Abstract W MP55: Inflammatory Biomarkers and Incident Stroke in the Framingham Offspring Study.

Background: Inflammatory cascades are believed to be involved in pathogenesis of small vessel disease and atherothrombosis. We related a comprehensive panel of inflammatory biomarkers to risk of incident ischemic stroke (IS) in a community-dwelling sample Methods: Stroke-free Framingham Offspring attending exam cycle 7 (1998-2001) had multiple serum inflammatory biomarkers measured. Fourteen biomarkers representing various components of the inflammatory cascade, including systemic inflammation (C-reactive protein [CRP], interleukin-6, monocyte chemotactic protein 1, tumor necrosis factor-α, tumor necrosis factor receptor 2 [TNFr2], osteoprotegerin and fibrinogen), vascular inflammation (intercellular adhesion molecule-1, CD40 ligand, P-selectin, lipoprotein-associated phospholipase A2 mass and activity, total homocysteine [tHcy] and vascular endothelial growth factor [VEGF]) and oxidative stress (myeloperoxidase) were selected. Cox proportional hazard models were used to relate individual biomarkers to risk of incident IS. Model A included age and sex. Model B additionally adjusted for systolic blood pressure, hypertension treatment, current smoking, diabetes, cardiovascular disease, and atrial fibrillation. Hazard ratios (HR) are presented as per 1 SD increment. Results: In 3224 participants (age: 61±9 years, 54% women), 98 experienced incident IS (mean follow-up of 9.8 [±2.2] years). In Model A, log-CRP (HR: 1.28 [95%CI 1.04-1.56]), log-TNFR2 (HR: 1.33 [95%CI 1.09-1.63]), tHcy (HR: 1.32 [95%CI 1.11-1.58]) and VEGF (HR: 1.25 [95%CI 1.07-1.46]) were associated with risk of incident IS. All associations, except for CRP, remained significant in Model B {log-TNFR2 (1.24 [1.02-1.51]), tHcy (1.20 [1.01-1.43]), VEGF (1.21 [1.04-1.42]) and CRP (1.13 [0.92-1.40])}. Addition of these 4 biomarkers to the clinical Framingham Stroke Risk Profile score improved stroke risk prediction (net reclassification improvement: 0.34; p<0.05 using boundaryless models). Conclusions: Higher levels of four biomarkers: CRP, tHcy, TNFR2 and VEGF increased risk of incident ischemic stroke. Further research is required to confirm their utility in improving stroke risk prediction, and explore their role as potential therapeutic targets.