JUXTALUMENAL LOCATION OF PLAQUE NECROSIS AND NEOFORMATION IN SYMPTOMATIC CAROTID STENOSIS

Purpose: The structural features that underlie carotid plaque disrupti on and symptoms are largely unknown. We have previously shown that the chemical composition and structural complexity of critical carotid st enoses are related to plaque size regardless of symptoms. To further d etermine whether the spatial distribution of individual plaque compone nts in relation to the lumen corresponds to symptomatic outcome, we ev aluated 99 carotid endarterectomy plaques. Methods: Indications for op eration were symptomatic disease in 59 instances (including hemispheri c transient ischemic attack in 29, stroke in 19, and amaurosis fugax i n 11) and angiographic asymptomatic stenosis >75% in 40. Plaques remov ed after remote symp toms beyond 6 months were excluded. Histologic se ctions from the most stenotic region of the plaque were examined using computer-assisted morphometric analysis. The per cent area of plaque cross-section occupied by necrotic lipid core with or without associat ed 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 additiona l indication of plaque neoformation. Results: The mean percent angiogr aphic stenosis was 82% +/- 11% and 79% +/- 13% for the asymptomatic an d symptomatic groups, respectively (p > 0.05). The necrotic core was t wice as close to the lumen in symptomatic plaques when compared with a symptomatic 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 g roups (22% vs 26% and 7% vs 6%, respectively). There was no significan t relationship to symptom production of either the distance of calcifi cation from the lumen or of the percent area occupied by the lipid nec rotic core or calcification. The number of macrophages infiltrating th e 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 o r ulceration were more commonly observed in the symptomatic plaques th an in the asymptomatic plaques (32% vs 20%). None of the demographic o r clinical atherosclerosis risk factors distinguished between symptoma tic and asymptomatic plaques. Conclusions: These findings indicate tha t proximity of plaque necrotic core to the lumen and cellular indicato rs of plaque neoformation or inflammatory reaction about the fibrous c ap are associated with clinical ischemic events. The morphologic compl exity of carotid stenoses does not appear to determine symptomatic out come but rather the topography of individual plaque components in rela tion to the fibrous cap and the lumen. Imaging techniques that precise ly resolve the position of the necrotic core and evidence of inflammat ory reactions within carotid plaques should help identify high-risk st enoses before disruption and symptomatic carotid disease.