(Stroke. 1996;27:654-660.)
© 1996 American Heart Association, Inc.
Articles |
From INSERM U 258 (C.B.-K., P.D.), Centre de Diagnostic et de Prévention Neurovasculaire (P.J.T.), and INSERM U 360 (C.B.), Paris; and Centre d'examen EVA (C.M.), Nantes, France.
Correspondence to Claire Bonithon-Kopp, MD, PhD, INSERM U 258, Hôpital Broussais, 96 rue Didot, 75674 Paris Cedex 14, France.
| Abstract |
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Methods B-mode ultrasound examinations of the carotid arteries and risk factor assessment were made in 1272 participants in the EVA (Etude sur le vieillissement artériel) Study, a longitudinal study designed to evaluate vascular and cognitive aging in men and women aged 59 to 71 years. Ultrasound examinations included measurements of intima-media thickness (IMT) and interadventitial and lumen diameters of the common carotid arteries and quantification of atherosclerotic plaques in extracranial carotid arteries.
Results Men showed greater IMT and interadventitial and lumen diameters of the common carotid arteries than did women. In both sexes, common IMT and plaque score were positively associated with common interadventitial and lumen diameters. Stepwise multiple regression analysis showed that male sex, body height and weight, common IMT, plaque score, systolic blood pressure, and alcohol consumption were positively and independently related to lumen diameter. On the other hand, an independent negative association was observed between low-density lipoprotein cholesterol and lumen diameter.
Conclusions In 59- to 71-year-old subjects, increased IMT and atherosclerotic plaques were accompanied by an increase in lumen diameter of the common carotid arteries, indicating an overcompensation. Luminal enlargement observed with several risk factors and with high blood pressure in particular might be partially counteracted by high lipid levels.
Key Words: aging carotid arteries epidemiology ultrasonics
| Introduction |
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The present analysis, based on baseline data from the EVA Study, aimed to examine the cross-sectional relationships between ultrasonographic measurements of common carotid interadventitial and lumen diameters and both common IMT and atherosclerotic plaques and to determine which factors may influence these associations in an elderly general population.
| Subjects and Methods |
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Ultrasonography
Ultrasound examinations were performed by four sonographers
using 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 a software specially designed for longitudinal studies (EUREQUA,
TSI).27
Details of the protocol have been described elsewhere.15 All measurements were made at the time of examination. Briefly, it involved scanning of the common carotid arteries, the carotid bifurcations, and the origin (first 2 cm) of the internal carotid arteries. The IMT was measured on the far wall of the mid and distal common carotid artery as the distance between the lumen-intima interface and the media-adventitia interface28 with the use of an automated edge detection algorithm. One transversal and two longitudinal measurements of IMT were completed on both the right and left common carotid arteries at a site free of any discrete plaques. Optimal images showing the far wall were stored on an optical disk. On such images, the lumen-intima interface is often more difficult to visualize on the near wall than the media-adventitia interface, and thus we chose to measure the interadventitial diameter (defined as the distance between both media-adventitia interfaces) rather than the lumen diameter. On each side, the lumen diameter was computed as the interadventitial diameter minus twice the transversal IMT. Generally, the means of the right and left IMT and diameters were used in the analysis.
Both near and far walls of all arterial segments were
scanned longitudinally and transversely to assess the occurrence of
plaques, defined as localized echo structures encroaching into the
vessel lumen for which the IMT was
1 mm. The quantification of plaque
thickness was made by measuring the IMT at the site of maximal
encroachment perpendicular to the vessel wall, and the sonographer
could be computer-assisted in the identification of interfaces and
placement of electronic calipers by examining the inflections of the
density profile curve taken at the site of plaque. When several plaques
were present on the same arterial segment (ie, common
carotid artery or bifurcation or origin of the internal carotid
artery), the examination was focused on that showing the greatest
encroachment into the lumen. When a plaque was mineralized, the
sonographer had to obtain the best incidence so that the plaque could
be visualized on the far wall, and an estimation of the IMT was made by
extrapolating the adjacent media-adventitia interface. A plaque
score was computed by averaging all plaque thicknesses measured on
longitudinal views and graded as follows: 0, no plaque; 1, mean
thickness
1 mm and
2 mm; 2, mean thickness >2 mm and
3 mm; and
3, mean thickness >3 mm. For all arterial segments,
optimal longitudinal and transverse images were stored on an optical
disk.
For quality assessment, a rereading study was made on random subsamples of images of both common carotid arteries and bifurcation or origin of internal carotid arteries as described elsewhere.15 Mean absolute differences and correlation coefficients between repeated readings were, respectively, 0.06 mm and 0.82 for longitudinal common IMT (n=81), 0.22 mm and 0.92 for common interadventitial diameter (n=81), 0.24 mm and 0.90 for common lumen diameter (n=74), and 0.40 mm and 0.78 for plaque thickness (n=52). In a previous work from our group, it was shown that both the interobserver and intraobserver variabilities of common IMT associated with the scanning procedure were substantially reduced after the repositioning functions of the EUREQUA software were used. The aforementioned variabilities (expressed as absolute differences and correlation coefficients) were 0.10 mm, r=.58 and 0.10 mm, r=.62, respectively, with standard procedures, whereas corresponding values obtained with repositioning procedures were 0.07 mm, r=.71 and 0.06 mm, r=.77, respectively.27
Ultrasound examinations performed early in the study (June to October 1991) were considered unreliable and were excluded from the analysis (n=77). Subjects with missing data for IMT or interadventitial diameter measurements because of poor interface visualization (n=40) were also excluded. Thus, the study sample was composed of 1272 subjects (523 men and 749 women).
Medical History
All participants were administered a standardized questionnaire
that gave information about demographic background, occupation, medical
history, drug use, and personal habits such as cigarette and alcohol
consumption. With respect to smoking behavior, subjects were classified
as current smokers, former smokers, and never smokers. Alcohol
consumption was determined from the subject's estimate of the average
amount of alcoholic beverages ingested weekly and expressed in
milliliters of alcohol per day. Two independent measurements of
systolic and diastolic blood pressures were made
with a digital electronic tensiometer (SP9 Spengler) after a 10-minute
rest, and the mean was used in the analysis. Hypertension was
defined as systolic blood pressure
160 mm Hg or
diastolic blood pressure
95 mm Hg or use of
antihypertensive drugs. The body mass index was computed as weight (in
kilograms) divided by height (in meters) squared. A subject was
considered diabetic if he reported medical history of diabetes or use
of antidiabetic drugs or had a fasting plasma glucose level
7.8
mmol/L (1.40 g/L). History of coronary heart disease was
defined as self-reported history of myocardial infarction or angina
pectoris.
Laboratory Methods
Blood samples were drawn between 8 and 9 AM after a
12-hour fast. Total cholesterol and
triglyceride assays were performed by enzymatic methods
with the use of the PAP enzymatic cholesterol kit
(Reference 61227) and the PAP enzymatic triglyceride kit
(Reference 759350), respectively, supplied by Biomérieux. Glucose
was determined by the enzymatic glucose oxidase method (Reference
61274, Boehringer). HDL cholesterol was measured
enzymatically after precipitation of apolipoprotein B-containing
lipoproteins with phosphotungstic acid and Mg2+ ions
(precipitant: Reference 543004, Boehringer). LDL
cholesterol was computed with the Friedewald
formula.29 All determinations were made daily.
Statistical Analysis
Standard procedures from the Statistical Analysis System
(SAS) were used for univariate and
multivariate analyses. Descriptive data on
common interadventitial and lumen diameters and their associations with
IMT and plaque score were given separately in men and women.
Two-way ANOVA was used to examine whether the associations between
common carotid diameters and IMT divided according to approximate
quartiles were modified by the presence of carotid plaques. Because of
the similarity of the associations between common carotid diameters and
IMT, plaque score, and conventional risk factors in men and women,
results were presented in both sexes combined after adjustment
for sex and height by either ANOVA or linear regression
analysis according to the categorical or continuous nature of
the risk factor. The independent predictors of lumen diameter were
examined in a stepwise regression model in which IMT (as a continuous
variable), plaque score, and each risk factor significantly
associated with lumen diameter in preceding analyses were
introduced as independent variables (F statistic to enter and to
stay in the model with a value of P<.05).
| Results |
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The regression coefficients of common interadventitial and lumen
diameters on common IMT are first described for the right and left side
separately in Table 2
. Since the associations were very
close for each side, the mean (right and left/2) diameters and IMT were
used in subsequent analyses. As shown in Table 3
, there was a progressive increase in both
interadventitial and lumen diameters according to the quartile of IMT
and to plaque score in men as well as in women. Body height was an
important determinant of interadventitial and lumen diameters in both
sexes (correlation coefficients ranging from 0.11 to 0.18). Thus,
subsequent analyses were performed in the whole population
after systematic adjustment for sex and height. The
Figure
shows the mean sex- and height-adjusted lumen
diameter by quartiles of IMT and plaque status (presence or absence).
The positive association between lumen diameter and IMT was similar in
subjects with and in those without carotid plaques (the interaction
term between IMT and plaque status was not significant in each sex
separately or in both sexes).
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The sex- and height-adjusted associations between common carotid
diameters and conventional risk factors are shown in Table 4
(categorical variables) and Table 5
(continuous variables). Interadventitial and lumen diameters
increased in subjects with a clinical history of hypertension,
diabetes, or coronary heart disease. Greater diameters were
also observed in drinkers of >40 mL/d of alcohol. Interadventitial
diameter was slightly increased in ex-smokers and current smokers
compared with nonsmokers, but this trend was not significant with lumen
diameter. As indicated in Table 5
, the strongest correlate of both
interadventitial and lumen diameters was systolic blood
pressure. Positive associations were also found between both common
carotid diameters and age, diastolic blood pressure, body
weight, alcohol consumption (as a continuous variable),
triglycerides, and blood glucose. Weak negative
associations were observed between HDL cholesterol and
interadventitial diameter and between LDL cholesterol and
lumen diameter.
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All variables significantly associated with lumen diameter were
considered as candidate variables in a stepwise multiple regression
model. A preliminary multiple regression analysis had revealed
that cardiovascular risk factors and use of
antihypertensive, hypolipidemic, or antidiabetic drugs had no modifying
effect on the relationships between lumen diameter and both common IMT
and plaque score (interaction terms between each risk factor or drug
use and IMT or plaque score were all insignificant). Stepwise multiple
regression analysis presented in Table 6
showed that male sex, systolic blood pressure, body height,
IMT, plaque score, body weight, and alcohol consumption were
independently and positively associated with lumen diameter, whereas
LDL cholesterol remained negatively related to lumen
diameter. Altogether, these variables explained 31.9% of the lumen
diameter variance. On the other hand, age, diabetes,
triglycerides, glucose, and coronary heart disease
did not enter the regression model. Exclusion of subjects who reported
a clinical history of coronary heart disease did not
consistently affect these results. Since many subjects were
receiving drugs likely to alter the relationships between lumen
diameter and some risk factors, stepwise regression analysis
with the same candidate variables was repeated in subjects free of
any treatment for hypertension,
hypercholesterolemia, or diabetes. All
variables except for alcohol consumption remained independently
associated with lumen diameter. However, we noted that the association
between lumen diameter and IMT was reduced by approximately 35% mainly
because this association was much more pronounced in subjects taking
antihypertensive drugs.
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| Discussion |
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Several considerations should be kept in mind before interpreting these results. First, our population sample was composed of elderly subjects who volunteered to participate in the study. Because of possible survival and self-selection biases, we cannot exclude the possibility that subjects with severe atherosclerosis inducing lumen narrowing were more likely to refuse to participate. This is suggested by the scarcity of hemodynamically significant stenoses observed in the study subjects and their low mean levels of common IMT. Thus, it is clear that the positive associations we found between lumen diameter and alterations of arterial wall can only be generalized to elderly persons with a low degree of atherosclerosis. Second, an important limitation of our ultrasound methodology lies in the inability of our B-mode system to standardize the image recording according to the stage of the cardiac cycle, which may introduce a nonnegligible source of variability in our measurements and thus lead to decreased statistical power. However, because the systolic expansion of the arterial lumen is accompanied by a concomitant diminution of the wall thickness, this methodological limitation cannot be responsible for a spurious positive association and may only lead to an underestimation of the true relationship between lumen diameter and IMT. Third, this study is cross-sectional and thus does not allow us to determine the temporal sequence of the observed modifications.
In fact, the associations we found between common lumen diameter and
both common IMT and plaque score are compatible with previous
pathoanatomic observations suggesting that coronary arteries
tend to enlarge in response to
atherosclerosis.21 22 23 Recently, a large
B-mode ultrasonographic study performed in men and women aged 45 to 64
years extended these findings to carotid arteries.24 Some
of their results showing a small negative correlation between lumen
diameter and IMT in the common carotid arteries contrast with ours,
which suggest an overcompensation of the arterial lumen in
the presence of increased IMT. These discrepancies are probably due at
least partially to differences in ultrasound methodology since in our
study IMT was never measured at the site of plaques (no IMT values
>1.5 mm), which are more likely to induce a lumen narrowing. Glagov et
al22 demonstrated that the positive correlation between
artery size and plaque area was particularly strong in the sections of
the coronary arteries with
20% stenosis and that the
decline in lumen area became evident only for stenosis values
>40%. On the other hand, our study was performed in elderly subjects,
and mechanisms by which lumen area and intima-media thickening are
mutually adapted might be altered in the presence of degenerative
changes in connective tissue associated with aging. The independent
contribution of plaque score and increased IMT to increased lumen
diameter may indicate that luminal enlargement reflects generalized
atherosclerosis. However, it may also suggest that
mechanisms underlying the association between luminal enlargement and
increased IMT in the common carotid arteries may be different in part
from those underlying its association with
atherosclerosis. Furthermore, our study suggests that
the mutual adaptation of lumen diameter and IMT does not depend on
whether subjects have confirmed lesions of
atherosclerosis.
Several cardiovascular risk factors were independently related to increased lumen diameter, which partially explains its association with IMT or plaque score. In addition to nonmodifiable risk factors such as sex and body height, increased systolic blood pressure appeared as one of the most important correlates of increased lumen diameter. An association between hypertension or high blood pressure and enlargement of the common carotid artery was reported in several noninvasive studies with the use of either B-mode ultrasonography10 12 30 31 or echo-tracking techniques32 33 but not in all.8 11 12 34 In our elderly population, the independent contribution of IMT and increased blood pressure, a known correlate of IMT, to increased lumen diameter suggests that the latter is not solely a compensatory response to wall thickening. It may also be due to the fatiguing effects of elevated blood pressure and cyclic stress on elastic fibers over many years, resulting in degenerative changes and stiffening of the arterial wall.26 Other cardiovascular risk factors weakly contributed to increased lumen diameter in our population. As far as we know, the associations we observed between lumen diameter and both alcohol consumption and LDL cholesterol (inverse association) have never been described and thus need confirmation. There are few data concerning the relation of alcohol consumption to arterial wall characteristics. No association was found with IMT in the present study15 or in a previous ultrasonographic study in middle-aged subjects.35 Moreover, no association has been reported between alcohol intake and carotid35 or aortic36 distensibility. Since alcohol intake has been positively associated with internal dimension of the left ventricle independently of blood pressure in a nonalcoholic general population,37 we cannot exclude that some common mechanisms might underlie the association between alcohol consumption and increased vascular and ventricular internal dimensions. The most intriguing finding from this study was the weak negative association between LDL cholesterol and common lumen diameter. We are not aware of previous ultrasonographic studies that examined such an association in large populations. In a pathoanatomic study on coronary arteries, total cholesterol was not predictive of lumen area23 and thus we cannot exclude that our finding may have been due to chance. On the other hand, a paradoxical increase in aortic distensibility with total or LDL cholesterol contrasting with the effects of blood pressure has been reported,36 38 but not consistently.39 We have no clear explanation of the mechanisms by which lipid disorders might inhibit the general trend of the common carotid artery to dilate with aging and hypertension. Our data only suggest that intima-media thickening and early atherosclerotic plaques are not involved in the reduction of the lumen diameter associated with increased lipid levels.
In conclusion, our study indicates that increased common lumen diameter was independently associated with increased IMT, atherosclerotic plaques, and several modifiable lifestyle risk factors. It suggests that carotid arterial enlargement accompanying aging and high blood pressure may be partially counteracted by high lipid levels in elderly subjects. These results need to be confirmed in younger populations, and longitudinal studies are required to determine their significance with regard to the progression of atherosclerosis and development of symptoms.
| Selected Abbreviations and Acronyms |
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| Acknowledgments |
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Received October 26, 1995; revision received January 2, 1996; accepted January 5, 1996.
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J. E. Ostberg, A. E. Donald, J. P. J. Halcox, C. Storry, C. McCarthy, and G. S. Conway Vasculopathy in Turner Syndrome: Arterial Dilatation and Intimal Thickening without Endothelial Dysfunction J. Clin. Endocrinol. Metab., September 1, 2005; 90(9): 5161 - 5166. [Abstract] [Full Text] [PDF] |
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M. L. Bots, D. E. Grobbee, A. Hofman, and J. C.M. Witteman Common Carotid Intima-Media Thickness and Risk of Acute Myocardial Infarction: The Role of Lumen Diameter Stroke, April 1, 2005; 36(4): 762 - 767. [Abstract] [Full Text] [PDF] |
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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] |
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M.L. Eigenbrodt, Z. Bursac, E.P. Eigenbrodt, D.J. Couper, R.E. Tracy, and J.L. Mehta Mathematical estimation of the potential effect of vascular remodelling/dilatation on B-mode ultrasound intima-medial thickness QJM, November 1, 2004; 97(11): 729 - 737. [Abstract] [Full Text] [PDF] |
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R. M.A. Henry, P. J. Kostense, J. M. Dekker, G. Nijpels, R. J. Heine, O. Kamp, L. M. Bouter, and C. D.A. Stehouwer Carotid Arterial Remodeling: A Maladaptive Phenomenon in Type 2 Diabetes but Not in Impaired Glucose Metabolism: The Hoorn Study Stroke, March 1, 2004; 35(3): 671 - 676. [Abstract] [Full Text] [PDF] |
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G. Chironi, J. Gariepy, N. Denarie, M. Balice, J.-L. Megnien, J. Levenson, and A. Simon Influence of Hypertension on Early Carotid Artery Remodeling Arterioscler Thromb Vasc Biol, August 1, 2003; 23(8): 1460 - 1464. [Abstract] [Full Text] [PDF] |
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J. G. Terry, R. Tang, M. A. Espeland, D. H. Davis, J. L.C. Vieira, M. F. Mercuri, and J. R. Crouse III Carotid Arterial Structure in Patients With Documented Coronary Artery Disease and Disease-Free Control Subjects Circulation, March 4, 2003; 107(8): 1146 - 1151. [Abstract] [Full Text] [PDF] |
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A. Iannuzzi, M. De Michele, S. Panico, E. Celentano, R. Tang, M. G. Bond, L. Sacchetti, F. Zarrilli, R. Galasso, M. Mercuri, et al. Radical-Trapping Activity, Blood Pressure, and Carotid Enlargement in Women Hypertension, February 1, 2003; 41(2): 289 - 296. [Abstract] [Full Text] [PDF] |
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A. Scuteri, C.-H. Chen, F. C.P. Yin, T. Chih-Tai, H. A. Spurgeon, and E. G. Lakatta Functional Correlates of Central Arterial Geometric Phenotypes Hypertension, December 1, 2001; 38(6): 1471 - 1475. [Abstract] [Full Text] [PDF] |
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U. G.R. Schulz and P. M. Rothwell Major Variation in Carotid Bifurcation Anatomy: A Possible Risk Factor for Plaque Development? Stroke, November 1, 2001; 32(11): 2522 - 2529. [Abstract] [Full Text] [PDF] |
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T. Mannami, S. Baba, and J. Ogata Potential of Carotid Enlargement as a Useful Indicator Affected by High Blood Pressure in a Large General Population of a Japanese City : The Suita Study Stroke, December 1, 2000; 31(12): 2958 - 2965. [Abstract] [Full Text] [PDF] |
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Y. Jiang, K. Kohara, and K. Hiwada Association Between Risk Factors for Atherosclerosis and Mechanical Forces in Carotid Artery Stroke, October 1, 2000; 31(10): 2319 - 2324. [Abstract] [Full Text] [PDF] |
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A. Gnasso, C. Motti, C. Irace, C. Carallo, L. Liberatoscioli, S. Bernardini, R. Massoud, P. L. Mattioli, G. Federici, and C. Cortese Genetic Variation in Human Stromelysin Gene Promoter and Common Carotid Geometry in Healthy Male Subjects Arterioscler Thromb Vasc Biol, June 1, 2000; 20(6): 1600 - 1605. [Abstract] [Full Text] [PDF] |
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L. A. Bortolotto, O. Hanon, G. Franconi, P. Boutouyrie, S. Legrain, and X. Girerd The Aging Process Modifies the Distensibility of Elastic but not Muscular Arteries Hypertension, October 1, 1999; 34(4): 889 - 892. [Abstract] [Full Text] [PDF] |
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Y. Nagai, E J. Metter, and J. L Fleg Increased carotid artery intimal-medial thickness: risk factor for exercise-induced myocardial ischemia in asymptomatic older individuals Vascular Medicine, August 1, 1999; 4(3): 181 - 186. [Abstract] [PDF] |
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K. Jensen-Urstad, M. Jensen-Urstad, and J. Johansson Carotid Artery Diameter Correlates With Risk Factors for Cardiovascular Disease in a Population of 55-Year-Old Subjects Stroke, August 1, 1999; 30(8): 1572 - 1576. [Abstract] [Full Text] [PDF] |
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C. Carallo, C. Irace, A. Pujia, M. S. De Franceschi, A. Crescenzo, C. Motti, C. Cortese, P. L. Mattioli, and A. Gnasso Evaluation of Common Carotid Hemodynamic Forces : Relations With Wall Thickening Hypertension, August 1, 1999; 34(2): 217 - 221. [Abstract] [Full Text] [PDF] |
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S. Kiechl and J. Willeit The Natural Course of Atherosclerosis : Part II: Vascular Remodeling Arterioscler Thromb Vasc Biol, June 1, 1999; 19(6): 1491 - 1498. [Abstract] [Full Text] [PDF] |
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P. Pauletto, P. Palatini, S. Da Ros, V. Pagliara, N. Santipolo, S. Baccillieri, E. Casiglia, P. Mormino, and A. C. Pessina Factors Underlying the Increase in Carotid Intima-Media Thickness in Borderline Hypertensives Arterioscler Thromb Vasc Biol, May 1, 1999; 19(5): 1231 - 1237. [Abstract] [Full Text] [PDF] |
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M. Zureik, P.-J. Touboul, C. Bonithon-Kopp, D. Courbon, I. Ruelland, and P. Ducimetiere 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, February 1, 1999; 19(2): 366 - 371. [Abstract] [Full Text] [PDF] |
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K. Demuth, N. Moatti, O. Hanon, M. O. Benoit, M. Safar, and X. Girerd Opposite Effects of Plasma Homocysteine and the Methylenetetrahydrofolate Reductase C677T Mutation on Carotid Artery Geometry in Asymptomatic Adults Arterioscler Thromb Vasc Biol, December 1, 1998; 18(12): 1838 - 1843. [Abstract] [Full Text] [PDF] |
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Y. Nagai, E. J. Metter, C. J. Earley, M. K. Kemper, L. C. Becker, E. G. Lakatta, and J. L. Fleg Increased Carotid Artery Intimal-Medial Thickness in Asymptomatic Older Subjects With Exercise-Induced Myocardial Ischemia Circulation, October 13, 1998; 98(15): 1504 - 1509. [Abstract] [Full Text] [PDF] |
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S. Rosfors, S. Hallerstam, K. Jensen-Urstad, M. Zetterling, and C. Carlstrom Relationship Between Intima-Media Thickness in the Common Carotid Artery and Atherosclerosis in the Carotid Bifurcation Stroke, July 1, 1998; 29(7): 1378 - 1382. [Abstract] [Full Text] [PDF] |
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J. Gariepy, J. Salomon, N. Denarie, F. Laskri, J. L. Megnien, J. Levenson, and A. Simon Sex and Topographic Differences in Associations Between Large-Artery Wall Thickness and Coronary Risk Profile in a French Working Cohort : The AXA Study Arterioscler Thromb Vasc Biol, April 1, 1998; 18(4): 584 - 590. [Abstract] [Full Text] [PDF] |
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M. L. Bots, A. Hofman, and D. E. Grobbee Increased Common Carotid Intima-Media Thickness : Adaptive Response or a Reflection of Atherosclerosis? Findings From the Rotterdam Study Stroke, December 1, 1997; 28(12): 2442 - 2447. [Abstract] [Full Text] |
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Y. Watanabe, T. Ishigami, Y. Kawano, T. Umahara, A. Nakamori, S. Mizushima, K. Hibi, I. Kobayashi, K. Tamura, H. Ochiai, et al. Angiotensin-Converting Enzyme Gene I/D Polymorphism and Carotid Plaques in Japanese Hypertension, September 1, 1997; 30(3): 569 - 573. [Abstract] [Full Text] |
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J. F. Polak, R. A. Kronmal, G. S. Tell, D. H. O'Leary, P. J. Savage, J. M. Gardin, G. H. Rutan, and N. O. Borhani Compensatory Increase in Common Carotid Artery Diameter: Relation to Blood Pressure and Artery Intima-Media Thickness in Older Adults Stroke, November 1, 1996; 27(11): 2012 - 2015. [Abstract] [Full Text] |
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