Systolic Blood Pressure Levels and Probable Dementia : Secondary Analysis of a Randomized Clinical Trial

Abstract

AbstractBackgroundDespite a significant 19% reduction in risk for mild cognitive impairment, the primary Systolic Blood Pressure Intervention Trial (SPRINT) analysis lacked sufficient evidence to assert statistical significance for the 17% reduction in probable dementia alone in intensive blood pressure (BP) control, defined as a target systolic BP < 120 mmHg, compared to the standard target of < 140 mmHg (p = 0.10). However, early termination of SPRINT may have caused these analyses to be under‐powered. We applied the statistical framework of joint models for longitudinal data and time‐to‐event outcomes to analyze the effect of systolic BP levels on probable dementia using the SPRINT data.MethodsSPRINT was a multicenter randomized clinical trial that enrolled patients ≥50 years of age with hypertension and increased cardiovascular risk but without diabetes or history of stroke. In this secondary analysis, the primary outcome was occurrence of adjudicated probable dementia after randomization. Secondary outcomes included adjudicated mild cognitive impairment and a composite outcome of mild cognitive impairment or probable dementia. To analyze these outcomes, we applied joint longitudinal and survival models. In the longitudinal component of the joint model, systolic BP levels were modeled as a quadratic function of time since randomization, accounting for correlation in repeated measurements and for assignment to intensive BP control versus standard care. In the survival component, multi‐variable adjustment for race, education, and age at baseline was applied.ResultsOver a median follow up of 5.2 years, a total of 325 probable dementia and 640 mild cognitive impairment events occurred. After multi‐variable adjustment (as above), the hazard ratio per 10 mmHg decrease in systolic BP was 0.89 (95% confidence interval [CI] 0.79, 0.99) for probable dementia, 0.89 (95% CI 0.82, 0.96) for mild cognitive impairment, and 0.90 (95% CI 0.84, 0.97) for their composite outcome (Table). Dynamic predictions after 2 years of follow‐up provide a descriptive summary of systolic BP levels and predicted risk of probable dementia or mild cognitive impairment (Figure).ConclusionReducing systolic BP decreases the risk of both probable dementia and mild cognitive impairment.