title: Association of homocysteine and asymmetric dimethylarginine with atherosclerosis and cardiovascular events in maintenance hemodialysis patients.
abstract: BACKGROUND
  Homocysteine (Hcy) and asymmetric dimethylarginine (ADMA) recently were recognized as potential risk factors for atherosclerosis in the general population, and the metabolism of each of these substances seems to be closely related. This study investigates the association between these substances and whether elevated serum Hcy and ADMA levels are related to high risk for atherosclerosis and cardiovascular events in maintenance hemodialysis (HD) patients.
  
  
  METHODS
  A study was made of 197 HD patients (132 men, 65 women; mean age, 56.9 +/- 8.6 years) for the correlation between plasma total Hcy (tHcy) and ADMA concentrations and the association of these substances with atherosclerotic indices of cervical intima-media thickness, plaque diameter, aortic calcification index, and aortic elongation. Cardiovascular events were followed up for 5 years in these patients.
  
  
  RESULTS
  Mean plasma tHcy (37.3 +/- 25.8 micromol/L) and ADMA (0.77 +/- 0.16 micromol/L) levels were significantly greater in HD patients than in healthy subjects. Plasma tHcy level did not correlate with plasma ADMA level (r = -0.1; P = not significant). Although ADMA level was associated significantly with atherosclerotic indices from a simple regression analysis, this association was less from multiple regression analysis. When patients were classified into 3 groups according to ADMA level, cardiovascular events during 5 years were significantly greater in the group with the highest ADMA levels than in the other groups, confirmed by using a Cox proportional hazard model. However, no association was found between tHcy levels and atherosclerotic indices or cardiovascular events.
  
  
  CONCLUSIONS
  ADMA level emerged as a potential risk factor for cardiovascular events that might be mediated in part by atherosclerosis in HD patients. Conversely, neither high nor low plasma tHcy levels were associated with atherosclerotic indices and cardiovascular events. This result for our HD patients does not fulfill the terms of traditional epidemiology and paradoxical reverse epidemiology of Hcy.
authors.affiliation: Department of Clinical Nutrition, School of Food and Nutritional Sciences and COE Program in the 21st Century, University of Shizuoka, Japan. kumagai@u-shizuoka-ken.ac.jp
authors.forename: Hiromichi
authors.initials: H
authors.lastname: Kumagai
authors.forename: Miyuki
authors.initials: M
authors.lastname: Sakurai
authors.forename: Takako
authors.initials: T
authors.lastname: Takita
authors.forename: Yukitaka
authors.initials: Y
authors.lastname: Maruyama
authors.forename: Shuichi
authors.initials: S
authors.lastname: Uno
authors.forename: Naoki
authors.initials: N
authors.lastname: Ikegaya
authors.forename: Akihiko
authors.initials: A
authors.lastname: Kato
authors.forename: Akira
authors.initials: A
authors.lastname: Hishida
mesh_terms: D001120:Arginine / Q000031:analogs & derivatives* / Q000097:blood; D050197:Atherosclerosis / Q000097:blood* / Q000453:epidemiology; D002318:Cardiovascular Diseases / Q000097:blood* / Q000453:epidemiology; D015897:Comorbidity; D005260:Female; D006710:Homocysteine / Q000097:blood*; D006801:Humans; D007676:Kidney Failure, Chronic / Q000097:blood* / Q000453:epidemiology / Q000628:therapy; D008297:Male; D008875:Middle Aged; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D016016:Proportional Hazards Models; D012044:Regression Analysis; D006435:Renal Dialysis; D012307:Risk Factors
chemical_list: D006710:Homocysteine; C018524:N,N-dimethylarginine; D001120:Arginine; D019001:Nitric Oxide Synthase