© 2000 American Heart Association, Inc.
Atherosclerosis and Lipoproteins |
Common Carotid Intima-Media Thickness Predicts Occurrence of Carotid Atherosclerotic Plaques
Longitudinal Results From the Aging Vascular Study (EVA) Study
From the National Institute of Health and Medical Research (INSERM) Unit 258 (M.Z., P.D., D.C.), INSERM Unit 360 (C.B.), Centre de Diagnostic et de Prévention Neurovasculaire (P.-J.T.), Paris; Registre Bourguignon des Cancers Digestifs (C.B.-K.), Dijon; and Centre d’examen EVA-INSERM (C.M.), Nantes, France.
Correspondence to Mahmoud Zureik, MD, PhD, INSERM U 258, Hôpital Paul Brousse, 16 av. Paul Vaillant Couturier, 94807 Villejuif Cedex, France. E-mail zureik{at}vjf.inserm.fr
 |
Abstract |
|---|
 Top Abstract IntroductionMethodsResultsDiscussionReferences |
|---|
Abstract—The role of the increase in the common carotid artery (CCA) intima-media wall thickness (IMT) in the atherosclerotic process is questionable. This longitudinal study examined the predictive value of CCA-IMT measured at baseline examination (at sites free of plaques) on the occurrence of atherosclerotic plaques in the extracranial carotid arteries during 4 years of follow-up study in a sample of 1010 subjects aged 59 to 71 years. Ultrasound examinations were performed at baseline and 2 years and 4 years later. The occurrence of carotid plaques during follow-up was defined as the appearance of
1 plaque in previously normal
carotid segments and/or the appearance of new plaques in the carotid
segments that previously had plaques. Carotid plaque occurrence was
observed in 185 subjects (18.3%). Age- and sex- adjusted odds ratios
of carotid plaque occurrence were 2.66 (95% CI 1.58 to 4.46,
P<0.001) in subjects having intermediate baseline
CCA-IMT values (quartiles 2 and 3) and 3.67 (CI 2.09 to 6.44,
P<0.001) in those having the highest baseline CCA-IMT
values (quartile 4) compared with those having the lowest baseline
CCA-IMT values (quartile 1). Multivariate adjustment
for major cardiovascular risk factors did not alter the
results. These findings were observed for men and women as well as for
subjects with and without carotid plaques at baseline. This 4-year
longitudinal study shows that CCA-IMT predicts carotid plaque
occurrence in a large sample of relatively old subjects. It extends the
findings obtained from cross-sectional studies and suggests that
increased intima-media thickness might occur in an earlier phase of the
atherosclerotic process.
Key Words: carotid arteries • atherosclerosis • plaque • intima-media thickness • longitudinal studies
|
Introduction |
|---|
|
TopAbstractIntroductionMethodsResultsDiscussionReferences |
|---|
A growing number of epidemiological studies and clinical trials use common carotid artery (CCA) intima-media wall thickness (IMT), obtained by noninvasive high-resolution B-mode ultrasonography, as an early marker of systemic atherosclerosis.1 2 3 4 5 6 7 8 9 10 11 12 13 Good-quality images of the far wall of the straight part of the CCA are easy to obtain, and IMT can be reliably measured in nearly all subjects.14 15 Furthermore, increased CCA-IMT has been shown to be associated with the main cardiovascular risk factors,1 2 3 4 5 6 16 17 18 19 the presence of other localizations of atherosclerosis,20 21 22 23 24 and an increased risk of coronary heart disease (CHD) and stroke.25 26 27 28 29
However, the role of increasing CCA-IMT in the atherosclerotic process is questionable.30 CCAs are less prone to atherosclerosis than are carotid bifurcations (CBs) and internal carotid arteries (ICAs). Furthermore, varying degrees of association between CCA-IMT and of the extent and severity of coronary artery disease have been observed.30 31 32
One way to investigate the significance of increased IMT with regard to atherosclerosis is to study its relationship with confirmed atherosclerotic plaques in the same arterial system. Several cross-sectional studies have reported positive associations between CCA-IMT and the presence of plaques in the carotid arteries.19 33 34 35 36 37 38 In a previous investigation involving the Aging Vascular Study (EVA) study based on the baseline examination data, we also reported that higher CCA-IMT (measured at sites free of any discrete plaque) was related to locally detected atherosclerotic plaques in a large population of relatively aged subjects.6 However, cross-sectional results do not allow for the determination of the temporal sequence and the possible direction of the relationships that would permit prediction at the individual level. Longitudinal studies are thus needed. A possible association between CCA-IMT and the subsequent development of carotid atherosclerotic plaques could suggest that intimal-medial thickening might occur in an earlier phase of the atherosclerotic process and would provide an indirect validation for the use of increased CCA-IMT measurements as an early marker of atherosclerosis.
In the present investigation, based on the 4-year longitudinal data of the EVA study, we assessed the associations of CCA-IMT and carotid plaque occurrence during the follow-up in a population of 1010 subjects aged 59 to 71 years.
|
Methods |
|---|
|
TopAbstractIntroductionMethodsResultsDiscussionReferences |
|---|
Details of the EVA study have been reported previously.6 18 Briefly, the EVA study is a longitudinal study of cognitive and vascular aging. The initial study population was composed of volunteers aged 59 to 71 years who were recruited from the electoral rolls of the city of Nantes (western France). During the baseline visit, which took place between June 1991 and July 1993, high-resolution ultrasound examinations of the carotid arteries were performed in 1384 of the 1389 recruited subjects. Ultrasound examinations of the carotid arteries were repeated after 2 and 4 years. The study protocol was approved by the Comité d’Ethique du Center Hospitalier Universitaire du Kremlin-Bicêtre, and written informed consent was obtained from all participants.
Ultrasonography
Ultrasound examinations at baseline, at 2-year follow-up, and at
4-year follow-up were performed with the use of the Aloka SSD-650, with
a transducer frequency of 7.5 MHz. This system provides an axial
resolution of 0.30 mm. Acquisition, processing, and storage of
B-mode images were computer-assisted with software specially designed
for longitudinal studies (EUREQUA, France).39
Details of the protocol have been described elsewhere.6 18 At each examination, it involved scanning of the CCAs, of the CBs, and of the origin (first 2 cm) of the ICAs. All measurements were made by the sonographer at the time of examination (online), with accuracy of the electronic calipers of the instrument to the nearest 0.1 mm. The IMT was measured on the far wall of the mid and distal CCA as the distance between the lumen-intima interface and the media-adventitia interface40 by using an automated edge-detection algorithm. One transversal and 2 longitudinal measurements of IMT were completed on the right and left CCAs, and the mean of the 4 right and left longitudinal CCA-IMT measurements was used in the analysis. All measurements of CCA-IMT were made at a site free of any discrete plaques. No attempt was made to measure IMT in the CB-ICAs.
Near and far walls of all arterial segments (ie, CCA or
CB-ICA) were scanned longitudinally and transversally to assess the
presence of plaques. The presence of plaques was defined as localized
echo structures encroaching into the vessel lumen for which the
distance between the media-adventitia interface and the internal side
of the lesion was 1 mm. When a plaque was present, optimal
frozen images (1 longitudinal and 1 transversal view), showing the
plaque in its greatest thickness, were selected by the sonographer and
stored on an optical disk. When several plaques were present on the
same arterial segment, the number of plaques was
recorded, and examination was centered on the segment showing the
greatest encroachment into the lumen. In the absence of plaques, no
measurement was made in the CB-ICAs, but optimal frames (1 longitudinal
and 1 transversal) were selected and stored on the optical disk. For
each image stored at baseline or at the 2-year follow-up, a mask was
constructed. It consisted of recording the anatomic situation
of the investigated territory, the type of echographic cut, and the
orientation of the anterior lateral or posterior cuts of the ultrasound
beam in relation to the neck. The position of the head in the dorsal
decubitus position (30° or 60° toward the right or left) and the
inclination of the ultrasound bundle in relation to the neck axis were
also recorded. Using a mouse, the sonographer drew a characteristic
outline of the image frozen on the screen. Image and mask archiving
were separately stored on the optical disk.
At the 2-year examination, the sonographer recalled information from the corresponding optical disk, which had been defined at baseline examination on the right and left segments. The real-time echographic image and the fixed contours recorded during the baseline examination were superimposed upon the screen. The sonographer then produced a beam that coincided with the echographic and contour image. At the 4-year examination, masks constructed during the 2-year follow-up were recalled.
The same 4 sonographers performed ultrasound examinations at baseline, at the 2-year follow-up, and at the 4-year follow-up. For each subject, we attempted to have the 2-year and 4-year follow-up examinations performed by the sonographer who had performed the baseline examination. This was the case for 76% of the subjects.
Reproducibility of the scanning and reading procedures has been
reported elsewhere.6 Briefly, random subsamples of images
(n=81) of CCAs recorded by the 4 sonographers were sent for
measurements to a single expert sonographer (P.-J.T), who was not aware
of the measurement results obtained at the EVA Center. Agreement
between the 2 readings of CCA-IMT was good (correlation 0.82,
coefficient of variation 9.1%, mean absolute difference 0.06 mm,
and mean percent difference 8.9%). In a previous published study by
our group, it was shown that the intrasonographer and intersonographer
variabilities of CCA-IMT associated with the scanning procedure were
substantially reduced after using the repositioning functions of the
EUREQUA software.39 To study the reproducibility of plaque
detection, 75 baseline examination images of CB-ICA with plaques as
defined by the sonographers and 80 images of CB-ICA without plaques
were randomly chosen and sent to the expert sonographer to assess
blindly the presence or the absence of plaques. The 
coefficients
for agreement between the 2 readings were 0.86 for longitudinal views
and 0.91 for transverse views.
Medical History and Standard Biological Procedures
Medical information, obtained at baseline examination by a
standardized questionnaire, included demographic background,
occupation, medical history, drug use, and personal habits, such as
cigarette smoking. Self-reported personal history of myocardial
infarction or angina pectoris (personal history of CHD) was also
recorded. Subjects were classified as those who had ever smoked and
nonsmokers. Two independent measurements of systolic and
diastolic blood pressure were made with a digital
electronic tensiometer (SP9 Spengler) after a 10-minute rest, and the
mean value was used in the analysis. Subjects with
systolic blood pressure 160 mm Hg or
diastolic blood pressure 95 mm Hg and/or subjects
who were using antihypertensive drugs were considered to be
hypertensive.41 Subjects who were not hypertensive (as
defined above) and who had systolic blood pressure between 140
and 159 mm Hg or diastolic blood pressure between 90
and 94 mm Hg were considered to be borderline
hypertensive.41
Hypercholesterolemia was defined as total
cholesterol level 6.2 mmol/L (2.40 g/L) or use of
lipid-lowering drugs.42 Subjects who reported a medical
history of diabetes or use of antidiabetic drugs or who had a fasting
plasma glucose level 7.0 mmol/L (1.26 g/L) were considered to be
diabetic.43 Impaired fasting glucose was defined in
nondiabetic subjects as fasting plasma glucose levels of 6.1 to
6.9 mmol/L.43 Body mass index was computed as weight
(in kilograms) divided by squared height (in meters).
Data Analysis
The occurrence of carotid plaques during the follow-up (at
2-year examination or/and at 4-year examination) was defined as the
occurrence of 1 plaque in previously normal segments (thereafter
called "appearance of plaques") and/or the occurrence of new
plaques in segments that previously had plaques (thereafter called
"increase in plaque number"). Baseline CCA-IMT was used as a
continuous as well as a categorical variable. The CCA-IMT values
were divided into 3 categories according approximately to 25th and 75th
sex-specific values (quartile 1, quartiles 2 and 3, and quartile
4). The cutoff points were 0.575 mm and 0.750 mm for
men and 0.550 mm and 0.725 mm for women. The second and third
quartiles were considered together because a preliminary
analysis indicated that similar proportions of carotid plaque
occurrence were observed in these 2 categories.
Standard procedures from the Statistical Analysis System (SAS
Institute) were used for univariate and
multivariate analyses. Distributions of plaque
occurrence according to baseline cardiovascular risk
factors and CCA-IMT categories were compared by
2 tests. Baseline
cardiovascular risk factors considered in the
analysis were body mass index, smoking habits, hypertension,
hypercholesterolemia, diabetes, and personal
history of CHD. For multivariate analyses, we
used dichotomic multiple logistic regression models, with plaque
occurrence (yes, no) as the dependent variable and items that could
play a role in plaque prediction (baseline
cardiovascular risk factors and CCA-IMT categories) as
independent variables. We preferred to present logistic
regression rather than Cox regression results because the time of
plaque occurrence was largely imprecise (there were only 2 follow-up
examinations). Nevertheless, the patterns of results obtained by Cox
regression models were very similar to those obtained by logistic
regression (data available from the authors).
Multivariate-adjusted odds ratios (ORs) and 95% CIs of
plaque occurrence according to baseline CCA-IMT categories, independent
of baseline cardiovascular risk factors, were estimated
by a multivariate logistic regression model; the first
quartile, with the lowest values of CCA-IMT, was used as the
reference.
Subjects who were examined during the training period (between June and December 1991) were considered to have unreliable initial ultrasound examinations on the basis of interreader reproducibility studies and were systematically excluded from statistical analysis (n=235). Of the 1149 subjects with reliable baseline ultrasound measurements, 110 subjects (9.6%) did not participate in the follow-up survey, and 1039 subjects (90.4%) underwent at least 1 follow-up B-mode ultrasound examination (947 had 2 follow-up examinations, and 92 had only 1 follow-up examination). Twelve subjects with plaque in the common carotid arteries at baseline were excluded from analyses because an alteration of the arterial wall in the vicinity of a plaque is possible, and IMT was measured in the CCAs. Two subjects who underwent carotid artery surgery during follow-up and 15 subjects who apparently had regression of carotid plaque number during follow-up were also excluded from the analyses. Thus, the final sample was composed of 1010 subjects. At baseline, there were no differences between subjects who were ultimately included for analyses and those who did not participate in the follow-up survey regarding sex (59.7% versus 58.7% women, respectively; P=0.49), age (65.1±3.0 versus 64.9±3.0 years, respectively; P=0.45), and CCA-IMT (0.66±0.11 versus 0.67±0.13 mm, respectively; P=0.39). However, the prevalence of personal history of CHD (5.5% versus 10.4%, P=0.07) and that of carotid plaques at baseline (19.3% versus 30.2%, P=0.03) were lower in subjects who were included in the analyses versus those who were not. .
|
Results |
|---|
|
TopAbstractIntroductionMethodsResultsDiscussionReferences |
|---|
The number of subjects who had an occurrence of carotid atherosclerotic plaques during follow-up was 185 (18.3%). One hundred ninety-six subjects (19.3%) had carotid plaques at baseline examination. Higher plaque occurrence was observed in these subjects compared with those without plaques at baseline (33.2% versus 14.7%, respectively; P<0.001). Among subjects with carotid plaques at baseline, 27 (13.8%) had an appearance of plaques in previously normal segments, 28 (14.3%) had an increase in plaque number in segments that previously had plaques, and 10 (5.1%) had an appearance and an increase in plaque number. The plaque occurrence in each segment (left and right CCAs and CB-ICAs) is shown in Table 1
. No statistically significant
difference was observed between left and right sites. The number of
subjects with plaque occurrence in 1, 2, and 2 segments was 119, 63,
and 3, respectively.
|
Baseline age was positively associated with carotid plaque occurrence.
The OR of plaque occurrence associated with a 5-year increase in age
was 1.32 (CI 1.01 to 1.72, P<0.05). Men had higher plaque
occurrence than women (23.6% versus 14.8%, respectively;
P<0.001, OR 1.78, and CI 1.29 to 2.45). Hypertension,
hypercholesterolemia, and history of ever
having smoked were also associated with higher plaque occurrence (Table 2).
|
Baseline CCA-IMT and Carotid Plaque Occurrence During
Follow-Up
The distribution and ORs of carotid plaque occurrence associated
with quartiles of CCA-IMT are shown in Table 3. Age- and sex- adjusted ORs of carotid
plaque occurrence were 2.66 (CI 1.58 to 4.46, P<0.001) in
subjects having the intermediate baseline CCA-IMT values (quartiles 2
and 3) and 3.67 (CI 2.09 to 6.44, P<0.001) in those having
the highest baseline CCA-IMT values (quartile 4) compared with those
having the lowest baseline CCA-IMT values (quartile 1). After
adjustment for age, sex, hypertension,
hypercholesterolemia, diabetes, smoking, and
personal history of CHD, the ORs did not markedly change (Table 3). After further adjustment for the presence of carotid plaques
at baseline, the associations were attenuated but remained highly
significant (Table 3). These associations were
consistently observed in men and in women (Table 3).
|
When CCA-IMT was used as a continuous variable, multivariate ORs of plaque carotid occurrence associated with a 0.10-mm increase in CCA-IMT were 1.24 (CI 1.06 to 1.43, P<0.005) in all subjects, 1.23 (CI 1.02 to 1.51, P<0.05) in men, and 1.27 (CI 1.02 to 1.60, P<0.01) in women.
Significant associations between baseline CCA-IMT and carotid plaque
occurrence were observed in subjects with carotid plaque at baseline
and in those without (Table 4).
These associations were stronger in subjects with carotid plaque at
baseline, although the interaction terms were not statistically
significant.
|
In subjects with carotid plaque at baseline, the multivariate-adjusted mean of baseline CCA-IMT was not different between subjects who had an appearance of plaques in previously normal segments and those who had an increase in plaque number in segments that previously had plaques (0.70±0.25 versus 0.73±0.26 mm, respectively; P=0.41).
When we defined, a posteriori, the plaques as a localized protrusion of
the vessel wall into the lumen with a thickness of 1.2 mm (or
1.5 mm) instead of 1 mm, multivariate ORs
of plaque occurrence associated with quartile 1, quartiles 2 and 3, and
quartile 4 of CCA-IMT were 1, 2.25 (P<0.01), and 2.71
(P<0.0001), respectively, with use of a 1.2-mm cutoff
(n=166 for number of subjects who had plaque occurrence) and 1, 2.29
(P<0.01), and 3.15 (P<0.0001), respectively,
with use of a 1.5-mm cutoff (n=145).
|
Discussion |
|---|
|
TopAbstractIntroductionMethodsResultsDiscussionReferences |
|---|
Baseline CCA-IMT was an independent predictor of carotid plaque occurrence in this longitudinal study performed in a large sample of relatively aged subjects. The association of CCA-IMT with plaque occurrence was observed for men and women as well as for subjects with and without carotid plaques at baseline. In the EVA study, the magnitude of the longitudinal associations between CCA-IMT and carotid plaques (OR 1.24 for 0.10-mm increase in baseline CCA-IMT) was comparable to that previously reported in the cross-sectional analysis (OR 1.18).6
Several cross-sectional studies have reported positive associations
between carotid intima-media thickening and locally carotid
atheromatous plaques.6 19 33 34 35 36 37 38 Our
longitudinal results extend the findings of cross-sectional studies and
suggest that increased wall thickness may precede plaque formation. In
a previous longitudinal study conducted by our group that used less
sophisticated ultrasound methods, increased baseline CCA-IMT among 308
middle-aged women predicted the 2-year development of carotid
plaques.44 Compared with the previous study, the
present study was conducted in a far larger population with a
longer follow-up duration. More precise and more reliable
ultrasonographic assessments of IMT and plaque were obtained (for IMT
measurements, precision was to the nearest 0.10 mm instead of
0.25 mm, with use of mask and repositioning functions with
software specially designed for longitudinal studies). In addition,
only the presence or the absence of an intimal-medial thickening was
recorded by the sonographer in the previous study.44
In the EVA study, subjects with intermediate values of CCA-IMT,
compared with subjects with the lowest values, had a 2-fold risk of
developing carotid plaque (Table 3
), and the higher risk was not
limited to those with the highest values. These findings, if confirmed,
might provide new insight into strategies for very early prevention of
atherosclerosis in the population.
The associations of CCA-IMT with carotid plaque occurrence seemed to be more pronounced in subjects with plaques at baseline than in those without (although not having a plaque does not rule out the presence of plaque in nonvisualized segments of the carotid arterial bed). This could suggest that increased CCA-IMT is a more powerful marker of atherosclerosis in subjects with more advanced atherosclerosis. A longer period of follow-up might be needed for an increased wall thickness to predict plaque occurrence in subjects at an early step of atherosclerotic development.
An association between CCA-IMT and the development of carotid plaque does not necessarily imply that all components of increased CCA-IMT are due to atherosclerosis. First, the ultrasound technique is unable to differentiate the intimal from the medial layer, and the anatomic structure involved in the arterial wall thickening cannot be determined. Second, some intimal and medial hypertrophy could be considered to be a nonatherosclerotic adaptive response to aging and mechanical variations in the arteries.45 46 47 Third, some factors could be specifically associated with increased IMT alone or with plaque alone. In a recent report from the EVA study, we found that parental history of premature death from CHD was strongly associated with the presence of plaque in the extracranial carotid arteries but not with increased CCA-IMT.48 This suggests that heritable factors might be specifically involved in plaque formation but not in diffuse intima-media thickening.48
However, the fact that increased IMT and focal plaques share a number of common atherosclerotic risk factors suggests that they are dependent, at least in part, on the same physiopathological process. Increased IMT, rather than plaque formation, might then be an earlier response to this process. Indeed, adjustment for major cardiovascular risk factors did not modify our results, suggesting that the observed associations were largely independent of these factors, but it is obvious that a lot of unknown and, to a lesser extent, unmeasured factors are involved in the atherosclerotic process, and these factors could not be taken into account at present. For instance, low wall shear stress in the carotid arteries could be implicated as a possible common link between carotid intima-media thickening and focal plaques.49 50 51
Methodological Aspects
In the present study, we used a methodological approach that
clearly differentiates between diffuse intimal-media thickening and
plaque. IMT was measured in the mid and distal portions of the CCA on a
segment free of any focal atherosclerotic lesion, and the mean rather
than the maximum value of 4 measurements was used. Because of the
possible alteration of the arterial wall in the vicinity of
a plaque, we further excluded the few subjects who had plaques in the
CCA at baseline. Furthermore, after the exclusion of the 16 subjects
who developed plaques in the CCA during follow-up results were very
similar to those reported in the present study (data not shown).
Thus, increased IMT was likely to represent diffuse thickening
of the arterial wall rather than confirmed
atherosclerosis or eccentric thickening. IMT was
measured at the CCAs. B-mode ultrasound is a noninvasive technique that
can directly visualize and assess the wall thickness and plaque status
on several arterial segments of the carotid arteries.
However, there are large variations in IMT according to the
arterial site (ICA and CB show greater IMT than does
CCA21 52 53 ). Risk factors for
atherosclerosis and CHD were more strongly associated
with the ICA-IMT than with the CCA-IMT.54 Despite the
lesser atherosclerotic involvement of the CCA, it increasingly becomes
the site of choice for measurements of IMT. Assessment and
quantification of the IMT in the ICA and CB are far more difficult for
various technical and methodological reasons (eg, tortuosity, proximity
to the mandible, and reproducibility),53 and greater
reliability of IMT measurements from the common carotid arteries is
obtained.
Study Limitations
Our population consisted of an elderly sample of volunteers who
agreed to undergo follow-up examinations. The potential effects, on the
observed associations, of selective survival as well as self-selection
biases leading to an underrepresentation of diseased persons
could not be ruled out. In fact, the prevalence of carotid plaques at
baseline was lower than the prevalence observed in population-based
studies of aged subjects.21 38 In addition, a relatively
low prevalence of CHD at baseline was observed. The prevalence of CHD
in men and women aged 60 to 65 years was 2.5% and 9.1%, respectively,
compared with 3.7% and 13.1%, respectively, observed in the Third
French Monitoring Trends and Determinants in
Cardiovascular Disease Population Survey (P.
Ducimetière, personal communication, 1999). In spite of
the high participation rate in the follow-up survey (90%), subjects
who participated tended to have a lower prevalence of CHD and of
carotid plaques at baseline than did those who did not.
A selection bias due to the exclusion of the 15 subjects with apparent
regression of carotid plaque number might also have taken place.
However, the small number of these events, with some of them possibly
due to misclassification, prevents any adequate analysis. When
subjects with plaque regression were added to those without carotid
plaque occurrence, results were similar to those reported in Tables 3 and 4.
A definition of plaque as a localized protrusion of the vessel wall
into the lumen with a thickness of 1 mm was used in our
protocol. Although a similar cutoff value was also used by several
other investigations,55 56 57 58 59 one could argue that this
value is relatively low and that a minor wall irregularity may be
mistakenly considered as a plaque. We do not think that our liberal
definition of plaque could explain our findings. Results of the
reproducibility study for the presence (or the absence) of plaque were
satisfactory. In addition, reanalysis of our data by use of a
more restrictive definition of plaque thickness (1.2 or 1.5
mm) also showed a strong association between baseline CCA-IMT and the
occurrence of carotid plaques.
In conclusion, this 4-year longitudinal study shows that an increase in baseline CCA-IMT, measured at sites free of any discrete plaque, is associated with subsequent carotid plaque occurrence. Even if increased CCA-IMT and carotid plaque might be due, at least in part, to shared atherosclerotic risk factors, intima-media changes might be an earlier response to the atherosclerotic process. From a practical viewpoint, our results suggest that noninvasive B-mode ultrasonographic measurement of CCA-IMT could be considered a useful early marker of the development of the carotid atherosclerosis.
|
Acknowledgments |
|---|
The EVA study was organized with an agreement between INSERM and the Merck, Sharp and Dohme-Chibret Co. It is also supported by the EISAI Co (France). We thank the ultrasound physicians, Drs J.M. Fève, C. Leroux, and I. Ruelland. We acknowledge C. Delanoe and S. Bachelier for their secretarial and technical assistance at the EVA Center.
Received June 9, 1999; accepted November 25, 1999.
|
References |
|---|
|
TopAbstractIntroductionMethodsResultsDiscussionReferences |
|---|
1. Heiss G, Sharrett AR, Barnes R, Chambless LE, Szklo M, Alzola C. Carotid atherosclerosis measured by B-mode ultrasound in populations: associations with cardiovascular risk factors in the ARIC study. Am J Epidemiol. 1991;134:250–256.
2.
O’Leary DH, Polak JF, Wolfson SK, Bond MG, Bommer W,
Sheth S, Psaty BM, Sharrett AR, Manolio TA. Use of sonography to
evaluate carotid atherosclerosis in the elderly: the
Cardiovascular Health Study. Stroke. 1991;22:1155–1163.
3. Salonen R, Salonen JT. Determinants of carotid intima-media thickness: a population-based ultrasonography study in Eastern Finnish men. J Intern Med. 1991;229:225–231.[Medline] [Order article via Infotrieve]
4.
Bots ML, Breslau PJ, Briët E, de Bruyn AM, van
Vliet HHDM, van den Ouweland FA, de Jong PTVM, Hofman A, Grobbee DE.
Cardiovascular determinants of carotid artery disease:
the Rotterdam Elderly Study. Hypertension. 1992;19:717–720.
5.
Willeit J, Kiechl S. Prevalence and risk factors of
asymptomatic extracranial carotid artery
atherosclerosis: a population-based study.
Arterioscler Thromb. 1993;13:661–668.
6.
Bonithon-Kopp C, Touboul PJ, Berr C, Leroux C, Mainard
F, Courbon D, Ducimetière P. Relation of intima-media thickness
to atherosclerotic plaques in the carotid arteries: the EVA study.
Arterioscler Thromb Vasc Biol. 1996;16:310–316.
7.
Blankenhorn DH, Zelzer RH, Craxford DW, Barth JD, Liu
C, Mack WJ, Alaupovic P. Beneficial effects of colestipol-niacin
therapy on the common carotid artery two-and four-year reduction of
intima-media thickness measured by ultrasound. Circulation. 1993;88:20–28.
8.
Salonen R, Nyyssönen K, Porkkala E, Rummukainen
J, Belder R, Park JS, Salonen JT. Kuopio
Atherosclerosis Prevention Study (KAPS): a
population-based primary preventive trial of the effect of LDL lowering
on atherosclerotic progression in carotid and femoral arteries.
Circulation. 1995;92:1758–1764.
9. Zanchetti A. Trials investigating the anti atherosclerotic effects of antihypertensive drugs. J Hypertens. 1996;14:S77–S77.
10.
Hodis HN, Mack WJ, LaBree L, Selzer RH, Liu C, Kiu CH,
Alaupovic P, Kwong-Fu H, Azen SP. Reduction in carotid
arterial wall thickness using lovastatin and
dietary therapy a randomized, controlled clinical trial. Ann
Intern Med. 1996;124:548–556.
11.
Borhani NO, Mercuri M, Borhani PA, Buckalew VM,
Canossa-Terris M, Carr AA, Kappagoda T, Rocco MV, Schnaper HW, Sowers
JR, Bond MG. Final outcome results of the Multicenter Isradipine
Diuretic Atherosclerosis Study (MIDAS): a
randomized controlled trial. JAMA. 1996;276:785–791.
12.
MacMahon S, Sharpe N, Gamble G, Hart H, Scott J, Simes
J, White H. Effects of lowering average or below-average
cholesterol levels on the progression of carotid
atherosclerosis: results of the lipid
atherosclerosis substudy. Circulation. 1998;97:1784–1790.
13. Zanchetti A, Bond M. G, Hennig M, Neiss A, Mancia G, Dal Palù C, Hansson L, Magnani B, Rahn KH, Reid J, Rodicio J, Safar M, Eckes L, Ravinetto R. Risk factors associated with alterations in carotid intima-media thickness in hypertension: baseline data from the European Lacidipe Study on Atherosclerosis. J Hypertens. 1998;16:949–961.[Medline] [Order article via Infotrieve]
14. Smilde TJ, Wollersheim H, Van Langen H, Stalenhoef AF. Reproducibility of ultrasonographic measurements of different carotid and femoral artery segments in healthy subjects and in patients with increased intima-media thickness. Clin Sci. 1997;93:317–324.[Medline] [Order article via Infotrieve]
15. Bots ML, Mulder PG, Hofman A, van Es GA, Grobbee DE. Reproducibility of carotid vessel wall thickness measurements: the Rotterdam Study. J Clin Epidemiol. 1994;47:921–930.[Medline] [Order article via Infotrieve]
16.
Lassila HC, Sutton-Tyrrell K, Matthews KA, Wolfson SK,
Kuller LH. Prevalence and determinants of carotid
atherosclerosis in healthy postmenopausal women.
Stroke. 1997;28:513–517.
17.
Wendelhag I, Wiklund O, Wikstrand J.
Arterial wall thickness in familial
hypercholesterolemia: ultrasound measurement of
intima-media thickness in the common carotid artery. Arterioscler
Thromb. 1992;12:70–77.
18.
Zureik M, Touboul PJ, Bonithon-Kopp C, Courbon D, Berr
C, Leroux C, Ducimetière P. Cross-sectional and longitudinal
associations between brachial pulse pressure and common carotid
intima-media thickness in a general population: the EVA study.
Stroke. 1999;30:550–555.
19. Gnasso A, Irace C, Mattioli PL, Pujia A. Carotid intima-media thickness and coronary heart disease risk factors. Atherosclerosis. 1996;119:7–15.[Medline] [Order article via Infotrieve]
20.
Wofford JL, Kahl FR, McKinney WM, Toole JF, Crouse JR.
Relation of extent of extracranial carotid artery
atherosclerosis as measured by B-mode ultrasound to the
extent of coronary atherosclerosis.
Arterioscler Thromb. 1991;11:1786–1794.
21.
O’Leary DH, Polak JF, Kronmal RA, Kittner SJ, Bond MG,
Wolfson Jr SK, Bommer W, Price TR Gardin JM, Savage PJ. Distribution
and correlates of sonographically detected carotid artery disease in
the Cardiovascular Health Study. Stroke. 1992;23:1752–1760.
22. Bots Ml, Witteman JCM, Grobbee DE. Carotid intima-media thickness in elderly women with and without atherosclerosis of the abdominal aorta. Atherosclerosis. 1993;102:99–105.[Medline] [Order article via Infotrieve]
23. Gariepy J, Simon A, Massonneau M, Linhart A, Levenson J. Wall thickening of carotid and femoral arteries in male subjects with isolated hypercholesterolemia. Atherosclerosis. 1995;113:141–151.[Medline] [Order article via Infotrieve]
24.
Allan PL, Mowbray PI, Lee AJ, Fowkes GR. Relationship
between carotid intima-media thickness and symptomatic and
asymptomatic peripheral arterial
disease: the Edinburgh Artery Study. Stroke. 1997;28:348–353.
25.
Salonen JT, Salonen R. Ultrasonographically assessed
carotid morphology and the risk of coronary heart disease.
Arterioscler Thromb. 1991;11:1245–1249.
26.
Chambless LE, Heiss G, Folsom AR, Rosamond W, Szklo M,
Sharrett AR, Clegg LX. Association of coronary heart disease
incidence with carotid arterial wall thickness and major
risk factors: the Atherosclerosis Risk in Communities
(ARIC) Study, 1987–1993. Am J Epidemiol. 1997;146:483–494.
27.
Belcaro G, Nicolaides AN, Laurora G, Cesarone MR, De
Sanctis M, Incandela L, Barsotti A. Ultrasound morphology
classification of the arterial wall and
cardiovascular events in a 6-year follow-up study.
Arterioscler Thromb Vasc Biol. 1996;16:851–856.
28.
Bots ML, Hoes AW, Koudstaal PJ, Hofman A, Grobbee DE.
Common carotid intima-media thickness and risk of stroke and myocardial
infarction: the Rotterdam Study. Circulation. 1997;96:1432–1437.
29.
O’Leary DH, Polak JF, Kronmal RA, Manolio TA, Burke
GL, Wolfson JR. Carotid-artery intima and media thickness as a risk
factor for myocardial infarction and stroke in older subjects.
N Engl J Med. 1999;340:14–22.
30.
Adams MR, Nakagomi A, Keech A, Robinson J, McCredie R,
Bailey BP, Freedman SB, Celermajer DS. Carotid intima-media thickness
in only weakly correlated with the extent and severity of
coronary artery disease. Circulation. 1995;92:2127–2134.
31.
Geroulakos G, O’Gorman DJ, Kalodiki E, Sheridan DJ,
Nicolaides AN. The carotid intima-media thickness as a marker of the
presence of severe symptomatic coronary artery
disease. Eur Heart J. 1994;15:781–785.
32.
Hulthe J, Wikstrand J, Emanuelsson H, Wilkund O, de
Feyter PJ, Wendelhag I. Atherosclerotic changes in the carotid
artery bulb as measured by B-mode ultrasound are associated with the
extent of coronary atherosclerosis.
Stroke. 1997;28:1189–1194.
33. Veller MG, Fisher CM, Nicolaides AN, Renton S, Geroulakos G, Stafford NJ, Sarker A, Szendro G, Belcaro G. Measurement of the ultrasonic intima-media complex thickness in normal subjects. J Vasc Surg. 1993;17:719–725.[Medline] [Order article via Infotrieve]
34. Li R, Duncan BB, Metcalf PA, Crouse JR, Sharrett AR, Tyroler HA, Barnes R, Heiss G, for the Atherosclerosis Risk in Communities (ARIC) Study Investigators. B-mode–detected carotid artery plaque in a general population. Stroke. 1994;25:2377–2383.[Abstract]
35.
Persson J, Formgren J, Israelsson B, Berglund G.
Ultrasound-determined intima-media thickness and
atherosclerosis: direct and indirect validation.
Arterioscler Thromb. 1994;14:261–264.
36.
Suurküla M, Agewall S, Fagerberg B, Wendelhag I,
Widgren B, Wikstrand J. Ultrasound evaluation of atherosclerotic
manifestations in the carotid artery in high-risk patients.
Arterioscler Thromb. 1994;14:1297–1304.
37.
Rosfors S, Hallerstam S, Jensen-Urstad K, Zetterling M,
Carlström C. Relationship between intima-media thickness in the
common carotid artery and atherosclerosis in the
carotid bifurcation. Stroke. 1998;29:1378–1382.
38.
Ebrahim S, Papacosta O, Whincup P, Wannamethee G,
Walker M, Nicolaides AN, Dhanjil S, Griffin M, Belcaro G, Rumley A,
Lowe GDO. Carotid plaque, intima media thickness,
cardiovascular risk factors, and prevalent
cardiovascular disease in men and women: the British
Regional Heart Study. Stroke. 1999;30:841–850.
39. Touboul PJ, Prati P, Scarabin PY, Adrai V, Thibout E, Ducimetière P. Use of monitoring software to improve the measurement of carotid wall thickness by B-mode imaging. J Hypertens. 1992;10(suppl 5):S37–S41.
40.
Pignoli P, Tremoli E, Poli A, Oreste P, Paoletti R.
Intimal plus medial thickness of the arterial wall: a
direct measurement with ultrasound imaging. Circulation. 1986;74:1399–1406.
41. Subcommittee of WHO/ISH Mild Hypertension Liaison committee. Summary of 1993 World Health Organization-International Society of Hypertension guideline for the management of mild hypertension. BMJ. 1993;307:1541–1546.
42.
Expert Panel on Detection, Evaluation, and Treatment of
High Blood Cholesterol in Adults. Summary of the second
report of the National Cholesterol Education Program (NCEP)
Expert Panel on Detection, Evaluation, and Treatment of High Blood
Cholesterol in Adults. JAMA. 1993;269:3015–3023.
43. The Expert Committee on the Diagnosis and Classification of Diabetes Mellitus. Report of the Expert Committee on the Diagnosis and Classification of Diabetes Mellitus. Diabetes Care. 1997;20:1183–1197.[Medline] [Order article via Infotrieve]
44.
Bonithon-Kopp C, Scarabin PY, Taquet A, Touboul PJ,
Malmejac A, Guize L. Early carotid atherosclerosis in
healthy middle-aged women: a follow-up study. Stroke. 1993;24:1837–1843.
45. Glagov S, Zarins C, Giddens DP, Ku DN. Hemodynamics and atherosclerosis. Arch Pathol Lab Med. 1988;112:1018–1031.[Medline] [Order article via Infotrieve]
46. Glagov S, Zarins CK. Is intimal hyperplasia an adaptive response or a pathologic process?: observations on the nature of nonatherosclerotic intimal thickening. J Vasc Surg. 1989;10:571–573.
47. Bots ML, Hofman A, Grobbee DE. Increased common carotid intima-media thickness: adaptive response or a reflection of atherosclerosis?: findings from the Rotterdam Study. Stroke. 1997;28:442–447.
48.
Zureik M, Touboul PJ, Bonithon-Kopp C, Courbon D,
Ruelland I, Ducimetière P. Differential association of common
carotid intima-media thickness and carotid atherosclerotic plaques with
parental history of premature death from coronary heart
disease: the EVA study. Arterioscler Thromb Vasc Biol. 1999;19:366–371.
49.
Gnasso A, Carallo C, Irace C, Spagnuolo V, De Novara G,
Mattioli PL, Pujia A. Association between intima-media thickness and
wall shear stress in common carotid arteries in healthy male subjects.
Circulation. 1996;94:3257–3262.
50.
Kornet L, Lambregts J, Hoeks APG, Reneman RS.
Differences in near-wall shear rate in the carotid artery within
subjects are associated with different intima-media thicknesses.
Arterioscler Thromb Vasc Biol. 1998;18:1877–1884.
51.
Gnasso A, Irace C, Carallo C, De Franceschi MS,
Motti C, Mattioli PL, Pujia A. In vivo association between low wall
shear stress and plaque in subjects with asymmetrical carotid
atherosclerosis. Stroke. 1997;28:993–998.
52.
Crouse JR, Craven TE, Hagaman AP, Bond MG. Association
of coronary disease with segment-specific intimal-medial
thickening of the extracranial carotid artery. Circulation. 1995;92:1141–1147.
53.
Espeland MA, Tang R, Terry JG, Davis DH, Mercuri
M, Crouse JR III. Associations of risk factors with segment-specific
intimal-medial thickness of the extracranial carotid artery.
Stroke.. 1999;30:1047–1055.
54.
O’Leary DH, Polak JF, Kronmal RA, Savage PJ, Borhani NO,
Kittner SJ, Tracy R, Gardin JM, Price TR, Furberg CD. Thickening of the
carotid wall: a marker for atherosclerosis in the
elderly?: Cardiovascular Health Study Collaborative
Research Group. Stroke. 1996;27:224–231.
55.
Tell GS, Howard G, McKinney WM, Toole JF. Cigarette
smoking cessation and extracranial carotid
atherosclerosis. JAMA. 1989;261:1178–1180.
56.
Handa N, Matsumoto M, Maeda H, Hougaku H, Ogawa S,
Fukunaga R, Yoneda S, Kimura K, Kamada T. Ultrasonic evaluation of
early carotid atherosclerosis. Stroke. 1990;21:1567–1572.
57.
Prati P, Vanuzzo D, Casaroli M, Di Chiara A, De Biasi
F, Feruglio GA, Touboul PJ. Prevalence and determinants of carotid
atherosclerosis in a general population.
Stroke. 1992;23:1705–1711.
58.
Lemne C, Jogestrand T, de Faire U. Carotid intima-media
thickness and plaque in borderline hypertension. Stroke. 1995;26:34–39.
59.
McQuillan BM, Beilby JP, Nidorf M, Thompson PL, Hung
J. Hyperhomocysteinemia but not the C677T mutation of
methylenetetrahydrofolate reductase is
an independent risk determinant of carotid wall thickening: the Perth
Carotid Ultrasound Disease Assessment Study (CUDAS).
Circulation. 1999;99:2383–2388.
This article has been cited by other articles:
 |
|
 |
|
  K. S. Stamatelopoulos, G. D. Kitas, C. M. Papamichael, E. Chryssohoou, K. Kyrkou, G. Georgiopoulos, A. Protogerou, V. F. Panoulas, A. Sandoo, N. Tentolouris, et al. Atherosclerosis in Rheumatoid Arthritis Versus Diabetes: A Comparative Study Arterioscler Thromb Vasc Biol, October 1, 2009; 29(10): 1702 - 1708. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. L. Sacco, S. H. Blanton, S. Slifer, A. Beecham, K. Glover, H. Gardener, L. Wang, E. Sabala, S.-H. H. Juo, and T. Rundek Heritability and Linkage Analysis for Carotid Intima-Media Thickness: The Family Study of Stroke Risk and Carotid Atherosclerosis Stroke, July 1, 2009; 40(7): 2307 - 2312. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J.-P. Empana, Y. Dauvilliers, J.-F. Dartigues, K. Ritchie, J. Gariepy, X. Jouven, C. Tzourio, P. Amouyel, A. Besset, and P. Ducimetiere Excessive Daytime Sleepiness Is an Independent Risk Indicator for Cardiovascular Mortality in Community-Dwelling Elderly: The Three City Study Stroke, April 1, 2009; 40(4): 1219 - 1224. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Iwamoto, A. Yokoyama, Y. Kitahara, N. Ishikawa, Y. Haruta, K. Yamane, N. Hattori, H. Hara, and N. Kohno Airflow Limitation in Smokers Is Associated with Subclinical Atherosclerosis Am. J. Respir. Crit. Care Med., January 1, 2009; 179(1): 35 - 40. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Debette, N. Leone, D. Courbon, J. Gariepy, C. Tzourio, J.-F. Dartigues, K. Ritchie, A. Alperovitch, P. Ducimetiere, P. Amouyel, et al. Calf Circumference Is Inversely Associated With Carotid Plaques Stroke, November 1, 2008; 39(11): 2958 - 2965. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Beaussier, I. Masson, C. Collin, E. Bozec, B. Laloux, D. Calvet, M. Zidi, P. Boutouyrie, and S. Laurent Carotid Plaque, Arterial Stiffness Gradient, and Remodeling in Hypertension Hypertension, October 1, 2008; 52(4): 729 - 736. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. Prati, A. Tosetto, D. Vanuzzo, G. Bader, M. Casaroli, L. Canciani, S. Castellani, and P.-J. Touboul Carotid Intima Media Thickness and Plaques Can Predict the Occurrence of Ischemic Cerebrovascular Events Stroke, September 1, 2008; 39(9): 2470 - 2476. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Genoud, V. Wietlisbach, F. Feihl, A. Mermod, D. Morin, R. Darioli, P. Nicod, V. Mooser, B. Waeber, D. Hayoz, et al. Surrogate Markers for Atherosclerosis in Overweight Subjects With Atherogenic Dyslipidemia: The GEMS Project Angiology, August 1, 2008; 59(4): 484 - 492. [Abstract] [PDF]
|
|
|
|
 |
|
 F. A. Benedetto, G. Tripepi, F. Mallamaci, and C. Zoccali Rate of Atherosclerotic Plaque Formation Predicts Cardiovascular Events in ESRD J. Am. Soc. Nephrol., April 1, 2008; 19(4): 757 - 763. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Debette, D. Courbon, N. Leone, J. Gariepy, C. Tzourio, J.-F. Dartigues, P. Barberger-Gateau, K. Ritchie, A. Alperovitch, P. Amouyel, et al. Tea Consumption Is Inversely Associated With Carotid Plaques in Women Arterioscler Thromb Vasc Biol, February 1, 2008; 28(2): 353 - 359. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. M. Tuomainen, K. Nyyssonen, J. A. Laukkanen, T. Tervahartiala, T.-P. Tuomainen, J. T. Salonen, T. Sorsa, and P. J. Pussinen Serum Matrix Metalloproteinase-8 Concentrations Are Associated With Cardiovascular Outcome in Men Arterioscler Thromb Vasc Biol, December 1, 2007; 27(12): 2722 - 2728. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Dumont, M. Zureik, D. Cottel, M. Montaye, P. Ducimetiere, P. Amouyel, and T. Brousseau Association of arginase 1 gene polymorphisms with the risk of myocardial infarction and common carotid intima media thickness J. Med. Genet., August 1, 2007; 44(8): 526 - 531. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J.-P. Empana, M. Zureik, J. Gariepy, D. Courbon, J. F. Dartigues, K. Ritchie, C. Tzourio, A. Alperovitch, and P. Ducimetiere The Metabolic Syndrome and the Carotid Artery Structure in Noninstitutionalized Elderly Subjects: The Three-City Study Stroke, March 1, 2007; 38(3): 893 - 899. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Debette, J.-C. Lambert, J. Gariepy, N. Fievet, C. Tzourio, J.-F. Dartigues, K. Ritchie, A.-M. Dupuy, A. Alperovitch, P. Ducimetiere, et al. New Insight Into the Association of Apolipoprotein E Genetic Variants With Carotid Plaques and Intima-Media Thickness Stroke, December 1, 2006; 37(12): 2917 - 2923. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Laurent, J. Cockcroft, L. Van Bortel, P. Boutouyrie, C. Giannattasio, D. Hayoz, B. Pannier, C. Vlachopoulos, I. Wilkinson, H. Struijker-Boudier, et al. Expert consensus document on arterial stiffness: methodological issues and clinical applications Eur. Heart J., November 1, 2006; 27(21): 2588 - 2605. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Zureik, S. Czernichow, D. Courbon, J. Blacher, P. Ducimetiere, S. Hercberg, M. E. Safar, and P. Galan Parental Longevity, Carotid Atherosclerosis, and Aortic Arterial Stiffness in Adult Offspring Stroke, November 1, 2006; 37(11): 2702 - 2707. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. A Wyman, M. E Mays, P. E McBride, and J. H Stein Ultrasound-detected carotid plaque as a predictor of cardiovascular events Vascular Medicine, May 1, 2006; 11(2): 123 - 130. [Abstract] [PDF]
|
|
|
|
|
|
S. Makita, M. Nakamura, and K. Hiramori The Association of C-Reactive Protein Levels With Carotid Intima-Media Complex Thickness and Plaque Formation in the General Population Stroke, October 1, 2005; 36(10): 2138 - 2142. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Elbaz, M. Ripert, B. Tavernier, B. Fevrier, M. Zureik, J. Gariepy, A. Alperovitch, and C. Tzourio Common Carotid Artery Intima-Media Thickness, Carotid Plaques, and Walking Speed Stroke, October 1, 2005; 36(10): 2198 - 2202. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. F. Drager, L. A. Bortolotto, M. C. Lorenzi, A. C. Figueiredo, E. M. Krieger, and G. Lorenzi-Filho Early Signs of Atherosclerosis in Obstructive Sleep Apnea Am. J. Respir. Crit. Care Med., September 1, 2005; 172(5): 613 - 618. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. P. Engebretson, I. B. Lamster, M. S.V. Elkind, T. Rundek, N. J. Serman, R. T. Demmer, R. L. Sacco, P. N. Papapanou, and M. Desvarieux Radiographic Measures of Chronic Periodontitis and Carotid Artery Plaque Stroke, March 1, 2005; 36(3): 561 - 566. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. O. Talbott, J. V. Zborowski, M. Y. Boudreaux, K. P. McHugh-Pemu, K. Sutton-Tyrrell, and D. S. Guzick The Relationship between C-Reactive Protein and Carotid Intima-Media Wall Thickness in Middle-Aged Women with Polycystic Ovary Syndrome J. Clin. Endocrinol. Metab., December 1, 2004; 89(12): 6061 - 6067. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Zureik, J. Gariepy, D. Courbon, J.-F. Dartigues, K. Ritchie, C. Tzourio, A. Alperovitch, A. Simon, and P. Ducimetiere Alcohol Consumption and Carotid Artery Structure in Older French Adults: The Three-City Study Stroke, December 1, 2004; 35(12): 2770 - 2775. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. L. Schott, R. P. Wildman, S. Brockwell, L. R. Simkin-Silverman, L. H. Kuller, and K. Sutton-Tyrrell Segment-Specific Effects of Cardiovascular Risk Factors on Carotid Artery Intima-Medial Thickness in Women at Midlife Arterioscler Thromb Vasc Biol, October 1, 2004; 24(10): 1951 - 1956. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S.-H. H. Juo, H.-F. Lin, T. Rundek, E. A. Sabala, B. Boden-Albala, N. Park, M.-Y. Lan, and R. L. Sacco Genetic and Environmental Contributions to Carotid Intima-Media Thickness and Obesity Phenotypes in the Northern Manhattan Family Study Stroke, October 1, 2004; 35(10): 2243 - 2247. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Zureik, P. Galan, S. Bertrais, L. Mennen, S. Czernichow, J. Blacher, P. Ducimetiere, and S. Hercberg Effects of Long-Term Daily Low-Dose Supplementation With Antioxidant Vitamins and Minerals on Structure and Function of Large Arteries Arterioscler Thromb Vasc Biol, August 1, 2004; 24(8): 1485 - 1491. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Zureik, S. Kony, C. Neukirch, D. Courbon, B. Leynaert, D. Vervloet, P. Ducimetiere, and F. Neukirch Bronchial Hyperresponsiveness to Methacholine Is Associated With Increased Common Carotid Intima-Media Thickness in Men Arterioscler Thromb Vasc Biol, June 1, 2004; 24(6): 1098 - 1103. [Abstract] [Full Text]
|
|
|
|
 |
|
 M. J. Boot, R. P.M. Steegers-Theunissen, R. E. Poelmann, L. van Iperen, and A. C. Gittenberger-de Groot Homocysteine Induces Endothelial Cell Detachment and Vessel Wall Thickening During Chick Embryonic Development Circ. Res., March 5, 2004; 94(4): 542 - 549. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. Heude, P. Ducimetiere, and C. Berr Cognitive decline and fatty acid composition of erythrocyte membranes--The EVA Study Am. J. Clinical Nutrition, April 1, 2003; 77(4): 803 - 808. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. Risley, P. Jerrard-Dunne, M. Sitzer, A. Buehler, S. von Kegler, and H. S. Markus Promoter Polymorphism in the Endotoxin Receptor (CD14) Is Associated With Increased Carotid Atherosclerosis Only in Smokers: The Carotid Atherosclerosis Progression Study (CAPS) Stroke, March 1, 2003; 34(3): 600 - 604. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. C. Wascher, B. Paulweber, L. Malaimare, A. Stadlmayr, B. Iglseder, I. Schmoelzer, and W. Renner Associations of a Human G Protein {beta}3 Subunit Dimorphism With Insulin Resistance and Carotid Atherosclerosis Stroke, March 1, 2003; 34(3): 605 - 609. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Zureik, J.-M. Bureau, M. Temmar, C. Adamopoulos, D. Courbon, K. Bean, P.-J. Touboul, A. Benetos, and P. Ducimetiere Echogenic Carotid Plaques Are Associated With Aortic Arterial Stiffness in Subjects With Subclinical Carotid Atherosclerosis Hypertension, March 1, 2003; 41(3): 519 - 527. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. Browne, D. Meeking, K. Shaw, and M. Cummings Review: Endothelial dysfunction and pre-symptomatic atherosclerosis in type 1 diabetes -- pathogenesis and identification The British Journal of Diabetes & Vascular Disease, January 1, 2003; 3(1): 27 - 34. [Abstract] [PDF]
|
|
|
|
|
|
M. T. Magyar, Z. Szikszai, J. Balla, A. Valikovics, J. Kappelmayer, S. Imre, G. Balla, V. Jeney, L. Csiba, and D. Bereczki Early-Onset Carotid Atherosclerosis Is Associated With Increased Intima-Media Thickness and Elevated Serum Levels of Inflammatory Markers Stroke, January 1, 2003; 34(1): 58 - 63. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 F. Weber Risk factors for subclinical carotid atherosclerosis in healthy men Neurology, August 27, 2002; 59(4): 524 - 528. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Zureik, L. Robert, D. Courbon, P.-J. Touboul, L. Bizbiz, and P. Ducimetiere Serum Elastase Activity, Serum Elastase Inhibitors, and Occurrence of Carotid Atherosclerotic Plaques: The Etude sur le Vieillissement Arteriel (EVA) Study Circulation, June 4, 2002; 105(22): 2638 - 2645. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Zureik, F. Kauffmann, P.-J. Touboul, D. Courbon, and P. Ducimetiere Association Between Peak Expiratory Flow and the Development of Carotid Atherosclerotic Plaques Arch Intern Med, July 9, 2001; 161(13): 1669 - 1676. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Paterniti, M. Zureik, P. Ducimetiere, P.-J. Touboul, J.-M. Feve, and A. Alperovitch Sustained Anxiety and 4-Year Progression of Carotid Atherosclerosis Arterioscler Thromb Vasc Biol, January 1, 2001; 21(1): 136 - 141. [Abstract] [Full Text] [PDF]
|
|
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||