The perfect biomarker in acute coronary syndrome: a challenge for diagnosis, prognosis, and treatment.

The use of biomarkers is one of the most important strategies for risk stratification among the increasing number of patients admitting to hospitals for acute coronary syndrome (ACS). The revolutionary benefit of using cardiac-specific troponins in this setting is the excellent specificity and sensitivity for myocardial injury, and several studies have confirmed the superiority of troponins as compared with creatine kinase-MB (CK-MB) for this purpose. The discovery of troponins as valuable markers for predicting mortality in unstable angina led to ‘The Joint European Society of Cardiology/American College of Cardiology Committee Consensus for the redefinition of myocardial infarction’ from 2000 which included elevated troponins as an obligatory criterion in the diagnostics of acute myocardial infarction (AMI). These changes in the guidelines have increased the incidence of diagnosed AMI and expanded the groups of patients with a high risk for coronary events. Increasing numbers of patients in need of percutaneous coronary intervention (PCI) are a challenge for the capacity of invasive centres. Those at high risk need to be identified at an early time point in order to optimize treatment for ACS patients. Biomarkers are important tools in this setting and provide potential information regarding early detection of subclinical disease, risk stratification, selection of therapy and monitoring disease progression or treatment efficacy. Elevated troponins are today the most important tool for selection of non-ST-segment elevation acute coronary syndromes (NSTE-ACS) for coronary angiography and PCI. However, the golden moment for optimal outcome of coronary revascularization is within 4 h after the onset of occlusive coronary thrombosis. Troponins are not necessarily elevated in serum before 12 h after onset of symptoms and are not optimal for identification of patients without ST-segment elevation on ECG that would benefit from early revascularization. Data from the OPERA registry have demonstrated similar 1 year mortality among ST-segment elevation myocardial infarction (STEMI) and non-ST-segment elevation myocardial infarction (NSTEMI) patients from 56 centres in France in 2002 and 2003, despite different management and guidelines. This suggests that NSTEMI patients at high risk would obviously benefit from earlier revascularization than stated in today’s guidelines. Thus, increasing interest in early detection markers of myocardial injury has evolved over the last few years. In this respect, we are still searching for the perfect biomarker or set of biomarkers that would identify patients with increased risk at the earliest time point, and allow a better selection for early PCI, which in turn may increase survival among NSTEMI patients. McCann et al. report a prospective study on early biomarkers of AMI that addresses this very important issue. The authors included 415 patients from a single centre during 3 years from August 2003 with acute ischaemic-type chest pain of ,24 h duration. AMI was defined according to the guidelines using cardiac troponin T (cTnT) and ECG. The study demonstrates that assessment of heart fatty acid-binding protein (H-FABP) identifies AMI ,4 h after onset of symptoms, with a sensitivity superior to cTnT. However, the lack of specificity in detecting AMI is obviously a major disadvantage of using H-FABP in this setting. H-FABP is also compared with several other biomarkers such as N-terminal pro-brain natriuretic peptide (NT-proBNP), d-dimer, high sensitivity C-reactive protein (hsCRP), myeloperoxidase (MPO), and matrix metalloproteinase-9 (MMP-9), which gave no additional information to cTnT regarding early sensitivity. The traditional marker of early myocardial injury, myoglobin, is not compared with H-FABP in the study, but was reported as less reliable than H-FABP in a previous study. H-FABP is a 15 kDa protein thought to be involved in myocardial lipid homeostasis, and is present in substantial amounts in the