Association between fibrinogen and fibrinogen γ′ and atherosclerotic plaque morphology and composition in symptomatic carotid artery stenosis: Plaque-At-RISK study

Introduction: Von Willebrand Factor (VWF), ADAMTS13, fibrinogen and fibrinogen gamma' are associated with an increased risk of ischemic stroke. Carotid atherosclerosis is an important risk factor for ischemic stroke. Characteristics of the vulnerable plaque; intraplaque hemorrhage (IPH), plaque ulceration and lipid-rich necrotic core (LRNC) can be visualized with imaging techniques. Since atherosclerosis might attribute to the association between coagulation factors and ischemic stroke risk, the aim of this study is to investigate the association between coagulation factors and atherosclerotic plaque characteristics in more detail. Materials and methods: In 182 patients of the Plaque-At-RISK study (prospective multicenter cohort study) with a recent transient ischemic attack (TIA) or ischemic stroke and a symptomatic mild-to-moderate carotid artery stenosis, we measured VWF antigen (VWF:Ag), ADAMTS13 activity, fibrinogen (Clauss), and fibrinogen gamma'. Presence of plaque ulceration, IPH volume and LRNC volume were determined by Multidetector-Row Computed Tomography (MDCTA, n = 160) and Magnetic Resonance Imaging (MRI, n = 172). Linear regression analysis was used to assess the association between imaging biomarkers and coagulation factors. Results: VWF:Ag or ADAMTS13 levels were not significantly associated with plaque ulceration, IPH and LRNC. We found an inverse association between fibrinogen and fibrinogen gamma' and IPH volume (B = -23.40mm(3)/g/L, p = 0.01 and B = -161.73mm(3)/g/L, p = 0.01) and between fibrinogen and fibrinogen gamma' and LRNC volume (B = -38.89mm(3) g/L, p < 0.01 and B = -227.06mm(3) g/L, p = 0.01). Additional adjustments for C-reactive protein (CRP) did not change the results. Conclusions: Fibrinogen and fibrinogen gamma' are inversely associated with IPH volume and LRNC volume, independent of inflammation.