Full Text Review

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
Prepared by Ariane Mackey, MD, FRCPC, Fellow (Cerebro-Vascular),
Division of Neurology, Department of Medicine, Robert Cote, MD, FRCPC,
Division of Clinical Epidemiology, and Renaldo N. Battista, MD, ScD, FRCPC,
Director, Division of Clinical Epidemiology, Montreal General Hospital
These recommendations were finalized by the Task Force in January 1994
Contents
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 its 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
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.
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.
Figure
1.
Full Citation
Link to Structured Abstract of
this review
Link to Summary Table of this
review
Link to Selected References list of this review
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