Abstract

Introduction: Measures of cardiac structure and function provide important diagnostic and prognostic information for heart failure (HF). Few studies have assessed the associations of circulating metabolites with cardiac structure and function. Hypothesis: We hypothesize that circulating metabolites that reflect aging process are associated with cardiac structure and function measures and incident HF. Methods: Participants from the Atherosclerosis Risk in Communities (ARIC) study visit 5 and the Hispanic Community Health Study / Study of Latinos (HCHS/SOL) study visit 1 who had serum metabolite measures but not prevalent HF were included. Linear regressions were used to examine the associations of metabolites with ten cardiac structure and function variables adjusting for clinical risk factors in each race and study strata, followed by random-effect meta-analyses. The Cox regression was applied to examine the relationship between those identified metabolites and incident HF post visit 5 in ARIC. Results: Among 589 analyzed metabolites, 179 were associated with cardiac structure or function measures in 706 Blacks, 3,358 Whites, and 1,380 Hispanics (FDR < 0.05). Forty-one metabolites were related to two or more measures, where 22 were associated with incident HF (308 HF cases, p<0.05, Figure). Metabolites were more associated with cardiac size or diastolic function compared to systolic function measures, i.e., C-glycosyltryptophan, an amino acid that is strongly correlated with age, was positively associated with left ventricular mass index (LVMI) and left atrial volume index(LVAI), as well as an increased risk of HF (HR=1.48); and dodecadienoate (12:2), a dicarboxylate that may have anti-aging property, was negatively associated with LVMI and LVAI, as well as a decreased risk of HF (HR=0.84). Conclusions: We identified multiple metabolites associated with cardiac structure and function measures in multi-ethnic populations, highlighting metabolic pathways in aging and their impact on HF.

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