Abstract TP571: Coated-Platelets, RANTES and IL-7 Correlate With Silent Brain Infarction in Carotid Stenosis

Abstract

Background: Silent brain infarction (SBI) is associated with both cognitive decline and recurrent stroke. While cortical SBI may have an embolic source, the etiology of subcortical SBI (80% of SBI) is less clear. We now examine the association between coated-platelets (procoagulant platelets observed upon dual agonist stimulation with collagen and thrombin), soluble mediators of inflammation, cell adhesion, angiogenesis and coagulation and SBI in carotid stenosis patients. Methods: Asymptomatic patients with ≥50% carotid stenosis were enrolled, coated-platelets assayed, and plasma obtained for measurement of 58 plasma biomarkers. Presence and location of SBI, defined as a focal, ≥ 3mm cavitary lesion with T1 hypointensity and T2 hyperintensity features on MRI within 12 months of enrollment, were recorded. Variables correlating (p<0.10) with SBI were included for multiple regression and retained if p<0.05. Results: Thirty-two subjects were analyzed. Cardiac ejection fraction (r= -0.34, p=0.0325), coated-platelets (r=0.5471, p=0.0014) and IL-7 (r=0.35, p=0.0498) correlated with overall SBI number. Antiplatelet use (r= -0.63, p=0.0001), coated-platelets (r=0.43, p=0.0152) and RANTES (r=0.39, p=0.0283) correlated with cortical SBI number. Beta blocker use (r= -0.40, p=0.0238) and coated-platelets (r=0.52, p=0.0030) correlated with subcortical SBI number, with a trend for correlation between IL-7 and subcortical SBI number (r=0.35, p=0.0518). Multivariate analysis revealed coated-platelet levels ≥40.5% and lack of beta blocker use were associated with subcortical SBI (OR=35.22, p=0.0057 and OR=10.74, p=0.0347 respectively). Discussion: Our results demonstrate a strong association between coated-platelets and SBI regardless of anatomic location. We have also identified two inflammatory mediators associated with cortical (RANTES) and subcortical (IL-7) SBI location. Our findings suggest protective effects of antiplatelet use for cortical SBI and beta blocker use for subcortical SBI. Altogether, these data support a thrombotic mechanism of SBI with differing auxiliary mechanisms for cortical and subcortical SBI that may involve alternate inflammatory pathways.