The Association between Trimethylamine N-Oxide and Its Predecessors Choline, L-Carnitine, and Betaine with Coronary Artery Disease and Artery Stenosis

BACKGROUND: Trimethylamine N-oxide (TMAO) and its predecessor products, choline, L-carnitine, and betaine, were reported to be associated with cardiovascular events risk. However, the association of TMAO and its predecessors with extent of artery stenosis in coronary artery disease (CAD) and in different gender is still unknown. Our aim is to investigate the association of plasma TMAO and its predecessors in CAD and extent of artery lesion in different gender. METHODS: 94 CAD patients and 75 healthy controls (CON) were enrolled. Fasting plasma TMAO, choline, L-carnitine, and betaine were detected using liquid chromatography-tandem mass spectrometry. RESULTS: Elevated plasma TMAO but not choline, L-carnitine, or betaine was observed in CAD (1.46(0.8–2.32) μM) and severe artery stenosis patients (S) (1.62(0.91–2.81) μM) compared with controls and mild artery stenosis (M) (1.18(0.67–1.7) μM in CON; 1.27(0.77–1.82) μM in M, p < 0.05). TMAO was an independent risk factor of CAD and severe artery stenosis (CAD : OR = 1.81, 95%CI: 1.07–3.09, p=0.03; S : OR = 1.36, 95%CI: 1.01–1.84, p=0.04). TMAO was more sensitive in diagnosing CAD and severe artery stenosis from controls in men rather than in women by ROC analysis (AUC for men and women in CAD: 0.64 versus 0.57; AUC for men and women in S: 0.64 versus 0.58), while the combined four metabolites greatly improved diagnostic accuracy in women with CAD and severe artery stenosis (AUC in CAD: 0.64, AUC in S: 0.68). CONCLUSION: The associations of TMAO with CAD and severe artery stenosis were sex-related. TMAO alone was more powerful in determining CAD and artery stenosis in men than women, while a combination of TMAO, choline, L-carnitine, and betaine could be potential biomarkers for diagnosing CAD and artery stenosis in both men and women.