Plasma arginine/ADMA ratio as a sensitive risk marker for atherosclerosis: Shimane CoHRE study

Abstract

Background: Asymmetric dimethylarginine (ADMA), which acts an endogenous inhibitor of nitric oxide synthase (NOS), is involved in the pathogenesis of cardiovascular disease. Arginine (Arg) may regulate vascular endothelial function, since Arg is the substrate of NO competing with ADMA. In our previous study, low Arg/ADMA ratio is an independent risk for microangiopathy-related cerebral damage. Purpose: Here, we performed a cross-sectional study to evaluate the association between the Arg/ADMA ratio and the maximal intima-media thickness (IMT) in the carotid artery. Subjects and Methods: Participants were 785 community-dwelling Japanese people without any severe disorders. Plasma concentration of Arg and ADMA in fasting blood sample was determined using HPLC. IMT was measured in the bilateral carotid artery by ultrasonography. Results: Among quartiles stratified by the Arg/ADMA ratio, ANOVA showed a significant difference in IMT and the IMT in Q1 (the lowest quartile) was significantly higher than that in Q4 (the highest quartile). In multiple linear regression analysis, age, the male gender, lower BMI, the presence of hypertension and lower Arg/ADMA ratio were independently correlated with IMT, while IMT was not correlated with Arg or ADMA alone. In addition, the Arg/ADMA ratio was associated with IMT independent of age, sex, BMI and the presence of hypertension with odds ratio 0.21 (95%CI: 0.05–0.88) in multiple logistic regression analysis for IMT 1.5 mm or more. Conclusion: Imbalance of Arg and ADMA is independently involved in the progression of atherosclerosis, and the Arg/ADMA ratio may be a sensitive marker for atherosclerosis.