Abstract 019: Changes in Gut Microbial Metabolites and Risk of Coronary Heart Disease in US Women: the Nurses’ Health Study

Introduction: Circulating levels of gut microbial metabolites, trimethylamine N-oxide (TMAO) and its nutrient precursors of choline and L-carnitine, have been suggested as risk factors for coronary heart disease (CHD). Whether changes in gut microbial metabolites are associated with the CHD incidence remains unknown. Hypothesis: We assessed the hypothesis that long-term (over 10 years) changes in plasma levels of TMAO, choline, and L-carnitine would be associated with the risk of CHD. Methods: This prospective nested case-control study included a total of 768 women (385 incident cases of fatal CHD and nonfatal myocardial infarction and 383 controls) who had data on blood concentrations of TMAO, choline, and L-carnitine at 2 time points, 10 years apart (1989-90, and 2000-01). We identified incident cases of CHD from the date of the second blood collection through 2014. Results: Higher TMAO levels at the second collection were associated with higher risk of CHD (relative risk (RR) 1.22 [95% CI: 1.05, 1.42] per 1 SD increment in log-transformed TMAO) in multivariate analyses controlling for traditional risk factors. Compared with women with low TMAO levels (lower two tertiles) at both time points, the RR was 1.74 (95% CI: 1.05, 2.89) for those with elevated levels of TMAO (the highest tertile) at both time points. Regardless of metabolite levels at the first collection, increases in TMAO or L-carnitine from the first to second collections were significantly associated with an increased risk of CHD (Fig. panels A-B). Women who had increases in both TMAO and L-carnitine had a particularly elevated risk of CHD (RR 2.12, 95% CI: 1.25, 3.59), as compared to those with decreases in both metabolites. Adherence to healthy dietary habits attenuated the associations of TMAO with CHD risk (Fig. panel C). Conclusions: Long-term increases in TMAO were significantly predictive of subsequent risk for CHD among women. The associations may be modified by the nutrient metabolite precursor, L-carnitine, and adherence to healthy dietary habits.