Abstract
Background: Cardiometabolic conditions accelerate white-matter hyperintensity (WMH) accumulation-a vascular injury marker linked to increased Alzheimer's disease risk-yet how these relationships vary by race and ethnicity in males is poorly understood. Objective: To quantify racial ethnic-specific associations between cardiometabolic risk factors, blood-pressure indices, and WMH volume in Non-Hispanic White (NHW), Non-Hispanic Black (NHB), and Hispanic males. Methods: We analyzed 1378 males (558 NHW, 375 NHB, 445 Hispanic) from the Healthy Aging Brain Study-Health Disparities. Five binary exposures (hypertension, diabetes, dyslipidemia, obesity, tobacco dependence), four continuous blood-pressure metrics (systolic, diastolic, pulse, mean arterial pressure), and a principal-component cardiometabolic score were regressed on log-transformed, intracranial volume-adjusted WMH volume in race-stratified models. Results: Hispanic males exhibited the broadest vulnerability: hypertension, diabetes, and tobacco dependence each predicted higher WMH (β range 0.60-0.77, p ≤ 0.002), and the composite score had the strongest association (β = 0.26, 0.13-0.39, p < 0.001). Additionally, every 10-mm Hg rise in systolic, diastolic, pulse, or mean arterial pressure further increased WMH in Hispanic males (e.g., systolic β = 0.18, 0.11-0.26), an effect absent in NHW and NHB males. Conclusions: Cardiometabolic and hemodynamic drivers of WMH differ markedly across racial and ethnic groups of males, with Hispanic males showing the most pervasive risk profile, NHB males selective associations, and NHW males limited links. Tailored vascular-risk interventions may be essential to curb WMH-related pathways to Alzheimer's disease in racially and ethnically diverse male populations.