TMAO, formed by gut microbiota, associates with incident MACE and mortality
Gut microbiota-dependent trimethylamine N-oxide in acute coronary syndromes: a prognostic marker for incident cardiovascular events beyond traditional risk factorsLiterature - Li XS, Obeid S, Klingenberg R, et al. - Eur Heart J, 2017, Epub ahead of print
- Within the first 30 days and 6 months, Cleveland patients with higher average plasma TMAO levels at presentation experienced incident MACE more often. Also after 7 years, TMAO levels were on average higher in patients that died (all P<0.001). This was a dose-dependent relationship as patients with the lowest quartile TMAO levels had the highest survival rates, whereas patients of the highest TMAO quartile had the lowest survival rates (log rank all quartiles P<0.001).
- The frequency of experiencing MACE at 30 days and 6 months following presentation increased with increasing quartiles of TMAO levels as follows: 30-day and 6-month frequency of 30.1% and 31.6% in quartile 1, 32.6% and 37.1% in quartile 2, 40.2% and 43.9% in quartile 3, and 49.6% and 53.4% in quartile 4 (P< 0.01 for trend).
- After multivariable correction, TMAO levels predicted risk of MACE at 30 days (OR 4th vs. lowest quartile 6.30, 95% CI: 1.89-21.00, P<0.01) and 6 months (OR 4th quartile 5.65, 95% CI: 1.91-16.74, P<0.01) and 7-years mortality (HR 4th quartile 1.81, 95% CI: 1.04-3.15, P<0.05).
- Among patients who were initially cTnT-negative at presentation, TMAO levels were higher amongst those who had subsequently experienced an incident MACE at 30 days (median IQR 5.5 µM (3.5-9.9) vs. 3.7 µM (3.4-6.9), P<0.001) and 6 months (median IQR 5.3 µM (3.3-9.6) vs 3.7 µM (2.4-6.8), P<0.0001), compared with those who did not. Also for cTnT negative patients the frequency of MACE at 30 days and 6 months increased with TMAO quartiles (P trend < 0.05) and remained a significant predictor for MACE at 30 days (OR 4th quartile 5.83, 95% CI: 1.79-19.03, P<0.01) and 6 months (OR 4th quartile 5.51, 95% CI: 1.90-16.01, P<0.001) in a multivariate analysis.
- The Swiss cohort showed similar results; higher average TMAO levels amongst patients who experienced adverse outcomes, including 1-year MACE (3.75 mM (2.14–7.04), n= 190, vs. 2.80 µM (1.91–4.55), n= 1493; P<0.001), and 1-year mortality (5.95 mM (2.79–13.08), n= 71, vs. 2.82 mM (1.92–4.61), n= 1612; P<0.001). Also quartile levels of TMAO associated with long-term incident MACE risk (log rank P<0.001) and elevated levels of TMAO remained a significant predictor of MACE (HR 4th quartile [adjusted] 1.57, 95% CI: 1.03-2.41, P<0.05).
TMAO levels were associated with short-term risk of MACE and long-term mortality in two independent ACS cohorts comprising sequential patients who presented with complaint of chest pain and suspected ACS. The relationship with risk of incident MACE was dose-dependent. Therefore, gut microbiota-dependent metabolite, TMAO, may serve as a clinically useful and potentially modifiable prognostic marker.