Abstract P1038: Blood Metabolomic Signatures of Incident Coronary Heart Disease in Racially and Ethnically Diverse Populations

Background: Metabolic perturbation has been characterized in coronary heart disease (CHD), yet the comprehensive metabolic fingerprint of incident CHD and potential racial/ethnical differences remain unclear. Hypothesis: Circulating metabolite alterations are associated with CHD risk, but associations vary across race/ethnicity. Methods: We included 22,566 CHD-free individuals of multi-ethnic groups from 7 studies in the Trans-Omics for Precision Medicine Program ( Fig.a ). Associations between metabolites (1245 named metabolites) and incident CHD were assessed by study/race-specific Cox proportional hazards regression. Results were pooled via random-effect meta-analyses. Results: Over an average of 7.5~17.0 yrs of follow-up 1124 incident CHD cases were recorded. We found that 280 metabolites were associated with incident CHD after adjusting for sociodemographic, behavioral factors, medications use, physical activity, and diet (FDR < 0.05), with over 64% were independent of other major cardiometabolic traits ( Fig.b ). Over 90% of these metabolites showed positive associations, with strongest associations in metabolites of glycerolipids, phosphatidylethanolamine, fatty acids, lactoyl amino acid, histidine, aromatic amino acids, and branched amino acids ( Fig.b ). Race-specific analyses identified 70 metabolites presenting significant race/ethnicity differences (FDR<0.05) in associations with CHD, with 34 being race/ethnicity specific metabolites that were not found in all participants (16 in Blacks, 11 in Whites and 7 in Hispanics; Fig.c-e ). For example, guanidinosuccinate, a known uremic toxin, was associated with increased risk of CHD only in US Hispanics, reinforcing the chronic kidney disease (CKD)-cardiovascular diseases continuum, especially for populations at high risk of CKD. Conclusion: Our study characterized the most comprehensive metabolic signatures of incident CHD and revealed substantial racial differences, further emphasizing the need of multi-ethnic resources to uncover metabolic perturbation underlying CHD.