Impact of TMAO Levels on Coronary Microvascular Dysfunction and Prognosis in STEMI Patients

Abstract

AIMS:

Coronary microvascular dysfunction (CMD) following ST-elevation myocardial infarction (STEMI) is a significant predictor for adverse clinical outcomes. However, physiology assessment to diagnose CMD is infrequently performed due to technical difficulties, and the mechanisms of CMD remain poorly understood. This study aims to investigate the potential of Trimethylamine N-oxide (TMAO), a gut microbiota-derived metabolite associated with endothelial dysfunction and atherosclerosis, as a biomarker for CMD.

METHODS AND RESULTS:

Methods: In this prospective, observational cohort study, 210 STEMI patients with multivessel coronary artery disease (CAD) were enrolled after primary percutaneous coronary intervention (PCI). At 3 months post-revascularization, patients underwent coronary physiology assessments, including coronary flow reserve (CFR), fractional flow reserve (FFR), and index of microcirculatory resistance (IMR) via bolus thermodilution. CMD was defined by an IMR ≥ 25 or a CFR < 2.0 and FFR > 0.80. Plasma TMAO, C-reactive protein (CRP), and brain natriuretic peptide (BNP) levels were collected 24 hours post-PCI and 3 months post-procedure. In the absence of an established TMAO threshold, receiver operating characteristic (ROC) curve analysis, including the Delong test and Youden index, was performed to compare the diagnostic value of the biomarkers to determine the optimal TMAO cutoffs for CMD detection. Results: Of the 210 patients enrolled, 85 (40.48%) were female, with a median age of 65 years [interquartile range (IQR): 58.00, 76.00] and a median body mass index (BMI) of 27.39 kg/m² (IQR: [24.56, 30.69]). The area under the ROC curve of TMAO after primary PCI was 0.55 (95% CI 0.46–0.64; p=0.426), while at 3-month follow-up it was 0.80 (95% CI 0.73–0.87; P < 0.001), with an optimal cutoff value of 3.91 yielding a sensitivity of 0.75 (95% CI 0.63–0.86) and a specificity of 0.82 (95% CI 0.76–0.88). The diagnostic performance of TMAO at 3 months was superior to both BNP and CRP, which had an area under the ROC curve of 0.62 and 0.67, respectively. Based on this analysis, patients were classified into low (n=140) and high (n=70) TMAO groups using TMAO≥ 3.91 as the cut-off. Females comprise a higher percentage in the high TMAO group (55.71% vs. 32.86%). Other clinical characteristics and risk factors, such as a history of stroke and CAD, were similar between TMAO groups. In multivariable logistic regression analysis, TMAO levels at 3 months were independently associated with CMD. The cubic spline curve of TMAO at 3 months and the odds of CMD showed a sharp increase in the odds of developing CMD when TMAO was between 3 and 6 μM.

CONCLUSION:

This study demonstrates the potential of TMAO as a biomarker for CMD in STEMI patients. TMAO at 3 months has a better diagnostic performance than traditional biomarkers and is independently associated with an increased risk of CMD. These results suggest that monitoring plasma TMAO levels could be an effective non-invasive strategy in identifying patients with an elevated risk of CMD.