Intensive versus standard blood pressure control and overall brain small vessel disease burden: a post-hoc analysis of the SPRINT randomized clinical trial.

Abstract

The benefits of improved systolic blood pressure (SBP) control on stroke, coronary heart disease, and heart failure are well-established, yet its effect on overall cerebral small vessel disease (SVD) burden remains uncharacterized. We examined the association between intensive SBP control and change in SVD burden. We conducted a post-hoc analysis of the Systolic Blood Pressure Intervention Trial (SPRINT), a multicenter randomized clinical trial. Of 1267 hypertensive individuals aged ≥50 years without diabetes or prior stroke screened for the brain MRI substudy, 663 and 442 participants completed brain MRI that met quality control criteria and had complete data on SVD indicators at baseline and at a median of 3.9 (interquartile range, 3.6-4.1) years after randomization, respectively. From November 2010 to March 2013, participants were randomly assigned to an intensive SBP target of <120 mmHg (n = 348) or a standard target of <140 mmHg (n = 315). Post-hoc outcome was change in a global SVD factor, longitudinally validated using confirmatory factor analysis and designed to capture overall SVD-related vascular brain injury by integrating three complementary imaging endophenotypes: periventricular white matter hyperintensities, white matter free water, and basal ganglia perivascular spaces. This trial is registered with ClinicalTrials.gov (NCT01206062). Mean [SD] baseline age was 68.1 (8.6) years; 263 [40%] participants were women. Compared with standard SBP treatment, intensive treatment was associated with significantly less SVD progression (standardized mean difference [Cohen's d] = -0.40 [95% CI, -0.62 to -0.17]). We also observed gradually more favorable SVD burden changes with greater attained SBP reductions, demonstrating a clear dose-response relationship: 21.2% (95% CI, 7.4%-35%), 26.3% (13.1%-39.5%), and 39.4% (24.2%-54.5%) less progression relative to baseline SVD burden for SBP reductions of 0-10 mmHg, 10-20 mmHg, and ≥20 mmHg, respectively. Among hypertensive adults, targeting an SBP of <120 mmHg, compared with <140 mmHg, was associated with less progression of SVD burden. Even modest SBP reductions of ≤10 mmHg conferred measurable brain benefits, with larger reductions providing incrementally greater protection against SVD progression. National Institutes of Health, National Heart, Lung, and Blood Institute, National Institute of Diabetes and Digestive and Kidney Diseases, National Institute on Aging, and National Institute of Neurological Disorders and Stroke.