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.

Plasma asymmetric dimethylarginine predicts death and major adverse cardiovascular events in individuals referred for coronary angiography

“…Furthermore, when comparing with both large studies, our study subjects were older, with lower BMI, and more likely to have diabetes, suggesting our cohort may be composed of relatively higher risk population. Nevertheless, our results showed that in addition to all-cause mortality and MACE, plasma ADMA remained a significant independent risk factor in the combined end-points of MACE and TVR, which was similar to the results of our previous report and a recent study investigating the role of plasma ADMA level and restenosis after elective coronary angioplasty [18,27]. The relation of ADMA and restenosis after PCI deserves further detailed investigation in larger cohort.…”

Titanium-nitride-oxIde-coated stents multicenter registry in diaBEtic patienTs: the TIBET registry

“…A recent study demonstrated that asymmetric dimethylarginine, a nitric oxide synthase inhibitor that increases in diabetics, was an independent predictor of restenosis following PCI [37]. Moreover, new-generation DES demonstrated a different vascular response compared to earlier FDA-approved ones, even when implanted sideby-side in the same vessel [38].…”

Association of midregional proadrenomedullin with coronary artery stenoses, soft atherosclerotic plaques and coronary artery calcium

“…This process contributes to the pathogenesis of several cardiovascular disorders, including arteriosclerosis and restenosis [15,16]. Anti-proliferative actions of ADM have been found in rat cardiac fibroblasts and VSMCs [17,18].…”