Sex differences in the association of cardiometabolic risk scores and blood pressure measurements with white matter hyperintensities in diverse older adults-HABS-HD.

Introduction: We aimed to determine whether cardiometabolic risk factors and blood-pressure (BP) metrics were differentially associated with white matter hyperintensities volume (WMHV) in males versus females in the Health and Aging Brain Study-Health Disparities. Methods: We analyzed 3,585 community-dwelling adults (2,207 females) from non-Hispanic White, non-Hispanic Black, and Hispanic groups who underwent BP measurement and WMHV quantification. Linear regression models assessed (i) individual risk factors (diabetes, hypertension, dyslipidemia, obesity, tobacco dependence), (ii) a composite risk score, and (iii) four BP metrics (systolic, diastolic, pulse pressure, mean arterial pressure), each including a sex-interaction term and adjusting for age, education, race/ethnicity, and scanner. A second BP model also controlled for all five risk factors. Results: Diabetes (β = 0.46, 95% CI 0.28-0.64), hypertension (β = 0.47, 0.30-0.64), and higher composite risk (β = 0.19, 0.12-0.26) were associated with greater WMHV. Diastolic BP (β = 0.18, 0.11-0.26) and mean arterial pressure (β = 0.14, 0.07-0.21) related to larger WMHV, with diastolic BP remaining significant after full adjustment (β = 0.14, 0.07-0.22). No sex interactions survived correction. Discussion: These findings underscore the importance of aggressive cardiometabolic and BP control, particularly diastolic BP, to mitigate WMHV in both sexes.