Abstract
Introduction: Trimethylamine-N-oxide (TMAO), a diet-derived, gut microbial-host co-metabolite, has been associated with adverse cardiovascular outcomes in patient populations. However, the evidence is lacking from prospective studies conducted in general populations and in non-Western populations. Hypothesis: TMAO level is associated with risk of coronary heart disease (CHD) in general populations. Methods: We examined associations of urinary TMAO and its precursors (i.e., choline, betaine, and carnitine) with risk of CHD in a case-control study nested within two prospective cohorts of Chinese adults, including 275 incident CHD cases and 275 individually matched controls. Results: Urinary TMAO, but not its precursors, was associated with risk of CHD. Odds ratio (OR, 95% CI) for the highest vs. lowest quartiles of TMAO was 1.91 (1.08-3.35; p-trend=0.008) after adjusting for CHD risk factors including obesity, diet, lifestyles, and metabolic diseases and 1.75 (0.96-3.18; p-trend=0.03) after further adjusting for potential confounders/mediators including central obesity, dyslipidemia, low-grade inflammation, and intakes of seafood and deep-fried meat/fish, which were associated with TMAO level in our study. OR was 1.30 (1.03-1.63) per standard deviation increase in log-TMAO in the fully-adjusted model. History of diabetes modified the TMAO-CHD association. A high TMAO level (≥ vs. <median) showed ORs of 6.21 (1.64-23.6) and 1.56 (1.00-2.43) among diabetic and non-diabetic participants, respectively (p-interaction=0.02). History of diabetes also modified the associations of choline, betaine, and carnitine with risk of CHD with significant positive associations being found among diabetics but null associations among total and non-diabetic participants. Conclusions: Our study suggests that TMAO may play a role in the development of CHD, highlighting the importance of diet-gut microbiota-host interplay in cardiometabolic health.
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