Gallstone disease and increased risk of mortality: Two large prospective studies in US men and women

Abstract

Background and aim: Gallstone disease has been related to a higher prevalence and incidence of chronic conditions, such as dyslipidemia, obesity, and cardiovascular disease (CVD). However, limited data are available regarding whether gallstone disease is related to mortality.

Methods: We examined the relationship of a history of gallstone disease and risk of death, using Cox proportional hazards regression analysis, among 86 030 women from the Nurses' Health Study and 43 949 men from the Health Professionals Follow-up Study.

Results: During the up-to 32 years of follow-up, 34 011 all-cause deaths were confirmed, of which 8138 were CVD deaths and 12 173 were cancer deaths. For the participants with a history of gallstone disease compared with those without, the hazard ratio of total mortality was 1.16 (95% confidence interval 1.13, 1.20), of CVD mortality 1.11 (1.05, 1.17), of cancer mortality 1.15 (1.09, 1.20), and of other mortality 1.19 (1.14, 1.25) from a pooled-analysis of women and men (all P < 0.001). The multi-adjusted associations between gallstone disease and total mortality persisted among women and men, and among participants with various risk profiles including the different status of body mass index, hormone therapy use, diabetes, hypertension, and hypercholesterolemia (all P for interaction ≥ 0.09).

Conclusion: These data suggest that gallstone disease is associated with a higher risk of total mortality and disease-specific mortality, including CVD and cancer mortality, independent of various traditional risk factors.

Keywords: cohort studies; gallstone disease; mortality.

Figure 1.. Pooled-analyzed hazard ratios of mortality comparing participants with a history of gallstone disease to those without, among 86,030 women from NHS and 43,949 men from HPFS.

Model 1 adjusted for age; Model 2 adjusted for age (months), body mass index (kg/m²), white race (yes/no), marital status (yes/no), smoking status (never, past, current smoker), smoking amount and duration (0, 0–9, 10–24, 25–44, ≥45 pack years), alcohol drinking status (women: 0, 0.1–4.9, 5.0–9.9, 10.0–14.9, ≥15.0 g/d; men: 0, 0.1−4.9, 5.0−9.9, 10.0−14.9, 15.0−29.9, or ≥30.0 g/d), physical activity (in quintile), family history of myocardial infarction (yes/no), diabetes (yes/no), and cancer (yes/no); post-menopausal hormone replacement (premenopausal, postmenopausal and HT nonuser, postmenopausal and current HT user, postmenopausal and past HT user, missing; NHS only), modified Alternative Health Eating Index Score (alcohol excluded; in quintiles), dietary cholesterol intake (in quintiles), daily energy intake (in quintiles); status of hypertension (yes/no), diabetes (yes/no), hypercholesterolemia (yes/no); regular aspirin use (yes/no). P for heterogeneity in Model 2 was 0.003 for all-cause death, 0.12 for CVD-death, 0.96 for cancer-death, and 0.003 for other death.

Figure 2.. Stratified analysis of the association between gallstone history and total mortality.

Covariates include age (months), body mass index (BMI, kg/m²), white race (yes/no), marital status (yes/no), smoking status (never, past, current smoker), smoking amount and duration (0, 0–9, 10–24, 25–44, ≥45 pack years), alcohol drinking status (women: 0, 0.1–4.9, 5.0–9.9, 10.0–14.9, ≥15.0 g/d; men: 0, 0.1−4.9, 5.0−9.9, 10.0−14.9, 15.0−29.9, or ≥30.0 g/d), physical activity (in quintile), family history of myocardial infarction (yes/no), diabetes (yes/no), and cancer (yes/no); post-menopausal hormone replacement (premenopausal, postmenopausal and HT nonuser, postmenopausal and current HT user, postmenopausal and past HT user, missing; NHS only), modified Alternative Health Eating Index Score (AHEI, alcohol excluded; in quintiles), dietary cholesterol intake (in quintiles), daily energy intake (in quintiles); status of hypertension (yes/no), diabetes (yes/no), hypercholesterolemia (yes/no); regular aspirin use (yes/no). indicates a lower level of the stratifying variable, i.e., age < 55 years, BMI < 30 kg/m², weight circumference, physical activity, and AHEI score was lower than the cohort-specific median, nondrinker, nonsmoker, free of type 2 diabetes, high cholesterol, or hypertension, and hormone therapy nonuser in women; indicates a higher level of the stratifying variable.