Plaque Fibrous Cap Status is Linked to Increased Risk of Recurrent Ischaemic Events Prior to Carotid Endarterectomy in Patients with Symptomatic Carotid Artery Stenosis

Daina Kashiwazaki; Shusuke Yamamoto; Emiko Hori; Naoki Akioka; Noriko Okuno; Kyo Noguchi; Satoshi Kuroda

doi:10.1016/j.ejvs.2026.02.016

Plaque Fibrous Cap Status is Linked to Increased Risk of Recurrent Ischaemic Events Prior to Carotid Endarterectomy in Patients with Symptomatic Carotid Artery Stenosis

Eur J Vasc Endovasc Surg. 2026 Feb 16:S1078-5884(26)00149-8. doi: 10.1016/j.ejvs.2026.02.016. Online ahead of print.

Authors

Daina Kashiwazaki¹, Shusuke Yamamoto², Emiko Hori², Naoki Akioka², Noriko Okuno³, Kyo Noguchi⁴, Satoshi Kuroda²

Affiliations

¹ Department of Neurosurgery, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Toyama, Japan. Electronic address: dkashiwa@med.u-toyama.ac.jp.
² Department of Neurosurgery, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Toyama, Japan.
³ Department of Pathology, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Toyama, Japan.
⁴ Department of Radiology, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Toyama, Japan.

PMID: 41708048
DOI: 10.1016/j.ejvs.2026.02.016

Abstract

Objective: Carotid plaque with thin or disrupted fibrous cap (TDFC) is an underlying cause of ischaemic stroke; however, no histopathological study has investigated potential associations between fibrous cap (FC) status, inflammation markers, and neurological outcomes. The objective of this study was to evaluate these associations in patients with carotid artery stenosis planned for carotid endarterectomy (CEA).

Methods: This was a prospective, single centre, observational study of patients with carotid artery stenosis who underwent CEA. All patients underwent assessment of cerebral haemodynamic state using ¹²³I-N-isopropyl-p-iodoamphetamine single photon emission computed tomography. Asymptomatic patients were included as a control. Histopathological TDFC sites were classified as shoulder involved, mid, or no TDFC to facilitate intergroup comparisons of demographics, cerebral infarction patterns, plaque composition, cerebral haemodynamics, TDFC site evaluated by magnetic resonance imaging, frequency of ischaemic stroke from index event to CEA, matrix metalloproteinase-9 (MMP-9) and cluster of differentiation 68 (CD68) levels, and 3 month modified Rankin Scale (mRS) scores.

Results: Of 151 patients enrolled, shoulder involved, mid, and no TDFC was identified in 88 (58.3%), 42 (27.8%), and 21 (13.9%) patients, respectively. In 25 asymptomatic subjects, no plaques with TDFC were observed. C reactive protein levels in shoulder involved TDFC were statistically significantly higher than those of the other types (p = .020). Median (interquartile range [IQR]) MMP-9 and CD68 positive macrophage counts were highest in shoulder involved TDFC (102 [IQR 59] and 141 [IQR 50], respectively) compared with the other types. Shoulder involved TDFC experienced watershed cerebral infarctions, had more diffusion weighted imaging positive lesions (p < .001), and experienced recurrent neurological symptoms prior to CEA more frequently as well as the worst 3 month post-stroke mRS scores (p < .001).

Conclusion: FC status affects cerebral infarction patterns in shoulder involved TDFC, which is associated with local inflammation and watershed cerebral infarctions. Collectively, these processes may influence recurrent neurological symptoms prior to CEA and contribute to poor 3 month mRS scores.

Keywords: Carotid endarterectomy; Carotid stenosis; Diffusion weighted imaging; Fibrous cap; Ischaemic events; Shoulder.