Histological Features of Carotid Plaque in Patients With Ocular Ischemia Versus Cerebral Events

Abstract

T he risk of ipsilateral ischemic stroke in patients with recent ocular ischemic events is less than half that of otherwise similar patients with recent cerebral ischemic events, [1][2][3] and in those with carotid stenosis, their prognosis is similar to that in patients with asymptomatic stenosis. 4,5 Consequently, in patients with ≥70% carotid artery stenosis in the European Carotid Surgery Trial and North American Symptomatic Carotid Endarterectomy Trial (NASCET), the absolute reduction in 5-year risk of ipsilateral ischemic stroke with surgery was ≈5% for patients with recent ocular events and 17% for those with cerebral events, 4,5 despite a lower procedural risk in the patients with ocular events only. 4,5 Across all carotid endarterectomy trials and case-series, the 30-day risk of stroke in patients with ocular ischemic events is less than half that in patients with cerebral events independent of degree of carotid artery stenosis, 6 and the same difference has been observed in the procedural risk of carotid stenting. 7The reasons for the relatively low risk of ipsilateral ischemic stroke in patients with carotid stenosis and ocular ischemic events are not fully understood. However, the fact that these patient groups have the same prevalence of previous coronary heart disease and peripheral vascular disease and the same risk of future coronary events 5,[8][9][10] suggests that the lower stroke risk in patients with ocular events only may reflect differences in local carotid plaque pathology. The only previous study comparing histological plaque features from patients with ocular versus cerebral ischemic events suggested that patients with ocular events may have more stable plaques, 11 but the number of cases was too small to allow reliable adjustment for differences in other risk factors. We aimed to study carotid plaque composition in a larger number of consecutive patients undergoing carotid endarterectomy for symptomatic stenosis to compare features in those who had cerebral events within the last 6 months versus those with ocular events only.Background and Purpose-Patients with carotid artery stenosis and ocular ischemic events have a much lower risk of future ipsilateral ischemic stroke on medical treatment and lower procedural risks for endarterectomy and stenting than patients with cerebral ischemic events, and are closer in risk to patients with asymptomatic stenosis. The reasons for this difference in prognosis are not fully understood, but may reflect differences in carotid plaque pathology. Methods-In consecutive patients undergoing carotid endarterectomy for recently symptomatic stenosis (Oxford Plaque Study, Athero-Express Study), we compared carotid plaque histology (using validated semiquantitative scales) in those who had cerebral events within the last 6 months (n=1317) versus those with ocular events only (n=323 All patients (and their relevant imaging) were reviewed by a neurologist before carotid endarterectomy. Patients were categorized as having only ocular ischemic events or cerebral...

Plaque Inflammation and Unstable Morphology Are Associated With Early Stroke Recurrence in Symptomatic Carotid Stenosis

“…This finding is supported by other studies, which have reported associations between lower plaque fibrous content and greater likelihood of clinical symptoms and of cerebral compared with ocular events. 14,15 In our study, early stroke recurrence was also associated with fibrous cap disruption on bivariate but not multivariate analysis. This is consistent with previous cross-sectional studies, which found that thrombosis and cap rupture were highly associated with symptomatic (but not asymptomatic) plaque, 13 and with angiographic data, in which surface irregularity and ulceration were associated with cap rupture and late stroke recurrence at all grades of stenosis severity.…”

“…11,12 Cross-sectional studies have reported higher prevalence of carotid plaque inflammation in symptomatic patients 13,14 and in those with cerebral compared with ocular clinical events. 15 Longitudinal data from the Athero-Express study have established an association between a subpopulation of macrophages expressing matrix metalloproteinase-12 and late occurrence of major cardiovascular events and stroke 16 and between macrophageexpressed proteins, such as matrix metalloproteinase-8 and adipocyte fatty acid-binding protein, and late major cardiovascular events (but not stroke alone). 17,18 Longitudinal studies using 18-fluorodeoxyglucose positron emission tomography to image plaque inflammation have reported improved risk stratification for late vascular events by addition of plaque 18-fluorodeoxyglucose uptake data to the Framingham risk score.…”

“…Stroke recurrence was found in 14.7% (8/34) of those with hemispheric stroke or TIA as their index event, whereas 40% (4/10) of those with retinal embolism as their index event had stroke recurrence. The median interval between the index event and stroke recurrence was 16 days (interquartile range, [2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20] and between stroke recurrence and CEA was 9 days (interquartile range, 4-11). An additional 20.5% (9/44) who had not had a stroke recurrence had a TIA recurrence before CEA.…”

7.0 T MRI Detection of Cerebral Microinfarcts in Patients with a Symptomatic High-Grade Carotid artery Stenosis

“…Patients with infarcts and cerebral symptoms were found to profit more from carotid endarterectomy (CEA), compared with patients with just ocular symptoms. 6,7 Therefore, sensitive detection of brain lesions in patients with carotid artery disease may be fundamental for identifying patient (sub)groups with the highest risk of recurrent stroke who might benefit most from carotid surgery.…”

Non-invasive Carotid Artery Imaging to Identify the Vulnerable Plaque: Current Status and Future Goals

“…4,5 Several structural plaque characteristics are proposed that distinguish the "vulnerable" from the "non-vulnerable" plaque, which includes plaque ulceration, intraplaque haemorrhage (IPH), thin or ruptured fibrous cap (FC), lipid-rich necrotic core, and the presence of calcification. 6 Inflammation may also play a role in the development and progression of disease as well as identifying the vulnerable plaque.…”