This Article Abstract Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Crouse, J. R. Articles by Bond, M. G. Search for Related Content PubMed PubMed Citation Articles by Crouse, J. R., III Articles by Bond, M. G.

(Circulation. 1995;92:1141-1147.)
© 1995 American Heart Association, Inc.

Articles

Association of Coronary Disease With Segment-Specific Intimal-Medial Thickening of the Extracranial Carotid Artery

John R. Crouse, III, MD; Timothy E. Craven, MSPH; Amy P. Hagaman, MA; M. Gene Bond, PhD

From the Departments of Medicine and Public Health Sciences and the Division of Vascular Ultrasound Research, Bowman Gray School of Medicine of Wake Forest University, Winston Salem, NC.

	Abstract

Top Abstract Introduction Methods Results Discussion References

 
Background Several investigators have evaluated relations between risk factors and intimal-medial thickness (IMT) of the extracranial carotid arteries and between IMT and clinical cardiovascular disease. Different indexes of IMT have been used as referents. We compared the strength of association of various IMT measurements with coronary artery disease as measured at coronary angiography.

Methods and Results We quantified the mean of the IMT for 12 sites of the extracranial carotid arteries (common carotid, bifurcation, internal carotid, near and far walls, and left and right sides [mean aggregate]) as well as for various combinations of sites (eg, segment-specific means, far walls only, maximum of any site) in 270 patients with or free of coronary artery disease. Models including age and all the indexes of IMT identified the mean aggregate as the only variable independently associated with the status of coronary atherosclerosis for the group as a whole. Next most strongly correlated was the mean common plus bifurcation. When classification algorithms were tested for ability to correctly classify case patients and control subjects, the mean bifurcation, mean common plus bifurcation, and mean aggregate were most strongly related to case-control status; however, the predictive power of the mean common was also strong.

Conclusions These data support use of the mean aggregate extracranial carotid IMT for correlation with the status of coronary atherosclerosis; however, the data also support use of the mean common plus bifurcation, since there is little increase in predictive power of the mean aggregate over this index. Use of the common carotid alone is also justifiable and may be preferable for certain analyses.

Key Words: coronary disease • carotid arteries

	Introduction

Top Abstract Introduction Methods Results Discussion References

 
A number of studies have quantified the association of intimal-medial thickness (IMT) of the extracranial carotid arteries and the status of coronary atherosclerosis.^{1 2 3 4 5 6 7} More recently, an association has been observed between atherosclerosis of the common carotid artery and incident coronary heart disease (CHD).⁸ In addition, studies have shown that factors that reduce risk of coronary artery disease (CAD) can influence progression rates of extracranial carotid atherosclerosis as measured by B-mode^{9 10 11} or Doppler¹² ultrasound, and extracranial carotid atherosclerosis has been shown to progress faster in individuals with adverse levels of CAD risk factors^{13 14 15} and in individuals who themselves have coronary artery disease.¹⁶ IMT of the extracranial carotid arteries has often been quantified as the mean of IMT from 12 sites at three segments (left and right side, near and far wall of the common carotid, bifurcation, and internal carotid artery) or, alternatively, as the mean of IMT at 4 sites for each segment.¹⁷ Few data suggest a stronger association of CAD with disease at one or the other of these segments or, alternatively, with the mean aggregate. To investigate segment-specific associations with CAD in more detail, we quantified IMT of the extracranial carotid arteries in 270 individuals who were recruited as part of a study of risk factors for individuals undergoing coronary angiography, and we related IMT at the individual segments and sites to the status of coronary atherosclerosis.

	Methods

Top Abstract Introduction Methods Results Discussion References

 
Population
The population recruited for this study is an extension of populations described previously, drawn from individuals undergoing cardiac catheterization at Bowman Gray School of Medicine.² The study includes individuals who have undergone cardiac catheterization to define the status of coronary atherosclerosis. Inclusion criteria include age 45 years and catheterization that identifies "case patients" (50% stenosis of one or more vessels) and "control subjects" (no lumen irregularities). Equal numbers of case patients, control subjects, men, and women were recruited according to a stratified random sampling strategy. Patients with coronary stenosis of <50% were excluded ("nonobstructive" CAD). Exclusion criteria include clinical instability (patients with myocardial infarction within the past 6 weeks, cardiogenic shock, or other evidence of clinical instability), previous coronary artery bypass surgery or angioplasty, use of certain medications or presence of certain clinical conditions that would alter plasma lipids (use of hypolipidemic drugs or thyroid medication, use of cortisone, liver disease, alcohol abuse, creatinine 2.5, or heparin use), or certain unusual conditions, for example, individuals with carcinoma. In addition, patients with prevalent symptomatic cerebrovascular disease are excluded (stroke, transient ischemic attack, endarterectomy). Participants all provided informed consent.

For this study, individuals underwent initial risk factor profile testing approximately 6 to 8 weeks after their catheterization at a Preventive Cardiology Outpatient Clinic.

Clinical Evaluation
At the time of their clinic visit, participants were interviewed by the study coordinator using a standardized questionnaire. She obtained information regarding their heart and vascular disease history, vascular disease risk factor status, menstrual status, medications, and prior diagnostic evaluations. Participants also underwent measurement of height, weight, blood pressure, waist and hip girth, and cardiovascular disease risk factors. The presence of hypertension was defined by a history of the disease or a systolic blood pressure >150 mm Hg or a diastolic blood pressure >90 mm Hg. The presence of diabetes was defined by history of the disease or by a fasting glucose level of >140 mg/dL. Smoking status was recorded as the number of pack-years smoked.

Lipoprotein Analysis
Plasma total cholesterol and triglyceride and lipoprotein cholesterol were quantified in the Centers for Disease Control and Prevention–standardized Lipid Laboratory of the Bowman Gray School of Medicine according to the Lipid Research Clinics Program procedures.¹⁸ Cholesterol and triglyceride determinations were done on the Technicon RA-500 by enzymatic methods. For the determination of plasma HDL cholesterol concentrations, the heparin-manganese precipitation procedure as described in the Lipid Research Clinics manual was used. For total and HDL cholesterol determinations, the RA-500 enzymatic method was used with the Technicon reagent substituted by the Boehringer-Mannheim (BMD) high-performance cholesterol reagent.¹⁹ HDL plus LDL cholesterols were recovered after ultracentrifugation (in the 1.006 infranatant), and LDL was quantified as the difference between the 1.006 infranatant cholesterol and the cholesterol in the infranatant after precipitation of LDL.

Ultrasound
The ultrasound methodology for this trial was similar to one previously described.²⁰ A Biosound 2000 II s.a. high-resolution ultrasound unit equipped with an 8-MHz transducer was used. Images were transcribed on SVHS 1/2-in videotape. An RMI 414B tissue-mimicking phantom was used to monitor and ensure instrument performance. Sonography and reading were done by trained and certified sonographers and ultrasound readers with regular quality control. Patients are examined in the supine position, and each carotid wall and segment is interrogated independently from continuous angles to identify the thickest intima-media site. Each scan of the common carotid artery begins just above the clavicle, and the transducer is moved cephalad through the bifurcation and along the internal carotid artery. Three segments are identified on each side: the distal 1.0 cm of the common carotid proximal to the bifurcation, the bifurcation itself, and the proximal 1.0 cm of the internal carotid artery. At each of the three segments for both near and far wall in the left and right carotid arteries, the sonographer identifies two interfaces: on the near wall, the first interface (interface 2) is the adventitial-medial boundary and the second (interface 3) is the intima-lumen boundary; on the far wall, the first interface (interface 4) is the lumen-intima and the second (interface 5) is medial-adventitial. Thus, 2-3 and 4-5 define IMTs on the near and far walls, respectively. When these interfaces have been demonstrated, the sonographer reduces gain and time-gain control settings as low as possible to decrease artifacts and then records the video images that include the maximum 2-3 and 4-5 IMTs at each of the 12 segments. Readers examine the videotapes and identify frames that demonstrate the maximum 2-3 and 4-5 IMTs within each segment. Frames are captured electronically and displayed on high-resolution monitors, and wall maximum thicknesses are calculated at each site.

Statistical Evaluation
For this study, case patients and control subjects were compared on the basis of several B-mode ultrasound characteristics of the extracranial carotid arteries. The segment-specific mean of the maximum of 4 sites for each of three segments (near and far wall, left and right side) was calculated (mean common, mean bifurcation, mean internal), as well as the mean of the aggregate of all 12 sites (4 sites at each of three segments, mean aggregate) and the mean of the far wall at each of 6 sites. In addition, the segment-specific maximum (maximum of the four wall thicknesses at each of the three segments) was identified (max common, max bifurcation, max internal) and the maximum of all 12 sites (max aggregate).

Statistical Methods
Descriptive statistics were computed for variables of interest. Statistics computed included means, SDs, and percentiles of continuous variables (eg, age, lipid levels, IMT measurements) and frequencies and relative frequencies of categorical factors (eg, diabetes status, hypertension history) by case-control status and by sex. Variables were examined to verify that assumptions of statistical techniques were met. Univariable comparisons of mean lipid levels and IMT measurements between case and control groups were made with unpaired t tests. Univariable comparisons of case-control differences in categorical factors were performed with ² tests. Associations between IMT measurements were examined with Pearson correlation coefficients both overall and by sex.²¹

The logistic discriminant function was used to examine the differential abilities of each of the nine IMT measurements to effectively predict case-control status after age differences between case patients and control subjects were controlled for. This was done by use of separate logistic regression models, one for each IMT variable, each of which included age as a covariable. Comparisons between models were performed by examining medians and interquartile ranges of the resubstitution predicted probabilities of correct classification (ie, the probability of being a case for case patients and one minus the probability of being a case for control subjects²² ). Forward stepwise logistic regression was used to examine which IMT measurement or combination of measurements was best at predicting case or control status. Each IMT measurement was included as a candidate for selection after age was forced into the model. When variable selection was performed, the most significant (smallest P value) IMT with a value of P<.05 was selected first, then the next most significant factor with a value of P<.05 was entered after the factor(s) already selected was controlled for. Stepping continued until all factors with (type III) values of P<.05 were entered, and any factors that stepped into the model that became nonsignificant at a later step were removed.²³

	Results

Top Abstract Introduction Methods Results Discussion References

 
Of 280 individuals recruited for this study, data were available for IMT of all three segments (common carotid, bifurcation, and internal carotid) in 270 participants. The internal carotid artery could not be interrogated at all in 10 participants. Therefore, the analysis of associations of carotid arterial measurements with the status of coronary atherosclerosis was confined to the 270 individuals for whom information regarding IMT at one or more sites for each of the three arterial segments was available. Clinical characteristics of the 280 participants originally enrolled are provided in Table 1. Individuals with CAD were older than those free of CAD and in general had higher total and LDL cholesterol, lower HDL cholesterol, more pack-years of smoking, and a greater prevalence of diabetes and hypertension. Because of the strong and consistent association of age with both the status of coronary atherosclerosis and IMT (data not shown), all analyses have been adjusted for age.

View this table: [in this window] [in a new window]   Table 1. Risk Factors in Patients With CAD and in CAD-Free Control Subjects

In this as in several other studies,^{20 24 25} there was a differential rate of "missing data" for scanning the common carotid, bifurcation, and internal carotid arteries. More than 99% of sites could be evaluated in the common carotid artery and 94% in the bifurcation, but only 78% could be evaluated in the internal carotid. The worst two sites in this regard were the near wall of the left and right internal carotid arteries, where 27% and 30% of the attempted interrogations were unsuccessful.

Mean and maximum age-adjusted IMTs for (1) the aggregate of all three segments, (2) the three segments individually, (3) the common plus bifurcation, and (4) the bifurcation plus internal in 270 participants with and without coronary artery disease are presented in Table 2. This table also shows data for the mean aggregate for the far wall only. There are significant differences between case patients and control subjects for the group as a whole and for men and women separately for every index of IMT. In general, the case-control differences in the mean bifurcation, the mean bifurcation plus common, and the mean aggregate were greater than differences in other indexes of IMT for the group as a whole (T=5.84, 5.85, and 5.93, respectively). For men, case-control differences in the mean bifurcation, the mean common plus bifurcation, the mean internal, and the mean aggregate were greatest (T=3.70, 3.85, 3.97, and 4.19, respectively), whereas in women, the case-control differences in the mean bifurcation, the mean common plus bifurcation, the max bifurcation, and the max aggregate were greatest (T=4.47, 4.31, 4.58, and 5.03, respectively). In the group as a whole and for men and women separately, the case-control differences in the mean bifurcation, the mean common plus bifurcation, and the mean aggregate were consistently large, whereas the differences in the common carotid were relatively small compared with other indexes of IMT. Of interest, while there were large differences in mean internal associated with the status of coronary atherosclerosis in men, these differences were considerably less in women. Similarly, the max aggregate, which showed the largest difference associated with the status of coronary atherosclerosis in women, showed the smallest difference in men. Evaluation of data from the far wall only did not result in greater case-control differences than the mean aggregate (T for the mean aggregate far wall only for the group as a whole and for men and women separately was T=5.34, 3.43, 4.05, respectively; for the mean aggregate, T=5.93, 4.19, 4.08, respectively). SEMs were consistently lowest for the common carotid, followed by the common carotid plus bifurcation and the mean aggregate. SEMs were consistently considerably higher for the maximum indexes.

View this table: [in this window] [in a new window]   Table 2. Mean Segment-Specific IMT in Patients With CAD and in CAD-Free Control Subjects

As shown in Table 3, segment-specific indexes and aggregate indexes were highly correlated with one another (correlation coefficients range from r=.395 to r=.945). In general, the mean of the bifurcation, internal, and common carotid were correlated with one another in the group as a whole and in men and women separately (correlation coefficients range from r=.466 to r=.707), with the bifurcation and the internal carotid showing the strongest association with one another (r=.653, r=.707, and r=.588 for the group as a whole and for men and women separately), as has previously been noted.²⁶ Correlations of the segment-specific maxima with one another were weaker than for the means (range of correlations, from r=.395 to r=.612) but also were strongest for the association of the bifurcation with the internal carotid artery (r=.578, r=.612, and r=.530 for the group as a whole and for men and women separately). The segment-specific and aggregate maxima were highly correlated with the mean segment-specific and mean aggregate indexes of IMT (range of correlation coefficients, from r=.87 to r=.94), and the mean aggregate index correlated with the mean segment-specific indexes, whereas the maximum aggregate index correlated with the maximum segment-specific indexes (correlations were stronger with the bifurcation and internal than with the common carotid artery).

View this table: [in this window] [in a new window]   Table 3. Correlation Coefficient for Interassociation Among IMT Segments

Next, we carried out logistic regression to estimate the independent association of age and the nine measures of carotid IMT with the status of coronary atherosclerosis (Table 4). In this analysis, the mean aggregate was the only variable selected for the group as a whole. The maximum aggregate was selected for women, and both the maximum and mean aggregates were selected for men. Other IMT thickness measures did not remain significant in multivariable analysis because of intercorrelations among sites as described above. We repeated this analysis incorporating only the five mean indexes (three mean segment-specific indexes, the mean common plus bifurcation, and the mean aggregate). In this analysis, the mean aggregate was the only variable selected for the group as a whole and for men, whereas the mean bifurcation was selected for women. In models including only the mean internal, mean bifurcation, mean common, and mean common plus bifurcation, the mean common plus bifurcation was selected for the group as a whole, the mean internal was selected for men, and the mean bifurcation was selected for women.

View this table: [in this window] [in a new window]   Table 4. Results of Forward Stepwise Multivariate Selection Procedures for Logistic Regression Models to Predict the Status of Coronary Atherosclerosis as a Function of Age and Measures of Carotid IMT Overall and by Sex

Finally, we tested individual classification algorithms for their ability to correctly classify case patients and control subjects (Table 5). In this analysis, including age and IMT in the model, the mean bifurcation, the mean common plus bifurcation, and the mean aggregate consistently showed greater power to discriminate case patients from control subjects for the group as a whole and for men and women separately compared with other IMT indexes. The analyses described above (Table 4) identify the mean aggregate (for all patients and for men) and the mean bifurcation (for women) as the best discriminators of CAD case patients from control subjects after exclusion of the (relatively unstable) maximum indexes. Table 5 provides an estimate of the additional power associated with the mean aggregate (for the group as a whole and for men) and of the bifurcation (for women) over the mean common plus bifurcation, and therefore, of the increase in predictive power associated with quantification of the mean internal. For the group as a whole, the median probability of correct classification is .649 for the mean aggregate and .639 for the mean common plus bifurcation. For men, the corresponding probabilities are .646 and .620. For women, the internal is one of the weakest predictors, and the median probabilities for the mean bifurcation versus the mean common plus bifurcation are .656 versus .655. Thus, information from the internal carotid adds very little to the predictive power of the mean common plus bifurcation in any group. Furthermore, increase in predictive power associated with the mean aggregate compared with the mean common carotid was not dramatic (eg, median probability of correct classification for the mean aggregate for all patients was P=.649 and for the mean common, P=.607).

View this table: [in this window] [in a new window]   Table 5. Logistic Models to Predict CAD Status as a Function of Age and Each of the 11 Segment-Specific and Aggregate IMT Measures

	Discussion

Top Abstract Introduction Methods Results Discussion References

 
Many investigators have evaluated associations of risk factors¹⁷ and of change in risk factor levels^{9 10 11 12 27} with extracranial carotid IMT. Others have evaluated associations of extracranial carotid IMT with presence or absence² and extent²⁸ of CAD at angiography as well as with CHD.^{1 3 4 5 6 7} Stenosis of the carotid arteries measured by Doppler^{29 30 31} or by B-mode⁸ ultrasound has also been shown to correlate with CHD incidence. An early evaluation of measurement reliability suggested that an aggregate measure of extracranial carotid IMT extent that incorporates information from the near and far walls of each of three extracranial carotid segments (common, bifurcation, internal carotid) on the left and right sides had greater stability than measurements at individual sites and that incorporation of information from several sites with potentially variable response to risk factors and variable susceptibility to atherosclerosis was advantageous³² ; subsequently, many epidemiological studies have used the mean aggregate IMT as an index of disease of the extracranial carotid arteries^{1 2 6 19 25 26 28} (reviewed in Reference 17). Most clinical trials that have used B-mode ultrasound to evaluate outcome have also focused on the mean aggregate IMT (12 sites) of the extracranial carotid arteries.^{10 11 27} However, several observers have had difficulty in scanning the internal carotid artery, for various technical reasons, including its tortuosity, proximity to the mandible, etc,^{33 34} or have used computerized methods that may be best suited for quantification of the IMT of the far wall of the common carotid artery.⁹ Partly for these reasons, these investigators and others have focused attention on the common carotid artery for epidemiological studies^{4 7 35 36 37} and clinical trials,⁹ and recently, investigators have reported good reliability for measurements confined to the common carotid arteries for computerized⁹ as well as visual³⁸ readings. Use of information from the common carotid only has been criticized because the common carotid is not predisposed to develop stenotic disease. Use of information from the near walls of arteries has also been criticized because of the lesser validity of ultrasound measurements in relation to pathology from these sites compared with far walls.^{39 40}

Another approach to quantification of carotid arterial disease (as in the Cardiovascular Health Study) has been to measure the far wall IMT of the common carotid and internal carotid (really internal carotid plus bifurcation) separately and, in addition, to obtain Doppler ultrasound quantification of percent stenosis of the internal carotid.^{3 41} These data can be used either separately or in the aggregate to characterize individuals according to "wall thickening" or "plaque."

A final alternative to use of the mean of various measurements at segments or in the aggregate is to use the single maximum IMT observed over all sites. The approach that quantifies mean IMT has the advantage of stability and of capturing extent of disease, whereas the approach that quantifies the maximum focuses on severity of disease and probably better identifies arterial plaques. Both approaches are likely to be informative in cross-sectional studies; for longitudinal studies, the greater stability associated with mean measurements is likely to improve analytic power.

The present study identifies strong associations of coronary artery status with mean (near plus far wall) IMT at each of three carotid segments as well as with the mean aggregate IMT. Associations of IMT with CAD were no stronger when information from only the far wall was used, and measurement variability of data from the far wall exceeded that of the near plus far wall. Individual segment-specific and aggregate maxima were strongly correlated with CAD. However, variability of the index represented by the maximum of all sites was greater than for any other index.

In multivariate analysis of the entire roster of potential predictors for the group as a whole, the mean aggregate appeared most informative. In sex-specific analysis for women, the maximum aggregate was most informative, and for men, the mean and maximum aggregates were both predictive, further supporting the importance of the maximum index in cross-sectional analysis. When the individual maximum measurements were not included in the predictive equations, the mean aggregate was most predictive in the group as a whole and in men, whereas the mean of the bifurcation was strongest in women. Including only the segment-specific means in the predictive equation, the mean common plus bifurcation had the strongest predictive power for the status of coronary atherosclerosis in the group as a whole, whereas the mean bifurcation was strongest in women and the mean internal in men. However, from the classification algorithms, the differences in predictive power associated with various indexes of carotid arterial disease were trivial in comparison with the strength of association of each with CAD.

Thus, for cross-sectional studies including men and women, the mean aggregate and/or the individual maximum is the best index of extracranial carotid disease because of their strength of association with CAD. For studies of disease progression or clinical trials, the mean aggregate is probably preferable because of its smaller measurement variability. For those investigators who would prefer not to include the internal carotid in analysis because of difficulty in visualization and lesser stability of measurements of this segment, an ideal B-mode protocol for cohort studies or clinical trials would most likely include the mean of the near and far walls of both the common carotid artery and the bifurcation. Both segments are easily accessible, and inclusion of data from the bifurcation would probably expand the informativeness above that of either segment alone. In our analysis, adding information from the internal carotid to that from the common and bifurcation provided very little additional power to categorize the status of coronary atherosclerosis.

On the other hand, much of the literature that associates extracranial carotid disease with incident CHD focuses on stenosis of the internal carotid artery (eg, see Reference 29); one other study in which segment-specific analyses were compared with one another for ability to predict prevalent CHD found stenosis of the internal carotid artery to be most highly predictive.³ Salonen and Salonen⁸ observed the highest correlation with incident CHD to be plaque or stenosis of the common carotid/bifurcation. Thus, for prediction of incident CHD, an index of stenosis by Doppler or one derived from the maximum IMT observed at all sites may be as strong as or stronger than the mean aggregate index.

Finally, these data also support use of the common carotid artery alone, particularly for studies of associations of risk factors with carotid arterial disease, cohort studies, or clinical trials, in that it, too, is associated with the status of coronary atherosclerosis. It is excellent in regard to measurement stability, and since it is much easier to interrogate than other segments, it may be ideal for certain (eg, computerized) measurements.

	Acknowledgments

 
This research was supported by grant RO-1 HL-35333 from the NHLBI.

	Footnotes

 
Reprint requests to Dr John R. Crouse III, Department of Medicine, Bowman Gray School of Medicine, Medical Center Blvd, Winston-Salem, NC 27157.

Received November 22, 1994; revision received February 27, 1995; accepted February 27, 1995.

	References

Top Abstract Introduction Methods Results Discussion References

 

1. Gostomzyk JG, Heller WD, Gerhardt P, Lee PN, Keil U. B-scan ultrasound examination of the carotid arteries within a representative population (MONICA project Augsburg). Klin Wochenschr. 1988;66(suppl 11):58-65.
   
2. Craven TE, Ryu JE, Espeland MA, Kahl FR, McKinney WM, Toole JF, McMahan MR, Thompson C, Heiss G, Crouse JR. Evaluation of the associations between carotid artery atherosclerosis and coronary artery stenosis: a case control study. Circulation. 1990;82:1230-1242. [Abstract/Free Full Text]
   
3. O'Leary DH, Polak JF, Kronmal RA, Kittner SJ, Bond MG, Wolfson SK Jr, Bommer W, Price TR, Gardin JM, Savage PJ. Distribution and correlates of sonographically detected carotid artery disease in the cardiovascular health study. Stroke. 1992;23:1752-1760. [Abstract/Free Full Text]
   
4. Megnien JL, Sene V, Jeannin S, Hernigou A, Plainfosse MC, Merli I, Atger V, Moatti N, Levenson J, Simon A. Coronary calcification and its relation to extracoronary atherosclerosis in asymptomatic hypercholesterolemic men. Circulation. 1992;85:1799-1807. [Abstract/Free Full Text]
   
5. Bruckert E, Giral P, Salloum J, Kahn JF, Dairou F, Truffert J, Reverdy V, Thomas D, Evans J, Grosgogeat Y. Carotid stenosis is a powerful predictor of a positive exercise electrocardiogram in a large hyperlipidemic population. Atherosclerosis. 1992;92:105-114. [Medline] [Order article via Infotrieve]
   
6. Nishino M, Sueyoshi K, Yasuno M, Yamada Y, Abe H, Hori M, Kamada T. Risk factors for carotid atherosclerosis and silent cerebral infarction in patients with coronary heart disease. Angiology. 1993;44:432-440.
   
7. Geroulakos G, O'Gorman D, Nicolaides A, Sheridan D, Elkeles R, Shaper AG. Carotid intima-media thickness: correlation with the British regional heart study risk score. J Intern Med. 1994;235:431-433. [Medline] [Order article via Infotrieve]
   
8. Salonen JT, Salonen R. Ultrasonographically assessed carotid morphology and the risk of coronary heart disease. Arterioscler Thromb. 1991;11:1245-1249. [Abstract/Free Full Text]
   
9. Blankenhorn DH, Selzer RH, Crawford DW, Barth JD, Liu C, Mack WJ, Alaupovic P. Beneficial effects of colestipol-niacin therapy on the common carotid artery. Circulation. 1993;88:20-28. [Abstract/Free Full Text]
   
10. Crouse JR III, Byington RP, Bond MG, Espeland MA, Craven TE, Sprinkle JW, McGovern ME, Furberg KD. Pravastatin, lipids, and atherosclerosis in the carotid arteries (PLAC-II). Am J Cardiol. 1995;75:455-459. [Medline] [Order article via Infotrieve]
    
11. Furberg CD, Byington RP, for the ACAPS Group. ACAPS: effects of lovastatin on progression of carotid atherosclerosis and clinical events. Circulation. 1993;88(pt 2):I-386. Abstract.
    
12. Sutton-Tyrrell K, Wolfson SK Jr, Kuller LH. Blood pressure treatment slows the progression of carotid stenosis in patients with isolated systolic hypertension. Stroke. 1994;25:44-50. [Abstract]
    
13. Grotta JC, Yatsu FM, Pettigrew LC, Rhoades H, Bratina P, Vital D, Alam R, Earls R, Picone C. Prediction of carotid stenosis progression by lipid and hematologic measurements. Neurology. 1989;39:1325-1331. [Abstract/Free Full Text]
    
14. Salonen R, Salonen JT. Progression of carotid atherosclerosis and its determinants: a population-based ultrasonography study. Atherosclerosis. 1990;81:33-40. [Medline] [Order article via Infotrieve]
    
15. Salonen JT, Yla-Herttuala S, Yamamoto R, Butler S, Korpela H, Salonen R, Nyyssonen K, Palinski W, Witztum JL. Autoantibody against oxidised LDL and progression of carotid atherosclerosis. Lancet. 1992;339:883-887. [Medline] [Order article via Infotrieve]
    
16. Tanaka H, Nishino M, Ishida M, Fukunaga R, Sueyoshi K. Progression of carotid atherosclerosis in Japanese patients with coronary artery disease. Stroke. 1992;23:946-951. [Abstract/Free Full Text]
    
17. Crouse JR, Thompson CJ. Evaluation of methods for quantifying lumen stenosis and atherosclerosis. Circulation. 1993;87(suppl II):II-17-II-33.
    
18. Manual of Laboratory Operations: Lipid Research Clinics Program, Vol 1, Lipid and Lipoprotein Analysis. Bethesda, Md: National Heart and Lung Institute, National Institutes of Health; 1974. DHEW publication NIH 75-628. Revised 1982.
    
19. Ryu JE, Howard G, Craven TE, Bond MG, Hagaman AP, Crouse JR. Postprandial triglyceridemia and carotid atherosclerosis in middle-aged subjects. Stroke. 1992;23:823-828. [Abstract/Free Full Text]
    
20. Crouse JR, Byington RP, Bond MG, Espeland MA, Sprinkle JW, McGovern M, Furberg CD. Pravastatin, lipids, and atherosclerosis in the carotid arteries: design features of a clinical trial with atherosclerosis outcome. Control Clin Trials. 1992;13:495-506. [Medline] [Order article via Infotrieve]
    
21. Snedecor GW, Cochran WG. Statistical Methods. 6th ed. Ames, Iowa: Iowa State University Press; 1967.
    
22. Cox DR. Analysis of Binary Data. New York, NY: Chapman & Hall; 1970.
    
23. Hosmer D, Lemeshow S. Goodness-of-fit tests for the multiple logistic regression model. Commun Stat Part A Theor Meth. 1980;A9:1043-1069.
    
24. Riley WA, Barnes RW, Applegate WB, Dempsey R, Hartwell T, Davis VG, Bond MG, Furberg CD. Reproducibility of noninvasive ultrasonic measurement of carotid atherosclerosis: the Asymptomatic Carotid Artery Plaque Study. Stroke. 1992;23:1062-1068. [Abstract/Free Full Text]
    
25. Howard G, Sharrett AR, Heiss G, Evans GW, Chambless LE, Riley WA, Burke GL, for the ARIC Investigators. Carotid artery intimal-medial thickness: distribution in general populations as evaluated by B-mode ultrasound. Stroke. 1993;24:1297-1304. [Abstract/Free Full Text]
    
26. Howard G, Burke GL, Evans GW, Crouse JR III, Riley W, Arnett D, de Lacy R, Heiss G. Relationships of intimal-medial thickness among sites within the carotid artery as evaluated by B-mode ultrasound. Stroke. 1994;25:1581-1587. [Abstract]
    
27. The MIDAS Research Group, Furberg CD, Byington RP, Borhani NA. Multicenter Isradipine Diuretic Atherosclerosis Study (MIDAS): design features. Am J Med. 1989;86:37-39. [Medline] [Order article via Infotrieve]
    
28. Wofford JL, Kahl FR, McKinney WM, Toole JF, Crouse JR. Relation of extent of extracranial carotid artery atherosclerosis as measured by B-mode ultrasound to the extent of coronary atherosclerosis. Arterioscler Thromb. 1991;11:1786-1795. [Abstract/Free Full Text]
    
29. Chambers BR, Norris JW. Outcome in patients with asymptomatic neck bruits. N Engl J Med. 1986;315:860-865. [Abstract]
    
30. Hennerici M, Hulsbomer HB, Hefter H, Lammerts D, Rautenberg W. Natural history of asymptomatic extracranial arterial disease: results of a long-term prospective study. Brain. 1987;110:777-791. [Abstract/Free Full Text]
    
31. Aronow WS, Schoenfeld MR. Forty-five month follow-up of extracranial carotid arterial disease for new coronary events in elderly patients. Coron Artery Dis. 1992;3:249-251.
    
32. Crouse JR, Harpold GH, Kahl FR, Toole JF, McKinney WM. Evaluation of a scoring system for extracranial carotid atherosclerosis extent with B-mode ultrasound. Stroke. 1986;17:270-275. [Abstract/Free Full Text]
    
33. Salonen R, Seppanen K, Rauramaa R, Salonen JT. Prevalence of carotid atherosclerosis and serum cholesterol levels in eastern Finland. Arteriosclerosis. 1988;8:788-792. [Abstract/Free Full Text]
    
34. Wendelhag I, Wiklund O, Wikstrand J. Arterial wall thickness in familial hypercholesterolemia. Arterioscler Thromb. 1992;12:70-77. [Abstract/Free Full Text]
    
35. Poli A, Tremoli E, Colombo A, Sirtori M, Pignoli P, Paoletti R. Ultrasonographic measurement of the common carotid artery wall thickness in hypercholesterolemic patients. Atherosclerosis. 1988;70:253-261. [Medline] [Order article via Infotrieve]
    
36. Bonithon-Kopp C, Scarabin PY, Taquet A, Touboul PJ, Malmejac A, Guize L. Risk factors for early carotid atherosclerosis in middle-aged French women. Arterioscler Thromb. 1991;11:966-972. [Abstract/Free Full Text]
    
37. Pauciullo P, Iannuzzi A, Sartorio R, Irace C, Covetti G, DiCostanzo A, Rubba P. Increased intima-media thickness of the common carotid artery in hypercholesterolemic children. Arterioscler Thromb. 1994;14:1075-1079. [Abstract/Free Full Text]
    
38. Persson J, Stavenow L, Wikstrand J, Israelsson B, Formgren J, Berglund G. Noninvasive quantification of atherosclerotic lesions. Arterioscler Thromb. 1992;12:261-266. [Abstract/Free Full Text]
    
39. Pignoli P, Tremoli E, Poli A, Oreste P, Paoletti R. Intimal plus medial thickness of the arterial wall: a direct measurement with ultrasound imaging. Circulation. 1986;74:1399-1406. [Abstract/Free Full Text]
    
40. Wendelhag I, Gustavsson T, Suurkula M, Berglund G, Wikstrand J. Ultrasound measurement of wall thickness in the carotid artery: fundamental principles and description of a computerized analysing system. Clin Physiol. 1991;11:565-577. [Medline] [Order article via Infotrieve]
    
41. O'Leary DH, Polak JF, Wolfson SK Jr, Bond MG, Bommer W, Sheth S, Psaty BM, Sharrett AR, Manolio TA. Use of sonography to evaluate carotid atherosclerosis in the elderly. Stroke. 1991;22:1155-1163.[Abstract/Free Full Text]
    

This article has been cited by other articles:

				F. Sen, M. Demirturk, N. Abaci, E. Golcuk, H. Oflaz, A. Elitok, F. Kutluturk, H. Issever, N. E. Unaltuna, and N. C. Ozbey Endothelial nitric oxide synthase intron 4a/b polymorphism and early atherosclerotic changes in hypopituitary GH-deficient adult patients Eur. J. Endocrinol., May 1, 2008; 158(5): 615 - 622. [Abstract] [Full Text] [PDF]

				M. Amato, P. Montorsi, A. Ravani, E. Oldani, S. Galli, P. M. Ravagnani, E. Tremoli, and D. Baldassarre Carotid intima-media thickness by B-mode ultrasound as surrogate of coronary atherosclerosis: correlation with quantitative coronary angiography and coronary intravascular ultrasound findings Eur. Heart J., September 1, 2007; 28(17): 2094 - 2101. [Abstract] [Full Text] [PDF]

				C.-M. Yu, Q. Zhang, L. Lam, H. Lin, S.-L. Kong, W. Chan, J. W.-H. Fung, K. K K Cheng, I. H.-S. Chan, S. W.-L. Lee, et al. Comparison of intensive and low-dose atorvastatin therapy in the reduction of carotid intimal-medial thickness in patients with coronary heart disease Heart, August 1, 2007; 93(8): 933 - 939. [Abstract] [Full Text] [PDF]

				K. Takebayashi, M. Suetsugu, S. Wakabayashi, Y. Aso, and T. Inukai Retinol Binding Protein-4 Levels and Clinical Features of Type 2 Diabetes Patients J. Clin. Endocrinol. Metab., July 1, 2007; 92(7): 2712 - 2719. [Abstract] [Full Text] [PDF]

				M. J Roman, T. Z Naqvi, J. M Gardin, M. Gerhard-Herman, M. Jaff, and E. Mohler American Society of Echocardiography Report: Clinical application of noninvasive vascular ultrasound in cardiovascular risk stratification: a report from the American Society of Echocardiography and the Society for Vascular Medicine and Biology Vascular Medicine, August 1, 2006; 11(3): 201 - 211. [PDF]

				A. A. Meyer, G. Kundt, M. Steiner, P. Schuff-Werner, and W. Kienast Impaired Flow-Mediated Vasodilation, Carotid Artery Intima-Media Thickening, and Elevated Endothelial Plasma Markers in Obese Children: The Impact of Cardiovascular Risk Factors Pediatrics, May 1, 2006; 117(5): 1560 - 1567. [Abstract] [Full Text] [PDF]

				S. Abdelghaffar, M. El Amir, A. El Hadidi, and F. El Mougi Carotid Intima-Media Thickness: An Index for Subclinical Atherosclerosis in Type 1 Diabetes J Trop Pediatr, February 1, 2006; 52(1): 39 - 45. [Abstract] [Full Text] [PDF]

				K. Watanabe, S. Sugiyama, K. Kugiyama, O. Honda, H. Fukushima, H. Koga, Y. Horibata, T. Hirai, T. Sakamoto, M. Yoshimura, et al. Stabilization of Carotid Atheroma Assessed by Quantitative Ultrasound Analysis in Nonhypercholesterolemic Patients With Coronary Artery Disease J. Am. Coll. Cardiol., December 6, 2005; 46(11): 2022 - 2030. [Abstract] [Full Text] [PDF]

				V. Aboyans, J. Guilloux, P. Lacroix, C. Yildiz, A. Postil, and M. Laskar Common carotid intima-media thickness measurement is not a pertinent predictor for secondary cardiovascular events after coronary bypass surgery. A prospective study Eur. J. Cardiothorac. Surg., September 1, 2005; 28(3): 415 - 419. [Abstract] [Full Text] [PDF]

				J. G. Terry, J. J. Carr, R. Tang, G. W. Evans, E. O. Kouba, R. Shi, D. R. Cook, J. L.C. Vieira, M. A. Espeland, M. F. Mercuri, et al. Coronary Artery Calcium Outperforms Carotid Artery Intima-Media Thickness as a Noninvasive Index of Prevalent Coronary Artery Stenosis Arterioscler. Thromb. Vasc. Biol., August 1, 2005; 25(8): 1723 - 1728. [Abstract] [Full Text] [PDF]

				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]

				T. Ogata, M. Yasaka, M. Yamagishi, O. Seguchi, K. Nagatsuka, and K. Minematsu Atherosclerosis Found on Carotid Ultrasonography Is Associated With Atherosclerosis on Coronary Intravascular Ultrasonography J. Ultrasound Med., April 1, 2005; 24(4): 469 - 474. [Abstract] [Full Text] [PDF]

				A.A. Meyer, M.S. Joharchi, G. Kundt, P. Schuff-Werner, G. Steinhoff, and W. Kienast Predicting the risk of early atherosclerotic disease development in children after repair of aortic coarctation Eur. Heart J., March 2, 2005; 26(6): 617 - 622. [Abstract] [Full Text] [PDF]

				M. Juonala, J. S.A. Viikari, T. Laitinen, J. Marniemi, H. Helenius, T. Ronnemaa, and O. T. Raitakari Interrelations Between Brachial Endothelial Function and Carotid Intima-Media Thickness in Young Adults: The Cardiovascular Risk in Young Finns Study Circulation, November 2, 2004; 110(18): 2918 - 2923. [Abstract] [Full Text] [PDF]

				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]

				A Kablak-Ziembicka, W Tracz, T Przewlocki, P Pieniazek, A Sokolowski, and M Konieczynska Association of increased carotid intima-media thickness with the extent of coronary artery disease Heart, November 1, 2004; 90(11): 1286 - 1290. [Abstract] [Full Text] [PDF]

				L. L. Schott, R. P. Wildman, S. Brockwell, L. R. Simkin-Silverman, L. H. Kuller, and K. Sutton-Tyrrell Segment-Specific Effects of Cardiovascular Risk Factors on Carotid Artery Intima-Medial Thickness in Women at Midlife Arterioscler. Thromb. Vasc. Biol., October 1, 2004; 24(10): 1951 - 1956. [Abstract] [Full Text] [PDF]

				F. Orio Jr., S. Palomba, T. Cascella, B. De Simone, S. Di Biase, T. Russo, D. Labella, F. Zullo, G. Lombardi, and A. Colao Early Impairment of Endothelial Structure and Function in Young Normal-Weight Women with Polycystic Ovary Syndrome J. Clin. Endocrinol. Metab., September 1, 2004; 89(9): 4588 - 4593. [Abstract] [Full Text] [PDF]

				M. Zureik, P. Galan, S. Bertrais, L. Mennen, S. Czernichow, J. Blacher, P. Ducimetiere, and S. Hercberg Effects of Long-Term Daily Low-Dose Supplementation With Antioxidant Vitamins and Minerals on Structure and Function of Large Arteries Arterioscler. Thromb. Vasc. Biol., August 1, 2004; 24(8): 1485 - 1491. [Abstract] [Full Text] [PDF]

				A. H. Slyper What Vascular Ultrasound Testing Has Revealed about Pediatric Atherogenesis, and a Potential Clinical Role for Ultrasound in Pediatric Risk Assessment J. Clin. Endocrinol. Metab., July 1, 2004; 89(7): 3089 - 3095. [Abstract] [Full Text] [PDF]

				G. B. J. Mancini, B. Dahlof, and J. Diez Surrogate Markers for Cardiovascular Disease: Structural Markers Circulation, June 29, 2004; 109(25_suppl_1): IV-22 - IV-30. [Full Text] [PDF]

M. Zureik, S. Kony, C. Neukirch, D. Courbon, B. Leynaert, D. Vervloet, P. Ducimetiere, and F. Neukirch Bronchial Hyperresponsiveness to Methacholine Is Associated With Increased Common Carotid Intima-Media Thickness in Men Arterioscler. Thromb. Vasc. Biol., June 1, 2004; 24(6): 1098 - 1103. [Abstract]