Role of inflammation in stroke and atherothrombosis

Abstract

The onset of cerebral ischaemia triggers a cascade of proinflammatory molecular and cellular events. Clinical studies suggest that the strength of this acute response is important in early and late clinical outcomes, early clinical worsening, and extent of brain damage. Variables that are predictors of adverse stroke outcome include erythrocyte sedimentation rate, and levels of C-reactive protein (CRP), interleukin-6, tumour necrosis factor-alpha and intercellular adhesion molecule-1. Current data indicate that inflammation serves to fuel atherosclerosis and can act as the link between atherosclerosis and atherothrombosis. Growing evidence indicates that platelets act as prominent players in the inflammatory component of these disease processes. Thus, upon activation, platelets release a series of cytokines and growth factors and express CD40 ligand, which interacts with the CD40 receptor on other major cell types involved in atherosclerosis/atherothrombosis. In healthy volunteers, CD40L expression in platelets is not significantly inhibited by acetylsalicylic acid (ASA) alone, but is inhibited after treatment with the ADP-receptor antagonist clopidogrel or with clopidogrel plus ASA. Of a range of potential inflammatory biomarkers that have been reported in the literature, the best studied is CRP. Such biomarkers may have clinical utility for refined identification of patients at high risk for atherothrombosis in different arterial beds and for monitoring of therapeutic agents in clinical trials.