Published: May 2016
Carotid artery stenosis (CAS), atherosclerotic narrowing of the extracranial carotid arteries, is clinically significant because CAS is a risk factor for ischemic stroke, which affects more than 600,000 American adults each year. Ischemic stroke accounts for the vast majority of strokes, and atherothrombosis of large arteries including the carotids cause about 15% of all ischemic strokes.1 The definition of hemodynamically significant CAS varies from study to study ranging in degree of stenosis from 50% to 70% and greater. The U.S. Preventive Services Task Force considers CAS of 60% to 99% to be clinically relevant.2 Carotid intima-media thickness (CIMT), a measurement of the intimal and medial layers of the carotid artery walls, is used to detect early atherosclerotic disease.Increased CIMT is associated with risk of myocardial infarction and stroke, but whether its use results in measurable health benefits remains unclear.3
The risk factors for CAS are similar to those for atherosclerosis in other vascular beds: advanced age, tobacco smoking, hyperlipidemia, hypertension, diabetes, and physical inactivity. The prevalence of CAS is slightly higher in men than women.4
Hypertension is a strong risk factor for CAS. In the Systolic Hypertension in the Elderly Program study, systolic blood pressure greater than 160 mm Hg was the strongest independent predictor of CAS.5 The Framingham Heart Study showed twice the risk for CAS of 25% or greater for every 20 mm Hg elevation in systolic blood pressure.6
Smokers are more likely than non-smokers to have significant CAS.7,8 Current smokers are more likely to have significant CAS compared with former smokers and the degree of stenosis is associated with the number of cigarettes smoked over time.6,9
The association between elevated blood cholesterol levels and ischemic stroke is not as strong as that of cholesterol and myocardial infarction (MI) with large epidemiologic studies showing mixed results. Nevertheless, hypercholesterolemia was associated with CAS in the Framingham Heart Study and with carotid atherosclerosis as reflected by carotid intima-media thickness (IMT) in several other studies.6,10-12
Diabetes is associated both with carotid IMT and CAS and their progression.13-18 About 1% of asymptomatic persons 65 years of age and older are estimated to have CAS of 60% to 99%.19 In one study, 7% of all first ischemic strokes occurred in patients with CAS of greater than 60%.20
Studies suggest that 5% of individuals with CAS of 70% or more will have a stroke within 5 years9 and quality, long-term data beyond 5 years are lacking. Although there are no validated models for predicting stroke in CAS, including risk factors for stroke itself (hypertension, smoking, high blood cholesterol, and diabetes), men, age older than 65 years, and the physically inactive are more likely to have a stroke related to CAS.21 In the Northern Manhattan Study, blacks and Hispanics had more strokes than whites with CAS.20
Atherosclerotic carotid disease occurs when lipoprotein accumulates in the intima of the artery and is oxidatively modified. When this occurs, cytokine release ultimately leads to monocyte deposition in the artery wall. These monocytes then transform into foam cells, causing smooth muscle cells to migrate to the intima and form a lipid-laden plaque with a fibrous cap. These plaques tend to occur at arterial branch points. As atherosclerosis progresses, it may completely occlude the artery lumen, or the plaque may rupture, sending thrombus more distally resulting in a transient ischemic attack (TIA) or stroke.
Carotid artery stenosis may be entirely asymptomatic. Symptoms occur when plaque ruptures and causes an embolism more distally. The type of symptoms depends on where the thromboembolism occurs. Most carotid artery TIAs and strokes occur in the distribution of the middle cerebral artery (MCA), which may lead to contralateral hemiplegia or sensory loss of the lower face or arm and contralateral homonymous hemianopia. A left MCA stroke may cause expressive aphasia. A right MCA stroke may cause unilateral neglect.
The clinical finding of a carotid bruit on auscultation is non-specfic; therefore, hemodynamically significant CAS cannot be determined by physical examination alone.22
Of the imaging modalities available for diagnosis of CAS, duplex ultrasound (DUS) is often used because it requires no radiation or intravenous contrast and is relatively inexpensive compared with computed tomography and magnetic resonance angiography (Figure 1). Duplex ultrasound uses blood velocity to determine the presence and severity of stenosis in conjunction with B-mode grayscale imaging of plaque. There are many velocity criteria for determining degree of stenosis, some more widely accepted than others. The Society of Radiologists in Ultrasound (SRU) consensus criteria defines critical stenosis (greater than 70%) as a peak systolic velocity greater than 230 cm/s along with an end diastolic velocity greater than 100 cm/s and an internal carotid artery to common carotid artery ratio greater than 4.0 (Table 1).23 Peak systolic velocity greater than 125 cm/s but less than the criteria for critical stenosis constitutes 50% to 69% stenosis. The accrediting organization for vascular laboratories, recently recommended that laboratories without rigorously validated internal criteria use the SRU criteria.24
|Degree of stenosis, %||ICA PSV, cm/sec||Plaque estimate, %*||ICA/CCA PSV ratio||ICA EDV, cm/sec|
|≥70 but less than near occlusion||>230||≥50||>4.0||>100|
|Near occlusion||High, low, or undetectable||Visible||Variable||Variable|
|Total occlusion||Undetectable||Visible, no detectable lumen||Not applicable||Not applicable|
* Plaque estimate (diameter reduction) with gray-scale and color Doppler ultrasound.
CCA = common carotid artery; EDV = end diastolic velocity; ICA = internal carotid artery; PSV = peak systolic velocity.
From Grant E G, Benson C B, Moneta G L, et al. Carotid artery stenosis: Gray-scale and Doppler US diagnosis—Society of Radiologists in Ultrasound Consensus Conference. Radiology 2003;229:340-346. Copyright ©2003 by Radiological Society of North America (RSNA). Reprinted by permission of RSNA.
The main disadvantage of DUS is that very tight stenosis may be interpreted as total occlusion, which is problematic because total occlusions cannot be revascularized. Additionally, DUS may overestimate the degree of stenosis compared with digital subtraction angiography, the gold standard,25,26 and the accuracy of the test depends on the operator.27 Nevertheless, the sensitivity and specificity when compared with angiography for detecting stenosis 70% or greater ranges from 85% to 90%.28-30
Computed tomography angiography (CTA) allows imaging of the carotid arteries from the aortic arch to the circle of Willis with 100% sensitivity and 63% specificity (Figure 2). Disadvantages of CTA include use of iodinated contrast, which may be contraindicated in patients with renal insufficiency, and radiation exposure. As with ultrasound, it may be difficult to differentiate a sub-total from a total occlusion with CTA and the degree of CAS may be overestimated.31 Images may also be subject to artifact from metal dental work and heavily calcified plaques.
Similarly, magnetic resonance angiography (MRA) allows imaging from the aortic arch to the brain with sensitivity approaching 100% and specificity of 82% to 95%32-36 and has the advantage of no radiation exposure.37 Contrast-enhanced MRA is superior to non-enhanced MRA in evaluating the carotid arteries but as with CTA, patients with renal insufficiency are not good candidates for contrast-enhanced MRA and MRA may overestimate the degree of stenosis. Individuals with pacemakers and other implants may not be able to undergo MRA.
Conventional catheter angiography is the gold standard imaging modality to which non-invasive imaging techniques have been compared, although its use today is often reserved for cases of diagnostic uncertainty and those in which catheter-based revascularization is planned. In the major endarterectomy trials, different methods of measuring the degree of stenosis were used, although the method used in the North American Symptomatic Carotid Endarterectomy Trial (NASCET) is probably the most widely accepted, in which the residual lumen of the stenotic segment is compared with the normal distal ICA.1 The advantages of catheter angiography over CTA and MRA are that small amounts of contrast may be used and images are not subject to artifact from metal implants or calcium deposits. The major disadvantage is the small risk of stroke, typically less than 1% with experienced operators.38-46
|Duplex ultrasound||Relatively inexpensive
No radiation or contrast
|Tight stenosis may be interpreted as total occlusion
May overestimate degree of stenosis
|Computed tomographic angiography||Non-invasive
Complete imaging of carotid arteries
Need for iodinated contrast
Tight stenosis may be interpreted as total occlusion
Artifact from dental work, metal implants, calcification
|Magnetic resonance angiography||Non-invasive
Complete imaging of carotid arteries
|Need for contrast
May overestimate degree of stenosis
Usually contraindicated in patients with pacemakers, other metal implants
|Conventional angiography||Gold standard imaging||Invasive test
Small risk of stroke
Guidelines issued in 2011 by the American Heart Association (AHA), American Stroke Association, and other bodies recommend DUS as the first-line imaging in asymptomatic patients with suspected CAS or a carotid bruit as well as in those with transient neurologic symptoms that are suspected to be ischemic. CTA or MRA are options when DUS is not readily available or when results are equivocal.47 The Society for Vascular Surgery (SVS) guidelines, also issued in 2011, recommend against screening of asymptomatic patients with carotid bruit and no other risk factors for atherosclerosis.48 The U.S. Preventive Services Task Force recommends against screening for CAS in asymptomatic persons.48
Control of hypertension is critical in preventing stroke.49,50 Although it is clear that uncontrolled hypertension is associated with the development of carotid atherosclerosis, it is less clear whether treatment of hypertension prevents progression of carotid lesions. Antihypertensive therapy has been shown to be beneficial for persons with atherosclerosis but normal blood pressure in the Heart Outcomes Prevention Evaluation Study, in which participants randomized to ramipril had lower incidence of stroke than those on placebo.51 Current practice guidelines recommend treating patients with asymptomatic CAS to a blood pressure less than 140/90 mm Hg, a strong (Class I) recommendation. This recommendation is the same for symptomatic patients outside the hyperacute period, but the optimal blood pressure level remains undefined.47
Patients with established CAS should be asked about smoking status at every visit and current smokers should be offered smoking cessation interventions. Current guidelines make no specific recommendations regarding methods of smoking cessation, but options include behavioral interventions, nicotine replacement therapy, bupropion, and varenicline. The Food and Drug administration advises caution in using varenicline in those with known cardiovascular disease, but two recent meta-analyses have shown no significant increase in cardiovascular events.52,53 A third meta-analysis showed a significant increase in cardiovascular events in varenicline users, but the absolute rate of events was low (1% for active-therapy patients, compared with 0.8% for those receiving placebo) and more participants in the placebo group were lost to follow-up.54 Taking these studies as a whole, varenicline, which is highly efficacious compared with other interventions, likely remains an important therapy in helping patients quit smoking.
|Box 2. Medical Management of Carotid Stenosis|
Although there is abundant evidence that reduction of cholesterol reduces the risk of stroke in all patients with atherosclerosis,55-57 there is less evidence for the benefit of statins in stroke prevention in patients with extracranial CAS. In the Stroke Prevention by Aggressive Reduction in Cholesterol Levels trial of patients with carotid atherosclerosis, atorvastatin compared with placebo reduced the risk of stroke by a third and major coronary events by more than 40%.58 Statins also slow the progression of carotid atherosclerosis as measured by IMT.59-61
Current guidelines call for the addition of a bile acid sequestrant or niacin to aid in achieving optimal cholesterol levels, but recent evidence calls the benefit of niacin into question.62,63
It is unknown whether aspirin prevents stroke in asymptomatic patients with CAS. In patients with prior history of TIA or stroke, aspirin reduces the risk of stroke.64 The combination of aspirin at doses of 75 mg to 162 mg daily plus clopidogrel is no better than aspirin alone in the prevention of stroke65-66 and aspirin (a total of 50 mg daily) plus extended-release dipyridamole is superior to aspirin 50 mg daily.67 Aspirin plus dipyridamole has not been studied compared with the more usual dosing of aspirin (81–325 mg) commonly available in the U.S. There is no benefit to anticoagulation with warfarin in patients with CAS.68
It is unclear whether intensive control of blood glucose can reduce stroke risk, but since it reduces MI risk, it is a part of risk modification for those with asymptomatic and symptomatic CAS.
Recommendations on when to intervene surgically or with a catheter-based procedure for CAS depend on the degree of stenosis and whether the patient is symptomatic or asymptomatic. Recommendations for carotid endarterectomy (CEA) in symptomatic patients with greater than 70% stenosis are based on the NASCET and the European Carotid Surgery Trial, both of which compared CEA with best medical therapy at the time, aspirin.69-71 Both trials were initiated before statins were widely available. In NASCET, although stroke and death rates at 30 days were higher in the CEA group than in the non-surgical group, at 2 years CEA patients had much lower rates of stroke (16% vs. 32%). Patients older than 75 had greater benefit.72 Findings in the MRC European Carotid Surgery Trial were similar, with higher rates of stroke and death in the surgery group at 30 days, but lower rates of stroke at 3 years (12% vs. 22%).70,71
Carotid endarterectomy for asymptomatic people was studied in the Asymptomatic Carotid Atherosclerosis Study (ACAS) and the Asymptomatic Carotid Surgery Trial (ACST). Again, best medical therapy at the time was aspirin. The ACAS and ACST trials randomized participants with 60% to 99% stenosis to CEA or aspirin. The ACAS trial showed about half the rates of ipsilateral stroke in the CEA group at 3 years, 5% compared with 11%.73 Rates of stroke in the ACST trial were also about half at 3 years in the CEA group, 6% vs. 12%.74 In this trial, men appeared to benefit more than women, and the benefit in patients older than 75 was uncertain, probably due to relatively small numbers of these people in the trial.
Since these trials were performed, carotid artery stenting (CAS) has emerged as an alternative to CEA. The Carotid Revascularization Endarterectomy vs. Stenting Trial (CREST), which randomized both symptomatic and asymptomatic patients with carotid atherosclerosis to carotid artery stenting vs. CEA, found no difference in the composite of stroke, MI, or death within 30 days and ipsilateral stroke during long-term follow-up.75 There were more strokes and fewer MIs at 30 days in the carotid artery stenting group, and patients 70 and older had overall better outcomes with CEA. The Stenting and Angioplasty with Protection in Patients at High Risk for Endarterectomy (SAPPHIRE) trial randomized "high-risk" patients, including those with previous CEA, to carotid artery stenting vs. CEA. It found that carotid artery stenting was non-inferior to CEA at one year using the composite endpoint of stroke, MI, or death within 30 days and death or ipsilateral stroke within a year. Similar to CREST, older patients in the SAPPHIRE trial did better with CEA.76
The AHA guidelines recommend treating hypertension to maintain blood pressure below 140/90 mm Hg in asymptomatic CAS patients.47 In patients with symptomatic CAS who are outside the hyperacute period, blood pressure probably should be treated, but the benefit of treating to a specific target has not been established in relation to risk of exacerbating cerebral ischemia. All patients with CAS should be encouraged to quit smoking and offered cessation interventions, and all should be treated with a statin to reduce LDL cholesterol below 100 mg/dl, with an optional goal below 70 mg/dl in those with history of ischemic stroke. Similarly, patients with diabetes should be treated to an LDL below 70 mg/dl.
The AHA guidelines also recommend aspirin 75 mg to 325 mg daily for all patients with CAS to lower the risk of MI. Those with a history of ischemic stroke or TIA should get aspirin or aspirin-dipyridamole over aspirin plus clopidogrel. Clopidogrel and ticlopidine are alternatives in those who cannot take aspirin for reasons other than bleeding. Anticoagulation is not recommended unless the patient has another indication such as atrial fibrillation or a mechanical heart valve.
The SVS guidelines recommend that all patients with CAS be treated for hypertension and hypercholesterolemia and offered smoking cessation therapies, along with antiplatelet therapy.48
The AHA recommends CEA for symptomatic patients with average or low surgical risk and stenosis >70% by noninvasive imaging or >50% on catheter angiography. Carotid artery stenting can be used for symptomatic patients with the same degree of stenosis and favorable risks for endovascular intervention, when the anticipated periprocedural stroke and mortality rate is less than 6%. The AHA encourages practitioners to consider individual patient factors including life expectancy in determining which asymptomatic patients should be revascularized.
The SVS recommends medical management only for symptomatic patients with stenosis less than 50% and asymptomatic patients with stenosis less than 60%. The SVS prefers CEA to carotid artery stenting, except possibly in patients younger than 70 years.
Carotid stenosis is a risk factor for ischemic stroke. Imaging for CAS includes duplex ultrasound, CTA, MRA, and catheter angiography, but ultrasound is usually the preferred initial imaging modality. All patients with CAS should have medical management that includes control of hypertension, cholesterol levels, and diabetes, administration of antiplatelet agents, and smoking cessation. Selection of appropriate patients for revascularization depends on the degree of stenosis and presence or absence of symptoms.
Natalie S. Evans, MD, no disclosures.