Uncontrolled Hypertension Systolic and Diastolic Blood Pressure and
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 mm. Hg and/or DBP > 90 mm. Hg, 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 mm. Hg 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/m 2 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, mm. Hg 117. 0 12. 8 129. 6 7. 2 144. 9 11. 4 147. 5 9. 8 <0. 0001 DBP, mm. Hg 73. 8 8. 9 81. 7 5. 9 88. 0 7. 4 89. 2 6. 9 <0. 0001 MAP, mm. Hg 88. 2 9. 2 97. 7 5. 3 107. 0 5. 8 108. 6 5. 8 <0. 0001 PP, mm. Hg 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 Hazard Ratio P for trend < 0. 0001
Multivariable HRs According to Increase in BP 10 mm. Hg HR for PAD 2. 0 1. 5 1. 0 0. 5 Per 10 mm. Hg increase in BP variable 0 LRT: df: SBP DBP 184. 23 10 169. 61 10 SBP and DBP 184. 31 11 PP MAP PP and MAP 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) 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.
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