Abstract MP24: Atherogenic Gut Microbial Metabolite Scores and Risk of Coronary Heart Disease Among Women in the Nurses’ Health Study

Introduction: Recent evidence suggests that dietary proteins modulate the microbial composition and metabolite production to influence host physiology. Gut-microbiota-related metabolites, such as trimethylamine N-oxide (TMAO) and its precursors, phenylacetylglutamine (PAGln) and p-tolyl (cresol) sulfate, have been recently implicated as atherogenic metabolites derived from the microbial metabolism of protein foods (such as red meat) and amino acids. Hypothesis: We tested a hypothesis that combined effects of atherogenic gut microbiota-related metabolites may be strongly related to the risk of incident coronary heart disease (CHD) among women. Methods: We conducted a prospective nested case-control study of 762 incident cases of CHD (fatal CHD and nonfatal myocardial infarction) and 762 matched controls identified over 10-14 years of follow-up. Plasma metabolites (TMAO, N,N,N-trimethyllysine, PAGln, and p-tolyl (cresol) sulfate) were measured at baseline. We regressed the CHD outcome against metabolites using conditional logistic regression and then calculated an atherogenic microbial metabolite score (AMMS) of CHD by summing the β effects of metabolites. Results: Every 1 SD increment of AMMS was associated with a matching factor-adjusted RR of 1.28 (95% CI: 1.15, 1.44) and a multivariable-adjusted RR of 1.26 (1.12, 1.42) for CHD controlling for demographic, dietary, and lifestyle factors, postmenopausal hormone use, and body mass index. Dose-response analysis showed a linear relation between AMMS and the risk of CHD ( P <0.001). In addition, there was a 1.20 (1.06, 1.36) times increased risk of CHD per 1 SD of AMMS after adjusting for common metabolic comorbidities (diabetes, hypertension, and dyslipidemia). The highest quintile (Q5) group had an adjusted RR of 1.60 (1.08, 2.37) for CHD, as compared to the lowest quintile (Q1) ( Fig ). Conclusions: Atherogenic gut microbiota-related metabolite scores were significantly associated with risk of incident CHD among women without prior CHD.