Abstract P427: Coronary Artery Calcium Assessed Years Before Was Positively Associated with Subtle White-matter Injury in Asymptomatic Middle-aged Men: the Framingham Heart Study

Introduction: Using magnetic resonance (MR) diffusion tensor imaging (DTI), we previously showed a cross-sectional association between carotid-femoral pulse wave velocity (CFPWV), a measure of aortic stiffness, and subtle white-matter injury in clinically asymptomatic middle-age adults. Although coronary artery calcification (CAC) predicted cerebral small vessel diseases evident in conventional MR technique in some studies, it remains unclear whether CAC predicts DTI-based subtle white matter injuries. Hypothesis: CAC and CFPWV are associated with global measures of subtle white-matter injury in middle-aged adults free of clinical brain diseases. Methods: We studied third-generation participants of the Framingham Heart Study who were assessed for CAC (2002-2005), CFPWV, and brain DTI (2009-2013). After excluding prevalent stroke, dementia, other neurological conditions, or those with missing data, 1052 participants (women, 45.4%, mean age: 45.4 years) were analyzed. Two DTI-based outcomes were examined (average within voxels from the white matter mask): free water (FW) and FW-corrected fractional anisotropy (FA). Using linear regression, we calculated slopes of the outcomes per 20-80 th percentiles higher CAC (log-transformed Agatston score) or CFPWV (negative inverse) after adjustment for age and age squared at CAC or CFPWV, time between at CAC/CFPWV and DTI exam, systolic blood pressure, diabetes, total cholesterol, medication(s) for hypertension or dyslipidemia, smoking, and total cranial volume. Results: After multivariable adjustment, in men, CAC was associated only with FA (p=0.033), whereas CFPWV was associated only with FW (p=0.030) ( Figure ). No associations were observed in women. Conclusions: In men, CAC assessed at >7.5 years earlier was associated with worse FA, while CFPWV assessed at 1.7 years earlier was associated with worse FW. CAC may be a sensitive maker to predict subtle white-matter injury in asymptomatic middle-aged men.