Cholecystitis May Decrease the Risk of Sudden Death: A 2-Sample Mendelian Randomization Study

Some observational studies have highlighted a significant association between cholecystitis and factors leading to sudden death; however, the specific relationship between the 2 has not been fully elucidated. The primary objective of this study was to elucidate the causal interplay between cholecystitis and augmented risk of sudden cardiac death. We used large-scale genetic summary data from genome-wide association study, genetic summary statistics were sourced from 3 eminent repositories: the UK Biobank (N = 463,010), the FinnGen consortium (N = 215,027), and the European Bioinformatics Institute (N = 471,251). By employing 2-sample Mendelian randomization (MR) to decipher the causal interplay between cholecystitis and sudden death etiologies, a meta-analytical approach was employed to amalgamate the findings derived from these disparate data sources. The primary MR methodologies used included inverse variance weighting with random effects, inverse variance weighting with fixed effects, maximum likelihood, MR-Egger, and weighted median. Subsequently, we performed heterogeneity testing, polyvalency examination, and sensitivity analysis to bolster the robustness of causal relationship assessments. Meta-analysis and amalgamating variegated data sources revealed a statistically significant inverse correlation between cholecystitis and ventricular arrhythmias (odds ratio, 0.896; 95% confidence interval: 0.826–0.971; P = .008). Similarly, an inverse association was observed between cholecystitis and aortic aneurysm (odds ratio, 0.899; 95% confidence interval: 0.851–0.951, P < .001). This study substantiates the absence of a direct causal link between cholecystitis and cerebrovascular accidents (P = .771), pulmonary embolism (P = .071), and acute myocardial infarction (P = .388). A direct causal correlation existed between cholecystitis and sudden death associated with ventricular arrhythmias and aortic aneurysms. The onset of cholecystitis may mitigate the risk of sudden death due to ventricular arrhythmias and aortic aneurysms.