Interrelation between plaque surface morphology and degree of stenosis on carotid angiograms and the risk of ischemic stroke in patients with symptomatic carotid stenosis. On behalf of the European Carotid Surgery Trialists' Collaborative Group.

BACKGROUND AND PURPOSE: The risk of ischemic stroke distal to an atherothrombotic carotid stenosis increases with the degree of stenosis. The main mechanism of stroke is thought to be embolism from fissured or ruptured plaque, but there are few published data on the relationship between plaque morphology and severity of stenosis and their independent effects on the risk of ischemic stroke. We sought to determine the interrelation between plaque surface morphology, degree of carotid stenosis, and the risk of ipsilateral ischemic stroke. METHODS: Severity of stenosis and plaque surface morphology were assessed on angiograms of the symptomatic carotid artery in 3007 patients in the European Carotid Surgery Trial and were related to baseline clinical characteristics, pathological characteristics of plaques examined at endarterectomy, and the risks of carotid territory ipsilateral ischemic stroke and other vascular events on follow-up. RESULTS: The early risk of ipsilateral ischemic stroke on medical treatment was closely related to the degree of carotid stenosis. However, the initial degree of carotid stenosis was not predictive of strokes occurring >2 years after randomization. Angiographic plaque surface irregularity and plaque surface thrombus at endarterectomy increased in frequency as the degree of stenosis increased (both P<0.0001). However, the degree of stenosis was still predictive of the 2-year risk of stroke on medical treatment after correction for plaque surface irregularity. Angiographic plaque surface irregularity was an independent predictor of ipsilateral ischemic stroke on medical treatment at all degrees of stenosis (hazard ratio=1.80; 95% CI, 1. 14 to 2.83; P=0.01). This relationship was maintained when the analysis was confined to strokes occurring >2 years after randomization (hazard ratio=2.75; 95% CI, 1.30 to 5.80; P=0.01). Neither the degree of stenosis nor plaque surface irregularity was predictive of the "background" stroke risk after endarterectomy or the risk of nonstroke vascular events. CONCLUSIONS: Angiographic plaque surface irregularity is associated with an increased risk of ipsilateral ischemic stroke on medical treatment at all degrees of stenosis. The increase in stroke risk with degree of stenosis is partly accounted for by the parallel increase in plaque surface irregularity and thrombus formation, but the degree of narrowing of the vessel lumen is still an independent predictor of ischemic stroke within 2 years of presentation.