Abstract 1155: Symptomatic Low- And High-degree Carotid Stenoses Exhibit Similar Features Of Plaque Instability

Abstract

Background: Carotid endarterectomy (CEA) for symptomatic carotid stenosis is recommended for patients with the >70% (NASCET) stenosis but not for those with <50%. Since low-degree stenoses may still cause strokes, refined risk stratification is necessary, which could be improved by incorporating biological features of plaque instability. In order to challenge risk-stratification by the degree of stenosis, we compared biological features of carotid plaques from symptomatic patients with <50% stenosis vs. >70% and explored mechanisms behind plaque instability in low-degree stenoses. Methods: CEA specimens were retrieved from symptomatic patients with >70% (n=204) and <50% stenosis (n=34), all part of the Biobank of Karolinska Endarterectomies (BiKE). Patient demographics, plaque morphology from image analyses of preoperative computed tomography angiography (CTA), and RNA-seq analyses of lesions were used for comparisons. Plaque biology was assessed by transcriptomics using principal component analyses (PCA), differential gene expression (DGE)- and gene-set enrichment analyses (GSEA). Immunohistochemistry (IHC) was used to study proteins corresponding to upregulated genes. Results: The demographics of the two groups were statistically similar. They also showed similar plaque morphology with respect to intraplaque hemorrhage (IPH), plaque burden and fibrous cap thickness, whereas calcification was higher in the <50% group and lipid-rich necrotic core higher in the >70% group. PCA analysis indicated poor clustering, while DGE and GSEA identified enrichment of genes and pathways related to tissue hypoxia and angiogenesis in <50% lesions. Corresponding proteins were detected by IHC in neo-vascularized plaque regions. Conclusions: Plaques from symptomatic patients with <50% carotid stenoses exhibit largely similar morphological and biological features as those from >70% stenoses, emphasizing the need for improved stratification of patients for CEA of symptomatic carotid stenosis. However, pathways associating plaque burden, hypoxia and angiogenesis were particularly enriched in low-grade stenosis lesions suggesting mechanisms behind plaque instability and symptoms in patients with both low- and high-degree stenosis.