Dementia risk with antihypertensive use and blood pressure variability

OBJECTIVE: To determine the association between discrete antihypertensive drug classes and incident dementia controlling for blood pressure variability (BPV) in the preceding 4 years. METHODS: A total of 6,537 participants (mean age 79 years, 62% women) in a prospective population-based cohort were followed up for incident dementia. A 4-year time lag period was created to classify drug exposure and measure blood pressure. BPV (percent coefficient of variation [CV]) was regressed against 9 antihypertensive drug classes (BPVreg). Cox regression models were employed to determine hazard ratios (HRs) for incident dementia thereafter according to drug class, adjusted for mean blood pressure, covariates, and BPV or BPVreg. RESULTS: Over a median 8.4 years follow-up (interquartile range 6.7-9.0), lower dementia risk was associated with nondihydropyridine calcium channel blocker (HR 0.56; 95% confidence interval [CI] 0.31-1.00, p = 0.05) and loop diuretics (HR 0.45; 95% CI 0.22-0.93, p = 0.03) after adjusting for CV-BPV. Similar findings were obtained in analyses restricted to antihypertensive drug users for nondihydropyridine calcium channel blocker (HR 0.52; 95% CI 0.28-0.95, p = 0.03) and loop diuretics (HR 0.40; 95% CI 0.19-0.83, p = 0.01). All systolic BPV × antihypertensive drug interaction terms were not different from p < 0.05. CONCLUSIONS: Nondihydropyridine calcium channel blocker and loop diuretics were associated with a reduced dementia risk independent of CV-BPV in the preceding 4 years. Systolic BPV was not the primary mechanism through which antihypertensive drug classes lower dementia risk.