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ONLINE SUPPLEMENT
Extra-Renal Atherosclerotic Disease Blunts Renal Recovery in patients with
Renovascular Hypertension
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METHODS:
Patient selection and data collection:
Subjects with atherosclerotic renovascular disease (ARVD) were identified from Mayo Clinic
Radiology database, which includes patients who had agreed to have their data used for
research purposes. From this database, we selected ARVD patients who were seen at Mayo
Clinic, Rochester, MN between January 1, 2004 and August 31, 2012 and had an
echocardiogram done within a 2-year period. Imaging criteria for diagnosis of hemodynamically
significant renal artery stenosis included renal artery Doppler ultrasound velocity acceleration
(peak systolic velocity >200 cm/s), or magnetic resonance (MR) /computed tomography (CT)
angiography with evident stenosis >60% and/or post-stenotic dilation (1). Individuals were
excluded from study if they had: 1) End stage renal disease (ESRD), on chronic maintenance
dialysis at the time of entry into the study 2) History of solid organ transplantation 3) Significant
valvular heart disease 4) History of pregnancy in past 12 months and (5) If no follow up data
was available post revascularization.
Clinical parameters:
The Modification in Diet in Renal Disease (MDRD) equation was used to calculate estimated
glomerular filtration rate (eGFR, mL/min per 1.73 m2) as: 175 x SCr (exp[-1.154]) x Age (exp[0.203])x (0.742 if female) x (1.21 if black) (2). Cardiac outcomes were obtained from the
echocardiography database.
Echocardiographic parameters:
Left ventricular mass index (LVMI) was determined using the American Society of
Echocardiography-recommended formula (3) (4). LV relative wall thickness (RWT) was
calculated as (2*PWTd)/LVIDd, where PWTd is the posterior wall thickness and LVIDd, the LV
internal diameter at end diastole (5) (6). Cardiac geometry was classified as follows: i) Normal:
LVMI ≤ 95 g/m2 in women or ≤ 115 g/m2 in men and RWT ≤ 0.42; ii) Concentric remodeling:
LVMI ≤ 95 g/m2 in women or ≤ 115 g/m2 in men and RWT > 0.42; iii) Eccentric hypertrophy:
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LVMI > 95 g/m2 in women or > 115 g/m2 in men and RWT ≤ 0.42; or iv) Concentric
hypertrophy: LVMI > 95 g/m2 in women or > 115 g/m2 in men and RWT > 0.42 (5) (6). Left atrial
volume was measured off-line using the biplane area-length method (5). All of the volume
measurements were indexed to body surface area. Diastolic function was graded as normal;
grade I (mild dysfunction): delayed relaxation mitral inflow pattern, mitral E/A ratio <0.8,
predominant systolic flow in the pulmonary venous flow (S>D), annular e' <8 cm/s (septal and
lateral), and E/e' ratio <8 (septal and lateral)); grade II (moderate dysfunction): pseudo-normal
mitral inflow pattern, mitral E/A ratio ≥1, and average E/e' ratio (septal and lateral) is >10) or
grade III (severe diastolic dysfunction): restrictive mitral inflow pattern, E/A ratio ≥2, deceleration
times (DT) <160 ms, isovolumetric relaxation period (IVRT) ≤60 ms, systolic filling fraction ≤40
percent, and average E/e' ratio ≥13)(7-9).
Statistical analysis:
The Shapiro-Wilk test was used to test for deviation from normality. Normally distributed data
are expressed as mean ± standard deviation. Median and interquartile range (IQR) are used for
non-normally distributed data. Final outcomes were adjusted for gender, baseline blood
pressure, HDL, LDL cholesterol levels, Diabetes Mellitus, peripheral artery disease,
cerebrovascular disease, and family history of coronary artery disease, statin use, number of
anti-hypertensive medications, baseline serum creatinine; and left ventricular ejection fraction
(differences that were statistically significant among the groups).
Results:
In order to evaluate the effects of additional vascular diseases, we studied revascularization
outcomes in ARVD patients with and without diabetes mellitus (Table-1s), cerebrovascular
(Table-2s), or peripheral vascular disease (Table-3s). These comorbidities were also
associated with negatives outcomes, suggesting involvement of diffuse atherosclerosis. A
relatively small number of ARVD patients with diabetes mellitus may account for the greater
decline in systolic blood pressure compared to ARVD patients without diabetes.
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Figure legend:
Figure-1s-One-year outcomes post-revascularization of ARVD based on (A) presence (ARVDDM) or absence (ARVD) of diabetes mellitus (B) presence (ARVD-PAD) or absence (ARVD) of
peripheral arterial disease; (C) presence (ARVD-CVD) or absence (ARVD) of cerebrovascular
disease. Psys, mean change in systolic blood pressure; Pdia, mean change in diastolic blood
pressure; SCR, median change in serum creatinine; GFR,median change in eGFR; and Uprot,
median change in proteinuria excretion. * P<0.05 after adjustment for clinically significant
variables including gender, baseline blood pressure and renal function. Details are provided in
the supplementary material (Table-1s-3s).
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Table-1s. One-year outcomes post-revascularization of ARVD based on presence (ARVDDM) or absence (ARVD) of Diabetes.
ARVD-DM
ARVD
(N=36)
(N=95)
Unadjusted P
value
Adjusted* P
value
141±21**
140±15
0.76
0.0033
-9.8±23
-5±25
0.33
<.0001
66±14**
67±11**
0.91
0.016
-6.9±15
-6±15
0.73
<.0001
1.5(0.74.8)**
1.3(0.7-8.6)
0.16
<.0001
0.1(-1-+1.7)
0(-1.0-+7.1)
0.59
0.07
42(12-85)
46(4.5-82)
0.19
<.0001
-4.2(-29-+38)
-0.4(-38+46.7)
0.10
0.077
180(281064)
124(213707)
0.79
0.13
-27(-1880+737)
6(-1000+2862)
0.12
0.46
Outcomes
Systolic blood pressure
(mmHg)
Δchange(mmHg)
Diastolic blood pressure
(mmHg)
Δchange(mmHg)
Serum creatinine(mg/dl)
Δchange(mg/dl)
eGFR(ml/min/1.73m²)
Δchange(ml/min/1.73m²)
Proteinuria(mg/dl)
Δchange(mg/dl)
eGFR, estimated glomerular filtration rate.*after adjustment for gender, baseline blood pressure,
HDL, LDL cholesterol levels, peripheral artery disease, cerebrovascular disease, Coronary
artery disease (CAD), family history of CAD, statin use, number of anti-hypertensive
medications, baseline serum creatinine; and left ventricular ejection fraction in a multivariate
model. **P<0.05 vs. pre-revascularization. Data are presented as Median (range), N (%), or
Mean ±SD; as appropriate.
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Table-2s. One-year outcomes post-revascularization of ARVD based on presence (ARVDCVD) or absence (ARVD) of Cerebrovascular disease.
ARVD-CVD
ARVD
(N=68)
Systolic blood pressure
(mmHg)
Δchange(mmHg)
(N=63)
Unadjusted P
value
Adjusted* P
value
142±16
140±18**
0.32
0.0025
-4.5±26
-8±23
0.39
<.0001
66±13**
66±11**
0.97
0.009
-4.1±14
-8±16
0.12
<.0001
1.4(0.78.6)**
1.2(0.7-4.4)
0.24
0.006
0.1(-0.7+7.1)
0(-1.2-+1.3)
0.10
0.03
43(4.5-83)**
46(13-85)
0.29
0.0044
-3.3(-29+29)
-0.4(-38+46.7)
0.20
0.09
193(213707)
98(31-1381)
0.08
0.26
13(-1880+2862)
-8(-729+194)
0.16
0.39
Outcomes
Diastolic blood pressure
(mmHg)
Δchange(mmHg)
Serum creatinine(mg/dl)
Δchange(mg/dl)
eGFR(ml/min/1.73m²)
Δchange(ml/min/1.73m²)
Proteinuria(mg/dl)
Δchange(mg/dl)
eGFR, estimated glomerular filtration rate.*after adjustment for gender, baseline blood pressure,
HDL, LDL cholesterol levels, Diabetes Mellitus, peripheral artery disease, coronary artery
disease (CAD), family history of CAD, statin use, number of anti-hypertensive medications,
baseline serum creatinine; and left ventricular ejection fraction in a multivariate model. **P<0.05
vs. pre-revascularization. Data are presented as Median (range), N (%), or Mean ±SD; as
appropriate.
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Table-3s. One-year outcomes post-revascularization of ARVD based on presence (ARVDPAD) or absence (ARVD) of Peripheral artery disease.
ARVD-PAD
ARVD
(N=45)
Systolic blood pressure
(mmHg)
Δchange(mmHg)
(N=86)
Unadjusted P
value
Adjusted* P
value
142±18
140±17**
0.64
0.0041
-4.7±28
-7±23
0.61
<.0001
66±14
67±11**
0.84
0.014
-4.6±15
-7±15
0.40
<.0001
1.4(0.98.6)**
1.2(0.7-4.4)
0.16
0.009
0.1(-1-+7.1)
0(-1.2-+2.1)
0.21
0.04
42(5-81)
47(11-85)
0.08
0.006
-3.2(-29+47)
-0.6(-38+37.8)
0.78
0.12
226(371644)
106(213707)
0.48
0.33
12(-1880+1187)
0(-1000+2862)
0.68
0.43
Outcomes
Diastolic blood pressure
(mmHg)
Δchange(mmHg)
Serum creatinine(mg/dl)
Δchange(mg/dl)
eGFR(ml/min/1.73m²)
Δchange(ml/min/1.73m²)
Proteinuria(mg/dl)
Δchange(mg/dl)
eGFR, estimated glomerular filtration rate.*after adjustment for gender, baseline blood pressure,
HDL, LDL cholesterol levels, Diabetes Mellitus, cerebrovascular disease, coronary artery
disease (CAD), family history of CAD, statin use, number of anti-hypertensive medications,
baseline serum creatinine; and left ventricular ejection fraction in a multivariate model. **P<0.05
vs. pre-revascularization. Data are presented as Median (range), N (%), or Mean ±SD; as
appropriate.
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