Abstract TMP98: Increased Fractalkine and Decreased RANTES Concentrations Predict Progression of Carotid Stenosis Severity at Twenty Months

Abstract

Introduction: Studies have demonstrated that progression of carotid stenosis severity in asymptomatic patients is associated with increased stroke risk. Identifying stenosis progression mechanisms would improve risk prediction and development of novel targeted treatments. We now examine the association between soluble mediators of inflammation, cell adhesion, angiogenesis and coagulation and progression of stenosis severity in asymptomatic carotid stenosis. Methods: Asymptomatic patients with 50-79% carotid stenosis were enrolled and carotid Doppler surveillance performed every 6-12 months. Plasma was obtained at baseline for measurement of 50 plasma biomarkers of inflammation, cell adhesion, and angiogenesis. Carotid stenosis progression was confirmed by blinded adjudication. Variables associated with progression of stenosis severity (p<0.15) were included in multivariate analysis. Variables retained as significant were included in cox proportional hazard analysis. Results: We enrolled 108 patients (96% male, 34% smokers, average HgA1c 6.6% and average LDL 86 mg/dL). Stenosis severity progressed in 14 (13%) over 20 ± 11 months. Fractalkine (p=0.018), IL-7 (p=0.087), IL-18 (p=0.087), PAI1 (p=0.0871), IL-13 (p=0.0939), and RANTES (p=0.0097) were included in multivariate analysis. Fractalkine (OR = 5.5, p=0.0157) and RANTES (OR = 0.133, p=0.0127) were retained in the final model. Fractalkine concentrations ≥16.9 pg/ml yielded a HR of 4.67 (95% CI 1.3, 16.8; p=0.0093) and RANTES concentrations ≥430 pg/ml yielded a HR of 0.16 (95% CI 0.036, 0.728; p=0.0121) for stenosis progression. Conclusions: Our results show that increased Fractalkine and decreased RANTES concentrations predicted carotid stenosis severity progression at 20 months. Fractalkine is increased in human coronary and carotid artery plaques and prolongs survival of monocytes/macrophages contributing to atherosclerosis progression in Apo E -/- mice. RANTES binds endothelial CCR receptors facilitating migration of T cells and monocytes into the intima. Decreased RANTES levels have been linked to adverse coronary artery disease outcomes. Further study to clarify the role of Fractalkine and RANTES in atherosclerosis progression is warranted.