Exploring optimal serum selenium range for heart failure prevention: A U-shaped association and mediation by hepatic...

ObjectiveThe relationship between serum selenium levels and heart failure risk remains unclear. This study aimed to investigate the potential nonlinear association between serum selenium level and heart failure risk and explore whether hepatic steatosis and dyslipidemia mediate this relationship.MethodsData from 6969 adults in the National Health and Nutrition Examination Survey 2017-2020 cohort were analyzed. Logistic regression, restricted cubic spline, and random forest models were used to assess associations between serum selenium level and heart failure risk. Mediation analysis was used to evaluate the indirect effects of hepatic steatosis and lipid parameters. Mendelian randomization was used to infer causality.ResultsA U-shaped association was identified between serum selenium level and heart failure risk (P for nonlinearity = 0.003), with the lowest risk observed at 150-160 µg/L. Both low and high selenium levels were associated with increased heart failure risk. Hepatic steatosis and lipid markers partially mediated this association. Mendelian randomization analysis suggested a potential causal effect of genetically predicted serum selenium level on heart failure risk.ConclusionThese findings highlight a nonlinear association between selenium exposure and heart failure and suggest possible metabolic pathways underlying this association. However, further research is needed before any clinical recommendations can be made.