In-hospital dynamics of trimethylamine N-oxide (TMAO) predicts major adverse cardiovascular events in patients with acute myocardial infarction
Authors: Aleksova A , Fluca A L , Stornaiuolo M , Pani B , Derin A , D'errico S , Novellino E , Sinagra G , Janjusevic M 
Published: June 2024

Abstract

Background
It is widely recognized that gut microbiota and certain diets have a tremendous impact on various cardiovascular diseases (CVD). The gut microbiota-dependent metabolite, trimethylamine N-oxide (TMAO), alters lipid metabolism, endothelial function, leads to oxidative stress, platelet reactivity, inflammation, thrombosis and arteriosclerosis. TMAO is a result from animal food fermentation, such as red meat, egg yolk, and dairy products rich in choline, L-carnitine, and phosphatidylcholine. In addition to diet, circulating TMAO levels are also significantly influenced by genetic factors and overall body condition (presence of co-morbidities).

Purpose
Given the high mortality rate among patients with CVD, it is essential to improve risk stratification protocol. This study aims to evaluate both the in-hospital variation and the long-term effects of TMAO in AMI patients. Previous studies that yield conflicting results attempted to investigate the influence of TMAO by using just one measurement of this molecule.

Methods
Blood samples of AMI survivals were collected on admission and on discharge. The endpoint was a three-point major adverse cardiovascular events (MACE) composed as all-cause mortality, reinfarction and development of heart failure.

Results
The total cohort included 149 patients with AMI, of which 77% were male and the mean age was 64(11) years. The most common pro-atherosclerotic risk factors were hypertension (54.4%) and dyslipidaemia (51%). Median TMAO values was significantly higher on admission than on discharge, (7.81 [3.47 –19.98] vs 3.45 [2.3 – 4.78] μM, respectively, p&lt;0.001).
Using measurements taken at discharge, we determined the TMAO cut-off using continuous hazard ratio analysis. We identified a linear association between values exceeding 3.45 μM and MACE incidence. Afterward, we divided the cohort into 2 groups: LL/HL (low-low/high-low), consisting of 75 patients (50.3%) whose TMAO levels persistently remained below the cut-off or were initially higher and decreased during hospitalization and HH/LH (high-high/low-high), consisting of 74 patients (49.7%) whose TMAO levels remained high or were initially lower and then increased over the cut-off value during hospitalisation.
During the 30 months follow-up, 21.5% of patients experienced the endpoint. Survival analysis showed that patients in the HH/LH group were more likely to experience MACE (p=0.05) (Fig. 1a). The multivariate Cox analysis showed that patients in the HH/LH group were at more than twice the risk of MACE than those in the LL/HL group. In addition, older age and worse left ventricular systolic function were identified as independent predictors of MACE during long-term follow-up (Fig. 1b).

Conclusions
AMI patients with consistently elevated or increasing levels of TMAO experience poorer outcomes. Understanding the dynamics of TMAO values during hospitalisation is predictive of patient outcome.