(Circulation. 1999;99:1141-1146.)
© 1999 American Heart Association, Inc.
Clinical Investigation and Reports |
Endogenous Nitric Oxide Synthase Inhibitor
A Novel Marker of Atherosclerosis
From the Department of Internal Medicine III and the Cardiovascular Research Institute, Kurume University School of Medicine (H. Miyazaki, H. Matsuoka, M.U., S.U., S.O., T.I.), Kurume, Japan, and the Section of Vascular Medicine, Falk Cardiovascular Research Center, Stanford University School of Medicine (J.P.C.), Stanford, Calif.
Correspondence to Hidehiro Matsuoka, MD, PhD, The Cardiovascular Research Institute, Department of Internal Medicine III, Kurume University School of Medicine, 67 Asahi-machi, Kurume, Fukuoka, 830-0011 Japan. E-mail matsuoka{at}med.kurume-u.ac.jp
Background—Exposure to risk factors such as hypertension or hypercholesterolemia decreases the bioavailability of endothelium-derived nitric oxide (NO) and impairs endothelium-dependent vasodilation. Recently, a circulating endogenous NO synthase inhibitor, asymmetric dimethylarginine (ADMA), has been detected in human plasma. The purpose of this study was to examine the relationship between plasma ADMA and atherosclerosis in humans.
Methods and Results—Subjects (n=116; age, 52±1 years;
male:female ratio, 100:16) underwent a complete history and physical
examination, determination of serum chemistries and ADMA levels, and
duplex scanning of the carotid arteries. These individuals had no
symptoms of coronary or peripheral artery disease
and were taking no medications. Univariate and
multivariate analyses revealed that plasma
levels of ADMA were positively correlated with age
(P<0.0001), mean arterial pressure
(P<0.0001), and 
glucose (an index of glucose
tolerance) (P=0.0006). Most intriguingly, stepwise
regression analysis revealed that plasma ADMA levels were
significantly correlated to the intima-media thickness of the carotid
artery (as measured by high-resolution ultrasonography).
Conclusions—This study reveals that plasma ADMA levels are positively correlated with risk factors for atherosclerosis. Furthermore, plasma ADMA level is significantly correlated with carotid intima-media thickness. Our results suggest that this endogenous antagonist of NO synthase may be a marker of atherosclerosis.
Key Words: aging • risk factors • diabetes mellitus • dimethylarginine • hypertension • smoking
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