966
Risk Factors for Early Carotid Atherosclerosis
in Middle-Aged French Women
Claire Bonithon-Kopp, Pierre-Yves Scarabin, Anne Taquet, Pierre-Jean Touboul,
Alain Malmejac, and Louis Guize
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The prevalence of carotid atherosclerosis and of its risk factors was examined in 517 apparently
healthy French women, aged 45-54 years. Early phases of carotid atherosclerosis were assessed
by B-mode ultrasonography. An intimal-medial thickening was found in 30.4% of the women
and atheromatous plaques in 8.7%. The prevalence rate of carotid atherosclerosis increased
with age, smoking, and postmenopausal status. However, after adjustment for the effect of age,
postmenopausal women did not have more atherosclerotic lesions than did premenopausal
women. No significant associations were found between carotid atherosclerosis and triglyceride,
apolipoprotein A-I, body mass index, blood glucose, fibrinogen, plasma viscosity, or hematocrit.
The mean age-adjusted levels of total cholesterol, low density lipoprotein cholesterol, apolipoprotein B, and systolic and diastolic blood pressures significantly increased with the severity of
carotid atherosclerosis, whereas high density lipoprotein cholesterol significantly decreased.
Multiple regression analysis showed that age, smoking, high density lipoprotein cholesterol, low
density lipoprotein cholesterol (or apolipoprotein B), and systolic (or diastolic) blood pressure
were significantly and independently related to the severity of carotid atherosclerosis. In
conclusion, the association of early carotid lesions with major cardiovascular risk factors
suggests that carotid atherosclerosis may be used as a marker of the general atherosclerotic
process. (Arteriosclerosis and Thrombosis 1991;ll:966-972)
A lthough risk factors for stroke have been exten/ \
sively investigated, relatively few studies
.Z A . have related risk factors to atherosclerosis of
the extracranial and/or intracranial arterial system.
Some of these studies are autopsy studies whose
results, obtained for populations that were not randomly selected, may be difficult to generalize.1 Most
other studies are angiographic or ultrasound studies
of patients or other highly selected populations,
providing information about quite advanced atherosclerotic lesions of the intracranial and/or extracranial arteries.2-17 In addition, few studies included
women, and generally the small sample size of these
studies does not allow examination of the specific risk
factors for atherosclerosis in women. The recent
availability of noninvasive procedures such as highFrom the Unite de Recherche d'Epidemiologie Cardiovasculaire (C.B.-K., P.-Y.S.,), INSERM U 258, Hopital Broussais,
ANVAS (A.T., P.-J.T.), and the Centre d'Investigations PreCltniques de Paris (A.M., L.G.), Paris.
Supported in part by grants from the Laboratoires Hoechst, the
Caisse Nationale d'Assurance-Maladie des Travailleurs Salaries
(CNAMTS), and the Association des Societes d'Assurance pour la
Prevention en Matiere de Sante (APMS), Paris.
Address for correspondence: Claire Bonithon-Kopp, MD, PhD,
Unite de Recherche d'Epidemiologie Cardiovasculaire, INSERM
U 258, Hopital Broussais, 96 rue Didot, 75674 Paris, France.
Received June 12, 1990; revision accepted March 12, 1991.
resolution B-mode ultrasonography allows the detection of minimal lesions of the arterial wall without
hemodynamic disturbances in subjects from the general population. The investigation of the risk factors
for early atherosclerosis may lead to a better understanding of the pathogenesis of atherosclerosis and
may provide new insight on strategies for early prevention of atherosclerosis in the population.
Thus, the present study examines the risk factors
for early carotid atherosclerosis assessed by highresolution B-mode ultrasonography in a population
of apparently healthy middle-aged French women.
Methods
Population
The study population consisted of apparently
healthy Caucasian women who volunteered for a
standard health checkup. Under the French Social
Security System, all members are entitled to a free
checkup every 5 years. Women who requested a
checkup at the Centre d'Investigations Pre-Cliniques
de Paris were invited to participate in the study if
they were aged 45-54 years, born in France, and gave
an informed consent to further clinical and biologic
investigations. The proportion of women who refused
to participate was very low (=5%). During their visit,
history of coronary heart disease and diabetes, smok-
Bonithon-Kopp et al Risk Factors for Early Atherosclerosis
ing habits, sex hormone use, and menopausal status
were obtained by standardized self-administered
questionnaire. Women were classified as smokers if
they smoked at least one cigarette per day and as
nonsmokers if they had never smoked or had stopped
smoking at the time of the examination. They were
considered premenopausal if they had menstruated
within the last 3 months. They were considered
postmenopausal if their menopause was surgically
induced (bilateral oophorectomy and/or hysterectomy) or if the menses had ceased naturally for at
least 6 months before the examination. Blood pressure was measured with a sphygmomanometer in the
supine position after a 10-minute rest. The body
mass index was computed as weight (kg) divided by
height squared (m2).
Ultrasonographic Evaluation of the Carotid Arteries
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The ultrasonographic evaluation of the carotid
arteries was made in 517 women free of coronary
heart disease and diabetes who were consecutively
recruited between January 1988 and November 1989.
B-mode ultrasound imaging with 7.5-MHz transducers having an axial resolution of 0.5 mm was performed by a single trained physician. Subjects were
examined in the supine position. The study protocol
entailed scanning the carotid bifurcations and the
near and far walls of the right and left common
carotid arteries (CCAs) in their mid and distal portions. The carotid bifurcation was defined on a
longitudinal B-mode scan as the intermediate portion between the distal part of the CCA and the
origins of the internal carotid artery (ICA) and the
external carotid artery (ECA). The increasing diameter of the distal part of the CCA served as a
landmark for the proximal limit of the carotid bifurcation. Lines drawn through the tip of the flow
divider perpendicular to the axes of both the ICA
and the ECA served as distal limits of the carotid
bifurcation. All measurements were made at the time
of scanning with the instrument's electronic calipers
to the nearest 0.25 mm. Two types of lesions were
noted by the physician: intimal-medial thickening
and atheromatous plaque.
Measurement of intimal-medial thickening. The intimal-medial thickness was measured on a longitudinal
B-mode scan of the mid CCA. Only the far wall was
considered. The midportion of the CCA was chosen
because of its parallelism with the axis of the neck. Its
B-mode scan pattern is characterized by two
echogenic lines separated by a hypoechoic or anechoic
space. The outer line corresponds to the medialadventitial interface, and the inner line corresponds to
the luminal-intimal interface. Thus, the distance between the two parallel lines represents the intimalmedial thickness.18 Previous studies showed that the
mean intimal-medial thickness of the CCA assessed
by B-mode ultrasonography in normal subjects was
about 0.50 mm.1819 The distribution of intimal-medial
thickness in these studies led us to consider the
arterial wall thickness as abnormal if it was greater
967
TABLE 1. Categories of Carotid Atherosclerosis
Categories
Definitions
Normal
(coded as 0)
Arterial wall thickness of the mid CCA
<0.75 mm
No plaques on the CCA and carotid
bifurcation
Intimal-medial
thickening
(coded as 1)
Arterial wall thickness of the mid CCA
>0.75 mm
No plaques on the CCA and carotid
bifurcation
Plaque
(coded as 2)
Echostructure encroaching into the
lumen of the CCA and/or carotid
bifurcation with thickness >1.75 mm
With or without intimal-medial
thickening of the mid CCA
CCA, common carotid artery.
than or equal to 0.75 mm. Because curved interfaces
do not reflect the ultrasound perpendicularly, the
ultrasonographable interfaces are less sharp in the
carotid bifurcation. Thus, no attempt was made to
measure the intimal-medial thickening at this site.
Measurement of plaque thickness. The mid CCA,
distal CCA, and carotid bifurcation of both sides
were scanned. Measurement of plaque thickness was
generally made on longitudinal B-mode scans. Transverse B-mode scans were used only if they provided a
better visualization of plaque than did the longitudinal B-mode scans (plaques of the anterior wall). A
localized echo structure encroaching into the vessel
lumen was considered to be a plaque if the distance
between the medial-adventitial interface and the
internal side of the lesion was greater than or equal
to 1.75 mm. In view of the characteristics of our
B-mode system, we chose a cut point of 1.75 mm to
avoid any confusion with an intimal-medial thickening, especially in the carotid bifurcation.
Categories of carotid atherosclerosis. As shown in
Table 1, the severity of carotid atherosclerosis was
graded into three categories: normal, intimal-medial
thickening (when no other lesion was noted in the CCA
and the carotid bifurcation), and plaque. The interobserver reproducibility of the severity of carotid atherosclerosis was assessed in 24 subjects who were hospitalized either for vascular or orthopedic rehabilitation.
None had any history or symptoms of cerebrovascular
disease. The patients were scanned by two independent
observers 1 day apart (one of these observers also
performed the B-mode scans in the population study).
A single B-mode scan reading was made by each
observer at the time of scanning, K Statistics were used
to assess the interobserver reproducibility. The K coefficient was 0.62, indicating that agreement between the
two observers was substantial (95% confidence interval,
0.35-0.89; p<0.001).
Biologic Measurements
Blood samples were drawn from each subject between 9 AM and 12 PM. Total cholesterol, triglyceride,
968
Arteriosclerosis and Thrombosis Vol 11, No 4 July/August 1991
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and glucose were assayed enzymatically on a Hitachi
737 Analyzer (Boehringer Mannheim GmbH, Mannheim, FRG). High density lipoprotein (HDL) cholesterol was measured enzymatically after precipitation
with phosphotungstic acid and Mg2"1" ions, a method
selected by the lipids-lipoproteins commission of the
French Society of Clinical Biology.20 Low density
lipoprotein (LDL) cholesterol was computed with the
Friedewald formula.21 Apolipoproteins (apos) A-I
and B were assayed with an immunonephelometric
fixed-time method on a Behring nephelometric analyzer (Behringwerke AG, Marburg, FRG) with Behring antisera and standards. Citrated platelet-poor
plasma was used to measure plasma fibrinogen according to the method of von Clauss.22 Plasma viscosity was measured in duplicate by the Myrenne
capillary viscosimeter. Most determinations were
performed daily. Plasma samples for determinations
of apolipoproteins were stored at 4°C until assay
within a week, and those for determinations of
plasma viscosity were stored at -180°C until assay
within 2 weeks. The majority of women had fasted,
but 15% of them had taken a light continental breakfast (without milk, butter, and sugar) before blood
collection. No significant differences in blood glucose
or blood lipids were seen between fasting and nonfasting blood samples except for HDL cholesterol, which
was slightly increased in nonfasting women. However,
as the inclusion of these women did not alter the
relations between the biologic variables and carotid
atherosclerosis, statistical analysis was performed on
data from the whole population.
Statistical Analysis
Standard procedures from Statistical Analysis Systems (SAS, Cary, N.C.) were used for univariate and
multivariate analyses. Mean age-adjusted levels of
cardiovascular risk factors according to the three
classes of carotid atherosclerosis were obtained by
analysis of covariance and significance tests from
logistic regression. The independent associations between the severity of atherosclerosis and the cardiovascular risk factors were tested with multiple logistic
regressions in which a three-class severity of carotid
atherosclerosis was introduced as a dependent variable and the cardiovascular risk factors were introduced as independent variables (either quantitative
or dichotomous variables). Probability values lower
than 0.05 were considered significant.
Results
The prevalence rates for intimal-medial thickening and plaques in women aged 45-54 were 30.4%
and 8.7%, respectively. Only 60.9% of the women
were free of any carotid lesions. Ninety-five percent
of the atheromatous plaques were located at the
carotid bifurcations and only 4.5% at the CCAs.
Fifteen percent of the women with plaques had
bilateral atheromatous lesions. As shown in Figure 1,
the prevalence rate of all types of carotid lesions
significantly increased with age; two thirds of the
p<0.001*
H
Normal
PH Thickening
•
45 • 49 years
Plaque
50 - 54 years
FIGURE 1. Bar graph of prevalence rates (%) of carotid
atherosclerosis according to age in 517 middle-aged French
women *by logistic regression of a three-class severity of
carotid atherosclerosis (normal, thickening, and plaque) on
age (45-49-year age group coded as 0 and 50-54-year age
group coded as 1).
women had no carotid lesions in the 45-49-year age
group, whereas it was the case for only half the
women in the 50-54-year age group. The significant
positive association between smoking and the severity of atherosclerosis is shown in Figure 2. After
controlling for the effect of age (as a continuous
variable) in multiple logistic regression, this association became highly significant (p< 0.004). The prevalence rate for carotid lesions was also significantly
higher in postmenopausal women than in premenopausal women (see Figure 3). However, the association between menopausal status and the severity of
atherosclerosis was no longer significant after adjustment for age. Similar results were found after exclusion of women who had received sex hormones. No
p=0.046*
H
Normal
i^i Thickening
•
Plaque
= 30
Non - Smokers
Smokers
FIGURE 2. Bar graph of prevalence rates (%) of carotid
atherosclerosis according to smoking categories *by logistic
regression of a three-class severity of carotid atherosclerosis
(normal, thickening, and plaque) on smoking categories.
Bonithon-Kopp et al
•
Normal
[Hi Thickening
I
60
Independent variables
I Plaque
50
40
2
969
TABLE 3. Multiple Logistic Regression of Severity of Carotid
Atherosclerosis on Major Cardiovascular Risk Factors
p-= 0.049*
70
Risk Factors for Early Atherosclerosis
30
Regression
coefficient
SEM
p value
Systolic blood pressure
0.020
0.005
0.001
Age
0.128
0.034
0.001
Smoking
0.531
0.199
0.008
LDL cholesterol
0.005
0.002
0.031
HDL cholesterol
-0.014
0.006
0.033
LDL, low density lipoprotein; HDL, high density lipoprotein.
20
10
Premenopause
Postmenopause
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FIGURE 3. Bar graph of prevalence rates (%) of carotid
atherosclerosis according to menopausal status *by logistic
regression of a three-class severity of carotid atherosclerosis
(normal, thickening, and plaque) on menopausal status,
which could be defined in 478 women.
significant associations were observed with logarithmically transformed triglyceride, apo A-I, blood glucose, body mass index, fibrinogen, plasma viscosity,
and hematocrit values. Table 2 shows the mean
age-adjusted levels of the major cardiovascular risk
factors according to the severity of carotid atherosclerosis. Total cholesterol, LDL cholesterol, apo B,
and systolic and diastolic blood pressures significantly increased after adjustment for age, whereas
HDL cholesterol significantly decreased with the
severity of carotid atherosclerosis. The decrease in
apo A-I in women with atherosclerotic lesions was
only of borderline significance after adjustment for
age, whereas the rise in fibrinogen in these women
did not reach the significance level. The independent
associations between carotid atherosclerosis and age,
systolic blood pressure, smoking, HDL cholesterol,
or LDL cholesterol were examined in a five-variable
logistic model presented in Table 3. All variables
independently contributed to the prediction of the
severity of carotid atherosclerosis. The strongest predictors were age and systolic blood pressure. Similar
results were obtained when apo A-I and apo B were
introduced in the regression model instead of HDL
cholesterol and LDL cholesterol (p<0.077 for apo
A-I, p< 0.022 for apo B). The substitution of diastolic
blood pressure (/?<0.0011) for systolic blood pressure did not change the results.
Discussion
The prevalence of carotid atherosclerosis is not
well documented in the general population, particularly in women. Until noninvasive procedures were
developed, ethical considerations prevented any investigation of the carotid arteries in healthy subjects.
Most of the previous studies were performed either
in subjects with symptoms of cerebral ischemia or
other vascular disease or in subjects at high risk for
ischemic arterial disease. Moreover, they used different methods to assess carotid atherosclerotic lesions, which makes comparisons between them diffi-
TABLE 2. Age-Adjusted Lipids, Lipoproteins, and Other Cardiovascular Risk Factors According to Severity of
Carotid Atherosclerosis
Variables
Normal
(i=315)
Carotid atherosclerosis
Thickening
(« = 157)
Plaque
(n=45)
p value*
218.6±2.2
68.6±0.8
136.3±2.0
170.8±1.4
107.6±1.5
225.5±3.1
65.2±1.2
145.6±2.8
167.9±2.0
115.6±2.1
226.5±5.8
64.2±2.2
148.9+5.3
165.4+3.7
116.0±4.0
0.047
0.006
0.002
0.093
0.002
126.8±0.9
82.2+0.6
305.3±3.1
132.8±1.3
85.8±0.8
310.9±4.4
132.9±2.3
85.6±1.6
311.9+8.4
0.001
0.001
0.271
Lipids and lipoproteins
Total cholesterol (mg/dl)t
HDL cholesterol (mg/dl)
LDL cholesterol (mg/dl)
Apolipoprotein A-I (mg/dl)
Apolipoprotein B (mg/dl)
Other risk factors
Systolic blood pressure (mm Hg)
Diastolic blood pressure (mm Hg)
Fibrinogen (mg/dl)
Values are mean±SEM.
HDL, high density lipoprotein; LDL, low density lipoprotein.
'Significance tests obtained from logistic regression with the three-class severity of carotid atherosclerosis as the
dependent variable and age and each cardiovascular risk factor as independent variables.
tTo convert cholesterol into millimoles per liter, multiply values by 0.026.
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cult. The prevalence rates and the clinical and
biologic determinants of carotid atherosclerosis assessed by B-mode ultrasonography have not yet been
investigated in healthy women.
The prevalence rates of early carotid lesions were
relatively high in these apparently healthy women
aged 45-54. Because the study subjects were recruited among volunteers, the generalization of our
results to other female populations should be applied
with caution. Although the participation rate was
very high, we cannot exclude a self-selection bias
leading to an overrepresentation of women at high
risk of cardiovascular disease. On the other hand,
women who voluntarily have a health checkup are
known to have a high socioeconomic status and to
pay great attention to their health; therefore, an
underrepresentation of high-risk women is also possible. However, the percentage of women with atheromatous plaques of the carotid arteries (8.7%) was
comparable to that found in another study. Among
66 women of the same age range referred to a
neurological clinic in Paris for a general checkup or
symptoms usually unrelated to cerebrovascular disease, 13.6% presented minimal plaques with a less
than 15% diameter reduction at the ultrasound examination that included continuous-wave Doppler
and duplex scanning.23 Women with intimal-medial
thickening were considered to have normal carotid
arteries. None had stenosis of 15-50% diameter
reduction, which is not surprising given the small
sample size.
The present study shows that the major coronary
risk factors, that is, age, blood pressure, cigarette
smoking, and blood lipid and lipoprotein levels, are
independently associated with early phases of carotid
atherosclerosis. Women with intimal-medial thickening also have a higher risk profile than do women
without any lesions. Although risk factors for symptomatic cerebrovascular disease have been extensively investigated, relatively few studies have related
these risk factors to carotid atherosclerosis in populations including women.2-17 These studies largely
differ in the type of population and methods used to
assess carotid atherosclerosis, which makes comparisons difficult. Angiography can be used only in highly
selected populations, whereas ultrasonography allows the study of healthy subjects as well as symptomatic patients. Whereas angiography and pulsewave Doppler sonography measure arterial stenosis,
B-mode ultrasonography measures the arterial wall
thickness and thus is capable of detecting early
atheromatous lesions before they induce disturbed
flow patterns.
Age and hypertension are the two factors that have
been most consistently associated with stroke24 and
carotid atherosclerosis. High blood pressure (or hypertension) was found to be a risk factor for advanced carotid atherosclerosis in patients with symptomatic cerebrovascular disease examined either with
angiography24'6'910'1317 or with B-mode ultrasonography.15 It was also found in neurologically asymptom-
atic patients hospitalized for coronary angiography
examined with B-mode ultrasonography.1112 It has
also been reported that high systolic and diastolic
blood pressures were significantly associated with the
progression of angiographic arteriosclerotic lesions in
the carotid arteries.13 However, two ultrasonographic
studies performed with hypertensive subjects failed
to find any association between blood pressure and
carotid atherosclerosis.25'26 These negative findings
may be partly explained by the small variation of
blood pressure in hypertensive populations. However, the severity of carotid atherosclerosis assessed
with B-mode ultrasonography was not related to
blood pressure levels or duration of hypertension in a
randomly selected population sample of Finnish men
with a wide range of blood pressure.27 In contrast
with this latter study, the present work suggests that,
at least in women, increased blood pressure is a
strong predictor of early carotid atherosclerosis. It is
interesting to note that the increase in systolic or
diastolic blood pressure was still apparent in women
with intimal-medial thickening. The significance of
thisfindingis questionable. Whether increased blood
pressure is a cause or a consequence of the thickening of the arterial wall cannot be determined from
this cross-sectional study.
The relation of cigarette smoking with the risk of
stroke is not well established. However, a recent
meta-analysis suggested that there was a small increased risk in smokers and exsmokers compared
with that for nonsmokers.28 There is also some
evidence that cigarette smoking is positively associated with carotid atherosclerosis in patients with
symptomatic ischemic arterial disease, as based on
both angiographic 5 ' 61013 ' 17 and ultrasonographic 11121516 studies. In accordance with our results,
smoking is suggested to be an independent risk factor
for carotid atherosclerosis in healthy populations
examined either with B-mode27 or duplex14 ultrasonography. Smoking seems to be associated not only
with the presence or the severity of atheromatous
plaques but also with an increase in the intimalmedial thickness of the carotid arteries14 and with the
progression of the intimal-medial thickening.29
Although there is no clear evidence that blood
lipid levels are risk factors for clinical manifestations
of cerebral ischemia, studies linking total cholesterol
and/or lipoproteins to carotid atherosclerosis have
yielded more consistent results, as recently reviewed.30 Most studies performed in men and women
with symptomatic cerebrovascular disease or in
asymptomatic patients at high risk for vascular disease showed an association between an adverse lipid
profile and the prevalence or the severity of carotid
atherosclerosis assessed by angiography3'6'9'10'13 or
ultrasonography.7'81112 One study, however, failed to
find any differences in plasma lipids and lipoproteins
in patients with angiographically documented carotid
atherosclerosis compared with those without atherosclerotic lesions.2 Only two ultrasonographic studies
have examined the relation between plasma lipid
Bonithon-Kopp et al Risk Factors for Early Atherosclerosis
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concentration and carotid atherosclerosis in apparently healthy male populations. One of them found
that men with carotid stenosis measured by multigate
pulsed Doppler had lower HDL to total cholesterol
ratios than did men without carotid stenosis.31 The
other study showed that LDL cholesterol but not
HDL cholesterol was significantly associated with the
degree of carotid atherosclerosis assessed by B-mode
ultrasonography.27 Our results indicate that, at least
in women, both HDL and LDL cholesterol are
independent risk factors for early carotid atherosclerosis but are less powerful predictors than other risk
factors such as age, smoking, or blood pressure.
Although apolipoproteins have been reported to be
more strongly associated with coronary atherosclerosis than are lipoproteins,32 few data are available with
respect to carotid atherosclerosis. One study of 30
men and women with familial hypercholesterolemia
showed that the severity of carotid stenosis assessed
by duplex ultrasonography was positively associated
with LDL cholesterol and apo B and negatively with
HDL cholesterol and apo A.8 Our study suggests that
apolipoproteins and lipoproteins show a similar pattern of associations with the carotid lesions. Apolipoproteins do not seem to improve the prediction of
carotid atherosclerosis.
The present study failed to find any significant
associations between the severity of carotid atherosclerosis and body mass index, triglyceride, blood
glucose, hemorheological parameters, and menopausal status. Fibrinogen is a strong predictor of
myocardial infarction and stroke in men,33-36 and it
has been reported to be a risk factor for myocardial
infarction but not for stroke in women.36 Its relations
with carotid atherosclerosis are somewhat conflicting. In one angiographic study of subjects with symptomatic cardiovascular disease, fibrinogen was associated with the presence of atheroma at the carotid
bifurcation but not with its progression within 2
years.13 On the other hand, fibrinogen was no longer
significantly related to B-mode carotid lesions in
healthy Finnish men after adjustment for the other
cardiovascular risk factors.27
The role of the menopause on the incidence of
cardiovascular disease is debated.37-38 A better
knowledge of the menopausal effects on the atherosclerotic process may help clarify the situation. Our
study suggests that menopause has little influence on
the development of carotid atherosclerotic lesions.
However, menopause may act as a promoting factor
for atherosclerotic lesions in other arterial sites. It
has been reported that aortic atherosclerosis diagnosed by radiographic detection of calcified deposits
in the abdominal aorta is more common in postmenopausal women than in premenopausal women, even
after adjustment for other cardiovascular risk factors.39 It is clear that further ultrasonographic studies
are needed to ascertain the menopausal effects on
early atherosclerosis in various arterial sites.
Our failure to find any significant association between carotid atherosclerosis and menopausal status
971
or some biologic risk factors may also be due to a lack
of statistical power. There is, especially, some variability in assessing atherosclerotic lesions with
B-mode ultrasonography. In the present study the
interobserver reproducibility of the severity of carotid atherosclerosis (in three classes) assessed in a
small group of patients was 0.62. Sources of variability also exist in the interpretation of the B-scans.40 A
previous study reported that the between-reader
agreement ranged from 0.34 for the ECA to 0.65 for
the ICA, and the within-reader agreement ranged
from 0.64 for the ECA to 0.73 for the ICA. In a few
cases, our B-mode scans might have been of poor
quality either because of anatomic characteristics or
because of obesity. Thus, it is likely that misclassifications have occurred in some instances, resulting in
an underestimation of the actual relation of the
severity of atherosclerosis to risk factor levels.
Despite these limitations, B-mode ultrasonography
represents a unique tool to detect minimal changes of
the arterial wall in population studies. Until now, little
has been known about the anatomic basis and the
clinical relevance of an intimal-medial thickening. An
increase in the arterial wall thickness was found in
hypercholesterolemic subjects compared with controls.19 A population-based study showed that age,
LDL cholesterol, smoking, blood leukocyte count, and
platelet aggregability were the strongest predictors of
the progression of the intimal-medial thickening
within 2 years in men.29 In the present study, the
high-risk profile found in women with intimal-medial
thickening suggests that arterial wall thickening may
be the early phase of the atherosclerotic process. Its
later development in atheromatous plaques needs to
be confirmed in longitudinal studies.
In conclusion, B-mode ultrasonography may be a
useful method to detect early atherosclerotic lesions
and to monitor their progression in a general population. Whether early carotid atherosclerosis may be
relevant to clinical manifestations of ischemic arterial
disease deserves further investigation.
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KEY WORDS
atherosclerosis
cardiovascular risk factors
epidemiology • women
carotid
Risk factors for early carotid atherosclerosis in middle-aged French women.
C Bonithon-Kopp, P Y Scarabin, A Taquet, P J Touboul, A Malmejac and L Guize
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Arterioscler Thromb Vasc Biol. 1991;11:966-972
doi: 10.1161/01.ATV.11.4.966
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