title: Juxtalumenal location of plaque necrosis and neoformation in symptomatic carotid stenosis.
abstract: OBJECTIVE
  The structural features that underlie carotid plaque disruption and symptoms are largely unknown. We have previously shown that the chemical composition and structural complexity of critical carotid stenoses are related to plaque size regardless of symptoms. To further determine whether the spatial distribution of individual plaque components in relation to the lumen corresponds to symptomatic outcome, we evaluated 99 carotid endarterectomy plaques.
  
  
  METHODS
  Indications for operation were symptomatic disease in 59 instances (including hemispheric transient ischemic attack in 29, stroke in 19, and amaurosis fugax in 11) and angiographic asymptomatic stenosis > 75% in 40. Plaques removed after remote symptoms beyond 6 months were excluded. Histologic sections from the most stenotic region of the plaque were examined using computer-assisted morphometric analysis. The percent area of plaque cross-section occupied by necrotic lipid core with or without associated plaque hematoma, by calcification, as well as the distance from the lumen or fibrous cap of each of these features, were determined. The presence of foam cells, macrophages, and inflammatory cell collections within, on, or just beneath the fibrous cap was taken as an additional indication of plaque neoformation.
  
  
  RESULTS
  The mean percent angiographic stenosis was 82% +/- 11% and 79% +/- 13% for the asymptomatic and symptomatic groups, respectively (p > 0.05). The necrotic core was twice as close to the lumen in symptomatic plaques when compared with asymptomatic plaques (0.27 +/- 0.3 mm vs 0.5 +/- 0.5 mm; p < 0.01). The percent area of necrotic core or calcification was similar for both groups (22% vs 26% and 7% vs 6%, respectively). There was no significant relationship to symptom production of either the distance of calcification from the lumen or of the percent area occupied by the lipid necrotic core or calcification. The number of macrophages infiltrating the region of the fibrous cap was three times greater in the symptomatic plaques compared with the asymptomatic plaques (1114 +/- 1104 vs 385 +/- 622, respectively, p < 0.009). Regions of fibrous cap disruption or ulceration were more commonly observed in the symptomatic plaques than in the asymptomatic plaques (32% vs 20%). None of the demographic or clinical atherosclerosis risk factors distinguished between symptomatic and asymptomatic plaques.
  
  
  CONCLUSIONS
  These findings indicate that proximity of plaque necrotic core to the lumen and cellular indicators of plaque neoformation or inflammatory reaction about the fibrous cap are associated with clinical ischemic events. The morphologic complexity of carotid stenoses does not appear to determine symptomatic outcome but rather the topography of individual plaque components in relation to the fibrous cap and the lumen. Imaging techniques that precisely resolve the position of the necrotic core and evidence of inflammatory reactions within carotid plaques should help identify high-risk stenoses before disruption and symptomatic carotid disease.
authors.affiliation: Department of Surgery, University of Chicago, IL 60637, USA.
authors.forename: H S
authors.initials: HS
authors.lastname: Bassiouny
authors.forename: Y
authors.initials: Y
authors.lastname: Sakaguchi
authors.forename: S A
authors.initials: SA
authors.lastname: Mikucki
authors.forename: J F
authors.initials: JF
authors.lastname: McKinsey
authors.forename: G
authors.initials: G
authors.lastname: Piano
authors.forename: B L
authors.initials: BL
authors.lastname: Gewertz
authors.forename: S
authors.initials: S
authors.lastname: Glagov
mesh_terms: D000368:Aged; D001161:Arteriosclerosis / Q000473:pathology* / Q000601:surgery; D002114:Calcinosis / Q000473:pathology; D002339:Carotid Arteries / Q000473:pathology*; D016893:Carotid Stenosis / Q000473:pathology* / Q000601:surgery; D005260:Female; D006801:Humans; D008264:Macrophages / Q000473:pathology; D008297:Male; D009336:Necrosis