Abstract 16444: Gut Microbiota Derived Metabolite, Ursodeoxycholic Acid, and the Risk of Cardiovascular Disease

Introduction: Gut microbial metabolites have been recognized as risk factors for cardiometabolic diseases. The associations between plasma levels of the gut microbiota derived metabolites with cardiovascular disease (CVD) have not been comprehensively examined. Our objective was to investigate the association between 6 secondary bile acids including ursodeoxycholic acid and CVD. Ursodeoxycholic acid is used to dissolve cholesterol gall stones to treat cholestatic liver diseases.

Hypothesis: Gut microbiota derived metabolites are associated with CVD.

Methods: We performed a secondary analysis of data from the cross-sectional Metabolic Syndrome in Men (METSIM) cohort. Our study included 915 men aged 45-73 years (age = 54.94 ± 5.04 years, BMI = 27.31 ± 3.44), randomly selected from the population register of Kuopio, Eastern Finland, from 2005 to 2010. The associations between 6 secondary bile acids (ursodeoxycholic acid, glycoursodeoxycholate, glycolithocholate sulfate, taurocholenate sulfate, taurochenodeoxycholate, and glycocholenate sulfate) and the risk of CVD were investigated. Kaplan-Meier analysis with Cox proportional-hazards regressions were conducted for the time-to-event analysis to determine hazard ratios (HR) and 95% confidence intervals (CI) for CVD. Adjustments were made for traditional cardiovascular risk factors (age, systolic blood pressure, low-density and high-density lipoprotein cholesterol levels, triglyceride levels, smoking status, high-sensitivity C-reactive protein, estimated glomerular filtration rate, and alcohol consumption).

Results: Participants were stratified into groups according to quartile metabolites levels and CVD. During a median follow-up of 16 years, n = 62 (7%) of patients experienced CVD. Only ursodeoxycholic acid was significantly associated with CVD risk. Cox regression analyses showed that the adjusted HR for CVD was higher in patients in quartile 4 (HR: 2.8, 95% [CI]: 1.35-4.6; p =0.008) than in quartile 1. The Kaplan-Meier analysis indicated that patients in quartile 4 had a significantly lower event-free survival (p = 0.037) compare to quartile 1.

Conclusions: Ursodeoxycholic acid, a secondary bile acid, was positively associated with an increased risk of CVD.