Relationship of baseline plasma ADMA levels to... : Coronary Artery Disease (original) (raw)

Pathophysiology and Natural History

Relationship of baseline plasma ADMA levels to cardiovascular outcomes at 2 years in men with acute coronary syndrome referred for coronary angiography

Cavusoglu, Erdala b; Ruwende, Cyrilc; Chopra, Vineetb; Yanamadala, Sunithac; Eng, Calvinb; Pinsky, David J.c; Marmur, Jonathan D.a

aDivision of Cardiology, Department of Medicine, SUNY Downstate Medical Center, Brooklyn, New York

bDivision of Cardiology, Department of Medicine, Bronx Veterans Affairs Medical Center, Bronx, New York

cDivision of Cardiovascular Medicine, Department of Medicine, University of Michigan, Ann Arbor, Michigan, USA

Correspondence to Dr Erdal Cavusoglu, MD, SUNY Downstate Medical Center, 450 Clarkson Avenue, Box 1257, Brooklyn, NY 11203-2098, USA

Tel: +1 718 270 7352; fax: +1 917 677 4794; e-mail: [email protected]

Received 27 September 2008 Revised 6 November 2008 Accepted 18 November 2008

Abstract

Background

Nitric oxide (NO) is produced from L-arginine by NO synthase and is an important molecule with antiatherogenic properties. Asymmetric dimethylarginine (ADMA) acts as an endogenous inhibitor of endothelial NO synthase. As such, it has been associated with endothelial dysfunction and elevated circulating levels of ADMA have been found in patients with cardiovascular risk factors. In addition, high baseline plasma levels of ADMA have been shown to be an independent predictor of adverse outcomes in a variety of patient populations. However, there are very limited data in patients with acute coronary syndromes (ACS).

Methods

This study investigated the long-term prognostic significance of baseline plasma ADMA levels in a well-characterized cohort of 193 men with ACS who were referred for coronary angiography. All patients were followed up prospectively for the development of vascular outcomes.

Results

After controlling for a variety of baseline variables (including established biomarkers such as high-sensitivity C-reactive protein and fibrinogen), plasma ADMA levels (analyzed as the upper tertile of baseline values compared with the lower two tertiles) were a strong and independent predictor of each of the individual endpoints of all-cause mortality [hazard ratio (HR): 2.45, 95% confidence interval (CI): 1.08–5.57; _P_=0.0325] and myocardial infarction (HR: 2.28, 95% CI: 1.14–4.57; _P_=0.0204) when using a Cox proportional hazards model. In addition, baseline ADMA values were also an independent predictor of the composite outcome of all-cause mortality, fatal or nonfatal myocardial infarction, or stroke (HR: 1.81, 95% CI: 1.01–3.25; _P_=0.0482).

Conclusion

These data show that elevated baseline levels of ADMA are a strong and independent predictor of cardiovascular outcomes (including mortality) in patients with ACS.