Objective The purpose of this study was to assess the risk factors for cholesterol polyp formation in the gallbladder. Method This was a multicenter retrospective study based on pathology. From January 2016 to December 2019, patients receiving cholecystectomy and non-polyp participants confirmed by continuous ultrasound follow-ups were reviewed. Patients in the cholesterol polyp group were recruited from three high-volume centers with diagnosis of pathologically confirmed cholesterol polyps

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... er than 10mm. Population characteristics and medical data were collected within 24 hours of admission before surgery. The non-polyp group included participants from hospital physical examination center database. They had at least two ultrasound examinations with the interval longer than 180 days. Data from the final follow-up of the non-polyp group were analyzed. The risk factors for cholesterol polyp formation were analyzed by comparing the two groups. Results A total of 4 714 participants were recruited, including 376 cholesterol polyp patients and 4 338 non-polyp participants. In univariate analysis, clinical risk factors for cholesterol polyp were age, male gender, higher body mass index (BMI), higher low-density lipoprotein (LDL), lower high-density lipoprotein (HDL), higher aspartate aminotransferase (AST), and alanine aminotransferase (ALT). In multivariate logistic analysis, independent risk factors were age>50 years (OR=3.41, 95% CI 2.61-4.47, p<0.001), LDL>2.89mmol/L (OR=1.45, 95% CI 1.13-1.87, p=0.003), AST>40IU/L (OR=3.58, 95% CI 2.03-6.31, p<0.001) and BMI>25kg/m² (OR=1.62, 95% CI 1.23-2.13, p<0.001). Conclusion Age, LDL, AST and BMI are strong risk factors for cholesterol polyp formation. Older overweight patients with polyps, accompanied by abnormal lipid levels, are at high risk of cholesterol polyps.