Carotid Artery Plaque: Symptoms and Percent Stenosis Are Only Part of the Story

Abstract & Commentary

Synopsis: These results demonstrate a major role of carotid thrombosis and inflammation in ischemic stroke in patients affected by carotid atherosclerotic disease.

Source: Spagnoli LG, et al. Extracranial Thrombotically Active Carotid Plaque as a Risk Factor For Ischemic Stroke. JAMA. 2004;292:1845.

Patient suitability for carotid artery revascularization, either endarterectomy (CEA) or stenting, is determined by 2 factors: the percent stenosis and the presence or absence of symptoms. In severe (> 70%) disease, there may be significant flow limitation on a mechanical basis. This, however, is thought to be a minor contributor to stroke, since most patients can compensate with an intact Circle of Willis. Rather, it is believed that thrombi forming at the site of carotid stenosis, propagate distally to the brain, producing TIA or stroke, or to the ophthalmic circulation, producing amaurosis fugax. Some carotid lesions are prone to produce stroke as a result of thrombosis, while others will remain asymptomatic, potentially for long periods of time. The pathological analyses of carotid plaque morphology presented here, provide elegant clinicopathological correlation for this hypothesis.

In a collaborative effort between the Mayo Clinic and the University of Rome, pathology from carotid plaques obtained at the time of CEA was studied. A total of 269 plaques were analyzed; 96 from patients with major ipsilateral stroke, 91 from patients with TIA, and 82 from asymptomatic patients. Stroke and TIA cases were carefully chosen to reflect true symptomatic carotid disease, with exclusion of patients having probable cardiac embolic sources, or patients with distal atherosclerotic disease of > 50% severity.

A thrombotically active plaque (TAP) was observed in 71/96 stroke patients (74%), compared with 32/91 TIA patients (35%, P <0.001), and 12/82 asymptomatic patients (15%, P <0.001). All 32 patients with stroke within the past 2 months had TAP, while TAP was still present in the majority of patients (54%) who had strokes as remotely as 13 to 24 months prior to CEA. Plaque morphology, in association with thrombosis, was defined as either plaque rupture or erosion. In cases of rupture, there was complete disruption of the fibrous cap over an underlying lipid pool. Erosion was defined as plaque de-endothelialization, but not direct contact with the lipid pool. The vast majority of stroke patients (90%) had plaque rupture, while erosion was a more common finding in TIA (present in 11/32 plaques with TAP).

Among stroke patients, ruptured plaques were more frequently and densely affected by inflammation, compared with both TIA and asymptomatic patients. These plaques contained monocytes, macrophages, and T-lymphocytes, and showed a high expression of IL-6, an inflammatory marker.

Commentary

These data support the fact that not all carotid stenoses are created equal, and that severity of lumen stenosis is not the sole determinant of stroke risk. The challenge is to discover methods short of direct pathology from CEA to non-invasively detect these changes. While carotid duplex ultrasonography may identify soft vs hard plaque and occasionally identify thrombus, other methods such as high resolution CT scanning may be more useful and less user dependent in defining this anatomy. Screening for inflammatory markers, such as cytokines or C-reactive protein, may also provide clues to why patients have a more aggressive type of atherosclerotic biology.

The clinical implications of these data are myriad. For patients with a recent stroke, understanding of plaque morphology would be helpful to determine the optimal timing for CEA. While revascularization is typically delayed by weeks to months to allow the stroke to heal and minimize risk of reperfusion bleeding, if a large burden of active clot were identified, more urgent intervention could be pursued. Plaque morphology might also have important implications in choosing between CEA and carotid artery stenting. Perhaps most importantly, plaque morphology could be crucial in choosing optimal asymptomatic patients for intervention. Given its marginal benefit, CEA would be much more appropriate for patients having an aggressive, as opposed to a benign, natural history. — Alan Z. Segal

Dr. Segal, Assistant Professor, Department of Neurology, Weill-Cornell Medical College, Attending Neurologist, New York Presbyterian Hospital, is Assistant Editor of Neurology Alert.