Abstract Body: 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.