Correlation Between Coronary Artery Lesions And EMPs、hs-CRP In Patients With Acute Myocardial Infarction

BackgroundWith the rapid development of social economy in China,great changes have taken place in the way of life of the people.Especially the aging of population and the accelerating process of urbanization,the risk factors of cardiovascular disease in China are gradually highlighted,leading to the increasing number of cardiovascular diseases in china.It is estimated that the number of cardiovascular diseases in China is 290 million,among which coronary heart disease has reached 11 million.According to the "2016 China health and family planning" statistical yearbook,the mortality rate of acute myocardial infarction(AMI)has been increasing rapidly since 2005,which has brought serious burden to the national economy,and has higher mortality and disability rate.According to statistics,in 2015 the medical expenses reached 15 billion 340 million yuan,caused a huge economic burden to patients,families and society,has become a major public health problem in China’s economic development,the prevention and treatment of AMI is urgent.The basic cause of acute myocardial infarction is atherosclerosis(As).Atherosclerotic plaques cause severe stenosis of the lumen and lack of blood supply to the heart,while the collateral circulation is not fully established.On this basis,once the blood supply is further reduced or interrupted,myocardial ischemia can be caused by severe and lasting acute ischemia for more than 30 minutes.Endothelial dysfunction is a key factor in the occurrence of atherosclerosis and initial stage.The endothelial cells are not only the material exchange between blood and tissue barrier,but also the largest endocrine organ,which can generate bioactive substances to maintain the normal function of vascular permeability,vascular,fibrinolytic activity and inflammatory reaction.Changes in normal metabolism of endothelial cells can lead to vascular damage.Endothelial microparticles(EMPs)refers to the vascular endothelial cells in a variety of physical and chemical stimuli caused by the formation of the membrane to the formation of the diameter of about 0.05-1.0 mu m ultramicro vesicles.Chemical(such as apoptosis inducers,growth factors,stimulants)and physical factors(blood flow shear stress)are involved in stimulating the formation of microparticles in endothelial cells.Recent studies showed that inflammatory reaction and endothelial microparticles in blood coagulation,cell proliferation,apoptosis,angiogenesis and other processes.EMPs is involved in the occurrence and development of cardiovascular events,which is mainly related to promoting inflammation,promoting coagulation and aggravating vascular endothelial dysfunction.EMPs affects vasoconstriction and relaxation by reducing the NO production.1).Reducing NO utilization,and increasing the expression of tight vasoactive substances in three ways.According to the research,EMPs in the blood of patients with metabolic syndrome can reduce the production of NO and O2-,thereby affecting the contractile and diastolic functions of the blood vessels.2).Promoting the nitration of endothelial cell related proteins.Boulanger CMet al revealed that on the mouse vascular endothelial acute myocardial infarction model,vasoconstrictor effect caused by the micro particles did not result from reducing the production of NO or increase the degradation of NO,but from cutting down the NO bioavailability to reduce the effects of NO,which may be related to micro granules to promote vascular endothelial NO receptor nitration,reduce its binding with the NO phase,thus reducing the vasorelaxant effect of NO.Meanwhile,EMPs have been found to inhibit endothelium-dependent vasodilation via eNOS/caveolin-1 pathway.Furthermore,lymphatic EMPs can decrease the availability of NO by inhibiting the xanthine oxidase receptor pathway and increasing the production of reactive oxygen species in the blood.In addition,lymphocyte derived microparticles not only reduce NO utilization,but also reduce the utilization of prostacyclin via prostacyclin,resulting in persistent low reactivity of the vessels.3).Upregulating the tight vasoactive substances.In some pathological conditions,endothelial cells can generated four arachidonic acid(Arachidonic,Acid,AA)which was transferred to the cell micro particles generated by the decomposition of thromboxane A2(Thromboxane,TXA2),which can cause a strong contraction of blood vessels.The main marker of endothelial cell microparticles distinguished from other microparticles is the specific glycoprotein embedded on its membrane surface,which is mainly derived from its primary cells.In normal condition,the cell surface is not or only contains a small amount of adhesion protein,but in pathological state,when the cells are stimulated to disintegrate,the surface adhesion protein level is also significantly increased,and finally the shedding of micro particles contains specific marker proteins.EMP are associated with coronary heart disease,sleep apnea syndrome,hypertension,nephrotic syndrome,ankylosing spondylitis and other related diseases.Fan et.al found that EMPs increased significantly in the blood of patients with diabetes,hyperlipidemia,coronary heart disease,cancer and other metabolic syndrome.Abbas M and other studies suggest that different phenotypes of EMPs have different functions in different diseases.In previous studies,inflammatory factors(such as complement,lipid peroxide and TNF-alpha)were used to stimulate endothelial cells cultured in vitro,it activated endothelial cells to release CD62(+)EMPs,the mitomycin C was used on the surface to induce apoptosis of endothelial cells after endothelial cells express CD31(+),so that different types of stimuli the endothelial cells release microparticles of different types.Generally speaking,EMPs are thought to result apoptosis of endothelial cells,which can be used as markers of endothelial damage.Meanwhile,Bernal-Mizrachi found that in patients with coronary artery disease CD31(+)EMPs was distinctly elevated than that of healthy people,the levels of CD31(+)EMPs in patients with acute myocardial infarction were significantly higher than those of patients with unstable angina,and CD31(+)EMPs in unstable angina pectoris patients was significantly increased than that in patients with stable angina pectoris,CD31(＋)EMPs in patients with primary myocardial infarction was obviouly higher than that in patients with recurrent myocardial infarction and unstable angina pectoris,suggesting that CD31(+)EMPs is related to the severity of coronary heart disease.Therefore,CD31(+)EMPs may be an important factor leading to plaque instability,suggesting that CD31(+)EMPs is closely related to the severity of coronary heart disease,and that CD31(+)EMPs can be an independent predictor of vascular events in high-risk patients with coronary heart disease.C-reactive protein(CRP)is a sensitive index of inflammation.As the most important factor in the process of inflammation,it has become a research hotspot in recent years.Thomas A et al.pointed out that high sensitivity C-reactive protein(hs-CRP)is the best inflammatory marker and the most powerful factor in predicting cardiovascular disease.There was no significant seasonal and seasonal variation of CRP concentration in plasma,and there was no significant difference between healthy individuals in day and night,and was not affected by diet.Therefore,the value of CRP at any time has clinical reference value.The inflammatory response of atherosclerotic plaques is an important cause of plaque rupture and instability.Biasucci believes that in the process of atherosclerotic plaque formation,CRP and foam cell deposition in the arterial wall,where CRP can be combined with lipoprotein,activate complement system,resulting in a large number of inflammatory mediators,release oxygen free radicals,resulting in vascular intimal injury,vascular spasm and unstable plaque shedding,lumen stenosis and atherosclerotic aggravating the occurrence of myocardial infarction.Therefore,CRP is an important marker of acute myocardial infarction.However,CRP levels in patients with mild to moderate coronary artery stenosis are higher than those with severe stenosis,and CRP levels are lower in patients with secondary coronary occlusion than in the former two groups.So that there was no significant correlation between CRP and the severity of coronary artery stenosis,possible reasons:1.because the inflammation reaction of the whole body of arteriosclerosis,coronary artery lesions can not reflect the severity of chronic stable;2.CRP may be related to atherosclerosis to unstable state(UA,AMI)the change of the current caused by the pathophysiology;3.the mechanism of myocardial ischemia,hypoxia,or necrosis in atherosclerosis,including coronary artery spasm and microcirculation of coronary artery lesions.At present,there is no report about the severity of coronary lesions and the counts of hs-CRP and CD31(+)/CD42(-)EMPs in acute myocardial infarction.In the past literature,Genesini integral was used as an index to evaluate the degree of coronary artery lesion,TIMI flow classification was used to evaluate the degree of coronary artery lesion in acute myocardial infarction,and to explore the relationship between CD31(+)/CD42(-)EMPs,Hs-CRP level changes have not been reported.Whether CD31(+)/CD42(-)EMP and hs-CRP are associated with the severity of coronary artery disease in acute myocardial infarction requires further clarification and further study.ObjectiveIn order to understand whether patients with acute myocardial infarction endothelial cells participated in the pathogenesis and development of observation in patients with acute myocardial infarction.To understand the association of CD31(+)/CD42(-)endothelial microparticles(CD31(+)/CD42(-)EMPs)、high sensitive C reactive protein(hs-CRP)with the lesion of coronary artery in patients with acute myocardial infarction,whether CD31(+)/CD42(-)EMPs and hs-CRP are related to the severity of disease,which provide theoretical support for the clinical assessment of severity of acute myocardial infarction and risk stratification.SubjectAll participants in the study signed the informed consent,we prospectively enrolled 160 patients with acute myocardial infarction who were first admitted within 12 hours from September 2014 to November 2016 in our cardiovascular interventional cente.AMI diagnostic criteria are established according to the standard of Cardiology of the Chinese Medical Association.Among these patients,there were 99 cases of STEMI,61 cases of NSTEMI,92 cases for males and 68 cases for females.According to the results of coronary angiography and clinical data of the patients after admission,criminals blood vessels flow by TIMI blood flow classification,the patients were divided into three groups(group 1,TIMI grade 0 flow;group 2 TIMI flow grade 1-2;group 3,TIMI grade 3 flow)by TIMI blood flow classification with 69 cases in Group1,46 cases in Group2,45 cases in Group3.At the same period,52 patients with suspected coronary heart disease were selected as the control group,coronary angiography showed that all 11 showed stenosis<50%and all coronary blood flow were TIMI 3 level.MethodsAll patients underwent coronary angiography and were recorded coronary TIMI blood flow grade.Gensini integral were calculated according to the number of coronary lesions and its location.The levels of CD31(+)/CD42(-)EMPs in all patients’ serum were measured by flow cytometry inmmedately after admission,and high sensitive C reaction protein(hs-CRP),cardiac troponin I(cTNI),creatine kinase(CK-MB),and N-terminal pronatriuretic peptide(NT-proBNP)were examined within 24h after admission.The correlation between CD31(+)/CD42(-)EMPs and Gensini integral,hs-CRP,cTNI,CK-MB and NT-proBNP were analyzed by statistical software.The statistical analysis of The test data were analyzed using SPSS 20.0 statistical software,all data need to be checked by normality test and homogeneity of variance.The measurement data are expressed by(x±s),the differences between groups were compared using one-way ANOVA or rank sum test,linear correlation analysis was used to analyze the correlation among variables,Non-normal distribution data were analyzed by rank correlation analysis.The enumeration data were represented by the number of cases and percentage(%),and χ2 test were used respectively.The correlation between the four groups of CD31(+)/CD42(-)EMPs and Genesini integral,hs-CRP,cTNI,CK-MB,NT-proBNP were analyzed by unary linear correlation analysis,when the data do not meet the normal distribution,the Spearman correlation analysis were choosen,P<0.05 showed a statistically significant difference.Results1.According to different TIMI blood flow of coronary artery disease shows:thecoronary blood flow was significantly related to CD31(H+)/CD42(-)EMPs and hs-CRP in acute myocardial infarction:The CD31(+)/CD42(-)EMPs and hs-CRP levels in the four groups of patients showed a trend of decreasing gradually with the grade of TIMI blood flow classification,the CD31(+)/CD42(-)EMPs and hs-CRP expression in patients of Group 1 is the highest,while the Group2 is lower than that of group 1,Group 3 was lower than that of group 2,and the control group was the lowest.And there were significant differences between the four groups,And the difference was statistically significant(P<0.05).The results showed that the coronary blood flow was significantly correlated with CD31(+)/CD42(-)EMPs and hs-CRP.2.According to the degree of coronary stenosis showed:the Gensini integral of Acute myocardial infarction is not correlated with CD31(+)/CD42(-)EMPs and hs-CRP:The Genesini integral of the Group 1 was the highest in the four groups,and there is no signicant difference between the Group 2 and Group 3(P=0.143),while obvious different from Group1(P<0.0001),the Genesini integral in Group 4 is the lowest.The r value and P value of relation of Genesini integral with CD31(+)/CD42(-)EMPs in the four groups were as follows:group 1:r=0.011 and p=0.9286;group 2:r=01604 and p=0.2868;group 3:r=0.009 and p=0.9431;group 4:r=0.1183 and p=0.4035.The Genesini integral and hs-CRP r value and P value of the four groups were as follows:group 1:r=0.062 and p=0.6129;group 2:r=0.091 and p=0.5495;group 3:r=0.2052 and p=0.1763;group 4:r=0.001 and p=0.7143.The results indicated that there was no significant correlation between Genesini integral and CD31(+)/CD42(-)EMPs and hs-CRP in AMI patients.3.CD31(+)/CD42(－)EMPs were positively correlated with hs-CRP,cTnI,CK-MB and NT-proBNP in patients with acute myocardial infarction:The CD31(+)/CD42(-)EMPs count,hs-CRP,cTNI,CK-MB,NT-proBNP levels in the four groups showed a gradual decline trend,and there were significant differences between the four groups.The difference was statistically significant(P<0.05).The r value and P value of CD31(+)/CD42(-)EMPs and hs-CRP in the four groups were as follows:group 1:r=0.7284 and p<0.001;group 2:r=0.9319 and p<0.001;group 3:r=0.8540 and p<0.001;group 4:r=0.031 and p=0.8274.The R value and P value of CD31(+)/CD42(-)EMPs and cTnI in the four groups were as follows:group 1:r=0.8361 and p<0.001;group 2:r=0.8939 and p<0.001;group 3:r=0.9304 and p<0.001;group 4:r=0.1580 and p=0.2634.The R value and P value of CD31(+)/CD42(-)EMPs and CK-MB in the four groups were as follows:group 1:r=0.8782 and p<0.001;group 2:r=0.9004 and p<0.001;group 3:r=0.8787 and p<0.001;group 4:r=0.2655 and p=0.067.The R value and P value of CD31(+)/CD42(-)EMPs and NT-proBNP in the four groups were as follows:group 1:r=0.9144 and p<0.001;group 2:r=0.8336 and p<0.001;group 3:r=0.8740 and p<0.001;group 4:r=0.035 and p=0.8016.The results suggested that:the first three groups of patients with CD31(+)/CD42(-)EMPs and hs-CRP,CK-MB,cTnl,NT-proBNP were positively correlated,and there was no significant correlation with the control group.Conclusions1.CD31(+)/CD42(-)EMPs was significantly related to the level of hs-CRP in patients with acute myocardial infarction,CD31(+)/CD42(-)EMPs and hs-CRP can reflect the severity of myocardial ischemia.The peripheral blood of CD31(+)/CD42(-)EMPsin patients with acute myocardial infarctionshowed a positive correlation with and cTnl,CK-MB and NT-proBNP.Therefore,CD31(+)/CD42(-)EMPs can be used as a measure of the severity of acute myocardial infarction and coronary artery disease severity index and risk stratification of acute myocardial infarction,which has a clinical and research significance in pathogenesis andprognosis of acute myocardial infarction.2.The levels of CD31(+)/CD42(-)EMPs and hs-CRP in patients with acute myocardial infarction are not correlated with the coronary Genesini integral,considering that that Genesini integral evaluation is more inclined to coronary artery stenosis and coronary microcirculation site with ignorance of Coronary microcirculation.Meanwhile it is difficult to accurately reflect the situation of patients with myocardial ischemia acute myocardial infarctionbecause of its simple calculation method and rough.While the use of TIMI flow grade assessment of coronary artery lesions can more accurately reflect myocardial perfusion in acute myocardial infarction,risk and prognosis.3.CD31(+)/CD42(-)EMPs and hs-CRP levels increased in patients with acute myocardial infarction,and there was a positive correlation between them,indicating that there was endothelial injury and inflammatory response in patients with acute myocardial infarction.Endothelial injury and inflammatory response interact with each other and further aggravate the disease.