Trimethylamine N-Oxide and Risk of Cardiovascular Disease and Mortality

Trimethylamine N-oxide (TMAO) is a gut microbiota-dependent metabolite produced from choline and phosphatidylcholine. Trimethylamine N-oxide was found associated with enhanced atherosclerosis and thrombosis in vitro and in vivo. We summarized available clinical studies which investigated TMAO's role in predicting prognostic outcomes, including mortality, in patients with cardiovascular diseases.

In chronic kidney disease cohorts, higher TMAO levels were significantly associated with higher mortality from 1.18 to 4.32 folds. Higher TMAO levels were not significantly associated with mortality in patient undergoing dialysis. In patients with peripheral artery disease, higher TMAO levels were associated with higher overall mortality from 1.38 to 2.06 folds. In patients with type 2 diabetes, higher TMAO levels were significantly associated with higher overall mortality 2.07 to 2.7 folds. In patients with heart failure, higher TMAO levels were associated with higher mortality or cardiac transplantation 1.18 to 1.79 folds. TMAO levels could potentially be integrated to existed risk stratification tools and could lead to novel prevention and treatment approaches to cardiovascular disease. Nonetheless, more studies would be needed to clarify predictive value of TMAO to specific groups of patients. Mechanisms how TMAO affect atherosclerosis and confounding effects of TMAO with traditional cardiovascular parameters should also be further investigated.