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(Stroke. 2008;39:1456.)
© 2008 American Heart Association, Inc.

Original Contributions

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

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

From Neurovascular Unit (J.A.-S., C.A.M., M.R., M.Rubiera) and Neurovascular Research Laboratory (I.F.-C., P.D., A.P., J.M.), Department of Neurology; Lipid Research Unit (P.C.), Department of Biochemistry; Magnetic Resonance Unit (A.R.), Department of Neuroradiology, Vall d’Hebron Universitary Hospital, Barcelona, Spain; Neurovascular Unit (J.F.A.), Department of Neurosciences, Germans Trias i Pujol Universitary Hospital, Universitat Autònoma de Barcelona, Badalona, Spain.

Correspondence to Juan F. Arenillas Lara, Stroke Unit, Department of Neurosciences, Germans Trias i Pujol Universitary Hospital, Autonomous University of Barcelona, Carretera de Canyet sn, 08916 Badalona, Barcelona, Spain. E-mail juanfarenillas{at}terra.es

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.

Key Words: fibrinolysis • inflammation • intracranial atherosclerosis • intracranial stenosis • progression