title: Presence of gallstones and the risk of cardiovascular diseases: The EPIC-Germany cohort study.
abstract: 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.
authors.affiliation: Department of Epidemiology, German Institute of Human Nutrition Potsdam-Rehbruecke, Germany janine.wirth@dife.de.
authors.forename: Janine
authors.initials: J
authors.lastname: Wirth
authors.affiliation: Department of Epidemiology, German Institute of Human Nutrition Potsdam-Rehbruecke, Germany.
authors.forename: Romina
authors.initials: R
authors.lastname: di Giuseppe
authors.affiliation: Department of Epidemiology, German Institute of Human Nutrition Potsdam-Rehbruecke, Germany.
authors.forename: Angelika
authors.initials: A
authors.lastname: Wientzek
authors.affiliation: Division of Cancer Epidemiology, German Cancer Research Center Heidelberg, Germany.
authors.forename: Verena A
authors.initials: VA
authors.lastname: Katzke
authors.affiliation: Department of Neurology, University of Heidelberg, Germany.
authors.forename: Manja
authors.initials: M
authors.lastname: Kloss
authors.affiliation: Division of Cancer Epidemiology, German Cancer Research Center Heidelberg, Germany.
authors.forename: Rudolf
authors.initials: R
authors.lastname: Kaaks
authors.affiliation: Department of Epidemiology, German Institute of Human Nutrition Potsdam-Rehbruecke, Germany.
authors.forename: Heiner
authors.initials: H
authors.lastname: Boeing
authors.affiliation: Department of Epidemiology, German Institute of Human Nutrition Potsdam-Rehbruecke, Germany Institute of Social Medicine, Epidemiology, and Health Economics, Charité University, Medical Center, Berlin, Germany.
authors.forename: Cornelia
authors.initials: C
authors.lastname: Weikert
mesh_terms: D000328:Adult; D000368:Aged; D002763:Cholecystectomy; D005260:Female; D042882:Gallstones / Q000175:diagnosis / Q000453:epidemiology* / Q000601:surgery; D005858:Germany / Q000453:epidemiology; D006801:Humans; D015994:Incidence; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009203:Myocardial Infarction / Q000175:diagnosis / Q000453:epidemiology*; D011379:Prognosis; D016016:Proportional Hazards Models; D011446:Prospective Studies; D018570:Risk Assessment; D012307:Risk Factors; D020521:Stroke / Q000175:diagnosis / Q000453:epidemiology*; D013997:Time Factors
keywords: Cholelithiasis; biliary tract calculi; coronary heart disease; gallbladder disease; gallstones; heart attack; myocardial infarction; smoking; stroke