Background: The benefits of improved systolic blood pressure (BP) control on stroke, coronary heart disease, and heart failure are well-established, yet its effect on overall cerebral small vessel disease (SVD), a major contributor to cognitive decline and dementia, remains uncharacterized. We examined the association between intensive BP control and longitudinal change in SVD burden in a randomized clinical trial.

Methods: We conducted a post-hoc analysis of the Systolic Blood Pressure Intervention Trial (SPRINT), a multicenter randomized clinical trial across 27 US sites. A total of 442 hypertensive individuals aged ≥50 years without diabetes or prior stroke completed multisequence brain MRI at baseline and at a median of 3.9 years (interquartile range, 3.6-4.1) after randomization. Participants were randomly assigned to an intensive systolic BP target of <120 mmHg (n=245) or a standard systolic BP target of <140 mmHg (n=197). The primary outcome was longitudinal change in a global SVD factor designed to capture overall SVD-related vascular brain injury by integrating multiple complementary SVD endophenotypes – including periventricular white matter hyperintensities, white matter free water, and basal ganglia perivascular spaces.

Results: Participant baseline characteristics by treatment group are presented in Table 1. Greater attained systolic BP lowering was associated with progressively larger reductions in SVD burden compared with increased BP, demonstrating a clear dose-response relationship (β_{0-10mmHg} = -0.083 [95%CI, -0.137, -0.029]; β_{10-20mmHg} = -0.103 [-0.156, -0.05]; β_{>20mmHg} = -0.154 [-0.216,-0.092]) – Figure 1. Consistent with this graded effect, participants randomized to the intensive BP treatment group experienced a significantly greater reduction in SVD burden compared with those in the standard BP treatment group (β_{intensive treatment} = -0.066 [95%CI,-0.106,-0.026], corresponding to a standardized mean difference [Cohen’s d] of -0.395 [-0.616, -0.174] between groups) – Figure 2.

Conclusions: Among hypertensive adults, targeting a systolic BP of <120 mmHg, compared with <140 mmHg, resulted in a greater reduction in SVD burden. Notably, even modest systolic BP reductions of ≤10 mmHg conferred measurable brain benefits, while larger BP reductions yielded gradually greater protection against SVD progression. These findings support BP lowering as a promising strategy for preserving vascular brain health and potentially mitigating SVD-related stroke and cognitive risk.