A novel predictor of restenosis and adverse cardiac events: asymmetric dimethylarginine

Abstract

The aim of this study is to investigate if serum asymmetric dimethylarginine (ADMA) levels can predict restenosis and major adverse cardiac events (MACE) in patients who undergo percutaneous coronary interventions. The most important cause of restenosis following percutaneous coronary intervention is neointimal hyperplasia. Nitric oxide (NO) prevents the neointimal hyperplasia growing. Asymmetric dimethylarginine is a competitive inhibitor of NO synthesis. The effect of ADMA on the restenosis has not yet been investigated. A total of 105 (80 male and 25 female) patients were included in our study. All patients underwent elective percutaneous transluminal coronary angioplasty (PTCA) with bare metal stent implantation or direct stenting for one coronary artery between September 2004 and January 2006. All patients were clinically followed for a period of 6 months, and a control angiography was performed at the end of this period. The probrain natriuretic peptide (pro-BNP), high-sensitivity Creactive protein (hs-CRP), and ADMA levels of the patients were evaluated before the procedure and 6 months afterwards. Biochemical parameters and angiographic features were evaluated in order to determine if they could predict the development of restenosis and MACE by using univariate and multivariate Cox regression analysis. The 65 (61.9%) patients (50 males and 15 females) who had not developed restenosis were designated as Group 1. The 27 (25.7%) patients (21 males and 6 females) who had developed restenosis were designated as Group 2. In terms of predicting the development of restenosis, the presence of diabetes mellitus (hazard ratio [HR]: 2.78; confidence interval [CI]: 1.25-6.20; P = 0.01), type of lesion (HR: 1.89; CI: 1.01-3.55; P = 0.04), form of procedure (HR: 0.30; CI: 0.11-0.81; P = 0.01), and ADMA (HR: 4.08; CI: 1.73-9.62; P = 0.001) were found to be significant in univariate Cox regression analysis. In contrast, only the levels of ADMA were found to be a significant predictor of restenosis in the multivariate Cox regression analysis (HR: 3.02; CI: 1.16-7.84; P = 0.02). The restenosis prediction of ADMA levels continued after excluding the patients with diabetes mellitus in the univariate and multivariate Cox regression analysis (HR: 5.23; CI: 1.99-13.76; P = 0.001 and HR: 5.61; CI: 1.79-17.62; P = 0.003, respectively). Regarding the development of cardiac events, hs-CRP (HR: 1.03; CI: 1.00-1.06; P = 0.01) and ADMA (HR: 17.1; CI: 3.06-95.8; P = 0.001) were found to be significantly correlated with adverse cardiac events in univariate Cox regression analysis, whereas only ADMA levels were significant in the multivariate Cox regression analysis (HR: 2.83; CI: 1.27-6.31; P = 0.01). The levels of ADMA obtained before the procedure predict the development of restenosis and MACE in patients who underwent elective PTCA and bare metal stent procedures.