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, 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.