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

Abstract

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). 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. 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 72, 131] and 141 [IQR 121, 171], respectively) compared with the other types. Shoulder involved TDFC experienced watershed cerebral infarctions, had more diffusion weighted imaging positive lesions (p < .001), and more frequently experienced recurrent neurological symptoms before CEA as well as the worst 3 month post-stroke mRS scores (p < .001). 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 before CEA and contribute to poor 3 month mRS scores.