ABSTRACT NUMBER: ESOC2026A480 VISIT-TO-VISIT BLOOD PRESSURE VARIABILITY AND CEREBRAL WHITE MATTER LESION PROGRESSION: A POOLED INDIVIDUAL PATIENT ANALYSIS OF SPRINT MIND AND ACCORD MIND RANDOMIZED TRIALS

Abstract Background and aims Visit-to-visit blood pressure variability (BPV) may contribute to white matter lesions (WML) progression, but previous evidence has been inconsistent and limited by methodological heterogeneity. We aimed to assess the association between BPV and WML progression and its mediating role in the neuroprotective effects of intensive BP control. Methods We pooled individual participant data from two randomized trials (ACCORD MIND and SPRINT MIND), both including MRI substudies with standardized BP measurements and long-term follow-up (mean 40 and 48 months, respectively). WML progression was quantified as absolute and annualized changes in abnormal white matter (AWM) volume, with inverse hyperbolic sine (asinh)-transformed total change as the primary metric. Results A total of 952 participants(mean age 64.8 years [SD 7.1]; 400 [42%] women) were included, contributing a median of 12 BP measurements. Median AWM volume increased from 1.69 mL to 2.58 mL(0.43 mL per year [SD 0.84]). Higher systolic BPV was independently associated with greater AWM volume progression (β = 0.017, 95%CI 0.001 to 0.033). Intensive BP control was associated with slower AWM volume progression(β = -0.270, 95%CI –0.393 to –0.146). Systolic BPV partially mediated the association between intensive BP control and reduced AWM volume progression(average causal mediation effect 0.014, 95%CI 0.001 to 0.034), accounting for 9.15% of the total effect. Conclusions Higher visit-to-visit systolic BPV was independently associated with faster WML progression. The benefit of intensive BP lowering on white matter integrity was partly mediated by reduced BPV, suggesting BP stability as a modifiable target to prevent white matter injury. Conflict of interest All authors: nothing to disclose.