Association of Blood Pressure Measurements with Peripheral Arterial Disease Events: A Reanalysis of the ALLHAT Data
Background—Current guidelines recommend treating hypertension in patients with peripheral arterial disease (PAD) to reduce the risk of cardiac events and stroke, but the effect of reducing blood pressure on lower extremity PAD events is largely unknown. We investigated the association of blood pressure with lower extremity PAD events using data from the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT).
Methods—ALLHAT investigated the effect of different antihypertensive medication classes (chlorthalidone, amlodipine, lisinopril, or doxazosin) on cardiovascular events. Using these data, the primary outcome in our analysis was time to first lower extremity PAD event, defined as PAD-related hospitalization, procedures, medical treatment, or PAD-related death. Given the availability of longitudinal standardized blood pressure measurements, we analyzed systolic blood pressure (SBP), diastolic blood pressure (DBP) and pulse pressure (PP) as time-varying categorical variables (reference categories 120-129 mm Hg for SBP, 70-79 mm Hg for DBP, and 45-54 mm Hg for PP) in separate models. We used extended Cox regression with death as a competing risk to calculate the association of each BP component with PAD events, and report the results as sub-distribution hazard ratios (HR) and 95% confidence intervals (CI).
Results—The present analysis included 33,357 patients with an average age of 67.4 years, 53.1% men, 59.7% white race, and 36.2% with diabetes mellitus. The median baseline blood pressure was 146/84 mm Hg. Participants were followed for a median of 4.3 (IQR 3.6-5.3) years, during which time 1,489 (4.5%) had a lower extremity PAD event, and 4,148 (12.4%) died. In models adjusted for demographic and clinical characteristics, SBP <120 mm Hg was associated with a 26% (CI 5-52%, P=0.015) higher hazard and SBP≥160 mm Hg was associated with a 21% (CI 0-48%, P=0.050) higher hazard for a PAD event, compared with SBP 120-129 mm Hg. In contrast, lower, but not higher, DBP was associated with higher hazard of PAD events: for DBP <60 mm Hg HR = 1.72 (CI 1.38 - 2.16). PP had a U-shaped association with PAD events.
Conclusions—In this re-analysis of data from ALLHAT, we found a higher rate of lower extremity PAD events with higher and lower SBP and PP, and with lower DBP. Given the recent revised blood pressure guidelines advocating lower SBP targets for overall cardiovascular risk reduction, further refinement of optimal blood pressure targets specific to PAD is needed.
Clinical Trial Registration—URL: www.clinicaltrials.gov Unique identifier: NCT00000542
- Received February 16, 2018.
- Revision received May 16, 2018.
- Accepted June 11, 2018.