Introduction: Associations of social determinants of health (SDOH) with subclinical cardiovascular disease (CVD), such as left ventricular mass index (LVMI) and coronary artery calcification (CAC), are poorly described. Mechanisms of such associations may involve epigenetic changes like DNA methylation. We sought to examine associations between selected SDOH measures and subclinical CVD, and potential mediation by GrimAge acceleration (GrimAA), a measure of epigenetic aging. Methods: We included 2932 Black and White adults from the CARDIA year 20 (Y20) exam (mean age 45y, 48% Black, 57% female). Associations between SDOH measures at Y20 (or cumulative up to Y20) and Y25 ln(CAC score +1) or LVMI (in g/m 2.7 ) were examined using linear regression. Statistical mediation analysis was used to estimate the proportion of associations attributable to GrimAA among 880 participants in whom it was measured. Results: All selected SDOH measures at Y20 - residential racial segregation (G* Score); census tract poverty; food insecurity; difficulty paying for basics, medications, or healthcare; and maximum years of participant or parental education - were associated with LVMI at Y25 (Table). For example, each 1% higher census tract poverty was associated with an average 0.95 g/m 2.7 higher LVMI. Several SDOH measures were also associated with CAC score at Y25. Similar associations were observed between cumulative SDOH exposures from Y0-Y20 and Y25 subclinical CVD. GrimAA mediated >30% of the statistical association between participant education and LVMI or CAC (Table), and >20% of the associations of residential segregation and census tract poverty with LVMI. Conclusions: SDOH metrics were significantly and longitudinally associated with subclinical CVD in midlife. DNA methylation, as represented by GrimAge acceleration, appears to statistically mediate these associations, suggesting possible molecular mechanisms by which SDOH may accelerate CVD risk.
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