Relation of baseline plasma ADMA levels to cardiovascular morbidity and mortality at two years in men with diabetes mellitus referred for coronary angiography.
BACKGROUND
Patients with diabetes mellitus (DM) have been shown to have higher levels of asymmetric dimethylarginine (ADMA), an endogenous inhibitor of endothelial nitric oxide (NO) synthase. Higher plasma levels of ADMA have been implicated in the pathogenesis of endothelial dysfunction and atherosclerosis by lowering NO levels. High baseline plasma levels of ADMA in patients with DM have been shown to predict diabetes related complications. However, there are limited data on the prognostic significance of baseline ADMA levels in patients with established DM.


METHODS
The present study investigated the long-term prognostic significance of baseline plasma ADMA levels in a well-characterized cohort of 170 high-risk diabetic men with known or suspected coronary artery disease who were referred for coronary angiography. All patients were followed prospectively for the development of vascular outcomes, including all-cause mortality.


RESULTS
After controlling for a variety of baseline variables (including established biomarkers such as hs-CRP 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 all-cause mortality (HR 2.63, 95% CI 1.13-6.11, p=0.0247) 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 or MI (fatal or non-fatal) (HR 2.44, 95% CI 1.26-4.72, p=0.0079), as well as the composite outcome of all-cause mortality, MI (fatal or nonfatal), or stroke (HR 2.00, 95% CI 1.10-3.62, p=0.0232).


CONCLUSIONS
These data demonstrate that elevated baseline levels of ADMA are a strong and independent predictor of cardiovascular outcomes (including all-cause mortality) in patients with DM.
Cavusoglu
Erdal
E
Division of Cardiology, Department of Medicine, SUNY Downstate Medical Center, Brooklyn, NY, United States. ECavusoglu@aol.com
Ruwende
Cyril
C
Chopra
Vineet
V
Poludasu
Shyam
S
Yanamadala
Sunitha
S
Frishman
William H
WH
Eng
Calvin
C
Pinsky
David J
DJ
Marmur
Jonathan D
JD
D000368:Aged; D001120:Arginine / Q000031:analogs & derivatives* / Q000097:blood; D017023:Coronary Angiography; D003327:Coronary Disease / Q000097:blood* / Q000000981:diagnostic imaging / Q000401:mortality; D048909:Diabetes Complications / Q000097:blood* / Q000401:mortality; D006801:Humans; D008297:Male; D009203:Myocardial Infarction / Q000401:mortality; D011379:Prognosis; D016016:Proportional Hazards Models; D020521:Stroke / Q000401:mortality
C487735:dimethylarginine; D001120:Arginine