title: Evaluation of asymmetric dimethylarginine and homocysteine in microangiopathy-related cerebral damage.
abstract: BACKGROUND
  Microangiopathy-related cerebral damage (MARCD) is an entity of cerebrovascular disease based on arteriosclerosis in deep white matter, which includes lacunar infarction and white matter hyperintensity (WMH). As asymmetric dimethylarginine (ADMA), an endogenous inhibitor of the nitric oxide (NO) synthases, and homocysteine are both potential risk factors for arteriosclerosis, the plasma levels of these two substances were evaluated in individuals with MARCD.
  
  
  METHODS
  Consecutive participants of a health examination (401 males and 311 females) were recruited for this cross-sectional study. All participants received an magnetic resonance imaging examination, and those with either lacunar infarction or WMH (grade > or =2) were classified into MARCD (+) (N = 146). The plasma ADMA concentration was measured with high performance liquid chromatography. The total homocysteine (tHcy) concentration was measured using a commercial kit.
  
  
  RESULTS
  The ADMA level (P < 0.001), symmetric dimethylarginine (SDMA) level (P < 0.05) and L-arginine (Arg)/ADMA ratio (P < 0.01) differed significantly between MARCD (+) and (-) according to nonparametric Wilcoxon test, while the tHcy level did not (P = 0.37). Classic risk factors such as age, blood pressure, and the presence of hypertension differed significantly between the two groups as well. In the logistic analysis, the association of Arg/ADMA with MARCD remained significant (odds ratio and 95% confidence interval, 0.19 (0.05, 0.73), P < 0.05) even after adjusting for the effects of age and hypertension.
  
  
  CONCLUSIONS
  ADMA and tHcy levels were studied in 712 subjects with or without MARCD. The Arg/ADMA ratio was suggested to be an independent risk factor for MARCD. A large-scale prospective study is warranted to confirm the causal relationship between Arg/ADMA and MARCD.
authors.affiliation: Department of Laboratory Medicine, Shimane University School of Medicine, Izumo, Japan.
authors.forename: Yoshitomo
authors.initials: Y
authors.lastname: Notsu
authors.forename: Toru
authors.initials: T
authors.lastname: Nabika
authors.forename: Hirokazu
authors.initials: H
authors.lastname: Bokura
authors.forename: Yoji
authors.initials: Y
authors.lastname: Suyama
authors.forename: Shotai
authors.initials: S
authors.lastname: Kobayashi
authors.forename: Schuhei
authors.initials: S
authors.lastname: Yamaguchi
authors.forename: Junichi
authors.initials: J
authors.lastname: Masuda
mesh_terms: D001120:Arginine / Q000031:analogs & derivatives* / Q000097:blood; D001161:Arteriosclerosis / Q000097:blood* / Q000453:epidemiology* / Q000473:pathology; D015415:Biomarkers; D001794:Blood Pressure / Q000502:physiology; D001925:Brain Damage, Chronic / Q000097:blood* / Q000453:epidemiology* / Q000473:pathology; D002544:Cerebral Infarction / Q000453:epidemiology / Q000473:pathology; D002561:Cerebrovascular Disorders / Q000097:blood* / Q000453:epidemiology* / Q000473:pathology; D002851:Chromatography, High Pressure Liquid; D003430:Cross-Sectional Studies; D005260:Female; D005919:Glomerular Filtration Rate / Q000502:physiology; D006710:Homocysteine / Q000097:blood*; D006801:Humans; D006973:Hypertension / Q000150:complications / Q000453:epidemiology; D007564:Japan / Q000453:epidemiology; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors*; D016017:Odds Ratio; D012044:Regression Analysis; D018570:Risk Assessment
chemical_list: D015415:Biomarkers; D006710:Homocysteine; C018524:N,N-dimethylarginine; D001120:Arginine; D019001:Nitric Oxide Synthase