No abstract

Background and Purpose-Acute disruption of atherosclerotic plaques precedes the onset of clinical syndromes, and studies have implicated a role for matrix metalloproteinases (MMPs) in this process. The aim of this study was to establish the character, level, and expression of MMPs in carotid plaques and to correlate this with clinical status, cerebral embolization, and histology. Methods-Plaques were obtained from 75 consecutive patients undergoing carotid endarterectomy and divided into 4 groups according to symptomatology (group 1, asymptomatic; group 2, symptomatic Ͼ6 months before surgery; group 3, symptomatic within 1 to 6 months; group 4, symptomatic within 1 month). All patients underwent preoperative and intraoperative transcranial Doppler monitoring. Plaques were subjected to histological examination and quantification of MMPs by zymography and ELISA. Results-The level of MMP-9 was significantly higher in group 4 (median 125.7 ng/mL for group 4, median Ͻ32 ng/mL for all other groups; Pϭ0.003), with no difference in the levels of MMPs 1, 2, or 3. Furthermore, the MMP-9 concentration was significantly higher in plaques undergoing spontaneous embolization (Pϭ0.019) and those with histological evidence of plaque instability (PϽ0.03). In situ hybridization demonstrated increased MMP-9 expression in highly symptomatic plaques in areas of intense inflammatory infiltrate. Conclusions-The concentration, production, and expression of MMP-9 is significantly higher in unstable carotid plaques.If this proves to be a causal relationship, MMP-9 may be a strong candidate for pharmacotherapy aimed at stabilizing plaques and preventing stroke. (Stroke. 2000;31:40-47.)

After referral, the Data Monitoring Committee invoked the stopping rule and the trial was suspended. The investigators and the Ethics Committee subsequently concluded that the trial could not be restarted--even in an amended format-primarily because of problems with informed consent. We review many of the ethical dilemmas encountered in the performance of this study. If future trials do suggest a selected role for CA, it is essential that both the inclusion and the exclusion criteria are fully documented.

10-12% of patients undergoing staged or synchronous procedures suffered death or major cardiovascular morbidity (stroke, MI) within 30 days of surgery. Overall, there was no significant difference in outcomes for staged and synchronous procedures and no comparable data for patients with combined cardiac and carotid disease not undergoing staged or synchronous surgery.

Carotid disease is an important aetiological factor in the pathophysiology of post-CABG stroke. However, even assuming that prophylactic carotid endarterectomy carried no additional risk, it could only ever prevent about 40-50% of procedural strokes.