Progression of symptomatic intracranial large artery atherosclerosis is associated with a proinflammatory state and impaired fibrinolysis

Juan F. Arenillas, José Álvarez-Sabín, Carlos A. Molina, Pilar Chacón, Israel Fernández-Cadenas, Marc Ribó, Pilar Delgado, Marta Rubiera, Anna Penalba, Alex Rovira, Joan Montaner

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73 Citations (Scopus)


BACKGROUND AND PURPOSE-: 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. CONCLUSION-: 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. © 2008 American Heart Association, Inc.
Original languageEnglish
Pages (from-to)1456-1463
Issue number5
Publication statusPublished - 1 May 2008


  • Fibrinolysis
  • Inflammation
  • Intracranial atherosclerosis
  • Intracranial stenosis
  • Progression


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