Risk Of Symptomatic Gallstones Research Articles

The Natural History of Asymptomatic Gallstones: A Longitudinal Study and Prediction Model

Despite the high prevalence of asymptomatic gallstones (AGs), there are limited data on their natural history. We aimed to determine the rate of symptom development in a contemporary population, determine factors associated with progression to symptomatic gallstones (SGs), and develop a clinical prediction model. We used a retrospective cohort design. The time to first SG was shown using Kaplan-Meier curves. Multivariable competing risk (death) regression analysis was used to identify variables associated with SGs. A prediction model for the development of SGs after 10 years was generated and calibration curves were plotted. Participants were patients with AGs based on ultrasound or computed tomography from the general medical population. From 1996 to 2016, 22,257 patients (51% female) with AGs were identified; 14.5% developed SG with a median follow-up period of 4.6 years. The cumulative incidence was 10.1% (±0.22%) at 5 years, 21.5% (±0.39%) at 10 years, and 32.6% (±0.83%) at 15 years. In a multivariable model, the strongest predictors of developing SGs were female gender (hazard ratio [HR], 1.50; 95% CI, 1.39-1.61), younger age (HR per 5 years, 1.15; 95% CI, 1.14-1.16), multiple stones (HR, 2.42; 95% CI, 2.25-2.61), gallbladder polyps (HR, 2.55; 95% CI, 2.14-3.05), large stones (HR, 2.03; 95% CI, 1.80-2.29), and chronic hemolytic anemia (HR, 1.90; 95% CI, 1.33-2.72). The model showed good discrimination (C-statistic, 0.70) and calibration. In general medical patients with AGs, symptoms developed at approximately 2% per year. A predictive model with good calibration could be used to inform patients of their risk of SGs.

Functional CT and MR Biliary Imaging in Patients With Unexplained Abdominal Pain and Controls

G A A b st ra ct s recruited into the European Prospective Investigation into Cancer-Norfolk (EPIC-Norfolk) with 23 658 completing 7-DFDs at enrolment. The cohort was monitored for 14 years for new symptomatic gallstones, with diagnoses confirmed by review of the clinical notes. The 7-DFDs recorded one week's diet including drink type, brands and volumes consumed. A representative sample of 3 970 and also those with gallstone disease had their 7-DFDs coded by nutritionists using a computer program containing nutrient information on 11 000 food and drink items. A cohort analysis used Cox regression modelling to estimatehazard ratios (HR) for men and women, comparing 1, 2 or 3+ cups (1 cup=250mls) of caffeinated coffee and tea intake per day versus zero intake as well as a binary variable of any caffeinated coffee vs none and decaffeinated coffee vs none. The analyses were adjusted for the risk factors: age, body mass index, energy intake, alcohol intake and physical activity in men, and also parity and hormone replacement therapy use in women. Results: 177 women (mean age of diagnosis 66.5 yrs SD=9.5 yrs) and 90 men (64.2 yrs SD=9.2 yrs) developed symptomatic gallstones. In men, caffeinated coffee intake was associated with a decreased risk of symptomatic gallstones (3+ cups day vs zero intake HR=0.48, 95% CI=0.26-0.89) with a significant trend across categories (per 1 cup increase HR=0.79, p=0.022). Drinking any caffeinated coffee compared to zero consumption in men, the HR was 0.58 (95% CI= 0.38-0.90, p=0.015). If all men consumed three or more cups of caffeinated coffee a day, then 26% of symptomatic gallstones could be prevented. No effects were found for tea and decaffeinated coffee consumption in men and any drink intake in women (any caffeinated coffee vs zero consumption HR=0.84 95% CI=0.60-1.17, p=0.30). Conclusion: The data suggests that caffeinated coffee may reduce the risk of symptomatic gallstones in men but not in women. Coffee should be measured in future studies investigating the aetiology of gallstones in men.

Caffeinated Coffee is Associated With a Reduction of Symptomatic Gallstones in Men. Data From a UK Prospective Cohort Study (EPIC-Norfolk) Using 7-Day Food Diaries

Introduction: Low iron intake reduces nitric oxide synthase (NOS) activity, which impairs gallbladder motility and bile flow. Low iron intake decreases activity of cholesterol 7-αhydroxlase, an enzyme which converts cholesterol to bile acids. Niacin increases plasma high density lipoprotein and lowers plasma triglycerides, both of which are associated with a lower incidence of gallstone disease. This study investigated dietary iron and niacin intake and the risk of developing symptomatic gallstones, for the first time using seven-day food diaries (7-DFDs), the most accurate feasible method of estimating food intake in large epidemiological studies. Methods: 25 639 participants (56% women), aged 40-74 yrs were recruited into the European Prospective Investigation into Cancer-Norfolk (EPIC-Norfolk) with 23 658 completing 7-DFDs at enrolment. The cohort was monitored for 14 years for new symptomatic gallstones, with diagnoses confirmed by review of the clinical notes. The 7-DFDs recorded one week's diet including food types, frequency of consumption, quantities and cooking methods. A representative sample of 3 970 and those with gallstone disease had their 7-DFDs coded by nutritionists using a computer program containing nutrient information on 11 000 food and 55 000 portion sizes. A cohort analysis used Cox regression to estimate sex specific hazard ratios (HR) for developing gallstones comparing fifths of dietary iron and niacin acid intake adjusted for age, body mass index, energy, alcohol and physical activity in men, and also parity and hormone replacement therapy use in women. Results: 177 women (mean age of diagnosis 66.5yrs SD=9.5yrs) and 90 men (64.2yrs SD= 9.2yrs) developed symptomatic gallstones. In women, increased dietary iron intake was associated with a decreased risk of symptomatic gallstones (highest vs lowest fifth, HR=0.36 95% CI=0.20-0.66; per fifth increase, HR=0.82 95% CI=0.72-0.94 p=0.003), although no effects were seen in men (per fifth increase, HR=0.97 95% CI=0.81-1.17). Increased dietary niacin intake was also associated with a decreased risk of disease in women (highest vs lowest fifth, HR=0.50 95% CI=0.30-0.83; per fifth increase, HR=0.86 95% CI=0.76-0.97 p=0.011), but no effects were found in men (per fifth increase, HR=0.96 95% CI=0.811.14). Conclusion: In women, gallstone disease may be prevented by increasing dietary iron and niacin intake, for which there are plausible biological mechanisms. No effects were found in men, although this could be due to a lack of power as only half the number of cases diagnosed and also that men are less likely to be iron deficient. These nutrients should be measured in future studies to confirm the association. Risk of developing symptomatic gallstones by fifths of dietary intake of iron and niacin in women and men.

S1238 Serum Lipids and the Risk of Developing Symptomatic Gallstones: A UK Prospective Cohort Study

Introduction The formation of gallstones may be influenced by alcohol consumption, physical activity and obesity through their effects on serum lipids. The aim of this study was to investigate if the serum levels of cholesterol, triglycerides, high density lipoprotein-cholesterol (HDL) and low density lipoprotein-cholesterol (LDL) were associated with the risk of symptomatic gallstones, for the first time in a European prospective cohort study. Methods A total of 21 850 men and women aged 45 to 74 years were recruited into the European Prospective Investigation into Cancer-Norfolk study between 1993 and 1997 and donated blood samples at enrolment. The cohort was then monitored over 14 years to identify participants who developed symptomatic gallstones, with each case reviewed by a physician to confirm the diagnoses. A cohort analysis was performed using Cox regression to estimate hazard ratios (HR) for developing symptomatic gallstones, in each gender, between quartiles of sex-specific serum lipid levels. In women, the HRs were adjusted for parity and hormone replacement therapy. Results During follow-up, 179 women and 81 men developed symptomatic gallstones at a median age of 61.8 years (range 42.7–76.5 years) with most patients presenting with biliary colic. Serum HDL was negatively associated with gallstones in both genders. For men, the highest compared to the lowest quartile of HR=0.22 (95% CI 0.10 to 0.53, p for trend across quartiles=0.001) and for women the HR=0.52 (95% CI 0.33 to 0.81, p for trend=0.004). Serum triglycerides were positively associated with gallstone disease in women (highest compared to lowest quartile HR=2.36, 95% CI 1.48 to 3.77, p for trend Conclusion This study confirmed that raised serum triglycerides are associated with an increased risk of symptomatic gallstones whereas raised serum HDL is associated with a decreased risk. These findings provide plausible biological mechanisms for how alcohol, physical activity and obesity influence the development of gallstones. If the latter are altered in public health programmes then the incidence of gallstones could be significantly reduced.

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

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.

15 Alcohol Intake and Development of Symptomatic Gallstones: An Inverse Association - A UK Prospective Cohort Study

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.

13 Physical Activity and Reduced Risk of Symptomatic Gallstones - a Prospective Cohort Study

13 Physical Activity and Reduced Risk of Symptomatic Gallstones - a Prospective Cohort Study

Association of coffee consumption with gallbladder disease.

Coffee consumption was recently shown to protect against symptomatic gallbladder disease in men. The authors examined the relation of ultrasound-documented gallbladder disease with coffee drinking in 13,938 adult participants in the Third National Health and Nutrition Examination Survey, 1988-1994. The prevalence of total gallbladder disease was unrelated to coffee consumption in either men or women. However, among women a decreased prevalence of previously diagnosed gallbladder disease was found with increasing coffee drinking (p = 0.027). These findings do not support a protective effect of coffee consumption on total gallbladder disease, although coffee may decrease the risk of symptomatic gallstones in women.

Antimicrobial Prophylaxis for Cholecystectomy in Diabetes

Two schedules of antimicrobial agents were compared in this prospective study of antimicrobial prophylaxis in diabetes mellitus patients undergoing cholecystectomy for symptomatic cholelithiasis. One hundred women grouped into two matched groups of 50 women each were studied. The results suggest that apart from a population of patients with identifiable risks of complications, a 24 hour, four dose antimicrobial prophylaxis is adequate and more cost effective than the five day schedule for most patients.

Risk of symptomatic gallstones in women with severe obesity

Although obesity is a well-recognized risk factor for gallstones, the excess risks associated with higher levels of obesity and recent weight change are poorly quantified. We evaluated these issues in the Nurses' Health Study. Among 90,302 women aged 34-59 y at baseline followed from 1980 to 1988, 2122 cases of newly diagnosed symptomatic gallstones occurred during 607,104 person-years of follow-up. From 1980 to 1986, 488 cases of newly diagnosed unremoved gallstones were documented. We observed a striking monotonic increase in gallstone disease risk with obesity; women with a body mass index (BMI) greater than 45 kg/m2 had a sevenfold excess risk compared with those whose BMI was less than 24 kg/m2. Women with a BMI greater than 30 kg/m2 had a yearly gallstone incidence of greater than 1% and those with a BMI greater than or equal to 45 kg/m2 had a rate of approximately 2%/y. Recent weight loss was associated with a modestly increased risk after adjustment for BMI before weight loss. Current smoking was an independent risk factor; women smoking greater than or equal to 35 cigarettes/d had a relative risk of 1.5 (95% CI 1.2-1.9).

Weight, diet, and the risk of symptomatic gallstones in middle-aged women.

To assess the risk factors for symptomatic gallstones, 88,837 women in the Nurses' Health Study cohort (age range, 34 to 59 years) were followed for four years after completing a detailed questionnaire about food and alcohol intake in 1980. A total of 433 cholecystectomies and 179 cases of newly symptomatic, unremoved gallstones, diagnosed by ultrasonographic examination or x-ray films, were reported during the four-year follow-up. The age-adjusted relative risk for very obese women, who had a Quetelet index of relative weight (weight in kilograms divided by the square of the height in meters) of more than 32 kg per square meter, was 6.0 (95 percent confidence interval, 4.0 to 9.0), as compared with women whose relative weight was less than 20 kg per square meter. For slightly overweight women (relative weight, 24 to 24.9 kg per square meter), the relative risk was 1.7 (95 percent confidence interval, 1.1 to 2.7). Overall, we observed a roughly linear relation between relative weight and the risk of gallstones. Among the 59,306 women whose relative weight was less than 25 kg per square meter, a high energy intake (greater than 8200 J per day), as compared with a low energy intake (less than 4730 J per day), was associated with an increased incidence of symptomatic gallstones (relative risk, 2.1; 95 percent confidence interval, 1.4 to 3.3), and an alcohol intake of at least 5 g per day was associated with a decreased incidence as compared with abstention (relative risk, 0.6; 95 percent confidence interval, 0.4 to 0.8). Parity did not appear to be an important risk factor after an adjustment was made for relative weight. These data support a strong association between obesity and symptomatic gallstones and suggest that even moderate overweight may increase the risk.