title: Progression of symptomatic intracranial large artery atherosclerosis is associated with a proinflammatory state and impaired fibrinolysis.
abstract: OBJECTIVE
  The molecular pathways involved in the progression of intracranial large artery atherosclerosis (ILA) are largely unknown. Our objective was to prospectively study the relationship between circulating levels of inflammatory markers and fibrinolysis inhibitors, and the risk of progression of symptomatic ILA.
  
  
  METHODS
  Seventy-five consecutive patients with first-ever symptomatic intracranial atherostenosis were studied. Blood levels of C-reactive protein (CRP), E-selectin, monocyte chemoattractant protein-1, intercellular adhesion molecule-1, matrix metalloproteinases 1, 2, 3, 8, 9, 10, and 13, plasminogen activator inhibitor-1 (PAI-1), and lipoprotein(a) were measured 3 months after the qualifying stroke or transient ischemic attack. Thereafter, patients underwent long-term transcranial Doppler follow-up to detect progression of ILA.
  
  
  RESULTS
  During a median follow-up time of 23 months, 25 (33%) patients showed ILA progression. Multivariable adjusted Cox regression models and Kaplan-Meier curves showed that high baseline level of CRP, E-selectin, intercellular adhesion molecule-1, matrix metalloproteinase 9, PAI-1, and lipoprotein(a) predicted ILA progression independently of vascular risk factors. Of them, only CRP (CRP>5.5 mg/L; HR, 5.4 [2.3 to 12.7]; P=0.0001) and PAI-1 (PAI-1>23.1 ng/mL; HR, 2.4 [1.0 to 5.8]; P=0.05) predicted ILA progression also independently of the other studied molecules.
  
  
  CONCLUSIONS
  Progression of symptomatic ILA is associated with a proinflammatory state, as reflected by high levels of inflammatory markers, and with defective fibrinolysis, as indicated by raised concentrations of endogenous fibrinolysis inhibitors.
authors.affiliation: Neurovascular Unit, Vall d'Hebron Universitary Hospital, Barcelona, Spain. juanfarenillas@terra.es
authors.forename: Juan F
authors.initials: JF
authors.lastname: Arenillas
authors.forename: José
authors.initials: J
authors.lastname: Alvarez-Sabín
authors.forename: Carlos A
authors.initials: CA
authors.lastname: Molina
authors.forename: Pilar
authors.initials: P
authors.lastname: Chacón
authors.forename: Israel
authors.initials: I
authors.lastname: Fernández-Cadenas
authors.forename: Marc
authors.initials: M
authors.lastname: Ribó
authors.forename: Pilar
authors.initials: P
authors.lastname: Delgado
authors.forename: Marta
authors.initials: M
authors.lastname: Rubiera
authors.forename: Anna
authors.initials: A
authors.lastname: Penalba
authors.forename: Alex
authors.initials: A
authors.lastname: Rovira
authors.forename: Joan
authors.initials: J
authors.lastname: Montaner
mesh_terms: D000368:Aged; D015415:Biomarkers / Q000032:analysis / Q000097:blood; D002097:C-Reactive Protein / Q000032:analysis / Q000378:metabolism; D002536:Cerebral Arteries / Q000000981:diagnostic imaging / Q000473:pathology / Q000503:physiopathology*; D018932:Chemokine CCL2 / Q000032:analysis / Q000097:blood; D018450:Disease Progression; D019040:E-Selectin / Q000032:analysis / Q000097:blood; D005260:Female; D005342:Fibrinolysis; D005500:Follow-Up Studies; D006801:Humans; D018836:Inflammation Mediators / Q000032:analysis / Q000097:blood*; D018799:Intercellular Adhesion Molecule-1 / Q000032:analysis / Q000097:blood; D002537:Intracranial Arteriosclerosis / Q000097:blood / Q000503:physiopathology*; D008074:Lipoproteins / Q000032:analysis / Q000097:blood; D008297:Male; D020782:Matrix Metalloproteinases / Q000097:blood; D008875:Middle Aged; D017395:Plasminogen Activator Inhibitor 1 / Q000032:analysis / Q000097:blood; D011237:Predictive Value of Tests; D011379:Prognosis; D011446:Prospective Studies; D017585:Ultrasonography, Doppler, Transcranial; D020293:Vasculitis, Central Nervous System / Q000097:blood / Q000150:complications / Q000503:physiopathology*
chemical_list: D015415:Biomarkers; C111835:CCL2 protein, human; D018932:Chemokine CCL2; D019040:E-Selectin; D018836:Inflammation Mediators; D008074:Lipoproteins; D017395:Plasminogen Activator Inhibitor 1; D018799:Intercellular Adhesion Molecule-1; D002097:C-Reactive Protein; D020782:Matrix Metalloproteinases