Abstract TP162: Specific Inflammatory Mediators Associated With Incident Ischemic Stroke and Individual Ischemic Stroke Subtypes

Abstract

Introduction: Epidemiological studies have shown that serum inflammatory markers are independently associated with ischemic stroke. We assessed the hypothesis that specific inflammatory mediator is associated with specific ischemic stroke subtypes in the Atherosclerosis Risk in Communities (ARIC) study. Methods: In the ARIC study, serum inflammatory mediators were assessed in a cohort of subjects without prior stroke. They included high sensitivity C-reactive protein (hs-CRP), interleukin 1ra (IL-1ra), and Intercellular Adhesion Molecule 1(sICAM1) and were followed for all vascular events. All stroke events were adjudicated and classified into stroke subtypes by standard definitions. Multivariable Cox proportional hazards models were used to study the relationship between elevated inflammatory markers (upper quartile compared with lower three quartiles) and ischemic stroke, as well as stroke subtypes (cardioembolic, lacunar or thrombotic). Results: At the fourth ARIC study visit, serum inflammatory mediators were assessed in a cohort of 5663 subjects (mean age±SD=62.3±5.6, 55% female, 83% white and 17% African-American). Over a 15-year follow-up, 237 (4.2%) subjects had incident ischemic stroke of which 47% were thrombotic, 26% were cardioembolic, and 20% were of the lacunar stroke subtype. After adjustment for Race/Center, Age, Gender, BMI, Hypertension, Diabetes, LDL Level, Smoking (3-levels), Pack Years, Education (3-levels), hs-CRP (adjusted HR 1.45, 95% CI 1.08-1.96), IL-1ra (adjusted HR 1.90, 95% CI 1.09-3.28) and sICAM1(adjusted HR 1.33, 95% CI 1.0-1.78) were associated with overall ischemic stroke. This was driven by associations between hs-CRP and thrombotic stroke (adjusted HR 1.73, 95% CI 1.14-2.61), IL-1ra and cardioembolic stroke (adjusted HR 3.42, 95% CI 1.23-9.53), and sICAM-1 and lacunar stroke (adjusted HR 1.92, 95% CI 1.05-3.50). Conclusions: Results from this prospective show an independent association between serum inflammatory mediators and incident ischemic stroke. These associations appear to be attributed to the association between specific inflammatory mediator and individual stroke subtype. These results shed light to the mechanism by which inflammatory mediators contribute to stroke risk.