Abstract
Background Trimethylamine-N-oxide ( TMAO ), a diet-derived, gut microbial-host cometabolite, has been associated with adverse cardiovascular outcomes in patient populations; however, evidence is lacking from prospective studies conducted in general populations and non-Western populations. Methods and Results We evaluated urinary levels of TMAO and its precursor metabolites (ie, choline, betaine, and carnitine) in relation to risk of coronary heart disease ( CHD ) among Chinese adults in a nested case-control study, including 275 participants with incident CHD and 275 individually matched controls. We found that urinary TMAO , but not its precursors, was associated with risk of CHD . The odds ratio for the highest versus lowest quartiles of TMAO was 1.91 (95% CI, 1.08-3.35; P(trend)=0.008) after adjusting for CHD risk factors including obesity, diet, lifestyle, and metabolic diseases and 1.75 (95% CI, 0.96-3.18; P(trend)=0.03) after further adjusting for potential confounders or mediators including central obesity, dyslipidemia, inflammation, and intake of seafood and deep-fried meat or fish, which were associated with TMAO level in this study. The odds ratio per standard deviation increase in log- TMAO was 1.30 (95% CI, 1.03-1.63) in the fully adjusted model. A history of diabetes mellitus modified the TMAO - CHD association. A high TMAO level (greater than or equal to versus lower than the median) was associated with odds ratios of 6.21 (95% CI, 1.64-23.6) and 1.56 (95% CI, 1.00-2.43), respectively, among diabetic and nondiabetic participants ( P(interaction)=0.02). Diabetes mellitus status also modified the associations of choline, betaine, and carnitine with risk of CHD ; significant positive associations were found among diabetic participants, but null associations were noted among total and nondiabetic participants. Conclusions Our study suggests that TMAO may accelerate the development of CHD , highlighting the importance of diet-gut microbiota-host interplay in cardiometabolic health.