The Changes And Clinical Significance Of Serum Visfatin And Syndecan-4Protein Level In Patients With ST-segment Elevation Myocardial Infarction Respectively

Backgroud:Myocardial infarction (MI) is the disease which is characterized by that coronary blood supply is drastically reduced or interrupted on the basis of coronary artery disease, leading to severe acute myocardial ischemia, eventually leading to myocardial necrosis. As a serious type of coronary heart disease, it’s clinical manifestations contains severe pain, fever, elevated white blood cell count and serum myocardial necrosis markers, progressive ECG changes, even arrhythmia, shock or heart failure.20-30minutes after coronary artery occlusion, part of corresponding myocardium has been necrotic, then begin the pathological process of acute myocardial infarction. During1-2hours, most of the myocardium undergo coagulatical necrosis, the myocardial interstitium undergoes congestion and edema, accompanied by a large number of inflammatory cell infiltration. Later, necrotic myocardial fibers gradually dissolve and become muscular melting stove, subsequently granulation tissues gradually form. Between acute myocardial ischemia and necrosis, there is another process. In fact, that the corresponding region of ST-segment elevation of electrocardiogram happens indicates the corresponding coronary occlusion and full-thickness myocardium injury, the vast majority of which will become necrotic tissues involving full thickness ventricular wall or most of the large bulk myocardium, accompanied by elevated myocardial necrotic markers. Such disorder is clinically diagnosed of ST-segment elevation myocardial infarction (STEMI). In regard to acute ST-segment elevation myocardial infarction, the principles of treatment include restoring myocardial blood perfusion as soon as possible in order to save the dying myocardiaium, preventing infarction expanding or narrowing the scope of myocardial ischemia, protection and maintenance of heart function, timely intervention of serious arrhythmia, pump failure, and a variety of complications, preventing sudden death, which can not only make patients go through the acute phase, but also maintain as much as functional myocardium after rehabilitation. How to detect unstable plaque and predict severe acute coronary events are the research focus of cardiology today. Therefore, that looking for myocardial necrosis markers characterized by simple detection methods, security, standardization, repeatable testing at different periods of the disease is of clinical significance of early diagnosis of acute myocardial infarction.As a new member of adipocytokines, Visfatin was discovered in2005by Fukuhara et al. The5’end of human visfatin gene is located in the upstream of the transcription initiation point3.2kb sequence, it has two special promoter region, including the proximal promoter region and the distal promoter region. Because of the different binding sites, visfatin expression varied in different tissues. Some studies had showed that visfatin played a role in anti-apoptosis, regulation of the immune response and regulation of glucose and lipid metabolism. Visfatin mainly expressed in macrophages invasing to adipose tissue, and concentration-depently downregulates PPARy mRNA and protein expression in order to activate inflammatory response. In recent years, Studies from Liu, Dahl et al have shown that visfatin as a new proinflammatory adipocytokine is closely related to atherosclerosis development, atherosclerotic plaque instability, acute coronary syndrome.syndecan-4is one member of transmembrane transporter proteoglycan syndecans family affiliated to heparan sulfate class. As a growth factor binding co-receptor, syndecan-4regulates a variety of cell biological effects and plays an important role in cell stretching, recognition, adhesion, migration and proliferation, as well as the inflammatory response. syndecan-4protein in blood vessel features include:viscoelastic maintenance of vascular viscoelasticity, permeability and the integrity of the blood vessel wall, preventing the loss of the vessel contents and infiltration of the vessel wall. It has been found that syndecan-4protein in the development of atherosclerosis (AS) and myocardial infarction (MI) have significantly been upregulated. However, the relationship of serum visfatin and syndecan-4protein level in STEMI patients are not yet entirely clear.Purpose:To observe the relationships between serum visfatin and syndecan-4protein and cardiac troponin I (cTnI), N-terminal pro-Btype natriuretic peptide (NT-proBNP), MYO, CK-MBm, total white blood cell (WBC) count, neutrophil count, monocyte count, echocardiography left ventricular parameters and the number of coronary lesions in patient of ST-elevated myocardial infarction, respectively. The clinical diagnostic value of serum visfatin and syndecan-4protein level as a potential biomarker in patient of ST-elevated myocardial infarction were evaluated, respectively.Subjects:Included sbujects are the patients who had been treated in the department of cardiology in NanFang hospital from December2011to June2012. Based on the ischemic chest pain history after admission, the results of selective coronary angiography, electrocardiogram, echocardiography examination and biomarkers of myocardial necrosis respectively,30patients were diagnosed of STEMI (24males,6females,39-78years old, average age:56.5±9.3years),51cases of chronic angina (40males,11females, average age:59.6±8.9years). And another22patients with normal coronary angiography were included as normal control group with non-coronary heart disease (16males and6females, average age:57.5±7.8years). According to the results of coronary angiography,81patients with coronary artery disease were divided into single-vessel leision subgroup (1lesion,25cases), double-vessel lesions subgroup (2lesions,20cases) and multi-vessel lesions subgroup(more than3lesions,36cases). All subjects signed informed consent of patients.STEMI diagnostic criteria are in line with the2007American College of Cardiology (ACC)/American Heart Association (AHA)/World Heart Federation (WHF)/European Society of Cardiology (ESC) guidelines.Exclusion criteria:①valvular heart disease, the primary cardiomyopathy patients;②acute or chronic inflammatory diseases;(3)autoimmune disease or connective tissue diseases;④patients with advanced liver or kidney disease;⑤blood diseases, malignant tumors⑥patients with trauma or surgery in the last three months.Methods:1. Demographic data collection:To gather general demographic information, including gender, age, height, body weight, body mass index, systolic blood pressure, diastolic blood pressure, smoking history, history of diabetes, history of coronary heart disease, and so on.2. Physical examination data collection:(1) ECG:all patients underwent eighteen body surface lead simultaneous ECG event recording. That ST segment changes of ECG happened in at least two leads, V1-V3≥0.2mV, and other leads (except aVR)≥0.1mV are the advanced period of ST-segment elevation.(2)echocardiography:All patients underwent echocardiography. Routinely determine the structure and size of the atrioventricular cavity, observe motion of ventricular wall. Left ventricular ejection fraction (LVEF), fractional shortening (FS), left ventricular end-diastolic diameter (LVEDd), left ventricular end-systolic diameter(LVEDs), left ventricular end-diastolic volume(LVEDV), left ventricular end-systolic volume (LVESV) and E/A values were detected, repectively. LVEF<50%was defined as left ventricular systolic dysfunction.(3) selective coronary angiography:patients with STEMI underwent emergency selective coronary angiography, patients with chronic angina and non-coronary heart disease from control group uderwent selective coronary angiography in one week after admission. The coronary heart disease diagnostic criteria were that coronary angiography showed at least one vessel lunmen diameter stenosis≥50%, including the left main coronary artery, the left anterior descending artery, the left circumflex artery or right coronary artery. According to the scope of coronary lesions, Coronary lesions are divided into one vessel lesion, two vessel lesions and multi-vessel lesions (more than3lesions), and left main artery disease was recorded as two lesions.(3) Biochemical blood specimens information collection: Patients with STEMI underwent venous blood sample collection before emergency coronary angiography. Chronic angina and non-coronary heart disease patients underwent elbow venous blood sample collection (fasting for more than10h) in the next morning after admission, some of the blood samples were sent to the laboratory of NanFang Hospital in order to detect cardiac troponin I (cTnI), cardiac enzymes (MYO and CK-MBm), N-terminal pro-B-type natriuretic peptide (NT-proBNP), total white blood cell count, neutrophil count, monocyte count, lymphocyte count, fasting plasma glucose (FPG), glycosylated hemoglobin (HbAlc), lipids (TG, TC, HDL-C, LDL-C), fibrinogen (Fbg-C), uric acid (UA) and creatinine (CR). To detect serum visfatin and syndecan-4protein, respectively, blood samples were immediately injected into the test tube and centrifuged within30min. The centrifugal conditions:3000rpm,15min, patient’s serum was obtained, serum visfatin and syndecan-4protein level were detected respectively.4. Detection of serum visfatin and syndecan-4protein level:①To detect serum visfatin level by using the ELISA method. The visfatin kit was purchased from Phoenix Pharmaceuticals, Inc.(Code NO.EK-003-80). The testing method was strictly in accordance with the instructions that came with the kit.②To detect syndecan-4protein level by using the ELISA. syndecan-4kit was purchased from Immuno-Biological Laboratories Co., Ltd.(Code NO.27188), the testing method are carried out strictly in accordance with the instructions that came with the kit.Statistical Methods:SPSS13.0statistical software was used for data analysis. Measurement data underwent normality test. If samples complied with the normal distribution, the data were expressed as mean±standard deviation (x±s), the sample not complying with the normal distribution were expressed as median(minimum, maximum). Single-factor analysis of variance (One-Way ANOVA) was used to compare the means of multiple-group of measurement data which comply with the complete randomized design data. If significant differences existed between the groups, homogeneity of variance test was carried out. If the data met the homogeneity of variance, SNK-q test was used to carry out multiple comparisons among means of groups; If the data don’t meet the homogeneity of variance, approximate F test Welch method was used, Dunnett’s T3test was used to carry out multiple comparisons among means of groups. Categorial data were expressed as the number of cases (%), non-parametric X2test was used to carry out comparisons among groups. Two variables non-parametric Spearman correlation analysis was used to determine serum visfatin and syndecan-4protein impact factors respectively and the correlations of possible related factors. Multivariate linear regression analysis was used to analyze the impact factors of the severity of coronary lesions. ROC curve was used to evaluate and compare the diagnostic value of serum visfatin and syndecan-4protein in patients of ST-elevated myocardial infarction, respectively. P<0.05was considered statistically significant.Results:1. Comparisons of general indicators between STEMI group and chronic angina pectoris, non-coronary heart disease control group, respectively.Statistical analysis showed that had no significant differences in age, sex, BMI, SBP, DBP, FPQ HbA1c, TG, TC, HDL-C, LDL-C, LYM, MONO, Fbg-C, UA, CR, Smoking among three groups(P>0.05). STEMI group, chronic angina group and non-coronary heart disease control group showed statistically significant differences in cTnl, MYO, CK-MBm, WBC, NEU, NT-proBNP, respectively (P<0.05). SNK multiple test results indicated that cTnI, MYO, CK-MBm, WBC, NEU, NT-proBNP levels in STEMI group were significantly higher than those of chronic angina and non-coronary heart disease control group respectvely (P<0.05).2. Comparisons of serum visfatin and syndecan-4protein level among three groups and correlation analysis of indicators Serum visfatin protein level in STEMI patients was significantly higher than chronic angina patients(P<0.05). Serum visfatin protein level in chronic angina patients was significantly higher than non-coronary heart disease control group (P <0.05). Spearman correlation analysis showed that serum visfatin protein level was significantly positively correlated with cTnI, MYO, CK-MBm, NT-proBNP, WBC, NEU, MONO and serum syndecan-4protein level in STEMI group respectively.Statistical analysis indicated that serum syndecan-4protein level in STEMI group was significantly higher than chronic angina group(P<0.05). Serum syndecan-4protein level in chronic angina group was significantly higher than non-coronary heart disease control group (P<0.05). Spearman correlation analysis showed that serum syndecan-4protein level was significantly positively correlated with cTnI, MYO,CK-MBm, NT-proBNP, WBC, NEU, MONO and serum visfatin in the STEMI group respectively.3.Comparisons of echocardiography diagram parameters among three groups. Correlation analysis of echocardiographic parameters with serum visfatin and syndecan-4protein levels, respectively.Statistical analysis showed that LVEDd, LVEDV, LVESV, FS, E/A had no significant differences among three groups(P>0.05), whereas LVED and LVEF had significantly statistical differences among three groups (P<0.05). SNK multiple comparisons results showed that LVEDs in STEMI group was higher than choronic angina group and non-coronary heart disease group respectively (P<0.05), LVEF in STEMI group was lower than chronic angina group and non-coronary heart disease group respectively (P<0.05).Spearman correlation analysis showed serum visfatin protein levels in STEMI group was positively correlated with LVEDs, and was negatively correlated with LVEF and FS respectively, and was not significantly correlated with LVEDd, LVEDV, LVESV and E/A respectively. Serum syndecan-4protein levels in STEMI group was positively correlated with LVESV, was negatively correlated with LVEF, and was not significantly correlated with LVEDd, LVEDs, LVEDV, FS and E/A, respectively.4. Correlations between the number of coronary lesions and serum visfatin and syndecan-4protein level, respectively.With the increasement of the number of coronary artery lesions, serum visfatin and Syndecan-4protein levels significantly increased, respectively. Compared with single-vessel or two-vessel disease groups respectively, serum visfatin and syndecan-4protein level in multi-vessel disease group significantly elevated, respectively(P<0.05). Multiple linear regression analysis showed that serum visfatin and syndecan-4protein level is an independent risk factor for coronary artery disease, respectively. The higher serum visfatin and syndecan-4level was, the higher the risk of coronary lesions severity was.5. The diagnostic value of serum visfatin and syndecan-4protein level in patients of STEMI, respectivelyThe results showed that AUCROC of serum visfatin in patients of STEMI was0.872(P=0.000,95%CI0.803-0.941), serum syndecan-4protein was0.855(P=0.000,95%CI0.781-0.928), which indicates that serum visfatin and syndecan-4protein level has a certain value as a potential biomarker for diagnosis of STEMI, respectively.6. Correlation analysis between serum visfatin and syndecan-4protein level Spearman correlation analysis showed that serum visfatin protein level was significantly positively correlated with syndecan-4protein level in STEMI patients.Conclusions:In summary, this study demonstrated that serum visfatin and syndecan-4protein level in patients of STEMI was significantly higher than chronic angina group and non-CHD control group respectively. Serum visfatin and syndecan-4protein levels were significantly positively correlated with cTnl, MYO, CK-MBm, NT-proBNP, WBC, NEU, MONO and coronary artery lesions variables in the STEMI group, respectively. Serum visfatin and syndecan-4protein levels were significantly negatively correlated with left ventricular ejection fraction in the STEMI group respectively. Serum visfatin protein levels were significantly positively correlated with syndecan-4protein levels in the STEMI group. Therefore, serum visfatin and syndecan-4protein levels was new potential biomarkers as detection of myocardial injury, evaluation of left ventricular function and speculated that the severity of coronary artery lesions, respectively.