The association between trimethylamine N-oxide levels and coronary microvascular dysfunction and prognosis in patients with ST-elevation myocardial infarction

Atherosclerosis. 2024 Nov:398:118597. doi: 10.1016/j.atherosclerosis.2024.118597. Epub 2024 Sep 12.

Abstract

Background and aims: Coronary microvascular dysfunction (CMD) is common after ST-elevation myocardial infarction (STEMI), leading to adverse clinical outcomes. However, its diagnosis remains difficult, and mechanisms elusive. This study explores the role of Trimethylamine N-oxide (TMAO), a gut microbiota metabolite, as a potential biomarker for diagnosing CMD in STEMI patients.

Methods: This prospective, observational study enrolled 210 STEMI patients with multivessel coronary artery disease who underwent primary percutaneous coronary intervention (PCI). TMAO levels were measured at baseline, 3 months, and 12 months post-PCI, whilst coronary physiology was assessed at 3 months. The primary endpoint was the incidence of CMD at 3 months, with the secondary endpoint being major adverse cardiovascular and cerebrovascular events (MACCE) at 12 months. An additional 59 consecutive patients were enrolled for validation.

Results: TMAO levels varied from baseline to 3 months, then stabilised. The areas under the ROC curve for baseline TMAO and TMAO at 3-month were 0.55 (95 % CI 0.46-0.64; p = 0.426), and 0.80 (95 % CI 0.73-0.87; p < 0.001), respectively. The optimal cut-off for TMAO at 3-month to diagnose CMD was 3.91, with similar sensitivity and specificity in the derivation and validation cohort. The incidence of MACCE was higher in patients with TMAO≥3.91 (41.4 % vs 10.7 %; p < 0.001). The addition of 3-month TMAO improved the diagnostic performance of traditional risk factors.

Conclusion: TMAO is a robust biomarker for CMD and is significantly associated with the incidence of MACCE. TMAO has the potential in guiding clinical decision-making and suggests an interplay between gut microbiota and CMD.

Keywords: Coronary microvascular dysfunction; Gut microbiota; Percutaneous coronary intervention (PCI); ST-Elevation myocardial infarction; Trimethylamine N-Oxide (TMAO).

Publication types

  • Observational Study

MeSH terms

  • Aged
  • Biomarkers* / blood
  • Coronary Artery Disease / blood
  • Coronary Artery Disease / diagnosis
  • Coronary Circulation
  • Female
  • Gastrointestinal Microbiome
  • Humans
  • Male
  • Methylamines* / blood
  • Microcirculation
  • Middle Aged
  • Percutaneous Coronary Intervention* / adverse effects
  • Predictive Value of Tests
  • Prognosis
  • Prospective Studies
  • Risk Factors
  • ST Elevation Myocardial Infarction* / blood
  • ST Elevation Myocardial Infarction* / diagnosis
  • Time Factors
  • Treatment Outcome

Substances

  • trimethyloxamine
  • Methylamines
  • Biomarkers