Cerebral White Matter Hyperintensities, Kidney Function Decline, and Recurrent Stroke After Intensive Blood Pressure Lowering: Results From the Secondary Prevention of Small Subcortical Strokes (SPS3) Trial

BACKGROUND: We aimed to determine whether cerebral white matter hyperintensities (WMHs) can distinguish stroke survivors susceptible to rapid kidney function decline from intensive blood pressure (BP) lowering. METHODS AND RESULTS: The SPS3 (Secondary Prevention of Small Subcortical Strokes) trial randomized participants with recent lacunar stroke to systolic BP targets of 130 to 149 and <130 mm Hg. We included 2454 participants with WMH measured by clinical magnetic resonance imaging at baseline and serum creatinine measured during follow‐up. We tested interactions between BP target and WMH burden on the incidence of rapid kidney function decline (≥30% decrease from baseline estimated glomerular filtration rate at 1‐year follow‐up) and recurrent stroke. Rapid kidney function decline incidence was 11.0% in the lower‐BP‐target arm and 8.1% in the higher‐target arm (odds ratio=1.40; 95% CI=1.07–1.84). Odds ratio for rapid kidney function decline between lower‐ and higher‐target groups ranged from 1.26 in the lowest WMH tertile (95% CI, 0.80–1.98) to 1.71 in the highest tertile (95% CI, 1.05–2.80; P for interaction=0.65). Overall incidence of recurrent stroke was 7.9% in the lower‐target arm and 9.6% in the higher‐target arm (hazard ratio=0.80; 95% CI, 0.63–1.03). Hazard ratio for recurrent stroke in the lower‐target group was 1.13 (95% CI, 0.73–1.75) within the lowest WMH tertile compared with 0.73 (95% CI, 0.49–1.09) within the highest WMH tertile (P for interaction=0.04). CONCLUSIONS: Participants with higher WMH burden appeared to experience greater benefit from intensive BP lowering in prevention of recurrent stroke. By contrast, intensive BP lowering increased the odds of kidney function decline, but WMH burden did not significantly distinguish this risk. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00059306.