Causality between cholecystectomy, blood lipids, and major adverse cardiac and cerebrovascular events: a Mendelian randomization analysis

Abstract

Abstract Background Several studies have provided evidence of changes in lipids and major adverse cardiac and cerebrovascular events (MACCE) after cholecystectomy. However, the results of these studies are controversial. Here, we performed Mendelian randomization (MR) to predict the effects of cholecystectomy on blood lipid levels and MACCE with less confounding. Methods Summary data on cholecystectomy, lipid levels, and MACCE were obtained from publicly available genetic databases and analyzed using two sets of genetic instruments. MR analyses were conducted using the inverse-variance weighted (IVW; primary method for causal inference in two-sample MR analysis) method. We performed multivariate MR (MVMR) to screen and prioritize the most likely causal lipids and analyzed the mediated effects of these lipids. Results Six types of MACCE, including angina, chronic ischemic heart disease, coronary heart disease, heart failure, myocardial infarction, and ischemic stroke, were found to have a negative association with cholecystectomy. Furthermore, we identified a decreased apolipoprotein B/apolipoprotein A1 (ApoB/ApoA1) ratio with subsequent coronary heart disease with a mediated proportion of 52.9% (95% CI: 21.5–97.5%, P = 0.000), chronic ischemic heart disease with a mediated proportion of 42.6% (95% CI: 23.1–91.6%, P = 0.000), and a reduced risk of myocardial infarction with a mediated proportion of 39.4% (95% CI: 24.8–95.5%, P = 0.000). Conclusions The findings present genetic evidence supporting the link between cholecystectomy, blood lipids, and MACCE, which may offer valuable insights into the mechanisms involved in the improvement of blood lipids and the prevention of MACCE following cholecystectomy.