Plasma Trimethylamine N-Oxide as a Novel Biomarker for Plaque Rupture in Patients With ST-Segment-Elevation Myocardial Infarction

Abstract

Background: Trimethylamine N-oxide (TMAO) is reported to promote the pathogenesis of atherosclerosis and be associated with cardiovascular events risk. It is unknown whether plasma TMAO is associated with plaque morphology in patients with acute myocardial infarction. We investigated the relationship between the culprit plaque morphology and plasma TMAO concentration in patients with ST-segment-elevation myocardial infarction.

Methods and results: A prospective series of 211 patients with ST-segment-elevation myocardial infarction who underwent preintervention optical coherence tomography examination for the culprit lesion were enrolled; 77 and 69 patients were categorized as plaque rupture and plaque erosion, respectively. Plasma TMAO levels, detected using stable isotope dilution liquid chromatography tandem mass spectrometry, were significantly higher in patients with plaque rupture than in those with plaque erosion (3.33 μM; interquartile range: 2.48-4.57 versus 1.21 μM; interquartile range: 0.86-1.91; P<0.001). After adjustments for traditional risk factors, elevated TMAO levels remained independently correlated with plaque rupture (adjusted odds ratio: 4.06, 95% CI, 2.38-6.91; P<0.001). The area under the receiver operating characteristic curve for plaque rupture versus plaque erosion was 0.89. At a cutoff level of 1.95 μM, TMAO had a sensitivity of 88.3% and specificity of 76.8% in discriminating plaque rupture from plaque erosion.

Conclusions: High levels of plasma TMAO independently correlated with plaque rupture in patients with ST-segment-elevation myocardial infarction. Moreover, TMAO might be a useful biomarker for plaque rupture to improve risk stratification and management in patients with ST-segment-elevation myocardial infarction.

Clinical trial registration: URL: https://www.clinicaltrials.gov . Unique identifiers: NCT03593928.

Keywords: atherosclerosis; biomarkers; isotopes; myocardial infarction; tandem mass spectrometry.