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J Am Coll Cardiol, 2004; 43:1177-1184, doi:10.1016/j.jacc.2003.09.063
© 2004 by the American College of Cardiology Foundation
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CLINICAL RESEARCH: ATHEROSCLEROSIS

Echolucent carotid plaques predict future coronary events in patients with coronary artery disease

Osamu Honda, MD*, Seigo Sugiyama, MD, PhD*,*, Kiyotaka Kugiyama, MD, PhD{dagger}, Hironobu Fukushima, MD*, Shinichi Nakamura, MD*, Shunichi Koide, MD*, Sunao Kojima, MD*, Nobutaka Hirai, MD*, Hiroaki Kawano, MD, PhD*, Hirofumi Soejima, MD, PhD*, Tomohiro Sakamoto, MD, PhD*, Michihiro Yoshimura, MD, PhD* and Hisao Ogawa, MD, PhD*{dagger}

* Department of Cardiovascular Medicine, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan
{dagger} Second Department of Internal Medicine, Graduate School of Yamanashi University, Yamanashi, Japan

Manuscript received April 23, 2003; revised manuscript received July 31, 2003, accepted September 29, 2003.

* Reprint requests and correspondence: Dr. Seigo Sugiyama, 1-1-1 Honjo, Kumamoto City, Kumamoto, Japan 860-8556.
ssugiyam{at}kumamoto-u.ac.jp


   Abstract
Top
 Abstract
Methods
 Results
 Discussion
 References
 
OBJECTIVES: The purpose of this study was to examine whether echolucent carotid plaques predict future coronary events in patients with clinically stable coronary artery disease (CAD).

BACKGROUND: Although rupture of coronary plaques is considered a major cause of acute coronary syndromes (ACS), the clinical estimation of coronary vulnerability still remains inconclusive. Ultrasound evaluation of carotid plaques with integrated backscatter (IBS) analysis can indicate the consistency/structure of the plaques. Lipid-rich lesions known as "unstable plaques" appear as echolucent plaques with low IBS values using this technique.

METHODS: We investigated the echogenicity of carotid plaques using ultrasound with IBS in 286 consecutive CAD patients (71 with ACS and 215 with stable CAD). Coronary plaque complexity was also determined angiographically in stable CAD patients followed up for 30 months or until the occurrence of coronary events.

RESULTS: The calibrated IBS values of carotid plaques in ACS patients were significantly lower than those in stable CAD patients (p < 0.01). Echolucent carotid plaques accurately predicted the existence of complex coronary plaques (predictive power of 83%). Kaplan-Meier analysis demonstrated a significantly higher probability of coronary events developing in patients with echolucent carotid plaques than in patients without this type of plaque (p < 0.001). The presence of echolucent carotid plaques in stable CAD patients predicted future coronary events independent of other risk factors (odds ratio 7.0, 95% confidence interval 2.3 to 21.4; p < 0.001).

CONCLUSIONS: Echolucent carotid plaques with low IBS values predicted coronary plaque complexity and the development of future coronary complications in patients with stable CAD. Qualitative evaluation of carotid plaques using ultrasound with IBS is a clinically useful procedure for risk assessment of CAD patients.

Abbreviations and Acronyms
  ACS = acute coronary syndromes
  AMI = acute myocardial infarction
  CAD = coronary artery disease
  (c)IBS = (calibrated) integrated backscatter
  IMT = intima-media thickness
  HDL = high-density lipoprotein
  hs-CRP = high-sensitivity C-reactive protein
  LDL = low-density lipoprotein
  OMI = old myocardial infarction
  PCI = percutaneous coronary intervention
  ROI = region of interest
  UAP = unstable angina pectoris

Acute coronary syndromes (ACS) are almost invariably associated with ruptured coronary plaques, commonly referred to as "unstable plaques" (1–4). Evaluation of not only the luminal stenoses but also the instability of atherosclerotic plaques is important in determining the extent of clinical disease activity and the risk of subsequent vascular complications. Coronary plaques can be examined by either intravascular ultrasound (5) or angioscopy (6), with both techniques identifying coronary plaque composition and the condition of the plaque surface. However, these techniques are invasive and, therefore, may not be practical for routine use in the management and risk assessment of patients with coronary artery disease (CAD) (7). Recent studies support the concept that plaque instability is not merely a local vascular incident but rather that plaque instability exists simultaneously at multiple sites in the systemic vascular bed (8,9). Thus, it is possible that coronary plaque vulnerability may be assessed by evaluating plaque characteristics such as stability, composition, and surface condition in other vessels such as the carotid arteries.

Non-invasive carotid artery ultrasound is an established, validated method for visualizing and quantifying atherosclerotic lesions (10–12). The intima-media thickness (IMT) of carotid arteries is associated with both coronary risk factors (13) and cardiovascular complications (14). Carotid plaque echogenicity has also been reported to be associated with stroke and other cerebrovascular events (15,16). Recent studies have assessed the composition of carotid plaques (17–19) by using ultrasound with integrated backscatter (IBS) analysis and showed histologically that echolucent plaques were lipid- and macrophage-rich (20) and therefore unstable (17–19). Currently, identifying a high-risk CAD population that is vulnerable to having coronary plaques is clinically difficult. In the present study, we measured the echogenicity of carotid plaques using IBS and investigated the association between carotid plaque echogenicity and angiographic coronary plaque complexity. We also examined whether echolucent carotid plaque with a low value of calibrated IBS (cIBS) predicted future coronary events in patients with clinically stable CAD.


   Methods
Top
 Abstract
 Methods
Results
 Discussion
 References
 
Study patients.   This study enrolled 286 consecutive patients with CAD: 71 patients with ACS (39 with acute myocardial infarction [AMI] and 32 with unstable angina pectoris [UAP]) and 215 patients with clinically stable CAD. All patients underwent elective or diagnostic catheterization at the Kumamoto University Hospital. A diagnosis of AMI was made if the patient had typical chest pain with ST-segment elevation on an electrocardiogram and an increase in the plasma level of creatine kinase-MB isoenzyme (CK-MB) to greater than twice the upper limit of the normal range. A diagnosis of UAP (Braunwald's class IIB or IIIB [21]) was made if the patient displayed characteristic symptoms at rest associated with transient ischemic ST-segment shifts and normal plasma levels of CK-MB and cardiac troponin T. Stable CAD was defined as a patient with no episodes of angina at rest but with angiographically documented organic stenosis >50% in at least one of the major coronary arteries. The exclusion criteria for the study included severe valvular heart disease, cardiomyopathy, trauma within the previous month, end-stage renal failure, cardiomyopathy, and malignant, infectious, chronic inflammatory, and autoimmune diseases. This study protocol was conducted in accordance with guidelines approved by the ethics committee at our institution.

Ultrasound evaluation.   A carotid ultrasound examination was performed in the ultrasound laboratory using an 11.0-MHz, linear-array transducer (SONOS-5500, Philips, Andover, Massachusetts) within one week after an acute coronary event in ACS patients and within a few days after admission but before coronary angiography in stable CAD patients. Patients with ACS who were in an unstable or severe condition one week after an acute coronary event, including patients receiving respiratory or circulatory support, were excluded from the study. Two operators performed all of the carotid scans without any information on the clinical characteristics of the patients. Each common, internal, and external carotid artery was imaged in the anterior oblique, lateral, and posterior oblique planes to identify atherosclerotic lesions. On a longitudinal image of each carotid artery, IMT was defined as the distance from the leading edge of the lumen-intima interface to the leading edge of the media-adventitia interface. Atherosclerotic plaque was defined as a lesion with a focal IMT of 1.1 mm or more, with a localized protrusion of the vessel wall into the lumen (22). Maximum IMT (IMTmax) was defined as the greatest axial thickness in the carotid arteries. In this study, we arbitrarily defined the cut-off point for increased IMTmax as 2.73 mm, which represented the 75th percentile of the distribution of IMTmax in ACS patients.

Measurement of IBS.   We measured the IBS values of all carotid atherosclerotic plaques, as described previously by Takiuchi et al. (19). For each plaque, conventional high-resolution, B-mode images were obtained, followed by the acquisition of 60 IBS images. Atherosclerotic plaques were analyzed using the manual definition mode to outline the region of interest (ROI), as shown in Figure 1. Instrument imaging adjustments, such as transmit power, focus, time-gain compensation, and gain setting, including the depth gain compensation curve, were all set at fixed values, with the system control remaining unchanged for the measurement of all plaques. The average power of the IBS signal within the ROI was measured and displayed in decibels for a total of 60 frames. In the case of heterogeneous plaques, we excluded excessively high echoic areas with acoustic shadowing, which indicated calcification from the ROI setting.



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  		Figure 1 Representative ultrasound images of atherosclerotic carotid plaques with low and high calibrated integrated backscatter (IBS) values. The red dotted line indicates region of interest in the plaque (intima-media complex), and the blue dotted line indicates region of interest in the adventitia using a manual outline definition mode. (Left) Low IBS plaque is identified by arrows. The calibrated IBS value and maximum intima-medial thickness (IMT) of this plaque are –17.6 dB and 2.1 mm, respectively. (Right) High IBS plaque is identified by arrowheads. The calibrated IBS value and maximum IMT of this plaque are –9.1 dB and 2.3 mm, respectively. CCA = common carotid artery; ICA = internal carotid artery.

 
We adopted the adventitia as the reference object and then expressed the relative IBS value of the intima-media complex as the difference in IBS values between the intima-media and adventitia (cIBS = intima-media IBS value – adventitia IBS value). In each patient, we selected plaque with the most echolucent cIBS value among all of the carotid plaques. The IBS values in the adventitia were within the dynamic range of the ultrasound machine, with no significant difference observed between patients with and those without echolucent carotid plaques (IBS: 53.1 ± 4.8 dB vs. 52.3 ± 5.0 dB, respectively; p = ns). In our study, the inter-observer variability for the repeated measurements of plaque IBS values was 0.7 ± 0.4 dB, whereas the intra-observer variability for these repeated measurements was 0.6 ± 0.4 dB. We arbitrarily defined the cut-off point for echolucent plaque as –13.4 dB, which was the 75th percentile of the cIBS values in the ACS patient group.

Determination of serum C-reactive protein.   High-sensitivity C-reactive protein (hs-CRP) in fasting serum samples was assayed by rate nephelometry (Dade Behring, Marburg, GMBH). In stable CAD patients, 90% had hs-CRP levels below 0.3 mg/dl and 99% had levels below 1.0 mg/dl.

Angiographic analysis.   Measurements of coronary stenosis and the definition of coronary complex plaques in patients with stable CAD were performed independently by two cardiologists who had no knowledge of the patients' clinical characteristics. Coronary lesions were considered complex if they caused at least 50% stenosis and had complex morphologic features such as eccentric lesions with a narrow neck, overhanging edges, irregular borders, or plaque ulceration (9,23,24).

Follow-up study.   After the angiographic data were obtained, the 215 patients with stable CAD were followed up every month at the hospital or at a home visit for a period of up to 30 months or until the occurrence of one of the following clinical coronary events: sudden hospitalization or coronary revascularization (e.g., percutaneous coronary intervention [PCI], coronary artery bypass graft surgery) due to recurrent or refractory angina pectoris, UAP, non-fatal AMI, or cardiac death. Patients with ACS were excluded from the follow-up analysis because they had a coronary event ratio significantly higher than that of stable CAD patients. All stable CAD patients received the standardized medical therapy outlined in Table 1. The cause of death was determined from an examination of hospital records. We found 23% of patients with stable CAD had PCI-mediated restenosis at follow-up coronary angiography. Revascularization therapy based only on angiographic data, including PCI-mediated restenosis, was not counted as a coronary event. The need for and timing of revascularization was decided by the attending physician and interventional cardiologists, independent of this prospective study. The attending physician and interventional cardiologist were blinded as to whether the patients had echolucent carotid plaques.


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  		Table 1 Baseline Clinical Characteristics of Patients With Stable Coronary Artery Disease With or Without Echolucent Carotid Plaque

 
Statistical analysis.   All descriptive data are expressed as the mean value ± SD. The Mann-Whitney U test was used to evaluate differences in plaque cIBS, IMTmax, and CRP between the two study groups. The frequencies for gender, smoking, hypertension, diabetes mellitus, medication therapy, invasive therapy, multi-vessel CAD, left main trunk lesion, left ventricular dysfunction, and history of old myocardial infarction (OMI) were compared between the two groups by using chi-square analysis. The mean values of continuous variables with a normal distribution, including age, body mass index, total cholesterol, high-density lipoprotein (HDL) cholesterol, low-density lipoprotein (LDL) cholesterol, and triglycerides, were compared between the two groups by using the unpaired t test. Survival analysis was carried out using the Kaplan-Meier method (log-rank test), according to the presence or absence of echolucent carotid plaques (cIBS value <–13.4 dB). The predictive value for coronary events during the follow-up period was assessed by Cox proportional hazards analysis. The continuous covariates in this analysis were age, body mass index, total cholesterol, HDL cholesterol, LDL cholesterol, triglycerides, hs-CRP, IMTmax, and plaque cIBS, and the categorical covariates were male gender, smoking, diabetes mellitus (25), hypertension (>140/90 mm Hg or taking any antihypertensive medications), history of OMI, and multi-vessel CAD.

The data were analyzed initially using a univariate model to determine the risk factors that had a significant association with future coronary events. Multivariate analysis was then applied using only the covariates that significantly predicted coronary events in the univariate analysis. In the logistic regression analysis, continuous covariates were expressed as categorized covariates (old age >75 years, high total cholesterol >240 mg/dl, low HDL cholesterol <40 mg/dl, high LDL cholesterol >160 mg/dl, hypertriglyceridemia >150 mg/dl, body mass index >25 kg/m2, and high hs-CRP >0.3 mg/dl), according to the cut-off points of the American Heart Association (26–29). Statistical significance was defined as p < 0.05. To evaluate the probability of predicting angiographic evidence of coronary plaques, a test of the sensitivity (SE) and specificity (SP) of the carotid plaques' echolucency, as compared with either smooth or complex coronary plaques, was carried out using the following equations. Sensitivity = number of patients with complex coronary plaques among patients with echolucent carotid plaques/number of tested patients with complex coronary plaques. Specificity = number of patients without complex coronary plaques among patients without echolucent carotid plaques/number of patients without complex coronary plaques. The pretest likelihood (PL) was defined as the probability that complex coronary plaques existed in the patient to be tested (PL = number of patients with complex coronary plaques/total number of stable CAD patients tested in present study) (30). The predictive power and the likelihood ratio were calculated according to Bayes' theorem (30). All analyses were carried out using StatView version 5.0 (Tokyo, Japan).


   Results
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 Abstract
 Methods
 Results
Discussion
 References
 
Carotid plaque evaluation in CAD patients.   Of the stable CAD patients, 79.2% had multiple carotid plaques, with 93.8% of the patients with echolucent plaques possessing multiple echolucent plaques in their carotid arteries. The cIBS values of all plaques examined in the study ranged from 4.1 to –28.9 dB. The standard variation of the cIBS value of multiple carotid plaques in each patient was 3.6 ± 1.8 dB. Figure 1 shows representative echolucent carotid plaques with a low cIBS value (–17.6 dB, IMT of 2.1 mm) and a high cIBS value (–9.1 dB, IMT of 2.3 mm). The median (inter-quartile range) cIBS values of carotid plaques in patients with ACS were significantly lower than those in stable CAD patients: –17.7 (–20.2 to –13.4) versus –13.7 (–18.3 to –9.8) dB (p = 0.007) (Fig. 2). However, patients with either ACS or stable CAD showed no significant difference in IMTmax (2.2 ± 0.8 mm vs. 2.2 ± 1.0 mm; p = 0.91) or in the frequency of traditional coronary risk factors (data not shown). Thus, the carotid plaques in patients with ACS were more echolucent than those in stable CAD patients, despite similar values of IMTmax.



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  		Figure 2 Comparison of calibrated integrated backscatter (IBS) values between patients with stable coronary artery disease (CAD) and patients with acute coronary syndrome (ACS). The dotted line indicates the cut-off level for echolucent plaque (–13.4 dB, which represents the 75th percentile of the distribution in patients with ACS). Box and whisker plot: lines within boxes represent median values; upper and lower lines of boxes represent 25th and 75th percentiles, respectively; and upper and lower bars outside of boxes represent 90th and 10th percentiles, respectively.

 
Baseline clinical characteristics and echolucent carotid plaques in stable CAD patients.   The baseline clinical characteristics of the patients with stable CAD with or without echolucent carotid plaques are shown in Table 1. The stable CAD patient group with echolucent carotid plaques had significantly higher levels of hs-CRP, lower levels of HDL cholesterol, and increased IMTmax and were predominantly male. Multivariate logistic regression analysis showed a significant and independent association between increased levels of hs-CRP and the presence of echolucent carotid plaques (odds ratio [OR] 3.5, 95% confidence interval [CI] 1.4 to 8.5; p < 0.01).

Ultrasound analysis of carotid plaques and angiographic morphology of coronary plaques in stable CAD patients.   Complex coronary plaques were found in 116 (54%) of 215 stable CAD patients, with 43 (20%) of these 215 patients having multiple complex plaques in their coronary arteries. The reproducibility of assessment in coronary plaque complexity was 93%. The significant risk factors for the presence of complex coronary plaques were carotid echolucency, high hs-CRP levels, increased IMTmax, low levels of HDL cholesterol, and male gender. On multivariate logistic regression analysis, using these parameters as covariates, carotid plaque echolucency was shown to be the strongest independent predictor of complex coronary plaques (OR 11.5, 95% CI 5.5 to 23.7; p < 0.001). Table 2 shows that patients with echolucent carotid plaques frequently had complex coronary plaques (p < 0.001, chi-square test). The pretest likelihood of complex coronary plaques was 54%, and we found that echolucent carotid plaques predicted the existence of complex coronary plaques with a sensitivity of 80%, a specificity of 81%, and a predictive power of 83%. The likelihood ratio for estimating the existence of complex coronary plaques was 4.2.


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  		Table 2 Relationship Between Echolucency of Carotid Plaques and Angiographic Complex Coronary Plaques

 
Prognostic value of echolucent carotid plaques in stable CAD patients.   All patients completed the follow-up period. Patients with stable CAD were followed from one to 30 months (mean 14). Patients with echolucent carotid plaques (n = 112) had 29 coronary events during the follow-up period, whereas patients without echolucent plaques (n = 103) had only four coronary events (p < 0.001) (Table 3). All but 1 of the 29 coronary events in the total echolucent group (i.e., 97%) were recorded in patients diagnosed with stable CAD with multiple echolucent carotid plaques. There were no significant differences in the dosages of administered medications between the patients with and those without coronary events (data not shown). Kaplan-Meier analysis in patients with stable CAD demonstrated that the presence of echolucent carotid plaques was associated with a significantly higher probability of developing coronary events (p < 0.001) (Fig. 3). Univariate Cox proportional hazards model analysis of the coronary risk factors and carotid ultrasound data showed that carotid plaque echolucency, IMTmax, multi-vessel CAD, and a history of OMI were all significant predictors of clinical coronary events (p < 0.01) (Table 4). Multivariate Cox proportional hazards model analysis of these four risk factors demonstrated that the presence of echolucent carotid plaques was the most significant and independent predictor of future coronary complications in patients with stable CAD (OR 7.0, 95% CI 2.3 to 21.4; p < 0.001) (Table 5). The absence of echolucent carotid plaques provided a significantly higher negative predictive value for future coronary complications (OR 0.1, 95% CI 0.03 to 0.27; p < 0.001).


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  		Table 3 Summary of Coronary Events During the Follow-Up Period in Patients With Stable Coronary Artery Disease

 


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  		Figure 3 Kaplan-Meier curves comparing the probability of developing a coronary event during a follow-up period of 30 months in 215 patients with stable coronary artery disease, grouped according to the presence or absence of echolucent carotid plaques. The solid line indicates patients with echolucent carotid plaques (n = 112), and the dotted line indicates patients without echolucent carotid plaques (n = 103).

 

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  		Table 4 Univariate Cox Proportional Hazards Analysis of Risk Factors for a Coronary Event in Patients With Stable Coronary Artery Disease

 

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  		Table 5 Multivariate Cox Proportional Hazards Analysis of Risk Factors for a Coronary Event in Patients With Stable Coronary Artery Disease

 

   Discussion
Top
 Abstract
 Methods
 Results
 Discussion
References
 
This study demonstrates, for the first time, that echolucent carotid plaques with low IBS values are strongly associated with the angiographic appearance of complex coronary plaques and that echolucent carotid plaque was a significant and independent predictor of future coronary events in stable CAD patients. Furthermore, the echolucent carotid plaque is a stronger indicator of future coronary events than increased IMT in carotid arteries. Thus, objective evaluation of carotid plaque quality, utilizing an ultrasound technique with IBS, is clinically and practically informative for risk stratification of patients with CAD.

It is important to evaluate plaque vulnerability as well as the degree of coronary stenosis when assessing disease activity and severity in atherosclerosis. Recent technologic advances have provided methods such as intravascular ultrasound (5) and angioscopy (6), which allow the direct examination of coronary plaques and provide information on coronary plaque composition and surface conditions. However, these techniques are invasive and are not practical on a routine basis for the management and risk assessment of CAD patients (7). Angiographically, the presence of coronary plaques with complex morphologic features correlates with pathologic plaque rupture, whereas superficial thrombus is recognized as the hallmark of ACS (9,23,24,31). It has been shown that such lesions are associated with rapid progression of coronary stenosis and general clinical instability in patients with stable CAD (31). Recent observations support the concept that plaque instability is not merely a local vascular incident, but that plaque destabilization occurs at multiple sites in the entire systemic vascular bed (8,9). Thus, it may be possible that the presence of unstable carotid plaques might reflect, in part, the activation of the systemic vascular tree, and that unstable coronary plaques may exist throughout the entire vasculature.

High-resolution carotid ultrasound detects lipids, thrombi, and hemorrhages in carotid plaques as echolucent structures (10–12) The echolucency of carotid plaque signifies a high lipid content and a higher risk for future ischemic cerebrovascular events (15,16). We recorded 11 cerebrovascular events, including ischemic stroke and transient ischemic attacks, in the present study, with 10 occurring in the echolucent group and only one in the echogenic group. This different prevalence was statistically significant (p < 0.01), indicating that carotid plaque echolucency by IBS assessment reflects carotid plaque vulnerability. Takiuchi et al. (19) reported on the usefulness of ultrasound IBS determination of atherosclerotic plaque tissue composition and found that echolucent plaques with a low IBS value appeared as lipid-rich unstable plaques. Similarly, Kawasaki et al. (32) demonstrated that IBS analysis was useful for evaluating plaque tissue components in echolucent plaque with low IBS values, indicating a lipid-rich condition in the carotid arteries. Recently, an investigation of plaque echolucency by IBS analysis was used clinically for investigating various vasculatures, including coronary arteries (32,33). The present study demonstrated that the IBS value of carotid plaques in patients with ACS was significantly lower than that in patients with stable CAD, despite comparable values of IMT. This suggested that carotid atherosclerotic plaques are more vulnerable in ACS patients than in stable CAD patients, and furthermore, that the echolucency of carotid plaques is a significant indicator of angiographically unstable coronary plaques and future coronary events in stable CAD patients. Non-invasive, easily repeatable, and inexpensive methods that detect instability of coronary lesions are needed for the management of high-risk CAD patients. In this regard, qualitative ultrasound evaluation of carotid plaque according to echogenicity provides clinically important information on coronary plaque vulnerability and future clinical outcome.

It is now widely accepted that inflammation has an important role in the genesis of plaque vulnerability (1–4). Pathologic investigations have shown that unstable plaques are characterized by active inflammation of the fibrous cap at the time of plaque disruption (3,4). In this study, the plasma levels of hs-CRP were significantly higher in patients with echolucent carotid plaques than in patients without such lesions. The higher levels of hs-CRP were found to be independently associated with the presence of echolucent carotid plaques. Clinical reports indicate that elevated levels of systemic inflammatory markers predict future cardiovascular complications (29). Our results suggest that echolucent plaques, in combination with elevated hs-CRP levels, indicate the presence of both ultrasonographically unstable and biochemically activated plaques.

Because the most echolucent plaque may, by itself, determine the risk for rupture, it is important to evaluate whether vulnerable plaques are present in the vascular tree rather than focusing on the number of plaques or the average vulnerability of several plaques. To identify high-risk patients with high sensitivity, we selected a value in each patient for the most echolucent plaque as the "targeted plaque" among all carotid plaques. We consider that monitoring of these targeted carotid plaques using IBS may provide us with a new clinical and practical strategy to treat patients with a high probability of coronary complex plaques, thereby preventing future cardiovascular complications in these patients.

It is well established that subjective assessment, gray-scale analysis, and IBS analysis are useful methods for evaluating atherosclerotic plaque echogenicity. Previously, Gronholdt et al. (34) reported that subjective assessment of carotid echolucency correlated with gray-scale analysis of plaque echogenicity. In our study, subjective evaluation of carotid plaque echolucency was found to correlate with objective cIBS-assisted evaluation (p < 0.001, chi-square test). The cIBS values were significantly higher in patients with subjectively echogenic plaques than in patients with subjectively echolucent plaques (–9.2 ± 3.6 vs. –18.8 ± 3.8, p < 0.001). Recently, Rossi et al. (35) reported that cIBS values in the carotid intima-media complex were significantly related to age in the normal healthy population, but not in hypertensive patients. We found no significant difference in carotid plaque cIBS values between young and old (age >75 years) CAD patients (cIBS median: –13.5 vs. –14.1 dB, p = 0.56).

This study was limited by the relatively small number of patients studied. We enrolled only stable CAD patients with mild stenotic lesions (>50% stenosis), as most acute coronary events appear to occur with low-grade or mild coronary stenosis. Low utilization of invasive therapy, instead of a high multi-vessel ratio, may frequently result in cases with mild stenotic coronary lesions and enrollment of patients with OMI or patients treated previously with invasive procedures such as PCI or coronary artery bypass graft surgery. A longitudinal, prospective study utilizing carotid ultrasound evaluation with IBS in a large number of patients with homogeneous risk is required in order to assess the precise prognostic value of echolucent carotid plaques in determining future cardiovascular events.

Conclusions.   Echolucent carotid plaques with low IBS values predict the presence of complex coronary plaques and the development of future coronary complications in stable CAD patients. Non-invasive and qualitative carotid plaque evaluation employing the ultrasound technique with IBS is clinically useful for the assessment of coronary plaque vulnerability and is informative in the risk stratification of CAD patients.


   Footnotes
 
This study was supported in part by Grants-in-Aid C(2)-14570679 (Ministry of Education, Culture, Sports, Science, and Technology, Tokyo) and 14C-4 (Ministry of Health, Labor, and Welfare, Tokyo); the Smoking Research Foundation, Tokyo; The Naito Foundation; Mochida Memorial Foundation for Medical and Pharmaceutical Research; Suzuken Memorial Foundation; and the Research Foundation for Community Medicine, "Research Meeting on Hypertension and Arteriosclerosis 2002," Tokyo, Japan. Drs. Honda and Sugiyama contributed equally to this work.


   References
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 Abstract
 Methods
 Results
 Discussion
 References
 

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