Presence of gallstones and the risk of cardiovascular diseases: The EPIC-Germany cohort study.

Background: Gallstones are common disorders associated with several cardiovascular risk factors. Gallstone formation and atherosclerosis may share key pathways, but studies on putative associations between gallstones and the risk of cardiovascular disease are sparse and non-conclusive. We studied the relationship between gallstones and the risk of subsequent cardiovascular diseases in the German arm of the European Prospective Investigation into Cancer and Nutrition (EPIC).

Methods: The study comprises 46,468 participants from EPIC-Potsdam and EPIC-Heidelberg aged 35-65 years, free of cardiovascular diseases and diabetes at baseline. Information about the gallstone status at baseline was ascertained via questionnaires. For all incident cases of myocardial infarction and stroke confirmation was obtained from the treating physician. Relative risks were estimated using Cox proportional hazards regression.

Results: During eight years of follow-up, 919 participants suffered a stroke or myocardial infarction. After multivariable adjustment for established risk factors, subjects with reported gallstones (n = 4828) had an increased risk of cardiovascular diseases (hazard rate ratio (HR) = 1.24, 95% confidence interval (CI): 1.02, 1.50). In individuals, who underwent a cholecystectomy before baseline a 1.32-fold increase in risk was observed (95%CI: 1.05, 1.65). HRs differed depending on the presence of selected established risk factors (e.g. HR for cardiovascular diseases regarding gallstones in smokers = 1.66, 95%CI: 1.20, 2.30, and non-smokers = 1.09, 95%CI: 0.86, 1.38).

Conclusions: Our results indicate an increased cardiovascular risk for gallstone formers, which cannot be counteracted by gallbladder removal and opens up perspectives for individualized prevention strategies.