Ischemia-modified Albumin, Cystatin C, NT-proBNP Joint Detection Value In The Early Diagnosis Of Acute Coronary Syndrome

Background:With the rapid social development, incidence of coronary heart disease,especially acute coronary syndrome(ACS) has increased gradually in China and became a public issue seriously affects people’s physical and mental health.ACS refers to a series of clinical symptom complex caused by sudden block of coronary blood flow and characterized by sudden onset,severe state of illness, high disability rate and fatality rate. According to continuous pathophysiologic process of myocardial ischemia, ACS can be divided into unstable angina(UA),acute non-ST-segment elevation myocardial infarction(NSTEMI) and acute ST-segment elevation myocardial infarction(STEMI).Due to various clinical manifestations and acute onset of patients with ACS,Timely diagnosis and treatment is of vital significance for patient prognosis.Therefore,it becomes the focus of researches of clinicians to seek for accurate and quick detection indexes.At present,diagnosis and risk assessment of ACS is mainly conducted on the basis of clinical manifestation, electrocardiogram(ECG) and myocardial enzymogram.Clinical manifest- ations of patients with ACS include stronger sense of subjectivity, higher specificity of ECG and sensitivity no less than 50% of the normal level. Besides, such patients can only be detected with traditional myocardial injury markers 6 to 12 hours after myocardial necrosis and only have a higher specificity against myocardial necrosis but produce negative results of reversible myocardial ischemia.Ischemia-modified Albumin(IMA)is one of the detection indexes for early diagnosis of ACS,which have been oftentimes reported both abroad and at home in recent years.[1,2]Different from traditional myocardial injury markers,IMA can be detected in the early reverse stage of ACS,which provides to some extent,effective reference for clinical diagnosis of patients with myocardial ischemia and makes it possible to determine whether the patients suffers from ACS and ASC risk stratification so as to reduce rate of missed diagnosis of patients at high risk of myocardial infarction.Cystatin C(Cys C),also known as half sarcosine C protease inhibitor, is expressed in myocardial cells.It is found by researches that,low content of Cys C is closely related to atherosclerosis, arterial aneurysm and acute myocardial infarction and this mechanism may be involved with failure to resist the disassociation of arterial elastin by cathepsin. It is also found by researches that, increase of Cys C content is the independent risk factor resulting onset of coronary heart disease. [3-5]N-terminal brain natriuretic peptide(NT-pro BNP) is a kind of lysates of brain natriuretic peptid(BNP).It is proved by studies that, NT-pro BNP is highly vauble in judging left ventricular dysfunction and prognosis, different- tiate clinical symptoms caused by cardiac from those caused by non- cardiac reasons.Besides, the rapid secretion and relatively long half-life period in case of heart failure of NT-pro BNP can be used as important sensitive index in judging the severity of ventricular dysfunction and cardiac dysfunction.[6] It is shown by recent studies that,content of NT-pro BNP in patients with ACS can rise and it is closely related to ACS prognosis. Clinical studies have shown that, transient hypoxia-ischemia can directly induce faster BNP genetic transcription and increased genetic expression and myocardial ischemia of patients with ACS can stimulate and increase NT-pro BNP expression and secretion.[7]Objective:To detect content of ischemia modified Albumin(IMA),Cystatin C(Cys C),N-terminal brain natriuretic peptide precursor(NT-pro BNP) in patients in early stage and analyze the value of combined detection of the three(IMA,Cys C and NT-pro BNP) for early diagnosis of patients with ACSMethod:The 150 suspected patients with acute coronary syndrome, who have been received and treated in our hospital from January, 2013 to June,2014 are selected as the subjects of the research. The diagnostic criteria are in line with the diagnosis and treatment guidelines issued by American College of Cardiology and American Heart Association(ACC/AHA) in 2007.The patie- nts are divided into different groups by the diagnosis criteria. The groups are as follows:unstable angina(UA)group consisting of 37 patients,non-ST- segment elevation myocardial infarction(NSTEMI) group consisting of 37 patients,St-segment elevation myocardial infarction(STEMI) group consisting of 36 patients,and non ischemic chest pain group(NICP) consisting of 40 patients. Meanwhile,50 cases of medical healthy subjects were choosed as the control group.The albumin cobalt binding test(ACB test) is applied for indirect determination of the concentration of ischemia modified albumin(IMA). Peripheral venous blood is collected within 6 hours after attack of chest pain of all patients.Immunization is used for determination of NT-pro BNP and enzyme linked immunosorbent assay(ELISA) is used for determination of Cys C;coronary angiogram is applied to detect the degree of coronary artery stenosis, which is measured by Gensini score system. And then the content of IMA,Cys C and NT-pro BNP of ACS group,NICP group and the three subgroups(UA subgroup,STEMI subgroup and NSTEMI subgroup)and the control group as well is compared.Besides,the receiver operating characteristic curve(ROC curve) is used to analyze the optimal cutoff value of the patients with ACS and healthy people.And then,a detection of the area under ROC curve of IMA,Cys C and NT-pro BNP of ACS group and the contrast group is also conducted.Finally, the specificity, sensitivity,positive predictive value and negative predicative value of IMA,Cys C and NT-pro BNP is compared for early diagnosis of ACS.Results:1 Compared with the control group, ACB value of the ACS group drops within 6 hours after acute chest pain and to which is lower than the average of NICP group with statistically significant comparative difference(P<0.05); but Cys C、NT-pro BNP of ACS group are higher than the control group and NICP group with statistically significant comparative difference(P<0.05);Gensini score of ACS group are higher than NICP group with statistically significant comparative difference(P<0.05);the comparative difference of NT-pro BNP among UA subgroup, STEMI subgroup and NSTEMI subgroup is of statistical significance(P<0.05),while,the comparative difference of ACB, Cys C,and Gensini score is of no statistical significance(P>0.05) among the three subgroups.It is concluded through regression analysis that, ACB value is negatively correlated with Gensini score(r=-0.554,P<0.01),Cys C,NT-pro BNP and Gensini score are positively correlated(r= 0.873,0.812,P<0.01).2 Area under the ROC curve(AUC) of ACB value,Cys C and NT- pro BNP of the ACS group and the control group is respectively 0.939,O.780 and 0.710;AUC of ACB value,Cys C and NT-pro BNP of the ACS group and the NICP group is respectively0.786,0.659 and 0.580;and the AUC of IMA+ Cys C+NT-Pro BNP combined detection of the ACS group and the control group is 0.943.After testing, IMA+Cys C+NT- Pro BNP combined detection is better in diagnosis than separate detection of any of the three indexes(P<0.05)and IMA is better than Cys C and NT-pro BNP with statistically significant comparative difference(P<0.05).3 Diagnostic sensitivity(80.0%)and negative predictive value(60.0%)of IMA detection are higher than that of Cys C(50.0% and 36.0% respectively) and NT-Pro BNP(41.8% and 31.9% respectively)and all the comparative differences all of statistical significance(P<0.05);while,when the three(IMA+ Cys C+NT-Pro BN)detections are used together,the sensitivity and NPV all higher(94.5% and 85.0% respectively) than that of any of the detections conducted separately and the comparative difference is of statistical signific- ance(P<0.05).Conclusions:1 Content of IMA,Cys C and NT-Pro BNP in blood of patients with acute coronary syndrome in six hours is higher than the control group,thus,it is indicated that the three indexes are of certain significance for early diagnosis of ACS.2 IMA,Cys C,NT-Pro BNP could be used for early diagnosis of suspected patients with ACS respectively and when used together,the detection results can yield higher sensitivity and negative predictive value.