The Effect Of Compound Panax Notoginseng Granule On Trimethylamine Oxide And Trimethylamine Of Acute Coronary Syndrome Patients

ObjectiveLatest studies have showed that the metabolites of gut microbiota,trimethylamine(TMA)and trimethylamine oxide(TMAO),are associated with the incidence and development of acute coronary syndrome(ACS).However,it is rarely reported on the intervention of Chinese medicine on TMA/TMAO.The objective is to observe the distribution of TMAO and TMA in patients with ACS.With the intervention of Compound Panax Notoginseng Granule,the Chinese medicine that can promote blood circulation and resolve phlegm,we aim to observe how the levels of TMAO and TMA will be impacted.MethodsCase control and prospective randomized controlled double-blind was applied when conducting the study.From June 2017 to November 2017,82 patients at Guangdong Provincial Hospital of Chinese Medicine meeting the diagnostic criteria of ACS and obstruction of phlegm and stasis syndrome were enrolled in the case group.In the same period,20 patients with normal coronary angiography were enrolled in the control group.An observational study was performed to compare the distribution difference of TMA/TMAO between two groups.Furthermore,in the intervention study,80 patients selected from the case group meeting the inclusion criteria were enrolled and randomized to Compound Panax Notoginseng Granule treatment(n=40)or placebo(n=40).In the case control study,the methods of liquid chromatogram combining with multiple reaction monitoring(LC-MRM)were used to measure the different plasma concentrations of TMAO and TMA between two groups.Meanwhile,the difference of clinical characteristic,score of obstruction of phlegm and stasis syndrome and levels of blood uric acid,blood lipid and high-sensitivity C-reactive protein(Hs-CRP)between two groups were compared.In the randomized-control study,on first day of admission the treatment group began to take the Compound Panax Notoginseng Granule and the placebo group to take the placebo granule for three months.Both groups took the granule one package a time and twice a day.After the treatment,the different changes of TMAO and TMA plasma levels,blood lipid levels,Hs-CRP levels and score of obstruction of phlegm and stasis syndrome between two groups were compared.We also compared the different incidence of major adverse cardiovascular event(MACE)and adverse drug reactions between two groups.In conclusion,we make the observation of the effect of Compound Panax Notoginseng Granule on plasma levels of TMAO and TMA and make the comprehensive evaluation of its therapeutic effect.Results1.In the case control study,with significant difference(P<0.05),the level of Hs-CRP and score of obstruction of phlegm and stasis syndrome are higher in case group than control group and the high density lipoprotein cholesterin(HDL-C)level are higher in control group.The difference of gender between two groups is significant(P<0.05).The amount of people with smoking history is larger in case group than control group significantly(P<0.05).Plasma level of TMAO is higher in case group than control group[1.93(1.23-3.14)vs 1.54(0.98-1.97)μmol/L]with significant difference(P<0.05).There is no significant difference of TMA plasma level between two groups(P>0.05).2.In the randomized-control study,the difference of gender,age,risk factor,coronary angiography,N-terminal pro-B-type natriuretic peptide(NT-proBNP)level,creatine kinase(CK)level,creatine kinase MB(CKMB)level,cardiac troponin I(cTnI)level and ultrasonic cardiogram between two groups are not significant(P>0.05).3.In the r andomized-control study,before treatment,the difference of TMAO levels between two groups is not significant(P>0.05).After treatment,TMAO levels of both groups are increased with no significant difference(P>0.05).And the levels of TMA are higher in control group than treatment group significantly(P<0.05)before treatment.Using analysis of covariance to adjust,after treatment,the levels of TMA decrease in treatment group and increase in control group,with significant difference(P<0.05).4.In the randomized-control study,before treatment,the difference of score of obstruction of phlegm and stasis syndrome between two groups is not significant(P>0.05).After treatment,the score of both group are reduced,which is more significantly in treatment group than control group(P<0.05).5.In the randomized-control study,before treatment,the difference of blood lipid levels between two groups is not significant(P>0.05).After treatment,the levels of low density lipoprotein cholesterin(LDL-C)reduce significantly in treatment group than control group(P<0.05).And the levels of Hs-CRP are higher in treatment group than control group significantly(P<0.05)before treatment.Using analysis of covariance to adjust,after treatment,the reduction of Hs-CRP levels in both groups are equality,without significant difference(P>0.05).6.In the randomi zed-control study,the incidence of MACE and adverse drug reactions are not significantly different between two groups(P>0.05).ConclusionThe increase level of TMAO is related to the incidence of ACS.The levels of TMAO in ACS patients are significant higher than the control group.Compound Panax Notoginseng Granule,the Chinese medicine of promoting blood circulation and resolving phlegm,can reduce the levels of gut microbiota metabolite TMA,the levels of LDL-C and the score of obstruction of phlegm and stasis syndrome in ACS patients with obstruction of phlegm and stasis syndrome.