Abstract P200: Cumulative Circulating Branched Chain Amino Acid Exposure in Young Adulthood and Incident Atherosclerotic Cardiovascular Disease (ASCVD) in Later Life: The CARDIA Study

Introduction: Circulating branched chain amino acid (BCAA) levels are associated with the development of diabetes mellitus (DM) and downstream ASCVD in middle-aged women. It is unknown if BCAAs in young adult men and women are associated with ASCVD events. BCAA levels may be dynamic in middle-aged adults prior to the development of DM or ASCVD events, thus cumulative BCAA measures in early life may better quantify exposure risk than a single measure at mid-life. Methods: We measured plasma BCAA levels in 3110 Coronary Artery Risk Development in Young Adults study participants using nuclear magnetic resonance (NMR) at Years (y) 2, 7, 15, and 20. To minimize missingness bias, BCAA levels were imputed for the residual 1835 participants without NMR measures. Cumulative BCAA exposure from 19-40y of age was calculated as the area under the curve using a spline-based mixed-effects model to estimate subject-specific BCAA trajectories from 19-40y. Sex-specific associations between cumulative BCAA exposure and incident ASCVD events after 40y of age were assessed by multivariable (Table) Cox proportional hazards regression models including BCAA levels and fasting blood glucose (FBG) at age 40y and further stratified by DM status. Results: Among 4945 participants (55.3% female), there were 255 ASCVD events and 675 DM cases over a median of 18.8 years of follow-up after age 40y. In adjusted models, cumulative BCAA exposure from 19-40y was associated with ASCVD events after 40y of age in women, but not men (Table). The associations in women were robust to adjustment for BCAAs and FBG at age 40y. There was no significant difference in the cumulative BCAA-ASCVD association among men or women who developed DM before ASCVD versus those who did not. Conclusions: Cumulative BCAA exposure in early adulthood is associated with ASCVD in women independent of mid-life BCAA levels. Elevated BCAA levels in women during early adulthood may reflect behaviors and/or metabolic pathways that increase risks for ASCVD independent of the development of hyperglycemia.