TMAO, a Prognostic Marker for Cardiovascular Events in ACS

Study Questions:

What is the relationship of trimethylamine N-oxide (TMAO) levels with incident cardiovascular risks among patients presenting with acute coronary syndrome (ACS)?


The authors investigated the relationship of TMAO levels with incident cardiovascular risks among sequential patients presenting with ACS in two independent cohorts. The US cohort (n = 530) was a single-center, prospective cohort study approved by a large cardiac center’s Institutional Review Board. The Swiss ACS Cohort is part of the Special Program University Medicine (SPUM), including all patients who underwent coronary angiography for ACS at one of the participating University Hospitals (Zurich, Bern, Lausanne, Geneva). Odds ratio (OR) for major adverse cardiac events (MACE) and corresponding 95% confidence interval (CI) were calculated using both univariable (unadjusted) and multivariable (adjusted) logistic regression models.


In the US cohort, comprised of sequential subjects (n = 530) presenting to the Emergency Department (ED) with chest pain of suspected cardiac origin, an elevated plasma TMAO level at presentation was independently associated with risk of MACE (including myocardial infarction, stroke, need for revascularization, or death) over the ensuing 30-day (fourth quartile [Q4] adjusted OR, 6.30; 95% CI, 1.89-21.0; p < 0.01) and 6-month (Q4 adjusted OR, 5.65; 95% CI, 1.91-16.7; p < 0.01) intervals. TMAO levels were also a significant predictor of the long-term (7-year) mortality (Q4 adjusted HR, 1.81; 95% CI, 1.04-3.15; p < 0.05). Interestingly, TMAO level at initial presentation predicted risk of incident MACE over the near-term (30 days and 6 months) even among subjects who were initially negative for troponin T (<0.1 ng/ml) (30 days; Q4 adjusted OR, 5.83; 95% CI, 1.79-19.03; p < 0.01). The prognostic value of TMAO was also assessed in an independent multicenter Swiss cohort of ACS patients (n = 1,683) who underwent coronary angiography. TMAO again predicted enhanced MACE risk (1 year; adjusted Q4 hazard ratio, 1.57; 95% CI, 1.03–2.41; p < 0.05).


The authors concluded that TMAO levels among patients presenting with chest pain predict both near- and long-term risks of incident cardiovascular events.


This study suggests that TMAO is an important prognostic marker in predicting both near- and long-term adverse cardiovascular events beyond traditional risk factors and laboratory tests in the setting of ACS. TMAO levels are modifiable, both with diet, and with potential therapeutics under development, and may offer new prospects for treatment strategies at both levels of primary and secondary prevention. The findings of this study need to be validated in additional prospective multicenter studies.

Clinical Topics: Acute Coronary Syndromes, Invasive Cardiovascular Angiography and Intervention, Noninvasive Imaging, Prevention, Interventions and ACS, Interventions and Imaging, Angiography, Nuclear Imaging, Diet

Keywords: Acute Coronary Syndrome, Angiography, Secondary Prevention, Cardiovascular Diseases, Chest Pain, Coronary Angiography, Diet, Emergency Service, Hospital, Myocardial Infarction, Primary Prevention, Risk Factors, Stroke, Troponin T

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