Uncontrolled Hypertension, Systolic and
Diastolic Blood Pressure and Development
of Symptomatic Peripheral Arterial Disease
in the Women’s Health Study (WHS)
Tiffany M. Powell, Robert J. Glynn, Mark A.
Creager, Paul M. Ridker, Aruna D. Pradhan
Harvard Medical School
Brigham and Women’s Hospital
The authors have no conflicts of interest related
to this research.
Peripheral Arterial Disease
• Increasing but under-diagnosed cardiovascular
health issue
• Affects up to 29% of Americans
• Hypertension linked to PAD development
• Lacking data on PAD risk prediction related to:
– Systolic blood pressure (SBP)
– Diastolic blood pressure (DBP)
Criqui,M.H. et al. Vasc Med 2001,
Murabito,J.M. et al. Am Heart J 2002
Uncontrolled Hypertension
• Up to two-thirds of Americans with hypertension are:
– Untreated
– Undertreated
• Control of hypertension to current guidelines
reduces coronary artery disease by 57%
• How does blood pressure and control status relate to
PAD risk?
Wang,T.J. et al., Circulation 2005
Systolic Blood Pressure and Diastolic Blood Pressure
Coronary Artery Disease
Cerebrovascular Disease
?
?
Peripheral Arterial Disease
Control Status
Women’s Health Study (WHS)
• Randomized, double-blind, placebo controlled
trial of low-dose aspirin and Vitamin E for the
primary prevention of cardiovascular disease
and cancer
• 39,876 U.S. female health professionals aged
45 years and older without prior history of CVD
• Self-reported systolic and diastolic blood pressure
categories as well as treatment status obtained at
baseline
Study Population
39,876 Women
515 Women
Missing Baseline
SBP
534 Women Missing
Baseline DBP
51 Women Missing
History and Treatment
of HTN
39,261 Women with Complete exposure Data
39,261 Women Free of Symptomatic PAD with Complete Data on Blood Pressure
Women with HTN
Uncontrolled
Without HTN
N = 30300
Treated and
Controlled
N = 2679
Untreated and
Uncontrolled
N = 3494
Undertreated and
Uncontrolled
N = 2788
HTN defined as reported
SBP > 140 mmHg and/or
DBP > 90 mmHg, or on antihypertensive therapy
PAD Events in WHS
• Sept 2005 – 482 self-reported cases of symptomatic
PAD
• Symptomatic PAD defined as:
– Intermittent claudication based on Edinburgh Claudication
Questionnaire
– Documented peripheral arterial surgery inclusive of
peripheral angioplasty or stenting
• 116 confirmed cases of PAD
Statistical Analysis
• Continuous BP values assigned using mid-point of reported BP
category.
• Cox Proportional Hazards Regression
• Hazard Ratios for incident PAD:
– According to treatment and BP control status
– SBP, DBP, Mean Arterial Pressure (MAP), Pulse Pressure
(PP) per 10 mmHg and BP categories
• Global model fit assessed by model log-likelihood statistics.
Models of PAD Risk
• Multivariate models adjusted for:
–
–
–
–
–
Age (logage)
Smoking (never/past/current)
Diabetes (no/yes)
BMI (continuous)
History of Elevated Cholesterol (no/yes cholesterol > 240
mg/dl)
– Postmenopausal HT
– Randomized treatment assignment with ASA/Vit E
Baseline Characteristics
No HTN
(N=30300)
Treated and
Controlled
(N=2679)
Hypertensive
(untreated)
(N=3494)
Hypertensive
(undertreated)
(N=2788)
p-value for
Trend
Age, yrs
53.8  6.6
56.7  7.4
57.2  7.8
58.2  7.8
<0.0001
BMI, kg/m2
25.3  4.5
28.0  5.7
28.5  5.9
29.2  6.0
<0.0001
7731 (25.5)
1203 (44.9)
1306 (37.4)
1373 (49.3)
0.04
Diabetes, %
496 (1.6)
191 (7.1)
182 (5.2)
305 (10.9)
0.003
Smoker, %
4097 (13.4)
310 (11.6)
447 (12.8)
323 (11.6)
<0.0001
Hyperlipidemia, %
Baseline Characteristics
Normotensive
(untreated)
(N=30300)
Normotensive
(treated)
(N=2679)
Hypertensive
(untreated)
(N=3494)
Hypertensive
(undertreated)
(N=2788)
p-value for
Trend
SBP, mmHg
117.0  12.8
129.6  7.2
144.9  11.4
147.5  9.8
<0.0001
DBP, mmHg
73.8  8.9
81.7  5.9
88.0  7.4
89.2  6.9
<0.0001
MAP, mmHg
88.2  9.2
97.7  5.3
107.0  5.8
108.6  5.8
<0.0001
PP, mmHg
43.2  10.0
47.9  7.5
56.9  14.2
58.3  11.7
<0.0001
Values are mean  SD
PAD Risk by Treatment and Control
Status
P for trend < 0.0001
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Multivariate Adjus ted
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Hazard Ratio
4.5
4.0
3.5
3.0
2.5
2.0
1.5
1.0
0.5
0.0
Multivariable HRs According to
Increase in BP
10mmHg
HR for PAD
2.0
1.5
1.0
0.5
Per 10 mmHg increase in BP variable
0
LRT:
df:
SBP
DBP
SBP and DBP
PP
MAP
PP and MAP
184.23
10
169.61
10
184.31
11
177.50
10
178.21
10
184.31
11
Hazard Ratio
Categories of Systolic Blood
Pressure
P for linear trend < 0.0001
Categories of Blood Pressure
Both Systolic and Diastolic Blood Pressure
SBP Categories
<120 mm Hg
Age-Adjusted
1.00 (reference)
Multivariable-Adjusted
1.00 (reference)
120 – 139 mm Hg
1.66 (0.97–2.84)
1.66 (0.95-2.89)
140 – 159 mm Hg
2.67 (1.36-5.28)
2.73 (1.35-5.51)
 160 mm Hg
4.06 (1.35-12.20)
3.84 (1.25-11.82)
P, linear trend
0.002
0.003
< 75 mm Hg
1.00 (reference)
1.00 (reference)
75 – 84 mm Hg
0.98 (0.59-1.62)
0.96 (0.57-1.61)
85 – 89 mm Hg
0.87 (0.46-1.67)
0.95 (0.49-1.84)
 90 mm Hg
1.10 (0.53-2.28)
1.16 (0.55-2.44)
0.96
0.76
DBP categories
P, linear trend
Limitations
• Self-reported blood pressure subject to
missclassification
• Findings limited to symptomatic disease
• Study population exclusively comprised of
women
Conclusions
• Uncontrolled hypertension is associated with
incident symptomatic PAD in women.
• While all blood pressure variables assessed were
associated with PAD incidence, SBP was the best
single predictor in this analysis.
Implications
• These data support a strong prognostic role for
systolic blood pressure in the development of PAD in
women.
• Identifies women with uncontrolled
hypertension as a high-risk population.
Questions ?