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.