Progression of Symptomatic Intracranial Large Artery Atherosclerosis Is Associated With a Proinflammatory State and Impaired Fibrinolysis

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 symptoma...

Full description

Saved in:
Bibliographic Details
Published in:Stroke (1970) 2008-05, Vol.39 (5), p.1456-1463
Main Authors: ARENILLAS, Juan F, ALVAREZ-SABIN, José, MONTANER, Joan, MOLINA, Carlos A, CHACON, Pilar, FERNANDEZ-CADENAS, Israel, RIBO, Marc, DELGADO, Pilar, RUBIERA, Marta, PENALBA, Anna, ROVIRA, Alex
Format: Article
Language:English
Subjects:
Aged
Atherosclerosis (general aspects, experimental research)
Biological and medical sciences
Biomarkers - analysis
Biomarkers - blood
Blood and lymphatic vessels
C-Reactive Protein - analysis
C-Reactive Protein - metabolism
Cardiology. Vascular system
Cerebral Arteries - diagnostic imaging
Cerebral Arteries - pathology
Cerebral Arteries - physiopathology
Chemokine CCL2 - analysis
Chemokine CCL2 - blood
Disease Progression
E-Selectin - analysis
E-Selectin - blood
Female
Fibrinolysis
Follow-Up Studies
Humans
Inflammation Mediators - analysis
Inflammation Mediators - blood
Intercellular Adhesion Molecule-1 - analysis
Intercellular Adhesion Molecule-1 - blood
Intracranial Arteriosclerosis - blood
Intracranial Arteriosclerosis - physiopathology
Lipoproteins - analysis
Lipoproteins - blood
Male
Matrix Metalloproteinases - blood
Medical sciences
Middle Aged
Neurology
Plasminogen Activator Inhibitor 1 - analysis
Plasminogen Activator Inhibitor 1 - blood
Predictive Value of Tests
Prognosis
Prospective Studies
Ultrasonography, Doppler, Transcranial
Vascular diseases and vascular malformations of the nervous system
Vasculitis, Central Nervous System - blood
Vasculitis, Central Nervous System - complications
Vasculitis, Central Nervous System - physiopathology
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary: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. 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. 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. 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.
ISSN:0039-2499
1524-4628
DOI:10.1161/STROKEAHA.107.498600