(P26-04-26) Trimethylamine-N-Oxide (TMAO)-Dietary Pattern Associated With Increased Risk of Atherosclerotic Cardiovascular Disease (ASCVD) in Postmenopausal Women

Objectives: TMAO is produced via oxidation of trimethylamine, a gut microbiota-derived metabolite, implicated in atherosclerosis and thrombosis, and influenced by habitual dietary intake. We developed a TMAO dietary pattern (TMAO-DP) predictive of plasma choline and TMAO concentrations. The association between the TMAO-DP and incident ASCVD is unknown.

Methods: Participants of the Women’s Health Initiative (WHI) Observational Study (OS) and Clinical Trials (CT) with cardiovascular disease biomarker data, free of self-reported history of myocardial infarction (MI), stroke, or congestive heart failure (CHD) at baseline (1993-98), and with complete covariate data were included (n=12,443). Women were followed for incident adjudicated ASCVD events (n=2,748) (i.e., first occurrence of fatal/nonfatal stroke, nonfatal MI, death due to CHD) through 2010. Cox proportional hazards regression was used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for incident ASCVD by quintile of TMAO-DP. Food groups in the TMAO-DP were energy-adjusted. In multivariable models, the baseline hazards were stratified by participation in the OS and CT arms, age, race, smoking status, income, antihypertensive and diabetes treatment, and adjusted for aspirin use. Linear trends were assessed using quintile medians as well as a continuous measure of TMAO-DP. Restricted cubic splines were used to evaluate non-linearity.

Results: Participants had a mean age of 65 years and were 63% White, 29% Black, and 8% Other race. In adjusted models, TMAO-DP was positively associated with ASCVD risk (Quintile 5 vs Quintile 1 HR=1.36, 95% CI 1.16-1.61). The quintile-median adjusted trend test supported an overall graded association (p-trend < 0.001). Each 1-unit increase in the TMAO-DP score was associated with a 5% higher ASCVD risk (HR=1.05, 95% CI 1.02-1.08) in the adjusted modeled.

Conclusions: Women who consumed a pro-atherogenic dietary pattern predictive of circulating TMAO and choline had increased risk of ASCVD, supporting the relevance of diet in primary prevention of ASCVD in women.

Funding Sources: The WHI program is funded by the National Heart, Lung, and Blood Institute, National Institutes of Health, U.S. Department of Health and Human Services. This research was supported in part by the Intramural Research Program of the National Institutes of Health.