In–hospital changes of plasma trimethylamine n–oxide (tmao) levels predicts major adverse cardiovascular events in patients with acute myocardial infarction

Abstract Background Trimethylamine N–oxide (TMAO), a gut microbiota–dependent metabolite, originates from choline, L–carnitine and phosphatidylcholine metabolism. It is abundant in animal–derived foods like red meat, and egg yolk. TMAO plays a crucial role in cardiovascular diseases (CVDs), altering lipid metabolism and endothelial function, inducing oxidative stress, platelet reactivity, inflammation, and arteriosclerosis. Aim and Methods Given the high mortality rate of CVDs patients, it is necessary to improve strategies to optimize stratification risk protocols. Previous studies about the impact of TMAO on outcomes relying on a singular measurement had yielded conflicting results. This study aims to assess the impact of in–hospital TMAO fluctuations in individuals with acute myocardial infarction (AMI). Blood samples from AMI survivors were obtained on admission and 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 comprised 149 AMI patients, with 77% males and a mean age of 64(11) years. Main pro–atherosclerotic risk factors included dyslipidaemia (51%) and hypertension (54.4%). Median TMAO values were significantly higher on admission than discharge (7.81[3.47–19.98] vs. 3.45[2.3–4.78] μM, respectively, p<0.01). TMAO measurements on discharge were used to determine the metabolite cut–off through continuous hazard ratio analysis, showing a linear association with values exceeding 3.45 μM and MACE incidence. The cohort was divided into two groups: low–low/high–low (LL/HL), with 75 patients (50.3%) with persistently low or initially higher and decreasing TMAO levels, and high–high/low–high (HH/LH), with 74 patients (49.7%) exhibiting consistently high or initially lower but increasing TMAO levels during hospitalization. Over the 30–months follow–up, 21.5% of patients experienced MACE. Survival analysis revealed that patients in the HH/LH group were more likely to experience the endpoint (p=0.05). Multivariate Cox analysis demonstrated that patients in the HH/LH group faced more than twice the risk of MACE compared to those in the LL/HL group, along with older age and impaired left ventricular systolic function. Conclusions AMI patients with consistently high or escalating TMAO levels face unfavourable outcomes. Understanding the dynamics of TMAO throughout hospitalization may be a predictive factor for patient outcomes.