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(Circulation. 2000;101:e160.)
© 2000 American Heart Association, Inc.

Circulation Electronic Pages

Is Asymmetric Dimethylarginine a Novel Marker of Atherosclerosis?

Rainer H. Böger, MD; Stefanie M. Bode-Böger, MD

Institute of Clinical Pharmacology, Hannover Medical School, Hannover, Germany

	Introduction

 
To the Editor:

In their article, Miyazaki et al¹ demonstrate a correlation between the plasma concentration of asymmetric dimethylarginine (ADMA) and carotid artery intima-media thickness in humans. In multivariate regression analyses, ADMA was the only significant predictor of carotid intima-media thickness besides age and impaired glucose tolerance. However, one critical factor must be carefully evaluated in the interpretation of these data: dimethylarginines are a pair of endogenous, dimethylated L-arginine analogues. ADMA inhibits nitric oxide (NO) synthase,² whereas its stereoisomer, symmetric dimethylarginine (SDMA), is biologically inactive.² Unfortunately, Miyazaki et al¹ gave only a brief description of the high performance liquid chromatographic (HPLC) method they used to quantify ADMA levels.

When examining the article to which they refer for a description of their method,³ it seemed that the investigators could not distinguish between ADMA and SDMA with the HPLC system. This is unfortunate because SDMA probably plays no role in vascular lesion formation and, thus, it may have unnecessarily blurred the results of Miyazaki et al.¹ An even greater correlation coefficient between ADMA and carotid artery intima-media thickening might have been found using an analytical method that could unequivocally differentiate between both stereoisomers. Alternatively, there could have been no correlation at all.

Several HPLC methods have been published for the quantitation of methylarginines since the discovery of their biological importance. A major portion of these methods have been unable to differentiate between ADMA and SDMA. Using a recently developed, specific HPLC method that allowed us to clearly separate ADMA and SDMA, we . . . [Full Text of this Article]

Hidehiro Matsuoka, MD, PhD; Hiroshi Miyazaki, MD; Michiaki Usui, MD; Seiji Ueda, MD; Seiya Okuda, MD, PhD; Tsutomu Imaizumi, MD, PhD

Department of Internal Medicine III, Kurume University School of Medicine, Kurume, Japan

John P. Cooke, MD, PhD

Falk Cardiovascular Center Stanford University School of Medicine, Palo Alto, Calif