Please note: In 2003, the CTF updated its Grades of Recommendations to include an "I Recommendation" for situations where insufficient evidence exists to allow a recommendation to be made.  (Formerly, these situations were captured under a "C Recommendation".)  This change is not retroactive, and all "C Recommendations" made prior to 2003 have not been reevaluated in light of the new "I" recommendation grade.  For a discussion of these recommendation grades, please link to the 2003 article in the Canadian Medical Association Journal here.

Asymptomatic Carotid Disease

Overview
In 1984 the Canadian Task Force did not recommend screening for cervical bruits in the context of a periodic health examination. There is currently no compelling data to recommend neck auscultation to detect a carotid bruit or noninvasive testing for carotid artery disease in asymptomatic patients with the ultimate objective of preventing stroke. Neck bruits are insensitive, non-specific markers for carotid stenosis. They are mostly considered, when present, as a general indicator of systemic atherosclerosis. Population-based studies show no increase in ipsilateral ischemic stroke in persons with asymptomatic neck bruits. Furthermore, among asymptomatic patients with carotid stenosis who do develop cerebrovascular symptoms most will have transient ischemic attacks (TIAs) rather than unheralded strokes. For most of these symptomatic patients efficacious stroke prevention interventions are available.

The role of prophylactic carotid endarterectomy or medical intervention such as antiplatelet drugs for asymptomatic patients is still undefined, whatever the degree of stenosis or clinical circumstance (incidental finding or preoperative assessment).

Patients with established risk factors for vascular disease should, however, be educated as to the symptoms of TIA and stroke, and their risk factors should be managed appropriately, especially control of blood pressure (Chapter 53) and cessation of smoking (Chapter 43).

Burden of Suffering
Stroke is one of the leading causes of mortality in Canada. It accounts for 7% of deaths; the overall stroke mortality rate is 55 and 44 per 100,000 annually in men and women respectively and reaches 885 and 768 per 100,000 in the elderly over 75 years of age.<1> In Canada, about 50,000 new strokes occur each year and the estimated prevalence of stroke survivors is 208,000.<2> Stroke-related neurological disability has a major impact on the patient, family members and caretakers; among survivors, 17% will remain institutionalized and 25% to 50% will need moderate to total assistance for activities of every day living.<2> The annual cost of stroke in Canada, including hospital costs and loss of productivity, is estimated to be $1.5 billion.

Extracranial carotid artery disease however plays a relatively minor role as an underlying cause of stroke. Indeed, cerebral ischemic infarcts constitute 70-85% of all strokes, about three-quarters of these are in the carotid territory and of those only 20 to 50% are associated with carotid stenosis.<3>

The prevalence of neck bruits in the normal adult population is about 3-4%. It increases with age reaching 8% in people over 75 years.<4,5> According to some population-based studies the prevalence of bruits also increases with hypertension, diabetes and female gender. In patients undergoing coronary artery bypass graft (CABG) or peripheral vascular reconstruction (PVR) asymptomatic bruits occur in approximately 10-20% of cases respectively.

Since cervical bruits inadequately predict the presence and degree of carotid disease, more recent studies have focused rather on the severity of arterial lesions based on non-invasive testing. In neurologically asymptomatic individuals, the prevalence of significant carotid artery stenosis ranges between 4% and 30% depending on the type of population studied. The presence and severity of extracranial carotid disease and stenosis increases with age, hypertension and peripheral and coronary vascular disease.

Stroke Risk
Population studies<4,5> have reported that patients with asymptomatic neck bruits are at increased risk for stroke: slightly more than 2% per year in the Evans County study (7.5 fold increase for men and 1.6 fold increase for women) and in the Framingham study the two year incidence of stroke was 3% in men and 4% in women, a 2 to 3 fold increased risk. In these studies, the presence of a bruit did not predict the type (thromboembolic, cardioembolic, lacunar or hemorrhagic) or the hemispheric location of the stroke. Most of the strokes either occurred in a different vascular territory or their presumed cause was unrelated to the carotid stenosis itself.

In more recent years, non-invasive imaging (ultrasonography), has shown that the risk of neurological events is directly correlated with the severity of carotid stenosis (Figure 1).<6-12> It has also been observed that rapid progression of carotid bifurcation plaque may herald a significant risk of stroke.<6,13> Correlation with plaque morphology such as ulceration or intraplaque hemorrhage as well as correlation with other risk factors is less well defined.

In a Canadian prospective referral population study of 696 patients with asymptomatic bruits followed on average for 3.5 years,<7> the annual stroke rate was 1.3% in patients with equal or less than 50% stenosis and 3.3% in those with greater than 50% stenosis. Ipsilateral stroke rate was 2.5% in patients with >50% stenosis. Other prospective studies of large populations of patients with asymptomatic bruits have shown similar results;<6,8-10,13> the overall risk of stroke is 1 to 2% annually, that is approximately three times the likelihood of having an ischemic stroke in an age- and sex-matched population without bruits.<11>

Cardiac Risk (Myocardial Infarction and Cardiac Death)
In the study by Norris and colleagues,<7> the annual rate of cardiac ischemic events and cardiac death was 9.9% in those with £ 50% stenosis and 14.8% in those with >50% stenosis. Similarly, in most surveys on asymptomatic carotid bruit or stenosis the major risk is cardiac, not cerebrovascular.<4,5,7> However this depends on the type of population studied and their initial cardiac status; in another ongoing prospective study,<10> in which patients with heart conditions requiring the obligatory use of aspirin were excluded, neurological events were more frequent among patients with asymptomatic bruits.

Maneuver

Auscultation
Neck bruits do not reliably predict presence or absence of underlying occlusive carotid disease. Cervical bruits may be due to other causes such as transmitted cardiac murmurs, anatomic variations, tortuosity, and hyperdynamic states.

Studies looking at the relationship between carotid bruit and corresponding stenosis have used different methodologies which limits comparability (populations with different prevalence of vascular disease, interobserver variability among clinicians about auditory characteristics of the bruit, different methods of imaging and different definition of carotid lesion severity). Depending on the method of assessment, the predictive value of a carotid bruit for ipsilateral moderate to severe stenosis ranges from approximately 16% to 75%.<3,12,14-17> Patients with asymptomatic bruits are less likely to have an underlying stenosis than patients with symptomatic bruits (cerebrovascular accident (CVA) or TIA).<3,18> According to some,<3> among patients with asymptomatic neck bruits, 17% had a >75% stenosis, while in patients with both carotid stroke and bruits, 60% had a >75% stenosis. Conversely, many patients with a high grade stenosis do not have a cervical bruit.<15,17,19,20>

Non-Invasive Testing
The most reliable non-invasive test used to evaluate the extracranial carotid arteries is Duplex scanning which combines two ultrasound techniques: a pulsed echo or B-mode ultrasound which can detect anatomic abnormalities and a Doppler ultrasound which provides functional information about blood flow. When compared to angiography, the test has been found to have a sensitivity (to detect >50% stenosis) of approximately 85% (range 82% to 100%) and a specificity ranging between 81% and 100%.<6,21> Information from the B-mode component of the Duplex is used to assess location and extension of atherosclerosis including minimal disease not causing changes in blood flow. It can also determine morphological characteristics of the plaque suggestive of intraplaque hemorrhage or ulceration, however the importance of these changes in the pathogenesis of cerebral ischemia remains controversial. These abnormalities appear to represent markers of the severity of the stenosis and plaque instability rather than playing a direct role in the pathogenesis of TIAs and stroke. Information from the Doppler component of the duplex scan provides blood flow information used to measure the degree of stenosis, which seems more relevant from a clinical viewpoint.

Carotid Doppler ultrasound is a reasonable and less expensive alternative providing an overall accuracy for lesions with a greater than 50% stenosis of 90% with a sensitivity of 87% to 89% and specificity of 92% to 97%.<21,22> A recent report from the North American Symptomatic Carotid Endarterectomy Trial (NASCET) has documented a specificity of 60% for Doppler ultrasound in detecting high-grade carotid stenosis and has suggested that angiography be required for accurate determination of operability. The lower specificity reported in this study results from an angiographical measurement approach that underestimates the degree of carotid stenosis when compared to the standard measurement approach used in most other studies. Also, determining the operability of lesions is not relevant in the context of asymptomatic carotid disease given that surgery is of unproven value.

Magnetic resonance angiography, another non-invasive but more expensive and less widely available method of imaging is not used routinely to screen persons with asymptomatic bruits.

Effectiveness of Prevention

Identification and Management of Risk Factors
Identification and treatment of hypertension as well as cessation of smoking are recommended for the prevention of cerebrovascular disease even in the absence of carotid stenosis (see Chapters 53 and 43). These are well established risk factors for stroke, as well as predictors for carotid artery atherosclerosis. Treatment of hypertension and cessation of smoking significantly reduces the incidence of cerebrovascular accidents.

The relation of blood lipids and lipoproteins to the occurrence of atherothrombotic brain infarction remains unclear. In a meta-analysis combining the results of ten studies, Qizilbash and associates<23> found the relative risk of stroke (mostly ischemic) to be 1.3 (95% confidence interval: 1.11-1.54) among patients with hypercholesterolemia (³220 mg/dl). Serum lipid levels have also been related to carotid artery atherosclerosis, however, it is not clear whether reduction of cholesterol levels has any effect on the cervical or intracranial atherothrombotic process, or on stroke risk. In middle aged men, lowering serum cholesterol does not reduce stroke mortality or morbidity according to a recent meta-analysis of thirteen randomized controlled trials (also see Chapter 54). Nevertheless, hypercholesterolemia should be managed appropriately especially considering it’s relationship to coronary artery disease.

Medical Management
Pharmacological management for patients with asymptomatic carotid disease has not been properly studied. Two primary prevention studies in healthy physicians assessing the effect of aspirin on occurrence of occlusive vascular events did not show any reduction of incidence in ischemic strokes (see Chapter 56). In those studies, no systematic neck auscultation or non-invasive testing was undertaken.

A prospective, randomized, double blind study looking at the efficacy of ASA 325 mg a day compared to placebo in preventing occurrence of vascular events in asymptomatic patients with significant (³50%) stenosis is currently underway.<24>

Therapies directed at regression of atheroma are also being assessed. Antiplatelets agents have been proven beneficial in reducing recurrent neurological events in symptomatic patients.<25> However, these results do not necessarily apply to asymptomatic persons especially when one considers their lower level of risk for ischemic events and the small but definite risk of hemorrhagic complications due to chronic aspirin use.

Prophylactic Carotid Endarterectomy

A) In Otherwise Healthy Individuals
There have been several case reports on the possible benefits of prophylactic carotid endarterectomy (CE) in asymptomatic individuals with carotid stenosis, however most of these small series have serious methodological flaws which make their results difficult to interpret. Three prospective randomized clinical trials have been published. One was terminated early because of higher than expected morbidity in the surgical group;<26> another had a complex design and many methodological inadequacies and gave no conclusions regarding the potential benefit of CE in patients with >90% stenosis.<27> In the third study<28> 444 men with asymptomatic stenosis >50% determined by angiography, were followed for an average of 47.9 months. The study showed no protective effect of surgery on the combined incidence of stroke and death though the incidence of ipsilateral neurological events (CVA and TIA) in the surgical group was 8% compared to 20.6% in the medical group. Indeed, the benefit of (CE) in asymptomatic patients should depend on stroke prevention and not only on reducing the number of TIAs since surgical intervention has recently been proven beneficial in patients with TIA or minor strokes and stenosis of between 70-99%.<29,30> It is hoped that the Asymptomatic Carotid Artery Stenosis Study (ACASS),<31> an ongoing randomized trial of CE in asymptomatic stenosis, will shed light on this still unresolved issue. Since the incidence of ipsilateral ischemic stroke is low<7,8,10> and considering that the morbidity-mortality of CE for asymptomatic lesions ranges from approximately 1 to 4.5%, and recognizing the inherent risk of intra-arterial angiography, prophylactic CE cannot be systematically recommended and remains of unproven benefit in this clinical context.

B) In Patients Undergoing Major Vascular Surgery
The question of whether prophylactic CE safely lowers the risk of perioperative stroke in asymptomatic patients with severe carotid stenosis undergoing major vascular surgery has not been addressed directly by a prospective randomized trial. In a recent prospective study of 358 patients undergoing CABG or PVR, none of 53 patients who had a >50% carotid stenosis, suffered an ipsilateral perioperative stroke.<32> According to others, patients with symptomatic coronary heart disease or peripheral vascular disease undergoing vascular surgery, in whom a carotid bruit or stenosis has been detected have a greater risk of stroke. However the exact incidence of thromboembolic events secondary to the stenotic process itself remains uncertain since perioperative strokes may be caused by a variety of pathogenetic mechanisms including embolism from the heart (thrombus, arrhythmias etc) or aorta and abnormalities of coagulation. Therefore, preoperative screening using neck auscultation and/or cervical ultrasonography of patients undergoing vascular surgery may fail to identify many who are at higher risk of sustaining strokes. Considering the above, and the fact that adding CE to a major vascular procedure often increases the risk of cardiac and cerebral complications and death,<33,34> performance of preventive carotid surgery in those asymptomatic patients cannot be justified at present.

Recommendations of Others
The recommendations of the U.S. Preventive Services Task Force on screening for cerebrovascular disease are currently under review.

The American College of Physicians also does not recommend routine diagnostic testing for carotid artery disease in patients with asymptomatic bruits. Concerning CE, they state that the procedure is "of most inappropriate use" in unselected asymptomatic patients with carotid artery abnormalities. However, they feel that CE may be indicated in patients with other risk factors for stroke, who have a high degree of stenosis (70% or greater), particularly when the contralateral artery is occluded and if surgery can be done at low risk. No recommendation was made regarding prophylactic CE before CABG.

A consensus report from the Asymptomatic Carotid Atherosclerosis Study Group concluded that baseline non-invasive evaluation of the carotid arteries was appropriate in persons considered to be at high risk for extracranial carotid artery disease. Those included patients with carotid bruits, with a strong family history of coronary and/or cerebrovascular disease and candidates for major vascular surgery.

The Ad Hoc Committee of the Joint Council of the Society for Vascular Surgery and the North American Chapter of the International Society for Vascular Surgery has recommended that patients with asymptomatic carotid artery diameter reduction of 75% or greater who are otherwise healthy and have a projected life expectancy greater than 5 years, should be considered for surgery if the operative morbidity and mortality is less than 3%.

Conclusions and Recommendations
Asymptomatic carotid stenosis is generally associated with systemic atherosclerosis and its known complications such as myocardial infarction, stroke and peripheral vascular disease. Identification and management of risk factors associated with these conditions is mandatory as well as patient education explaining the symptoms of TIAs, which would then require further evaluation and specific intervention, either medical or surgical. Screening the population for cervical bruits and stenoses would identify only a relatively small fraction of individuals at high risk for stroke or TIA. It could be a cost effective procedure if it led to prevention of a substantial number of strokes without further risk to the patient, but since the efficacy of any specific prophylactic method, medical or surgical, remains unproven, (in fact C and D Recommendations, respectively) routine auscultation or non-invasive testing of carotids in unselected individuals cannot be systematically recommended at the present time (D Recommendation). However, in centers where prospective trials are ongoing, screening of asymptomatic patients is highly encouraged.

Unanswered Questions (Research Agenda)
Whether pharmacological or surgical therapy is safe and beneficial in asymptomatic persons with carotid bruits or stenosis is currently under investigation.<24,31> When those answers become available, firmer recommendations regarding screening, for asymptomatic bruits or stenosis and, in some patients, for periodic non-invasive testing to detect rapidly progressing stenosis might be made. Other areas of interest include identification of subgroups of patients who have inadequate collateral circulation and may be at higher risk of sustaining an ipsilateral ischemic stroke. This aspect is being studied using techniques such as single photon emission computed tomography (SPECT) and transcranial Doppler. Carotid angioplasty might also have a role in asymptomatic patients. This, of course, will depend on the risk/benefit ratio of the procedure which is currently being assessed in a randomized, multicenter trial in patients with symptomatic and asymptomatic cerebrovascular disease – the Carotid and Vertebral Artery Transluminal Angioplasty Study (CAVATAS).

Evidence
The literature was identified with a MEDLINE search for the years 1988 to August 1993 using the following key words: asymptomatic neck bruits (cervical bruit or carotid bruit), carotid stenosis, carotid artery disease, carotid ultrasound, duplex sonography, stroke risk factors, carotid endarterectomy.

This review was initiated in January, 1993 and recommendations were finalized by the Task Force in January, 1994. A technical report with a full reference list is available upon request.

Acknowledgements
We would like to thank Ms. Diane Telmosse for her excellent secretarial assistance.

Full Citation
Mackey A, Cote R, Battista RN. Asymptomatic carotid disease. In: Canadian Task Force on the Periodic Health Examination. Canadian Guide to Clinical Preventive Health Care. Ottawa: Health Canada, 1994; 692-704.