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 PressureSystolic Blood Pressure and Diastolic Blood Pressure

Peripheral Arterial DiseasePeripheral Arterial Disease

Coronary Artery DiseaseCoronary Artery Disease Cerebrovascular DiseaseCerebrovascular Disease

Control StatusControl 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

39,261 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

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

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 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

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

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

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

Categories of Systolic Blood Pressure

P for linear trend < 0.0001

Haz

ard

Rat

io

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

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 ?