Abstract 4054: Determinants of Circulating Asymmetric Dimethylarginine, Monomethylarginine and L-Arginine: A Population-Based Study
Background: Increased levels of asymmetric dimethylarginine (ADMA) and L-monomethylarginine (L-NMMA), endogenous inhibitors of nitric oxide synthase (NOS), have been implicated in endothelial dysfunction associated with cardiovascular risk factors (CVRF), but population-based studies examining the determinants of these NOS inhibitors are lacking. We examined the relation between CVRF and circulating NOS inhibitors (ADMA, L-NMMA) and the natural substrate for NOS, L-Arginine (L-Arg).
Methods: We correlated the presence of CVRF with circulating ADMA, L-NMMA and L-Arg levels measured by liquid chromatography-tandem mass spectrometry among 697 adults aged 20–80 years in a population-based study.
Results: Results of stepwise regression with ADMA, L-NMMA or L-Arg as the predicted variables are summarized in the Table⇓. Increasing age and decreasing high-density lipoprotein cholesterol (HDL-C) levels independently predicted higher ADMA levels. Increasing age, increasing low-density lipoprotein cholesterol (LDL-C) and decreasing HDL-C independently predicted higher L-NMMA levels. In contrast, increasing age, male gender and decreasing HDL-C independently predicted lower L-Arg levels. Levels of ADMA and L-NMMA increased steeply when HDL-C fell below 40 mg/dL whereas L-Arginine increased linearly with increasing HDL-C levels above 40 mg/dL. Therefore, the ADMA/L-Arg ratio increased linearly with decreasing HDL-C across all values (p<0.0001). Diabetes mellitus, smoking and hypertension did not predict ADMA, L-NMMA, or L-Arg levels and were not retained in any stepwise regression model.
Conclusions: Our study reveals an independent correlation between the presence of various CVRF and elevated endogenous NOS inhibitors and/or lower levels of L-Arg. Our study supports the role of increased assymetric L-Arg methylation in endothelial dysfunction associated with CVRF such as aging, low HDL-C, high LDL-C and male gender in the general population.