Antihypertensive Drug Use, Blood Pressure Variability, and Incident Stroke Risk in Older Adults

Study Questions:

Is the use of antihypertensive drugs associated with incident stroke in older adults, and does blood pressure variability affect stroke risk in this population?


The authors used data from the Three-City Study, a French prospective multisite cohort study evaluating the determinants of stroke and dementia to answer the study questions. Adults older than age 64 years underwent serial evaluations every 2 years for up to 12 years. Subjects without a history of hypertension (or taking antihypertensive drugs) and those with a history of stroke were excluded from these analyses. Antihypertensive drugs were categorized into subtypes. Blood pressure variability (BPV) was calculated using the coefficient of variation method (standard deviation/mean). The diagnosis of stroke was adjudicated by a blinded expert panel. Regressions of systolic and diastolic BPV (BPVreg) were performed to account for polypharmacy. Incident stroke was analyzed with Cox proportional hazard models after adjustment for covariates and BPVreg. Subjects were censored after stroke, death, or study drop-out.


There were 5,951 subjects included. The median age was 74 years, and 60% were women. The median follow-up was 9.1 years. There were 273 subjects who had a stroke during the study period. The subjects with incident stroke were more likely to be older, diabetic, and had higher average systolic and diastolic blood pressures. Βeta-blockers were the most common blood pressure medication (in 21%), followed by angiotensin-converting enzyme inhibitors (17%), potassium-sparing diuretics (12%), and others. Only 3% were taking a thiazide diuretic. Most subjects (62%) were on blood pressure monotherapy, although 29% were taking two antihypertensives. Stroke risk was increased with angiotensin receptor blockers (ARBs) (hazard ratio [HR] range, 1.56-1.61) and beta-blockers (HR range, 1.41-1.43). Accounting for BPVreg did not change the association between stroke and ARBs and beta-blockers. Systolic and diastolic BPVreg were not associated with an increased risk of incident stroke. Higher mean systolic blood pressures (per 10 mm Hg increase, HR, 1.22; 95% confidence interval [CI], 1.21-1.23) and mean diastolic blood pressures (per 5 mm Hg increase, HR, 1.12; 95% CI, 1.10-1.14) increased stroke risk.


Use of ARBs and beta-blockers was associated with an increased risk of stroke in this elderly cohort. Increased BPV was not associated with an increased risk of stroke.


There is a dearth of evidence to guide blood pressure management for primary prevention of stroke in older adults. Recently, BPV, independent from absolute blood pressure, has emerged as a potential risk factor for stroke. Certain classes of antihypertensive drugs increase BPV, while others decrease it. This study is the first to look at the association between BPV and stroke risk in the elderly. The low frequency of thiazide diuretic use is somewhat surprising in a study that evaluated primary prevention, and argues for some caution in generalizing these results. The lack of association between BPV, and stroke was unexpected, but may relate to how BPV was calculated, that subjects were evaluated every 2 years, that this was a primary prevention study, or BPV may simply be less of a risk factor in the elderly. While the findings of this study should be considered preliminary given its observational nature, since other studies have shown an increased risk of stroke with beta-blockers, the finding of increased stroke risk in patients taking ARBs and beta-blockers may lead providers to consider alternative agents unless there is a clear indication for an ARB or beta-blocker.

Clinical Topics: Geriatric Cardiology, Heart Failure and Cardiomyopathies, Prevention, Hypertension, Sleep Apnea

Keywords: Adrenergic beta-Antagonists, Angiotensin Receptor Antagonists, Angiotensin-Converting Enzyme Inhibitors, Antihypertensive Agents, Blood Pressure, Dementia, Diabetes Mellitus, Diuretics, Potassium Sparing, Geriatrics, Hypertension, Polypharmacy, Primary Prevention, Risk Factors, Sodium Chloride Symporter Inhibitors, Stroke, Systole

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