Causal associations between circulation β-carotene and cardiovascular disease: A Mendelian randomization study

Abstract

The causal association between circulating β-carotene concentrations and cardiovascular disease (CVD) remains controversial. We conducted a Mendelian randomization study to explore the effects of β-carotene on various cardiovascular diseases, including myocardial infarction, atrial fibrillation, heart failure, and stroke. Three single nucleotide polymorphisms (SNPs) associated with the β-carotene levels were obtained by searching published data and used as instrumental variables. Genetic association estimates for 4 CVDs (including myocardial infarction, atrial fibrillation, heart failure, and stroke) in the primary analysis, blood pressure and serum lipids (high-density lipoprotein [HDL] cholesterol, LDL cholesterol, and triglycerides) in the secondary analysis were obtained from large-scale genome-wide association studies (GWASs). We applied inverse variance-weighted as the primary analysis method, and 3 others were used to verify as sensitivity analysis. Genetically predicted circulating β-carotene levels (natural log-transformed, µg/L) were positively associated with myocardial infarction (odds ratio [OR] 1.10, 95% confidence interval [CI] 1.02–1.18, P = .011) after Bonferroni correction. No evidence supported the causal effect of β-carotene on atrial fibrillation (OR 1.02, 95% CI 0.96–1.09, P = .464), heart failure (OR 1.07, 95% CI 0.97–1.19, P = .187), stroke (OR 1.03, 95% CI 0.93–1.15, P = .540), blood pressure (P > .372) and serum lipids (P > .239). Sensitivity analysis produced consistent results. This study provides evidence for a causal relationship between circulating β-carotene and myocardial infarction. These findings have important implications for understanding the role of β-carotene in CVD and may inform dietary recommendations and intervention strategies for preventing myocardial infarction.