Association of Local Wall Shear Stress with Plaque Features in Carotid Artery Disease: Insights from Histopathological and Neutrophil Extracellular Trap Analysis

Introduction: Local hemodynamic conditions influence atherosclerotic plaque biology; however, their relationship with plaque characteristics in carotid artery disease remains incompletely understood. Methods: In this single-center observational study using retrospectively collected data, we analyzed 49 patients who underwent carotid endarterectomy with preoperative computed tomography angiography. Computational fluid dynamics was used to quantify local minimum and maximum wall shear stress (WSS_min and WSS_max) within each plaque. Associations between regional WSS patterns and clinical and radiological features were evaluated. Histopathological evaluation using hematoxylin and eosin staining was performed in a subset of 17 lesions, with exploratory assessment of neutrophil extracellular traps (NETs) using citrullinated histone H3 immunostaining. Results: WSS_min was preferentially observed in ulcerated plaque regions and was associated with symptomatic presentation, particularly in analyses restricted to ulcerated lesions. In contrast, WSS_max correlated with stenosis severity and was predominantly observed in asymptomatic lesions. Histopathological analysis demonstrated multilayered lesion architecture and inflammatory changes in WSS_min regions, whereas WSS_max regions more frequently exhibited plaque rupture. However, the luminal surface was often covered by endothelium, and thick fibrous caps were also observed. In paired analyses, NET accumulation was higher in WSS_min regions than in WSS_max regions. Conclusions: Local wall shear stress is associated with plaque features and distinct histopathological characteristics in carotid artery disease. These findings suggest that regional hemodynamic conditions contribute to plaque biology and provide complementary insights beyond conventional morphological evaluation, while remaining hypothesis-generating and requiring validation in larger studies.