Vitamin D and heart failure: A two-sample mendelian randomization study

The relationship between vitamin D and heart failure (HF) has attracted significant interest, but the association between the two in previous studies remains uncertain. Therefore, we used two-sample Mendelian randomization (MR) to investigate a causal association between 25-hydroxyvitamin D (25OHD) and HF risk.This study utilized summary statistics from the most extensive genome-wide association studies for 25OHD and HF. To make the results more reliable, we used several methods based on three assumptions for MR analysis. We also used the multivariable MR adjusting for hypertension, BMI, diabetes, chronic kidney disease to further elucidate the association between 25OHD and HF. Considering the potential pleiotropy, we performed an MR analysis with conditionally independent genetic instruments at core genes to further determine the relationship between vitamin D and heart failure. We found that per 1 SD increase in standardized log-transformed 25OHD level, the relative risk of HF decreased by 16.5% (OR: 0.835, 95% Cl: 0.743-0.938, P = 0.002), and other MR methods also showed consistent results. The multivariable MR also reported that per 1 SD increase in standardized log-transformed 25OHD level, the relative risk of HF decreased. And the scatter plots showed a trend towards an inverse MR association between 25OHD levels, instrumented by the core 25OHD genes, and HF.In summary, we found a potential inverse association between elevated 25OHD levels and the risk of HF, which suggested that timely 25OHD supplementation or maintaining adequate 25OHD concentrations may be an essential measure for HF prevention in the general population.