Blood plasma metabolites and heart failure risk: insights from Mendelian randomization analysis

Abstract Background Heart failure remains a leading cause of mortality and disability worldwide. Blood plasma metabolites play a crucial role in influencing heart failure, yet they are subject to numerous confounding factors. Mendelian randomization analysis provides a powerful tool for assessing causal relationships between them. Methods We conducted a Mendelian randomization analysis using a meta-analysis comprising 115,150 heart failure cases (155,331 controls) and 1400 serum metabolites. Various methods including Inverse variance weighting (IVW), MR Egger, Weighted median, and Weighted mode were employed to estimate causal effects. Sensitivity analyses were conducted using Cochran’s Q test, MR Steiger test, leave-one-out analyses, funnel plot, and MR-PRESSO. Results Following rigorous selection, among the 1400 blood plasma metabolites, 71 metabolites including Sphingomyelin, Myristate, AMP to methionine ratio showed significant associations with increased risk of heart failure. Additionally, 40 metabolites including Glycine, octadecenedioylcarnitine (C18:1-DC), 1-palmitoyl-2-dihomo-linolenoyl-GPC (16:0/20:3n3 or 6) exhibited significant associations with decreased risk of heart failure. Conclusion Identified blood plasma metabolites provide crucial insights into screening and prevention strategies for heart failure. Further validation is warranted through animal models and large-scale cohorts.