Determinants for gallstone formation – a new data cohort study and a systematic review with meta-analysis*

Objective: Only few determinants of gallstone formation have been identified in cohort studies. The aim was to identify further determinants for gallstones in a Danish cohort and to perform a meta-analysis of results from existing cohorts. Material and methods: Data from a cohort study was used. Gallstone incidence was assessed through repeated ultrasound examinations. Body mass index (BMI), blood pressure, self-rated health, lifestyle variables, blood lipids, and use of female sex hormones were measured at the baseline examination. Statistical analyses included logistic regression. Based on a prospective protocol, a systematic review of the literature was performed identifying all articles dealing with determinants of incident gallstones. Meta-analyses of comparable determinants were performed through fixed effect models. Results: Participants with no gallstones at baseline and with at least one re-examination were followed-up completely (mean 11.6 years, N = 2848). The overall cumulative incidence of gallstones was 0.60% per year. Independent positive determinants for incident gallstones were age, female sex, non-high density lipoprotein (non-HDL) cholesterol, and gallbladder polyps. In addition, BMI was positively associated in men. The systematic review additionally identified associations for comorbidities, parity, and dietary factors. Meta-analysis confirmed the significant associations for incident gallstones and age, female sex, BMI, and non-HDL cholesterol. No significant associations were found for blood pressure, smoking, alcohol consumption, HDL cholesterol, or triglycerides in meta-analyses. Conclusions: Age, female sex, BMI, non-HDL cholesterol, and polyps are independent determinants for gallstone formation. Incident gallstones and the metabolic syndrome share common risk factors. More studies are needed for further exploration.