A Mendelian randomization analysis found a potential inverse relationship between elevated 25-hydroxyvitamin D (25OHD) and heart failure (HF) risk. These findings were published in Nutrition, Metabolism and Cardiovascular Diseases.

Investigators with the Affiliated Hospital of Southwest Jiaotong University in China sourced single nucleotide polymorphism (SNP) data from a genome-wide association study that used the UK Biobank cohort in combination with summary-level genetic information about HF from the HF Molecular Epidemiology for Therapeutic Targets Consortium. The investigators in this analysis used a Mendelian randomization approach to test whether there may be a relationship between 25OHD and HF.

Three SNPs that are closely related with obesity, chronic kidney disease, and myocardial infarction were removed from the analysis. The Mendelian randomization analysis included 162 linkage disequilibrium-independent instrument variables related with 25OHD.

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For every standard deviation increase in standardized log-transformed 25OHD levels, the risk for HF decreased by 16.5% (odds ratio [OR], 0.835; 95% CI, 0.743-0.938; P =.002). This relationship was confirmed by 4 alternative Mendelian randomization approaches (OR range, 0.724-0.835) and the multivariate Mendelian randomization approach (OR, 0.811).

No evidence for horizontal pleiotropy (P =.284), heterogeneity (P =.121), or outliers (P =.541) were observed.

Genes involved with 25OHD synthesis (DHCR7 and CYP2R1) and metabolism (GC and CYP24A1) were identified.

The major limitation of this study is that the analysis is based on data from individuals with European ancestry, which calls in to question the generalizability of these findings.

“…we found an inverse association between elevated vitamin D levels and the risk of HF,” the study authors wrote. “However, the exact mechanism between vitamin D and HF is unclear, and more research is still needed to explore the issue.”


Luo Q, Yan W, Nie Q, Wang H. Vitamin D and heart failure: a two-1 sample Mendelian randomization study. Nutr Metab Cardiovasc Dis. Published online August 10, 2022. doi:10.1016/j.numecd.2022.08.003