Intra-hospital variation of gut microbiota product, trimethylamine N-oxide (TMAO) predicts future major adverse cardiovascular events after myocardial infarction

Background and Aims Trimethylamine N-oxide (TMAO) has been associated with atherosclerosis and poor outcome. We evaluated the prognostic impact of intra-hospital TMAO variation on patient outcome. Methods and Results Blood samples from 149 patients with acute myocardial infarction (AMI) were taken on admission and discharge. Plasma TMAO was determined by HPLC-MS. The endpoint was a composite three-point MACE (major adverse cardiovascular events) including all-cause mortality, re-infarction or the heart failure (HF) development.Median TMAO concentration on admission was significantly higher than on discharge, (respectively, 7.81 [3.47 – 19.98] vs 3.45 [2.3 – 4.78] μM,p<0.001). After estimating the 3.45 μM TMAO cut-off with the analysis of continuous hazard ratio, we divided our cohort into two groups. The first group included 75 (50.3%) patients whose TMAO levels remained below or decreased under cut-off (low-low/high-low; LL/HL), while the second group included 74 (49.7%) patients whose TMAO levels remained high or increased above the cut-off during hospitalisation (high-high/low-high; HH/LH).During the median 30-month follow-up, 21.5% patients experienced the composite endpoint. At Kaplan-Meier analysis, a trend of increasing MACE risk was observed in patients in the HH/LH group (p=0.05). At multivariable Cox analysis, patients from HH/LH group had more than two times higher risk of MACE during the follow-up than LL/HL group (HR=2.15 [95% CI, 1.03 - 4.5], p=0.04). Other independent predictors of MACE were older age and worse left ventricular systolic function. Conclusions In patients with AMI, permanently high or increasing TMAO levels during hospitalisation are associated with a higher risk of MACE during long-term follow-up.