Dataset Information

Gut Dysbiosis and Immune System in Atherosclerotic Cardiovascular Disease (ACVD).

ABSTRACT: Atherosclerosis is a leading cause of cardiovascular disease and mortality worldwide. Alterations in the gut microbiota composition, known as gut dysbiosis, have been shown to contribute to atherosclerotic cardiovascular disease (ACVD) development through several pathways. Disruptions in gut homeostasis are associated with activation of immune processes and systemic inflammation. The gut microbiota produces several metabolic products, such as trimethylamine (TMA), which is used to produce the proatherogenic metabolite trimethylamine-N-oxide (TMAO). Short-chain fatty acids (SCFAs), including acetate, butyrate, and propionate, and certain bile acids (BAs) produced by the gut microbiota lead to inflammation resolution and decrease atherogenesis. Chronic low-grade inflammation is associated with common risk factors for atherosclerosis, including metabolic syndrome, type 2 diabetes mellitus (T2DM), and obesity. Novel strategies for reducing ACVD include the use of nutraceuticals such as resveratrol, modification of glucagon-like peptide 1 (GLP-1) levels, supplementation with probiotics, and administration of prebiotic SCFAs and BAs. Investigation into the relationship between the gut microbiota, and its metabolites, and the host immune system could reveal promising insights into ACVD development, prognostic factors, and treatments.

SUBMITTER: Yoo JY

PROVIDER: S-EPMC8780459 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Importance:Current guidelines recommend statin therapy for millions of US residents for the primary prevention of atherosclerotic cardiovascular disease (ASCVD). It is unclear whether traditional prediction models that do not account for current widespread statin use are sufficient for risk assessment. Objectives:To examine the performance of the Pooled Cohort Equations (PCE) for 5-year ASCVD risk estimation in a contemporary cohort and to test the hypothesis that inclusion of statin therapy improves model performance. Design, Setting, and Participants:This cohort study included adult patients in the Veterans Affairs health care system without baseline ASCVD. Using national electronic health record data, 3 Cox proportional hazards models were developed to estimate 5-year ASCVD risk, as follows: the variables and published ? coefficients from the PCE (model 1), the PCE variables with cohort-derived ? coefficients (model 2), and model 2 plus baseline statin use (model 3). Data were collected from January 2002 to December 2012 and analyzed from June 2016 to March 2020. Exposures:Traditional ASCVD risk factors from the PCE plus baseline statin use. Main Outcomes and Measures:Incident ASCVD and ASCVD mortality. Results:Of 1?672?336 patients in the cohort (mean [SD] baseline age 58.0 [13.8] years, 1?575?163 [94.2%] men, 1?383?993 [82.8%] white), 312?155 (18.7%) were receiving statin therapy at baseline. During 5 years of follow-up, 66?605 (4.0%) experienced an ASCVD event, and 31?878 (1.9%) experienced ASCVD death. Compared with the original PCE, the cohort-derived model did not improve model discrimination in any of the 4 age-sex strata but did improve model calibration. The PCE overestimated ASCVD risk compared with the cohort-derived model; 211?237 of 1?136?161 white men (18.6%), 29?634 of 218?463 black men (13.6%), 1741 of 44?399 white women (3.9%), and 836 of 16?034 black women (5.2%) would be potentially eligible for statin therapy under the PCE but not the cohort-derived model. When added to the cohort-derived model, baseline statin therapy was associated with a 7% (95% CI, 5%-9%) lower relative risk of ASCVD and a 25% (95% CI, 23%-28%) lower relative risk for ASCVD death. Conclusions and Relevance:In this study, lower than expected rates of incident ASCVD events in a contemporary national cohort were observed. The PCE overestimated ASCVD risk, and more than 15% of patients would be potentially eligible for statin therapy based on the PCE but not on a cohort-derived model. In the statin era, health care professionals and systems should base ASCVD risk assessment on models calibrated to their patient populations.

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Gut Dysbiosis and Immune System in Atherosclerotic Cardiovascular Disease (ACVD).

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