Gallstone Disease and Increased Risk of Ischemic Heart Disease: Causal Association or Epiphenomenon?

Abstract

Gallstone disease (GD) is a major health problem in developed societies, affecting ≤15% of the general population.1 Although many risk factors for gallstone formation are not modifiable, obesity, diabetes mellitus, metabolic syndrome, rapid weight loss, and a sedentary lifestyle are risk factors for GD that can be changed.1 Moreover, the chronic use of some drugs (eg, octreotide, thiazide diuretics, and some oral contraceptives) may also increase the risk of developing GD.1 In contrast, long-term statin use seems to prevent gallstone formation, possibly by decreasing biliary cholesterol secretion and saturation and inhibition of cholesterol crystal formation.1,2 The rising pandemic of obesity and the metabolic syndrome is likely to lead to an increase in the prevalence of gallstones in many parts of the world in the foreseeable future. See accompanying article on page 2232 Interestingly, in this issue of the journal, Lv et al3 examined the association between GD (as diagnosed by a standardized questionnaire) and the risk of incident ischemic heart disease (IHD) among 199 292 men and 288 081 women aged 30−79 years in the China Kadoorie Biobank study. Participants with a previous history of cancer, IHD, and stroke at baseline were excluded from the study. At baseline, 5.8% of 487 373 adult participants reported the presence of GD (men 3.7%; women 7.3%). During a median follow-up period of 7.2 years, there were 10 245 incident cases of IHD (≈90% nonfatal) in men and 14 714 (≈95% nonfatal) in women. The authors found that GD was associated with an increased incidence of IHD events (ie, a combined end point inclusive of fatal and nonfatal events), independently of multiple cardiovascular risk factors. As compared with those subjects without GD at baseline, the multivariate-adjusted hazard ratios for IHD were, respectively, 1.11 (95% confidence interval 1.02−1.22) …