Asymmetric Dimethylarginine and the Risk of Cardiovascular Events and Death in Patients With Coronary Artery Disease

Abstract

Abstract-As a competitive inhibitor of endothelial nitric oxide synthase, asymmetric dimethylarginine (ADMA) has been related to atherosclerotic disease. Little is known about the prognostic impact of baseline ADMA determination. Key Words: asymmetric dimethylarginine Ⅲ cardiovascular risk Ⅲ coronary artery disease T he endothelium plays a crucial role in the regulation of vascular tone. 1 A factor of prime importance to maintain endothelial homeostasis is nitric oxide. 2 Apart from its vasodilating effects, nitric oxide released from the endothelial nitric oxide synthase mediates many protective functions against atherosclerosis, such as reduction of adhesion molecule expression and leukocyte adhesion, as well as reduction of proinflammatory cytokines. It further controls smooth muscle cell proliferation and platelet aggregation and balances profibrinolytic activities.Substrate for endothelial nitric oxide synthesis is the amino acid L-arginine. 3 The endothelium is also capable of producing methylated amino acids such as asymmetric dimethylarginine (ADMA), which are able to out-compete L-arginine as a substrate for endothelial nitric oxide synthase, leading to endothelial dysfunction 4 (for review see Cooke 5 ). Importantly, endothelial dysfunction in coronary 6 and peripheral arteries 7 and the degree of oxidative stress within vascular tissue 7 have been recently identified to be independent predictors of future cardiovascular events.Evidence has emerged that circulating levels of ADMA are elevated in patients with cardiovascular risk factors and renal failure and are, in part, associated with the presence of endothelial dysfunction. 4,8 -11 However, it remains unclear whether measurement of levels of ADMA improves cardiovascular risk prediction, in particular, in comparison with traditional risk factors and newly discussed biomarkers such as C-reactive protein or B-type natriuretic peptide.With the present study, we, therefore, addressed the hypothesis that circulating levels of ADMA are independently Original

Effect of supplementation with B vitamins and antioxidants on levels of asymmetric dimethylarginine (ADMA) and C-reactive protein (CRP): a double-blind, randomised, factorial design, placebo-controlled trial

“…Unlike the majority of previous studies such as [58,59], we did not see significantly higher baseline CRP levels among smokers within this study; although a current meta-analysis should confirm the relationship between smoking status and CRP [60], as results have not always been consistent [61]. However, we did show that smokers had significantly higher baseline ADMA levels than non-smokers within this population, which has been previously reported in some [62][63][64], although not all [65,66] studies. When the analysis (percentage of baseline ADMA and CRP at 8 weeks) was stratified by smoking status, we observed no statistically significant differences between the four groups in response to supplementation.…”

Asymmetric Dimethylarginine and Clinical Outcomes in Chronic Kidney Disease

“…With regard to the composite outcomes, the estimated study power in this study was 0.71. Although the mortality rate was relatively low in our high-risk population, in comparison with other similar studies (15,21), the eGFR of our population with CKD was relatively higher, which might be associated with the better outcome of our high-risk cohort. In addition, antiplatelet agents (86.9%) and statins (60.4%) were administered commonly in our patients, which might be another contributing factor to the better outcome in our patients.…”

“…Several studies have shown that plasma ADMA level may predict the progression of renal injury in patients with early-stage CKD (12,13). In addition, high plasma ADMA level has been reported to be an independent risk factor for cardiovascular disease and allcause mortality in a community-based population (14), in patients with coronary artery disease (CAD) (15,16), and in patients with ESRD (17,18). However, evidence about the association between ADMA and patients with mild to moderate CKD is limited.…”

Asymmetric dimethylarginine, arginine and homoarginine at 11–13 weeks’ gestation and preeclampsia: a case–control study

“…8,9 Studies have demonstrated a significant association between elevated ADMA levels and cardiovascular disease. 10,11 Infusion of ADMA is associated with endothelial dysfunction. 12 The ratio of L-arginine to ADMA is associated with altered NOS activity 13 and is a useful index for evaluating the effects of ADMA.…”