Gallstone Disease and the Risk of Cardiovascular Disease.
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ABSTRACT:
SUBMITTER: Fairfield CJ
PROVIDER: S-EPMC6456597 | biostudies-literature | 2019 Apr
REPOSITORIES: biostudies-literature
Publications
Gallstone Disease and the Risk of Cardiovascular Disease.
Fairfield Cameron J CJ Wigmore Stephen J SJ Harrison Ewen M EM
Scientific reports 20190409 1
Gallstone disease (GD) is one of the most common presentations to surgical units worldwide and shares several risk factors with cardiovascular disease (CVD). CVD remains the most common cause of death worldwide and results in considerable economic burden. Recent observational studies have demonstrated an association between GD and CVD with some studies demonstrating a stronger association with cholecystectomy. We present the findings of a meta-analysis assessing the relationship between GD and C ...[more]
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Project description:ObjectiveTo investigate whether gallstone disease (GD) increases the risk of developing cardiovascular disease (CVD) in a large population-based cohort.MethodsA study population including 6,981 patients with GD was identified from The Taiwan National Health Insurance Research Database between 2004 and 2005. GD patients were defined as patients with principal discharge diagnoses of cholelithiasis using the ICD-9-CM code 574. 27,924 patients without GD were randomly selected and matched for age and gender. All patients were followed for 6 years or until diagnosis for CVD. Cox proportional hazards regression model was used to assess the risk of developing CVD with adjustment for age, gender and co-morbid conditions.ResultsDuring the six years follow-up period, 935 patients with GD and 2,758 patients without GD developed CVD. Patients with GD had an elevated risk of CVD (HR, 1.32; 95% CI, 1.22-1.43) when compared with those without GD. Similar relationship was observed when CVD was categorized i.e. stroke (HR, 1.15; 95% CI, 1.01-1.32), coronary heart disease (HR, 1.42; 95% CI, 1.28-1.58) and heart failure (HR, 1.31; 95% CI, 1.00-1.73). When GD was classified according to the level of severity, using patients without GD as reference, the risks of CVD were elevated in patients with non-severe GD (HR, 1.34; 95% CI, 1.24-1.46) as well as those with severe GD (HR, 1.20, 95% CI, 1.02-1.40), after adjusting for age, gender and comorbidities. In age-stratified analysis, patients aged 18-40 years with GD were at higher risk of developing CVD (HR, 1.42; 95% CI, 1.09-1.84) than older GD patients.ConclusionThis study found an increased risk of CVD in patients diagnosed with GD. The excess risk was particularly high in younger GD patients. Prevention of GD could help reduce the risk of developing CVD, and the better effect could be achieved for the younger age groups.
| S-EPMC3789705 | biostudies-literature
Project description:PurposePatients who undergo bariatric surgery are at risk for developing cholesterol gallstones. We aimed to identify risk factors that are associated with symptomatic gallstone disease and gallstone formation after bariatric surgery.Materials and methodsWe included participants of the UPGRADE trial, a multicenter randomized placebo-controlled trial on the prevention of symptomatic gallstone disease with ursodeoxycholic acid (UDCA) after bariatric surgery. The association between patient characteristics and symptomatic gallstone disease, and gallstone formation was evaluated using logistic regression analysis.ResultsOf 959 patients, 78 (8%) developed symptomatic gallstone disease within 24 months. Risk factors were the presence of a pain syndrome (OR 2.07; 95% CI 1.03 to 4.17) and asymptomatic gallstones before surgery (OR 3.15; 95% CI 1.87 to 5.33). Advanced age (OR 0.95; 95% CI 0.93 to 0.97) was protective, and UDCA prophylaxis did not reach statistical significance (OR 0.64; 95% CI 0.39 to 1.03). No risk factors were identified for gallstone formation, whereas advanced age (OR 0.98; 95% CI 0.96 to 1.00), statin use (OR 0.42; 95% CI 0.20 to 0.90), and UDCA prophylaxis (OR 0.47; 95% CI 0.30 to 0.73) all reduced the risk.ConclusionYoung patients with a preoperative pain syndrome and/or asymptomatic gallstones before bariatric surgery are at increased risk for symptomatic gallstone disease after surgery. Whether statins, either alone or in combination with UDCA prophylaxis, can further reduce the burden of gallstones after bariatric surgery should be investigated prospectively.
| S-EPMC8933359 | biostudies-literature
Project description:ObjectiveGallstone disease (GSD) is related to multiple cardiovascular risk factors; the present study was to prospectively examine the association between GSD and ischemic heart disease (IHD).Approach and resultsWe examined the association of GSD with IHD among 199 292 men and 288 081 women aged 30-79 years in the China Kadoorie Biobank study. Participants with cancer, heart disease, and stroke at baseline were excluded. Cox proportional hazards regression model was used to estimate the association of GSD with IHD. The prevalence of self-reported GSD was 3.7% in men and 7.3% in women at baseline. During 3 431 124 person-years of follow-up between 2004 and 2013 (median, 7.2 years), we documented 10 245 incident IHD cases in men and 14 714 in women. As compared with men without GSD at baseline, the multivariate-adjusted hazard ratio for IHD was 1.11 (95% confidence interval, 1.02-1.22) for men with GSD; the respective hazard ratio was 1.27 (95% confidence interval, 1.20-1.34) in women and 1.23 (95% confidence interval, 1.17-1.28) in the whole cohort. The sex difference in IHD risk associated with GSD was statistically significant (P=0.009 for interaction with sex). In addition, we found that the association between GSD and IHD was stronger in nonhypertensive than in hypertensive women (P<0.001 for interaction).ConclusionsIn this large prospective study, the presence of GSD was associated with an increased risk of incident IHD, independent of other risk factors of cardiovascular disease. Our findings suggest novel prevention strategy to mitigate heart disease through improvement of gastrointestinal health.
| S-EPMC4587542 | biostudies-literature
Project description:Objective: Given the association between physical activity and the reduced risk of gallstone disease as suggested in observational studies, a Mendelian randomization study was conducted to evaluate the causal nature of this association in genetic epidemiology. Study: Including self-reported and accelerometer-based physical activity traits, the independent genetic variants associated with physical activity were selected from the corresponding genome-wide association studies as instrumental variables. The summary-level data for gallstone disease were sourced from the UK Biobank (7,682 cases and 455,251 non-cases) and FinnGen consortium (23,089 cases and 231,644 non-cases). Then, two-sample Mendelian randomization analysis was conducted. Inverse-variance weight (IVW), weighted median, and Mendelian randomization-Egger regression were determined through Mendelian randomization analyses. To ensure the robustness of the results, sensitivity analyses were also carried out in the study. Results: The negative causality between the genetically predicted accelerometer-based "average acceleration" physical activity and the risk of gallstone disease was suggested in the UK Biobank study (p = 0.023, OR = 0.93, 95% CI: 0.87-0.99), and accelerometer-based "overall activity" physical activity and the risk of gallstone disease in the UK Biobank study (p = 0.017, OR = 0.38, 95% CI: 0.17-0.84). With accelerometer-based "average acceleration" physical activity negatively correlated with gallstone disease in the FinnGen consortium data (p = 0.001, OR = 0.94, 95% CI: 0.90-0.97). As for self-reported moderate-to-vigorous physical activity, however, there was no causality observed in both pieces of data. Conclusion: Our studies provide the evidence suggesting a casual association between physical activities and gallstone disease through analysis of genetic data. As indicated by the research results, there is a possibility that a higher level of physical activities could mitigate the risk of gallstone disease.
| S-EPMC9763559 | biostudies-literature
Project description:Vegetarian diets may lower symptomatic gallstone disease via cholesterol lowering. This study aimed to examine the risk of symptomatic gallstone disease (GSD) in Taiwanese vegetarians vs. nonvegetarians in a prospective cohort and to explore if this association is related to cholesterol concentration. We prospectively followed 4839 participants, and in the 29,295 person-years of follow-up, 104 new incident GSD cases were confirmed. Diet was assessed through a validated food frequency questionnaire. Symptomatic GSD was ascertained through linkage to the Taiwan National Health Insurance Research Database. Blood cholesterol profiles were measured at recruitment. Cox regression was applied to assess the effect of diet on symptomatic GSD, adjusting for age, education, smoking, alcohol, physical activities, diabetes, kidney diseases, body mass index, lipid-lowering medication, and hypercholesterolemia. Vegetarian diet was associated with a decreased risk of symptomatic GSD compared with nonvegetarian diet in women (hazard ratio [HR], 0.52; 95% confidence interval [CI], 0.28⁻0.96) but not in men. In women, nonvegetarians with hypercholesterolemia had 3.8 times the risk of GSD compared with vegetarians with normal cholesterol (HR, 3.81, 95% CI, 1.61⁻9.01). A vegetarian diet may therefore protect against GSD independent of baseline hypercholesterolemia. A nonvegetarian diet and hypercholesterolemia may have an additive effect in increasing GSD risk in women.
| S-EPMC6412457 | biostudies-literature
Project description:Background & aimsAdiposity has been consistently associated with gallstone disease risk. We aimed to characterize associations of anthropometric measures (body mass index [BMI], recent weight change, long-term weight change, waist circumference, and waist-to-hip ratio) with symptomatic gallstone disease according to strata of gallstone disease polygenic risk score (PRS).MethodsWe conducted analysis among 34,626 participants with available genome-wide genetic data within 3 large, prospective, U.S. cohorts-the Nurses' Health Study (NHS), Health Professionals Follow-Up Study, and NHS II. We characterized joint associations of PRS and anthropometric measures and tested for interactions on the relative and absolute risk scales.ResultsWomen in the highest BMI and PRS categories (BMI ≥30 kg/m2 and PRS ≥1 SD above mean) had odds ratio for gallstone disease of 5.55 (95% confidence interval, 5.29 to 5.81) compared with those in the lowest BMI and PRS categories (BMI <25 kg/m2 and PRS <1 SD below the mean). The corresponding odds ratio among men was 1.65 (95% confidence interval, 1.02 to 2.29). Associations for BMI did not vary within strata of PRS on the relative risk scale. On the absolute risk scale, the incidence rate difference between obese and normal-weight individuals was 1086 per 100,000 person-years within the highest PRS category, compared with 666 per 100,000 person-years in the lowest PRS category, with strong evidence for interaction with the ABCG8 locus.ConclusionsWhile maintenance of a healthy body weight reduces gallstone disease risk among all individuals, risk reduction is higher among the subset with greater genetic susceptibility to gallstone disease.
| S-EPMC8720320 | biostudies-literature
Project description:Background/objectivesIndividuals with Gilbert's syndrome (GS) harbor mutations in the UGT1A1 gene and are known to have elevated levels of bilirubin, which enhances the risk for gall stone formation. The aim of this study is to screen Indian patients with GS for the incidence of gall stone disease.MethodsIndividuals with persistently elevated serum bilirubin levels were genotyped for two polymorphisms (rs8175347; rs4148323) in UGT1A1 gene to confirm GS in them. Flanking regions of the above polymorphisms were amplified followed by direct sequencing. Ultrasonography was done to detect gallstone disease. Clinical data, including assessment of liver function, circulating levels of total and direct bilirubin, as well as routine hematological parameters were obtained as per standard procedures (Autoanalyzer).ResultsOf the total 1621 individuals subjected to genotyping, 1191 (1149 males of 29.6 ± 11.3 years with mean BMI of 22.1 ± 3.7 kg/m2 and 42 females of 30.8 ± 14.8 years with mean BMI of 20.9 ± 3.7 kg/m2) were confirmed to have GS. Gall bladder abnormalities including cholelithiasis (n = 106/1191; 8.9%), polyps (n = 18/1191; 1.5%) and gallbladder wall thickening (n = 17/1191; 1.4%) were noted. Incidence of gall stone disease was observed in 103 males (out of 1149) and 3 females (out of 42) indicating the risk of the disease to be 9.0% and 7.1% respectively in males and females with GS.ConclusionEarly recognition of GS by genetic analysis is required before these patients with intermittent episodes of jaundice run the risk of unnecessary operations on their bile ducts from the mistaken assumption ascribing the jaundice to a stone which has been left behind.
| S-EPMC6286431 | biostudies-literature
Project description:BackgroundGallstone disease is associated with p.D19H of ABCG8 as well as alterations of cholesterol and bile acid metabolism. However, molecular mechanisms have not been fully elucidated. It is important to understand the link between the sterol transporters ABCG5/8 and NPC1L1 and intestinal cholesterol absorption as well as de novo synthesis in gallstone patients stratified according to 19H risk allele. Moreover, the functional importance of the 19H variant on intestinal ABCG8 feature remains to be clarified.MethodsMeasurements of serum surrogate markers of cholesterol absorption (plant sterols: sitosterol, campesterol) and synthesis (cholesterol precursor: lathosterol) were carried out by gas chromatography/mass spectrometry (GC/MS). For expression studies, total RNA was isolated from 168 ileal biopsies of study participants with (34) and without gallstone disease (134). Messenger RNA was measured by LightCycler real-time PCR. Genomic DNA was obtained from blood leukocytes. Genotype frequencies of p.D19H were established using MALDI-TOF mass spectrometry.ResultsCompared to controls, cholesterol absorption but not synthesis in gallstone carriers was diminished by about 21% based on low serum sitosterol (P = 0.0269) and campesterol (P = 0.0231) to cholesterol ratios. D19H was found to be significantly associated with gallstones (odds ratio [OR] = 2.9, P = 0.0220, 95% confidence interval [CI]:1.22-6.89), particularly in the overweight cohort (OR = 3.2, P = 0.0430, 95% CI:1.07-9.26). Cholesterol absorption was about 24% lower in individuals carrying p.D19H compared to wild type (Psitosterol = 0.0080, Pcampesterol = 0.0206). Moreover, irrespective of phenotype, carriers of p.D19H displayed a significant lower absorption than carriers of the major allele. The most pronounced effect on cholesterol absorption ratio was observed for serum campesterol levels (wild type controls to mutated controls 28%, P = 0.0347 and wild type controls to gallstone carriers with 19H allele 37%, P = 0.0030). Notably, ABCG5/8 and NPC1L1 expression was similar in gallstone carriers and controls regardless of p.D19H presence.ConclusionsBoth gallstone disease and p.D19H of ABCG8 are associated with diminished cholesterol absorption. However, p.D19H is not responsible for the differences in small intestinal sterol transporter expression.
| S-EPMC3598676 | biostudies-literature
Project description:BackgroundGallstone disease has been associated with colorectal cancer and some form of polyps, although the findings are inconclusive. It remains unknown whether gallstone disease influences the initiation of colorectal cancer.MethodsWe prospectively assessed the association of gallstone disease with risk of colorectal cancer precursors, including conventional adenomas and serrated polyps, in the Nurses' Health Study (1992-2012), the Nurses' Health Study II (1991-2011), and the Health Professionals Follow-up Study (1992-2012). Gallstone diseases were assessed using biennial follow-up questionnaires. Self-reported polyp diagnosis was confirmed by review of medical records. Logistic regression models were used to calculate the ORs with adjustment for smoking and other potential confounders.ResultsAmong participants who had undergone a total of 323,832 endoscopies, 16.5% had gallstone disease and 11.3% received cholecystectomy. We documented 1,724, 1,212, and 1,943 cases of conventional adenomas and 1,470, 1,090, and 1,643 serrated polyps in patients with gallstones, cholecystectomy, and either of them, respectively. The OR for adenomas was 1.00 [95% confidence interval (CI): 0.95-1.06] for gallstones, 0.99 (95% CI, 0.93-1.06) for cholecystectomy, and 1.00 (95% CI, 0.95-1.05) for either exposure. The corresponding ORs for serrated polyps were 0.98 (95% CI, 0.92-1.04), 0.99 (95% CI, 0.93-1.06), and 0.97 (95% CI, 0.92-1.03), respectively.ConclusionsGallstone disease is not associated with colorectal polyps.ImpactPatients with gallstones appear to have similar risk of colorectal polyps compared with those without and may therefore follow average-risk colorectal cancer screening guidelines.
| S-EPMC8643323 | biostudies-literature
Project description:Biliary lipids are a family of four dissimilar molecular species consisting of a mixture of bile salts (substituted cholanoic acids), phospholipids, mostly (>96%) diacylphosphatidylcholines, unesterified cholesterol, and bilirubin conjugates known trivially as lipopigments. The primary pathophysiological defect in cholesterol gallstone disease is hypersecretion of hepatic cholesterol into bile with less frequent hyposecretion of bile salts and/or phospholipids. Several other gallbladder abnormalities contribute and include hypomotility, immune-mediated inflammation, hypersecretion of gelling mucins, and accelerated phase transitions; there is also reduced intestinal motility that augments "secondary" bile salt synthesis by the anaerobic microflora. Cholesterol nucleation is initiated when unilamellar vesicles of cholesterol plus biliary phospholipids fuse to form multilamellar vesicles. From these "plate-like" cholesterol monohydrate crystals, the building blocks of macroscopic stones are nucleated heterogeneously by mucin gel. Multiple Lith gene loci have been identified in inbred mice, paving the way for discovery of an ever-increasing number of LITH genes in humans. Because of the frequency of the metabolic syndrome today, insulin resistance and LITH genes all interact with a number of environmental cholelithogenic factors to cause the gallstone phenotype. This review summarizes current concepts of the physical-chemical state of biliary lipids in health and in lithogenic bile and outlines the molecular, genetic, hepatic, and cholecystic factors that underlie the pathogenesis of cholesterol gallstones.
| S-EPMC2674701 | biostudies-literature