doi: 10.1161/hc2601.091704
(Circulation. 2001;104:68.)
© 2001 American Heart Association, Inc.
Clinical Investigation and Reports |
Ultrasonic Echolucent Carotid Plaques Predict Future Strokes
From the Department of Internal Medicine and Therapeutics (A8) (H. Hashimoto, K.K., H. Hougaku, Y.S., M.S., Y.N., M.M., M.H.), and Department of Diagnostic Medicine (S.I., H.Y.), Osaka University Graduate School of Medicine, Osaka, Japan.
Correspondence to Drs Hiroyuki Hashimoto and Masayasu Matsumoto, Division of Strokology, Department of Internal Medicine and Therapeutics, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka 565-0871, Japan. E-mail mlg{at}dadlnet.dk
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Abstract |
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 Top Abstract IntroductionMethodsResultsDiscussionReferences |
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Background—We tested prospectively the hypothesis that stroke development can be predicted by echolucency of carotid atherosclerotic plaques in previously symptomatic and asymptomatic patients.
Methods and Results—We
followed incidence of ipsilateral ischemic strokes for 4.4
years in 111 asymptomatic and 135 symptomatic
patients with 
50% relevant carotid artery stenosis. At
inclusion, echogenicity of carotid plaques and degree of
stenosis were evaluated with high-resolution B-mode ultrasound
with computer-assisted image processing and Doppler ultrasound,
respectively. We observed 44 ipsilateral ischemic strokes. In
symptomatic patients, relative risk of ipsilateral
ischemic stroke for echolucent versus echorich plaques was 3.1
(95% CI, 1.3 to 7.3), whereas for 80% to 99% versus 50% to 79%
stenosis, the relative risk was 1.4 (95% CI, 0.7 to 3.0).
Relative to symptomatic patients with echorich 50% to 79%
stenotic plaques, those with echorich 80% to 99%
stenotic plaques, echolucent 50% to 79% stenotic
plaques, and echolucent 80% to 99% stenotic plaques had
relative risks of ipsilateral ischemic strokes of 3.1 (95%CI,
0.7 to 14), 4.2 (95% CI, 1.2 to 15), and 7.9 (95% CI, 2.1 to 30),
equivalent to absolute risk increases of 11%, 18%, and 28%. This was
not observed in previously asymptomatic
patients.
Conclusions—Echolucent
plaques causing 50% diameter stenosis by Doppler
ultrasound are associated with risk of future stroke in
symptomatic but not asymptomatic individuals.
This suggests that measurement of echolucency, together with degree of
stenosis, may improve selection of patients for carotid
endarterectomy.
Key Words: arteriosclerosis • stroke • carotid arteries • ultrasonics • follow-up studies
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Introduction |
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TopAbstractIntroductionMethodsResultsDiscussionReferences |
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Benefit of prophylactic carotid endarterectomy in patients with severe carotid stenoses and previous focal neurological symptoms has been demonstrated in 2 randomized multicenter trials1 2 ; however,
7 operations were performed to avoid 1 stroke. In the only similar
trial studying previously asymptomatic patients with severe
carotid stenoses, 20 operations were needed to prevent a single
stroke.3 Most cerebrovascular events are associated with carotid stenoses <75%, indicating atheroembolic rather than low-flow genesis.4 Therefore, noninvasive identification of plaque types prone to rupturing and causing embolic stroke would help to improve the effectiveness of this operation. Ultrasonic measurement of plaque echolucency, indicating plaques with lipid-rich cores,5 6 7 8 9 10 11 12 is one such promising measurement; subjectively evaluated echolucency of carotid plaques on ultrasound B-mode imaging was associated with the presence or development of neurological events.4 13 14 15 16 17 The ability of objective computer-assisted ultrasound evaluation of plaque echolucency to predict stroke incidence, however, has not been reported in a prospective study.
We tested prospectively the hypothesis that stroke
development can be predicted by echolucency of carotid atherosclerotic
plaques in symptomatic and asymptomatic
patients with 50% carotid
stenosis.
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Methods |
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TopAbstractIntroductionMethodsResultsDiscussionReferences |
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Subjects
The study included 246 consecutive patients recruited from 1556 patients referred for carotid ultrasound examination at Rigshospitalet (Copenhagen University Hospital) from 1994 to 1996 (Table 1
). Entry criterion was a degree of carotid
stenosis 50% ipsilateral to previously
symptomatic (n=135) or asymptomatic hemispheres
(n=111).
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Symptomatic patients had experienced ischemic strokes with moderate disabilities (n=31), minor ischemic strokes with no residual deficits (n=47), transient ischemic attacks (TIA; n=45), or amaurosis fugax (AF; n=12) on the side related to the relevant carotid stenosis. The reasons for including symptomatic carotid patients in this study and thereby renouncing from carotid endarterectomy were age >70 years (n=26), severe illness (n=10), patient refusal of operation (n=12), moderate neurological deficits remaining after stroke (n=31), symptoms >6 months ago (n=25), or degree of stenosis <70% (n=33).
Of the asymptomatic patients, 46 were duplex scanned for carotid bruit or various nonspecific, nonhemispheric symptoms such as dizziness and vertigo. The remaining 65 patients in the asymptomatic group had experienced hemispheric symptoms contralateral to the asymptomatic stenotic artery followed up in this study.
The 1310 excluded patients were those with carotid stenosis <50%, occlusion of both internal carotid arteries, severe neurological disability, fatal cancer, severe dementia, or endarterectomy of the vessel that otherwise could have been followed up. Of the 246 patients included in the present study, 137 were also studied in a previous publication.13
The study was approved by the Medical Ethics Committee for Copenhagen and Frederiksberg (No. KF 01-062/94). All patients gave informed consent.
Ultrasound Examination
At inclusion, echogenicity of carotid plaques was
evaluated with high-resolution B-mode ultrasound and computer-assisted
image processing. The B-mode and corresponding color Doppler images
of the carotid artery plaques were recorded onto super-VHS
videotape, digitized with a Targa 2000 frame grabber, and processed
with the software program Image-Pro Plus, version 1.2.01, for Windows
(Media Cybernetics). Outlines of an area of plaque, blood, and
brightest adventitia at the level of the plaque were drawn on the
B-mode image. In case of echolucency, corresponding color Doppler
images or video sequences of the same plaque helped to detect the exact
borders of the carotid artery plaque. The gray-scale value of each
pixel in these 3 outlined regions (0 to 255; 0=black and 255=white)
were used to calculate median gray-scale
values.13 A standardization
method of B-mode images was
used18 ; the median
gray-scale value of the plaque was adjusted linearly so that the median
value of blood was 0 and that of adventitia was 190. In case of
acoustic shadowing from a plaque, the shadow region was not included in
the outline. The mean of the standardized median gray-scale values of
the plaque was used to divide plaques into echolucent (<74) and
echorich (74), respectively. The coefficient of variation for
gray-scale measurements was 5.5% when 58 consecutively chosen images
were reprocessed by the same ultrasonographer (M.-L.M.G.) to obtain a
second set of gray-scale
values.8
Degree of stenosis was determined by routine
Doppler criteria as <50%, 50% to 79%, 80% to 99%, or
occlusion. A systolic velocity >120 cm/s equals 50%
stenosis, and a diastolic velocity >135 cm/s
equals 80% stenosis, validated by angiography as the gold
standard.19 Ultrasound
examinations and computer processing of images were performed by an
experienced ultrasonographer (M.-L.M.G.) before end-point
identification.
End Points
Neurological and cardiac symptoms occurring during
the 4.4-year observation period were noted (by M.-L.M.G.) at each
6-month visit or during a final telephone interview. Subsequently,
neurological symptoms were further evaluated by a neurological
consultant (S.V.) on the basis of collected copies of medical
reports from hospitals and/or general practitioners. The
consultant was not aware of results from the ultrasound
examinations.
The primary end point of the study was ischemic stroke developed ipsilateral to the relevant carotid stenosis. Secondary end points were ipsilateral AF and TIA. Tertiary end points were coronary events such as myocardial infarction, onset of angina pectoris, PTCA, or CABG and total mortality.
Ischemic strokes were defined as focal neurological symptoms lasting >24 hours (with or without persisting disabilities) for which CT showed corresponding ischemic infarction and ruled out cerebral hemorrhage. Hemorrhagic strokes (n=4) were excluded as events. Patients with bilateral hemispheric symptoms and those with known cardiac mural thrombus (as verified on echocardiography) were excluded from the analysis because of suspected cardioembolic origin (n=5). TIA was defined as ipsilateral focal neurological symptoms lasting <24 hours. AF was temporary monocular blindness ipsilateral to the relevant carotid artery stenosis.
Causes of death were obtained from the Danish Registry of Causes of Death. Follow-up was 100%.
Statistical Analysis
Data were stratified a priori in
symptomatic and asymptomatic patients but were
also analyzed combined. Kaplan-Meier curves for event-free
survival and log-rank tests evaluated the differences between 2 plaque
types (echolucent versus echorich or 80% to 99% stenosis
versus 50% to 79% stenosis) with the Statistica program
(Statsoft). Relative risks (with 95% CIs) of primary, secondary, and
tertiary end points for plaque type (echolucent versus echorich, 80%
to 99% stenosis versus 50% to 79% stenosis, or
combinations of these versus echorich 50% to 79% stenosis)
were calculated with the Cox regression model with the use of SPSS
(SPSS Inc). Cox regression models with plaque type as a predictor of
end points adjusted for either age or age and other risk factors (sex,
hypertension, smoking, diabetes mellitus, and atrial fibrillation).
Censorship was as follows: (1) for the primary end point ipsilateral
ischemic stroke, it was death, ipsilateral
endarterectomy, or ipsilateral ischemic
stroke; (2) for the secondary end point ipsilateral TIA and AF, it was
death, ipsilateral endarterectomy, ipsilateral
ischemic stroke, or ipsilateral TIA or AF; (3) for the tertiary
end point cardiac event, it was death or cardiac event; and (4) for the
tertiary end point death, it was death only. Interaction between plaque
type and symptomatic/asymptomatic status was
tested in a Cox model in which both these factors, the 2-way
interaction term between these 2 factors, and age were entered; the
likelihood ratio test determined statistical significance. Values of
P
0.05 were considered
significant.
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Results |
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TopAbstractIntroductionMethodsResultsDiscussionReferences |
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The 246 patients were followed up for an average of 4.4 years; those surviving were followed up from 3.0 to 5.8 years. Risk factors for stroke, previous focal neurological symptoms, and lipid profiles of participants are shown in Table 1
. Risk factor and lipid profiles were similar in
previously symptomatic and asymptomatic
patients.
We observed 44 ipsilateral ischemic strokes, 35
ipsilateral AF or TIA, 36 coronary events, and 64 deaths
(Table 2). Seventeen patients underwent carotid
endarterectomy.
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Stroke Predicted by Plaque Echolucency or
Stenosis
Patients with echolucent plaques experienced more
ipsilateral ischemic strokes compared with those with echorich
plaques
(Figure 1; log-rank
P=0.02). This was found in
previously symptomatic patients
(Figure 2, top right; log-rank
P=0.005; at 4.4 years, 29%
versus 12%) but not in previously asymptomatic patients
(Figure 2, top left; log-rank
P=0.85). On Cox regression
adjusted for age, symptomatic patients with echolucent
plaques versus echorich plaques had a 3.1-fold (95% CI, 1.3 to 7.3)
risk of ipsilateral ischemic stroke
(Table 3). When the analysis also was adjusted for
other risk factors for stroke, the results were similar.
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|
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There was a weak trend suggesting that those with 80% to
99% versus 50% to 79% carotid stenosis experienced more
ipsilateral ischemic strokes
(Figure 1; log-rank
P=0.18). In previously
symptomatic patients, there was a similar trend
(Figure 2, bottom right; log-rank
P=0.11; at 4.4 years, 28%
versus 18%) but not in previously asymptomatic patients
(Figure 2, bottom left; log-rank
P=0.93). On Cox regression,
symptomatic patients with 80% to 99% versus 50% to 79%
carotid stenosis had a nonsignificant 1.4-fold (95% CI, 0.7 to
3.0) risk of ipsilateral ischemic stroke
(Table 3).
Symptomatic/asymptomatic status did
not interact statistically with echogenicity or stenosis
severity on ipsilateral ischemic strokes (Cox regression,
P=0.13 and
P=0.42). Neither plaque
echolucency nor percent stenosis was associated with incidence
of ipsilateral TIA/AF, cardiac events, or total deaths
(Table 3).
Stroke Predicted by Plaque Echolucency and
Stenosis
Among previously symptomatic patients
and relative to those with echorich 50% to 79% stenotic
plaques, those with echorich 80% to 99%, echolucent 50% to 79%, and
echolucent 80% to 99% stenotic plaques had relative risks of
ipsilateral ischemic strokes of 3.1 (95% CI, 0.7 to 14), 4.2
(95% CI, 1.2 to 15), and 7.9 (95% CI, 2.1 to 30), respectively
(Table 4). This is equivalent to absolute risk increases in
the 3 latter groups of 11%, 18%, and 28%, respectively. This was not
observed among previously asymptomatic patients
(Table 4).
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Discussion |
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TopAbstractIntroductionMethodsResultsDiscussionReferences |
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Important new results from this prospective study include the following: (1) objectively measured echolucent carotid plaques compared with echorich plaques predict a 3.1-fold risk of ipsilateral ischemic strokes (equivalent to 17% absolute risk increase) in previously symptomatic but not in previously asymptomatic patients, and (2) among previously symptomatic patients, echolucent 80% to 99% stenotic plaques predict an 8-fold risk compared with echorich 50% to 79% stenotic plaques (equivalent to 28% absolute risk increase). Our data suggest that if computer-assisted measurement of echolucency is used selectively in symptomatic patients, this ultrasound evaluation may improve the selection of patients for carotid endarterectomy.
Supporting our findings, the only other follow-up study
investigating 4886 asymptomatic individuals found that
subjectively evaluated echolucent plaques compared with echorich
plaques conferred a relative risk for ischemic stroke of 2.5
(95% CI, 1.4 to 4.5).17
After adjustment for conventional risk factors, echolucent plaques had
a relative risk of 1.7
(P=0.015), whereas degree of
stenosis 50% (versus <50%) showed a relative risk of 2.3
(P=0.004).17
The mechanism behind the association between plaque echolucency and increased stroke incidence is not completely resolved. El-Barghouty et al6 found that the content of soft tissue (ie, lipid and hemorrhage) in the plaque was associated with plaque echolucency. Conversely, a highly fibrous tissue content was associated with echorich plaques.6 We and others have confirmed these findings.8 12 Thus, because echolucency is associated with lipid-rich carotid plaques6 7 8 14 and coronary plaques rich in lipid are thought to be most prone to rupturing and causing clinical events,11 it seems possible that carotid echolucent plaques are those most prone to rupture and thus cause embolic stroke.
An association between plaque echolucency and stroke incidence was observed in previously symptomatic but not in asymptomatic individuals. Because statistical evidence of an interaction between echolucency and symptomatic/asymptomatic status on stroke incidence was not found, a possible explanation for the absence of association in asymptomatic patients is lack of power. Alternatively, echolucency could reflect different pathogeneses in the 2 types of patients: a previous plaque rupture with thrombus formation and intraplaque hemorrhage leading to embolization in symptomatic patients but relatively stable lipid-rich plaque content in asymptomatic patients. B-mode ultrasound imaging cannot reliably determine whether hypoechoic/echolucent material represents lipid, hemorrhage, or thrombus. However, the latter 2 possibilities are not very likely because plaque hemorrhage (including thrombus and constituting <1% of the plaque) was not associated with plaque echolucency, as was "lipid," an eosinophilic, amorphous substance histochemically identical with cholesterol and its esters (constituting 40% of the plaque).5 8 Moreover, thrombus is not always present in plaques from patients with recent symptoms, although it may be found in as many as 80% of asymptomatic patients.9 The presence of thrombosis is probably intermittent, reflecting the dynamic process of rupture, thrombus formation, healing, and remodeling of the plaque.11
The absence of a significant association between severity of
stenosis and stroke incidence in the present study was
unexpected and probably due to a lack of power because several previous
studies have indicated such
findings.20 21
Both the European Carotid Surgery
Trial1 and the North American
Symptomatic Carotid Endarterectomy
Trial2 found stroke
incidences in symptomatic patients resembling our incidence
rate of 21% at 4.4 years: 17% cumulative risk of ipsilateral stroke
in 3 years and 26% risk in 2 years of follow-up in medically treated
patients with >70% stenosis, respectively. Correspondingly,
in the Asymptomatic Carotid Atherosclerosis
Study, the 5-year cumulative risk of ipsilateral stroke was 11% in in
asymptomatic patients with 60%
stenosis.3
In the present study, 26% of carotid stenosis patients died during 4.4 years of follow-up. This demonstrates that we studied a very sick population of patients, which has the advantage that a large number of end points accumulated over a relatively short period of time. Nevertheless, it would also have been interesting to study a younger, less diseased population of patients in whom the strength of echo as a noninvasive procedure in predicting first-time stroke could be tested.
Potential study limitations include the fact that we were
not able to exclude ischemic strokes of origins other than the
carotid plaques, ie, strokes occurring as a result of lesions in the
aorta or intracranial vessels; however, strokes thought to be of
cardioembolic origin and hemorrhagic strokes were excluded.
Reproducibility of the ultrasound evaluation could be another
limitation. Few results have been published on reproducibility of
computer-assisted ultrasound imaging, but those existing are very
promising.8 18
Elatrozy et al18 found
coefficients of variation among 4 observers of 4.7%. The coefficient
of variation in this study for intraobserver variation was
5.5%,8 a high degree of
agreement on repeated examinations. Furthermore, ultrasound B-mode
imaging suffers from limitations like acoustic shadowing resulting from
calcifications in the plaque, speckle diffraction, and angle
dependence.22 These problems
might be reduced with a newly available technique, multiangle spatial
compound imaging.23 This
technique combines images from multiple different scanning angles,
thereby reducing speckle and angle dependence and improving image
quality. The ultrasound procedure is fast and relatively inexpensive
and includes both measurement of degree of stenosis and
gray-scale level in the plaque. MRI may also be a good discriminator of
vulnerable carotid plaque features in vitro and probably in
vivo.24 25 26
This method has a higher spatial resolution than ultrasound B-mode and
does not suffer from acoustical shadows. However, this method is still
very expensive, and its use in plaque characterization is limited
mainly to research. Furthermore, MRI has to overcome flow and motion
artifacts and overestimation of degree of stenosis.
In conclusion, the present results suggest that
measurement of carotid plaque echolucency, together with severity of
stenosis, may improve patient selection for carotid
endarterectomy. Because definite benefit for
surgery applies to all symptomatic individuals with a
stenosis of 50%,2
plaque texture or echogenicity might be particularly useful to inform
patients of an excess risk. Furthermore, in countries where not all
symptomatic patients with 50% stenosis are
offered an operation, additional information on plaque echolucency may
help doctors offer a limited number of operations to those with
potentially the most benefit. Finally, ultrasound echolucency can also
add to the strength of operation indication in cases of
"borderline" severity of stenosis (
50%), single
neurological events as opposed to multiple events, and AF, which does
not carry the same high risk as hemispheric symptoms, TIA, or
stroke.
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Acknowledgments |
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The Center for Atherosclerosis Detection by Ultrasound was supported by the Danish Medical and Technical Research Council. We appreciate the technical assistance of Jens Wilhjelm, who provided the standardized ultrasonic measures, and the secretarial assistance of Ming Yuan Gao.
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Footnotes |
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Reprint requests to Dr Marie-Louise Moes Grønholdt, Blomstervaenget 18, DK-2800 Lyngby, Denmark.
Received February 2, 2001; revision received April 10, 2001; accepted April 11, 2001.
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References |
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M. Maynar, S. Baldi, R. Rostagno, T. Zander, M. Rabellino, R. Llorens, J. Alvarez, and F. Barajas Carotid Stenting without Use of Balloon Angioplasty and Distal Protection Devices: Preliminary Experience in 100 Cases AJNR Am. J. Neuroradiol., August 1, 2007; 28(7): 1378 - 1383. [Abstract] [Full Text] [PDF]
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 J. J. Cao, A. M. Arnold, T. A. Manolio, J. F. Polak, B. M. Psaty, C. H. Hirsch, L. H. Kuller, and M. Cushman Association of Carotid Artery Intima-Media Thickness, Plaques, and C-Reactive Protein With Future Cardiovascular Disease and All-Cause Mortality: The Cardiovascular Health Study Circulation, July 3, 2007; 116(1): 32 - 38. [Abstract] [Full Text] [PDF]
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G. Ostling, B. Hedblad, G. Berglund, and I. Goncalves Increased Echolucency of Carotid Plaques in Patients With Type 2 Diabetes Stroke, July 1, 2007; 38(7): 2074 - 2078. [Abstract] [Full Text] [PDF]
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S. Prabhakaran, T. Rundek, R. Ramas, M. S.V. Elkind, M. C. Paik, B. Boden-Albala, and R. L. Sacco Carotid Plaque Surface Irregularity Predicts Ischemic Stroke: The Northern Manhattan Study Stroke, November 1, 2006; 37(11): 2696 - 2701. [Abstract] [Full Text] [PDF]
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 S. Sirivella and I. Gielchinsky Clinical outcomes of surgery of mitral valve regurgitation and coronary artery bypass grafting Interactive CardioVascular and Thoracic Surgery, August 1, 2006; 5(4): 392 - 397. [Abstract] [Full Text] [PDF]
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R. Sztajzel, I. Momjian-Mayor, M. Comelli, and S. Momjian Correlation of Cerebrovascular Symptoms and Microembolic Signals With the Stratified Gray-Scale Median Analysis and Color Mapping of the Carotid Plaque Stroke, March 1, 2006; 37(3): 824 - 829. [Abstract] [Full Text] [PDF]
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N. Takaya, C. Yuan, B. Chu, T. Saam, H. Underhill, J. Cai, N. Tran, N. L. Polissar, C. Isaac, M. S. Ferguson, et al. Association Between Carotid Plaque Characteristics and Subsequent Ischemic Cerebrovascular Events: A Prospective Assessment With MRI--Initial Results Stroke, March 1, 2006; 37(3): 818 - 823. [Abstract] [Full Text] [PDF]
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N.F. Fanning, T.D. Walters, A.J. Fox, and S.P. Symons Association between Calcification of the Cervical Carotid Artery Bifurcation and White Matter Ischemia. AJNR Am. J. Neuroradiol., February 1, 2006; 27(2): 378 - 383. [Abstract] [Full Text] [PDF]
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Y. K. Mishra, S. Mittal, P. Jaguri, and N. Trehan Coapsys Mitral Annuloplasty for Chronic Functional Ischemic Mitral Regurgitation: 1-Year Results Ann. Thorac. Surg., January 1, 2006; 81(1): 42 - 46. [Abstract] [Full Text] [PDF]
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 J. Aoki, A. C. Abizaid, P. W. Serruys, A. T.L. Ong, E. Boersma, J. E. Sousa, and N. Bruining Evaluation of Four-Year Coronary Artery Response After Sirolimus-Eluting Stent Implantation Using Serial Quantitative Intravascular Ultrasound and Computer-Assisted Grayscale Value Analysis for Plaque Composition in Event-Free Patients J. Am. Coll. Cardiol., November 1, 2005; 46(9): 1670 - 1676. [Abstract] [Full Text] [PDF]
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B. A. Wasserman, R. J. Wityk, H. H. Trout III, and R. Virmani Low-Grade Carotid Stenosis: Looking Beyond the Lumen With MRI Stroke, November 1, 2005; 36(11): 2504 - 2513. [Abstract] [Full Text] [PDF]
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D. R. Wong, A. K. Agnihotri, J. W. Hung, G. J. Vlahakes, C. W. Akins, A. D. Hilgenberg, J. C. Madsen, T. E. MacGillivray, M. H. Picard, and D. F. Torchiana Long-Term Survival After Surgical Revascularization for Moderate Ischemic Mitral Regurgitation Ann. Thorac. Surg., August 1, 2005; 80(2): 570 - 577. [Abstract] [Full Text] [PDF]
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 B Wolff, H J Grabe, H Volzke, J Ludemann, C Kessler, J B Dahm, H J Freyberger, U John, and S B Felix Relation between psychological strain and carotid atherosclerosis in a general population Heart, April 1, 2005; 91(4): 460 - 464. [Abstract] [Full Text] [PDF]
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R. Sztajzel, S. Momjian, I. Momjian-Mayor, N. Murith, K. Djebaili, G. Boissard, M. Comelli, and G. Pizolatto Stratified Gray-Scale Median Analysis and Color Mapping of the Carotid Plaque: Correlation With Endarterectomy Specimen Histology of 28 Patients Stroke, April 1, 2005; 36(4): 741 - 745. [Abstract] [Full Text] [PDF]
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I. Goncalves, M. W. Lindholm, L. M. Pedro, N. Dias, J. Fernandes e Fernandes, G. N. Fredrikson, J. Nilsson, J. Moses, and M. P.S. Ares Elastin and Calcium Rather Than Collagen or Lipid Content Are Associated With Echogenicity of Human Carotid Plaques Stroke, December 1, 2004; 35(12): 2795 - 2800. [Abstract] [Full Text] [PDF]
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 K. C. Wang, D. Saloner, and J. H. Rapp Characteristics of Carotid Plaque as Risk Factors for Stroke Perspectives in Vascular Surgery and Endovascular Therapy, September 1, 2004; 16(3): 193 - 199. [Abstract] [PDF]
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G. M. Biasi, A. Froio, E. B. Diethrich, G. Deleo, S. Galimberti, P. Mingazzini, A. N. Nicolaides, M. Griffin, D. Raithel, D. B. Reid, et al. Carotid Plaque Echolucency Increases the Risk of Stroke in Carotid Stenting: The Imaging in Carotid Angioplasty and Risk of Stroke (ICAROS) Study Circulation, August 10, 2004; 110(6): 756 - 762. [Abstract] [Full Text] [PDF]
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A. Lombardo, L. M. Biasucci, G. A. Lanza, S. Coli, P. Silvestri, D. Cianflone, G. Liuzzo, F. Burzotta, F. Crea, and A. Maseri Inflammation as a Possible Link Between Coronary and Carotid Plaque Instability Circulation, June 29, 2004; 109(25): 3158 - 3163. [Abstract] [Full Text] [PDF]
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 S. Golemati, T. J. Tegos, A. Sassano, K. S. Nikita, and A. N. Nicolaides Echogenicity of B-mode Sonographic Images of the Carotid Artery: Work in Progress J. Ultrasound Med., May 1, 2004; 23(5): 659 - 669. [Abstract] [Full Text] [PDF]
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O. Honda, S. Sugiyama, K. Kugiyama, H. Fukushima, S. Nakamura, S. Koide, S. Kojima, N. Hirai, H. Kawano, H. Soejima, et al. Echolucent carotid plaques predict future coronary events in patients with coronary artery disease J. Am. Coll. Cardiol., April 7, 2004; 43(7): 1177 - 1184. [Abstract] [Full Text] [PDF]
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R. Kern, K. Szabo, M. Hennerici, and S. Meairs Characterization of Carotid Artery Plaques Using Real-time Compound B-mode Ultrasound Stroke, April 1, 2004; 35(4): 870 - 875. [Abstract] [Full Text] [PDF]
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H. Yamagami, K. Kitagawa, Y. Nagai, H. Hougaku, M. Sakaguchi, K. Kuwabara, K. Kondo, T. Masuyama, M. Matsumoto, and M. Hori Higher Levels of Interleukin-6 Are Associated With Lower Echogenicity of Carotid Artery Plaques Stroke, March 1, 2004; 35(3): 677 - 681. [Abstract] [Full Text] [PDF]
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B. Wolff, H. Volzke, J. Ludemann, D. Robinson, D. Vogelgesang, A. Staudt, C. Kessler, J. B. Dahm, U. John, and S. B. Felix Association Between High Serum Ferritin Levels and Carotid Atherosclerosis in the Study of Health in Pomerania (SHIP) Stroke, February 1, 2004; 35(2): 453 - 457. [Abstract] [Full Text] [PDF]
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R. A. Levine and J. Hung Ischemic mitral regurgitation, the dynamic lesion: clues to the cure J. Am. Coll. Cardiol., December 3, 2003; 42(11): 1929 - 1932. [Full Text] [PDF]
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D. Paparella, L. L. Mickleborough, S. Carson, and J. Ivanov Mild to moderate mitral regurgitation in patients undergoing coronary bypass grafting: effects on operative mortality and long-term significance Ann. Thorac. Surg., October 1, 2003; 76(4): 1094 - 1100. [Abstract] [Full Text] [PDF]
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C. Denzel, K. Balzer, K.-M. Muller, F. Fellner, C. Fellner, and W. Lang Relative Value of Normalized Sonographic In Vitro Analysis of Arteriosclerotic Plaques of Internal Carotid Artery Stroke, August 1, 2003; 34(8): 1901 - 1906. [Abstract] [Full Text] [PDF]
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 S.C. Kofoed, H.H. Wittrup, H. Sillesen, and B.G. Nordestgaard Fibrinogen predicts ischaemic stroke and advanced atherosclerosis but not echolucent, rupture-prone carotid plaques: The Copenhagen City Heart Study Eur. Heart J., March 2, 2003; 24(6): 567 - 576. [Abstract] [Full Text] [PDF]
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 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]
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 G. D. Kolovou, D. Ch. Daskalova, M. Hatzivassiliou, N. Yiannakouris, N. D. Pilatis, M. Elisaf, D. P. Mikhailidis, M. A. Cariolou, and D. V. Cokkinos The Epsilon 2 and 4 Alleles of Apolipoprotein E and Ischemic Vascular Events in the Greek Population -- Implications for the Interpretation of Similar Studies Angiology, January 1, 2003; 54(1): 51 - 58. [Abstract] [PDF]
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G. A. Tolis Jr, D. P. Korkolis, G. S. Kopf, and J. A. Elefteriades Revascularization alone (without mitral valve repair) suffices in patients with advanced ischemic cardiomyopathy and mild-to-moderate mitral regurgitation Ann. Thorac. Surg., November 1, 2002; 74(5): 1476 - 1481. [Abstract] [Full Text] [PDF]
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E. Mohler III Vascular calcification: good, bad or ugly? Vascular Medicine, August 1, 2002; 7(3): 161 - 162. [PDF]
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M. Hollander, M.L. Bots, A. I. del Sol, P.J. Koudstaal, J.C.M. Witteman, D.E. Grobbee, A. Hofman, and M.M.B. Breteler Carotid Plaques Increase the Risk of Stroke and Subtypes of Cerebral Infarction in Asymptomatic Elderly: The Rotterdam Study Circulation, June 18, 2002; 105(24): 2872 - 2877. [Abstract] [Full Text] [PDF]
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J. L. Hunt, R. Fairman, M. E. Mitchell, J. P. Carpenter, M. Golden, T. Khalapyan, M. Wolfe, D. Neschis, R. Milner, B. Scoll, et al. Bone Formation in Carotid Plaques: A Clinicopathological Study Stroke, May 1, 2002; 33(5): 1214 - 1219. [Abstract] [Full Text] [PDF]
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K. Sheikh, E. B. Mathiesen, K. H. Bonaa, and O. Joakimsen Cholesterol and Carotid Stenosis Stroke, January 1, 2002; 33(1): 321 - 322. [Full Text] [PDF]
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