title: High plasma dimethylarginine levels are associated with adverse clinical outcome after stroke.
abstract: OBJECTIVE
  Increased levels of asymmetric dimethylarginine (ADMA), an endogenous inhibitor of nitric oxide synthase, have been observed in patients with cardiovascular risk factors and atherosclerosis and in patients with a history of stroke. The role of ADMA and its analogue symmetric dimethylarginine (SDMA) in acute ischemic stroke is yet unclear. We hypothesized that plasma dimethylarginine levels increase in the hyper-acute phase after ischemic stroke and that their time course is related to stroke outcome.
  
  
  METHODS
  Plasma dimethylarginines ADMA and SDMA and L-arginine levels were measured in 67 patients at 6, 12, 24 hours, as well as 3 and 7 days after stroke onset using high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS-MS). Data were compared to control data from 32 age-adjusted healthy volunteers. Clinical outcome was assessed using the modified Rankin Scale (mRS) at 90 days after stroke.
  
  
  RESULTS
  At baseline, plasma ADMA levels were higher in stroke patients than in controls, whereas plasma SDMA and L-arginine levels did not differ from control subjects. The time courses of ADMA and SDMA were related to the clinical outcome. Binary logistic regression analysis showed that ADMA levels of ≥ 0.566 µmol/L at day 3, ≥ 0.530 µmol/L at day 7 and SDMA levels of ≥ 0.59 µmol/L at 24 hours predicted an unfavorable clinical outcome.
  
  
  CONCLUSIONS
  An increase of both ADMA and SDMA plasma levels within the first 72 hours after the onset of ischemic stroke predicts a poor outcome.
authors.affiliation: Department of Neurology, Hannover Medical School, Hannover, Germany. worthmann.hans@mh-hannover.de
authors.forename: Hans
authors.initials: H
authors.lastname: Worthmann
authors.forename: Shufen
authors.initials: S
authors.lastname: Chen
authors.forename: Jens
authors.initials: J
authors.lastname: Martens-Lobenhoffer
authors.forename: Na
authors.initials: N
authors.lastname: Li
authors.forename: Milani
authors.initials: M
authors.lastname: Deb
authors.forename: Anita Blanka
authors.initials: AB
authors.lastname: Tryc
authors.forename: Annemarie
authors.initials: A
authors.lastname: Goldbecker
authors.forename: Qiang
authors.initials: Q
authors.lastname: Dong
authors.forename: Jan Thomas
authors.initials: JT
authors.lastname: Kielstein
authors.forename: Stefanie Margarethe
authors.initials: SM
authors.lastname: Bode-Böger
authors.forename: Karin
authors.initials: K
authors.lastname: Weissenborn
mesh_terms: D000368:Aged; D001120:Arginine / Q000031:analogs & derivatives* / Q000097:blood; D016022:Case-Control Studies; D002851:Chromatography, High Pressure Liquid; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D015203:Reproducibility of Results; D020521:Stroke / Q000097:blood* / Q000473:pathology; D053719:Tandem Mass Spectrometry
chemical_list: C487735:dimethylarginine; D001120:Arginine