Abstract
Introduction: Diastolic dysfunction is one key causal factor for heart failure with preserved ejection fraction (HFpEF). We conducted a metabolome-wide association study to identify novel diastolic function-related metabolites in relatively young and healthy adults. Hypothesis: We hypothesized that serum metabolites could predict diastolic function and thus potentially serve as biomarkers for subclinical disease. Methods: The study cohort consisted of 1,038 participants of the Bogalusa Heart Study (34.9% black, 57.3% females, aged 33.6-57.5 years). Diastolic function was assessed via 2D and tissue doppler echocardiography, and included peak early filling velocity (E), peak velocity caused by atrial contraction (A), medial mitral annular velocity (e’), left ventricular isovolumic relaxation time (IVRT), as well as deceleration time (DT). Untargeted metabolomic analysis of fasting serum samples was conducted. Multivariable-adjusted linear regression models were employed to assess the relationship of metabolites with echocardiographic measures of diastolic function. Results: Following quality control, 1202 metabolites were tested for association with E/A ratio, E/e’ ratio, IVRT, and DT. After Bonferroni correction, 9 novel metabolites, derived from amino acid, cofactor, energy, lipid, and nucleotide pathways, were significantly associated with diastolic function in blacks with nominal significance and consistent effect direction in whites (Table). Of these significant metabolites, 2 and 6 metabolites were associated with the E/A ratio and E/e’ ratio, respectively. No significant associations of metabolites with IVRT or DT were found. Fatty acid metabolism was the biological sub-pathway most represented in significant diastolic function-metabolite associations. Conclusion: The current study identified novel metabolites associated with diastolic function, suggesting that the serum metabolome, and its underlying biological pathways, may be implicated in HFpEF pathogenesis.
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