Intestinal Microbial Metabolite Trimethylamine Oxide And The Pathological Characteristics And Prognosis Of Acute Myocardial Infarction Plaques

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 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(STEMI).Methods and Results:A prospective series of 211 patients with STEMI who underwent pre-intervention optical coherence tomography(OCT)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[IQR]:2.48-4.57 vs.1.21 μM;IQR: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%confidence interval:2.38-6.91,P<0.001).The area under the receiver operating characteristic curve(AUC)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 STEMI.Moreover,TMAO might be a useful biomarker for plaque rupture to improve risk stratification and management in patients with STEMI.Background:Trimethylamine N-oxide(TMAO)has been demonstrated to promote the pathogenesis of atherosclerosis.It is unknown whether plasma TMAO is associated with neoatherosclerosis,an important underlying mechanism of very late stent thrombosis(VLST).We investigated the relationship between neoatherosclerosis and plasma TMAO concentration in patients with ST-segment elevation myocardial infarction caused by VLST.Methods:Optical coherence tomography(OCT)was used to evaluate the culprit lesion morphology.Thirty consecutive patients with VLST were enrolled;17 patients were identified as neoatherosclerosis and 13 without neoatherosclerosis.Patients with neoatheroslcerosis were further divided into two subgroups,including 11 patients with plaque rupture and 6 without plaque rupture,respectively.Results:The plasma TMAO levels were significantly higher in patients with VLST than in healthy individuals(3.64 μM[2.08-4.58]vs.1.47μM[0.89-2.75],p<0.001).Within VLST patients,plasma TMAO levels were significantly higher in patients with neoatherosclerosis than in those without neoathersclerosis(4.35 μM[3.43-5.37]vs.2.02μM[1.30-3.59];p<0.001).The logistic analysis revealed that plasma TMAO was a predictor of neoatherosclerosis(odds ratio:3.35,95%confidence interval:1.40-8.03;p=0.007).In addition,patients with neoatherosclerosis with plaque rupture had significantly elevated plasma TMAO concentration than those without plaque rupture(5.29 μM[4.35-7.21]vs.3.63 μM[3.02-3.92];p=0.012).The area under receiver operating characteristic curve for patients with neoatherosclerosis versus those without neoatherosclerosis was 0.87,the corresponding sensitivity and specificity was 0.77 and 0.88,respectively.Conclusions:High plasma TMAO predicted neoatherosclerosis in patients with VLST.Background:The gut microbiota dependent metabolite trimethylamine N-oxide(TMAO)is demonstrated to promote atherosclerosis and cardiovascular diseases.Plasma TMAO levels correlated with the coronary atherosclerotic burden in patients with stable coronary diseases.However,the association between plasma TMAO levels and the coronary atherosclerotic burden in patients with ST-segment elevation myocardial infarction(STEMI)is not yet investigated.Methods:The study cohort comprised of two independent cohorts,including 335 patients with STEMI who accepted emergent percutaneous coronary interventions in Fuwai hospital,and another 53 healthy volunteers to provide the normal reference values of TMAO.The atherosclerotic burden of coronary arteries was calculated by number of diseased coronary vessels and the SYNTAX scores.Plasma TMAO levels were detected using stable isotope dilution liquid chromatography tandem mass spectrometry OResults:The plasma TMAO levels in patients with STEMI and healthy controls were 2.18μM(1.34-3.90)and 1.23 μM(0.84-2.42),respectively.Regarding the 335 STEMI patients,plasma TMAO levels were significantly elevated in patients with multi-vessel disease and intermediate-high SYNTAX scores than in those with single-vessel disease and low SYNTAX(2.46 vM[1.47-3.99]vs.1.65 μM[1.01-3.09],P<0.001 and 3.34 μM[1.87-4.58]vs.1.93 μM[1.27-3.34],P<0.001,respectively).The ordinal logistic regression analysis revealed that elevated plasma TMAO was associated with high SYNTAX score and multi-vessel disease(OR 1.17,95%CI:1.09-1.27;P<0.001 and OR 1.16,95%CI:1.04-1.30;P=0.008,respectively).After adjustment for several traditional cardiac risk factors,high plasma TMAO remained independently predicted high SYNTAX scores and multi-vessel disease(OR 1.16,95%CI:1.06-1.29;P=0.001;OR 1.15,95%CI:1.01-1.32;P=0.035,respectively).Conclusions:Plasma TMAO concentrations independently predicted coronary atherosclerotic burden in patients with STEMI.Moreover,plasma TMAO might serve as a potential biomarker to improve the risk stratification of STEMI patients,as well to reduce the progression of atherosclerotic burden.Background:trimethylamine N-oxide(TMAO)and Myeloperoxidase(MPO)are novel biomarkers appeared to involved in different pathophysiological processes of coronary artery diseases(CAD).TMAO,a gut microbiota dependent metabolite,was reported to be atherogenic and associated with the clinical outcomes of patients with CAD.MPO was an inflammatory biomarker released at neutrophil activation and was demonstrated to be involved in the pathogenesis and progression of atherosclerosis.MPO also relates to the prognosis of CAD patients.However,the utility of the combination of TMAO and MPO is unknown.In this study,we investigated the value of the combination of MPO and TMAO in predicting the clinical outcomes of patients with ST-segment elevation myocardial infarction(STEMI).Methods:Consecutive patients with STEMI who underwent primary percutaneous coronary intervention were prospectively enrolled in this study.The primary endpoints of this study was major adverse cardiovascular events(MACE),including a composite of all-cause mortality,nonfatal myocardial infarction,and stroke.The second endpoint was all-cause mortality.Plasma TMAO concentration was detected using stable isotope dilution high-performance liquid chromatography with online electrospray ionization tandem mass spectrometry and plasma MPO level was quantified by enzyme-linked immunosorbent assay using a commercial kit.Area under the receiver-operator characteristic curve(AUC)and net reclassification improvement(NRI)and integrated discrimination improvement(IDI)were calculated to evaluate the increment of predictive value for the combination of MPO and TMAO in predicting adverse clinical outcomes.Results:Four hundred fifty-eight consecutive patients with STEMI were enrolled in this study.Of them,41 patients suffered MACE and 26 patients had all-cause mortality at 1 year follow up.Plasma TMAO and MPO each independently predicted MACE for patients with STEMI(HR 5.27,95%CI:2.11-13.16,P<0.01 and HR 2.59,95%CI:1.31-5.12,P<0.01,respectively).ROC curve indicated that the AUC of TMAO,MPO and their combination in predicting MACE of STEMI patients was 0.727,0.658,and 0.774,respectively.The combination of TMAO and MPO significantly improved the predictive value of TMAO(NRI 53.8%,P=0.001;IDI 7%P=0.005)and MPO(NRI 49.5%,P<0.001;IDI 4.3%,P=0.010)alone in predicting the MACE of STEMI patients.Kaplan-Meier curve indicated that there existed a graded increased risk of MACE between patients with different plasma TMAO and MPO levels.Cox regression analysis showed that patients with high plasma level of TMAO and MPO had an independent increased risk of MACE compared to those with low plasma level of TMAO and MPO(HR 11.43,95%CI:2.65-49.32;P<0.01).In addition,the combination of TMAO and MPO also significantly improved the predictive value of TMAO or MPO alone in predicting the all-cause mortality of patients with STEMI.Conclusions:Plasma level of MPO and TMAO each independently predicted the clinical outcomes of patients with STEMI.Furthermore,the combination of TMAO and MPO enables more accurate prediction of adverse cardiovascular events compared to TMAO or MPO alone.