Association Between Plasma Trimethylamine N-oxide and Neoatherosclerosis in Patients With Very Late Stent Thrombosis

Abstract

BackgroundTrimethylamine N-oxide (TMAO) has been shown to promote the development of atherosclerosis. However, the relationship between plasma TMAO and neoatherosclerosis, an important underlying mechanism of very late stent thrombosis (VLST), is unknown. MethodsThis post hoc study investigated the association between TMAO and neoatherosclerosis in 2 independent cohorts. These included a control group of 50 healthy volunteers and a study cohort of 50 patients with VLST who presented with ST-segment elevation myocardial infarction and underwent optical coherence tomography examination. Of the 50 patients with VLST, 23 had neoatherosclerosis and 27 did not have neoatherosclerosis. Patients with neoatherosclerosis were further divided into 2 subgroups, including 14 patients with plaque rupture and 9 without plaque rupture. ResultsThe plasma TMAO levels, detected using mass spectrometry, were significantly higher in patients with VLST than in healthy individuals (median [interquartile range], 2.50 [1.67-3.84] vs 1.32 [0.86-2.44] μM; P < 0.001). Among the patients with VLST, the plasma TMAO levels were significantly higher in patients with neoatherosclerosis than in those without neoatherosclerosis (3.69 [2.46-5.29] vs 1.96 [1.39-2.80] μM; P < 0.001). In addition, in patients with neoatherosclerosis, patients with plaque rupture had significantly higher plasma TMAO concentrations than those without plaque rupture (4.51 [3.41-5.85] vs 2.46 [2.05-3.55] μM; P = 0.005). Multivariate analysis indicated that TMAO was an independent predictor of neoatherosclerosis (odds ratio, 3.41; 95% confidence interval, 1.59-7.30; P = 0.002). Moreover, the area under the receiver operating characteristic curve for TMAO, differentiated by neoatherosclerosis, was 0.85. ConclusionsPlasma TMAO was significantly correlated with neoatherosclerosis and plaque rupture in patients with VLST.