Cerebral small vessel disease and effects of intensive versus standard blood pressure treatment on cardiovascular outcomes and adverse events

Objectives: The safety of intensive blood pressure lowering in patients with preexisting cerebral small vessel disease (CSVD) remains unclear. Methods: We used data from 759 participants in Systolic Blood Pressure Intervention Trial (SPRINT) who completed a baseline MRI, and categorized participants by the median abnormal white matter hyperintensity volume (WMHv, <3.2 cm 3 versus ≥3.2 cm 3 ). We estimated the association of the baseline WMHv with cardiovascular outcomes and adverse events using Cox proportional hazards models adjusted for treatment assignment, age, sex, MRI scanner, and intracranial volume. We used stratified analysis to determine the effect of intensive versus standard treatment by the baseline WMHv. Results: The mean age of the participants was 68 ± 9 years and 39% were female. In adjusted models, adults with WMHv above the median had an increased risk of the primary cardiovascular composite outcome [hazard ratio (HR) 2.59, 95% confidence interval (CI) 1.39, 4.81], all-cause mortality (HR 2.06, 95% CI 0.97, 4.37), and mild cognitive impairment or probable dementia (HR 1.76, 95% CI 0.99, 3.13). While the effects of intensive versus standard blood pressure treatment were similar for most outcomes by WMHv, intensive treatment was associated with a higher risk for mild cognitive impairment or probable dementia among adults with a WMHv above the median (HR 2.36, 95% CI 1.20, 4.66), but not among adults with a WMHv below the median (p-value for interaction = 0.09). Conclusions: In this posthoc analysis of SPRINT, adults with a higher WMHv were at a higher risk for adverse cardiovascular and cognitive outcomes. Among these adults, intensive blood pressure treatment reduced cardiovascular events, while its effects on the risk of cognitive impairment or dementia in this subgroup merit further study.