Correlation Between Plasma TMAO Levels And Severity Of Coronary Artery Disease And Effects Of Ezetimibe On Plasma TMAO Levels

Objective This study was designed to investigate the correlation between gut microbiota metabolite TMAO and severity of coronary artery disease and effects of lipid-lowering drugs(ezetimibe)on plasma TMAO levels.Materials and methods One hundred and seventeen hospitalized patients were enrolled from Department of Cardiology of the xinhua hospital affiliated to Shanghai jiaotong university of medicine dating from November 2015 to January 2016 for the first time,all patients were checked by CAG(coronary angiography),20 patients who wereexcluded of CHD by CAG were control group,(mean age 62±8.6years old).120 cases diagnosed as CHDwere test group(mean age 65.92±8.72 years old).All the subjects were measured by TG,TC,LDL-c,HDL-c,UA,Cys-C HBA1 c,Hs-CRP,NT-pro BNP,e GFR and other indicators at baseline.By color doppler echocardiography to determine LVEF.Plasma TMAO levels were measured by liquid chromatography tandem(HPLC-MS/MS).Grouping: All patients with suspected coronary heart disease(CHD)accepted coronary angiography and were divided into CHD group and control group,120 CHD cases were divided into Three groups by the results of coronary angiography:single vesseldisease group(37 cases),the double vesseldisease group(40 cases),and multi-vesseldisease group(43cases);2,according to whether the patient has DM or HBP,the CHD group was divided into two groups,40 patients with DM,80 cases of non-DM(mean age);and 47 cases with HBP,73 cases of non-HBP;3,We studied the correlation between the plasma TMAO levels and Gensini score,patients with CHD were divided into divided into low score group(51 cases),the high score group(69 cases mean age)according to the results of the Gensini score.Interventions: All patients with CHD were randomly divided into 3 groups:simvastatin group(simvastatin 10 mg/d),ezetimibe group(10 mg/d),ezetimibe + simvastatin group(ezetimibe 10 mg + 10 mg of simvastatin)and control group,last for 1 month of therapy.all patients maintained balanced diet and had not taken antibiotics or probiotics within the past month.After 1 month therapy,Plasma TMAO level,TG,TC,LDL-c,HDL-c levels weremeasured by The same method.This study was designed to investigate the effects of lipid-lowering drugs(simvastatin and ezetimibe)on plasma TMAO levels.Results 1.Compared with the CHD group,Plasma TMAO levels were significantly higher than the control group(P<0.05),while the Gensini score was significantly higher than the control group,either(P<0.05).2.Compared with the CHD subgroup,Plasma TMAO levels were significantly higher in the group of higher Gensini score(>30 score)than the group of lower Gensini score(<30 score)(P<0.05).3.Plasma TMAO levels in single,double and multi-vessel disuse of CHD Was gradually higher,the difference between multi-vessel disuse or double disuse Was statistically significant(P<0.05).4.In CHD+DM group,Plasma TMAO levels was significantly Higher than that in the CHD group(P<0.05),while there was no significant difference between CHD+HBP group and CHD group.5.In CHD group,Plasma TMAO levels and Gensini score which represents the severity of coronary artery disease was positively correlated significantly(r = 0.711,P < 0.05).Serum Hcy levels were positively correlated with Gensini score,the difference Was statistically significant(r=0.607,P<0.05).and Plasma TMAO levels were positively correlated with Serum Hcy levels,the difference Was statistically significant(r=0.834,P<0.05).6.After 1 month therapy of ezetimibe or simvastatin singlely,Plasma TMAO levels were lower than before but there was no statistical difference.After the intervention of ezetimibe and simvastatin treatment,plasma TMAO levels were significantly decrease(P<0.05).Conclusion Plasma TMAO levels,coronary artery lesion counts,coronary stenosis Gensini score were positively correlated,suggesting that TMAO were correlated with the severity of coronary atherosclerosis.Plasma TMAO levels may be an independent risk factor for coronary heart disease.In CHD patients with diabetes mellitus,plasma TMAO levels were significantlyincreased,indicating that diabetes mellitus may disturb the metabolism of TMAO.disease.Plasma TMAO levels is positively correlated with HCY.After the Intervention of ezetimibe and simvastatin treatment,plasma TMAO levels were significantly decreased,This may have significance for the treatment of CHD.