title: Low plasma arginine:asymmetric dimethyl arginine ratios predict mortality after intracranial aneurysm rupture.
abstract: BACKGROUND
  Asymmetrical dimethylarginine (ADMA), an endogenous inhibitor of nitric oxide synthases, predicts mortality in cardiovascular disease and has been linked to cerebral vasospasm after aneurysmal subarachnoid hemorrhage (SAH). In this prospective study, we assessed whether circulating ADMA, arginine:ADMA ratio, and nitrite/nitrate levels were associated with survival and cerebral vasospasm in SAH patients.
  
  
  METHODS
  One hundred and eleven patients were observed day 1 to 15 after SAH, with serial measurements of transcranial Doppler flow velocities (VMCA) and plasma biomarkers. Clinical status was assessed by the World Federation of Neurosurgical Societies grading scale.
  
  
  RESULTS
  Overall 30-day mortality was 18%, but differed between patients grouped by low, midrange, and high arginine:ADMA ratio in the first week after SAH. Mortality rates were 14/37, 1/37, and 5/37 in the 3 groups, respectively (P-logrank=0.0003). Cox regression showed that low versus midrange or high arginine:ADMA was associated with a hazard ratio of 4.1 independent of World Federation of Neurosurgical Societies grade (95% confidence interval, 1.5-10.9; P=0.006). ADMA or arginine:ADMA had no association to VMCA, but there was an inverse relationship between VMCA and nitrite/nitrate levels (P<0.0001). The NOS3 894G/G genotype was associated with 15% lower VMCA (P=0.01). ATbG-NOS3 haplotype homozygosity was associated with up to 64% higher nitrite/nitrate levels (P=0.003).
  
  
  CONCLUSIONS
  This study suggests that plasma arginine:ADMA ratios predict mortality after SAH. Both clinical and physiological measures of changes in cerebral hemodynamics are coupled to the nitric oxide system.
authors: Department of Neuroscience and Pharmacology, Faculty of Health, University of Copenhagen, Denmark. jmyrup@gmail.com
authors: Jonatan Myrup
authors: JM
authors: Staalsø
authors: Anita
authors: A
authors: Bergström
authors: Troels
authors: T
authors: Edsen
authors: Pia
authors: P
authors: Weikop
authors: Bertil
authors: B
authors: Romner
authors: Niels Vidiendal
authors: NV
authors: Olsen
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D017542:Aneurysm, Ruptured / Q000097:blood / Q000401:mortality*; D001120:Arginine / Q000031:analogs & derivatives* / Q000097:blood*; D015415:Biomarkers / Q000097:blood; D001783:Blood Flow Velocity; D005260:Female; D006801:Humans; D002532:Intracranial Aneurysm / Q000097:blood / Q000401:mortality*; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D011446:Prospective Studies; D020301:Vasospasm, Intracranial / Q000097:blood / Q000401:mortality*
chemical_list: D015415:Biomarkers; C018524:N,N-dimethylarginine; D001120:Arginine