Extracranial Carotid Artery Disease
I. OUTLINE
Stroke is the third leading cause of death in developed nations. Up to 88% of strokes are ischemic in nature. Extracranial carotid artery atherosclerotic disease is the third leading cause of ischemic stroke in the general population and the second most common non-traumatic cause among adults <45 years of age.
When considered as an independent diagnosis separate from other cardiovascular diseases, stroke is the third leading cause of death in developed nations and a leading cause of long-term disability
Approximately 87% of all strokes are ischemic, 10% are hemorrhagic, and 3% are subarachnoid hemorrhages
II. Introduction
Extracranial atherosclerotic disease accounts for up to 15–20% of all ischemic strokes. While intracranial atherosclerotic disease has shown to be consistently more common among Blacks, Hispanics and Asians compared to Whites, the racial differences for extracranial atherosclerotic disease is less apparent. The racial differences for extracranial atherosclerotic disease is less apparent
- Atheroembolism of cholesterol crystals or other debris
- Artery to artery embolism of thrombus
- Structural disintegration of the wall (dissection)
- Acute thrombotic occlusion
- Reduced cerebral perfusion with plaque growth
In symptomatic patients, there is a clear correlation between the degree of stenosis and the risk of stroke. In the North America Symptomatic Carotid Endarterectomy Trial (NASCET), the stroke rate after 18 months of medical therapy without revascularization was 19% in patients with 70–79% stenosis, 28% in patients with 80–89% stenosis, and 33% in patients with 90–99% stenosis.
This correlation is less apparent in asymptomatic patients. In the Asymptomatic Carotid Atherosclerosis Study (ACAS) and the Asymptomatic Carotid Surgery Trial (ACST), asymptomatic patients with 60–80% stenosis had higher strokes rates compared to those with more severe stenosis. The presence of a carotid bruit also does not appear to be a reliable predictor of stroke risk in asymptomatic patients. Despite the Framingham Heart Study population showing that asymptomatic patients with carotid bruit had a fold increased incidence of strokes compared to those without carotid bruit, less than half of these stroke events involved the ipsilateral cerebral hemisphere.
While the degree of carotid stenosis remains the main determinant of disease severity, additional imaging markers of plaque vulnerability are also important in determining the risk for transient ischemic attack (TIA) and strokes. Imaging markers for plaque vulnerability on ultrasonography include:
- Ulceration
- Echolucency
- Intraplaque hemorrhage
- High lipid content
Thin or ruptured fibrous caps, intraplaque hemorrhage and large lipid-rich or necrotic plaque cores, and overall plaque thickness seen on magnetic resonance imaging (MRI) have also been associated with subsequent ischemic events
III. Evaluation of Carotid Atherosclerotic Disease
Carotid US should be performed in asymptomatic patients with two or more of the following risk factors:
- Hypertension
- Hyperlipidemia
- Family history of atherosclerosis or ischemic stroke before 60 years of age
- Tobacco smoking
Carotid US should also be performed annually to assess the progression or regression of disease and response to therapeutic measures in patients with >50% stenosis. Once stability has been established or a patient’s candidacy for further intervention has changed, longer intervals may be appropriate.
Despite varying results between imaging centers and operators, the overall sensitivity and specificity for detection of occlusion or stenosis >70% have been reported to be 85–90% when compared to catheter angiography.
MRA has the benefit of its relative insensitivity to arterial calcification. Contrast-enhanced MRA allows for more detailed evaluation of the cervical arteries, especially in lesions with a slow blood flow when compared to non-contrasted studies.
Unlike both MRA and carotid US, CTA provides direct imaging of the arterial lumen, making it suitable for evaluation of stenosis. It is an accurate test to determine severity of stenosis and is highly accurate for detection or exclusion of complete occlusions as well.
Catheter angiography is useful in patients with renal insufficiency. Selective angiography of a single suspected vascular territory could provide definitive imaging with limited exposure to contrast material and is unlikely to exacerbate renal insufficiency
IV. Medical Management
Several randomized, controlled, double-blinded studies have shown that dual antiplatelet combination therapy is not superior to single agents. Despite clopidogrel monotherapy showing equal efficacy and lower hemorrhage risk than aspirin plus extended release dipyridamole, and equal efficacy with aspirin plus clopidogrel the variations in response to clopidogrel due to genetic factors and drug interactions makes it crucial for individualized treatment selection for optimum stroke prevention.
Antihypertensive therapy also reduces the risk for recurrent strokes by 24%. As such, antihypertensive treatment is recommended for all patients with concurrent hypertension and asymptomatic extracranial carotid atherosclerotic disease, with a goal blood pressure below 140/90 mmHg.
Epidemiological studies have consistently shown a positive association between cholesterol levels and carotid artery atherosclerosis. Lipid-lowering therapy with statins has been shown to reduce the risk of ischemic stroke in patients with atherosclerosis.
In general, intervention when indicated should be done within 6 months of original presentation. However, intervention within 2 weeks of the index event is reasonable for patients with no contraindications for early revascularization.
The indications for intervention will be discussed in detail in the sections below. The general contraindications for interventions include:
- Severe, disabling stroke [(mRS) score >=3]
- Chronic total carotid artery occlusion
- Carotid stenosis <50%
- Extreme high-risk for peri-procedural complications
Carotid revascularization is not recommended for patients with near–complete occlusion or stenosis <50% since the risk for stroke is low in these patients. Revascularization has also not shown to have any benefit in these patients. Carotid revascularization is also not recommended for patients with cerebral infarction causing severe disability that precludes preservation of useful function.
V. Carotid Endarterectomy
A meta-analysis of these three trials showed that CEA was most effective in patients with >70% stenosis without complete or near occlusion. Benefits of CEA in patients with 50–69% stenosis were only modest, but increased with time. Surgery offered little to no long-term benefits in patients with complete or near occlusion. When the combined outcome of perioperative stroke or death and fatal or disabling ipsilateral ischemic stroke was considered, the clinical benefits of CEA were only evident in patients with 80–99% stenosis.
VI. Carotid Angioplasty and Stenting
CAS has shown varying outcome differences when compared to CEA based on different patient factors. CAS appears to be a good alternative to CEA in certain patient groups, such as those with unfavorable surgical anatomy, include:
Anatomical Considerations
Several patient anatomic factors are considered to be unfavorable for endovascular intervention, including:
Noninvasive imaging at the 1-month interval, followed by the 6-month interval, and then annually after revascularization is recommended for both CAS and CEA patients. Regular imaging allows for adequate assessment of ipsilateral carotid patency and to exclude development of contralateral lesions. Once stability has been established, surveillance at longer intervals may be appropriate. Surveillance may not be indicated when the patient is no longer a candidate for intervention.
In patients with recurrent symptomatic carotid stenosis, a repeat CEA or CAS can be considered, using the same criteria as recommended for initial revascularization (discussed previously). Repeat intervention is also recommended when duplex ultrasonography and an additional confirmatory imaging (MRA, CTA or catheter angiography) shows rapidly progressive restenosis, indicating risk of complete occlusion. A repeat CEA can be considered under the hands of an experienced surgeon. CAS is an alternative to repeat CEA in patients with recurrent stenosis after CEA, and may be appropriate in asymptomatic patients with restenosis >80% or symptomatic restenosis >50%. Repeat intervention can also be considered in patients with asymptomatic recurrent stenosis, using the same criteria for initial intervention, but should not be performed in patients with <70% stenosis.
Summary
In summary, there are several imaging modalities that are available for the screening and diagnosis of carotid atherosclerotic disease, and treatment consists mainly of medical and interventional management.
Carotid US has a relatively low cost, minimal side effects and discomfort, and is widely available. It should be utilized as the initial screening tool for both symptomatic and asymptomatic patients with suspected carotid disease. Other more advanced non-invasive imaging, such as MRA and CTA, can be employed when US yields equivocal results, or is not available. MRA and CTA are helpful in determining the exact severity of stenosis and anatomical details in patients undergoing interventional management. Catheter angiography remains the gold standard for diagnosing carotid atherosclerotic disease and for grading stenosis degree. However, due to its inherent cost and risk for complications such as ischemic strokes, it should be reserved for patients in whom noninvasive imaging is contraindicated, inconclusive, does not provide adequate delineation of the disease, or yields discordant results.
Medical therapy consists mainly of antithrombotic therapy and risk factor modification. Dual antiplatelet combination therapy has not been shown to be superior to single agents. Anticoagulation with warfarin along with its potential risk for increased hemorrhagic complications also has not been shown to be superior to antiplatelet agents. Comprehensive risk factor management should be employed in these patients, including blood pressure control, cholesterol management, diabetes management, weight loss, cessation of smoking and other lifestyle modifications.
Randomized trials such as NASCET, ECST, ACAS, ACST, SPACE, EVA-3S, SAPHIRE and CREST have shown that revascularization decreases the long-term risk for adverse ischemic events in both asymptomatic patients with non-occlusive severe stenosis (>70%) and symptomatic patients without a devastating stroke (mRS >3), and moderate to severe stenosis (>50%). However, patient comorbidities, overall life expectancy and risk for peri-procedural complications, such as ischemic stroke, MI and death, must be taken into account.
Key Points
- Asymptomatic patients without risk factors should not be screened for carotid atherosclerotic disease.
- Carotid ultrasound should be the initial screening tool for symptomatic patients.
- Medical management, including antiplatelet therapy, is indicated in all symptomatic patients with carotid atherosclerotic disease, independent of degree of stenosis.
- In general, carotid revascularization is indicated in symptomatic patients with non-occlusive moderate to severe stenosis (>50%) and asymptomatic patients with severe stenosis (>70%).
- When revascularization is indicated, patient anatomy, risk factors and plaque factors should be considered in the decision for carotid endarterectomy versus angioplasty and stenting.
I. OUTLINE
Stroke is the third leading cause of death in developed nations. Up to 88% of strokes are ischemic in nature. Extracranial carotid artery atherosclerotic disease is the third leading cause of ischemic stroke in the general population and the second most common non-traumatic cause among adults <45 years of age.
When considered as an independent diagnosis separate from other cardiovascular diseases, stroke is the third leading cause of death in developed nations and a leading cause of long-term disability
Approximately 87% of all strokes are ischemic, 10% are hemorrhagic, and 3% are subarachnoid hemorrhages
II. Introduction
- Epidemiology
Extracranial atherosclerotic disease accounts for up to 15–20% of all ischemic strokes. While intracranial atherosclerotic disease has shown to be consistently more common among Blacks, Hispanics and Asians compared to Whites, the racial differences for extracranial atherosclerotic disease is less apparent. The racial differences for extracranial atherosclerotic disease is less apparent
- Natural History
- Atheroembolism of cholesterol crystals or other debris
- Artery to artery embolism of thrombus
- Structural disintegration of the wall (dissection)
- Acute thrombotic occlusion
- Reduced cerebral perfusion with plaque growth
In symptomatic patients, there is a clear correlation between the degree of stenosis and the risk of stroke. In the North America Symptomatic Carotid Endarterectomy Trial (NASCET), the stroke rate after 18 months of medical therapy without revascularization was 19% in patients with 70–79% stenosis, 28% in patients with 80–89% stenosis, and 33% in patients with 90–99% stenosis.
This correlation is less apparent in asymptomatic patients. In the Asymptomatic Carotid Atherosclerosis Study (ACAS) and the Asymptomatic Carotid Surgery Trial (ACST), asymptomatic patients with 60–80% stenosis had higher strokes rates compared to those with more severe stenosis. The presence of a carotid bruit also does not appear to be a reliable predictor of stroke risk in asymptomatic patients. Despite the Framingham Heart Study population showing that asymptomatic patients with carotid bruit had a fold increased incidence of strokes compared to those without carotid bruit, less than half of these stroke events involved the ipsilateral cerebral hemisphere.
While the degree of carotid stenosis remains the main determinant of disease severity, additional imaging markers of plaque vulnerability are also important in determining the risk for transient ischemic attack (TIA) and strokes. Imaging markers for plaque vulnerability on ultrasonography include:
- Ulceration
- Echolucency
- Intraplaque hemorrhage
- High lipid content
Thin or ruptured fibrous caps, intraplaque hemorrhage and large lipid-rich or necrotic plaque cores, and overall plaque thickness seen on magnetic resonance imaging (MRI) have also been associated with subsequent ischemic events
III. Evaluation of Carotid Atherosclerotic Disease
- Carotid Ultrasound
Carotid US should be performed in asymptomatic patients with two or more of the following risk factors:
- Hypertension
- Hyperlipidemia
- Family history of atherosclerosis or ischemic stroke before 60 years of age
- Tobacco smoking
Carotid US should also be performed annually to assess the progression or regression of disease and response to therapeutic measures in patients with >50% stenosis. Once stability has been established or a patient’s candidacy for further intervention has changed, longer intervals may be appropriate.
Despite varying results between imaging centers and operators, the overall sensitivity and specificity for detection of occlusion or stenosis >70% have been reported to be 85–90% when compared to catheter angiography.
- Computed Tomography Angiography (CTA) and Magnetic Resonance Angiography (MRA)
MRA has the benefit of its relative insensitivity to arterial calcification. Contrast-enhanced MRA allows for more detailed evaluation of the cervical arteries, especially in lesions with a slow blood flow when compared to non-contrasted studies.
Unlike both MRA and carotid US, CTA provides direct imaging of the arterial lumen, making it suitable for evaluation of stenosis. It is an accurate test to determine severity of stenosis and is highly accurate for detection or exclusion of complete occlusions as well.
- Catheter Angiography
Catheter angiography is useful in patients with renal insufficiency. Selective angiography of a single suspected vascular territory could provide definitive imaging with limited exposure to contrast material and is unlikely to exacerbate renal insufficiency
IV. Medical Management
- Antithrombotic Therapy
Several randomized, controlled, double-blinded studies have shown that dual antiplatelet combination therapy is not superior to single agents. Despite clopidogrel monotherapy showing equal efficacy and lower hemorrhage risk than aspirin plus extended release dipyridamole, and equal efficacy with aspirin plus clopidogrel the variations in response to clopidogrel due to genetic factors and drug interactions makes it crucial for individualized treatment selection for optimum stroke prevention.
- Treatment of Hypertension
Antihypertensive therapy also reduces the risk for recurrent strokes by 24%. As such, antihypertensive treatment is recommended for all patients with concurrent hypertension and asymptomatic extracranial carotid atherosclerotic disease, with a goal blood pressure below 140/90 mmHg.
- Treatment of Hyperlipidemia
Epidemiological studies have consistently shown a positive association between cholesterol levels and carotid artery atherosclerosis. Lipid-lowering therapy with statins has been shown to reduce the risk of ischemic stroke in patients with atherosclerosis.
- Diabetes Mellitus Management
- Smoking Cessation
- Obesity and Physical Inactivity
- Interventional Management
In general, intervention when indicated should be done within 6 months of original presentation. However, intervention within 2 weeks of the index event is reasonable for patients with no contraindications for early revascularization.
The indications for intervention will be discussed in detail in the sections below. The general contraindications for interventions include:
- Severe, disabling stroke [(mRS) score >=3]
- Chronic total carotid artery occlusion
- Carotid stenosis <50%
- Extreme high-risk for peri-procedural complications
Carotid revascularization is not recommended for patients with near–complete occlusion or stenosis <50% since the risk for stroke is low in these patients. Revascularization has also not shown to have any benefit in these patients. Carotid revascularization is also not recommended for patients with cerebral infarction causing severe disability that precludes preservation of useful function.
V. Carotid Endarterectomy
- Carotid Endarterectomy in Symptomatic Patients
A meta-analysis of these three trials showed that CEA was most effective in patients with >70% stenosis without complete or near occlusion. Benefits of CEA in patients with 50–69% stenosis were only modest, but increased with time. Surgery offered little to no long-term benefits in patients with complete or near occlusion. When the combined outcome of perioperative stroke or death and fatal or disabling ipsilateral ischemic stroke was considered, the clinical benefits of CEA were only evident in patients with 80–99% stenosis.
- Carotid Endarterectomy in Asymptomatic Patients
VI. Carotid Angioplasty and Stenting
CAS has shown varying outcome differences when compared to CEA based on different patient factors. CAS appears to be a good alternative to CEA in certain patient groups, such as those with unfavorable surgical anatomy, include:
- High carotid bifurcation or arterial stenosis above the level of the second cervical vertebra
- Arterial stenosis below the clavicle (intrathoracic)
- Contralateral carotid occlusion
- Contralateral vocal cord paralysis
- Previous ipsilateral CEA
- Prior radical neck surgery or radiation
- Prior tracheostomy
- Carotid Angioplasty and Stenting in Asymptomatic Patients
- New York Heart Association class III or IV heart failure
- Chronic obstructive pulmonary disease
- >50% contralateral carotid artery stenosis
- Prior CEA or CAS
- Prior coronary artery bypass graft surgery
- Carotid Angioplasty and Stenting in Symptomatic Patients
Anatomical Considerations
Several patient anatomic factors are considered to be unfavorable for endovascular intervention, including:
- Type II or III aortic arch
- Arch vessel origin stenosis >50%
- Common and internal carotid artery tortuosity >30°
- Significant plaque calcifications
- Long segment stenosis
Noninvasive imaging at the 1-month interval, followed by the 6-month interval, and then annually after revascularization is recommended for both CAS and CEA patients. Regular imaging allows for adequate assessment of ipsilateral carotid patency and to exclude development of contralateral lesions. Once stability has been established, surveillance at longer intervals may be appropriate. Surveillance may not be indicated when the patient is no longer a candidate for intervention.
In patients with recurrent symptomatic carotid stenosis, a repeat CEA or CAS can be considered, using the same criteria as recommended for initial revascularization (discussed previously). Repeat intervention is also recommended when duplex ultrasonography and an additional confirmatory imaging (MRA, CTA or catheter angiography) shows rapidly progressive restenosis, indicating risk of complete occlusion. A repeat CEA can be considered under the hands of an experienced surgeon. CAS is an alternative to repeat CEA in patients with recurrent stenosis after CEA, and may be appropriate in asymptomatic patients with restenosis >80% or symptomatic restenosis >50%. Repeat intervention can also be considered in patients with asymptomatic recurrent stenosis, using the same criteria for initial intervention, but should not be performed in patients with <70% stenosis.
Summary
In summary, there are several imaging modalities that are available for the screening and diagnosis of carotid atherosclerotic disease, and treatment consists mainly of medical and interventional management.
Carotid US has a relatively low cost, minimal side effects and discomfort, and is widely available. It should be utilized as the initial screening tool for both symptomatic and asymptomatic patients with suspected carotid disease. Other more advanced non-invasive imaging, such as MRA and CTA, can be employed when US yields equivocal results, or is not available. MRA and CTA are helpful in determining the exact severity of stenosis and anatomical details in patients undergoing interventional management. Catheter angiography remains the gold standard for diagnosing carotid atherosclerotic disease and for grading stenosis degree. However, due to its inherent cost and risk for complications such as ischemic strokes, it should be reserved for patients in whom noninvasive imaging is contraindicated, inconclusive, does not provide adequate delineation of the disease, or yields discordant results.
Medical therapy consists mainly of antithrombotic therapy and risk factor modification. Dual antiplatelet combination therapy has not been shown to be superior to single agents. Anticoagulation with warfarin along with its potential risk for increased hemorrhagic complications also has not been shown to be superior to antiplatelet agents. Comprehensive risk factor management should be employed in these patients, including blood pressure control, cholesterol management, diabetes management, weight loss, cessation of smoking and other lifestyle modifications.
Randomized trials such as NASCET, ECST, ACAS, ACST, SPACE, EVA-3S, SAPHIRE and CREST have shown that revascularization decreases the long-term risk for adverse ischemic events in both asymptomatic patients with non-occlusive severe stenosis (>70%) and symptomatic patients without a devastating stroke (mRS >3), and moderate to severe stenosis (>50%). However, patient comorbidities, overall life expectancy and risk for peri-procedural complications, such as ischemic stroke, MI and death, must be taken into account.
Key Points
- Asymptomatic patients without risk factors should not be screened for carotid atherosclerotic disease.
- Carotid ultrasound should be the initial screening tool for symptomatic patients.
- Medical management, including antiplatelet therapy, is indicated in all symptomatic patients with carotid atherosclerotic disease, independent of degree of stenosis.
- In general, carotid revascularization is indicated in symptomatic patients with non-occlusive moderate to severe stenosis (>50%) and asymptomatic patients with severe stenosis (>70%).
- When revascularization is indicated, patient anatomy, risk factors and plaque factors should be considered in the decision for carotid endarterectomy versus angioplasty and stenting.