Abstract
Coronary artery calcification (CAC) is an established indicator of atherosclerosis and the incidence of cardiovascular disease. Currently, there is no effective pharmacological intervention to reverse CAC. The gut microbiota, circulating metabolites, immune cells, and inflammation-related proteins have all been implicated in the mechanisms underlying CAC. However, the causal relationships and specific mechanisms connecting these factors remain unclear. This study aims to elucidate the causal relationships among the gut microbiota, circulating metabolites, immune cells, and inflammation-related proteins with the risk of CAC using Mendelian randomization (MR) methods. A bidirectional, 2-sample univariate MR analysis was conducted using data from a genome-wide association study to explore potential causal relationships among 4 exposure factors and the incidence of CAC. The inverse-variance-weighted approach, complemented by a series of sensitivity analyses, was employed to strengthen the conclusions. All analyses were conducted using R software (version 4.3.1). The MR results indicated that 10 types of gut microbiota, 60 circulating metabolites, 21 immune cells, and 6 inflammation-related proteins were either negatively or positively associated with CAC. Reverse MR analysis found that there was no bidirectional causal relationship. The MR analysis method was employed to investigate the pathogenesis of CAC from a genetic perspective. Due to the challenges associated with clinical trials, analyzing the influence of risk factors on outcomes through comprehensive genetic data has emerged as a significant trend in disease research.