title: 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.
  
  
  OBJECTIVE
  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.
  
  
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Laboratory Medicine, Shimane University Faculty of Medicine, Shimane, Japan.
authors.forename: Yoshitomo
authors.initials: Y
authors.lastname: Notsu
authors.affiliation: Department of Laboratory Medicine, Shimane University Faculty of Medicine, Shimane, Japan. Electronic address: syano@med.shimane-u.ac.jp.
authors.forename: Shozo
authors.initials: S
authors.lastname: Yano
authors.affiliation: Department of Laboratory Medicine, Shimane University Faculty of Medicine, Shimane, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Shibata
authors.affiliation: Department of Laboratory Medicine, Shimane University Faculty of Medicine, Shimane, Japan.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Nagai
authors.affiliation: Department of Functional Pathology, Shimane University Faculty of Medicine, Shimane, Japan.
authors.forename: Toru
authors.initials: T
authors.lastname: Nabika
mesh_terms: D000368:Aged; D001120:Arginine / Q000031:analogs & derivatives* / Q000097:blood; D050197:Atherosclerosis / Q000097:blood* / Q000503:physiopathology; D015415:Biomarkers / Q000097:blood; D001794:Blood Pressure; D015992:Body Mass Index; D002339:Carotid Arteries / Q000000981:diagnostic imaging*; D017536:Carotid Artery, Common / Q000000981:diagnostic imaging; D059168:Carotid Intima-Media Thickness; D015331:Cohort Studies; D003430:Cross-Sectional Studies; D005260:Female; D006801:Humans; D006973:Hypertension / Q000097:blood / Q000503:physiopathology; D007564:Japan; D008297:Male; D008875:Middle Aged; D012307:Risk Factors
chemical_list: D015415:Biomarkers; C018524:N,N-dimethylarginine; D001120:Arginine
keywords: Arginine; Asymmetric dimethylarginine (ADMA); Atherosclerosis; Intima-media thickness (IMT)