(Stroke. 2000;31:622.)
© 2000 American Heart Association, Inc.
Original Contributions |
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?
From the Department of Clinical Neurology (P.M.R.), Radcliffe Infirmary, Oxford, UK; and the Department of Clinical Neurosciences (C.P.W.), Western General Hospital, Edinburgh, UK.
Correspondence to Dr P.M. Rothwell, Department of Clinical Neurology, Radcliffe Infirmary, Woodstock Road, Oxford OX2 6HE, UK. E-mail peter.rothwell{at}clneuro.ox.ac.uk
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Abstract |
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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.
Key Words: carotid arteries • carotid endarterectomy • risk factors • stroke • ischemia
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Introduction |
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TopAbstractIntroductionSubjects and MethodsResultsDiscussionReferences |
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Atherothrombotic stenosis of the origin of the internal carotid artery (ICA) is a common cause of carotid territory ischemic stroke.1 2 The risk of stroke increases with the severity of carotid stenosis and is reduced after carotid endarterectomy.3 4 However, because even with severe recently symptomatic carotid stenosis, only about one third of patients have a stroke on medical treatment alone, endarterectomy can be helpful in only a minority of patients. To maximize the effectiveness of endarterectomy, it is necessary to identify and operate on patients with a high risk of stroke without surgery. Plaque surface thrombus formation and distal embolism are important mechanisms of stroke in patients with carotid stenosis,5 6 7 and angiographic plaque surface irregularity is associated with an increased risk of ischemic stroke at all degrees of stenosis,8 9 but there also is evidence that hemodynamic factors may be important. A proportion of patients with a recently symptomatic severe carotid stenosis or occlusion have diminished perfusion of the ipsilateral cerebral hemisphere and cannot increase perfusion in response to raised levels of carbon dioxide.10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 Consistent results have been obtained from studies with transcranial Doppler ultrasound,10 11 12 13 single-photon emission computed tomography,14 15 16 positron emission tomography,15 22 23 24 and other imaging techniques.17 18 19 20 21 Such patients also have metabolic changes in the affected hemisphere that are consistent with ischemia in the absence of any evidence of cerebral infarction.25 26 27 28 Both the perfusion deficit and the metabolic changes can be reversed after carotid endarterectomy and extracranial/intracranial bypass graft surgery.19 22 29 30 31
It is conceivable that indexes of reduced cerebral perfusion might be useful in the identification of patients with carotid stenosis who are at a particularly high risk of ischemic stroke. For example, 2 small studies have recently shown that reduced cerebral perfusion is associated with an increased risk of stroke on medical treatment in patients with unilateral carotid occlusion,13 24 but no such link has yet been demonstrated in patients with carotid stenosis. Using carotid angiograms of patients with recently symptomatic carotid stenosis who were randomized in the European Carotid Surgery Trial (ECST), we studied the effect of a number of angiographic indices that would be expected to reduce cerebral perfusion pressure on the risk of ipsilateral carotid territory ischemic stroke on medical treatment.
The most direct angiographic correlate of ipsilateral poststenotic perfusion pressure is likely to be the degree of narrowing of the distal ICA. In some patients with a tight carotid stenosis, the normal ICA distal to the stenosis is narrowed or collapsed on the angiogram,32 33 34 indicating particularly low poststenotic intraluminal pressure. Low flow is frequently manifest at angiography as delayed filling of the distal ICA with contrast medium. Such patients are often assumed to have a high risk of stroke and to require urgent endarterectomy. To test this assumption, we identified narrowing of the ICA with use of the ratio of the ICA lumen diameter to the common carotid artery (CCA) lumen diameter (ICA/CCA). We defined the normal range of the ICA/CCA ratio in patients with 0% to 49% stenosis and then related the presence or absence of narrowing of the ICA to the risk of ipsilateral ischemic stroke on medical treatment in patients with more severe stenosis. We also related stroke risk to the length of the hemodynamically important section of the symptomatic stenosis, 50% to 99% stenosis and occlusion of the contralateral carotid artery, and 50% to 99% stenosis and occlusion of the ipsilateral external carotid artery. We had good intracranial views in only a minority of patients and were therefore unable to look in a consistent way for the presence of distal collateral vessels.
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Subjects and Methods |
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TopAbstractIntroductionSubjects and MethodsResultsDiscussionReferences |
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We studied the carotid angiograms and clinical characteristics of patients randomized in the ECST. The methods and results of the trial have been published previously.3 Briefly, patients with recent ocular or carotid territory cerebral ischemia who had evidence of carotid stenosis on an angiogram were randomized to receive carotid endarterectomy and best medical treatment versus best medical treatment alone. Baseline clinical data were recorded and patients were followed by a physician at 4 months, 12 months, and annually thereafter.
Carotid Angiography
Carotid angiograms were performed on all patients before
randomization and sent to the trial center. Details of the angiographic
techniques have been published previously.35 The
present study was confined to the 3007 (99.6%) of the 3018 ECST
patients in whom a randomization angiogram was available in the trial
center. In patients with bilateral symptoms, the designation of the
symptomatic carotid artery in the ECST is explained
elsewhere.3 The following assessments were made on all
angiograms for the purpose of the present study:
Degree of Carotid Stenosis
The degree of stenosis of both ICAs was measured by 2
independent observers (P.M.R. and C.P.W.) using the ECST
method.36 Details of the reproducibility of this
measurement and the equivalence with other methods have been published
previously.36 37 The mean of the 2 measurements was used
in all analyses.
Normal ICA/CCA Lumen Ratio
We proposed to identify poststenotic narrowing using the
ratio of the diameter of a representative section of
the normal disease-free distal ICA to that of a disease-free portion of
the CCA. These measurements were made by a single observer on all
available angiograms of the symptomatic and contralateral
carotid arteries in the main trial office. To determine the
reproducibility of measurement of the ICA/CCA ratio, a second
independent observer made the same measurements on a consecutive series
of 976 angiograms of the symptomatic artery with a full
range of stenoses. The second observer was blind to the
measurements of the first observer, and no marks had been placed on the
angiograms.
We have shown previously, in a subset of 1001 ECST patients, that the
mean ratio was relatively constant in patients with 
69% ECST
stenosis but then fell significantly as stenosis
increased further.36 It has also been shown that
arterial stenoses of <50% do not cause any
reduction in flow or pressure distal to the
lesion.32 38 39 To define the normal range of the ICA/CCA
ratio, we therefore studied patients with 0% to 49% stenosis.
We determined the ICA/CCA ratio on angiograms of patients with 0% to
49% symptomatic stenosis and in patients with 0%
to 49% stenosis of the contralateral carotid artery.
Poststenotic Narrowing of the ICA
We proposed to define the cutoff point for poststenotic
narrowing as an ICA/CCA ratio of >2 SDs below the overall mean ratio
found in patients with 0% to 49% stenosis (ie, below the 2.5
percentile). Patients with 70% to 99% ECST stenosis and an
ICA/CCA ratio below this level were defined as having
poststenotic narrowing.
Stenosis or Occlusion of the Ipsilateral External
Carotid Artery
The degree of stenosis of the external carotid artery
ipsilateral to the symptomatic carotid stenosis was
measured by 1 observer using a method similar to the ECST method of
measuring the degree of stenosis of the ICA (ie, the
denominator was the estimated normal lumen diameter at the site of
maximum stenosis).
Stenosis or Occlusion of the Contralateral Carotid
Artery
The degree of stenosis of the ICA contralateral to the
symptomatic stenosis was measured by 1 observer
using the ECST method.
Length of the Hemodynamically Significant Portion
of the Stenosis
The length of an arterial stenosis has been
shown to have a measurable hemodynamic
effect.32 38 39 The effect is greatest when the degree of
stenosis of the vessel is severe.38 We defined the
hemodynamically significant portion of the
stenosis as the length of that portion of the stenosis
where the lumen was narrowed by >50%. This was recorded as a
ratio with the diameter of a disease-free portion of the CCA.
Plaque Surface Morphology
Carotid plaque surface morphology was classified by 1 observer
as smooth or irregular, as we previously defined.9
Outcome Events
Details of any strokes or deaths occurring during follow-up were
obtained at clinical review. Clinical details, results of any
investigations, and any postmortem information were sent to the main
trial center for classification by a trial neurologist (C.P.W. or
P.M.R.). Classifications of all strokes and deaths were then reviewed
by an independent blinded audit committee. For the purpose of the
present study, the analysis of the risk of ipsilateral
carotid territory ischemic stroke is restricted to first
strokes lasting >7 days (ie, "major" ischemic strokes).
Where CT brain scan was not available or where the scan was performed
>30 days after the stroke, the stroke was categorized as
ischemic. A disabling stroke was defined as one in which the
Rankin scale score at 6 months after the stroke was 
3.3
Transient ischemic attacks that occurred during follow-up were
recorded but were not submitted for blinded audit.
Statistical Analysis
All actuarial risks of ischemic stroke were performed
with Kaplan-Meier survival analysis and censoring for nonstroke
death. Survival analyses, multiple logistic regression
analyses, and Cox’s proportional hazards modeling were
performed with SPSS for Windows version 7.0.
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Results |
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TopAbstractIntroductionSubjects and MethodsResultsDiscussionReferences |
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Of the 3007 patients studied, 1208 patients were randomized to receive medical treatment alone and 1799 patients were randomized to undergo surgery. Of the patients randomized to undergo surgery, 1739 (97%) underwent carotid endarterectomy. The median time from the last ischemic symptoms referable to the symptomatic artery and randomization was 47 days (interquartile range 21 to 91 days). Mean follow-up was 6.4 years (range 1 to 13). Patient characteristics, the trial results, and the morbidity and mortality rates for surgery are reported elsewhere.3
Normal ICA/CCA Ratio
Measurements of the ICA and CCA lumen diameters were made on
angiograms of 2901 (96.5%) symptomatic carotid arteries
and 2211 nonoccluded contralateral carotid arteries. A comparison of
measurements made by 2 independent observers on a consecutive sample of
976 symptomatic arteries of all degrees of stenosis
is shown in Figure 1
. Overall agreement
was good, particularly at low ICA/CCA ratios. To assess whether the
normal premorbid ICA/CCA ratio on the symptomatic side
could be estimated from the ratio on the contralateral side, the ratios
on the symptomatic and contralateral sides were compared in
the 653 patients with stenosis of <50% on both sides. The
correlation between the ICA/CCA ratio of the symptomatic
artery and that of the contralateral artery was very poor
(r=0.07, P=0.08). Whether one ICA is narrowed
therefore could not be determined relative to the contralateral ICA,
and it was necessary to define an absolute value of the ICA/CCA ratio
below which an ICA could be said to be narrowed.
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The degree of stenosis was in the range of 0% to 49% in 1034
symptomatic arteries and 1932 contralateral arteries. The
measurement characteristics of the ICA/CCA ratio in these samples are
given in Table 1. The
distributions of the measurements in the 2 samples were virtually
identical. In both samples, the ICA/CCA ratio was normally distributed
with a fairly narrow range. The mean (SD) ratios in the
symptomatic and contralateral arteries were 0.62 (0.1) and
0.63 (0.1), respectively. The lower limit of the 95% range was 0.42 in
both samples. The lower limit of normal of the ICA/CCA ratio was
therefore defined as 0.42. The distribution of ICA/CCA ratios in both
samples combined is shown in Figure 2.
There were 316 angiograms of the contralateral ICA in which there was
no discernible stenosis. In this group, the mean ratio was 0.63
(SD 0.1, median 0.62, 95% range 0.44 to 0.80). Given the relatively
small number of cases in this group, the results were
consistent with a lower limit of normal for the ICA/CCA ratio
of 
0.42.
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Poststenotic Narrowing of the Symptomatic ICA
The mean ICA/CCA ratio on the symptomatic side
remained constant until the degree of stenosis exceeded 70%
(Figure 3). Thereafter, the mean ratio in
each decile fell as stenosis increased (ANOVA,
P<0.0001). The mean (SE) ratios were 70% to 79%, n=383,
0.60 (0.006); 80% to 89%, n=399, 0.55 (0.005); and 90% to 99%,
n=166, 0.46 (0.015). As a result, the proportion of patients with an
ICA/CCA ratio of <0.42 increased with the severity of stenosis
(Figure 4). The ratio was <0.42 in 149
(8%) patients with 50% to 99% stenosis and in 102 (18%)
patients with 80% to 99% stenosis. The number of patients
with significant stenosis of the contralateral carotid artery
was much lower, but poststenotic narrowing of the ICA also
increased with the severity of stenosis: 20 of 1928 (1%)
patients with 0% to 69% stenosis and 19 of 283 (7%) patients
with 70% to 99% stenosis (Fisher’s exact test,
P<0.0001). The interobserver agreement for the assessment
of poststenotic narrowing (ie, an ICA/CCA ratio of <0.42) was
good: both observers agreed in 937 of 976 cases (96%; 
=0.61, 95%
CI 0.5 to 0.72, P<0.00001).
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The baseline clinical and imaging characteristics of patients with an
ICA/CCA ratio of <0.42 and those with a ratio of >0.42 are given in
Table 2. An ICA/CCA ratio of <0.42 was
associated with presentation with an ipsilateral major
nondisabling ischemic stroke and the presence of infarction in
the territory of the symptomatic artery on the
randomization CT brain scan. The association with infarction on CT
brain scan remained significant after correction for confounding by the
degree of carotid stenosis in a multiple regression
analysis.
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Stroke Risk
The risk of ischemic stroke on medical treatment distal to
the symptomatic carotid stenosis increased as the
severity of stenosis increased and then fell in those patients
with poststenotic narrowing of the ICA (Figure 5). In patients with 70% to 99%
symptomatic stenosis randomized to medical
treatment, the 5-year actuarial risk of ipsilateral carotid territory
ischemic stroke was 8% in the 45 patients with narrowing and
25% in patients without narrowing (log rank test, P=0.02).
The 5-year risk of disabling or fatal ipsilateral carotid territory
ischemic stroke was also lower in patients with
poststenotic narrowing, but this did not reach statistical
significance (log rank test, P=0.1): 2.2% versus 9.4%.
There was a similar trend in the 5-year risk of ipsilateral cerebral
transient ischemic: 9% versus 16% (log rank test,
P=0.1). The risk of stroke in patients without narrowing was
22% distal to 80% to 89% stenosis and 32% distal to 90% to
99% stenosis (Figure 5). In a Cox proportional
hazards analysis, with all of the baseline clinical and
angiographic characteristics listed in Table 2
taken into
account, including the degree of symptomatic carotid
stenosis, poststenotic narrowing was a significant
predictor of a reduced risk of stroke in the medical group as a whole
(hazard ratio 0.40, 95% CI 0.17 to 0.94, P=0.03). In
contrast, there was no difference in the 5-year actuarial risk of
ischemic stroke in other territories (contralateral carotid and
vertebrobasilar) between patients with and those without narrowing of
the symptomatic ICA: 10% versus 10% (log rank test,
P=0.8).
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The prevalence of 50% to 99% stenosis or occlusion of the
ipsilateral external carotid artery and the contralateral carotid
artery both increased with the degree of stenosis of the
symptomatic ICA. It was necessary, therefore, to correct
for this in the analysis of the relationship between these
factors and the risk of carotid territory ischemic stroke on
medical treatment. After correction for severity of
symptomatic carotid stenosis, none of these other
angiographic indices thought to possibly be associated with reduced
cerebral perfusion were independently associated with stroke risk
(Table 3).
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Discussion |
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TopAbstractIntroductionSubjects and MethodsResultsDiscussionReferences |
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Definition of Poststenotic Narrowing of the ICA
Williams and Nicoliades40 showed that the ICA/CCA ratio ranged from 0.5 to 1.0 in angiograms of 61 normal carotid bifurcations. We found similar results in 316 ECST patients with normal contralateral carotid arteries and defined the properties of the ratio with precision in nearly 3000 symptomatic and contralateral carotid arteries with 0% to 49% stenosis. Measurement of the ICA/CCA ratio had good interobserver reproducibility. We have shown that the ICA begins to narrow when the degree of stenosis reaches 70% with the ECST method (50% stenosis with the North American Symptomatic Carotid Endarterectomy Trialists [NASCET] method). It is difficult to identify minor degrees of narrowing in individual patients because of the variation in the normal ICA/CCA ratio. Minor narrowing is only apparent when considering the mean ICA/CCA ratio in a population of patients (Figure 3
). Moreover, it was not possible
to use the ICA/CCA ratio of the contralateral ICA as a standard with
which to compare the ratio on the symptomatic side. The
correlation between the ICA/CCA ratio on the symptomatic
and contralateral sides was very poor even when the degree of
stenosis was <50% on both sides. To define narrowing of the
ICA with a degree of certainty, we therefore had to use a cutoff point
below which we could confidently say that the majority of cases had
definite narrowing. We defined the cutoff point as 2 SDs below the mean
ICA/CCA ratio in patients with 0% to 49% stenosis (ie, a
level at which only 2.5% of the normal population would be expected to
lie). Although 2 SDs about the mean is the most frequently used
standard by which to define the normal range for a variable, it is
a compromise. On the one hand, it limits the proportion of normal
arteries that would be misdiagnosed as narrowed to 2.5%, but on the
other hand, it means that a patient in whom the original ICA/CCA ratio
was 0.8 will have to develop a major degree of narrowing before being
included. More detailed analysis of the relationship between
narrowing of the ICA and the risk of stroke, with the ICA/CCA ratio
used as a continuous variable, may be possible if studies such as
ECST and NASCET are combined to produce a dataset with a sufficiently
large number of patients.
Stroke Risk in Patients with Poststenotic Narrowing of
the ICA
Despite the limitations of defining narrowing of the ICA using a
single cutoff point, the classification does appear to be clinically
useful. Patients with a 70% to 99% symptomatic carotid
stenosis and an ICA/CCA ratio of <0.42 had a significantly
lower risk of ipsilateral carotid territory ischemic stroke on
medical treatment than did patients with the same range of
stenosis and no narrowing. Contrary to the current clinical
impression, patients with recently symptomatic tight
carotid stenosis and narrowing of the distal ICA are not at a
high risk of stroke. This is consistent with the finding of a
low risk of stroke on medical treatment in patients with severe
stenosis and almost complete collapse of the distal ICA (the
"carotid string sign") in NASCET.34 Our data suggest
that the low risk extends to patients with less marked degrees of
poststenotic narrowing of the ICA. It is interesting to note
that Norris and Zhu41 reported a fall in the risk of
cerebral ischemic events in patients with very severe, or
"critical," carotid stenosis in their ultrasound-based
study of asymptomatic carotid stenosis. More work
is required to define the Doppler ultrasound characteristics of
patients with poststenotic narrowing on angiography.
Low-Flow Cerebral Protection Hypothesis
It is interesting to speculate as to why patients with
poststenotic narrowing should be at a lower risk of ipsilateral
ischemic stroke than patients with the same degree of
stenosis but no narrowing, despite having similar clinical
characteristics and similar plaque surface morphology.
Poststenotic narrowing must indicate low intraluminal pressure
due to reduced flow across the stenosis. This is seen as
delayed filling of the distal ICA on injection of contrast during
conventional angiography.42 One possible explanation for
the low risk of stroke in patients with poststenotic narrowing
is that blood flow across the stenosis is now too low to
dislodge emboli from the surface of the plaque or to carry large emboli
to the brain. It has been suggested that both cerebral microemboli and
cerebral hypoperfusion are usually required to cause major cerebral
infarction.43 Patients with poststenotic narrowing
of the ICA are likely to have poor perfusion of the ipsilateral
cerebral hemisphere, but they are less likely to have cerebral emboli.
The number of microemboli detected with transcranial
Doppler scanning of the middle cerebral artery distal to
symptomatic carotid stenoses falls significantly as
the degree of stenosis exceeds 90%44 and is
particularly low in patients with poststenotic narrowing (Prof
Hugh Markus, personal communication). Our data are consistent
with the hypothesis that in the absence of cerebral emboli,
hypoperfusion alone is usually insufficient to cause major cerebral
infarction.
It is paradoxical that patients with poststenotic narrowing of the ICA have a low risk of stroke on follow-up but a high frequency of major stroke in the past and a high frequency of infarction in the ipsilateral cerebral hemisphere compared with patients without poststenotic narrowing. However, this is not inconsistent with our hypothesis. The high risk of ipsilateral cerebral infarction in the past suggests that these patients may well have relatively poor cerebral perfusion reserve. In combination with cerebral embolism, this would lead to a high risk of stroke. However, poor perfusion reserve would be a risk factor only for cerebral infarction in the presence of cerebral emboli. When the stenosis becomes very severe and leads to poststenotic narrowing, the emboli rate and the stroke risk fall. In this respect, it may be relevant that the risk of stroke in patients with poststenotic narrowing is similar to that distal to symptomatic carotid occlusion.45 Moreover, recent results from the NASCET study directly support this hypothesis.46 An absence of angiographic collateral vessels feeding the cerebral hemisphere distal to the symptomatic carotid stenosis was associated with a high risk of stroke in patients who did not have poststenotic narrowing of the ICA but had no effect on stroke risk in patients with poststenotic narrowing. In other words, low poststenotic flow protected patients from the high stroke risk normally associated with absent collateral circulation.
Implications for Carotid Imaging, Carotid
Endarterectomy, and Measurement of Carotid
Stenosis
First, patients with very severe stenosis and narrowing of
the distal ICA may be misdiagnosed as having a complete occlusion with
noninvasive methods of imaging such as Doppler ultrasound and
magnetic resonance angiography. This has been regarded as one of the
main advantages of conventional arterial angiography.
However, although further work is required to determine whether these
patients derive any benefit from endarterectomy,
the low risk of stroke on medical treatment in patients with
poststenotic narrowing potentially reduces the importance of
misdiagnosis.
Second, contrary to the current clinical impression, patients with recently symptomatic severe carotid stenosis and narrowing of the distal ICA are at a relatively low risk of stroke and do not necessarily require urgent endarterectomy. However, there were too few patients with poststenotic narrowing in the ECST to allow us to sensibly consider the effectiveness of endarterectomy in this subgroup. We intend, therefore, in collaboration with Prof H.J.M. Barnett, to apply the same definition of poststenotic narrowing to patients with symptomatic carotid stenosis in the NASCET trial. The combination of data from the 2 trials should produce a subgroup of sufficient size to allow us to consider the effect of surgery.
Third, the gradual narrowing of the distal ICA as the severity of stenosis exceeds 70% with the ECST method (50% with the NASCET method)36 has implications for the measurement of carotid stenosis. Patients with and without poststenotic narrowing of the ICA who have the same degree of stenosis with the ECST method (or the common carotid method)36 will have different degrees of stenosis when measured with the NASCET method. Narrowing of the distal ICA will lead to underestimation of stenosis with use of the NASCET method. In NASCET, this problem was circumvented by the use of the near-occlusion category of stenosis.34 42 The assessment of near occlusion was based primarily on the presence on the randomization angiogram of collateral flow to the symptomatic hemisphere via the circle of Willis or the external carotid artery. Some of these patients had narrowing of the distal ICA, and some did not.
Other Potential Angiographic-Hemodynamic Correlates
Blood flow through an artery begins to fall when linear
stenosis exceeds 50%.32 38 39 However, although
patients with severe carotid stenosis often have reduced
perfusion reserve in the ipsilateral cerebral hemisphere and >50%
stenosis is necessary for this to occur, it is rarely
sufficient on its own.10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 Patients with
hemodynamic insufficiency often also have evidence of
reduced collateral flow, usually with 50% stenosis of the
contralateral ICA and evidence of collateral flow through the
ipsilateral external carotid artery. Severe stenosis or
occlusion of the contralateral ICA, or possibly even the ipsilateral
external carotid artery, might therefore exacerbate any
hemodynamic insufficiency by reducing collateral flow.
However, we found no association between these characteristics and the
risk of ipsilateral ischemic stroke on medical treatment in
ECST patients with 50% to 99% symptomatic
stenosis. Similarly, the length of an arterial
stenosis has been shown to have a measurable
hemodynamic effect.32 38 39 The effect is
greatest when the degree of stenosis of the vessel is
>50%.38 However, the length of the
hemodynamically significant portion of the
symptomatic carotid stenosis was unrelated to the
risk of stroke on medical treatment. It is possible that these
angiographic characteristics are too poorly correlated with cerebral
perfusion to have any effect on the risk of stroke on medical
treatment, particularly as we were unable to assess the presence or
absence of collateral flow via the external carotid circulation and the
circle of Willis. It is also possible that an effect was missed because
of an insufficient numbers of patients and strokes. However, despite
these limitations, occlusion of the contralateral carotid artery has
been shown consistently to be associated with an increased risk
of stroke due to carotid
endarterectomy.47 It is at least
possible to conclude that there was no evidence to suggest that these
angiographic characteristics are of major value in the identification
of patients at an especially high risk of stroke on medical
treatment.
Conclusions
Poststenotic narrowing of the ICA can be defined in a
reproducible and clinically useful way with the ICA/CCA ratio. Patients
with recently symptomatic severe carotid stenosis
who have a ratio that is below the lower limit of normal in patients
with 0% to 49% stenosis (0.4) have a significantly reduced
risk of stroke on medical treatment alone. This risk is comparable to
that distal to complete carotid occlusion. Further research is required
to determine whether such patients benefit from carotid
endarterectomy. Taken together with other recent
observations, these findings support the hypothesis that low flow alone
is not usually a sufficient cause of ischemic stroke distal to
symptomatic carotid stenosis. We suggest that in
patients with carotid stenosis, low poststenotic flow
may in fact protect the brain from infarction by reducing the frequency
of cerebral embolism.
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Acknowledgments |
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The ECST was funded by the United Kingdom Medical Research Council.
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Footnotes |
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A full list of collaborators is provided in Reference 3.
Received July 8, 1999; revision received November 8, 1999; accepted November 8, 1999.
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