| Abstract: |
Coronary artery disease is a major problem and a growing cause of both morbidity and mortality .The severity of coronary artery disease determines the clinical presentation and the pathogenesis of the disease. In addition, the strategy of the therapy will differ according to the underlying disease severity.Atherosclerosis was considered a blind lipid storage disease. Recent advances in basic science have established a fundamental role for inflammation in mediating all stages of this disease from initiation through progression and, ultimately, the thrombotic complications of atherosclerosis .These new findings provide important links between risk factors and the mechanisms of atherogenesis. Elevation in markers of inflammation predicts outcomes of patients with acute coronary syndromes, independently of myocardial damage. In addition, low-grade chronic inflammation, as indicated by levels of the inflammatory marker such as C-reactive protein, prospectively defines risk of atherosclerotic complications, thus adding to prognostic information provided by traditional risk factors .These new insights into inflammation in atherosclerosis not only increase our understanding of this disease, but also have practical clinical applications in risk stratification and targeting of therapy for this scourge of growing worldwide importance.The traditional biomarkers of myocardial necrosis were not cardio specific and also reflect myocyte injury but do not pinpoint the specific mechanism of injury and are not active contributors to pathophysiology of CAD. There is still a need of development of earlier markers that can reliably rule out myocardial damage from the emergency room at patient presentation and , hopefully, detect myocardial ischemia both with and without the presence of irreversible myocyte injury.So the purpose of this review is to provide an overview of the pathophysiology , clinical and analytical characteristics of biomarkers that may have potential clinical utility to identify and risk assessment of coronary artery disease patients.There are main classes of markers: markers of early injury\ ischemia, markers of inflammation and coronary plaque instability and disruption and markers of ventricular overload.*Markers of early injury/ischemia:Free fatty acids:These free fatty acids provide a sensitive guide for early myocardial injury as they appear in circulation before traditional markers of myocyte necrosis. Increased blood catecholamine in association with ischemia, also increase lipid hydrolysis within the heart cause this increase in free fatty acids. They also increase early in the presence of myocardial injury and ischemia independent of plaque rupture.Ischemia-modified albumin:It was observed that ischemia produce lower metal-binding capacity of albumin for cobalt than the albumin in the serum of normal individual. Ischemia-modified albumin increase within minutes after transient ischemia, so it was a good marker for early detection of cardiac ischemia.Heart-fatty acid binding protein:H-FABP is a relatively small protein, it comprise 4.8% of the total cytoplasmic protein of cardiac myocytes.H-FABP is released rapidly from the myocardium into the blood stream after ischemic injury. It alsoappears rapidly in urine, and the urinary concentration correlates with the severity of the myocardial injury. Plasma H-FABP increase within 3h of the onset of myocardial injury, and return to normal within 24h.It has been reported that H-FABP is a suitable marker for early detection of myocardial injury, estimation of myocardial infarction size and a good marker of reperfusion following AMI.Glycogen phospholyrase:It was a sensitive marker of early myocardial damage,it released within 2-4h after onset of myocardial damage, so it can help in diagnosis of AMI in first 4h after onset of pain.Myosin light chain:It is a part of sarcomere of cardiac muscle, appears in the serum 3-6h after the onset of pain and peak after about 4 days.It correlate with the severity and size of infarction.*Markers of inflammation, coronary plaque instability and disruption.C-reactive protein:CRP, an acute phase protein, is a marker of inflammatory process that contributes importantly to atherogenesis, plaque disruption and thrombosis. Products of thrombosis including platelet derived growth factor, augment production of CRP. More than simply a marker of inflammation, CRP may influence directly vascular vulnerability through reduced endothelial nitric oxide bioactivity thus CRP involved with the pathogenic mechanism that drive acute coronary syndromes. It also predicts the outcome of patients following presentation with AMI.sCD40L:sCD40L is derived from activated platelets , which is an important contributor to inflammatory process that lead to coronary thrombosis. Elevation of sCD40L indicates an increased risk of cardiac events in patients without myocardial necrosis.Choline:Early ischemic membrane damage lead to activation of phospholipase and release of choline into plasma, so it was considered as an early marker of myocardial ischemia.Pregnancy-associated plasma protein A:It was a proatherosclerotic molecule through its role in disrupting the integrity of the atheroma protective cap, so measurement of PAPP-A appeared to be valuable for detecting unstable AMI even in patients without elevation of biomarkers of necrosis, thus potentially identify high risk patients.Placental-growth factor:It is one of a family of platelet-derived proteins that function as a potent chemoattractants for monocyte and are involved in the regulation of vascular endothelial growth. It also appears to be involved in the inflammatory process, so it is a strong biomarker for prognosis of AMI patients.Myeloperoxidase:It has emerged as a potential participant in promotion and propagation of atherosclerosis from endothelial dysfunction up to thrombus formation, so measurement of MPO help to identify high risk patients.MMPs:It was the physiological regulators of extracellular matrix, so it partially responsible for the degradation of ground substance and vascular remodeling after cardiac injury.*Marker of ventricular overload:Brain natriuretic peptide:Acute ventricular dysfunction is a hallmark of sudden and prolonged myocardial ischemia, and is one of the first step in the ischemic cascade that lead to cell necrosis.It was found that Brain natriuretic peptide increases with ventricular stretch as occur with the beginning of ischemic event.BNP considered as a marker of early detection of myocardial ischemia.RecommendationThere is now accumulating evidence that these new biomarkers could help in early diagnosis and risk assessment of high risk patients early before occurrence of an adverse event and pointed to patients who are high risk to get myocardial ischemia.
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