Objective: This study examined the relationship of plasma trimethylamine N-oxide (TMAO), a gut microbiota-derived metabolite, with both disease severity and short-term prognosis in acute myocardial infarction (AMI) patients.

Methods: This retrospective observational study was performed at a single center and comprised 60 AMI patients along with 30 controls with angiographically normal or near-normal coronary arteries (stenosis <20% in all major epicardial vessels). Plasma TMAO levels were measured at admission via high-performance liquid chromatography-tandem mass spectrometry. The severity of coronary artery disease was graded according to the Gensini score. Patients were followed up for 6 months after discharge, and the occurrence of major adverse cardiovascular events (MACEs) within this period was ascertained retrospectively from hospital electronic medical records and routine cardiology follow-up documentation.

Results: Compared to controls, AMI patients had significantly higher plasma TMAO levels
(median 5.80 vs. 2.10 μmol/L, P < .001). Consistent with its elevation, TMAO demonstrated a strong positive correlation with the Gensini score (rs = 0.998, P < .001) and peak troponin I (rs = 0.996, P < .001). A high TMAO level (>5.80 μmol/L) was ndependently associated with an increased risk of 6-month MACE (hazard ratio = 2.45, 95% CI: 1.38-4.35, P = .002). Furthermore, incorporating TMAO into traditional clinical models enhanced their predictive performance, yielding a modest yet statistically significant improvement in the area under the curve from 0.880 to 0.884 (P = .012).

Conclusion: Elevated plasma TMAO is associated with more severe coronary artery disease, greater myocardial injury, and worse short-term prognosis in AMI patients, offering incremental prognostic value beyond conventional risk factors.