Abstract WP169: Coated-platelets and Tumor Necrosis Factor Alpha Predict TIA/stroke at Twenty-one Months in Asymptomatic Carotid Stenosis

Abstract

Background: The clinical spectrum of carotid atherosclerosis is well characterized, but the events leading to plaque instability and stroke are less understood. Evidence suggests that platelets serve as an interface among hemostasis, inflammation, and atherosclerosis. Coated-platelets, a subset of platelets with high procoagulant potential, are increased in asymptomatic carotid stenosis patients at high risk for stroke or TIA. We now examine the impact of other soluble mediators of inflammation, cell adhesion, angiogenesis and coagulation on the association between coated-platelets and TIA/stroke in asymptomatic carotid stenosis. Methods: Consecutive asymptomatic patients with ≥50% carotid stenosis were enrolled. Coated-platelet levels were assayed and plasma was obtained for measurement of 58 biomarkers. Patients were followed at 6-month intervals for intensive vascular risk reduction. Those with signs or symptoms of TIA/stroke underwent either brain CT or MRI. Rank order correlations between inflammatory marker concentrations, coated-platelet levels and TIA/stroke were determined using the Spearman correlation coefficient. Variables associated with TIA/stroke (p<0.15) were included in multivariate analysis. Results: We enrolled 117 patients (97% male, average age 71, 94% on statins, 96% on antiplatelets, and 33% currently smoking, average HgA1c 6.6% and average LDL 86 mg/dL). There were 6 strokes and 2 TIA’s ipsilateral to carotid stenosis during a mean 21.3 ± 6.7 months of follow-up (incidence of 3.89/100 person-years). Stepwise logistic regression identified TNF alpha (OR=11.1, p=0.0300) and coated-platelet group (OR=14.1, p=0.0167) as predictors of TIA/stroke ipsilateral to stenosis. Cox Proportional Hazard analysis yielded a TIA/stroke HR of 11.8 for the high coated-platelet group (95% CI 1.4, 96.1, p=0.0215) and 8.0 (95% CI 0.97, 66.3, p=0.0529) for the high TNF alpha group. Discussion: Coated-platelets and TNF alpha predict TIA/stroke in asymptomatic carotid stenosis at 21 months. These findings expand on our previous work in coated-platelets and asymptomatic carotid stenosis and suggest that coated-platelets may represent a common link between hemostatic and inflammatory mechanisms of plaque instability.