Sex-associated differences in the modulation of vascular risk in patients with asymptomatic carotid stenosis

In this study, we aimed to identify determinants of the different sex-related stroke risk in subjects with asymptomatic internal carotid artery (ICA) stenosis. In all, 492 women (44.4%) and 617 men (55.6%), with unilateral ⩾60% asymptomatic ICA stenosis, were prospectively evaluated with a median follow-up of 37 months (interquartile range, 26 to 43). Vascular risk profile, plaque characteristics, stenosis progression, and common carotid artery intima-media thickness were investigated. Outcome measure was the occurrence of ischemic stroke ipsilateral to ICA stenosis. Myocardial infarction, contralateral stroke and transient ischemic attack were considered as competing events. The incidence rate of ipsilateral stroke over the entire follow-up period was 0.16%: 0.09% (95% confidence interval (CI) 0.05 to 0.15) in women and 0.22% (95% CI 0.17 to 0.29) in men (log-rank test, P<0.001). Stenosis progression significantly influenced the risk of ipsilateral stroke in both men (subhazard ratio, SHR, 8.99) and women (SHR 4.89). Stenosis degree (71% to 90%, SHR 2.35; 91% to 99%, SHR 3.38) and irregular plaque surface (SHR 2.32) were relevant risk factors for ipsilateral stroke only in men. Our findings suggest that characteristics of the stenosis and plaque exert a different effect in modulating vascular risk in the two sexes. Understanding sex differences in cardiovascular disease could help to target sex-specific future therapies.     

Markers of lacunar stroke in patients with moderate internal carotid artery stenosis

The benefits of surgical correction of moderate internal carotid artery stenosis have been demonstrated only in symptomatic subjects. It is debatable whether patients with lacunar infarct ipsilateral to a moderate carotid stenosis may be considered symptomatic like those with large–artery stroke. The aim of the study was to seek markers capable of differentiating patients with lacunar or non–lacunar stroke ipsilateral to a moderate internal carotid artery stenosis.We enrolled 95 patients with a first stroke ipsilateral to a moderate (50–69 %) stenosis of the internal carotid artery and divided them into lacunar and non–lacunar stroke based on clinical presentation and neuroradiological findings; 34 subjects with asymptomatic moderate carotid stenosis and 31 normal individuals were also studied. Baseline characteristics; risk factors, cerebrovascular reactivity to hypercapnia evaluated by means of the breath–holding index (BHI), the presence and severity of carotid stenosis and intimamedia thickness (IMT) of the common carotid arteries were determined. There were 36 patients with lacunar and 59 with non–lacunar stroke. Degree of stenosis, and IMT and BHI ipsilateral to symptomatic stenosis were found to be significant independent predictors as each 10 % increase of stenosis carried a 4.3 higher probability of non–lacunar stroke (95 % CI: 1.91–9.51); each decimillimeter increment in IMT increased this probability by 1.45 (95 % CI: 1.10–1.92); and the risk odds ratio associated with each 0.1 increase in BHI was 1.88 (95 % CI: 1.33–2.66). A decrease in BHI of 0.1 thus carried a 90% greater probability of having a lacunar stroke. The results show that patients with moderate internal carotid artery stenosis and lacunar stroke can be differentiated from those with non–lacunar stroke on the basis of distinctive ultrasonographic findings. Further studies are needed to clarify whether our findings have pathogenetic implications and may be of help for the planning of different therapeutic strategies in patients with moderate internal carotid stenosis and lacunar or non–lacunar ipsilateral stroke.     

Transcranial Doppler waveform blunting in severe extracranial carotid artery stenosis

OBJECTIVE: To investigate the frequency of transcranial Doppler (TCD) waveform blunting in patients with severe (80-99%) symptomatic or asymptomatic extracranial carotid artery stenosis. BACKGROUND: Severe carotid artery stenosis has been identified as a risk factor for ischemic stroke. Blunted Doppler flow waveforms (reduced systolic flow velocity and pulsatility) of the middle cerebral artery (MCA) are inferred to reflect hemodynamic impairment, possibly indicating an increased risk of stroke. METHODS: The 114 consecutive patients (mean age 72.4 years, SD 9.0 years; 37% women; 46 clinically symptomatic, 68 asymptomatic) with 80-99% stenosis of the extracranial internal carotid artery (ICA), as determined by duplex sonography, were examined with TCD. Flow velocities, pulsatility index, and spectral waveforms of the MCA distal to the ICA stenosis were assessed blinded to the clinical status of the ICA: Doppler waveform blunting was defined as loss of the characteristic systolic peak. Odds ratios with 95% confidence intervals and chi(2) statistics were used to describe the association between waveform blunting and the symptomatic status of the ICA stenosis. RESULTS: Among symptomatic patients, 23 (50%) had completed strokes, and a further 23 (50%) had transient neurologic deficits in the territory of the stenotic ICA. Blunted spectral waveform was found in 37 (80%, 95% CI 68-92%) of the symptomatic and 25 (37%; 95% CI 25-49%) of the asymptomatic patients. Symptomatic patients had significantly increased odds of having blunted TCD waveforms (OR 7.5, 95% CI 3.1-18.1, p < 0.001). CONCLUSIONS: Our findings suggest that TCD waveform blunting in the MCA as here described may be an additional risk factor in the setting of severe extracranial carotid artery stenosis. A prospectively designed study to confirm our results seems warranted.     

Low risk of ischemic stroke in patients with reduced internal carotid artery lumen diameter distal to severe symptomatic carotid stenosis: cerebral protection due to low poststenotic flow? On behalf of the European Carotid Surgery Trialists' Collaborative Group

BACKGROUND AND PURPOSE: Patients with recently symptomatic severe carotid stenosis have a high risk of ischemic stroke on medical treatment. The main mechanism of stroke appears to be plaque surface thrombus formation and distal embolism. It is unclear to what extent reduction in blood flow across the stenosis, and the consequent reduction in cerebral perfusion pressure, is also important. Angiographic indices of reduced cerebral perfusion may identify patients at a particularly high risk of stroke who require urgent endarterectomy. The most direct angiographic correlate of poststenotic perfusion pressure is the degree of narrowing of the distal internal carotid artery (ICA) lumen. We sought to develop criteria for the definition of poststenotic narrowing of the ICA and to determine the effect of this and other angiographic characteristics likely to be associated with reduced cerebral perfusion on the risk of ipsilateral ischemic stroke in patients with recently symptomatic carotid stenosis. METHODS: We studied the carotid angiograms of 3007 patients in the European Carotid Surgery Trial. Poststenotic narrowing of the ICA was defined with use of the ratio of the lumen diameter of the ICA to that of the common carotid artery (CCA). The normal range of the ICA/CCA ratio was defined in 2966 symptomatic or contralateral carotid arteries with 0% to 49% stenosis. Arteries with 70% to 99% symptomatic stenosis and an ICA/CCA ratio below this range were categorized as narrowed. We related the presence of narrowing and other angiographic characteristics to the risk of ipsilateral ischemic stroke on medical treatment. RESULTS: An assessment of the ICA/CCA ratio had good interobserver reproducibility. Poststenotic narrowing of the ICA was defined as an ICA/CCA ratio of <0.42. The 5-year risk of ipsilateral carotid territory ischemic stroke on medical treatment was 8% in patients with 70% to 99% stenosis and narrowing of the ICA versus 25% in patients without narrowing (log rank test, P=0.02). This difference remained after correction for other clinical and angiographic variables (hazard ratio 0.40, 95% CI 0.17 to 0.94, P=0. 03). The other angiographic characteristics did not predict stroke. CONCLUSIONS: Poststenotic narrowing of the ICA was associated with a low risk of stroke on medical treatment. This suggests that low flow alone is not usually sufficient to cause ischemic stroke distal to symptomatic carotid stenosis. Poststenotic narrowing may be protective because blood flow distal to the stenosis is insufficient to carry emboli to the brain.     

Carotid endarterectomy: is it still a gold standard?

Extracranial internal carotid artery stenosis accounts for 15-20% of ischemic strokes. Carotid endarterectomy has high efficacy in stroke prevention in selected patients with symptomatic (age <80 years) and asymptomatic carotid stenosis (age <75 years). Randomized clinical trials demonstrated that carotid endarterectomy reduces the stroke risk, compared to medical therapy alone, for patients with 70-99% symptomatic stenosis with 16% absolute risk reduction at 5 years. The benefit for patients with 50-69% symptomatic stenosis is lower i.e. absolute risk reduction 4.6% at 5 years. Endarterectomy is not indicated for symptomatic patients with <50% stenosis. There is no need for time-delay for surgery in patients after transient ischemic attack or minor stroke. Patients with more extensive strokes or hemorrhage should undergo surgery after 4-6 weeks following initial symptoms. Carotid endarterectomy for asymptomatic stenosis reduces the risk of ipsilateral stroke, and any stroke, by approximately 30% over 3 years. However, the absolute risk reduction is small over the first few years and decision should be based on individual institutional experience. In all situations, the best medical therapy should accompany surgery. In the recent years, appearance of angioplasty, stenting, and distal protection procedures provides competitive alternatives to classical endarterectomy. However, long-term benefits of carotid angioplasty should be confirmed by bigger, randomized, comparative clinical trials.     

Natural history of asymptomatic carotid artery stenosis

The prevalence of carotid artery stenosis 50% or greater increases from about 1% in people aged 50 to 59 to about 10% in people older than 70. Although carotid stenosis accounts for about 10% of ischemic strokes, only a minority of patients with carotid stenosis will have a stroke. The annual risk of ipsilateral ischemic stroke is relatively low, ranging from 1.0 to 3.8% and is about half of that of any stroke. There is a relatively weak relationship between carotid stenosis severity and risk of ipsilateral stroke. In addition to stenosis severity, carotid plaque composition, which can be evaluated by several noninvasive imaging methods, may be an independent risk factor for stroke. There are few data supporting the use of hemodynamic impairment assessment to predict stroke risk. Nonstroke vascular events are about twice as likely in patients with carotid bruits compared with those without. Patients with asymptomatic carotid stenosis have a particularly high risk of cardiac events (about 3.5% per year). Therefore, the most important part of the management of patients with carotid stenosis is optimization of medical therapy. Much remains to be done to identify patients at particularly high risk of ipsilateral stroke, for whom carotid endarterectomy may be necessary in addition to medical therapy.     

Patterns of cerebral perfusion in patients with asymptomatic internal carotid artery disease

BACKGROUND: The perfusion profile of patients with asymptomatic internal carotid artery (ICA) disease has not been well studied. The purpose of this study is to describe the perfusion patterns of patients with asymptomatic ICA disease using computed tomography perfusion (CTP) and its potential value in identifying patients at higher risk for transient ischemic attacks (TIAs) or strokes. METHODS: We analyzed 32 patients with asymptomatic high grade ICA disease who had CTP and computed tomography angiography (CTA) of the head and neck. Twenty-four patients had severe ICA stenosis and eight had ICA occlusion. The degree of ipsilateral external carotid artery (ECA) and contralateral ICA stenosis, patency of the anterior communicating artery (ACOM), A1 segment and posterior communicating artery (PCOM) were evaluated in all patients. RESULTS: Sixteen patients had normal CTP and the other 16 patients had cerebral hypoperfusion, characterized by abnormalities in one or more of the three perfusion maps. Ipsilateral hypoplastic A1 segment was more frequent in the group with cerebral hypoperfusion (p = 0.025). Ipsilateral TIAs occurred in two patients, both with cerebral hypoperfusion. CONCLUSION: Cerebral hypoperfusion is present in half of the patients with asymptomatic ICA disease, predominantly in patients with a hypoplastic ipsilateral A1 segment. These patients likely represent a higher-risk group for symptomatic brain ischemia.     

Operative versus nonoperative management of asymptomatic high-grade internal carotid artery stenosis: improved results with endarterectomy

In a 4-year period, 129 asymptomatic high-grade (80-99%) internal carotid artery stenoses were identified in 115 patients. Because we previously demonstrated a strong relation between degree of carotid stenosis and subsequent development of ipsilateral related events (stroke, transient ischemic attack, and carotid occlusion), we changed our previous policy and began to offer carotid endarterectomy to good surgical risk patients referred to us with asymptomatic high-grade carotid stenosis. A total of 56 carotid endarterectomies were performed while 73 lesions were followed nonoperatively. Operated and nonoperated groups were similar with regard to age, prevalence of hypertension, cardiac disease, diabetes, and aspirin use. Life table analysis to 24 months revealed a higher rate of stroke (19 vs. 4%, p = 0.08), transient focal neurologic deficits (28 vs. 5%, p = 0.008), and carotid occlusion (29 vs. 0%, p = 0.003) in the nonoperated group. Eight of the 9 strokes in the nonoperated group occurred within 9 months of diagnosis of the high-grade lesion; none were preceded by a transient ischemic attack. There was 1 perioperative stroke (1.8%) but no in-hospital operative deaths and no difference in the late death rates of the two groups. This suggests that the preservation of neurologic status in patients with asymptomatic high-grade internal carotid artery stenosis can be improved by carotid endarterectomy.     

Antithrombotic treatment of ischemic stroke among patients with occlusion or severe stenosis of the internal carotid artery: A report of the Trial of Org 10172 in Acute Stroke Treatment (TOAST).

OBJECTIVE: To examine the responses to early IV administration of an anticoagulant or placebo started within 24 hours of stroke among persons with an ipsilateral occlusion or severe stenosis of the internal carotid artery (ICA) identified by carotid duplex imaging. BACKGROUND: Patients with ischemic stroke of the cerebral hemisphere secondary to an ipsilateral occlusion or severe stenosis of the ICA generally have a poor prognosis. Early, accurate identification of these patients might permit improved treatment. METHODS: Exploratory analysis of outcomes at 7 days and 3 months was performed among patients enrolled in the Trial of Org 10172 in Acute Stroke Treatment (TOAST) who had an ischemic stroke in the cerebral hemisphere ipsilateral to an occlusion or a stenosis >50% of the ICA identified by carotid duplex imaging. RESULTS: Regardless of treatment, patients with duplex evidence of an occlusion of the ICA had more severe strokes and poorer outcomes at 7 days and 3 months than patients who had a stenosis. Favorable outcomes at 7 days were noted in 64 of 119 patients given danaparoid (53.8%) and 41 of 108 patients treated with placebo (38.0%; p = 0.023). By 3 months, favorable outcomes were noted in 82 patients given danaparoid (68.3%) and 58 patients administered placebo (53.2%; p = 0.021). CONCLUSIONS: Early identification by duplex imaging of an occlusion or severe stenosis of the ICA ipsilateral to a hemispheric ischemic stroke might improve selection of patients who could be treated with emergent anticoagulation. Further testing of this approach is needed.     

Association Between Stroke Severity and 5-Year Mortality in Ischemic Stroke Patients with High-Grade Stenosis of Internal Carotid Artery

Background

The clinical presentations and outcomes of patients with high-grade stenosis of internal carotid artery (ICA) are highly variable. We investigate the influence of different stroke severity on outcomes of ischemic stroke patients with high-grade stenosis of ipsilateral ICA.

Patterns of perfusion-weighted imaging in patients with carotid artery occlusive disease

BACKGROUND: The importance of hemodynamic factors in the pathophysiology of stroke and transient ischemic attacks in patients with internal carotid artery (ICA) stenosis or occlusion remains controversial. OBJECTIVE: To investigate whether perfusion-weighted imaging (PWI) could identify pathophysiologically meaningful categories in patients with symptomatic and asymptomatic ICA occlusive disease. METHODS: Thirty-eight consecutive patients with occlusion (22 patients) or severe stenosis (16 patients) of the ICA, determined by ultrasonography or magnetic resonance angiography, were identified from the Beth Israel Deaconess Medical Center Stroke Database, Boston, Mass. Thirty-five patients were symptomatic (29 who had strokes and 6 who had transient ischemic attacks) and 3 were asymptomatic. All symptomatic patients underwent PWI within the first 24 hours after symptom onset. The patterns of PWI were analyzed according to the degree of ICA stenosis and the clinical presentation. RESULTS: Three patterns of perfusion abnormalities were identified: extensive hypoperfusion involving the middle cerebral arterial and/or anterior cerebral arterial territories (25 patients), localized perfusion deficits involving predominantly the ipsilateral border zone areas (8 patients), and normal perfusion (5 patients). All 3 patterns were found whether or not the ICA was occluded. Patients who had acute stroke most frequently had extensive perfusion deficits involving 1 or 2 territories while patients who had transient ischemic attacks often had hypoperfusion affecting the border zone regions. All asymptomatic patients had normal perfusion. CONCLUSIONS: In our sample the pattern of PWI related to the clinical presentation but not to the degree of ICA disease (occlusive vs severe stenosis). Our study findings add further support to the hypothesis that hypoperfusion is a major contributing factor in the pathophysiology of carotid artery occlusive disease.     

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.     

Risk of stroke during coronary artery bypass graft surgery in patients with internal carotid artery disease documented by angiography

We retrospectively identified 144 patients who underwent coronary artery bypass graft (CABG) surgery in the presence of angiographically documented greater than or equal to 50% internal carotid stenosis or occlusion. Of these, 115 patients had bilateral carotid lesions and received combined operations involving carotid endarterectomy on only one side. The remaining 29 patients, including 11 with bilateral carotid lesions, underwent coronary bypass alone. Nine cerebral infarcts occurred (6%), but only three strokes (2%) were appropriate to the cerebral hemisphere ipsilateral to unoperated carotid stenosis. There was one stroke (3%) among the 29 patients who did not undergo combined procedures. In the group of 115 patients with bilateral carotid disease who received unilateral combined carotid endarterectomy there were 8 perioperative strokes (7%), of which 6 were ipsilateral to the endarterectomy. Asymptomatic unilateral less than 90% ICA stenosis or ICA occlusion does not increase stroke risk during CABG surgery.     

Asymptomatic embolization predicts stroke and TIA risk in patients with carotid artery stenosis.

BACKGROUND AND PURPOSE: Improved methods of identifying patients at high risk of thromboembolism would allow improved targeting of therapy. One such situation is carotid artery stenosis. This is associated with an increased risk of stroke, which can be reduced by carotid endarterectomy. However, the risk-benefit ratio is low in patients with tight asymptomatic stenosis and moderate symptomatic stenosis. Most stroke in patients with carotid stenosis is believed to be embolic. Therefore, the detection of asymptomatic cerebral emboli using Doppler ultrasound may allow identification of a high-risk group. METHODS: Transcranial Doppler ultrasound was used to record for 1 hour the ipsilateral middle cerebral artery in 111 patients with >60% carotid artery stenosis (69 symptomatic, 42 asymptomatic). The Doppler audio signal was recorded onto digital audio tape for later analysis for embolic signals (ES) by an individual blinded to clinical details. In 67 subjects the relationship between ES and angiographically determined plaque ulceration was investigated. All subjects were followed up prospectively, and the relationship between ES and risk of future ipsilateral carotid artery territory ischemic events (TIA and stroke) was determined. RESULTS: ES were detected in 41(36.9%) subjects. In symptomatic patients there was a significant inverse relationship between the number of ES per hour and time elapsed since last symptoms (Spearman's rho=-0.2558, P=0.034). ES were more common in subjects with plaque ulceration, with a relative risk of 4. 94 (95% CI, 1.23 to 19.84; P=0.025) after controlling for both symptomatic status and degree of stenosis. The presence of ES at entry was predictive of TIA and stroke risk during follow up in both symptomatic (P=0.02) and asymptomatic patients (P=0.007). Considering all 111 patients, the presence of asymptomatic embolization was predictive of a further ischemic event, with an adjusted OR of 8.10 (95% CI, 1.58 to 41.57; P=0.01) after controlling for other cardiovascular risk factors, degree of stenosis, symptomatic status, and aspirin or warfarin use. CONCLUSIONS: Asymptomatic embolization in patients with carotid artery stenosis correlates with known markers of increased stroke risk and is an independent predictor of future stroke risk in patients with both symptomatic and asymptomatic carotid stenosis. It may allow identification of a high-risk group of patients who will particularly benefit from carotid endarterectomy. A large multicenter study is now required to confirm these findings.     

The prognosis of carotid siphon stenosis

We retrospectively reviewed the clinical course and angiograms of 15 patients with carotid siphon stenosis of 50% or greater. Fourteen had less than 50% stenosis at the origin of the ipsilateral internal carotid artery, and one had a greater degree of stenosis but underwent endarterectomy after an initial angiogram. Angiograms were examined for evidence of hemodynamic abnormalities in addition to residual lumen diameter. Seven patients initially had TIAs, 5 had strokes, and 3 were asymptomatic. In an average followup of 51 months (range 4-123 months) subsequent cerebral ischemic events occurred in 6 (40%), but only 1 had a stroke with a persisting neurological deficit that could be directly attributed to the siphon stenosis. Stenoses were hemodynamically significant by angiography in 5 of 7 TIA patients, and only 1 of 5 stroke patients. The incidence of subsequent ischemic events in this study was similar to 2 previous studies of siphon stenosis, however in this study most of the events ipsilateral to the siphon stenosis were TIAs or minor strokes. The association of hemodynamic angiographic abnormalities and initial TIAs but not strokes suggests that the mechanism producing ischemic symptoms may differ in patients with TIA and stroke who have carotid siphon stenosis.     

Carotid artery stenosis in ischemic stroke patients with nonvalvular atrial fibrillation.

PURPOSE: To study the prevalence, severity and clinical relevance of carotid atherosclerosis in ischemic stroke patients with nonvalvular atrial fibrillation (NVAF). MATERIAL AND METHODS: We reviewed carotid duplex sonography, computed tomography (CT) and clinical features in 103 consecutive ischemic stroke patients with NVAF. Both sonography and CT were performed within 3-7 days after stroke. There were 64 men and 39 women with a mean age at stroke onset of 69 years. RESULTS: High-grade (> or =50%) stenosis of the extracranial carotid artery was detected in 25 patients (24.3%), including 11 patients (10.6%) with internal carotid artery (ICA) occlusion. In 15 (66.7%) of the patients who had high-grade carotid stenosis, the lesion was ipsilateral to the infarct, including 8 ICA occlusions. Patients with high-grade stenosis smoked more cigarettes (p < 0.05) and had more peripheral vascular diseases (p < 0.05). Besides NVAF, all patients had more than one vascular risk factor. The clinical presentations (transient ischemic attacks, minor or major strokes) showed no significant difference between the groups of <50% and > or =50% stenosis. Clinical outcome was worse (dead and totally dependent in daily activities) in the group of high-grade stenosis (p < 0.05). Patients with high-grade carotid stenosis showed more cortical infarcts on cerebral CT (p < 0.01). Six out of 7 patients with a hemorrhagic transformation on the initial cerebral CT were in the low-grade carotid stenosis group, though this was statistically insignificant. CONCLUSIONS: Ischemic stroke with NVAF is not always cardiogenic. High-grade stenosis of the extracranial carotid artery is found in one fourth of ischemic stroke patients with NVAF and is related to more cortical infarction and worse clinical outcome. We speculate that ischemic stroke patients with NVAF who have high-grade carotid stenosis are less likely to develop hemorrhagic infarct. The pathogenesis of cerebral infarction and the therapeutic strategy in this clinical condition are complicated by the coexistence of carotid arterial lesions and cardiac disease.     

Long-term risk of stroke and other vascular events in patients with asymptomatic carotid artery stenosis

CONTEXT: The annual risk of ischemic stroke in patients with asymptomatic carotid artery stenosis is about 2% during the short-term (2-3 years), but the long-term risks of stroke and other vascular events are unknown, although they may affect surgical decision making. OBJECTIVE: To evaluate the long-term risk of stroke and other vascular events in patients with asymptomatic carotid artery stenosis. DESIGN: Cohort study with a median follow-up of 10 years (range, 5-18 years). SETTING: The teaching hospital of the University of Toronto, Toronto, Ontario. PATIENTS: From the initial cohort of 500 patients, 106 patients with asymptomatic carotid artery stenosis were selected because they had completed at least 5 years of follow-up. MAIN OUTCOME MEASURES: Ipsilateral stroke, myocardial infarction, and nonstroke vascular death. RESULTS: The 10- and 15-year actuarial risks of ipsilateral stroke were 5.7% (95% confidence interval [CI], 0%-12%) and 8.7% (95% CI, 1%-17%), respectively, in patients with 0% to 49% internal carotid artery stenosis, and 9.3% (95% CI, 1%-18%) and 16.6% (95% CI, 1%-32%) in patients with 50% to 99% internal carotid artery stenosis. The 10- and 15-year risks of myocardial infarction and nonstroke vascular death were 10.1% (95% CI, 4%-16%) and 24.0% (95% CI, 14%-34%). Age (P =.02), diabetes mellitus (P =.02), and internal carotid artery stenosis of 50% or more (P =.04) were predictive of increased risks of myocardial infarction and nonstroke vascular death. Internal carotid artery stenosis of 50% or more did predict the risk of ipsilateral stroke (P =.003) when all 181 asymptomatic carotid arteries were included. CONCLUSIONS: The annual stroke risk in patients with asymptomatic carotid artery stenosis was low and remained stable during long-term follow-up. Any benefit from carotid surgery is therefore unlikely to increase significantly with long-term follow-up. The high long-term risks of myocardial infarction and nonstroke vascular death suggest that prevention strategies should concentrate on coronary risk more than stroke risk.     

Prognosis of asymptomatic carotid occlusion

Ninety-four asymptomatic patients with internal carotid artery occlusion were followed for a mean of 44 months, 16% suffered strokes and 11.7% reported transient ischemic attacks (TIA). The annual stroke and TIA rates were 4.4% and 3.2%, respectively, the annual mortality was 11.3%. In 27 asymptomatic patients progression of extracranial arterial disease to occlusion was observed: 7.4% of these patients suffered from stroke and 18.5% reported TIA's during that period. Thus the annual stroke rate was lower (1.9%) but the TIA rate higher (4.7%) than post-occlusive rates. These data reflect an increase risk in patients with progressive high-degree carotid stenosis which continues after occlusion. This may favour carotid endarterectomy for selected patients in the pre-occlusive state because medical treatment has not been shown to prevent progression of stenosis to occlusion.     

Association between Ischemic Stroke and Vascular Shear Stress in the Carotid Artery

Background and Purpose

Vascular shear stress is essential for maintaining the morphology and function of endothelial cells. We hypothesized that shear stress in the internal carotid artery (ICA) may differ between patients with ischemic stroke and healthy control subjects.

Methods

ICA shear stress was calculated in 143 controls and 122 patients with ischemic stroke who had a normal ICA or an ICA with <50% stenosis. The stroke group included patients who presented with a first-ever or recurrent ischemic stroke but excluded cardioembolic stroke and uncertain etiologies. Of the 122 patients, 107 (87.7%) and 15 (12.3%) patients were categorized as first-ever and recurrent stroke, respectively.

Results

Carotid diameters were significantly larger, and both peak-systolic and end-diastolic velocities were significantly lower in patients with ischemic stroke than in controls (all p values <0.05). Mean values of peak-systolic and end-diastolic shear stress in both ICAs were significantly lower in patients with ischemic stroke in models that adjusted for age, sex, and vascular risk factors (p for trend <0.05). The ICA shear stress was lowest in patients with recurrent stroke or the subtype of small-vessel occlusion. Higher peak-systolic and end-diastolic shear stresses in both ICAs were independently and negatively associated with ischemic stroke after adjusting for potential confounders (all p values <0.05).

Conclusions

ICA shear stresses were significantly lower in patients with ischemic stroke than in control subjects. Future studies should attempt to define the causal relationship between carotid arterial shear stress and ischemic stroke.     

Clinical significance of the ophthalmic artery in carotid artery disease

A total of 141 subjects with tight stenosis (≥75%) or occlusion of internal carotid artery were followed up at intervals 3–6 months regularly for 40 ± 16 months. The direction of ophthalmic artery flow was used as a parameter of risk indicator on cerebral ischemic events. Eleven patients with bilateral carotid tight stenosis/occlusion were excluded in the analysis. Thus, the 130 carotid arteries were divided into three groups: (1) carotid artery with ipsilateral hemispheric TIA or stroke (85 patients), (2) carotid arteries with contralateral hemispheric TIA/stroke or VBI (15 patients), and (3) carotid arteries of asymptomatic patients (30 patients). The symptomatic carotid artery group (group 1) had significantly more often reversed ophthalmic flow than the other two groups (group 2 and 3, p < 0.001). During follow-up prospectively for four years, 41 patients had cerebral ischemic events, three had cardiac ischemic events and six died of malignancy. Patients with reversed OA flow had more often subsequent cerebral ischemic events than those with forward flow (27 vs 14, p = 0.010). However, the difference remained significant only in the asymptomatic patients (group 3, 4 vs 0, P < 0.001), not for groups 1 and 2, after further analysis. Our work supported that the clinical role of ophthalmic artery collateral varied between asymptomatic and symptomatic patients.