Determination of a reference value for N(G), N(G)-dimethyl-L-arginine in 500 subjects.
BACKGROUND
Asymmetric dimethylarginine (ADMA) acts as an endogenous inhibitor of NO-synthase. In the last years ADMA has emerged as a cardiovascular risk factor. The aim of this study was to determine a reference value for ADMA.


METHODS
Plasma samples of 500 healthy subjects in the 19-75 year age group were analyzed. Exclusion criteria from this study were smoking, any known significant disease, body-mass-index (BMI) above 30 kg m(-2), elevated plasma lipid levels, impaired renal function, hypertension, and intake of any medication. The ADMA levels were determined by ELISA, (DLD Diagnostics, Hamburg, Germany).


RESULTS
Mean ADMA plasma concentration of the total population was 0.69 micromol L(-1) (SD 0.20) and 95% of the measured values were in the range from 0.36 micromol L(-1) to 1.17 micromol L(-1). Women below 50 years of age had lower ADMA levels than men below 50 years of age [0.62 (0.17) micromol L(-1) vs. 0.69 (0.19) micromol L(-1); P = 0.001] and woman above 50 years of age had higher ADMA levels than men above 50 years of age [0.80 (0.22) micromol L(-1) vs. 0.73 (0.20) micromol L(-1); P = 0.036]. A regression analysis of ADMA levels and age was performed for each sex. The regression factor was r = 0.444 for women in a squared regression model (P < 0.001) and r = 0.212 for men in a linear regression model (P < 0.001).


CONCLUSIONS
The study was able to define a reference value for ADMA plasma levels with 0.36-1.17 micromol L(-1) and found sex dependent correlations between ADMA and age. Women showed a significant increase in ADMA plasma levels with onset of menopause.
Schulze
F
F
University Hospital Hamburg-Eppendorf, Centre for Experimental Medicine, Institute of Experimental and Clinical Pharmacology and Toxicology, Clinical Pharmacology Unit, Hamburg, Germany. fschulze@uke.uni-hamburg.de
Maas
R
R
Freese
R
R
Schwedhelm
E
E
Silberhorn
E
E
Böger
R H
RH
D000328:Adult; D000368:Aged; D000375:Aging / Q000502:physiology; D001120:Arginine / Q000031:analogs & derivatives* / Q000097:blood; D015415:Biomarkers; D002318:Cardiovascular Diseases / Q000097:blood / Q000209:etiology; D004791:Enzyme Inhibitors / Q000097:blood*; D004797:Enzyme-Linked Immunosorbent Assay / Q000592:standards; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors*; D012016:Reference Values; D012680:Sensitivity and Specificity; D012727:Sex Characteristics
D015415:Biomarkers; D004791:Enzyme Inhibitors; C018524:N,N-dimethylarginine; D001120:Arginine; D019001:Nitric Oxide Synthase