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Luigi Giusto Spagnoli, MD; Alessandro Mauriello, MD; Giuseppe Sangiorgi, MD; Stefano Fratoni, MD; Elena Bonanno, MD; Robert S. Schwartz, MD; David G. Piepgras, MD; Raimondo Pistolese, MD; Arnaldo Ippoliti, MD; David R. Holmes, Jr, MD

JAMA. 2004;292:1845-1852.

Context  Recent studies suggest that factors other than the degree of carotid stenosis are involved in ischemic stroke pathogenesis, especially modifications of plaque composition and related complications.

Objective  To examine the role of carotid plaque rupture and thrombosis in ischemic stroke pathogenesis in patients undergoing carotid endarterectomy, excluding those with possible cardiac embolization or with severe stenosis of the circle of Willis.

Design, Setting, and Patients  A total of 269 carotid plaques selected from an Interinstitutional Carotid Tissue Bank were studied by histology after surgical endarterectomy between January 1995 and December 2002. A total of 96 plaques were from patients with ipsilateral major stroke, 91 plaques from patients with transient ischemic attack (TIA), and 82 plaques from patients without symptoms.

Main Outcome Measures  Differences in the frequency of thrombosis, cap rupture, cap erosion, inflammatory infiltrate, and major cardiovascular risk factors between study groups.

Results  A thrombotically active carotid plaque associated with high inflammatory infiltrate was observed in 71 (74.0%) of 96 patients with ipsilateral major stroke (and in all 32 plaques from patients operated within 2 months of symptom onset) compared with 32 (35.2%) of 91 patients with TIA (P < .001) or 12 (14.6%) of 82 patients who were without symptoms (P < .001). In addition, a fresh thrombus was observed in 53.8% of patients with stroke operated 13 to 24 months after the cerebrovascular event. An acute thrombus was associated with cap rupture in 64 (90.1%) of 71 thrombosed plaques from patients with stroke and with cap erosion in the remaining 7 cases (9.9%). Ruptured plaques of patients affected by stroke were characterized by the presence of a more severe inflammatory infiltrate, constituted by monocytes, macrophages, and T lymphocyte cells compared with that observed in the TIA and asymptomatic groups (P = .001). There was no significant difference between groups in major cardiovascular risk factors.

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

Author Affiliations: Anatomic Pathology (Drs Spagnoli, Mauriello, Fratoni, and Bonanno), Department of Cardiovascular Diseases (Dr Sangiorgi), Division of Vascular Surgery (Drs Pistolese and Ippoliti), University of Rome Tor Vergata, Rome, Italy; Minnesota Cardiovascular Research Institute, Minneapolis (Dr Schwartz); Departments of Neurologic Surgery (Dr Piepgras) and Internal Medicine and Cardiovascular Diseases (Dr Holmes), Mayo Clinic and Mayo Foundation, Rochester, Minn.

Corresponding Author: Luigi Giusto Spagnoli, MD, Cattedra di Anatomia ed Istologia Patologica, Dipartimento di Biopatologia e Diagnostica per Immagini, Universita' di Roma Tor Vergata, Via Montpellier 1, 00133 Rome, Italy (spagnoli{at}uniroma2.it).

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