HYPERTENSION IN OSAHS
“CONSEQUENCE OR CO-EXISTENCE”
Dr C Ravindran MD,DTCD,MBA
Dean
Medical College, Calicut
principalmcc@gmail.com
ICS-Dr CV Ramakrishnan Oration 2010
Obstructive Sleep ApnoeaHypopnoea Syndrome
 OSAHS is a common but often unrecognized
entity
 Sleep disordered breathing occur in both men
(25%) and women (10%) of varying ethnic
groups
 Prevalence of symptomatic sleep apnea has
been reported to be 4% for men and 2% for
women
ICS-Dr CV Ramakrishnan Oration 2010
OSAHS
 Obstructive sleep apnea (OSA) is affecting an
estimated 15 million Americans, with a
prevalence that is probably also rising as a
consequence of increasing obesity.
 Epidemiologic data support a link between
obesity and hypertension as well as between
OSA and hypertension.
ICS-Dr CV Ramakrishnan Oration 2010
OSAHS & Cardiovascular disease
 Cardiovascular disease represents the
principal physical morbidity and cause of
death in OSAHS
-Hypertension
-Ischaemic heart disease
-Cerebrovascular disease
 The precise mechanisms are unclear but
are likely to be multifactorial.
Interaction Between Sleep
and Heart Pathology
Secondary
Primary
Sleep Apneas &
Hypopneas
Cardiovascular
Pathology
Secondary
Primary
ICS-Dr CV Ramakrishnan Oration 2010
What happens in OSA
Cardiometabolic consequence of Obstructive Sleep Apnea
ICS-Dr CV Ramakrishnan Oration 2010
ICS-Dr CV Ramakrishnan Oration 2010
Distribution by BMI
45
40
35
30
25
20
15
10
5
0
UNDERWEIGHT
NORMAL
OVERWEIGHT
OBESE
UN
DE
RW
EI
G
NO HT
O
VE RM
RW AL
EI
G
HT
M
O
O
RB B E
SE
ID
O
B
ES
E
MORBID OBESE
Harilakshmanan P, Ravindran C, Institute of Chest Diseases, Calicut
ICS-Dr CV Ramakrishnan Oration 2010
ICS-Dr CV Ramakrishnan Oration 2010
Metabolic Syndrome in OSA
 Whether OSA forms part of the metabolic
syndrome, or OSA itself is a syndrome with
multi-organ dysfunction
 Role of OSA in regulation of metabolism and
their interactions within the complex network
will determine the outcome in each
individual.
Cardiovascular morbidity in
obstructive sleep apnea
hypopnea syndrome – A cross
sectional study
Paulo Varghese Akkara, Suraj.K.P,.
Sajeev C.G, James.P.T, Ravindran. C
Institute of Chest Diseases, Medical College, Calicut
ICS-Dr CV Ramakrishnan Oration 2010
Cardiovascular co-morbidities
ICS-Dr CV Ramakrishnan Oration 2010
Cardiovascular risk factors
ICS-Dr CV Ramakrishnan Oration 2010
Echocardiographic parameters
ICS-Dr CV Ramakrishnan Oration 2010
VARIABLES
“P” VALUE
UNIVARIATE
“P” VALUE
MULTIVARIATE
MALE SEX
0.002
0.049
SYSTEMIC
HYPERTENSION
0.001
0.019
CORONARY
ARTERY DISEASE
0.002
0.169
COPD
0.007
0.303
DYSLIPIDEMIA
0.015
0.270
0.001
0.054
SMOKING
ICS-Dr CV Ramakrishnan Oration 2010
OSAHS and hypertension
 Up to 50-60% of patients with sleep apnea
may have hypertension .
 Prevalence of OSAHS is greater in
hypertensive patients than in general
population.
 Hypertension in patients with sleep apnea is
often resistant to antihypertensive therapy.
ICS-Dr CV Ramakrishnan Oration 2010
OSAS and hypertension
 Untreated OSA predisposes to an
increased risk of new hypertension, and
treatment of OSA lowers blood pressure,
even during the daytime.
ICS-Dr CV Ramakrishnan Oration 2010
JNC 7
 Seventh report of the Joint
National Committee on
Prevention, Evaluation, and
Treatment of High Blood
Pressure now recognizes sleep
apnea as an identifiable cause
of secondary hypertension .
ICS-Dr CV Ramakrishnan Oration 2010
Identifiable
Causes of Hypertension
Sleep apnea
Drug-induced or related causes
Chronic kidney disease
Primary aldosteronism
Renovascular disease
Chronic steroid therapy and Cushing’s syndrome
Pheochromocytoma
Coarctation of the aorta
Thyroid or parathyroid disease
ICS-Dr CV Ramakrishnan Oration 2010
Mechanism
 The variations in BP occur under the influence
of four predominant stimuli:
1. Oxygen desaturation
2. Increase in PCO2
3. Increased respiratory effort
4. Micro-arousal at the end of the apnea.
ICS-Dr CV Ramakrishnan Oration 2010
14 nights of intermittent hypoxia elevate day time
BP and sympathetic activity in healthy humans.
Tamisier 2010
 Model of intermittent hypoxia
 12 normal adults
 Day time BP elevated
 Increased muscle sympathetic nerve activity and
decreased baroreflex control
 No change in systemic inflammatory markers or
vascular reactivity
Wisconsin Sleep Cohort Study
 A prospective, population-based study of the
association between objectively measured sleepdisordered breathing and hypertension
 Hypertension is defined as a laboratory-measured
blood pressure of at least 140/90 mm Hg or the use of
antihypertensive medications.
 709 subjects with follow up of 4 years
 Age 30 – 65 years
Peppard et al: NEJM, 2000
ICS-Dr CV Ramakrishnan Oration 2010
The Wisconsin Sleep Cohort
Study
 Showed a linear relationship between
severity of sleep apnea and incidence of new
hypertension that was not explained by other
factors, such as baseline blood pressure, body
habitus, age, gender, and cigarette and
alcohol consumption
ICS-Dr CV Ramakrishnan Oration 2010
Peppard et al: NEJM, 2000
ICS-Dr CV Ramakrishnan Oration 2010
Adjusted odds ratios for the presence of incident
hypertension at 4-year follow-up according to the apneahypopnea index (AHI) at baseline.
Odds ratio
AHI >15
AHI 5-15
Odds ratio
AHI 0-5
AHI 0
0
1
2
3
4
ICS-Dr CV Ramakrishnan Oration 2010
Wisconsin Sleep Cohort Study
 SDB was accompanied by a substantially
increased risk of developing hypertension.
 Subjects with an apnoea/hypopnoea index (AHI)
of >15 events had a three-fold increased risk of
developing new hypertension over a 4-yr period.
ICS-Dr CV Ramakrishnan Oration 2010
Sleep Heart Health Study
 Cross-sectional analyses of participants in the
Sleep Heart Health Study, a communitybased multicenter study conducted between
November 1995 and January 1998
 6132 subjects
 Age 40 – 97 years
Nieto et al: Jama, 2000
ICS-Dr CV Ramakrishnan Oration 2010
Nieto et al: Jama, 2000
ICS-Dr CV Ramakrishnan Oration 2010
Sleep Heart Health Study
 In this study, the odds ratio (OR) in the group
with the most severe sleep apnea (AHI ≥ 30)
was 1.37 (95% confidence interval [CI], 1.03–
1.83; P for trend = 0.005) compared with those
with lowest AHI (< 1.5) after adjusting for
confounding factors, including obesity
ICS-Dr CV Ramakrishnan Oration 2010
ICS-Dr CV Ramakrishnan Oration 2010
OSAHS & Hypertension
 A large prospective study demonstrated a significant
risk for hypertension in the setting of underlying
OSA with an odds ratio for developing hypertension
of 2.895
 The data regarding refractory hypertension is even
more impressive, with one study demonstrating the
presence of OSA in 83% of patients who are
uncontrolled on three or more antihypertensive
medications.
 In a related study by the same authors, the treatment
of OSA completely abolished previously
uncontrolled hypertension.
ICS-Dr CV Ramakrishnan Oration 2010
Is Home monitoring useful in
OSA?
No. of patients diagnosed as hypertensive
According to each BP monitoring technique
Clinic BP
22
31%
Home BP
17
24%
24 h ABPM
51
72%
Masked Hypertension 41%
Nocturnal diastolic isolated HT 37%
Bague et al. Hypertension 2010 in revision
ICS-Dr CV Ramakrishnan Oration 2010
Resistant Hypertension
 Resistant or refractory HTN is a condition where
therapeutic plan including attention to lifestyle
measures and prescription of at least three drugs
at adequate doses has failed to lower systolic and
diastolic pressure to the targeted values
 5-18% of the hypertensive population in an HT
clinic.
 Patients with resistant hypertension are at
greater risk for stroke, renal insufficiency and co
- morbid cardiovascular events.
Mancia G et al: J Hypertens 2007;25:1105-87
OSA & Hypertension
Hypertensives studied = 61
Type
No.
OSA
No OSA
% of
Hypertensives
with OSA
Obese
Hypertensive
38
38
0
100
23
14
9
60.8
Non-obese
Hypertensive
Krishnakumar E V, Ravindran C, Institute of Chest diseases, Medical College, Calicut
ICS-Dr CV Ramakrishnan Oration 2010
OSA in Nonobese Patients
Science Daily (June 17, 2009)
 Fifty-four percent (2,906) of 5,426 non-obese
patients were OSA positive.
 57 percent of them were middle aged.
 Male prevalence and neck size were
significantly higher in the group with
moderate to severe OSA.
 Associations have been found between OSA
and serious medical conditions such as heart
disease, diabetes, obesity, hypertension and
increased risk for mortality.
Metabolic Syndrome in non-obese
 Significantly higher percentage of patients with OSAS (19%
vs 4%) had at least two of the following: hypertension,
hyperglycemia, and dyslipidemia.
 Apnea-hypopnea index value was the predictor of number of
metabolic syndrome parameters.
 Independent of visceral fat obesity, OSAS was associated
with hypertension, dyslipidemia, and hyperglycemia.
 It is possible that OSAS may predispose even non-obese
patients to the development of metabolic syndrome.
CHEST May 2007;131(5):1387-1392
 Epidemiologic- and clinic-based studies in
both adults and children have consistently
shown that blood pressure level and the risk
of hypertension increased with increasing AHI
levels after correction for confounders such
as obesity, age and gender.
N. Engl. J. Med.342(19),1378-1384 (2000).
 An AHI of greater than 15 was associated with
elevation of 3.6 mmHg and 1.8 mmHg for
systolic and diastolic blood pressure,
respectively( OR 1.8 )
 It is also showed that each additional apneic
event per hour of sleep was associated with
increases of 0.1 and 0.04 mmHg in systolic
and diastolic blood pressure, respectively
OSA & Childhood Hypertension
 Children with OSA had significantly higher BP
than normal healthy children during both sleep
and wakefulness.
 BP levels increased with the severity of OSA, and
children with moderate to severe disease (AHI
>5) were at significantly higher risk for nocturnal
systolic (OR 3.9 (95% CI 1.4 to 10.5) and
diastolic (OR 3.3 (95% CI 1.4 to 8.1)
hypertension.
Thorax63(9),803-809 (2008).
OSA & Hypertension in Pregnancy
 Hypertension is often associated with OSA.
 5 of 7 reported cases have also had preeclampsia.
Habitual snoring, the most common symptom of
OSA, has been associated with hypertension,
preeclampsia and intrauterine growth restriction.
 Nasal CPAP is the mainstay of therapy for OSA and
has been shown to significantly reduce blood pressure
and uric acid levels in women with preeclampsia
Am J Hypertens 2001; 14: 1090–5
OSA & Hypertension in Pregnancy
 Prevalence of OSA is high among those with
gestational hypertension/preeclampsia during
pregnancy.
 Incident snoring, which is a marker for OSA, is
associated with an increased risk of developing
gestational hypertension.
 Recent studies indicate that OSA per se is an
independent risk factor for gestational
hypertension/pre-eclampsia
 Contribute to other poor obstetrical outcomes
Indian J Med Res. 2010 Feb;131:285-301
OSA/HTN + CPAP
 118 patients with ODI of 17/hr on CPAP
Vs sub-therapeutic CPAP (1cm) x 4weeks
 Mean BP decreased by
2.4/3.4(sleep/wake) Vs an increase of 0.8
 CPAP > 5 hours needed
Pepperell et al
ICS-Dr CV Ramakrishnan Oration 2010
Changes in mean (MAP), systolic, and
diastolic blood pressure with effective
(closed bars) and sub-therapeutic (open
bars) CPAP.
ICS-Dr CV Ramakrishnan Oration 2010
OSA/HTN + CPAP
 32 patients on CPAP vs sub-therapeutic
CPAP (1cm) x 9 weeks
 SBP/DBP decreased by 10 mm vs no
change
 AHI decreased from 65 to 3 vs 65 to 33
Becker et al
ICS-Dr CV Ramakrishnan Oration 2010
N=768
Becker
et al: Circulation, 2003
ICS-Dr CV Ramakrishnan Oration 2010
Long-term Effect of Continuous Positive
Airway Pressure in Hypertensive Patients with
Sleep Apnea
 In non-sleepy hypertensive patients with
OSA, CPAP treatment for 1 year is associated
with a small decrease in BP.
 This effect is evident only in patients who use
CPAP for more than 5.6 hours per night.
Ferran Barbé1, Joaquín Durán- Cantolla, Francisco Capote et al: AJRCCM
2010;181:718-726
ICS-Dr CV Ramakrishnan Oration 2010
Comparison of Continuous Positive Airway
Pressure and Valsartan in Hypertensive
Patients with Sleep Apnea
 In an RCT, although the BP decrease was
significant with CPAP treatment, valsartan
induced a fourfold higher decrease in mean
24-hour BP than CPAP in untreated
hypertensive patients with OSA.
AJRCCM 2010; 182: 954-960
Conclusions
 Epidemiologic data suggest that sleep apnea is
an independent risk factor for hypertension.
 Studies support the concept that effective
CPAP therapy can have early and sustained
beneficial effect on daytime and nighttime
blood pressure.
 Obesity contributes to cardiovascular risk
associated with OSA and also to hypertension.
 Efforts to carefully screen and treat patients
with sleep apnea would impact on the risk of
and treatment for hypertension, and on
consequent cardiovascular morbidity and
ICS-Dr CV Ramakrishnan Oration 2010