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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.
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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
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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
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Systolic Blood Pressure and Diastolic Blood PressureSystolic Blood Pressure and Diastolic Blood Pressure
Peripheral Arterial DiseasePeripheral Arterial Disease
Coronary Artery DiseaseCoronary Artery Disease Cerebrovascular DiseaseCerebrovascular Disease
Control StatusControl Status?
?
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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
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Study Population
39,261 Women with Complete exposure Data
39,876 Women
515 Women Missing Baseline
SBP
534 Women Missing Baseline DBP
51 Women Missing History and Treatment
of HTN
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39,261 Women Free of Symptomatic PAD with Complete Data on Blood Pressure
Without HTNN = 30300
Treated and ControlledN = 2679
Untreated and Uncontrolled
N = 3494
Undertreated and Uncontrolled
N = 2788
Women with HTN
Uncontrolled
HTN defined as reported SBP > 140 mmHg and/or DBP > 90 mmHg, or on anti-hypertensive therapy
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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
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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.
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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
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Baseline CharacteristicsNo 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
Hyperlipidemia, % 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
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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
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PAD Risk by Treatment and Control Status
0.00.51.01.52.02.53.03.54.04.5
Normotens ive/U
ntreated
Normotens ive/T
reated
Hyperte
ns ive/U
ntreated
Hyperte
ns ive/U
ndertreated
Age Adjusted
Multivariate Adjusted
Haz
ard
Rat
io
P for trend < 0.0001
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SBPSBP
LRT:LRT: 184.23184.23
dfdf::
DBPDBP0
0.5
1.0
1.5
2.0
SBP and DBPSBP and DBP
169.61169.61 184.31184.31
PPPP
177.50177.50
MAPMAP
178.21178.21
PP and MAPPP and MAP
184.31184.31
HR
for P
AD
Per 10 mmHg increase in BP variable
1010 1010 1111 1010 1010 1111
Multivariable HRs According to 10mmHg Increase in BP
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Categories of Systolic Blood Pressure
P for linear trend < 0.0001
Haz
ard
Rat
io
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Categories of Blood PressureBoth Systolic and Diastolic Blood Pressure
SBP Categories Age-Adjusted Multivariable-Adjusted <120 mm Hg 1.00 (reference) 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
DBP categories
< 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)
P, linear trend 0.96 0.76
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Limitations
• Self-reported blood pressure subject to missclassification
• Findings limited to symptomatic disease
• Study population exclusively comprised of women
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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.
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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.
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Questions ?