Abstract and Introduction
Abstract
Most gallstones originate from cholesterol-supersaturated bile. Statins inhibit hepatic cholesterol biosynthesis and therefore may reduce the risk of gallstone disease. Population-based evidence, however, is sparse. Thus, the authors conducted a population-based case-control study using medical databases from northern Denmark (1.7 million inhabitants) to identify 32,494 cases of gallstones occurring between 1996 and 2008 and to identify age-, sex-, and county-matched population controls for each case. Cases and their matched controls who were exposed to lipid-lowering drugs were categorized as current users if their last prescription was redeemed ≤90 days before the case's diagnosis date; otherwise, they were categorized as former users. Conditional logistic regression was used to estimate adjusted odds ratios and 95% confidence intervals for gallstone disease in patients treated with lipid-lowering drugs. In current users, the adjusted odds ratios associating statin use with the occurrence of gallstone disease were 1.17 (95% confidence interval (CI): 1.06, 1.30) for those who had 1–4 prescriptions, 0.89 (95% CI: 0.80, 0.97) for those who had 5–19 prescriptions, and 0.76 (95% CI: 0.69, 0.84) for those who had ≥20 total prescriptions. In former users, the corresponding adjusted odds ratios were 1.24 (95% CI: 1.11, 1.39), 0.97 (95% CI: 0.86, 1.10), and 0.79 (95% CI: 0.64, 0.97), respectively. The use of other lipid-lowering drugs showed no similar association.
Introduction
The prevalence of gallstone disease in the Western world ranges from 6% to 50%, increasing with age and varying with geographic region. The risk increases with certain genetic factors, increasing age, female gender, and obesity. Gallstone disease is a chronic and usually asymptomatic condition, but it leads to severe complications in about 2% of symptomatic patients. Intense pain in the upper quadrant of the abdomen and acute cholecystitis are the most common complications and may require surgical removal of the gallbladder (cholecystectomy). Jaundice, pancreatitis, and cholangitis caused by stones that migrate from the gallbladder to the common bile duct are other severe complications. In the Western world, 80%–90% of gallstones originate from cholesterol-supersaturated bile, with the remainder formed as pigment stones, primarily from bilirubin and calcium.
In the liver, 3-hydroxy-3-methylglutaryl coenzyme A inhibitors (statins) inhibit cholesterol biosynthesis, and thus may prevent gallstone formation, gallstone recurrence, subsequent complications, and cholecystectomy. Evidence of the association between statins and gallstone disease is conflicting, although 3 recent studies—a US cohort study and case-control studies from United Kingdom and Israel—have shown a reduced risk of gallstone disease followed by cholecystectomy in people taking statins. These studies estimated the association between statins and severe gallstone disease only. In addition, the US study was based on questionnaire reports of gallstone disease and statin use, the UK study relied on information from general practitioners regarding in-hospital treatments, and the Israeli study lacked details of important covariates. There is, therefore, a need for evidence evaluating the association between statin use and the occurrence of more general gallstone disease in an unselected population. To address these limitations, we conducted a study using Danish population-based health registries with hospital-based information to evaluate the association between statin use (including intensity and duration) and gallstone disease.