Evaluation of asymmetric dimethylarginine and homocysteine in microangiopathy-related cerebral damage.
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.
Notsu
Yoshitomo
Y
Department of Laboratory Medicine, Shimane University School of Medicine, Izumo, Japan.
Nabika
Toru
T
Bokura
Hirokazu
H
Suyama
Yoji
Y
Kobayashi
Shotai
S
Yamaguchi
Schuhei
S
Masuda
Junichi
J
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
D015415:Biomarkers; D006710:Homocysteine; C018524:N,N-dimethylarginine; D001120:Arginine; D019001:Nitric Oxide Synthase