Increased plasma lipoprotein-associated phospholipase A2 (Lp-PLA2) levels are related to good collateral development in patients with isolated left coronary artery disease

Abstract

Development of coronary collaterals (CCs) is a time-dependent adaptive response to an ischemic process arising from the gradient between obstructed arteries and myocardial ischemia. It is a complex inter-relationship among various factors [1]. A complex interaction exists between new blood vessel formation and inflammation. However, little data are available on the relation between inflammation and the development of CCs [2,3]. Inflammation has emerged as central to the initiation and progression of atherosclerosis. The mechanism(s) underlining collateral artery growth closely resemble those of atherosclerosis. Lipoprotein-associated phospholipase A2(Lp-PLA2) is actively secreted by monocyte-derived macrophages in atherosclerotic plaque. Lp-PLA2 is a unique inflammatory biomarker, as it is highly vascular specific, has low biologic variability, and is directly related to the propensity of plaque rupture and the degree of inflammation present in the walls of coronary arteries [4]. The inflammatory process is also associatedwith an increased oxidant environment. In a recent study, it was indicated that oxidative stress may also play an important role in the development of CCs [5]. Ischemia modified albumin (IMA), the earliest ischemic marker, in atherosclerosis has been extensively studied, but, there is no data on the possible involvement of Lp-PLA2 and IMA in the development of coronary collaterals. In this prospective preliminary study, it was aimed to investigate the possible role and involvement of plasma Lp-PLA2, IMA and oxidant stress status in patients with isolated left coronary artery disease (CAD). This prospective study was conducted between January 2007 and September 2009 in our university hospital setting. Clinical indications were considered in all patients undergoing coronary angiography by using the standard femoral approach by the Judkins technique. Because the multi-vessel coronary disease has a significant influence on the development of collaterals, we mainly evaluated the single-vessel disease group, with ≥90% narrowing or total occlusion of the left anterior descending (LAD) and nonsignificant (b30%) narrowing of the non-LAD (5). The study was approved by the local Ethics Committee. Coronary collateral development was graded according to the Cohen– Rentrop method [6]. Classification of the patients according to the Rentrop's score yielded 24 of patients with poor developed CCs, (Rentrop's score of 0 to 1), and 21 had good developed CCs (Rentrop's score of 2 to 3). The Gensini score was computed for each patient from the coronary arteriogram by assigning a severity score to each coronary stenosis [7]. The levels of serum total cholesterol (TC), triglyceride (TG), LDL cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDLC) were determined by enzymaticmethods using a ROCHE autoanalyzer (Modular System,GmbH,Mannheim,Germany). hs-CRPwas assessed by the latex enhanced immunonephelometric method (DADE BEHRING, GmbH, Marburg, Germany). Lp-PLA2 concentration (mass) was measured by a turbidimetric immunoassay method (PLAC® test, diaDexus). Lp-PLA2 activity was measured in an autoanalyzer (Roche, Cobas-6000). The inter-assay coefficient of variation (CV) was 6.2%. Serum total antioxidative capacity (TAC), total oxidant status (TOS) and Oxidative Stress Index (OSI) were assayed as described previously [8]. Inter-assay CVswere 2.5% and 3.1% respectively. The IMA level was assayed by using Bar-Or et al.'s method [9]. The results were reported as absorbance units (AbsUs). Inter-assay CV was 4.2%. Of the inflammation markers, Lp-PLA2 was found to be significantly higher in patients with good CCs thanwith poor CCs (pb0.020) while hs-CRP was lower in patients with good CCs thanwith poor CCs. The results of the present prospective study demonstrated that Lp-PLA2 has an independent association with good coronary collateral development andwithGensini score in patientswith isolated left coroner artery involvement. This is the first report investigating the plasma Lp-PLA2 level in coronary collateral development. Lp-PLA2 plays a pivotal role for inflammatory progress of the atherosclerotic process [10]. Lp-PLA2 is a unique inflammatory biomarker, as it is highly vascular specific, and has low biologic variability compared to the hs-CRP (4). Little data are available on the relation between inflammation and the development of CCs [11]. In those studies, authors showed an inverse relationship between CRP and coronary collateral development. Similar distribution of the CRP level between poor and good CC groups was observed in the