Plasma levels of asymmetric dimethylarginine (ADMA) are related to intima-media thickness of the carotid artery: An epidemiological study

Asymmetric dimethylarginine (ADMA) is a circulating endogenous nitric oxide (NO) synthase inhibitor. It has been reported that plasma levels of ADMA are related to intima-media thickness (IMT) in small numbers. We investigated this issue in a large number of subjects without overt cerebro-cardiovascular diseases. A total of 712 subjects (305 men and 407 women; age, 62.6 ± 11.2 years) received a health examination in 1999 in a farming community. We measured blood pressure (BP), blood chemistries, and fasting plasma total ADMA levels. IMT of the common carotid artery was determined with the use of duplex ultrasonography as an index of atherosclerosis. Uni- and multi-variate analyses for determinants of IMT were performed. For the total population, the mean ADMA level was 0.50 μmol/l. By the use of multiple stepwise regression analysis, IMT was significantly associated with ADMA (p < 0.01), age (p < 0.001), and systolic BP (p < 0.001). Furthermore, when IMT was analyzed across the ADMA tertiles after adjustments for age, sex, and other confounders, analysis of co-variance showed a significant (p < 0.001) and linear association between IMT and ADMA levels. In conclusion, our study indicates that plasma level of ADMA is a strong and independent determinant of IMT of the carotid artery in the large number of subjects without overt cerebro-cardiovascular diseases.