Antihypertensive Drug Use, Blood Pressure Variability, and Incident Stroke Risk in Older Adults: Three-City Cohort Study

Background and Purpose— The aim was to determine the association between antihypertensive drug class and incident stroke controlling for long-term blood pressure (BP) variability (BPV) in people aged ≥65 years. Methods— The sample included 5951 participants (median age 74 years, 60% women) taking at least 1 drug for hypertension (3727/5951) or with systolic BP >140 mm Hg or diastolic BP >90 mm Hg. Participants were evaluated for incident fatal and nonfatal stroke to 12 years follow-up. BPV was calculated with the coefficient of variation method and regressed against 9 antihypertensive drug classes (BPV reg ). Hazard models were used to determine hazard ratios for incident stroke risk attributable to drug class, adjusted for BP, BPV reg , covariates, and delayed entry bias. Results— There were 273 incident strokes over a median of 9.1 years (interquartile range 6.4–10.4). Stroke risk was generally not reduced by BP-lowering drugs. Angiotensin receptor blockers (hazard ratio 1.56; 95% confidence interval 1.06–2.28; P =0.02) and β-blockers (hazard ratio 1.41; 95% confidence interval 1.03–1.92; P =0.03) were associated with an increased total stroke risk. Angiotensin receptor blockers and β-blockers were also associated with ischemic strokes after adjustment for systolic BPV. Diastolic BPV was associated with stroke risk in analyses stratified by systolic BP 140 to 160 mm Hg (per 0.10 increase in coefficient of variation, hazard ratio 1.59; 95% confidence interval 1.05–2.40; P =0.03). Conclusions— The angiotensin receptor blocker and β-blocker drug classes were associated with incident stroke and ischemic stroke in older adults. BPV was generally not associated with incident stroke.