(Stroke. 1997;28:2442-2447.)
© 1997 American Heart Association, Inc.
Articles |
Increased Common Carotid Intima-Media Thickness
Adaptive Response or a Reflection of Atherosclerosis? Findings From the Rotterdam Study
From the Department of Epidemiology and Biostatistics (M.L.B., A.H., D.E.G.), Erasmus University Medical School, Rotterdam, and the Julius Center for Patient Oriented Research (M.L.B., D.E.G.), Utrecht University, Utrecht, The Netherlands.
Correspondence to Prof D.E. Grobbee, MD, PhD, Department of Epidemiology and Biostatistics, Erasmus University Medical School, PO Box 1738, 3000 DR Rotterdam, The Netherlands.
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Abstract |
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Background and Purpose Carotid intima-media thickness (IMT) measurements are used widely to study atherosclerosis. Some have suggested that an increased IMT reflects a nonatherosclerotic adaptive response to changes in shear stress and tensile stress. This stems from the hypothesis that changes in shear stress and subsequently in lumen diameter are followed by changes in IMT to keep tensile stress constant. We studied the relation of common carotid IMT to common carotid end-diastolic lumen diameter and tensile stress, as approximated by mean arterial pressure · (lumen diameter/IMT)].
Methods A cross-sectional analysis was performed with data obtained from the first 1715 participants in the Rotterdam Study, a population-based cohort study among 7983 subjects aged 55 years and over who underwent ultrasonographic examination of the carotid arteries. End-diastolic lumen diameter and IMT of the common carotid arteries were evaluated and quantified.
Results With increasing IMT, inner and outer lumen diameters increased gradually, and beyond an IMT of 1.10 mm, the inner lumen diameter decreased. Tensile stress increased with increasing lumen diameter instead of being constant. The lumen-to-IMT ratio was constant across levels of mean arterial pressure.
Conclusions Our findings are compatible with the view that at lower degrees of IMT, the thickening appears to reflect an equilibrium state in which the effects of pressure and flow on the arteries are in balance, given a characteristic relation between shear stress and local transmural pressure. Beyond a certain level, IMT more likely may represent atherosclerosis. Regardless of whether common carotid IMT reflects local atherosclerosis, it may still serve as a graded marker for cardiovascular risk.
Key Words: cerebrovascular disorders • cardiovascular diseases • myocardial infarction • stenosis •
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Introduction |
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Carotid IMT measurements currently are used widely to study the presence and progression of atherosclerosis and its determinants.1 2 3 4 5 6 Carotid IMT measurements have been used as end points in intervention studies on the efficacy of lipid-lowering drugs in reducing the progression of atherosclerosis.7 8 9 Results showing that an increased carotid IMT is a predictor of myocardial infarction and stroke are emerging.10 11 12 These findings support the idea that IMT may be used as an intermediate or a proxy end point, a suitable alternative for cardiovascular morbidity and mortality.
Some have argued that common carotid IMT below certain levels may not reflect atherosclerosis but is merely an adaptive response to changes in shear stress and tensile stress.13 It has therefore been suggested that an increased IMT should be considered relative to its diameter.
Two major determinants of adaptive remodeling of the arterial wall in response to hemodynamic alterations are changes in shear stress and tensile stress. Shear stress deals with the gradient of velocities near the artery wall, a force that displaces the endothelium and the inner layers of the wall in the direction of the flow. Shear stress is a direct function of viscosity, blood flow, and lumen diameter. It has been shown that major changes in flow result in changes in shear stress, on which an endothelium-dependent change in inner lumen diameter may occur to restore shear stress to normal levels or to a new equilibrium.14 15 16 Tensile stress deals with the stretching force that is exerted in a direction tangential to the artery wall or perpendicular to a longitudinal section through the wall. The intraluminal pressure is a major determinant of tensile stress. Although the tensile stress may show variation across the wall, average values may be obtained by considering tensile stress to be a function of distending pressure, lumen diameter, and IMT.17 It has been proposed that changes in blood flow lead to changes in shear stress. Adaptive changes in lumen diameter may occur to restore shear stress, and then, in an attempt to maintain tensile stress constant, may lead to changes in IMT.13 18 This hypothesis assumes that both shear stress and tensile stress are kept relatively constant throughout the artery13 15 19 and indicates that changes in lumen diameter are followed by nonatherosclerotic adaptive changes in IMT.
We evaluated the relation of common carotid IMT to common carotid end-diastolic lumen diameter and tensile stress, as approximated by MAP · (lumen diameter/IMT). Furthermore, we studied the effects of adjustment for lumen diameter in the statistical analyses in studies that used IMT as both exposure and outcome measurement.
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Methods |
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Population
The Rotterdam Study is a single-center prospective follow-up study on disease and disability in the elderly in 7983 subjects, aged 55 years or over, living in the suburb of Ommoord in Rotterdam, The Netherlands, as detailed elsewhere.20 Baseline data were collected from March 1990 to July 1993 in a home interview and two visits at the research center. The overall participation rate of those invited for the study was 78%. The study was approved by the Medical Ethics Committee of Erasmus University, and written informed consent was obtained from all participants.
The present analysis is based on the first 1715 participants in whom carotid vessel characteristics (ie, lumen diameter and IMT) were evaluated and quantified.
Carotid Ultrasonography
Ultrasonography of both carotid arteries was performed with a
7.5-MHz linear array transducer with a ATL UltraMark IV Duplex scanner
as described in detail elsewhere.21 On a longitudinal
two-dimensional ultrasound image of the carotid artery, the near and
far wall of the carotid artery are displayed as two bright white lines
separated by a hypoechogenic space. The distance between the leading
edge of the first bright line on the far wall (lumen-intima
interface) and the leading edge of the second bright line
(media-adventitia interface) indicates the IMT of the far wall. For the
near wall, the distance between the lower edge of the first bright line
to the lower edge of the second bright line at the near wall provides
the best estimate of the near wall IMT.22 The inner lumen
diameter was assessed as the distance between the intima-lumen
interface at the near wall and the lumen-intima interface at the far
wall. When an optimal longitudinal image was obtained by following the
Rotterdam ultrasound protocol, it was frozen on the R wave of the ECG
and stored on videotape. This procedure was repeated three times for
each left and right carotid artery. The actual measurements of IMT and
lumen diameter were performed off-line. From the videotape, the frozen
images were digitized and displayed on the screen of a personal
computer with additional dedicated software. For both the left and
right carotid arteries, the average of the IMT (near and far wall) and
end-diastolic inner lumen diameter of each of the three
frozen images was calculated. For each individual, an outer lumen
diameter was calculated as the inner lumen diameter plus the near wall
IMT plus the far wall IMT. The common carotid artery and the carotid
bifurcation were evaluated off-line (from tapes) for the presence
(yes/no) of atherosclerotic lesions on both the near and the far wall
of the carotid artery. Plaques were defined as a focal widening
relative to adjacent segments, with the protrusion into the lumen
composed of either only calcified deposits or a combination of
calcification and noncalcified material. No attempt was made to
quantify the size or extent of the lesions. Reproducibility of IMT
measurements and plaques has been described
elsewhere.23 24
Cardiovascular Risk Factors
A history of myocardial infarction and stroke at baseline was
assessed by the questions, "Did you ever suffer from a myocardial
infarction for which you were hospitalized?" and "Did you ever
suffer from a stroke diagnosed by a physician?" A subject's smoking
status was classified as current, former, or never smoker. At the
research center, height and weight were measured, and body mass index
(kg/m2) was calculated. Sitting blood pressure was measured
at the right upper arm with a random-zero sphygmomanometer. The average
of two measurements obtained at one occasion and separated by a count
of the pulse rate was used in the present analysis.
Hypertension was defined as a systolic blood pressure of
160 mm Hg or over, a diastolic blood pressure of
95 mm Hg or over, or the current use of antihypertensive
drugs for the indication of hypertension. Diabetes mellitus was
considered present when subjects used oral blood-glucose–lowering
drugs or insulin.
A nonfasting venipuncture was performed with a 21-gauge butterfly needle with tube (Surflo winged infusion set).25 Serum total cholesterol was determined with an automated enzymatic procedure. HDL cholesterol was measured similarly, after precipitation of the non-HDL fraction with phosphotungstate-magnesium.
Data Analysis
First, the association of IMT and lumen diameter to
cardiovascular risk factors was evaluated by the use of
linear regression analysis. Second, the association between
inner and outer lumen diameter and IMT was studied with a linear
regression model in which common carotid IMT was categorized into 12
categories (11 dummy variables). The lowest category (common
carotid IMT <0.60 mm) was used as a reference category. Third,
the association between tensile stress and lumen diameter was evaluated
by the use of a linear regression model in which lumen diameter was
categorized into 7 categories (6 dummy variables). The association
between the lumen-to-intima–media thickness ratio and the MAP was
evaluated in a similar manner. Finally, the effect of adjustment for
differences in lumen diameter on the association between risk factors
and IMT was studied by the use of linear regression analysis,
whereas the effect of adjustment for differences in lumen diameter on
the association between IMT and cardiovascular disease
was evaluated with logistic regression analyses.
Analyses were done with STATA statistical software. Because
vascular adaptations are a local site-specific phenomenon and findings
were similar for the left and the right common carotid arteries, only
results of the right common carotid artery are shown.
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Results |
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General characteristics of the study population are given in Table 1
. Increasing age, male sex, increased
weight, increased body mass index, current smoking, elevated blood
pressure levels (systolic, diastolic, pulse, and
MAP), hypertension, lower heart rate, decreased HDL
cholesterol, diabetes mellitus, and previous myocardial
infarction and stroke were positively associated with an increased
common carotid IMT (Table 2). Similar
relations were found for increased end-diastolic lumen
diameter, except for heart rate, HDL cholesterol, diabetes
mellitus and stroke (no association), and height (positive
association). Increased total cholesterol was associated
with a reduced lumen diameter (Table 2).
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Fig 1 shows that with increasing common
carotid IMT, inner and outer lumen diameters gradually increase, and
beyond an IMT of 1 to 1.10 mm, the inner lumen diameter decreased.
The association with the inner lumen diameter was best characterized
with both IMT separately and squared in the linear regression model.
Linear regression coefficients, adjusted for age, sex, height, and
weight, were .054 mm (SEM .0054) and -.023 mm (SEM .0027),
respectively.
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Fig 2 shows that with increasing lumen
diameter tensile stress gradually increased with a mean increase in
tensile stress per 1-mm increase in outer lumen diameter of 47
mm Hg (95% CI, 37 to 57 mm Hg). Because the definition
of tensile stress may be applicable only for arteries with thin walls
relative to their diameters, we performed additional analyses
restricted to subjects with an IMT <0.80, 0.90, and <1 mm. The
magnitude of the association between tensile stress and lumen diameter
differed from the overall analyses: linear regression
coefficients per 1-mm change in outer lumen diameter were 124
mm Hg (95% CI, 109 to 138), 98 mm Hg (95% CI, 86 to
110), and 79 mm Hg (95% CI, 68 to 90).
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Although this may indicate that at a higher vessel wall thickness the assumption of the arterial wall being thin relative to its diameter might be violated, the direction of the associations did not differ across these groups.
Fig 3 shows that the lumen-IMT ratio
remained constant across all levels of MAP. This is indicative for a
well kept balance between lumen diameter and IMT across all levels of
MAP and also suggests that tensile stress increases with an increase in
MAP.
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Adjustment for lumen diameter reduced the magnitude of some associations between cardiovascular risk factors and IMT. The association for systolic blood pressure was 0.014 mm (95% CI, 0.011 to 0.017), 0.014 mm for smoking (95% CI, -0.004 to 0.034), and 0.050 mm for myocardial infarction (95% CI, 0.024 to 0.078) after adjustment for lumen diameter. Similarly, the associations of lumen diameter to atherosclerosis and cardiovascular disease were reduced when differences in IMT were taken into consideration. The associations of IMT to atherosclerosis and cardiovascular disease were not attenuated when lumen diameter was added to the logistic regression model; the relative risk of myocardial infarction per standard deviation increase in IMT was 1.37 (95% CI, 1.17 to 1.59) without and 1.35 (95% CI, 1.15 to 1.57) with adjustment for lumen diameter. For stroke, the relative risks were 1.37 (95% CI, 1.14 to1.64) and 1.38 (95% CI, 1.15 to1.64), respectively, whereas for the association with plaques in the carotid bifurcation relative risks of 1.81 (95% CI, 1.55 to 2.12) and 1.77 (95% CI, 1.51 to 2.08) were found.
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Discussion |
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The present population-based study showed a graded positive linear association between inner and outer lumen diameter and IMT up to an IMT of 1.0 to 1.1 mm, after which the inner lumen diameter decreased. Tensile stress of the distal common carotid artery gradually increased, instead of being relatively constant, with increasing outer lumen diameter. Complementarily, the ratio of lumen-to-IMT remained constant across all levels of MAP. These results are compatible with the idea that certain degrees of common carotid IMT appear to reflect an adaptive response, whereas beyond a certain degree, IMT increased more rapidly than lumen diameter and points toward the development of atherosclerotic thickening.
The present study is of a cross-sectional nature, which does not allow determination of the temporal relations among (change in) shear stress, lumen diameter, tensile stress, blood pressure, and (change in) IMT. Our findings should therefore be confirmed in longitudinal studies with repeated measurements of lumen diameter and IMT and preferably direct measurements of shear stress.
From studies on coronary arteries, it has been suggested that in the early development of atherosclerosis the outer diameter of the artery increases to preserve the inner lumen diameter.26 For the common carotid artery, an increase in outer diameter with increasing IMT has indeed been demonstrated.27 28 In the present study and in the EVA study among subjects aged 51 to 70 years,28 increased common carotid IMT was associated with an increased inner lumen diameter. In our study, inner lumen diameter decreased beyond a certain level of IMT, similar to findings in the Atherosclerosis Risk In Communities study, among subjects aged 45 to 64 years.27 The latter part of the curve may be explained by the presence of more severe atherosclerosis, such as the presence of intraluminal lesions (ie, plaques).
The first part of the curve has been suggested to reflect the
hypothesis that changes in blood flow lead to changes in shear stress
and that, to restore shear stress, it leads to adaptive changes in
lumen diameter, which then, in an attempt to maintain tensile stress
constant, may lead to changes in IMT.13 This hypothesis
assumes that both shear stress and tensile stress are kept relatively
constant throughout the artery. In the present study, no
information was available that allowed for the estimation of shear
stress. Tensile stress appeared to increase with increasing outer lumen
diameter instead of remaining constant. This suggests that compensatory
nonatherosclerotic adaptation of IMT may not completely restore the
level of tensile stress to the previous level. The results shown in Fig 3
indicate that intravascular pressure is important in the balance
between lumen diameter and IMT. Both of our observations support a
recently proposed pressure-shear hypothesis, which suggests that
adaptation of arteries in response to hemodynamic
changes occurs to maintain local wall shear stress at a set point that
is a function of local transmural pressure, which is an equilibrium
state in which the effects of pressure and flow on the arteries are in
balance, given a characteristic relation between shear stress and
pressure.29 These findings favor the opinion that at
certain levels an increased IMT reflects an adaptive response instead
of atherosclerosis. This may also explain why a large
number of cardiovascular risk factors are related to
both an increased IMT and lumen diameter.
How should lumen diameter, when it is a determinant of the thickness of the intima-media of the common carotid artery, be dealt with in the analysis? First, in analyses on the association between cardiovascular risk factors and IMT, the lumen diameter can be considered an intermediate variable in the chain that leads to an increased IMT. As a consequence, lumen diameter should, in principle, not be considered as a confounding variable of the observed association between risk factors and IMT and should therefore not be controlled for in the analyses. The same applies for the role of IMT in studies on the association between lumen diameter and cardiovascular disease. Adjustment for an intermediate variable will usually lead to attenuation of the associations. When, however, the main interest is whether the association between risk factors and IMT is independent of lumen diameter, one may want additionally to adjust for lumen diameter. Second, in analyses on the relation between IMT and cardiovascular disease, lumen diameter can be considered a preceding factor. There is no rationale to adjust for lumen diameter in such analyses, other than to assess the independent effects. Finally, in studies on the differences in common carotid IMT between subjects with and without certain characteristics in which a priori the size of the lumen diameter differs across groups, then additional adjustment for lumen diameter is appropriate. For example, the difference in common carotid IMT between men and women, as observed in several studies, has been interpreted as differences in the presence or extent of atherosclerosis. In our study, as in others,28 29 30 these differences were partly attributable to differences in end-diastolic lumen diameter and may therefore reflect differences in physiology instead of differences in atherosclerosis.
For observational and intervention studies, a question remains whether it matters very much should common carotid IMT below a certain degree not represent local atherosclerosis but merely reflect an adaptive response to altered flow, shear stress, and pressure. Obviously, the answer is "yes" when the main interest of research concerns atherosclerotic wall characteristics and its hemodynamic consequences. Compared with other large arteries, however, atherosclerosis of the common carotid artery tends to develop relatively late in life, and in nonhospitalized older subjects the presence of hemodynamically important stenosis is rare.31 In population-based studies on generalized atherosclerosis, lower degrees of common carotid IMT may indicate the presence of atherosclerosis elsewhere in the arterial system.21 22 23 24 Furthermore, for IMT ranging from 0.60 to 0.90 mm, graded associations have been found with cardiovascular risk factors and prevalent cardiovascular disease.32 Also, the risk of future cardiovascular and cerebrovascular disease increases gradually with increasing common carotid IMT.10 11 12 There appeared to be no clear cutoff point above which the risk increased more rapidly. Thus, even when IMT of the common carotid artery is unlikely to represent local atherosclerosis, measurement of IMT may be of use as a marker for total burden of atherosclerosis present in the individual, and it may serve as a graded marker for cardiovascular risk.
In conclusion, at lower degrees of IMT, the thickening may reflect an adaptive response to changes in shear stress, lumen diameter, tensile stress, and pressure instead of an atherosclerotic thickening. Beyond a certain level, the IMT more likely represents atherosclerosis. Apart from assessing independent associations for lumen diameter and IMT, there is no reason to adjust for lumen diameter in studies focusing on the relations between either cardiovascular risk factor and IMT or between IMT and disease. Regardless of whether common carotid IMT reflects local atherosclerosis, it may serve as a graded marker for cardiovascular risk.
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Selected Abbreviations and Acronyms |
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Acknowledgments |
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The Rotterdam Study is supported in part by the NESTOR program for geriatric research in The Netherlands (Ministry of Health and Ministry of Education), the Municipality of Rotterdam, the Netherlands Heart Foundation, the Netherlands Organization for Scientific Research (NWO), and the Rotterdam Medical Research Foundation (ROMERES). The contribution to the data collection of the general practitioners of the suburb of Ommoord, the field workers, ultrasound technicians, computer assistants, and laboratory technicians is gratefully acknowledged.
Received February 14, 1997; revision received June 23, 1997; accepted September 10, 1997.
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Q. Li, Y. Li, Z. Zhang, T. R. Gilbert, A. H. Matsumoto, S. E. Dobrin, and W. Shi Quantitative Trait Locus Analysis of Carotid Atherosclerosis in an Intercross Between C57BL/6 and C3H Apolipoprotein E-Deficient Mice Stroke, January 1, 2008; 39(1): 166 - 173. [Abstract] [Full Text] [PDF]
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C. Armstrong, S. Abilleira, M. Sitzer, H. S. Markus, and S. Bevan Polymorphisms in MMP Family and TIMP Genes and Carotid Artery Intima-Media Thickness Stroke, November 1, 2007; 38(11): 2895 - 2899. [Abstract] [Full Text] [PDF]
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R. Femia, M. Kozakova, M. Nannipieri, C. Gonzales-Villalpando, M. P. Stern, S. M. Haffner, and E. Ferrannini Carotid Intima-Media Thickness in Confirmed Prehypertensive Subjects: Predictors and Progression Arterioscler Thromb Vasc Biol, October 1, 2007; 27(10): 2244 - 2249. [Abstract] [Full Text] [PDF]
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M. Kozakova, C. Palombo, L. Mhamdi, T. Konrad, P. Nilsson, P. B. Staehr, M. Paterni, B. Balkau, and on behalf of the RISC Investigators Habitual Physical Activity and Vascular Aging in a Young to Middle-Age Population at Low Cardiovascular Risk Stroke, September 1, 2007; 38(9): 2549 - 2555. [Abstract] [Full Text] [PDF]
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 A. D. Augst, B. Ariff, S. A. G. McG. Thom, X. Y. Xu, and A. D. Hughes Analysis of complex flow and the relationship between blood pressure, wall shear stress, and intima-media thickness in the human carotid artery Am J Physiol Heart Circ Physiol, August 1, 2007; 293(2): H1031 - H1037. [Abstract] [Full Text] [PDF]
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 H. Yanai, H. Yoshida, Y. Tomono, and N. Tada Atherosclerosis imaging in statin intervention trials QJM, May 1, 2007; 100(5): 253 - 262. [Full Text] [PDF]
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 I. J. Kullo and A. R. Malik Arterial Ultrasonography and Tonometry as Adjuncts to Cardiovascular Risk Stratification J. Am. Coll. Cardiol., April 3, 2007; 49(13): 1413 - 1426. [Abstract] [Full Text] [PDF]
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 S. Aronson, M. L. Fontes, Y. Miao, D. T. Mangano, and for the Investigators of the Multicenter Study of Risk Index for Perioperative Renal Dysfunction/Failure: Critical Dependence on Pulse Pressure Hypertension Circulation, February 13, 2007; 115(6): 733 - 742. [Abstract] [Full Text] [PDF]
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 Y-f Cheung, S J Wong, and M H K Ho Relationship between carotid intima-media thickness and arterial stiffness in children after Kawasaki disease Arch. Dis. Child., January 1, 2007; 92(1): 43 - 47. [Abstract] [Full Text] [PDF]
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 R. Wunsch, G. de Sousa, A. M. Toschke, and T. Reinehr Intima-Media Thickness in Obese Children Before and After Weight Loss Pediatrics, December 1, 2006; 118(6): 2334 - 2340. [Abstract] [Full Text] [PDF]
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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]
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A. A. Meyer, G. Kundt, U. Lenschow, P. Schuff-Werner, and W. Kienast Improvement of Early Vascular Changes and Cardiovascular Risk Factors in Obese Children After a Six-Month Exercise Program J. Am. Coll. Cardiol., November 7, 2006; 48(9): 1865 - 1870. [Abstract] [Full Text] [PDF]
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P. Poirier, T. D. Giles, G. A. Bray, Y. Hong, J. S. Stern, F. X. Pi-Sunyer, and R. H. Eckel Obesity and Cardiovascular Disease: Pathophysiology, Evaluation, and Effect of Weight Loss: An Update of the 1997 American Heart Association Scientific Statement on Obesity and Heart Disease From the Obesity Committee of the Council on Nutrition, Physical Activity, and Metabolism Circulation, February 14, 2006; 113(6): 898 - 918. [Abstract] [Full Text] [PDF]
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 J. Nuver, A. J. Smit, J. van der Meer, M. P. van den Berg, W. T.A. van der Graaf, M. T. Meinardi, D. Th. Sleijfer, H. J. Hoekstra, A. I. van Gessel, A. M. van Roon, et al. Acute Chemotherapy-Induced Cardiovascular Changes in Patients With Testicular Cancer J. Clin. Oncol., December 20, 2005; 23(36): 9130 - 9137. [Abstract] [Full Text] [PDF]
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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]
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 M. Frick, H. F Alber, A. Rinner, A. Suessenbacher, H. Ulmer, S. P Schwarzacher, O. Pachinger, and F. Weidinger Relationship of sonographic wall components of the brachial artery to hypertension and coronary atherosclerosis Vascular Medicine, August 1, 2005; 10(3): 185 - 190. [Abstract] [PDF]
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M. Elovainio, L. Keltikangas-Jarvinen, M. Kivimaki, L. Pulkki, S. Puttonen, T. Heponiemi, M. Juonala, J. S. A. Viikari, and O. T. Raitakari Depressive Symptoms and Carotid Artery Intima-Media Thickness in Young Adults: The Cardiovascular Risk in Young Finns Study Psychosom Med, July 1, 2005; 67(4): 561 - 567. [Abstract] [Full Text] [PDF]
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 R. S. Reneman, J. M. Meinders, and A. P.G. Hoeks Non-invasive ultrasound in arterial wall dynamics in humans: what have we learned and what remains to be solved Eur. Heart J., May 2, 2005; 26(10): 960 - 966. [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.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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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]
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K. A. Matthews, K. Raikkonen, K. Sutton-Tyrrell, and L. H. Kuller Optimistic Attitudes Protect Against Progression of Carotid Atherosclerosis in Healthy Middle-Aged Women Psychosom Med, September 1, 2004; 66(5): 640 - 644. [Abstract] [Full Text] [PDF]
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 D. A Lawlor, S. Ebrahim, P. Whincup, J. Sterne, O. Papacosta, G. Wannamethee, S. Dhanjil, M. Griffin, A. N Nicolaides, and G. Davey Smith Sex differences in body fat distribution and carotid intima media thickness: cross sectional survey using data from the British regional heart study J Epidemiol Community Health, August 1, 2004; 58(8): 700 - 704. [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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M. L. Bots, G. W. Evans, W. A. Riley, and D. E. Grobbee Carotid Intima-Media Thickness Measurements in Intervention Studies: Design Options, Progression Rates, and Sample Size Considerations: A Point of View Stroke, December 1, 2003; 34(12): 2985 - 2994. [Abstract] [Full Text] [PDF]
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C. Foerch, A. Buehler, S. von Kegler, and M. Sitzer Intima-Media Thickness Side Differences Are Limited to the Common Carotid Artery Hypertension, December 1, 2003; 42 (6): e17 - e17. [Full Text] [PDF]
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 A. Oren, L. E. Vos, C. S. P. M. Uiterwaal, D. E. Grobbee, and M. L. Bots Cardiovascular Risk Factors and Increased Carotid Intima-Media Thickness in Healthy Young Adults: The Atherosclerosis Risk in Young Adults (ARYA) Study Arch Intern Med, August 11, 2003; 163(15): 1787 - 1792. [Abstract] [Full Text] [PDF]
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 P. G. Vlachoyiannopoulos, P. G. Kanellopoulos, J. P. A. Ioannidis, M. G. Tektonidou, I. Mastorakou, and H. M. Moutsopoulos Atherosclerosis in premenopausal women with antiphospholipid syndrome and systemic lupus erythematosus: a controlled study Rheumatology, May 1, 2003; 42(5): 645 - 651. [Abstract] [Full Text] [PDF]
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P. Jerrard-Dunne, M. Sitzer, P. Risley, D. A. Steckel, A. Buehler, S. von Kegler, and H. S. Markus Interleukin-6 Promoter Polymorphism Modulates the Effects of Heavy Alcohol Consumption on Early Carotid Artery Atherosclerosis: The Carotid Atherosclerosis Progression Study (CAPS) Stroke, February 1, 2003; 34(2): 402 - 407. [Abstract] [Full Text] [PDF]
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J. M. Sorof, A. V. Alexandrov, G. Cardwell, and R. J. Portman Carotid Artery Intimal-Medial Thickness and Left Ventricular Hypertrophy in Children With Elevated Blood Pressure Pediatrics, January 1, 2003; 111(1): 61 - 66. [Abstract] [Full Text] [PDF]
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K. J. Hunt, R. Duggirala, H. H.H. Goring, J. T. Williams, L. Almasy, J. Blangero, D. H. O'Leary, and M. P. Stern Genetic Basis of Variation in Carotid Artery Plaque in the San Antonio Family Heart Study Stroke, December 1, 2002; 33(12): 2775 - 2780. [Abstract] [Full Text] [PDF]
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T. Sasaki, M. Watanabe, Y. Nagai, T. Hoshi, M. Takasawa, M. Nukata, A. Taguchi, K. Kitagawa, N. Kinoshita, and M. Matsumoto Association of Plasma Homocysteine Concentration With Atherosclerotic Carotid Plaques and Lacunar Infarction Stroke, June 1, 2002; 33(6): 1493 - 1496. [Abstract] [Full Text] [PDF]
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M. Domanski, J. Norman, M. Wolz, G. Mitchell, and M. Pfeffer Cardiovascular Risk Assessment Using Pulse Pressure in the First National Health and Nutrition Examination Survey (NHANES I) Hypertension, October 1, 2001; 38(4): 793 - 797. [Abstract] [Full Text] [PDF]
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Y. Nagai, K. Kitagawa, M. Sakaguchi, Y. Shimizu, H. Hashimoto, H. Yamagami, M. Narita, T. Ohtsuki, M. Hori, and M. Matsumoto Significance of Earlier Carotid Atherosclerosis for Stroke Subtypes Stroke, August 1, 2001; 32(8): 1780 - 1785. [Abstract] [Full Text] [PDF]
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H. Hashimoto, K. Kitagawa, H. Hougaku, Y. Shimizu, M. Sakaguchi, Y. Nagai, S. Iyama, H. Yamanishi, M. Matsumoto, and M. Hori C-Reactive Protein Is an Independent Predictor of the Rate of Increase in Early Carotid Atherosclerosis Circulation, July 3, 2001; 104(1): 63 - 67. [Abstract] [Full Text] [PDF]
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 N. Kubis, A. Checoury, A. Tedgui, and B. I. Levy Adaptive common carotid arteries remodeling after unilateral internal carotid artery occlusion in adult patients Cardiovasc Res, June 1, 2001; 50(3): 597 - 602. [Abstract] [Full Text] [PDF]
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N. M. van Popele, D. E. Grobbee, M. L. Bots, R. Asmar, J. Topouchian, R. S. Reneman, A. P. G. Hoeks, D. A. M. van der Kuip, A. Hofman, and J. C. M. Witteman Association Between Arterial Stiffness and Atherosclerosis : The Rotterdam Study Stroke, February 1, 2001; 32(2): 454 - 460. [Abstract] [Full Text] [PDF]
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H. Tanaka, F. A. Dinenno, K. D. Monahan, C. A. DeSouza, and D. R. Seals Carotid Artery Wall Hypertrophy With Age Is Related to Local Systolic Blood Pressure in Healthy Men Arterioscler Thromb Vasc Biol, January 1, 2001; 21(1): 82 - 87. [Abstract] [Full Text] [PDF]
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J. O. Toikka, H. Laine, M. Ahotupa, A. Haapanen, J. S. A. Viikari, J. J. Hartiala, and O. T Raitakari Increased Arterial Intima-Media Thickness and In Vivo LDL Oxidation in Young Men With Borderline Hypertension Hypertension, December 1, 2000; 36(6): 929 - 933. [Abstract] [Full Text] [PDF]
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H. Tanaka, F. A. Dinenno, D. R. Seals, L. Kornet, R. S. Reneman, and A. P. G. Hoeks Age-Related Increase in Femoral Intima-Media Thickness in Healthy Humans Arterioscler Thromb Vasc Biol, September 1, 2000; 20(9): 2172 - 2172. [Full Text] [PDF]
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P.-J. Touboul, A. Elbaz, C. Koller, C. Lucas, V. Adrai, F. Chedru, P. Amarenco, and f. t. G. Investigators Common Carotid Artery Intima-Media Thickness and Brain Infarction : The Etude du Profil Genetique de l'Infarctus Cerebral (GENIC) Case-Control Study Circulation, July 18, 2000; 102(3): 313 - 318. [Abstract] [Full Text] [PDF]
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E. Stensland-Bugge, K. H. Bonaa, O. Joakimsen, and I. Njolstad Sex Differences in the Relationship of Risk Factors to Subclinical Carotid Atherosclerosis Measured 15 Years Later : The Tromso Study Stroke, March 1, 2000; 31(3): 574 - 581. [Abstract] [Full Text] [PDF]
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B. Bülow, L. Hagmar, J. Eskilsson, and E. M. Erfurth Hypopituitary Females Have a High Incidence of Cardiovascular Morbidity and an Increased Prevalence of Cardiovascular Risk Factors J. Clin. Endocrinol. Metab., February 1, 2000; 85(2): 574 - 584. [Abstract] [Full Text]
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R. S Reneman and A. P.G Hoeks Noninvasive vascular ultrasound: An asset in vascular medicine Cardiovasc Res, January 1, 2000; 45(1): 27 - 35. [Full Text] [PDF]
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M. J. Domanski, B. R. Davis, M. A. Pfeffer, M. Kastantin, and G. F. Mitchell Isolated Systolic Hypertension : Prognostic Information Provided by Pulse Pressure Hypertension, September 1, 1999; 34(3): 375 - 380. [Abstract] [Full Text] [PDF]
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F. Borson-Chazot, A. Serusclat, Y. Kalfallah, X. Ducottet, G. Sassolas, S. Bernard, F. Labrousse, J. Pastene, A. Sassolas, Y. Roux, et al. Decrease in Carotid Intima-Media Thickness after One Year Growth Hormone (GH) Treatment in Adults with GH Deficiency J. Clin. Endocrinol. Metab., April 1, 1999; 84(4): 1329 - 1333. [Abstract] [Full Text]
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B. van der Loo, R. Labugger, C. P. Aebischer, J. N. Skepper, M. Bachschmid, V. Spitzer, J. Kilo, L. Altwegg, V. Ullrich, and T. F. Luscher Cardiovascular Aging Is Associated With Vitamin E Increase Circulation, April 9, 2002; 105(14): 1635 - 1638. [Abstract] [Full Text] [PDF]
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