From the Department of Clinical Physiology (S.R., S.H., K.J.-U.) and the
Department of Medicine, Stroke Unit (M.Z., C.C.), Stockholm Söder
Hospital, Stockholm, Sweden.
Correspondence to Stefan Rosfors, Department of Clinical Physiology, Stockholm Söder Hospital, S-118 83 Stockholm, Sweden. E-mail Stefan.Rosfors{at}Fys.sos.sll.se
Methods—182 consecutive patients (mean age, 67 years) referred
for carotid duplex scanning were included. We measured IMT and
classified plaques by means of a high-resolution ultrasound
technique.
Results—IMT was correlated to age, male gender, ischemic
heart disease, and presence of plaques or stenoses in any of
the carotid bifurcations. In men, IMT was larger on the left than on
the right side. Plaques were seen in 163 carotid bifurcations, in 45 of
these with >50% stenosis. On the left side but not on the
right, there was a correlation between IMT in the CCA and presence of
plaques or stenoses in the carotid bifurcation. Echogenic
plaques were more common than echolucent, but the latter caused
significantly more stenoses. No relationship was found between
plaque echogenicity and IMT.
Conclusions—IMT of the CCA is correlated to the degree of
atherosclerosis in the carotid bifurcations in general
and on the left side also to the presence of plaques or
stenoses in the left carotid bifurcation. Our results support
earlier observations suggesting faster development of carotid
atherosclerosis on the left than on the right side.
Echogenic plaques were more common and generally smaller than
echolucent plaques, but there was no correlation between plaque
echogenicity and IMT.
High-resolution ultrasound is also commonly used to measure
intima-media thickness (IMT) of the distal common carotid artery (CCA)
below the carotid bifurcation.4 5 6 7 The
intima-media complex in the distal CCA starts to thicken early in the
atherosclerotic process,7 even though plaques are
seen infrequently at this location. An increased IMT may predict future
atherosclerotic morbidity, as it for example has been shown to
correlate with the likelihood of acute coronary
events.8 Moreover, in asymptomatic
subjects a correlation has been shown between IMT and the presence of
plaques in the femoral or carotid bifurcations9
and between IMT and number of carotid artery
plaques.7 However, less is known regarding the
relationship between IMT and the presence of carotid artery
stenosis. Prior to this, no study has been designed to evaluate
the morphologic appearance of the carotid plaques and its relationship
to the wall thickness in patients with various degrees of
atherosclerotic disease.
In the present ultrasonographic study atherosclerotic disease of
the carotid bifurcation and IMT in the distal CCA were evaluated in a
consecutive series of patients referred for carotid duplex examination.
Our particular aim was to describe and further investigate the
relationship between IMT and the extent of carotid artery disease with
special attention to plaque occurrence, plaque morphology and formation
of stenoses.
Risk factors for cerebrovascular disease known at the time of the
examination were searched for in the patients' records and in
other examinations, including ECG and
echocardiography (performed in most of the cases).
One or more risk factors (hypertension, ischemic heart disease,
diabetes mellitus, peripheral artery disease, or blood
lipid disorder) were found in 96 patients (53%). Twenty-seven percent
had hypertension, 30% had ischemic heart disease, and 8% had
diabetes.
Duplex Ultrasonography
At the end of the examination IMT was measured on both sides. The
subject's head was tilted to get the common carotid artery just
proximal to the bulb placed horizontally across the screen. The 7-MHz
probe was used together with the resolution box function of the system,
and settings were made to get an optimal picture of the carotid walls.
Magnified pictures were frozen incident with the R wave on the ECG.
Only the far walls of the artery were used for calculation. The IMT was
defined as the distance between the leading edge of the luminal echo to
the leading edge of the media/adventitia echo.12
IMT was measured over a length of 1 cm just proximal to the bulb. This
was accomplished by use of the calipers and the trace function of the
ultrasound system and calculation of the mean IMT over this
length.13 We never included plaques in the
measurements (see the definition below). At our laboratory, the
coefficients of variation for intraoperator and interoperator
variability for repeated examinations and measurements of IMT with this
technique are 4.6% and 7.7%,
respectively.13
A plaque was defined as >1 mm in diameter and >100% increase
compared with the thickness of adjacent wall
segments,5 with localization to the carotid
bifurcation or the proximal part of the internal carotid artery.
Classification of ultrasound plaque appearance was performed
independently from the videotape during a time period of 2 weeks after
inclusion of the last patient by 1 single operator blinded to all other
data. We used the most common classification system, with 5
categories2,14: (1) uniformly echolucent; (2)
dominantly echolucent, with echolucent areas >50%; (3) dominantly
echogenic, with echogenic areas >50%; (4) uniformly echogenic; and
(5) unclassified, due to heavy calcification and acoustic
shadowing.
Intraoperator variability for plaque characterization was evaluated by
analysis of 40 randomly selected plaques that were classified
in a blinded manner by the same operator twice within 1 week.
Evaluation through the use of
Statistical Methods
Carotid Artery Disease
Relationship Between IMT and Carotid Plaques
IMTmean was significantly higher in patients with
plaques on any side, even after adjustment for age, gender and
ischemic heart disease (P<0.05). An even more
evident difference was seen when IMTmean was
compared for patients with and without stenoses on any side
(P<0.001, after adjustment for age, gender and
ischemic heart disease). In univariate
analyses regarding IMTmean and age the
estimated progression rate of IMT was 0.010 mm/y for patients with
plaques and 0.006 mm/y for patients without plaques.
IMTmean with increasing degree of carotid artery
disease is shown in the Figure
IMTright for patients with a plaque (n=87) or a
stenosis (n=20) on the same side was 0.86 mm (CI, 0.81 to
0.90) and 0.92 mm (CI, 0.78 to 1.05), respectively. In a multiple
regression analysis, with adjustment for age and gender, no
significant relationship was found between
IMTright and the presence of a right-sided plaque
or stenosis. Of subjects with an IMTright
IMTleft for patients with a plaque (n=76) or a
stenosis (n=25) on the same side was 0.98 mm (CI, 0.90 to
1.05) and 1.09 mm (CI, 0.95 to 1.23), respectively. After
adjustment for age and gender, there still was a significant
relationship between IMTleft and the presence of
a left-sided plaque (P=0.009) or stenosis
(P=0.002). Of subjects with an IMTleft
When the left and right sides were analyzed separately, a
correlation between IMT and presence of plaques/stenoses on the
ipsilateral side was found only on the left side. There was a side
difference, with thicker IMT on the left side in men but not in women.
A side difference between IMT on the left and right sides has been
described earlier,5 16 17 strongly suggesting
that this was not a chance finding. One proposed explanation has been
that atherosclerosis develops faster on the left side
because of the anatomic difference between the sides and thus different
shear stress conditions.5 The discrepancy between
men and women in the present study might be result from the fact
that men develop atherosclerosis at an earlier age than
women. IMT was generally larger in men than in women, an observation
also found in other studies of similar design in the age group 60 to 70
years4 17 18 but not in healthy subjects of lower
ages.9 13
The recent interest in ultrasonographic classification of different
plaque types are based on the increasing number of observations
demonstrating that stenoses caused by echolucent plaques are
more prone to embolization and development of ipsilateral hemispheric
symptoms than are echogenic plaques.2 3 In our
study echogenic plaques were more common than echolucent. However,
echogenic plaques were in general smaller than echolucent plaques;
thus, the latter caused significantly more stenoses. Whether
this is caused by bleeding into the plaque, more advanced disease with
more lipid depositions, or both remains unclear. The carotid arteries
with the thickest IM were those with type 2 plaques in the carotid
bifurcation, although the difference between IMT in the groups of
plaque morphology did not reach statistical significance. Type 2
plaques contain a mixture of calcification and a significant amount of
echolucent material, such as hemorrhage and/or
lipids.19 They can be classified as both
heterogenic and echolucent and might represent a more advanced
stage of atherosclerosis. Type 2 plaques causing
stenoses, but not type 2 plaques in general, were predominantly
left sided. Moreover, 5 of 7 carotid occlusions were found on the left
side. These observations support the hypothesis stated above regarding
side difference in the development of
atherosclerosis.
In our study of elderly patients (median age, 69 years), age was still
the most important factor for determining IMT. The strong correlation
between age and IMT has earlier been established in groups of
patients/subjects with mean ages of 40 to 50
years5 13 16 as well as in elderly
patients/subjects with mean ages of 60 to 70
years.4 17 18 Using the same technique and
equipment as in the present study, we found
IMTmean to be 0.56 mm in healthy subjects of
mean age 40 years without carotid plaques13
compared with 0.77 mm in plaque-free subjects of mean age 62 years
in the present study. Our estimated rates of progression of IMT for
patients with and without plaques (0.010 mm/y and 0.006 mm/y,
respectively) fits well with those documented in a recent
report.9 However, various progression rates are
given in the literature,17 20 highlighting the
importance of a standardized technique for IMT measurements to provide
better possibilities for the comparison of study
results.6 In the present study we used the
most common approach so far: measurement of the mean thickness over a
1-cm length of the far wall of the distal common carotid artery.
Veller et al9 described a plaque incidence in
carotid or femoral arteries of 95% if IMTmean
exceeded 0.8 mm in a group of symptom-free, healthy volunteers. In
our elderly and more diseased patient group, carotid plaques were found
in 68% of those with IMTmean
Regarding risk factors for cerebrovascular disease, we found an
independent relationship only between IMT and ischemic heart
disease, which might demonstrate that other common risk factors lose
some of their importance as age increases. A limitation of our study is
the lack of measurement of blood lipid levels and lack of adjustment
for smoking habits. It is, however, worth noting that a study by Fabris
et al21 showed that the association between risk
factors and carotid atherosclerosis decreased with age
and that a correlation between carotid atherosclerosis
and cholesterol levels and cigarette smoking existed in
younger but not in elderly subjects. The correlations between IMT and
ischemic heart disease and male gender found in our study fit
with the previously described observation of higher subsequent risk of
acute coronary events in males with increased
IMT.8
In conclusion, we found the IMT of the CCA to be correlated to
the degree of atherosclerosis in the carotid
bifurcations in general and on the left side also to local
atherosclerosis in the left carotid bifurcation.
Echogenic plaques in the carotid bifurcation were more common than
echolucent, but the latter caused significantly more stenoses
with a predominance of the left side. We found no correlation between
IMT and plaque echogenicity. Our results support earlier observations
that suggest faster development of carotid
atherosclerosis on the left than on the right side.
Received November 13, 1997;
revision received March 26, 1998;
accepted April 24, 1998.
© 1998 American Heart Association, Inc.
Original Contributions
Relationship Between Intima-Media Thickness in the Common Carotid Artery and Atherosclerosis in the Carotid Bifurcation
Abstract
Top
Abstract
Introduction
Subjects and Methods
Results
Discussion
References
Background and Purpose—An increase
in intima-media thickness (IMT) in the common carotid artery (CCA) is
commonly used as a marker of atherosclerosis. The
purpose of this study was to investigate the relationship between IMT
in the CCA and atherosclerosis in the carotid
bifurcation.
Key Words: aging • atherosclerosis • carotid arteries • ultrasonography, Doppler
Introduction
Top
Abstract
Introduction
Subjects and Methods
Results
Discussion
References
One of the main
sources of cerebral thromboembolism is the carotid bifurcation.
Following cardiogenic embolism, it is the second largest cause of
stroke or transient ischemic attacks. Because the carotid
bifurcation is highly amenable to ultrasound imaging and Doppler
analysis, this technique (ie, duplex ultrasound) has
contributed significantly to our knowledge in this field. Recent
studies have shown that not only the degree of narrowing but also the
ultrasonographic appearance of the atherosclerotic plaque is of
importance in this respect.1 2 3
Subjects and Methods
Top
Abstract
Introduction
Subjects and Methods
Results
Discussion
References
Patients
All patients referred for carotid duplex scanning to the
Vascular Laboratory at the Department of Clinical Physiology at
Stockholm Söder Hospital during a 2-month period were entered in
a prospective study of carotid vessel wall disease approved by the
local ethic committee. Patients seen after carotid
endarterectomy (n=4) and those with poor
ultrasonographic recording quality with no clear delineation of
the intima-media complex (n=6) were excluded. Thus, a consecutive
series of 182 patients were included (90 men and 92 women; mean age, 67
[range, 37 to 88] years). One hundred fourteen patients (63%) were
referred from the Department of Neurology, 39 patients (21%) from
other departments within the hospital (mainly vascular surgery and
internal medicine), and 29 patients (16%) from physicians outside
the hospital.
Color duplex ultrasound scanning was performed with an Acuson
128XP with 5- or 7-MHz linear-array transducers. The carotid arteries
were scanned, and tape recordings were made of vessel walls and
blood flow velocities in all segments. A blood flow velocity >1.2 m/s
was used to define a stenosis with >50% lumen diameter
reduction.10 11 
statistics showed a good agreement
between these 2 analyses, with a weighted value of
0.75.15 The strength of agreement was slightly
better ( value, 0.80) when the comparison was restricted to only 2
groups (ie, echolucent 1 and 2 versus echogenic 3 and 4).
Data are presented as mean and 95% confidence interval
(CI). Paired or unpaired, 2-sided Student t tests were used
for comparison of IMT measures. When more than 2 groups were compared,
this was done with analyses of variance. If the F test
demonstrated a significant difference between the groups, each pair of
means was compared with the Duncan test. The 
2
test with Yates correction was used for comparison of proportions.
Regression or multiple regression analyses were used to
characterize relationships between variables. Statistical
significance was inferred at P<0.05.
Results
Top
Abstract
Introduction
Subjects and Methods
Results
Discussion
References
Intima-Media Measurements
IMT measurements are presented for each side separately
and as IMTmean (=right+left/2). IMT was
significantly larger on the left side compared with the right
(P<0.01). There was a positive linear relationship between
IMTmean and age (r=0.48; P<0.001).
The correlation between IMTmean and the presence
of risk factors for cerebrovascular disease was eliminated when age was
included in the regression analysis. When hypertension,
ischemic heart disease, and diabetes mellitus were tested
together with age in a multiple regression analysis, only
ischemic heart disease had an independent significant effect on
the thickness of the intima-media complex (P<0.05).
IMTmean was larger in men than in women
(P<0.01). The side difference with thicker intima-media on
the left side was seen only in men. The results are summarized in Table 1
.
View this table:
[in a new window]
Table 1. Intima-Media Thickness in the Distal Common Carotid
Artery Measured by Ultrasonography
Plaques were seen in 163 carotid bifurcations in 103 patients. In
45 of these bifurcations, the plaque caused a >50% stenosis
of the internal carotid artery, including 7 total occlusions. Echogenic
plaques (types 3 and 4; n=94) were more common than echolucent (types 1
and 2; n=57) (P<0.001). There was no significant side
difference regarding the occurrence of plaques or stenoses,
although 5 of 7 occlusions were left sided. Stenoses were more
frequently seen together with echolucent (24 of 57) than with echogenic
(14 of 94) plaques (P<0.001). In echolucent plaques but not
in echogenic, the stenoses were dominantly left sided
(P<0.05). Plaque morphology results are summarized in Table 2.
View this table:
[in a new window]
Table 2. Ultrasonographic Evaluation of Plaque Morphology
(Types 1–5) and Intima-Media Thickness in the Common Carotid Artery in
182 Patients (364 Carotid Bifurcations)
In a multiple regression model, only age, gender, and the presence
of stenosis on any side correlated independently with
IMTmean, thus explaining approximately 40% of
the IMT variance. The relative contribution of each variable is
shown in Table 3. There was no
relationship between plaque echogenicity and IMT. The highest IMT
values were seen in carotid arteries with heterogenic plaques (types 2
and 3). The same results were obtained if the analysis was
restricted only to plaques causing a stenosis (see Table 2
).
However, there was a wide overlap regarding IMT in the different groups
of plaque morphology, and ANOVA revealed no statistically significant
difference.
View this table:
[in a new window]
Table 3. Summary of Best Multivariate Model
for Prediction of Mean Intima-Media Thickness in the Common Carotid
Artery . Patients
with small plaques, ie, without stenoses, had thicker IM than
those without plaques (P<0.05), and thinner IM than those
with larger plaques causing stenoses (P<0.001). Of
subjects with an IMTmean 
0.8 mm, 68% had
plaques and 31% had stenoses in at least one of the carotid
bifurcations (Table 4).
View larger version (19K):
[in a new window]
Figure 1. Mean intima-media thickness (mean and 1 SD) in the common
carotid arteries in patients without plaques in the carotid
bifurcations (open bar, n=79), in patients with plaques but no
stenoses (shaded bar, n=64), and in patients with
stenoses (filled bar, n=39). By ANOVA: F=20.6,
P<0.001.
View this table:
[in a new window]
Table 4. Number of Subjects with Plaques and Stenoses
in the Carotid Bifurcation in Relation to the Mean Intima-Media
Thickness of the Right and Left Common Carotid Arteries
(IMTmean) 0.8 mm, 55% had a plaque and 12% had a stenosis in the
right carotid bifurcation (Table 5).
View this table:
[in a new window]
Table 5. Number of Subjects With Plaques and Stenoses
in the Right Carotid Bifurcation in Relation to the Intima-Media
Thickness of the Right Common Carotid Artery (IMTright) 0.8 mm, 53% had a plaque and 20% had a stenosis in the
left carotid bifurcation (Table 6).
View this table:
[in a new window]
Table 6. Number of Subjects With Plaques and Stenoses
in the Left Carotid Bifurcation in Relation to the Intima-Media
Thickness of the Left Common Carotid Artery (IMTleft)
Discussion
Top
Abstract
Introduction
Subjects and Methods
Results
Discussion
References
In this study of carotid artery wall disease we focused our
attention on the thickness of the intima-media complex in the CCA and
the morphological appearance of atherosclerotic plaques in the carotid
bifurcation. Our results show a correlation between
IMTmean in the CCA and the occurrence of plaques
and/or stenoses in any of the bifurcations, with the thickest
IM in those with more advanced atherosclerosis in the
carotid bifurcations. 0.8 mm and
in 86% of those with IMTmean 1 mm.
Plaques in the femoral arteries might explain this difference.
Acknowledgments
This study was supported by grants from the Karolinska Institute
and from local funds at Stockholm Söder Hospital.
References
Top
Abstract
Introduction
Subjects and Methods
Results
Discussion
References
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