Cholecystitis may decrease the risk of sudden death: A 2-sample Mendelian randomization study

Area of Science:

• Cardiovascular Genetics
• Gastroenterology
• Epidemiology

Background:

• Observational studies suggest a link between cholecystitis (gallbladder inflammation) and sudden death.
• The precise causal relationship between cholecystitis and sudden cardiac death risk remains unclear.
• Understanding this link is crucial for public health and clinical risk assessment.

Purpose of the Study:

• To investigate the causal interplay between cholecystitis and the risk of sudden cardiac death.
• To determine if cholecystitis influences the risk of specific sudden death etiologies.

Main Methods:

• Utilized large-scale genome-wide association study (GWAS) summary data from UK Biobank, FinnGen, and European Bioinformatics Institute.
• Employed two-sample Mendelian randomization (MR) analysis to assess causality.
• Applied various MR methodologies (IVW, MR-Egger, weighted median) and performed heterogeneity, pleiotropy, and sensitivity analyses.

Main Results:

• A statistically significant inverse correlation was found between cholecystitis and ventricular arrhythmias (OR=0.896, P=0.008).
• An inverse association was also observed between cholecystitis and aortic aneurysm (OR=0.899, P<0.001).
• No direct causal link was established between cholecystitis and cerebrovascular accidents, pulmonary embolism, or acute myocardial infarction.

Conclusions:

• Cholecystitis appears to have a protective effect against sudden death specifically due to ventricular arrhythmias and aortic aneurysms.
• The study suggests cholecystitis may mitigate the risk of these particular sudden death causes.
• Findings provide novel insights into the complex relationship between gallbladder disease and cardiovascular outcomes.