Relation Of Plasma Trimethylamine N-oxide Levels With Coronary Artery Disease In Patients With Hypertension

Objective:In recent years,the gut microbial metabolite trimethylamine N-oxide(TMAO)has been shown to be a risk factor for cardiovascular disease and is involved in the development of disease.More and more studies have shown that the gut microbial are associated to the pathogenesis of hypertension(HTN)and atherosclerosis.but its association with coronary artery disease(CAD)risk is unclear in HTN patients.Thus,we explored the relationship between plasma TMAO and CAD in this patient cohort.Methods:We enrolled 3 cohorts in this study,including 50 healthy controls,82 HTN patients,and 100 HTN-CAD patients.Coronary atherosclerotic burden was quantified using the Gensini score and number of coronary lesions.Plasma TMAO levels were measured by high performance liquid chromatography tandem-mass spectrometry.The receiver operating characteristic(ROC)analysis of plasma TMAO levels predicts the risk of HTN patients and HTN-CAD patients,and calculate the area under the curve(AUC),sensitivity,specificity,diagnostic threshold.Univariate and multivariate logistic analysis whether plasma TMAO level is an independent risk factor for CAD in HTN patients.In the HTN patients with CAD,the relationship between plasma TMAO level and Gensini high group(Gensini score ?40)and Gensini low group(Gensini score ?39)as well as multivessel disease group and single-vessel group was analyzed,Spearman correlation analysis was used to measure the correlation between plasma TMAO levels and Gensini score and vascular branch disease in patients with HTN-CAD.Results:Median plasma TMAO levels in the control,HTN,and HTN-CAD groups were0.99(0.73-1.27),1.92(1.6-2.48),and 3.12(2.47-3.61)?g/mL,respectively,and there were statistical differences between the groups(P <0.01).The receiver operating characteristic analysis revealed that the best cutoff value of plasma TMAO to predictHTN patients in healthy controls was 1.315ug/mL,90.2%sensitivity and 82%specificity(area under the curve(AUC): 0.925,95% confidence intervals(CI):0.88-0.969)and the best cutoff value of plasma TMAO to predict CAD in patients with HTN was 2.673ug/mL,69%sensitivity and 85.4% specificity(AUC: 0.822,95%CI: 0.759-0.884).Univariate and multivariate regression analysis shown that plasma levels of TMAO was an independent risk factor for CAD in HTN patients.In the 100 HTN patients with CAD,the plasma of TMAO levels were higher in the multivessel disease group than in the single-vessel disease group(p < 0.05)and plasma TMAO levels were significantly higher in the group with high Gensini scores than in the group with low Gensini scores(p < 0.01).Spearman correlation analysis of plasma TMAO levels with Gensini score and number of diseased vessels,the correlation coefficients were 0.299(P <0.01)and 0.246(P <0.05),respectively.Conclusions:TMAO is an independent risk factor of CAD in HTN patients.In HTN-CAD patients,TMAO was positively correlated with coronary atherosclerotic burden.