Abstract 013: Metabolomic Profiles And Ideal Cardiovascular Health: Insights From The Framingham Heart Study (fhs)

Introduction: The American Heart Association’s framework “ideal cardiovascular health” (CVH) focuses on modifiable risk factors to reduce the overall burden of cardiovascular disease (CVD). Metabolomics provide important pathobiological insights into risk factors and CVD development. Whether circulating metabolites relate to CVH status and mediate the relations of CVH score with atrial fibrillation (AF) and heart failure (HF) has not been explored. Hypothesis: We hypothesized: a) CVH score associates with metabolites; and b) metabolites mediate the relation of CVH score with incident AF and HF. Methods and Results: We analyzed 3056 adults (mean age 54 years; 54% women) in FHS Offspring Cohort (Exam 5); 2059 participants had metabolomics data. Each metabolite measurement was log transformed and standardized for data normalization. Using linear mixed models, CVH score was associated with 144 metabolites (false discovery rate, q-value < 0.05), adjusting for age, sex, estimated glomerular filtration rate (eGFR) and family structure. Of these 144 metabolites, 65 metabolites overlapped with key cardiometabolic components of the CVH score (body mass index, blood pressure, and fasting blood sugar). In mediation analyses (adjusting for age, sex, eGFR), no metabolites mediated the relation between CVH score and incident AF. However, 11 metabolites (C36:4 phosphatidylcholine, isocitrate, glycerol, ornithine, aminoadipate, 3-indolepropionic acid, cystathionine, asparagine, alpha-hydroxybutyrate, phosphorylated saccharides, and C52:5 triacylglycerol) partially mediated the association between CVH score and incident HF in multivariable-adjusted models. Conclusion: Multiple metabolites associate with the CVH score and many of the metabolites are specifically associated with the cardiometabolic components of the CVH score. Several metabolic signatures, particularly lipids and tricarboxylic acid cycle intermediates, partially mediated the relation between CVH score and incident HF. Our findings lend insight into the role of metabolites in the relations of modifiable cardiovascular risk factors with incident HF.