P291	Determination of a reference value for asymmetrical dimethylarginine in a cohort of 500 healthy subjects.
1F.Schulze, 2R.Maas, 2R.Freese, 1E.Schwedhelm, 1E.Silberhorn, 1R.H.Böger
1Universitätskrankenhaus Hamburg-Eppendorf, Hamburg, DE; 2Hamburg, DE & 2Hamburg, DE.

Introduction: In the last years asymmetric dimethylarginine (ADMA) has emerged as a cardiovascular risk factor. ADMA acts as an endogenous inhibitor of NO-synthase. All insights in ADMA plasma levels of healthy people so far derived from case control studies. These data of “normal” ADMA levels varied because different analytical methods were used. A second limitation is the small number of controls in these trials. To determine reference values for ADMA, we measured ADMA plasma levels in 500 healthy subjects of either sex. Methods: We analyzed plasma samples of 500 healthy subjects (aged 19 to 75 years) in this reference value study. Exclusion criteria from this study were smoking, any known significant disease, BMI above 30 kg/m2, elevated plasma lipid levels, impaired renal function, hypertension, or intake of any medication. ADMA levels were determined by ELISA. Results: The mean ADMA plasma concentration of the total population was 0.69 µmol/L (SD 0.20) and 95% of the measured values were in a range from 0.36 µmol/L (90%CI 0.32 - 0.38) to 1.17 µmol/L (90%CI 1.10 - 1.21). Men above (N = 81) and below the age of 50 years (N = 233) had no difference in mean ADMA levels (0.69 (SD 0.19) µmol/L vs. 0.73 (0.20) µmol/L; p=0.177). Women below the age of 50 years (N = 132) had lower ADMA levels than men of the same age (0.62 (0.17) µmol/L vs. 0.69 (0.19) µmol/L; p=0.001) and woman above the age of 50 years (N = 54) had higher ADMA levels than men of the same age (0.80 (0.22) µmol/L vs. 0.73 (0.20) µmol/L; 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). BMI was positively correlated with ADMA levels (ρ=0.152, p<0.001). There was no correlation between ADMA levels and blood pressure. Conclusion: We were able to define a reference value for ADMA plasma levels with 0.36 to 1.17 µmol/L for the ELISA. We found sex dependent correlations between ADMA and age, which may be explained by differences in hormonal status. Women showed a significant increase in ADMA plasma levels with onset of menopause. We found a positive correlation between ADMA plasma levels an BMI but no correlation with blood pressure in this healthy population.

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