Human Heart-Type Cytoplasmic Fatty Acid-Binding Protein (H-FABP) for the Diagnosis of Acute Myocardial Infarction. Clinical Evaluation of H-FABP in Comparison with Myoglobin and Creatine Kinase Isoenzyme MB

Abstract

Heart-type fatty acid-binding protein (H-FABP) is a low molecular weight cytoplasmic protein and present abundantly in the myocardium. When the myocardium is injured, as in the case of myocardial infarction, low molecular weight cytoplasmic proteins including H-FABP are released into the circulation and H-FABP is detectable in a blood sample. We have already developed a direct sandwich-ELISA for quantification of human H-FABP using two distinct types of monoclonal antibodies specific for human H-FABP. In this study we investigated the clinical validity of H-FABP as a biochemical diagnostic marker in the early phase of acute myocardial infarction (AMI). To evaluate the diagnostic usefulness of H-FABP in the early phase of AMI, blood samples were obtained from the following patients within 12 hours after the appearance of symptoms, and serum levels of H-FABP were compared with those of conventional diagnostic markers, such as myoglobin and creatine kinase isoenzyme MB (CK-MB). Blood samples were collected from patients with confirmed AMI (n=140), patients with chest pain who were afterwards not classified as AMI by normal CK-MB levels (non-AMI) (n=49) and normal healthy volunteers (n=75). The serum concentration of H-FABP was quantified with our direct sandwich-ELISA. The concentration of myoglobin mass was measured with a commercial RIA kit. The serum CK-MB activity was determined with an immuno-inhibition assay kit. The overall sensitivity of H-FABP, within 12 hours after the appearance of symptoms, was 92.9%, while it was 88.6% with myoglobin and 18.6% with CK-MB. The overall specificity of H-FABP was 67.3%, while it was 57.1% with myoglobin and 98.0% with CK-MB. The diagnostic efficacy rates with these markers were 86.2% (H-FABP), 80.4% (myoglobin) and 39.2% (CK-MB), respectively. The diagnostic validity of H-FABP was further assessed by receiver operating characteristic (ROC) curve analysis. The area under the curve (AUC) of H-FABP was 0.921, which was significantly greater than with myoglobin (AUC: 0.843) and CK-MB (AUC: 0.654). These parameters, such as sensitivity, specificity, diagnostic efficacy and diagnostic accuracy, obtained for patients with chest pain within 3 hours and/or 6 hours after the onset of symptoms were almost the same as those for patients within 12 hours after symptoms. H-FABP is more sensitive than both myoglobin and CK-MB, more specific than myoglobin for detecting AMI within 12 hours after the onset of symptoms, and shows the highest values for both diagnostic efficacy and ROC curve analysis. Thus, H-FABP has great potential as an excellent biochemical cardiac marker for the diagnosis of AMI in the early phase.

The Use of Biochip Cardiac Array Technology for Early Diagnosis of Acute Coronary Syndromes

“…One earlier study with the use of the same technology demon strated a 100% sensitivity for H-FABP and higher AUC (0.998) at cut-point of 5.08 ng/mL within 6 hours from the onset of chest pain (10). On average, the sensi tivity of H-FABP assays for the early diagnosis of AMI reaches 90% at 5-6 ng/mL as cut-off value (6)(7)(8)11).…”

Point-of-care test of heart-type fatty acid-binding protein for the diagnosis of early acute myocardial infarction

“…ii) steeper tissue-to-plasma gradient: The myocardial content of H-FABP (0.52 mg/g wet wt) is 4.5 fold lower than that of myoglobin (2.35 mg/g wet wt), yet the basic plasma level of H-FABP (2.8 μg/L) is 10-fold lower than the later (30 μg/L) [14,15] . So H-FABP tissue-to-plasma gradient is at least two-fold steeper than that of myoglobin.…”

Early Evaluation of Cardiac Chest Pain – Beyond History and Electrocardiograph

“…The gold standard in the care of a patient with cardiac chest pain is that an ECG and an abbreviated history and physical examination be obtained within 10 minutes of patient arrival. [8] The early diagnosis of acute myocardial infarction (AMI) is however sometimes difficult due to: [9] 1. Equivocal electrocardiogram (ECG) changes and other conditions with ECG changes that mimic acute myocardial infarction.…”