Trimethylamine-N-oxide has prognostic value in coronary heart disease: a meta-analysis and dose-response analysis

Background Previous clinical studies have suggested that trimethylamine-N-oxide (TMAO) could contribute to the development of atherosclerosis cardiovascular disease. However, the synthetic analysis in coronary heart disease (CHD) was not yet performed. We aimed to clarify the relationship between elevated plasma concentrations of TMAO and the incidence of major adverse cardiovascular events (MACE) in CHD patients. Methods Meta-analysis and dose-response analysis of hazard ratio data from prospective observational studies reporting on the association between TMAO plasma concentrations and the incidence of MACE in patients with CHD were conducted. Results Of the 2369 published articles identified in the search, seven papers, with data from nine cohort studies (10,301 patients), were included in the meta-analysis. Combined data showed that elevated plasma TMAO concentrations could increase 58% higher risk of MACE in patients with CHD (hazard ratios [HR]: 1.58; 95% confidence interval [CI] = 1.35-1.84, P = 0.000). For follow-up >= 1 year, it was associated with 62% higher risk of MACE in patients with longer-term than shorter-term (HR for follow-up >= 4 years: 1.96; 95% CI = 1.52-2.52 vs one to 3 years: 1.34; 95% CI = 1.26-1.43, P = 0.004). The dose-response analysis revealed a 'J' shaped association between TMAO concentration and the incidence of MACE (P = 0.033), with the concentration above 5.1 mu mol/L being associated with HR of > 1. Conclusions Elevated levels of TMAO are associated with an increased incidence of MACE in patients with CHD. TMAO concentration of 5.1 mu mol/L may be a cut-off value for prognosis.