Received on October 20, 2009
Accepted on October 22, 2009

Lipids, Lipoproteins, and Cardiovascular Risk Factors

Distribution of Asymmetric Dimethylarginine among 980 Healthy, Older Adults of Different Ethnicities

¹ Division of Cardiovascular Medicine, Stanford University School of Medicine, Stanford, CA, and Department of Cardiology, Hamburg University Heart Center, Hamburg, Germany
² Stanford Prevention Research Center, Stanford, CA
³ Department of Health Research and Policy, Stanford University School of Medicine, Stanford, CA
⁴ Division of Research, Kaiser Permanente of Northern California, Oakland, CA, and Department of Epidemiology and Department of Biostatistics and Medicine, University of California, San Francisco, CA
⁵ Division of Research, Kaiser Permanente of Northern California, Oakland, CA
⁶ Division of Cardiovascular Medicine, Stanford University School of Medicine, Stanford, CA
⁷ Division of Cardiovascular Medicine, Stanford Prevention Research Center, and Department of Health Research and Policy, Stanford University School of Medicine, Stanford, CA; Department of Cardiology, Hamburg University Heart Center, Hamburg, Germany, and Division of Research, Kaiser Permanente of Northern California, Oakland, CA; Department of Epidemiology and Department of Biostatistics and Medicine, University of California, San Francisco, CA

^* To whom correspondence should be addressed. E-mail: ptsao{at}stanford.edu.

BACKGROUND: Endothelium-derived nitric oxide plays a crucial role in the regulation of vascular tone and the development of cardiovascular disease. The endogenous nitric oxide synthase inhibitor asymmetric dimethylarginine (ADMA) has emerged as a novel cardiovascular risk factor. ADMA appears to be an independent predictor for cardiovascular and overall mortality. However, the majority of studies investigating the clinical role of ADMA were performed in European study populations with few individuals of other ethnicities.

METHODS: We performed a cross-sectional study of 980 healthy, older (age 60–72 years) individuals of different ethnicities living in the San Francisco Bay area and analyzed ADMA plasma concentrations and their relationship to other cardiovascular risk factors. Plasma ADMA concentrations were measured using a recently developed, highly sensitive ELISA.

RESULTS: In our entire sample, we were able to define a reference interval for ADMA plasma concentrations of 0.47 (90% CI 0.46–0.48) μmol/L to 0.85 (0.84–0.89) μmol/L. The mean ADMA concentration was 0.63 (SD 0.11) μmol/L (median 0.61 μmol/L). Mean ADMA concentrations were significantly lower in African Americans (0.60 μmol/L; P < 0.01) and mixed non-Hispanics (0.60 μmol/L; P < 0.05) compared with whites (0.63 μmol/L). ADMA was positively correlated with cystatin-C in both men ( = 0.29) and women ( = 0.37), and median plasma ADMA concentrations increased across cystatin-C quintiles.

CONCLUSIONS: ADMA varies nearly 2-fold across a healthy sample of older men and women, correlates with age, body mass index, and renal function, and is different across ethnic groups. Additional studies in a wider age range and including larger ethnic subgroups would be useful.