A Prediction Rule for Risk Stratification of Incidentally Discovered Gallstones: Results From a Large Cohort Study

BACKGROUND & AIMS: No one knows exactly what proportion of gallstones cause clinical events among subjects unaware of their gallstone status. We investigated the long-term occurrence of clinical events of gallstones and associations between ultrasound observations and clinical events.

METHODS: We analyzed data from 3 randomly selected groups in the general population of urban Copenhagen (30-70 y old) participating in an international study of cardiovascular risk factors (the MONICA study). In this study, participants (n=6037) were examined from 1982 through 1994, and underwent abdominal ultrasound examinations to detect gallstones. Our study population comprised 664 subjects with gallstones; subjects were not informed of gallstone status. Participants were followed for clinical events through central registers until December 31, 2011. Independent variables included ultrasound characteristics, age, sex, co-morbidity, and female-associated factors, which were analyzed using Cox regression.

RESULTS: Study participants were followed for median 17.4 y (range, 0.1-29.1 y); 99.7% of participants completed the study. A total of 19.6% participants developed events (8.0% complicated and 11.6% uncomplicated). Ten percent had awareness of their gallstones; awareness was associated with uncomplicated and complicated events. Stones larger than 10 mm were associated with all events (hazard ratio [HR], 2.31; 95% confidence interval [CI], 1.45-3.69), acute cholecystitis (HR, 9.49; 95% CI, 2.05-43.92), and uncomplicated events (HR, 2.55; 95% CI, 1.38-4.71), including cholecystectomy (HR, 2.69; 95% CI, 1.29-5.60). Multiple stones were associated with all events ([HR, 1.68; 95% CI, 1.00-2.81), complicated events (HR, 2.52; 95% CI, 1.05-6.04), and common bile duct stones (HR, 11.83; 95% CI, 1.54-91). There was an association between gallstones more than 5 y old and acute cholecystitis. Female sex was associated with all and uncomplicated events. We found a negative association between participants' age and all events, uncomplicated events, and acute cholecystitis. Co-morbidities and female-associated factors (intake of birth control pills or estrogens and number of births) were not associated with events. Compared with men with a single stone of ≤10 mm (reference), women with multiple stones >10 mm had the highest risk for events (HR, 11.05; 95% CI, 3.76-32.44; unadjusted absolute risk, 0.0235 events/person years).

CONCLUSIONS: Fewer than 20% of subjects with gallstones develop clinical events. Larger, multiple, and older gallstones are associated with events. Further studies are needed to confirm the prediction rules.