Inflammatory Biomarkers and Stroke Subtype An Important New Frontier

Inflammation is an established pathway in the formation, growth, and rupture of atherosclerotic plaques. Inflammation is thus essential to the pathogenesis of coronary heart disease and some types of ischemic stroke.1 The benefit of anti-inflammatory therapies, such as colchicine2 and the anti-IL1 beta canakinumab,3 is proven in patients with coronary heart disease, yet it remains unproven for patients with ischemic stroke. Compared with coronary heart disease, the etiology of stroke is more heterogeneous. Besides arterio-arterial atherogenic embolism, possible etiologies are penetrator artery occlusion, cardioembolism, and other mechanisms. Finding a stroke etiology remains elusive in up to 30%-40% of patients despite a full evaluation. Understanding whether the stroke etiology modifies the association between inflammatory markers and recurrence risk is an important step to improve selection of patients for randomized trials on anti-inflammatory agents. IL-6 and high-sensitive CRP (hs-CRP) have been implicated in a higher recurrence risk after ischemic stroke by both an individual participant data meta-analysis4 and a Mendelian randomization study,5 but granular, in vivo results stratified by stroke etiology are lacking.