14 Body Mass Index and the Risk of Symptomatic Gallstones - A Prospective Cohort Study in a UK Population

Abstract

Background. Obesity may predispose to the formation of gallstones by increasing both bile stasis and biliary cholesterol saturation. No prospective studies have investigated this hypothesis in both men and women in a European population. Furthermore, it is unknown if the association may be confounded by higher energy intake or lower physical activity. The current study aimed to investigate this relationship in a UK prospective study and to quantify, for the first time, the effect of Body Mass Index (BMI) adjusted for total energy intake and physical activity. Methods. The EPIC-Norfolk Study (European Prospective Investigation into Cancer) recruited 25, 639 men and women, aged 45-74 years between 1993-1997. Participants completed validated questionnaires assessing physical activity, alcohol consumption and total energy intake. Height and weight were measured at a baseline health examination. The cohort was monitored for participants who developed symptomatic gallstones over a ten-year period. The association between BMI and the risk of developing symptomatic gallstones was estimated using hazard ratios (HR) derived from Cox Regression models, adjusted for sex, age, physical activity, total energy intake and alcohol intake. BMI was modelled both as a categorical (< 25, 25 < 30, 30 < 35 and ≥ 35 kg/m2) and as a continuous exposure. Results. In the cohort, 266 participants (of whom 68.3% were women) developed symptomatic gallstones at a mean age of 61.8 years (range 42.7 76.5) with most presenting with biliary colic. Compared with the normal weight (BMI < 25 kg/m2) group, the hazard ratio for symptomatic gallstones in the 25 < 30 kg/m2 group was 1.61, (95 % CI 1.20 2.17, p=0.002) and was highest in the ≥ 35 kg/m2 group (HR= 3.33 (95 % CI 2.02 5.49, p < 0.001)). Overall, each 1 kg/m2 rise in BMI was associated with an increased hazard of symptomatic gallstones of 8% (95% CI 5 11, p < 0.001). The population attributable risk percent for symptomatic gallstones was 33 % for having a BMI ≥ 25 kg/ m2. Conclusions. Higher BMIwas associatedwith an increased risk of symptomatic gallstones, now reported for the first time in a prospective study in a European population in both men and women. If causal, achieving a BMI of < 25 kg/m2 would be associated with a reduction in incidence of symptomatic gallstones by a third. As the association was still significant after adjusting for physical activity and energy intake, this suggests that adiposity has specific biological mechanisms in the aetiology of gallstones.