Gallstones and Risk of Coronary Heart Disease: Prospective Analysis of 270 000 Men and Women From 3 US Cohorts and Meta-Analysis

Abstract

Objective: Gallstone disease has been related to cardiovascular risk factors; however, whether presence of gallstones predicts coronary heart disease (CHD) is not well established.

Approach and results: We followed up 269 142 participants who were free of cancer and cardiovascular disease at baseline from 3 US cohorts: the Nurses' Health Study (112 520 women; 1980-2010), Nurses' Health Study II (112 919 women; 1989-2011), and the Health Professionals Follow-up Study (43 703 men; 1986-2010) and documented 21 265 incident CHD cases. After adjustment for potential confounders, the hazard ratio for the participants with a history of gallstone disease compared with those without was 1.15 (95% confidence interval, 1.10-1.21) in Nurses' Health Study, 1.33 (95% confidence interval, 1.17-1.51) in Nurses' Health Study II, and 1.11 (95% confidence interval, 1.04-1.20) in Health Professionals Follow-up Study. The associations seemed to be stronger in individuals who were not obese, not diabetic, or were normotensive, compared with their counterparts. We identified 4 published prospective studies by searching PUBMED and EMBASE up to October 2015, coupled with our 3 cohorts, involving 842 553 participants and 51 123 incident CHD cases. The results from meta-analysis revealed that a history of gallstone disease was associated with a 23% (15%-33%) increased CHD risk.

Conclusion: Our findings support that a history of gallstone disease is associated with increased CHD risk, independently of traditional risk factors.

Keywords: adult; bile; cohort study; coronary disease; gallstones.

© 2016 American Heart Association, Inc.

Figures

Figure 1

Associations between history of gallstone disease and coronary heart disease risk stratified by age, obesity status, smoking status, diet, and physical activity. Red circles indicate the respective stratum with the lower risk values (age 2, non-smoker, and Alternative Healthy Eating Index and physical activity less than the cohort-specific median value, with normal blood cholesterol levels, without diabetes, without hypertension). Blue circles indicate the respective stratum with the higher (presumably riskier) values (i.e., age ≥55 years, BMI ≥30kg/m2, smoker, AHEI and physical activity greater than or equal to the cohort-specific median value, with high blood cholesterol levels, with diabetes, with hypertension). Cox proportional hazards models were adjusted for include age (months); race (white/nonwhite); family history of MI (yes/no); marital status (married/not married); smoking status (never smoked, past smoker, current smoker); body mass index (kg/m2); physical activity (metabolic equivalent task hours/d in quintiles); diabetes (yes/no); hypertension (yes/no); hypercholesterolemia (yes/no); regular use of aspirin (yes/no); daily intake of alcohol (0, 0.1–5.0, 5.0–9.9, 10.0–14.9, ≥15.0 g/d), daily intake of the energy-adjusted dietary cholesterol (g/d in quintiles), 2010 Alternate Healthy Eating Index (AHEI score in quintiles), and daily energy intake (kcal/d in quintiles). In NHS and NHS II, menopausal status (yes/no), postmenopausal hormone uses (yes/no), and uses of oral contraceptive pills (yes/no) were also considered as covariates.

Figure 2

Forest plot of the multivariate-adjusted risk ratio of coronary heart disease for history of gallstone disease in individual cohort studies and all studies combined in inverse weighted random-effects meta-analysis. Diamonds indicate point estimates; bars indicate 95% CIs; the size of the grey squares corresponds to the weight of the study in the meta-analysis. Abbreviations: EPIC, European Prospective Investigation into Cancer and Nutrition; HPFS, Health Professionals Follow-up Study; NHS, Nurses’ Health Study.