ABSTRACT NUMBER: ESOC2026A1683 BLOOD PRESSURE CHANGES AND THRESHOLD EFFECTS PREDICT WHITE MATTER HYPERINTENSITY PROGRESSION OVER THIRTEEN YEARS

Abstract Background and aims Blood pressure elevation is associated with white matter hyperintensity (WMH) burden, but whether blood pressure changes predict WMH progression and whether threshold effects exist remain unclear. We examined linear and non-linear relationships between blood pressure changes and WMH progression over 13 years. Methods 330 participants from a GeneSTAR cohort underwent brain MRI and blood pressure measurements at baseline and 13-year follow-up. WMH volumes were segmented from FLAIR, normalized to intracranial volume, and log transformed. Linear mixed-effects models examined associations between blood pressure changes and WMH progression, adjusting for age, sex, race, baseline blood pressure, and family clustering. Two-segment linear spline regression identified blood pressure thresholds where WMH relationships change. Results Increases in systolic blood pressure (SBP) predicted periventricular WMH progression (β=0.012, p=0.003) and total WMH progression (β=0.010, p=0.002). Increases in diastolic blood pressure (DBP) similarly predicted periventricular WMH (β=0.014, p=0.024) and total WMH progression (β=0.012, p=0.019). Spline analysis revealed significant SBP thresholds at 132 mmHg for periventricular WMH (slope difference=0.020, p=0.006) and 133 mmHg for total WMH (slope difference=0.020, p=0.001), indicating accelerated WMH accumulation above these values. No threshold effects were observed for DBP or deep WMH. Conclusions Blood pressure increases predict WMH progression with critical SBP thresholds at 132-133 mmHg, suggesting intensive blood pressure control targeting values above these thresholds may prevent accelerated periventricular white matter damage in at-risk populations. Conflict of interest Sarvin Sasannia: nothing to disclose; Mykola Matsyuk: nothing to disclose; Shimeng Wang: nothing to disclose; Jerry L. Prince: nothing to disclose; Lewis C. Becker: nothing to disclose; Lisa R. Yanek: nothing to disclose; Dhananjay Vaidya: nothing to disclose; Peter van Zijl: nothing to disclose; Linda Knutsson: nothing to disclose; Paul A. Nyquist: nothing to disclose