The Comparison Of IMA, H-FABP And Copeptin Evaluating The Accuracy Of Coronary Lesions In Patients With Acute Coronary Syndrome

BackgroundAcute coronary syndrome(ACS) is a clinical syndrome which the pathological basis is coronary atherosclerotic plaque rupture or erosion,secondary complete or incomplete occlusion thrombotic,which includes a series clinical symptoms of unstable angina,non-STsegment elevation myocardial infarction and ST-segment elevation myocardial infarction.Coronary plaque inflammation is a major factor leading to plaque instability,then the acute coronary syndrome, during which accompanied the release of inflammatory cytokines, coagulation system activation and thrombosis,myocardial necrosis and changes in ventricular pressure and so on.Rapid and accurate diagnosis of acute coronary syndrome and early identification and timely intervention given to patients help reduce the incidence of adverse events.ObjectiveBy detecting Ischemia-modified proteins(IMA)、Heart-type fatty acid binding protein(H-FABP) and copeptin(Copeptin) and other changes in the concentration of biomarkers of coronary heart disease in the blood of patients with different types of acute coronary syndrome,, and calculating the Gensini score for each group of patients with coronary artery disease, Analyzing the relationship between the measured index and acute coronary syndrome in order to identify the severity of coronary artery disease and the stability of the predictive value of these markers.Materials and Methods1、Subjects:Choozing the 220 cases of suspected acute coronary syndrome patients at the Qilu Hospital of Shandong University from February 2013 to July 2014 for the study,according to the clinical features and history the patients is divided into non-ischemic chest pain( NICP) of 57 cases and acute coronary syndrome(ACS) of 163 cases,among the patients with acute coronary syndrome is divided into unstable angina(UAP)of 82 cases, and patients with acute myocardial infarction(AMI) of 81 cases.Coronary angiography of all patients in one week while collecting patient’s IMA, H-FABP, and Copeptin and other related biochemical indicators.2、Diagnostic criteriaAll patients underwent coronary angiography are in line with the Chinese Medical Society of Cardiology indications listed in the?China percutaneous coronary intervention guidelines? in 2012.11/All patients underwent echocardiography, chest anteroposterior film, 18-lead ECG, liver function, kidney function, electrolytes and other tests after admission to rule out heart disease, valvular heart disease, severe arrhythmia, severe liver and kidney dysfunction, severe heart failure, bleeding disorders, cancer, acute and chronic infectious disease, thyroid disease, autoimmune disease, surgery within 3 months and not for other reasons who underwent coronary angiography.All patients were informed of the risks associated with surgery and signed a consent form.3、The diagnostic criteria and classification of ACSNICP group:Patients with unexplained chest discomfort(chest pain, chest tightness, etc.), the electrocardiogram, chest X-ray, echocardiography and other routine examination no abnormalities, coronary angiography see vascular stenosis <50%, excluding CHD who is normal set to the control group.UAP group:Onset angina: the course within two months of new-onset angina, and can be expressed as spontaneous labor onset seizures coexist, never a history of angina pectoris, or nearly half of the year but did not attack angina;Worsening pectoris angina: With previous history of angina, worsening angina within the past two months increased, the number of frequent seizures, prolonged or lower pain threshold(angina grade by at least one, or at least reach Ⅲgrade, nitroglycerin to relieve symptoms of weakened, the course in 2 months within);Resting angina:Episodes of angina at rest, and continued more than 20 min, with typical ST-T changes chest pain, but not elevated markers of myocardial injury.AMI group:Increased cardiac markers and / or decrease(preferably c Tn), of which there are at least 1 value exceeds the 99 th percentile of the upper reference value, and one of the following merger:1. ischemic symptoms. 2. Emerging meaningful ST-T changes(ST segment elevation for STEMI, non-ST-segment elevation for NSTEMI) or left bundle branch block(LBBB). 3. pathologic Q waves. 4. radiological evidence suggests that loss or wall motion abnormalities new hair viable myocardium.4、Coronary angiography and the judgment of the coronary lesion severityAll patients admitted line to the coronary angiography as soon as possible, using the German company Siemens DSA for each section of the blood vessel at least three position of projection, conventional Seldinger technique through the femoral artery or radial artery is completed, take the left anterior oblique conventional 30°, 45 °right anterior oblique axial projection and the first leg, the two physicians were analyzed by quantitative coronary angiography analysis(quantitifying coronary angiography, QAC law).The degree of coronary stenosis according to the criteria of the American Heart Association(AHA), and for the degree of stenosis <50% who included NICP group; where the degree of stenosis ≥50% were placed in the ACS group.According to Gensini scoring system for quantitative determination of each vascular lesions:Note: Each of the lesion score = stenosis scoring * lesion score, each patient into account the sum of all lesions scoring5、Collecting the patient’s general informationCollecting detailed clinical data of selected object such as:age, sex, height, weight, blood pressure, smoking, diabetes, hypertension, and previous surgery.5.1Smoking:Smoked≥5 years, the average daily smoking 10 or more. However, longterm smokers who quit less than six months.5.2Hypertension:According to the 2010 ?Chinese Hypertension Prevention Guide? standard, there is a clear history of hypertension, taking antihypertensive drugs or medication, measured three times daily quiet state extraordinary sitting right arm brachial artery blood pressure, systolic blood pressure(SBP)≥140 and/or diastolic blood pressure(DBP)≥90mm Hg.135.3Diabetes:According to the 2005 American Diabetes Association( ADA) diagnostic criteria for diabetes, or have a history of diabetes or are taking hypoglycemic agents. Polyuria, polydipsia polydipsia and unexplained weight loss and other symptoms of diabetes plus any time plasma glucose≥11.1mmol/L(200mg/dl)or FPG≥7.0mmol/L(126mg/dl) or OGTT 2h PG≥11.1mmol/L(200mg/dl).Repeat once confirmed, to establish the diagnosis.145.4Heart Failure:According to 2014?Chinese heart failure diagnosis and treatment guidelines? standard, with clinical symptoms of heart failure, signs and laboratory parameters(BNP rises), echocardiography showed LVEF≤50%. 156、Experimental parameters were measuredIMA and H-FABP detection:Application of flow cytometry in plasma concentrations. In strict accordance with the instructions steps. Flow cytometry principle: two different sizes of beads were wrapped after different specific antibody, is incubated with the sample, the sample is then combined with the test substance-specific antibodies. Then adding a second antibody to form the conjugate combined with biotin, and combined with the substance to be tested. Finally adding the bound fluorescein-PE Streptavidin, which previously has been added to the biotin-binding, releasing a fluorescent signal, and therefore, according to the bead size and fluorescence intensity can be distinguished test substance, the fluorescence intensity strong, indicating that the higher the content of the substance.Copeptin detection:In accordance with copeptin ELISA kit manual operation is performed strictly.7、Statistical analysisStatistical analysis was performed using SPSS19.0, all measurement data normality tests were performed, in line with the normal distribution of measurement data(x±s) indicate.Between the two groups were compared using the t test measurement data among groups were compared using analysis of variance was used to compare twenty-two LSD method. Count data usingχ2 test. Correlation analysis using Spearman rank correlation. P<0.05 was considered statistically significant.The results1、The clinical data were compared in each groupNICP group, UAP group, AMI group, no difference in each group(P = NS) in age, sex, smoking history, family history of coronary heart disease and so on. Hypertension, a history of glucose in the ACS group than NICP group(p = 0.003, p = 0.001), no difference(p = NS) between the ACS groups.Within each group the week before blood application β- blockers, calcium channel blockers, nitrates, statins lipid-lowering drugs, the ratio between aspirin, chlorine pyrrole mine differences in each group was not statistically significant(p = NS), but angiotensin ⅱreceptor antagonist or angiotensin-converting enzyme inhibitor in the proportion of applications NICP ACS group than in control group(P <0.05)(Table 1).Detected changes of indicators in each group2、Changes of different observations’ concentrations in each types of ACS and NICP( Table 2).IMA:The plasma IMA of each group of patients with acute coronary syndrome were higher than that of nonischemic chest pain(UAP:60.5±5.8ng/L,AMI:72.3±6.5ng/L vs NICP:57.4±11.1ng/L,p=0.048,p<0.001), and AMI group was significantly higher than UAP group(p=0.027).H-FABP:The plasma H-FABP of each group of patients with acute coronary syndrome were higher than that of nonischemic chest pain(UAP:3.26±1.83ng/L,AMI:3.85±1.71ng/L vs NICP:1.7±1.56ng/L,p=0.030,p<0.001),and AMI group was significantly higher than UAP group(p=0.029).Copeptin:The plasma Copeptin of each group of patients with acute coronary syndrome were higher than that of nonischemic chest pain(UAP:2.71±0.49ng/L,AMI:2.31±0.54ng/L vs NICP:1.97±0.47ng/L,p=0.026,p<0.001),and AMI group was significantly higher than UAP group(p=0.035).3、Correlation between detection index and Gensini scoreAnalysis The correlation between the various biomarkers and Gensini scores by linear correlation analysis,Skewed distribution underwent natural logarithmic transformation.Found there was positive correlationbetween IMA(r = 0.203, p = 0.026) and H-FABP(r = 0.335, p <0.001) and Gensini score(see Figure 7, Figure 8), and there was no correlation between the peptide hormone and Gensini score.4、diagnosis ACS by the area under the ROC curve of the biomarkersWith unstable angina and acute myocardial infarction as a test variable, with an area under the ROC curve of each biomarker for the diagnosis of ACS were: IMA: 0.743(95% CI: 0.610-0.819, p <0.001); H-FABP: 0.779(95% CI: 0.692-0.866, P <0.001); Copeptin: 0.675(95% CI: 0.560-0.775, p = 0.003)(Figure 9).5、Logistic regression analysis to calculate the diagnostic value of each variable on theACSUnivariate Logistic regression analysis showed that two yuan IMA, H-FABP, Copeptin predicting ACS has a certain significance(see Table 6). All test conditions indicators way into equation multivariate Logistic regression analysis, display IMA, H-FABP for ACS predictive value, 0R were 1.014(95% CI: 1.001-1.016, P <0.01) and 1.655(95% CI: 1.274-2.130, P <0.01)(Table 4).To value cutoff(Cutoff value) quartiles when the control group, all observations of ACS diagnosis has a certain value(see Table 5), in which the maximum value Copeptin. In terms of three kinds of markers any more than the normal two kinds of upper quartile is positive, the diagnostic value does not increase, 0R value of its diagnosis of coronary heart disease is 3.201, sensitivity 58.9%, specificity 69.0%, positive predictive value 83.50 k and negative predictive value 38.7%.6、Follow-up results30 cases of 220 cases of cardiovascular events during follow-up of patients with CCP, including 10 cases of death, reinfarction three cases, five cases of heart failure occurred, the rest are recurrent angina patients hospitalized.Gender, age, history of hypertension, diabetes, smoking history, history of hyperlipidemia and admission blood glucose levels, blood pressure, total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, and various biomarkers detected factors, etc., only found in age and incomplete revascularization is a risk factor for cardiovascular events,Age 0R is 1.146(95% CI: 1.001-1.475, p = 0.050), incomplete revascularization OR value is 1.488(95% CI: 1.116-2.252, p = 0.005).Conclusion1、Plasma IMA, H-FABP and copeptin elevated in patients with ACS, suggestingthese biomarkers may reflect the presence of coronary artery disease in patients withplaque instability. Among them, H-FABP maximum value for the diagnosis of coronaryartery disease, have greater clinical significance.2、IMA and H-FABP and Gensini scores were positively correlated, suggesting thatthese two biomarkers can reflect the extent of coronary lesions in acute coronarysyndrome.3、Patients with acute coronary revascularization syndrome, this study can notdetect biomarkers to predict the prognosis of patients, only age and incompleterevascularization is prognostic factors.