Evaluation Of Ischemia Modified Albumin On The Early Diagnostic Value In Acute Ischemic Chest Pain

BackgroundChest pain is the second common disease in the emergency department. But patients with acute chest pain suggestive of acute ischemic chest pain (ICP) present with a heterogeneousarray condition, including non-ischemic chest pain (NICP), transient myocardial ischemia, unstable angina (UA), non-ST-elevation myocardial infarction (NSTEMI) and ST-elevation myocardial infarction (STEMI). Ischemic chest pain is one kind of clinical syndrome owing to coronary atherosclerotic plaque rupture, which induces to form thrombus or concomitance coronary artery spasm to lead to coronary artery stenosis or occlusion. It includes UA, STEMI, and NSTEMI and belongs to emergency case of coronary atherosclerotic heart disease. Acute cardiac ischemia is the commom mechanism underlying ischemia chest pain that, when prolonged, may lead to myocardial damage and myocardial necrosis. Therefore, it is every important to search for not only an economy but also a sensitive accurate myocardial ischemic biomarker of earlier myocardial ischemia.Currently, biomarkers of myocardial ischemia have prodigious limited. Rest photonemission computed tomography has been reported as a safe and effective tool for assessing acute ischemia, but its sensitivity is limited by the requirement that the contrast agent be injected during active chest pain. Sensitivity of radionuclide imaging is limited by an injury threshold value of 10g myocardium, and specificity is affected by attenuation of artefacts. ECG has higher specificity in the diagnosis of ICP, but it's sensitivity lesses than 50%. With regard to biochemical markers of ischemia, initial data for glycogen phosphorylase-BB were encouraging, but these results have not been confirmed. Cardiac troponin T is the specificity protein of cadiocyte, it releases to blood when cadiocytes were damaged, but it is limited in the early diagnosis of myocardial ischemia and it doesn't necessarily rise in blood with reversible ischaemia. Serial or continuous monitoring kinesis variation recordings of biomarker of myocardial necrosis, such as cardiac troponins, myoglobin, and isoenzyme of creatine kinase MB, often are used to diagnose myocardial damage, but it takes about two to six hours for these biomarker to resease into the circulation. How to efficiently rule out ischemia chest pain quickly remains the most problem of emergency physician faced. If earlier myocardial ischemia can be founded, abreast evaluated and interfered, be reversible myocardial ischemia can be avoided or decreased. Thus clinical physician constantly dedicate to search for sensitive biomarkers of myocardial ischemia, which can be detection in reversible stage of earlier ischemia, this can conduce to the correct diagnosis andtreatment of patients with acute myocardial ischemia.There is no "gold standard" for accurately assessing myocardial ischemia. There is need for early and sensitive, a new biomarker of myocardial ischemia to identify lots of acute chest pain patients presenting with ischemia chest pain and who are at high risk for adverse cardiac events. Furthermore, the lace of sensitivity of available diagnostic tools precludes early discharge patients with non-ischemia chest pain. Some researcher observed a phenomenon of decrease in vitro binding of exogenous cobalt (Co²⁺) to the N-terminus of human serum albumin (HSA) in emergency chest pain patients with early onset unstable angina and myocardial infarction. HSA became IMA, and this change can be measured by the Albumin Cobalt Binding (ACB) test. The IMA has recognized as a maker for the acute myocardial ischemia.ObjectiveThe study is to confirm that IMA can identify ture ischemic chest pain, and to distinguish UA from AMI, and to make receiver operator characteristive (ROC) curve to get the cutoff of our own laboratory, and to evaluate the clinical performance of IMA. MethodsOne hundred and twenty nine patients who arrived at emergency department or cardiology department within six hours of clinical sign and symptoms of acute ischemic chest pain were taken as the target population. All enrolled patients had a 12 lead ECG and blood collected immediately after arrival, hereafter referred to as "presentation", and at least one other specimen collected between 6 and 24 h later, and underwent standardized triage, diagnostic procedures and treatment. Clinical physicians were blinded to the IMA results. Patients were designated as ICP group and NICP group and ICP group departed into UA group and AMI group furtherly based on the final diagnosis. IMA was measured by the Albumin Cobalt Binding test (ACB Test) and results of IMA showed with u/ml. ROC curve analysis was used to determine the optimal cutoff of this assay for identifying individuals with ICP from NICP. Results of IMA, ECG and cTnT were correlated with final diagnosis and their diagnostic sensitivity, specificity, negative predictive value, and positive predictive value were evaluated for ICP.Results1. There was an obvious distinction of IMA levels between the two groups (NICP and ICP). ICP group had a mean±SD of (86.00±11.67) U/ml, whereas NICP group had a lower mean±SD of (66.47±14.19) U/ml.2. ROC curve analysis was used to determine the optimal cutoff of this assay for identifying individuals with ICP from NICP. Sensitivity and specificity at a cutoff value of 77.90 U/ml were 87.8% and 72.9%. The area under the ROC curve was 0.837 (95%CI 0.765～0.909).3. There was no distinction of IMA levels between the UA group (84.32±9.36) U/ml and AMI group (80.92±12.24) U/ml.4. When used along, the sensitivity of IMA was significantly higher than that of cTnT (87.5% vs 18.5%, x²=77.728, P=0.000) and ECG (87.5% vs 40.6%, x²=38.781, P=0.000). When IMA was used with ECG, the sensitivity increased to 92.5% (x²= 49.000, P=0.000) and this was similar to that of IMA used with cTnT 90.1% (x²= 83.687, P=0.000). Sensitivity of the three tests combined was 96.3%, which was significantly greater than that of ECG and cTnT combined 50.6% (x²=79.246, P= 0.000).5. When used along, the negative predictive (NPV) of IMA was significantly higher than that of cTnT (77.2% vs 41.6%, x²=16.143, P =0.000), and also higher than that of ECG (77.2% vs 47.2%). When IMA was used with ECG, the PPV increased to 77.7% (x² =7.817, P=0.005) and this was similar to that of IMA used with cTnT 72.4% (x²= 8.784, P=0.003). NPV of the three tests combined was 86.9%, which was significantly greater than that of ECG and cTnT combined (x²=9.229, P=0.002).6. The specificity of IMA was significantly lower than that of ECG and cTnT. The positive predictive value of IMA was statistically equivalent to the PPV of cTnT or ECG.。Conclusions1. IMA can be used to distinguish ICP from NICP.2. IMA is a sensitive biomarker of the earlier ischemia, and it can't use to distinguish myocardial ischemia from myocardial necrosis.3. To compared with cTnT or ECG, IMA has higher sensitivity and NPV, which means, it can improve our ability to identify ischemic patients who are missed by current diagnostic strategies, or more confidently rule out patients who don't have ICP.