Key result
Higher baseline levels of circulating methionine sulfone increased the risk of incident heart failure by 29% (HR 1.29), and adding a 12-metabolite panel to clinical factors significantly improved risk discrimination.
Why the study?
Early predictors of heart failure remain poorly defined, motivating identification of plasma metabolites that independently predict incident HF.
Do baseline plasma metabolites independently predict incident heart failure and improve risk discrimination beyond conventional risk factors in Finnish men?
Cohort (n=10,115)
No
Do baseline plasma metabolites independently predict incident heart failure and improve risk discrimination beyond conventional risk factors in Finnish men?
Hazard Ratio: 1.29 (95% CI 1.2–1.39)
p-value: p=1.2x10^-11
Untargeted metabolomics identified 45 distinct metabolites associated with an increased or decreased risk of heart failure, which add prognostic value to conventional clinical risk factors.
Early predictors of heart failure (HF) remain poorly defined. We measured plasma metabolites in a population-based Finnish cohort to identify metabolites that independently predict incident HF. We also performed an exploratory analysis of whether selected metabolites improved discrimination beyond traditional clinical and laboratory factors. Untargeted LC–MS/MS quantified 1009 known metabolites in 10,115 men from the METSIM study. A total of 663 participants developed HF during 14.2-year follow-up. We applied Cox regression analysis to associate the clinical factors and metabolites alone and combined with the risk of HF. Genetic variants that were associated with metabolites and increased the risk of HF were identified. Forty-five metabolites (33 were novel) increased significantly the risk of HF, including markers of catecholamine turnover, polyamine catabolites, very-long-chain acyl-carnitines, and bile-acid sulfates. ROC analysis showed that adding 12 metabolites to the clinical model increased significantly the AUC from 0.775 to 0.795. The metabolites identified converged to the adrenergic/mitochondrial redox stress, nitrogen-polyamine flux, and membrane-lipid/bile-acid remodeling pathways. Ten metabolite-quantitative-trait loci included signaling, nitrogen handling, lipid remodeling, and nucleotide detoxification pathways to specific genes. We also showed that these metabolites add prognostic value to conventional risk factors and highlight pathways of early myocardial injury in patients with HF.
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Silva et al. (2026) conducted a cohort in Heart failure (n=10,115). Circulating plasma metabolites vs. Lower metabolite concentrations / standard clinical risk factors was evaluated on Incident heart failure (HR 1.29, 95% CI 1.20-1.39, p=1.2x10^-11). Higher baseline levels of circulating methionine sulfone increased the risk of incident heart failure by 29% (HR 1.29), and adding a 12-metabolite panel to clinical factors significantly improved risk discrimination.
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