title: Early circulating levels of endothelial cell activation markers in aneurysmal subarachnoid haemorrhage: associations with cerebral ischaemic events and outcome.
abstract: OBJECTIVE
  To investigate the relation of endothelial cell activation with delayed cerebral ischaemia (DCI) and outcome after subarachnoid haemorrhage (SAH).
  
  
  METHODS
  Concentrations of soluble (s) intercellular adhesion molecule-1, sE-selectin, sP-selectin, ED1-fibronectin, von Willebrand Factor (vWf), and vWf propeptide were measured within three days of SAH onset. The associations with poor outcome were investigated at three months in 106 patients. In 90 patients in whom the occurrence of cerebral ischaemia could be dated accurately, two analyses were undertaken: one for all ischaemic events (n = 32), including those related to treatment, and another for spontaneous DCI (n = 11). Concentrations of markers were dichotomised at their medians. The associations of endothelial cell activation markers with outcome were expressed as odds ratios (OR) from logistic regression and those with ischaemic events as hazard ratios (HR) derived from Cox regression.
  
  
  RESULTS
  Early vWf concentrations were associated with poor outcome (crude OR = 4.6 (95% CI, 2.0 to 10.9; adjusted OR = 3.3 (1.1 to 9.8). Early levels of vWf were also positively related to occurrence of all ischaemic events (crude HR = 2.3 (1.1 to 4.9); adjusted HR = 1.8 (0.8 to 3.9) and with occurrence of spontaneous DCI (crude HR = 3.5 (0.9 to 13.1); adjusted HR = 2.2 (0.5 to 9.8). None of the other markers showed any associations.
  
  
  CONCLUSIONS
  Concentrations of sICAM-1, sP-selectin, sE-selectin, and ED1-fibronectin do not predict the occurrence of DCI or outcome. The positive associations of raised early vWf concentrations with ischaemic events and poor outcome after SAH may reflect a predisposition to further ischaemic injury through formation of microthrombi in the cerebral circulation.
authors.affiliation: Department of Neurology, University Medical Centre Utrecht, Utrecht, Netherlands. c.j.m.frijns@neuro.azu.nl
authors.forename: C J M
authors.initials: CJ
authors.lastname: Frijns
authors.forename: R
authors.initials: R
authors.lastname: Fijnheer
authors.forename: A
authors.initials: A
authors.lastname: Algra
authors.forename: J A
authors.initials: JA
authors.lastname: van Mourik
authors.forename: J
authors.initials: J
authors.lastname: van Gijn
authors.forename: G J E
authors.initials: GJ
authors.lastname: Rinkel
mesh_terms: D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000097:blood; D001921:Brain / Q000000981:diagnostic imaging / Q000473:pathology; D002465:Cell Movement; D053331:Ectodysplasins; D004730:Endothelium, Vascular / Q000378:metabolism / Q000473:pathology; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005353:Fibronectins / Q000097:blood; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000097:blood; D002532:Intracranial Aneurysm / Q000097:blood / Q000150:complications* / Q000175:diagnosis*; D008279:Magnetic Resonance Imaging; D008297:Male; D008565:Membrane Proteins / Q000097:blood; D008875:Middle Aged; D019007:P-Selectin / Q000097:blood; D013345:Subarachnoid Hemorrhage / Q000097:blood / Q000175:diagnosis* / Q000209:etiology*; D014057:Tomography, X-Ray Computed; D048069:Tumor Necrosis Factors / Q000097:blood; D014841:von Willebrand Factor / Q000378:metabolism
chemical_list: D015415:Biomarkers; C506018:EDA protein, human; D053331:Ectodysplasins; D005353:Fibronectins; D008565:Membrane Proteins; D019007:P-Selectin; D048069:Tumor Necrosis Factors; D014841:von Willebrand Factor; D018799:Intercellular Adhesion Molecule-1