Vitamin A and vitamin B12 levels and coronary artery atherosclerosis: Univariate and multivariate Mendelian randomization analysis.

Coronary artery atherosclerosis (CAA) stands as a prominent etiological contributor to global cardiovascular morbidity and mortality. Its pathogenesis entails intricate interplays among genetic predisposition, environmental factors, and lifestyle determinants. Trace elements, though necessitated in minuscule quantities, have emerged as potential modulators of CAA progression, yet their exact impact remains unclear. We utilized Mendelian randomization (MR) analysis, employing genetic variants as instrumental variables to investigate the causal relationship between trace element levels and CAA. This study conducted a dual-sample MR analysis using data extracted from genome-wide association studies (GWAS) and the FinnGen database. To assess the statistical significance of these associations, we applied various MR statistical methods including MR-Egger, weighted median, and inverse variance weighted (IVW). Additionally, to further validate the robustness of our findings, multivariable MR analysis was performed. This approach allowed us to control for potential confounders, providing more precise causal inference results. The research findings reveal a significant negative correlation between vitamin A and the risk of CAA, indicating its role as a protective factor (according to the IVW method, odds ratio [OR] = 0.018, 95% confidence interval [CI] = 0.001-0.487, P = .017). Conversely, genetically predicted vitamin B12 shows a significant positive correlation with CAA risk, suggesting its role as a risk factor for CAA (OR = 1.268, 95% CI = 1.059-1.518, P = .01). However, in the multivariable regression analysis, both vitamin A and vitamin B12 remained significantly associated with CAA risk, with respective ORs of 0.020 (95% CI = 0.002-0.254, P = .003) and 1.252 (95% CI = 1.040-1.506, P = .018). This study elucidates the critical role of trace elements in the pathogenesis of CAA, providing a theoretical basis for personalized interventions and precision medicine. Further research could explore therapeutic strategies targeting trace element modulation to improve cardiovascular health.