Glycophorin C in atherosclerotic plaque is associated with major adverse cardiovascular events after carotid endarterectomy

Abstract

AbstractIntroductionHistological assessment studies have identified the presence of intraplaque hemorrhage (IPH) as an indicator of plaque instability and resulting ischemic cerebral sequelae. Although the presence of IPH has been studied extensively in relation to neurological symptoms preceding carotid endarterectomy (CEA) or as a predictor for postoperative risk of major adverse cardiovascular events (MACE), the degree of IPH has not been studied before. Glycophorin, an erythrocyte-specific protein, has been suggested as a marker for the degree of previous hemorrhages in atherosclerotic plaque since erythrocytes are prominently present in IPH. We hypothesized that quantified plaque glycophorin C, as a proxy for the degree of IPH, is associated with destabilizing plaque characteristics, preprocedural symptoms, and increased postoperative risk for MACE.MethodsWe quantified glycophorin C and six other plaque characteristics with the slideToolkit method. We used human atherosclerotic plaque samples from 1971 consecutive asymptomatic and symptomatic (carotid endarterectomy) patients in the Athero-Express Biobank.ResultsThe total area of glycophorin C in plaque was larger in individuals with a plaque with IPH compared to individuals with plaque without IPH (p<0.001). Quantified glycophorin C was significantly associated with ipsilateral pre-procedural neurological symptoms (OR:1.27, 95%CI:1.06-1.41, p=0.005). In addition, quantified glycophorin C was independently associated with an increased postoperative risk for MACE (HR:1.31, 95%CI:1.01-1.68, p=0.04). Stratified by sex, quantified glycophorin C was associated with an increased postoperative risk for MACE in male patients (HR:1.50, 95%CI:1.13-1.97, p=0.004), but not in female patients (HR:0.70, 95%CI:0.39-1.27, p=0.23).ConclusionQuantified glycophorin C, as a proxy for the degree of IPH, was independently associated with the presence of IPH, symptomatic preprocedural symptoms, and with an increased three-year postoperative risk of MACE. These findings indicate that quantified plaque glycophorin C can be considered as a marker for identifying male patients with a high residual risk for secondary MACE after CEA.