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


CONCLUSIONS
These data show that elevated baseline levels of ADMA are a strong and independent predictor of cardiovascular outcomes (including mortality) in patients with ACS.
Cavusoglu
Erdal
E
Division of Cardiology, Department of Medicine, SUNY Downstate Medical Center, Brooklyn, New York 11203-2098, USA. ECavusoglu@aol.com
Ruwende
Cyril
C
Chopra
Vineet
V
Yanamadala
Sunitha
S
Eng
Calvin
C
Pinsky
David J
DJ
Marmur
Jonathan D
JD
D054058:Acute Coronary Syndrome / Q000097:blood* / Q000150:complications / Q000000981:diagnostic imaging* / Q000401:mortality; D000368:Aged; D000789:Angina, Unstable / Q000097:blood / Q000000981:diagnostic imaging / Q000209:etiology* / Q000401:mortality; D001120:Arginine / Q000031:analogs & derivatives* / Q000097:blood; D015415:Biomarkers / Q000097:blood; D017023:Coronary Angiography; D005500:Follow-Up Studies; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000097:blood / Q000000981:diagnostic imaging / Q000209:etiology* / Q000401:mortality; D011379:Prognosis; D016016:Proportional Hazards Models; D011446:Prospective Studies; D018570:Risk Assessment; D012307:Risk Factors; D013997:Time Factors; D015854:Up-Regulation
D015415:Biomarkers; C018524:N,N-dimethylarginine; D001120:Arginine