Associations Between Vitamin D Levels and Risk of Heart Failure: A Bidirectional Mendelian Randomization Study

BACKGROUND: Although studies suggest that concentrations of serum 25-hydroxyvitamin D (25(OH)D) are lower in individuals with Heart Failure (HF), the beneficial effects of vitamin D supplementation are controversial. Therefore, in this study, we aimed to determine whether there is a causal relationship between serum Vitamin D (VD) levels and HF. METHODS: We obtained genetic instruments from the largest available genome-wide association study (GWAS) of European descent for 25(OH)D (443, 734 individuals) to investigate the association with HF (47,309 cases, 930,014 controls), and vice versa. Two-sample bidirectional Mendelian Randomization (MR) analysis was performed to infer the causality. In addition to the primary analysis using inverse variance-weighted (IVW) MR, we applied five additional methods to control for pleiotropy [MR-Egger, weighted median, Maximum-likelihood, MR-robust adjusted profile score (MR-RAPS) and MR-pleiotropy residual sum and outlier (MR-PRESSO)] and compared their respective MR estimates. We also performed a sensitivity analysis to ensure that our results were robust. RESULTS: Mendelian randomized analysis showed that increased serum 25(OH)D was associated with a lower risk of HF in the IVW method (odds ratio [OR] = 0. 81;95%CI, 0.70–0.94, P = 0.006). In the reverse MR analyses, the genetic predisposition to HF was negatively correlated with serum 25(OH)D level (OR = 0. 89;95%CI, (0.82–0.97), P = 0.009). CONCLUSION: Our study revealed the possible causal role of 25(OH)D on decreasing the risk for HF. Meanwhile, reverse MR analysis suggested that HF may be associated with lower vitamin D levels, it could be the potential implications for dietary recommendations.