The Significance Of Biochemical Markers Detection For Early Risk Stratification Among Patients With Acute Coronary Syndrome

BackgroundAcute coronary syndrome(ACS), is the phenomenon of the sudden onset of acute myocardial ischemia due to obstructed coronary blood flow. Currently around the world, ACS affects people's physical and mental health and also is a public health problem in the community. According to the common and continuous pathophysiology process, during the acute myocardial ischemia, ACS may classify as unstable angina(UA), non-ST segment elevation myocardial infarction(NSTEMI),ST segment elevation myocardial in- farcttion(STEMI).For ACS patients, accurate risk stratification in early hospitalization will determine whether a positive-invasive examination and treatment is essential. Among patients with chest pain, there is a wide range of prognosis. Low-risk patients only need a modest treatment, and high-risk patients need invasive treatment positively. Therefore, risk stratification will not only help determine an accurate prognosis and account for the patient's condition, should also be sub-detectable levels in patients with different medical needs. We can choose the appropriate treatment places from the emergency room of chest pain center to the coronary care unit, and treatment methods from the Drug conservative treatment to the emergency revascularization, and treat patients timely and avoid wasting medical resources.Because of its unique biological characteristics, cTnI has become the index with high sensitivity and specificity after cardiac cells injured,and has high clinical value for diagnosis of AMI and myocardial damage,monitoring the condition and evalution of prognosis. However it should be noted that cTnI is insufficient for early diagnosis of myocardial injury. At the same time,Currently the detection of cTnI is still affected by some kinds of factors.Therefore, in order to enhance the application value of cTnI,it is always to detect cTnI dynamically and combine with other test results,then analysis all comprehensivly.So,it has become a necessity that finding more new biochemical markers to apply to ACS for early diagnosis, prognosis and risk stratification.Coronary artery endothelial dysfunction, inflammation, plaque rupture and thrombosis contribute equally to the process. These factors interact with each other. According to the lastest research, throm- bosis,caused by the rupture of plaque due to ather-osclerosis and endothelial dysfunction, is the direct cause. Recently inflammation and immune abnormalities are considered the most important factors in these mechanisms, and even contribute more than the artery atherosclerosis and thrombosis formation. Studies have shown that in-flammatory factors closely related to plaque rupture and instability. These inflammatory factors including C-reactive protein (CRP) from the liver, interleukin -6 (IL-6) from the fat cells, intercellular adhesion molecule-1 (ICAM-1) from the endothelial cell, matrix metalloproteinase (MMPs) from the white blood cells,and myelo-peroxidase (MPO) from the platelet CD40, etc. Increased MMPs is closely related to the thinning of coronary ath-erosclerotic plaque fibrous cap, ultimately lead to un-stable angina pectoris and acute myocardial infarction. From stable angina to unstable angina pectoris, the ex-pression and activity of MMPs,found in ACS patients'serum and mononuclear cell, was significantly increased in each phases. Platelets play an important role in coronary atherosclerosis formation and progression, while CD40L contributes more to the mechanism. CD40L expression will rapidly increase in platelets surface after platelets are activated, and then soluble fragments of sCD40L are generated by hydrolysis. Through stimulating platelet-activating, sCD40L could intensify inflammation, and block re-endothelialization of damaged endothelium and stabi-lize platelet-rich thrombus and other mechanisms to pro-mote the progress of coronary atherosclerosis. Meanwhile, CD40-CD40L can influence atherosclerotic plaque stability by regulating the expression of MMPs in the plaque. Hs-CRP is found the most important inflammatory markers in acute coronary syndrome, and its main function is complement-activating and anti-inflammatory. Study found that serum hs-CRP in patients with unstable angina was significantly higher than in patients with stable angina pectoris. The marked increase of CRP in ACS patients will predict the occurrence of ACS, also will determine the severity of coronary heart disease, and it is also a prognosis for sudden death by cardiac rupture and cardiovascular events after stenting. Interleukin-6 (IL-6), also known as pro-inflammatory factors, can influence inflammation, host defense and tissue damage through regulating the humoral and cellular immune function, and contribute to the acute phase response and synthesis of liver cells. Compared to control group, IL-6 level was significantly high ex-pression in ACS patients. Serum IL-6 level reflects the severity of coronary artery disease and unstable angina pectoris, and prognosis of AMI. Myeloperoxidase (MPO) is a heme enzyme, released by activated neutrophils, mono-cytes and macrophages. The expression and increased activity of MPO promote the formation of atherosclerosis. Through the promotion of LDL oxidation in atherosclerotic plaque, damage of endothelial function, degradation of the extracellular matrix,MPO can affect the stability of atherosclerotic plaque, and as a new emerging inflammatory marker in the diagnosis and risk assessment of ACS, and as a better indicator of local inflammation. Adhesion molecule, between cells and cells, cells and extracellular matrixes, leads to local inflammatory reaction and is an important factor for thrombosis. Low-density lipoprotein (LDL) was modified into lipid-plaque by oxidation, gly-cation, aggregation, immune complex formation and other channels,and may cause inflammation to promote inter-cellular adhesion molecule (ICAM-1) to express increasely and local inflammatory cells to react intensively. Monocyte chemotactic factor (MCP-1) is the original dynamic factor in a network of inflammatory factors, and can promoting the inflammatory response by activating monocytes/macrophages specific chemotactic, and may be involved in the occurrence of coronary heart disease. Endothelial damage is considered to be the original dynamic factor of ACS, and the relationship with MCP-1 has raised concerns. The overexpression of MCP-1 is obviously observed in patients, who both have hypertension and atheromasia. So the detection of MCP-1 may reflect endothelial damage. MCP-1 not only contribute to the formation of AS, but also promote the instability of plaque. In short, the inflammatory response and vulnerable plaque rupture reinforce each other, and initiated the path-ophysiologic mechanism of ACS in a vicious cycle, and progressly formed the thrombosis, leading to clinical ACS. In addition, brain natriuretic peptide and myocardial injury markers,which have been applied to clinic, were shown to be a good prognostic value in ACS patients, and can provide clinical guidance through early diagnosis of ACS, risk stratification and prognosis evaluation.But the ACS is a complex pathophysiological process,a single biochemical marker can not fully explain the ACS change, development and prognosis.Therefore, choosing joint detection of biomarkers, which can reflect the different pathophysiology stages in ACS patients, through establishing risk prediction model to quantitatively evaluate short-term prognosis, as to provide positive clinical significance for the early diagnosis,risk, stratification, prognosis,treatment programs, has become a research hotspot both at home and abroad.objective1. To investigate the predicting value of plasm levels of cTnI Immediate admission on risk stratification and prognosis in patients with ACS.2. Preliminary investigation on the predicting value of multibiochemical markers strategy on risk stratification and prognosis in patients with ACS.Objects and MethodsObjects264 cases of patients(male 180 cases,female 84 cases,64(55-69)y) who with chief complaint of chest tightness or pain had been admitted to the Cardiology department of Southern Medical were enrolled between June 2008 and January 2010 continuously.xclusion criteria in this study were patients with history of heart-failure, pulmonary infarction, pericarditis, myocarditis, cardiomyopathy, aortic dissection, peripheral vascular disease, cerebrovascular disease, acute and chronic inflammation, immune and connective tissue diseases, fever, hyperthyroidism/secondary anemia caused by angina pectoris symptoms.MethodA history and physical examination, whole blood collection were obtained in all patients initially when they were admitted in hospital. Respectively check electrocardiogram and monitored myocardial enzymes, cardiac troponin I at the time of immediately after admission,6 hours,12 hours,24 hours(the initial cTn and maximum were recorded.) Recorded all patients' Vital Signs,coronary heart disease factors including smoking,hypertension,diabetes,etc. Monitored blood lipids, liver/kidney function and glycosylated hemoglobin,etc with fasting blood the next day morning. Collected all patients' venous blood 20ml,9ml was sent to clinical laboratory medicine to test hs-CRP, NT-proBNP, CK-MB and cTnI,the remaining 8ml was used to test MPO, MCP-1, sICAM-1, sCD40L, MMP-9, IL-6 and IL-27.Closely monitored and recorded all patients'condition at the time and after they were admitted,and according to whether the cardiac events occured,all patients were divided into cardiac events group(63 cases) and non-cardiac events group (201 cases). The patients in cardiac events group received coronary angiography within 24 hours and who in non-cardiac events group received CAG during hospitalization.Wilcoxon rank sum test andx2 test were used for comparisons of all continuous and categorical variables,respectively.Each biochemical marker was divided into two categories according to the cut-off value obtained by the area under the ROC curve. A stepwise logistic regression analysis was conducted filtering the following variables: NT-proBNP, CK-MB,hs-CRP, MPO, MCP-1, sICAM-1, sCD40L, MMP-9, IL-6 and IL-27.And established the forecasting model by the biochemical marker filtered,then the effectiveness of forecasting was evaluted by Jacknife method,and drawn ROC curve to evaluate the predictive value of model.Risult1. The result of single factor analysis showed that LVD, EF, glycosylated hemoglobin and cTnI were significant statistically on whether cardiac events occured.2. The result of multiple factor logistic analysis showed that glycosylated hemoglobin and cTnI were significant statistically on whether cardiac events occurred (P<0.05).cTnl is an independent predictor for forecasting of cardiac events.3. The sensitivity, specificity and accuracy of cTnI was 50.79%,77.11% and 70.83% respectively.ROC curve analysis showed that the area under the ROC curve was 0.64,which was bigger than 0.5,so that the level of cTnI has a predictive value.4. The differences of NT-proBNP, hs-CRP,MPO,sCD40L,MMP-9 and CK-MB was statistically significant between Emergency CAG group and elective CAG group (p<0.05); The level of MCP-1,sICAM-1,IL-6 and IL-27 were no statistically significant between two groups(p>0.05).The cut-off value of NT-proBNP,hs-CRP,MPO,MCP-1,sICAM-1,sCD40L,MMP-9,IL-6,IL-27 and CK-MB were 179pmol/L,8.35mg/L,0.319pg/ml,0.282pg/ml,0.1835ng/ml,0.2375ng/ml,0.141ng/ml,0.2215pg/ml,0.223ng/ml,21.6IU/L se-parately,which abtained by using ROC curve.Divided all biochemical markers into two groups according to their cut-off value.5. To whether there had been changed in condition as the dependent variable, The stepwise logistic regression analysis was used for correcting LVD,EF,Fasting blood glucose,Glycohemoglobin and cTnI, which had significant difference in single-factor analysis, and analysis of biochemical markers on the progression of ACS.6. The forecasting model created by the biochemical markers obtained from the stepwise logistic regression analysis: p=1+exp (5.6044-2.8821g1-2.2231g2-3.1025g3+2.6092g9-5.0741g10) Notes:g1:NT-proBNP,g2:hs-CRP,g3:MPO,g4:IL-27,g5:CK-MB Jacknife was used to forecast the validity of the model.and results show that its determine accuracy was 89.8%,and sentence error rate was 10.2%,diagnostic sensitivity and specificity were 76.2% and 94% respectively.Then draw ROC curve,the area under ROC curve was 98.1.7. Comparing with cTnI,multiple biochemical markers has a higher Sensitivity (76.2% and 50.79%), specificity (94% and 77.11%) and accuracy (89.8% and 70.83%).Conclusion1.The level of immediate cTnI in patients with ACS is an early independent predictor for cardiac events,so that it has a certain significance for risk stratification and evaluation of prognosis in patients with ACS early.2.The concentrations of plasm NT-proBNP, hs-CRP,MPO,sCD40L,MMP-9 and CK-MB in the clinical high-risk patients were higher than the low-risk patients.3. It is helpful for hospitalized patients with ACS to be risk stratification early by jointing detection of multiple biochemical markers.4.Forecast model of multiple biochemical markers has a higher sensitivity, specificity and accuracy for Prediction of early cardiac events in patients with ACS than cTnI...