Trimethylamine N-oxide and cardiovascular outcomes in patients with chronic heart failure after myocardial infarction

Aim Accumulating evidence has demonstrated that intestinal microbiota-dependent trimethylamine N-oxide (TMAO) is involved in the pathogenesis of various cardiovascular diseases. The present study was designed to investigate the prognostic value of TMAO in patients with chronic heart failure (CHF) after myocardial infarction (MI). Methods and results We included 1208 CHF patients after MI in a prospective cohort study and determined the association between plasma TMAO and cardiovascular outcomes using Cox regression analysis. Patients with elevated TMAO levels were more likely to be older and have histories of atrial fibrillation and diabetes. Cox regression analysis indicated that TMAO was a significant predictor of major adverse cardiac events (MACE) (hazard ratio = 2.31, 95% confidence interval 1.42-3.59, P < 0.01) following adjustment for conventional risk factors. Integrated discrimination and net reclassification improvements for MACE were markedly improved by addition of TMAO to the model of traditional risk factors. The Kaplan-Meier survival analysis showed that MACE risk increased with the elevation in TMAO levels and this positive correlation became more significant when TMAO levels were higher than the median. TMAO was also found to be an independent predictor of all-cause mortality (hazard ratio = 2.15, 95% confidence interval 1.37-3.24, P < 0.01) after adjusting for traditional risk factors. Conclusions Our study suggests that TMAO is a valuable prognostic indicator of MACE in patients with CHF after MI.