). The association between socioeconomic status and incidence hypertension was examined by Cox’s proportional hazard regression analysis.
Results: According to the aforementioned education categories, the prevaOHQFH RI K\SHUWHQVLRQ ZHUH DQG LQ PHQ DQG
18.6%, 21.4%, 32.0%, and 51.5% in women. Compared to highest education
JURXS UHIHUHQW WKH KD]DUG UDWLRV FRQ¿GHQFH LQWHUYDO IRU LQFLGHQW
K\SHUWHQVLRQDFURVVHGXFDWLRQDWWDLQPHQWFDWHJRULHVZHUH DQG 3 IRU WUHQG LQ ZRPHQ
DQG DQG 3 IRU WUHQG
LQPHQDIWHUDGMXVWLQJIRUFRQYHQWLRQDOULVNIDFWRUV7KHZRPHQ
in the lowest household income were more likely to have hypertension than
those who were in the highest household income. The incidence of hyperten-
sion had inverse association with household income level in women (p for
linear trend <.0001); multivariate adjusted hazard ratios were 1.00 (referHQFH DQG 3IRUOLQHDU
trend <0.0001).
Conclusions: The educational level and economic status has a stronger impact
RQK\SHUWHQVLRQLQ.RUHDQZRPHQWKDQLQPHQ7KHUHIRUHWKHVWUDWL¿HGLQWHQsive approach for women in low socioeconomic status, especially who have low
education attainment, is needed for prevention of hypertension.
9D.08
ADDITIVE INTERACTION OF ORAL HEALTH
DISORDERS ON RISK OF HYPERTENSION IN A
JAPANESE URBAN POPULATION: THE SUITA STUDY
Y. Iwashima 1, Y. Kokubo 2, T. Ono 3, Y. Yoshimuta 3, M. Kida 3, T. Kosaka 3,
Y. Maeda 3, Y. Kawano 1, Y. Miyamoto 2. 1 National Cerebral and
Cardiovascular Center, Division of Hypertension and Nephrology, Suita City,
Osaka, JAPAN, 2 National Cerebral and Cardiovascular Center, Division of
Preventive Cardiology, Suita City, Osaka, JAPAN, 3 Osaka University Graduate
School of Dentistry, Department of Prosthodontics, Gerodontology and Oral
Rehabilitation, Suita City, Osaka, JAPAN
Objective: This study assessed the relationship between different oral health
markers; periodontitis, gingival bleeding, tooth number, and occlusal status, and
hypertension in a Japanese urban population.
Design and method: A total of 1,643 participants with no prior cardiovascular
disease (mean age 66.6 years, 43.4% female) underwent comprehensive health
checkups including a lifestyle questionnaire and dental examination in the Suita
Study.
Results: In the multivariate-adjusted logistic model, none of the individual
oral health markers, namely severe periodontitis, gingival bleeding, lowest
quartile of tooth number, and malocclusion, was significantly associated
with increased odds of hypertension. The additive effects of oral health
markers on hypertension were examined, and showed that, compared with
subjects with no component of the oral health markers, the multivariate-adjusted odds ratio of hypertension in those with three or more components
ZDV &, S ,Q WKH VXESRSXODWLRQ ZLWKRXW DQtihypertensive medication (n=1148, 59.8% female), a significant graded
relationship between multivariate-adjusted systolic blood pressure and the
number of components was found (p for trend =0.03), and, compared with
subjects with no component of the oral health markers, having three or more
FRPSRQHQWV ZDV UHODWHG WR D KLJKHU V\VWROLF EORRG SUHVVXUH ȕ CI, 1.16-9.66, p=0.01).
Conclusions: There is an additive relationship between oral health disorders
and risk of hypertension. Our results suggest that the existence of moderate or
severe oral health disorders; that is, several concomitant oral health disorders, is
associated with risk of hypertension.
e130
9D.09
Journal of Hypertension Volume 32, e-Supplement 1, 2014
ASSOCIATION BETWEEN FREE TESTOSTERONE
AND HYPERTENSION, METABOLIC SYNDROME
AND SUBCLINICAL ORGAN DAMAGE IN
PERIMENOPAUSAL WOMEN
A. Olszanecka, K. Kawecka-Jaszcz, D. Czarnecka. I Department of
Cardiology, Interventional Cardiology and Hypertension, JUMC, Kraków,
POLAND
Objective: Cardiovascular disease affects men and women differently with women having a lower incidence and later onset of disease. Research has recently refocused interest on the cardiovascular role of androgens, shifting attention away
from estrogens toward testosterone and sex hormone-binding globulin (SHBG) as
potential mediators of increasing cardiovascular risk in women at midlife.
The aim of the study was to analyse the relationship between free testosterone
and SHBG with hypertension and metabolic syndrome in hypertensive women
dependent on their menopause status.
Design and method: 40 women with newly diagnosed, never treated mild and
moderate arterial hypertension and 40 age-matched normotensive controls were
included to the study. In all subjects anthropometrical measurements were perIRUPHGDQGKUEORRGSUHVVXUHPRQLWRULQJZDVSHUIRUPHG 6SDFH/DEV Asymptomatic organ damages were analyzed including echocardiographic examination with assessment of left ventricular mass (LVM), systolic and diastolic
IXQFWLRQ *(9LYLG FDURWLGXOWUDVRXQGZLWKPHDVXUHPHQWRILQWLPDPHGLD
thickness (IMT),and carotid-femoral pulse wave velocity (PWV) measurement
(Sphygmocor). Fasting blood sample was taken to measure glucose and lipids
concentration. The diagnosis of menopause was based on the data from history
DQGFRQ¿UPHGE\WKHVHUXP)6+FRQFHQWUDWLRQ !,8O 6HUXPWHVWRVWHURQH
and SHBG were measured. Free (FT) and bioavailable testosterone (BT) were
calculated according to Vermulen formula. Metabolic syndrome (MS) was de¿QHGIROORZLQJWKH,')UHFRPPHQGDWLRQV
Results: )7ZDVVLJQL¿FDQWO\KLJKHULQK\SHUWHQVLYHSRVWPHQRSDXVDOFRPSDUHG
to premenopausal women. FT was positively associated with LVM (r=0.32,
S GHFUHDVHGGLDVWROLFIXQFWLRQ ($UDWLRS EXWQRWZLWK
subclinical atherosclerosis (IMT r=0.19, p=0.3) neither arterial stiffness (r=0.16,
p=0.16).
,QGHSHQGHQWO\RIPHQRSDXVHVWDWXV)7ZDVVLJQL¿FDQWO\KLJKHULQZRPHQZLWK
MS (premenopausal with MS: 39.0 vs without MS 29.4, p=0.001, in postmenopausal 43.4 vs 33.5, p=0.01).
Conclusions: Free testosterone independently of menopause status is related
with metabolic syndrome and subclinical organ damage. Relationship between
FT and hypertension is detectable only in postmenopausal women. IndependentO\RIPHQRSDXVHVWDWXVHOHYDWHG)7LVDVVRFLDWHGZLWKZRUVHPHWDEROLFSUR¿OH
and hypertension prevention program should be implemented in this high cardiovascular risk population.
Abstracts
e131
ORAL SESSION
LATE-BREAKERS SESSION 3
LB03.01
1
24-HOUR AMBULATORY CENTRAL BLOOD
PRESSURE AND PRECLINICAL TARGET ORGAN
DAMAGE IN ADOLESCENTS AND YOUNG ADULTS
1
2
3
A. Ntineri , A. Kollias , A. Charokopakis , D. Georgakopoulos ,
I. Moyssakis 4, A. Vazeou 5, G.S. Stergiou 1. 1 Hypertension Center, STRIDE
Hellas 7, Third University Department of Medicine, Sotiria Hospital, Athens,
GREECE, 2 Department of Radiology, Evangelismos Hospital, Athens,
GREECE, 3 Department of Cardiology, P. and A. Kyriakou Children Hospital,
Athens, GREECE, 4 Cardiology Department, Laikon Hospital, Athens,
GREECE, 5 First Department of Pediatrics, P. and A. Kyriakou Children
Hospital, Athens, GREECE
Objective: There is evidence that in adolescents and young adults with elevated
peripheral blood pressure (BP) central (aortic) BP may be low, and there is uncertainty in their management. This pilot study investigated the relationship of
24-hour ambulatory central BP with preclinical target organ damage in adolescents and young adults.
Design and method: Apparently healthy adolescents and young adults referred
for elevated BP and healthy volunteers were subjected to: (1) 24-hour ambulatory peripheral and central BP monitoring simultaneously using a noninvasive brachial cuff-based oscillometric device (Mobil-O-Graph 24h PWA); (2)
24-hour pulse wave velocity (PWV) monitoring (Mobil-O-Graph 24h PWA);
(3) echocardiographic determination of left ventricular mass index (LVMI); (4)
ultrasonography of common carotid intima-media thickness (IMT).
Results: Data from 32 subjects were analyzed (mean age 18.2±4.8 years,
range 12-25 years, 24 males, mean body mass index 24.6±5.1 kg/m2, 7 with
hypertension [24-hour peripheral BP >95th percentile for adolescents or
>130/80 mmHg for adults], and 6 with high-normal BP [>90th percentile or
>125/75 mmHg, respectively]). There was a strong correlation between central and peripheral systolic BP (r=0.93, p<0.01), whereas the difference between peripheral and central systolic BP was inversely correlated to age (r=0.43, p=0.01). Males had larger peripheral-central systolic BP difference than
females (15.3±3.6 vs. 10.4±2.6 mmHg respectively, p<0.01 adjusted for age).
There was a consistent trend towards stronger correlations between indices of
WDUJHWRUJDQGDPDJHDQGFHQWUDOFRPSDUHGWRSHULSKHUDO%30RUHVSHFL¿FDOO\
LVMI was correlated with both central and peripheral systolic BP (r=0.51 and
0.47 respectively, both p<0.05); carotid IMT was correlated with both central
and peripheral pulse pressure (r= 0.46 and 0.36 respectively, both p<0.05); 24hour PWV was correlated with both central and peripheral systolic BP (r=0.96
and 0.92 respectively, both p<0.01).
Conclusions: These preliminary results suggest that in young individuals central 24-hour ambulatory BP appears to be more closely associated with preclinical target organ damage than peripheral BP. The role of ambulatory central BP
PRQLWRULQJLQLPSURYLQJFDUGLRYDVFXODUULVNVWUDWL¿FDWLRQLQ\RXQJLQGLYLGXDOV
deserves further investigation.
LB03.02
THE ROLE OF B3-ADRENERGIC RECEPTORS ON
CARDIOVASCULAR FUNCTION
F. Santos 1, N.Z. Preite 2, M.O. Ribeiro 2, M.C. Irigoyen 1, P. Fiorino 1, V. Farah 2.
1
Heart Institute of Medicine School of São Paulo University, São Paulo,
BRAZIL, 2 Mackenzie Presbyterian University, São Paulo, BRAZIL
Objective: The aim of the present study was to evaluate the cardiac function in
experimental model of B3 adrenergic receptor knockout mice.
Design and method: The male knockout and wild type mice for B3 receptor
were used (ARB3KO and WT, respectively). Blood pressure (BP) and heart rate
(HR) was directly measured through a carotid artery implanted. The BP and
HR variabilities were evaluated in time and frequency domain by Fourier Fast
Transform.
Results: 7KHUHZHUHQRVLJQL¿FDQWGLIIHUHQFHLQ%3RU+5EHWZHHQWKHJURXSV
However, in time domain the BP variability was higher, 96% of increase in
ARB3KO and the HR variability was 113% higher in ARB3KO. In frequency
domain the LF component for HR (25 ± 3 vs. 8 ± 2 ms²) and BP (38 ± 8 vs. 20 ±
3 mmHg²) were increased in ARB3KO when compared with WT. Moreover, the
sympathetic-vagal balance was increased in ARB3KO (2 ± 0.3) when compared
to WT (0.6± 0.1).
Conclusions: ,QFRQFOXVLRQRXUGDWDFRQ¿UPHGWKHFDUGLRSURWHFWLYHUROHRI%
adrenoreceptors since there was an increase in cardiac sympathetic modulation
determined by the absence of these receptors.
LB03.03
DIFFERENTIAL EFFECT OF EMBRYO TRANSFER
AND IN VITRO CULTURE ON THE PHOSPHATIDYL-3
KINASE (PI3K) SIGNALLING PATHWAY IN THE HEART
IN FETAL AND POSTNATAL LIFE
M. Padhee 1, C. McMillen 1, S. MaLaughlin 1, S. Zhang 1, D. Kleemann 2,
S. Walker 2, K. Botting 1, J. Morrison 1. 1 Sansom Institute for Health Research,
University of South Australia, Adelaide, AUSTRALIA, 27XUUHW¿HOG5HVHDUFK
Centre, South Australian Research and Development Institute, Adelaide,
AUSTRALIA
Objective: Previous studies have demonstrated that embryo transfer and in vitro
embryo culture result in increased relative heart weight in singleton, but not twin
fetal sheep. PI3K signalling pathway plays a major role in cardiovascular growth
and development. This study aims to investigate the impact of embryo transfer
and culture on the expression of molecules in the PI3K pathway in fetal life and
if these alterations persist into postnatal life.
Design and method: Embryos were either transferred to an intermediate ewe
(ET) or cultured in vitro in the absence (IVC) or the presence of human serum (IVCHS) for 6 d). Controls were naturally mated (NM) ewes. In addition,
methyl donor supplements were added to the media containing human serum
(IVCHS+M) in the postnatal cohort. Pregnant ewes (at 144/145d gestation) and
lambs (at 24 wks) were humanely killed. The protein expression of molecules in
WKH3,.SDWKZD\ZHUHTXDQWL¿HGXVLQJ:HVWHUQEORWWLQJ
Results: There was no change in the protein abundance of Akt but an increase
in phospho-mammalian target of rapamycin (mTOR), 4E binding protein 1
(4EBP1) and phospho-4EBP1 and a decrease in protein abundance of ribosomal
protein S6 (RPS6) and phospho-RPS6 in the heart of singletons fetal sheep in
all treatment groups. In the postnatal cohort, there was no change in the protein
abundance of Akt but an increased protein abundance of phospho-mTOR in the
males of IVC and IVCHS groups. In contrast to the fetal cohort, there was an
increase in RPS6 in the males of IVC and IVCHS groups and its phosphorylated
form in the IVC group with no change in 4EBP1 and phospho-4EBP1.
Conclusions: These data suggest that there is increased protein synthesis, which
may be responsible for the increased heart weight in fetal cohort. There was
also decreased ribosomal biogenesis which may be a compensatory response
WRWKHLQFUHDVHLQWUDQVODWLRQDOHI¿FLHQF\WREDODQFHWKHUHTXLUHPHQWVRIHQHUJ\
demand and supply in the cardiomyocytes . In contrast, there was evidence for
increased ribosomal biogenesis in heart of male lambs which may act as hypertrophic reserve for a subsequent response to hypertrophic stimuli.
LB03.04
ELEVATED AORTIC STIFFNESS IS ASSOCIATED WITH
MORE ADVANCED CARDIOVASCULAR DISEASE IN
STROKE PATIENTS
D. Gasecki 1, E. Swierblewska 2, A. Rojek 2, M. Kwarciany 1, K. Kowalczyk 1,
P. Boutouyrie 3, W.M. Nyka 1, S. Laurent 3, K. Narkiewicz 2. 1 Dept. of
Neurology of Adults, Medical University of Gdansk, Gdansk, POLAND,
2
Hypertension Unit, Dept. of Hypertension and Diabetology, Medical
University of Gdansk, Gdansk, POLAND, 3 Dept. of Pharmacology, HEGP,
APHP, Université Paris Decartes, INSERM U970, Paris, FRANCE
Objective: Aortic stiffness has been shown to be an independent predictor of
both ischemic stroke and myocardial infarction. In patients with acute ischemic
stroke increased arterial stiffness values are observed. Whether the aortic stiffness indexes discriminate stroke patients with previous myocardial infarction
(MI) and those free of MI remains unknown.
M
O
N
D
A
Y
O
R
A
L
S
e132
Journal of Hypertension Volume 32, e-Supplement 1, 2014
The aim of the study was to evaluate pulse wave velocity (PWV), augmentation
LQGH[ $,[ DQGEUDFKLDOSXOVHSUHVVXUH E33 LQSDWLHQWVZLWKWKH¿UVWHYHULVchemic stroke and history of previous MI (CAD+) vs. those free of MI (CAD-).
Design and method: We studied 120 patients (male 83 (69.2%), age (mean±SD)
62±12yrs) with acute ischemic stroke. Carotid-femoral (CF) PWV, AIx and bPP
were measured (SphygmoCor®) one week after stroke onset. We compared CFPWV, AIx, and bPP between stroke subgroups with different status of coronary
artery disease.
Results: While age, AIx, bPP were similar in the two stroke populations, CF3:9ZDVVLJQL¿FDQWO\KLJKHULQ&$'WKDQLQ&$' “YV“
P=0.04).
Conclusions: 2XU¿QGLQJVVXJJHVWWKDWDRUWLFVWLIIQHVVPHDVXUHGDV&)3:9LV
associated with clinically relevant differences in cardiovascular comorbidities in
patients with ischemic stroke.
LB03.05
HOME BLOOD PRESSURE AND CARDIOVASCULAR
OUTCOMES IN PATIENTS RECEIVING
ANTIHYPERTENSIVE DRUG THERAPY: A LARGESCALE PROSPECTIVE OBSERVATIONAL STUDY IN A
REAL-WORLD SETTING
K. Kario 1, I. Saito 2, T. Kushiro 3, S. Teramukai 4, Y. Ishikawa 5, Y. Mori 5,
F. Kobayashi 5, K. Shimada 6. 1 Division of Cardiovascular Medicine,
Department of Medicine, Jichi Medical University School of Medicine,
Tochigi, JAPAN, 2 Keio University, Kanagawa, JAPAN, 3 Life Planning Center
Foundation, Tokyo, JAPAN, 4 Innovative Clinical Research Center, Kanazawa
University, Kanazawa, JAPAN, 5 Daiichi Sankyo Co., Ltd., Tokyo, JAPAN,
6
Shin-Oyama City Hospital, Tochigi, JAPAN
Objective: Epidemiological studies indicated that morning home blood pressure (HBP) is more closely related to cardiovascular risk than clinic BP (CBP).
However, few studies have investigated the relationship between on-treatment
morning HBP and incidence of cardiovascular events in patients receiving antihypertensive treatment. We investigated the relationship between on-treatment
morning HBP throughout follow-up and incidence of cardiovascular events, using data from the Home blood pressure measurement with Olmesartan Naive
patients to Establish Standard Target blood pressure (HONEST) study.
Design and method: Data from a prospective 2-year observational study were
analyzed. Participants were outpatients with essential hypertension enrolled
in Japan between 2009 and 2010. They received olmesartan-based treatment
throughout follow-up. The primary endpoint was major cardiovascular events
(stroke, myocardial infarction, coronary revascularization procedures for angina
pectoris, or sudden death).
Results: There were 21 591 participants (mean age, 64.9 years; women,
50.6%). After mean follow-up of 2.02 years, morning HBP and CBP throughout follow-up (systolic BP/diastolic BP, mean±SD) were 135.2±10.8/79.0±8.4
mmHg and 135.2±11.5/77.4±8.6 mmHg, respectively. Cardiovascular events
occurred in 280 patients (6.46/1000 patient years). Risk for the primary endSRLQWZDVVLJQL¿FDQWO\KLJKHULQSDWLHQWVZLWKRQWUHDWPHQWPRUQLQJ+%3!
145 to 155 mmHg ( HR, 1.83; 95% CI, 1.12–2.99) and > 155 mmHg (HR,
5.03; 95% CI, 3.05–8.31) than < 125 mmHg, and with on-treatment CBP >
150 to 160 mmHg (HR, 1.69; 95% CI, 1.10–2.60) and > 160 mmHg (HR,
4.38; 95% CI, 2.84–6.75) than < 130 mmHg. Morning HBP associated with
minimum risk was 124 mmHg by spline regression analysis. Analyses using
data for both morning HBP and CBP showed that cardiovascular risk was increased in patients with morning HBP > 145 mmHg and CBP < 130 mmHg
(HR, 2.47; 95% CI, 1.20–5.08) compared to morning HBP < 125 mmHg and
CBP < 130 mmHg.
Conclusions: ,WLVHVVHQWLDOWRFRQWUROPRUQLQJ+%3WRPP+JDVD¿UVW
VWHSHYHQLQSDWLHQWVZLWKFRQWUROOHG&%37KHVHUHDOZRUOG¿QGLQJVHPSKDVL]H
the importance of HBP monitoring in clinical practice.
LB03.06
BETA BLOCKAGE LEADS TO LESS ASYMPTOMATIC
CARDIAC DAMAGE IN CORONARY PATIENTS
UNDERGOING CAROTID ENDARTERECTOMY
G. Galyfos, K. Filis, F. Sigala, K. Toutouzas, G. Zografos, E. Karanikola,
C. Zarmakoupis. 1st Department of Propedeutic Surgery, University of Athens
Medical School, Ippokration Hospital, Athens, GREECE
Objective: Beta blockage in patients scheduled for carotid endarterectomy
(CEA) has been proved to be protective against postoperative cardiac events in
the literature. We study the association of preoperative beta blockage with postoperative asymptomatic myocardial ischemia after CEA in coronary patients.
Design and method: The Vascular Study Group - Cardiac Risk Index (VSGRCI) for stratifying vascular patients into low, medium and high-cardiac risk
ZDVXVHGSURVSHFWLYHO\$OOSDWLHQWV Q ZHUHFODVVL¿HGEDVHGRQZKHWKHU
they received a beta blocker (Group A) or not (Group B). The rest of medical therapy was similar between all patients. All patients had cardiac troponin
I (cTnI) measurements preoperatively and on postoperative days 1, 3 and 7.
7URSRQLQYDOXHVUDQJLQJIURPWRQJPOZHUHFODVVL¿HGDVP\RFDUGLDO
LVFKHPLDYDOXHV!QJPOZHUHFODVVL¿HGDVP\RFDUGLDOLQIDUFWLRQ
Results: Mortality was 0.6%, the stroke rate was null and symptomatic myocardial infarction was null. Among the 70 low-risk patients, 8 had a myocardial
infarction. Among the 80 medium-risk patients, 10 had a myocardial ischemia
and 4 had a myocardial infarction. None of the high-risk patients showed any
cardiac ischemia. Patients in Group A were associated with a lower incidence
of postoperative myocardial ischemia than in Group B (p = 0.01). Beta blockDJHGLGQRWVKRZDQ\EHQH¿WLQORZULVNSDWLHQWVEXWZDVDVVRFLDWHGZLWKIHZHU
cardiac events in medium-risk patients (p = 0.018).
Conclusions: Preoperative beta blockage protects coronary patients against
DV\PSWRPDWLF P\RFDUGLDO LVFKHPLD DIWHU &($7KLV SURWHFWLRQ EHQH¿WV PHGLum-cardiac risk patients more than low-cardiac risk patients.
LB03.07
IMPROVEMENT IN CARDIOVALCULAR RISK
LEVEL TRANSLATES INTO SHORTER SICK LEAVE
EPISODES
L.M. Ruilope 1, C. Catalina-Romero 2, M. Cabrera-Sierra 2, M. Ruiz-Moraga 2,
C. Fernández-Labandera 2, L. Quevedo Aguado 2, M.A. Sánchez-Chaparro 3,
E. Calvo-Bonacho 2. 1 Hypertension Unit, Department of Nephrology, Hospital
12 de Octubre, Madrid, SPAIN, 2 Ibermutuamur (Mutua de Accidentes de
Trabajo y Enfermedades Profesionales de la Seguridad Social 274), Madrid,
SPAIN, 3 Department of Internal Medicine, University Hospital “Virgen de la
Victoria”, and University of Málaga, Málaga, SPAIN
Objective: To assess the impact of the improvement in cardiovascular risk
(CVR) on sickness absence.
Design and method: Prospective cohort study of 27,138 workers from the
ICARIA (Ibermutuamur Cardiovascular Risk Assessment) study. Workers’ CVR
was assessed by the SCORE system in two consecutive years (2005-2006). Cardiovascular risk was categorized in low and moderate-to-high and subjects were
¿QDOO\ FODVVL¿HG LQ WKUHH JURXSV FUHDWHG DFFRUGLQJ WR WKH FKDQJH RU VWDELOLW\
between the two measures of their CVR: always low CVR (25,275), always
moderate-to-high CVR (1,156), and improvement in CVR from 2005 to 2006
(707). Subjects with sickness absence were carried out during 1-year follow up.
The mean of sickness absence days generated by all episodes started in 2007 and
standard deviations were calculated for the three groups of change in CVR. The
total count of sickness absence days was the outcome in multivariate analyses.
Poisson regression was used to test the differences in sickness absence among
the three groups. Always low CVR workers were the reference group.
Results: The mean of sickness absence days was shorter in the group that improved their CVR (52.6 days ± 106.3), than for workers with always moderateto-high CVR (68.4days ± 112.4). After adjusting for sex and age, the total count
RIVLFNQHVVDEVHQFHGD\VGXULQJIROORZXSZDVVLJQL¿FDQWO\KLJKHULQWKHDOZD\V
moderate-high CVR group (RR=1.16; 95% CI: 1.09-1.23; p<0.001), and the
group of workers who improved their CVR level in the former year became similar to the group with always low CVR in terms of sickness absence (RR=1.03;
95% CI: 0.95-1.11; p=0.490).
Conclusions: 7KHFKDQJHLQ&95OHYHOWKURXJKRXWD\HDUSHULRGLVVLJQL¿cantly associated with changes in the subsequent sickness absence. Our results
suggest that the improvement in CVR level from moderate-to-high to low CVR
is associated with a decrease in sickness absence during the next year. The curUHQW¿QGLQJVDOVRVXJJHVWWKDW&95SUHYHQWLRQDPRQJWKHZRUNLQJSRSXODWLRQ
could be cost-effective because the decrease in CVR could be associated with a
decrease in the cost of sickness absence.
e133
Journal of Hypertension Volume 32, e-Supplement 1, 2014
LB03.08
THE CUSTO SCREEN 400 IS THE FIRST
AMBULATORY BP MEASUREMENT DEVICE TO PASS
THE EUROPEAN SOCIETY OF HYPERTENSION
INTERNATIONAL PROTOCOL 2010
T. Mengden 1, A. Wolf 2, B. Beime 3, P. Bramlage 3. 1 Kerckhoff Klinik
GmbH, Bad Nauheim, GERMANY, 2 Müller and Sebastiani GmbH,
Ottobrunn, GERMANY, 3 Institut für Pharmakologie und Präventive Medizin,
Cloppenburg, GERMANY
Objective: The aim of the present study was to validate the ambulatory blood
pressure monitoring (ABPM) device custo screen 400 according to the 2010
International Protocol of the European Society of Hypertension (ESH-IP 2010).
Design and method: The test strictly followed the recommendations of the ESHIP 2010. Systolic and diastolic blood pressure values (SBP / DBP) were sequentially measured in 33 adult subjects (13 males; 20 females) and compared with a
standard mercury sphygmomanometer (two observers) and a total of 99 comparison pairs evaluated. Furthermore we compared the accuracy of the custo screen
400 with previous validations of other devices according to the ESH-IP 2002.
Medicine, Mayo Clinic, Rochester, MN, USA, 2 Dipartimento di Scienze
Mediche, Università di Torino, Turin, ITALY, 3 Division of Biomedical Statistics
and Informatics, Mayo Clinic, Rochester, MN, USA
Objective: It is not known whether abnormal blood pressure (BP) responses
during dobutamine stress echocardiography (DSE) are more or less likely
WREHDVVRFLDWHGZLWKDEQRUPDOVWUHVVHFKRFDUGLRJUDSKLF¿QGLQJVRULIVXFK
¿QGLQJVDUHDVVRFLDWHGZLWKVLJQL¿FDQWFRURQDU\DUWHU\GLVHDVH &$' :H
VRXJKWWRGH¿QHWKHLPSDFWRIDEQRUPDO%3UHVSRQVHVRQWKHIUHTXHQF\RI
positive and falsely positive DSE results.
Design and method: :HLGHQWL¿HGDOOSDWLHQWV SWV ZKRXQGHUZHQW'6(DW
Mayo Clinic, Rochester MN, from Nov 2003 to Dec 2011. Pts with at least
PRGHUDWHYDOYXODUKHDUWGLVHDVHZHUHH[FOXGHG7KHSRSXODWLRQZDVVWUDWL¿HG
DFFRUGLQJ WR SHDN V\VWROLF %3 DFKLHYHG '6( ¿QGLQJV ZHUH DQDO\]HG DQG
DQJLRJUDSKLF¿QGLQJV ZLWKLQGD\VDIWHU'6( RISWVZLWKSRVLWLYH'6(
(mixed + ischemic) were examined. The positive predictive value (PPV) of
DSE was calculated for each BP response subgroup.
Results: The study population comprised 21,949 pts (mean age 67 ±12,
women 10,425, 47%). Pts with hypotensive response (peak systolic BP <82
mm Hg) and hypertensive responses (peak systolic BP >182 mm Hg) were
more likely to have a positive DSE result than those with a normal BP response (24% and 32% vs. 20%, p <.0001) (Figure). Out of 4,771 pts with
a positive DSE, 1,117 (24%) underwent coronary angiography within 30
days: in 814 pts (72%) obstructive CAD (>=50% coronary stenosis) was
FRQ¿UPHG7KHUDWHRIIDOVHSRVLWLYH¿QGLQJVZDVVLPLODUIRUSWVZKRKDGDQ
hypertensive response (30%) vs a normal BP response (27%) (Table).
Results: The custo screen 400 met the requirements of part 1 and 2 of the ESHIP 2010. The mean difference between the device and reference sphygmomanometer readings was -0.5 ± 4.5 mmHg for SBP and -0.1 ± 3.3 mmHg for DBP.
All but one measurement were within the absolute difference of 10 mmHg between the device and the observers for SBP and DBP. The percentage of absolute
differences between the device and the observers within a range of 5 mmHg was
85% (n=84) for SBP and 94% (n=93) for DBP.
A comparison of the absolute differences between the device and the observers
within a range of 5 mmHg for oscillometric ABPM devices validated according
to the ESH-IP 2002 demonstrated excellent accuracy (n=8; 2 devices with failed
validations not listed; best results only for devices with multiple validations).
Conclusions: The custo screen 400 ABPM device met the requirements of the
ESH-IP 2010, and can be recommended for ABPM in adults. To our knowledge, it
LVWKH¿UVWGHYLFHWRSDVVWKHUHYLVHG(6+,3DQGSURGXFHGH[FHOOHQWUHVXOWV
LB03.09
1,2
IMPACT OF ABNORMAL BLOOD PRESSURE
RESPONSES DURING DOBUTAMINE STRESS
ECHOCARDIOGRAPHY ON ECHO RESULTS AND
SUBSEQUENT CORONARY ANGIOGRAPHIC
FINDINGS
1
3
1
1
1
S. Abram , A. Arruda-Olson , C. Scott , P. Pellikka , V. Nkomo , J. Oh ,
A. Milan 2, R. McCully 1. 1 Division of Cardiovascular Diseases and Internal
Conclusions: Pts with abnormal BP responses during DSE are more likely
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a hypertensive response are not more likely to have falsely positive DSE results.