BACKGROUND AND PURPOSE: To determine the relationship between ulceration, thrombus, and calcification of carotid artery atherosclerotic plaques and symptoms of ipsilateral or contralateral stroke. METHODS: We compared microscopic plaque morphology from patients with and without stroke symptoms ipsilateral or contralateral to the plaque. Plaques were characterized for ulceration, thrombus, and calcification. We analyzed plaques from 241 subjects: 170 patients enrolled in the Asymptomatic Carotid Atherosclerosis Study (ACAS) and 71 patients enrolled in the North American Symptomatic Carotid Endarterectomy Trial (NASCET); 128 subjects had no history of stroke symptoms, 80 subjects had ipsilateral symptoms, and 33 had contralateral symptoms. RESULTS: Plaque ulceration was more common in plaques taken from symptomatic patients than those without symptoms (36% versus 14%; P<0.001); frequency of ulceration was similar for plaques associated with ipsilateral (34%) and contralateral (42%) symptoms. Thrombus was most common in plaques taken from patients with both ipsilateral symptoms and ulceration. The extent of calcification was unassociated with stroke symptoms. CONCLUSIONS: Carotid plaque ulceration and thrombosis are more prevalent in symptomatic patients. Ulceration is more common in symptomatic patients regardless of side of carotid symptoms, whereas thrombus is associated with ipsilateral symptoms and plaque ulceration. Preoperative identification of carotid ulceration and thrombus should lead to greater efficacy of stroke prevention by carotid endarterectomy.

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PubMed2005

Identification, prognosis, and management of patients with carotid artery near occlusion.

BACKGROUND AND PURPOSE: Two large trials indicated that endarterectomy was less beneficial for symptomatic patients with internal carotid artery (ICA) near occlusion than for patients who had severe stenosis without near occlusion. Near occlusions complicate ratio calculations of ICA stenosis and require attention to detail for identification. The goal is to provide diagnostic criteria, illustrate identifying features, estimate accuracy of identification, and assess prognosis for patients with near occlusion. METHODS: We re-reviewed 1216 patients with severe (> or =70%) stenosis on angiography in the North American Symptomatic Carotid Endarterectomy Trial and European Carotid Surgery Trial. One of 5 (n = 262) had 2 or more criteria for near occlusion: (1) delayed cranial arrival of ICA contrast compared with external carotid artery (ECA); (2) intracranial collaterals seen as cross-filling of contralateral vessels or ipsilateral contrast dilution; (3) obvious diameter reduction of ICA compared with opposite ICA; or (4) ICA diameter reduction compared with ipsilateral ECA. RESULTS: Interrater agreement, sensitivity, and specificity were excellent (0.88, 90.6%, and 93.8%, respectively). By intention to treat, 3-year risks of ipsilateral stroke for medically treated patients with near occlusion was 15.1% versus 10.9% for surgically treated (absolute risk reduction [ARR] = 4.2%; P value = .33). Patients who continued to receive treatment in the medical arm for the trial's duration had a 3-year risk of 18.3% (ARR = 7.4%; P value = .13). Medically treated patients with severe stenosis but without near occlusion had a 3-year risk of 26.0% versus surgically treated of 8.2% (ARR = 17.8%; P value < .001). CONCLUSION: It is crucial to identify near occlusions on vascular imaging. Although it still is reasonable to consider endarterectomy for these patients, the benefit is muted.

Carotid Stenosis↗

PubMed2004

The risk and benefit of endarterectomy in women with symptomatic internal carotid artery disease.

BACKGROUND AND PURPOSE: Perioperative risk and long-term benefit of carotid endarterectomy (CE) are not detailed in women with symptomatic internal carotid artery (ICA) stenosis. Our aim was to compare the efficacy of CE versus medical therapy in women and men with symptomatic ICA stenosis. METHODS: Data were taken from the North American Symptomatic Carotid Endarterectomy Trial (873 women, 2012 men) and the ASA and Carotid Endarterectomy trial (335 women, 813 men). RESULTS: The 30-day perioperative risk of death was higher in women than in men (2.3% versus 0.8%, P=0.002). Higher perioperative risk of stroke and death was also observed (7.6% versus 5.9%) but not statistically significant. With > or =70% stenosis, the 5-year absolute risk reduction (ARR) in stroke from CE was similar between women (15.1%) and men (17.3%). With 50% to 69% stenosis, CE was not beneficial in women (ARR=3.0%, P=0.94), contrary to men (ARR=10.0%, P=0.02). Medically treated women had low risk for stroke. A stroke prognosis instrument (SPI-II) assigned points to 7 factors that identified higher risk for medically treated women: 3 points for hemispheric (not retinal) event, history of diabetes, previous stroke; 2 for age older than 70 years, stroke (not transient ischemic attack); 1 for severe hypertension, history of myocardial infarction. CE was beneficial only for 29.0% of women with 50% to 69% stenosis who had the highest total score of 8 to 15 (ARR=8.9%). CONCLUSIONS: Women and men with > or =70% symptomatic stenosis had similar long-term benefit from CE, although the perioperative risks were higher for women. CE was not beneficial for women with 50% to 69% stenosis without other risk factors for stroke.

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PubMed2004

The inappropriate use of carotid endarterectomy.

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Canada↗

PubMed2004

Early risk of stroke after a transient ischemic attack in patients with internal carotid artery disease.

BACKGROUND: Transient ischemic attacks (TIAs) often herald a stroke, but little is known about the acute natural history of TIAs. Our objective was to quantify the early risk of stroke after a TIA in patients with internal carotid artery disease. METHODS: Using patient data from the medical arm of the North American Symptomatic Carotid Endarterectomy Trial, we calculated the risk of ipsilateral stroke in the territory of the symptomatic internal carotid artery within 2 and 90 days after a first-recorded hemispheric TIA. We also studied similar outcomes among patients in the trial who had a first-recorded completed hemispheric stroke. RESULTS: For patients with a first-recorded hemispheric TIA (n = 603), the 90-day risk of ipsilateral stroke was 20.1% (95% confidence interval [CI] 17.0%-23.2%), higher than the 2.3% risk (95% CI 1.0%-3.6%) for patients with a hemispheric stroke (n = 526). The 2-day risks were 5.5% and 0.0%, respectively. Patients with more severe stenosis of the internal carotid artery (> 70%) appeared to be at no greater risk of stroke than patients with lesser degrees of stenosis (adjusted hazard ratio 1.1, 95% CI 0.7-1.7). Infarct on brain imaging (adjusted hazard ratio 2.1, 95% CI 1.5-3.0) and the presence of intracranial major-artery disease (adjusted hazard ratio 1.9, 95% CI 1.3-2.7) doubled the early risk of stroke in patients with a hemispheric TIA. INTERPRETATION: Patients who had a hemispheric TIA related to internal carotid artery disease had a high risk of stroke in the first few days after the TIA. Early risk of stroke was not affected by the degree of internal carotid artery stenosis.

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PubMed2003

Side of brain infarction and long-term risk of sudden death in patients with symptomatic carotid disease.

BACKGROUND AND PURPOSE: Current publications suggest increased risk of sudden death in experimental animals with acute right insular lesions and in patients with recent right-sided brain infarction, particularly if the insula is involved. METHODS: Using 3 different time definitions, we related long-term risk of sudden death to presence and side of brain infarction on the baseline brain scan and handedness in 2885 patients with symptomatic carotid disease. RESULTS: In 1295 patients without brain infarction, 5-year risk of sudden death was 5.3% (24-hour definition); in those with left-sided infarction (n=471), 8.8%; in those with right-sided infarction (n=477), 6.0%; and in those with bilateral infarction (n=535), 9.7%. After accounting for differences of other risk factors (eg, previous myocardial infarction) in Cox regression, adjusted hazard ratios (HRs) compared with no infarction were as follows: left-sided HR, 1.45 (95% confidence interval [CI], 1.00 to 2.10); right-sided HR, 0.96 (95% CI, 0.62 to 1.47); and bilateral HR, 1.40 (95% CI, 0.98 to 2.00). Insular infarction occurred in 41 patients; none died suddenly. Left-handed or ambidextrous patients (n=183) had a lower risk of sudden death than right-handers; the adjusted HR for left-handed or ambidextrous patients was 0.24 (95% Cl, 0.07 to 0.70). These results were essentially the same for the 10- and 60-minute definitions of sudden death. CONCLUSIONS: In the long-term, left-sided, not right-sided, brain infarction is associated with increased risk of sudden death. Left-handed or ambidextrous patients have a lower risk of sudden death than right-handed patients, suggesting a role for the brain.

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PubMed2003

Development and progression of leukoaraiosis in patients with brain ischemia and carotid artery disease.

BACKGROUND AND PURPOSE: Leukoaraiosis (LA) or the presence of white matter changes, a frequent finding on brain CT scans of elderly individuals, is a risk factor for stroke and vascular death. The aim of the study was to seek development and progression of LA and associated risk factors in patients with symptomatic carotid artery disease. METHODS: Presence and extent of LA were determined on entry and follow-up CT scans from 685 patients in the North American Symptomatic Carotid Endarterectomy Trial. RESULTS: Among 596 patients without LA at entry, 107 (18.0%) developed restricted LA and 18 (3.0%) developed widespread LA during a mean follow-up of 6.1 years (range, 3.0 to 9.6 years). Older age was associated significantly with LA development (P<0.001). History of hypertension, diabetes mellitus, ischemic heart disease, and intermittent claudication had weak associations with LA development. During follow-up, 36.0% of patients who developed LA had 1 or more strokes, particularly of the lacunar type, in comparison to 23.5% of patients who did not develop LA (P=0.01). In patients who developed LA, the percentage with small deep infarcts (diameter < or =1.5 cm) increased from 34.4% on entry to 45.6% on follow-up CT scans compared with no increase (20.4% and 20.4%, respectively) in patients who did not develop LA. Among 89 patients who had restricted LA at entry, 28 (31.5%) progressed to widespread LA. Progression was associated with occurrence of strokes. CONCLUSIONS: LA is common in elderly patients with symptomatic cerebrovascular disease. Its development and progression are associated with higher occurrence of strokes, mainly of the lacunar type.

Age Factors↗

PubMed2003

Risk, types, and severity of intracranial hemorrhage in patients with symptomatic carotid artery stenosis.

BACKGROUND AND PURPOSE: We sought to report the occurrence and risk factors of intracranial hemorrhage during long-term follow-up of patients with internal carotid artery stenosis, with and without carotid endarterectomy. METHODS: From the prospective data of the North American Symptomatic Carotid Endarterectomy Trial, 3 types of intracranial hemorrhage were recognized: petechiae within infarction (PTI), intracerebral hematoma (ICH), and subarachnoid hemorrhage (SAH). The 30-day and 5-year risks of intracranial hemorrhage (PTI or ICH) were estimated from Kaplan-Meier event-free survival curves. Cox proportional-hazards regression modeling was used to identify risk factors. RESULTS: Of 1039 strokes that occurred in 749 of 2885 patients during an average follow-up of 5 years, there were 24 PTIs, 14 ICHs, and 1 SAH. The 5-year risk of intracranial hemorrhage was 1.7% in both medically and surgically treated patients, but the 30-day risk of 0.64% in surgically treated patients was 10 times higher than the risk of 0.07% in medically treated patients (P=0.01). Approximately 50% of all intracranial hemorrhages were either disabling or fatal, and ICHs were more likely to be fatal than PTIs. Old age, a history of hypertension, intermittent claudication and smoking, and infarct on brain images were risk factors for intracranial hemorrhage in medically treated patients, whereas diabetes mellitus was the sole risk factor in surgically treated patients. CONCLUSIONS: Intracranial hemorrhages are uncommon in patients with internal carotid artery stenosis but are associated with high mortality and morbidity. The risk factors for intracranial hemorrhage are different between medically and surgically treated patients.

Carotid Stenosis↗

PubMed2002

The appropriate use of carotid endarterectomy.

For the first 30 years after carotid endarterectomy was first developed, anecdotal evidence was used to identify patients with internal carotid artery disease for whom this procedure would be appropriate. More recently, the appropriateness of carotid endarterectomy for symptomatic patients and asymptomatic subjects has emerged from 7 randomized trials. Risk of stroke and benefit from the procedure are greatest for symptomatic patients with at least 70% stenosis of the internal carotid artery. Within this group, carotid endarterectomy is most beneficial for the following patients: otherwise healthy elderly patients, those with hemispheric transient ischemic attack, those with tandem extracranial and intracranial lesions and those without evidence of collateral vessels. Risk of perioperative stroke and death is higher in the following groups, although they still benefit: patients with widespread leukoaraiosis, those with occlusion of the contralateral internal carotid artery and those with intraluminal thrombus. Patients with 50% to 69% stenosis experience lesser benefit, and some other groups may even be harmed by carotid endarterectomy, including women and patients with transient monocular blindness only. The procedure is indicated for patients presenting with lacunar stroke and for those with a nearly occluded internal carotid artery, but the benefit is muted. Patients with less than 50% stenosis do not benefit. In the largest randomized trial of asymptomatic subjects, the perioperative risk of stroke and death was very low (1.5%), but the results indicated that a prohibitively high number of subjects (83) must be treated to prevent one stroke in 2 years. The subsequent literature reported higher perioperative risks (2.8% to 5.6%). In asymptomatic individuals nearly half of the strokes that occur may be due to heart and small-vessel disease. These limitations counter any potential benefit. Another trial is in progress and may identify subgroups of asymptomatic subjects who would benefit. Meanwhile, most individuals without symptoms fare better with medical care.

Adult↗

PubMed2002

Prognostic importance of leukoaraiosis in patients with symptomatic internal carotid artery stenosis.

BACKGROUND AND PURPOSE: Leukoaraiosis (LA) is a frequent finding on brain CT scans. This study examined patients with LA and symptomatic internal carotid artery disease. METHODS: Patients in the North American Symptomatic Carotid Endarterectomy Trial were evaluated for the extent of LA. Long-term prognosis and perioperative risk associated with carotid endarterectomy were assessed. RESULTS: Among 2618 patients, 493 had LA: 354 restricted and 139 widespread. Patients with LA were older, had a history of hypertension, had more hemispheric ischemic events (particularly stroke), and had small, deep brain infarcts. The 3-year risks of stroke for medically treated patients were 20.2% (no LA), 27.3% (restricted LA), and 37.2% (widespread LA) (P=0.01). For surgically treated patients, the risks were 14.2%, 25.4%, and 33.6%, respectively (P<0.001). With widespread LA, occurrence of disabling strokes doubled in medical patients and tripled in surgical patients. The 30-day perioperative risks of any stroke or death for surgical patients with 50% to 99% internal carotid artery stenosis were 5.3% (no LA), 10.6% (restricted LA), and 13.9% (widespread LA). Despite higher perioperative risk, endarterectomy reduced the absolute 3-year risk of stroke ipsilateral to the symptomatic 50% to 99% stenosed artery by 11.6% (P=0.46) for patients with widespread LA, 7.6% (P=0.39) with those with restricted LA, and 10.9% (P<0.001) for those with no LA. CONCLUSIONS: In patients with a transient ischemic attack or nondisabling stroke associated with internal carotid artery disease, presence of LA was associated with an increased risk of any stroke and of disabling or fatal stroke. Patients with widespread LA had the worst prognosis. Despite the higher perioperative risk, endarterectomy reduced the risk of stroke.

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PubMed2002

Identifying patients with symptomatic carotid artery disease at high and low risk of severe myocardial infarction and cardiac death.

BACKGROUND AND PURPOSE: The extent of cardiac investigation required in patients with coexistent symptomatic carotid and cardiac disease is unsettled. This study compared the outlook for patients symptomatic from carotid stenosis with and without a history of symptomatic ischemic heart disease (IHD). METHODS: The risk of combined outcome of severe myocardial infarction and cardiac death was evaluated in patients from the North American Symptomatic Carotid Endarterectomy Trial. RESULTS: A total of 1124 patients had a history of symptomatic IHD and 1691 did not. The median age was 66 years; 70% were male. With history of IHD at entry, the 5-year risk of combined outcome of severe myocardial infarction and cardiac death was 16.5% (95% CI, 13.9 to 19.0). Without history at entry, risk was 6.7% (95% CI, 5.1 to 8.3). Risk of unheralded severe MI and cardiac death was only 3.3%. One hundred ninety-four patients had > or =4 of the following risk factors: age > or =75 years, history of diabetes, history of hypertension, smoking in past year, left ventricular hypertrophy on ECG, myocardial infarction on ECG, or creatinine >115 micromol/L. The 5-year risk of severe myocardial infarction or cardiac death increased to 33.9% for patients with > or =4 risk factors and a history of IHD and to 23.5% for those without history of IHD. CONCLUSIONS: Most patients with symptomatic carotid stenosis without symptomatic IHD had a low risk of severe myocardial infarction and cardiac death. With many risk factors, these patients had a risk high enough to warrant cardiac investigations.

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