The Clinical Utility of Serum Apelin in Patients with Acute Coronary Syndrome and Established Coronary Artery Disease

Abstract

SUMMARY and CONCLUSION C oronary artery diseases (CAD) are diverse, with a spectrum that comprises various forms of angina pectoris, acute myocardial infarction (AMI) and sudden cardiac death. Coronary artery disease (CAD) is increasing in prevalence and is predicted to become the dominant cause of mortality worldwide. Coronary atherosclerosis with subsequent superimposition of an arterial thrombus over an underlying disrupted atherosclerotic plaque represents the major pathogenic process in CAD. A variety of inflammatory and other biochemical markers potentially related to atherogenesis have been identified, some of which may also originate from the adipose tissue, which is an active endocrine and paracrine organ that releases several bioactive mediators, including apelin. Apelin is a peptide isolated initially from the bovine stomach extract. It is synthesized and secreted by the adipose tissue suggesting a role as adipokine. It is synthesized as preproapelin and smaller peptides such as apelin -36, -12, -13 and -17 are subsequently produced by post-translational modification. All apelin peptides affect through APJ receptor, an orphan cell surface G protein-coupled receptor. Preproapelin and its receptor were detected in various parts of the body as heart, kidney, testis and adipose tissue. Several studies have shown that apelin functions in various organ systems, where it was reported to be involved in the regulation of blood pressure, cardiac contractility, water intake and angiogenesis. Circulating apelin levels are decreased in patients with CAD, which may reflect its prominent expression and function in cardiovascular tissues, cardiomyocytes, vascular smooth muscle cells, and endothelial cells. Apelin actions include enhancement of endothelium-dependent vasodilation, cardiac contractility and reduction of vascular wall inflammation, through nitric oxide (NO) dependent mechanism andan antagonistic effect on angiotensin II.Moreover, serum apelin level was independently associated with arterial stiffness and the presence of coronary plaque, even after adjusting for other cardiovascular risk factors and medication history in patients with endothelial dysfunction. In this regard, our study aimed to investigate the plasma apelin level in patients with CAD and to clarify the relationship between atherosclerosis and apelin. This study was conducted on sixty patients undergoing coronary angiography at the Cardiology Department of Ain Shams Hospital for evaluation of CAD, who were classified according to angiography into three subgroups: group IA (unstable angina group), group IB (acute myocardial infarction group) and group IC (asymptomatic CAD group), in addition to twenty five age- and sex- matched subjects serving as a control group. All participants were subjected toroutine investigations as (Fasting and 2hours postprandial blood glucose, fasting lipid profile, kidney function tests, liver function tests, ESR, and CBC), specific investigations as (Cardiac troponin-I (cTnI), total creatine kinase (TCK), and CK-MB) and Serum apelin levelsby ELISA technique. Results of the current study revealed a highly significant difference in serum level of apelin in patients’ group when compared to control group. A highly significant difference in serum level of apelin was also observed in AMI group when compared to UA or asymptomatic CAD group. A remarkable finding was that there was a significant negative correlation between apelin and LDL-C in both UA and asymptomatic CAD groups, while such correlation was not observed in AMI group. Also,a highly significant negative correlation between apelin and Gensini Score was found in all patient groups Receiver operating characteristic (ROC) curve analysis was applied to assess the diagnostic performance of serum apelin (ng/ml) for discriminating patient group (Gp I) from control group (Gp II). The best cutoff level of apelin was 3.7 ng/mL, its diagnostic sensitivity was 95%, specificity 92 %, positive predictive value 96.6%, negative predictive value 88.5% and the diagnostic efficiency was 94.1%. The area under the curve (AUC) was 0.984. Moreover, receiver operating characteristic (ROC) curve analysis was applied to assess the diagnostic performance of serum apelin (ng/mL) for discriminating UA patients (Gp IA) from AMI patients (Gp IB). The best cutoff level of apelin was 0.9 ng/mL, its diagnostic sensitivity was 90%, specificity 88%, positive predictive value 85.7%, negative predictive value 91.7% and the diagnostic efficiency was 88.9%. The area under the curve (AUC) was 0.927.