Impact of Asymmetric Dimethylarginine on Mortality After Acute Myocardial Infarction

Abstract

Objective-Asymmetrical dimethylarginine (ADMA) is an endogenous competitive inhibitor of nitric oxide (NO) synthases. From a prospective cohort of patients with acute myocardial infarction (MI), we aimed to analyze the predictive value of circulating ADMA concentrations on prognosis. Methods and Results-Blood samples from 249 consecutive patients hospitalized for acute MI Ͻ24 hours were taken on admission. Serum levels of ADMA and its stereoisomer, symmetrical dimethylarginine (SDMA), were determined using high-performance liquid chromatography. The independent predictors of ADMA were glomerular filtration rate, female sex, and SDMA (R 2 ϭ0. 25). Baseline ADMA levels were higher in patients who had died than in patients who were alive at 1 year follow-up (1.23 [0.98 Key Words: ADMA Ⅲ myocardial infarction Ⅲ prognosis E ndothelium-derived nitric oxide (NO) plays a pivotal role in coronary vessel homeostasis. In diseased states, such as acute myocardial infarction (MI), endothelial dysfunction linked to reduced NO bioavailability contributes to increased vasoconstrictor responses, adhesion of platelets and monocytes, and proliferation of vascular smooth muscle cells. 1 After an acute coronary event, a high frequency of transient endothelial vasomotor dysfunction has been reported in coronary arteries and in peripheral circulation. 2,3 Impaired endothelial vasodilatation is strongly associated with future cardiovascular (CV) events after an acute coronary syndrome. 4 Over the last decade, several studies have suggested that circulating concentrations of asymmetrical dimethylarginine (ADMA) may provide a marker of risk for atherosclerosis. 5 ADMA is an endogenous competitive inhibitor of all isoforms of NO synthases and may compete with L-arginine as the substrate for the enzyme. ADMA originates from the degradation of posttranslationally methylated proteins in the course of protein turnover. A minor part of circulating ADMA is excreted via renal elimination. The major catabolic pathway of circulating ADMA occurs via dimethylarginine dimethylarginohydrolase (DDAH), which is also thought to play a major role in impaired vascular homeostasis. 6 An association between high ADMA levels and a risk of acute coronary events has been demonstrated in middle-aged men. 7 In patients with documented coronary artery disease, baseline serum concentrations of ADMA independently predict CV events at 2 years follow-up. 8 Only few data are available on levels of ADMA during acute MI. 9 Moreover, there is currently no evidence indicating any prognostic impact of this factor in the setting of acute MI, in particular in comparison with traditional risk factors and biomarkers such as C-reactive protein (CRP) and N-terminal Pro-Brain Natriuretic Peptide (NT-proBNP).From a prospective cohort of patients with acute MI, the aim of the present study was to identify the determinants of ADMA levels and to analyze the predictive value of ADMA on mortality at long-term follow-up. MethodsFor detailed descriptions of the methods, please see sup...

Asymmetric Dimethylarginine and Mortality in Stages 3 to 4 Chronic Kidney Disease

“…Several prospective studies have suggested an association between ADMA and increased risk for CVD in non-kidney disease populations (22,23). There are limited data on the relationship between ADMA levels and CVD outcomes in patients with CKD.…”

Review article: Asymmetric dimethylarginine as a mediator of vascular dysfunction and a marker of cardiovascular disease and mortality: an intriguing interaction with diabetes mellitus

“…This was found in high-risk populations such as haemodialysis patients, 63 in patients with multi-organ failure treated on a multidisciplinary intensive care unit, 64 and in patients after acute myocardial infarction. 65 ADMA was also reported to be a risk marker for cardiovascular disease and mortality in medium-risk populations such as patients with stable coronary artery disease, [66][67][68] chronic heart failure, 69 peripheral arterial disease 70 and type 2 diabetes mellitus. 71 The relevance of ADMA as a prospective risk marker has been less clear for the general population, as a lower incidence of severe cardiovascular events and mortality in lowrisk cohorts necessitates huge patient numbers and very long follow-up periods.…”

ADMA and C-reactive protein as mortality predictors in dialysis patients

“…According to Zoccali et al [7], there are four mechanisms that may explain increased level of ADMA: increased methylation of proteins, increased protein turnover, reduced DDAH activity and impaired renal excretion. It is well documented that plasma ADMA concentration is associated with carotid intimathickness [8,9], left ventricular hypertrophy as well as cardiovascular complications [10]. Several studies have confirmed that ADMA is an independent predictor of all-cause mortality and CVD mortality in patients with ESRD [11] and peripheral arterial disease [12].…”