Carotid Plaque Echogenicity Research Articles

Increased thrombin generation in persons with echogenic carotid plaques

Echolucent carotid plaques are associated with higher risk for future ischemic cerebrovascular events (CVE) than echogenic plaques independent of the degree of stenosis. Elevated markers of thrombin generation are associated with atherosclerotic plaques and are increased in the acute and chronic phases of CVE. The present study was conducted to investigate the influence of plaque morphology on thrombin generation in persons with carotid stenosis. One hundred twenty-eight persons with carotid stenosis (>or=35% lumen diameter reduction) and 136 matched controls without stenosis were recruited from the health survey of the Tromsø Study. Blood samples were collected and plaque morphology determined by ultrasonography. Thrombin generation was assessed by thrombin-antithrombin complexes (TAT) and by prothrombin fragment 1+2 (F1+2). Persons with echogenic plaques (n = 63) had significantly higher levels of TAT (5.24 microg/l, 4.33-6.14) (mean, 95%CI) than persons with echolucent plaques (n = 65) (3.44 microg/l, 2.91-3.96, p < 0.001) and controls (n = 136) (3.33 microg/l, 3.06-3.60, p < 0.001). They also had significantly higher levels of F1+2 (2.14 nM, 1.83-2.45) than persons with echolucent plaques (1.54 nM, 1.38-1.71, p < 0.001) and controls (1.49 nM, 1.40-1.58, p < 0.001). TAT and F1+2 increased linearly with plaque echogenicity (p = 0.002 and p = 0.001, respectively) independent of the degree of stenosis. Increased thrombin generation was associated with a significant increase in plasma factor V levels among persons with echogenic plaques compared to echolucent plaques (p = 0.049) and controls (p = 0.025). The present findings indicate that increasing plaque echogenicity, rather than plaque echolucency and the degree of stenosis, is associated with thrombin generation in persons with carotid stenosis.

Circulating oxidized LDL is associated with the occurrence of echolucent plaques in the carotid artery in 61‐year‐old men

Objective. The aim of this study was to elucidate the relationship between the echogenicity of carotid artery plaques and the following risk factors: circulating oxLDL, hsCRP, the metabolic syndrome (MetS), and several of the traditional cardiovascular (CV) risk factors. Material and methods. A cross‐sectional population‐based study of 513 sixty‐one‐year‐old men. The levels of circulating oxLDL were determined in plasma samples by sandwich ELISA utilizing a specific murine monoclonal antibody (mAb‐4E6). High‐sensitivity CRP was measured in plasma by ELISA. Plaque occurrence, size and echogenicity were evaluated from B‐mode ultrasound registrations in the carotid arteries. Plaque echogenicity was assessed based on a four‐graded classification scale. Results. A higher frequency of echolucent carotid plaques was observed with increasing levels of oxLDL and systolic blood pressure (p = 0.008 and p = 0.041, respectively). Subjects with the MetS had a significantly higher frequency of echogenic plaques than subjects without the MetS (p = 0.009). In a multiple logistic regression analysis, oxLDL turned out to be independently associated with echolucent carotid plaques. Conclusions. The occurrence of echolucent carotid plaques was associated with oxLDL and systolic blood pressure, and oxLDL was associated with echolucent carotid plaques independently of systolic blood pressure.

The impact of carotid artery plaque echogenicity on the rate of solid cerebral microembolism during carotid artery stenting

The impact of carotid artery plaque echogenicity on the rate of solid cerebral microembolism during carotid artery stenting

Carotid Plaque Echogenicity and Risk of Nonvertebral Fractures in Women: A Longitudinal Population-Based Study

Atherosclerosis and osteoporosis appear to be related, but prospective studies on the relationship are sparse. In order to examine whether carotid artery plaques with different morphology predict nonvertebral fractures, we followed 2,733 women, aged 55-74 years (75% of the eligible population in Tromsø, Norway), for 6 years. At baseline, plaque morphology in terms of ultrasound echogenicity was categorized into three groups, ranging from low echogenicity (echolucent plaques with a high content of soft tissue) to strong echogenicity (echogenic plaques with a high content of dense fibrous tissue and calcified material). We found that the age-adjusted relative risk (RR) of fracture was significantly higher among women with echogenic plaques than among women without plaques: 1.7 (95% confidence interval [CI] 1.0-2.7). After adjustment for bone mineral density at baseline in addition to age, the RR was 1.6 (95% CI 1.0-2.6), and further adjustments for body mass index, body height, high-density lipoprotein cholesterol, smoking status, and muscle strength did not influence the association. Subjects with other plaque types were not at an increased risk compared to subjects without plaques: RR < or = 1.1, after multiple adjustments. We conclude that in the general population elderly women with echogenic carotid plaques are at higher risk of nonvertebral fractures than women without plaques.

Risk for transient ischemic attacks is mainly determined by intima-media thickness and carotid plaque echogenicity

Background Stenosis severity, plaque morphology, and intima-media thickness (IMT), all have been found to provide prognostic information in patients with asymptomatic carotid artery disease. However, limited data exist on the association between these parameters and the risk for transient ischemic attack (TIA). Methods We compared the ultrasonographic characteristics of 88 consecutive patients with first TIA without known cardioembolic source with those of 176 propensity-matched asymptomatic control subjects. Results IMT was higher in TIA patients compared to control subjects (0.74 ± 0.14 mm versus 0.68 ± 0.13 mm, p = 0.001). Plaques were found in 70.5% of patients and 64.8% of controls ( p = 0.407). Compared with controls, TIA patients demonstrated more frequently predominantly echolucent lesions (77.4% versus 56.1%, p = 0.005) and high-grade carotid stenoses (21.0% versus 9.6%, p = 0.042). TIA patients with low-to-moderate grade (<70%) lesions exhibited higher IMT and more prevalent echolucent morphology in comparison with their control counterparts. No significant differences were observed between groups regarding high-grade lesions. In multivariate models, IMT and plaque echogenicity, but not stenosis severity, emerged as independent determinants of risk. Conclusions Risk for TIA is primarily associated with IMT and plaque echogenicity, especially in the absence of high-grade lesions. Stenosis severity appears to be of limited prognostic value.

Serum osteoprotegerin is inversely associated with carotid plaque echogenicity in humans

Osteoprotegerin (OPG) is a member of the tumour necrosis factor superfamily involved in the regulation of bone metabolism and vascular calcification. High serum values of OPG are associated with cardiovascular disease in humans. The purpose was to investigate serum OPG levels in subclinical carotid atherosclerosis and the relation between OPG levels and plaque morphology. OPG levels were compared in 29 persons with echogenic carotid plaques, 30 persons with echolucent plaques and 41 persons without carotid plaques, all recruited from a population health study. Computerized assessment of plaque echogenicity was done by use of the gray scale median (GSM). Participants with echogenic carotid plaques had lower serum OPG level (1.23 ng/ml; 1.02–1.48) (geometric mean; 95% CI) than persons with echolucent plaques (1.76 ng/ml; 1.46–2.14) and those without plaques (1.89 ng/ml; 1.60–2.21). OPG and PTH were independently related to GSM. A significant trend for decrease in GSM across quartiles of OPG was found ( p = 0.003) which remained significant even after adjustment for PTH and smoking. The present study demonstrates lower serum OPG levels in persons with subclinical echogenic carotid plaques and identified an inverse relation between serum OPG and plaque echogenicity. The findings support the concept that OPG may play an important role in arterial calcification.

The Impact of Carotid Artery Plaque Echogenicity on the Rate of Solid Cerebral Microembolism during Carotid Artery Stenting

The Impact of Carotid Artery Plaque Echogenicity on the Rate of Solid Cerebral Microembolism during Carotid Artery Stenting

Mo-P4:285 Risk for transient ischemic attacks is mainly determined by intima-media thickness and carotid plaque thickness and carotid plaque echogenicity

Mo-P4:285 Risk for transient ischemic attacks is mainly determined by intima-media thickness and carotid plaque thickness and carotid plaque echogenicity

Elastin and Calcium Rather than Collagen or Lipid Content Are Associated With Echogenicity of Human Carotid Plaques

Elastin and Calcium Rather than Collagen or Lipid Content Are Associated With Echogenicity of Human Carotid Plaques

The impact of carotid artery plaque echogenicity on the rate of solid cerebral microembolism during carotid artery stenting

The impact of carotid artery plaque echogenicity on the rate of solid cerebral microembolism during carotid artery stenting

Stabilization of Carotid Atheroma Assessed by Quantitative Ultrasound Analysis in Nonhypercholesterolemic Patients With Coronary Artery Disease

This study examined whether intensive cholesterol-lowering therapy with statins in nonhypercholesterolemic patients is effective in improving echolucency of vulnerable plaques assessed by ultrasound with integrated backscatter (IBS) analysis. Atherosclerotic plaque stabilization is a promising clinical strategy to prevent cardiovascular events in patients with coronary artery disease (CAD). There is a correlation between coronary and carotid plaque instability, and echolucent plaques are recognized as vulnerable plaques. Consecutive nonhypercholesterolemic patients with CAD were randomly assigned Adult Treatment Panel-III diet therapy (diet group; n = 30) or pravastatin (statin group; n = 30). Echolucent carotid plaques were monitored by measuring intima-media thickness (IMT) and echogenicity by IBS for six months. Total cholesterol, low-density lipoprotein cholesterol (LDL-C), and high-sensitivity C-reactive protein were significantly decreased in the statin group (from 197 +/- 15 mg/dl to 170 +/- 18 mg/dl [p < 0.001]; from 131 +/- 14 mg/dl to 99 +/- 14 mg/dl [p < 0.001]; and from 0.11 [0.04 to 0.22] mg/dl to 0.06 [0.04 to 0.11] mg/dl [p < 0.05]; respectively), whereas only total cholesterol was moderately reduced (from 193 +/- 24 mg/dl to 185 +/- 22 mg/dl [p < 0.05]) and LDL-C and triglycerides insignificantly reduced in the diet group. Significant increases of echogenicity of carotid plaques were noted in the statin group but not in the diet group (from -18.5 +/- 4.1 dB to -15.9 +/- 3.7 dB [p < 0.001] and from -18.2 +/- 4.0 dB to -18.9 +/- 3.5 dB [p = 0.13]; respectively) without significant regression of plaque-IMT values in both groups. Statin therapy is rapidly effective in increasing echogenicity of vulnerable plaques without regression of plaque size in nonhypercholesterolemic patients with CAD. Quantitative assessment of carotid plaque quality by ultrasound with IBS is clinically useful for monitoring atherosclerotic lesions by evaluating vulnerability of atheroma.

W13-P-025 Serum osteoprotegerin is inversely associated with carotid plaque echogenicity in humans

W13-P-025 Serum osteoprotegerin is inversely associated with carotid plaque echogenicity in humans

Elastin and Calcium Rather Than Collagen or Lipid Content Are Associated With Echogenicity of Human Carotid Plaques

Echolucent carotid plaques have been associated with increased risk for stroke. Histological studies suggested that echolucent plaques are hemorrhage- and lipid-rich, whereas echogenic plaques are characterized by fibrosis and calcification. This is the first study to relate echogenicity to plaque composition analyzed biochemically. Echogenicity of human carotid plaques was analyzed by standardized high-definition ultrasound and classified into echolucent, with gray-scale median (GSM) <32 and echogenic with GSM > or =32. The biochemical composition of the plaques was assessed by fast-performance liquid chromotography and high-performance thin-layer chromotography. As assessed biochemically (milligrams per gram [mg/g]), echolucent plaques contained less hydroxyapatite (43.8 [SD 41.2] mg/g versus 121.6 [SD 106.2] mg/g; P=0.018), more total elastin (1.7 [SD 0.4] mg/g versus 1.2 [SD 0.4] mg/g; P=0.008), and more intermediate-size elastin forms (1.2 [SD 0.3] mg/g versus 0.8 [SD 0.4] mg/g; P=0.018). There was no difference in collagen amount between echogenic and echolucent plaques, neither biochemically (15.3 [SD 3.7] mg/g versus 14.4 [SD 3.4] mg/g) nor histologically (13.4 [SD 4.9] % versus 13.0 [SD 5.6] %). Cholesterol esters, unesterified cholesterol, and triglycerides were increased in plaques associated with symptoms (22.5 [SD 23.3] mg/g versus 13.3 [SD 3.2]; P=0.04), but no differences were detected between echolucent and echogenic plaques (13.5 [SD 4.0] versus 20.2 [SD 21.5] mg/g). Similar results were obtained by Oil Red O staining (symptomatic 7.6 [SD 4.7] % versus asymptomatic 4.2 [SD 3.6] %; P=0.03; echolucent 5.9 [SD 4.1] % versus echogenic 5.0 [SD 4.0] % of area). Echogenicity of carotid plaques is mainly determined by their elastin and calcium but not collagen or lipid content. In addition, echolucency is associated to higher elastin content.

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

ObjectivesThe purpose of this study was to examine whether echolucent carotid plaques predict future coronary events in patients with clinically stable coronary artery disease (CAD). BackgroundAlthough 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. MethodsWe 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. ResultsThe 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). ConclusionsEcholucent 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.

Higher Levels of Interleukin-6 Are Associated With Lower Echogenicity of Carotid Artery Plaques

Echo-lucent carotid plaques can be fragile and vulnerable to rupture, representing a risk factor for ischemic stroke. Given the studies showing that elevated levels of circulating inflammatory markers are predictive of cardiovascular events, we sought to determine whether higher levels of serum interleukin-6 (IL-6) and high-sensitivity C-reactive protein (hsCRP) are associated with lower echogenicity of carotid plaques. The study comprised 246 patients who had carotid atherosclerotic plaques as evidenced by ultrasound. Using acoustic densitometry, we quantified the echogenicity of the largest plaque in each patient by integrated backscatter analysis. Serum IL-6 and hsCRP levels were determined in all patients. Both log-transformed IL-6 and hsCRP concentrations were negatively correlated with carotid plaque echogenicity (r=-0.28, P<0.001, and r=-0.14, P<0.05, respectively). When traditional atherosclerotic risk factors, plaque thickness, and medication use were controlled for, IL-6 levels were inversely associated with plaque echogenicity (beta=-0.21, P<0.01), whereas such an association was of borderline significance for hsCRP (beta=-0.12, P=0.06). Higher IL-6 levels, in addition to hsCRP levels, appear to be associated with lower echogenicity of carotid plaques, suggesting a link between inflammation and potential risk of plaques.

What have we learned from the Imaging in Carotid Angioplasty and Risk of Stroke (ICAROS) study?

Carotid artery stenting (CAS) is used widely to treat carotid lesions. Indication to CAS is mostly based, both in trial and in clinical practice, on the percentage of stenosis and the presence or absence of preprocedural neurologic symptoms, whereas the features of the plaque are somehow disregarded and ignored. The most severe complication of CAS is stroke, related to cerebral embolization from carotid plaque. Several studies showed that echolucent plaques generate a higher number of embolic particles following carotid stenting. Echolucency can be measured using the gray scale median, which is an objective and quantitative computer-assisted grading of the echogenicity of carotid plaques. As previously demonstrated in the ICAROS study, carotid plaque echolucency is an independent risk factor for stroke in carotid stenting. Carotid plaque echolucency is one of the parameters that should be mandatory to be considered for indication to treatment.

Carotid plaque: comparison between visual and grey-scale median analysis.

Plaque morphology plays an important prognostic role in the occurrence of cerebrovascular events. Echolucent and heterogeneous plaques, in particular, carry an increased risk of subsequent stroke. Most of the trials emphasizing the relationship between plaque echo structure and stroke risk are based on high-resolution ultrasound (US) using a visual method of classification. More recently, several studies have suggested that the computerized measurement of the grey-scale median (GSM) may evaluate carotid plaque echogenicity more objectively and accurately. We sought to compare these two types of evaluations. We studied 68 consecutive patients, with 86 carotid bifurcation plaques causing 30% to 99% stenosis on duplex scanning. We assessed the GSM of these plaques and compared it to the visually evaluated echogenicity using the five-type classification system with vessel lumen and adventitia as reference structures. Plaque heterogeneity was also studied in a subgroup of 47 patients with 60 carotid stenoses by comparing visual analysis with the GSM method. The mean GSM value of the plaques increased with the plaque type. The difference of echogenicity between the five types of plaques was statistically significant (p < 0.02). We found a good concordance between visual analysis and the GSM method regarding plaque heterogeneity. Our results suggest that the visual evaluation of plaque echogenicity and heterogeneity based on the five-type classification correlates well with the computerized measurement of the GSM. The visual evaluation of carotid plaque remains, therefore, a valuable method in daily clinical practice.

Echogenic carotid plaques are associated with aortic arterial stiffness in subjects with subclinical carotid atherosclerosis.

A better understanding of the interrelationships between the structure and function of the large arteries would lead to optimize cardiovascular disease prevention strategies. In this study, we investigated the relationships of aortic arterial stiffness assessed by carotid-femoral pulse-wave velocity (PWV), with carotid plaque echogenicity assessed by B-mode ultrasound. We analyzed 561 subjects (without coronary heart disease or stroke) who were volunteers for free health examinations (age, 58.3+/-10.8 years; 32.6% women). Extracranial carotid plaque echogenicity was graded from 1 (plaque appearing black or almost black) to 4 (plaque appearing white or almost white) according to the Gray-Weale classification. Plaques of grades 1 and 2 were defined as echolucent plaques, and plaques of grades 3 and 4 were defined as echogenic plaques. Fifty-one subjects (9.1%) had echolucent carotid plaques, 109 (19.4%) had echogenic plaques, and 401 (71.5%) had no plaques. Subjects with echogenic plaques had higher PWV mean (12.9+/-2.8 m/s) compared with those without plaques (11.1+/-2.3 m/s, P<0.001) and compared with those with echolucent plaques (11.3+/-2.3 m/s, P<0.01). The PWV means in subjects without plaques and those with echolucent plaques were similar and not statistically different (P=0.55). When multivariate adjustment for major known cardiovascular risk factors was performed, these results were not markedly modified. Similar patterns of results were also observed in many subgroups according to age, gender, and hypertensive status. This study provides the first evidence that echogenic but not echolucent carotid plaques are associated with aortic arterial stiffness. This association applies to individuals with normal blood pressure and those with elevated blood pressure. Assessment of the joint and interaction effects of plaque morphology and arterial stiffness on the occurrence of cardiovascular events would permit a better identification of high-risk subjects.

Computerized Assessment of Carotid Plaque Echogenicity before Stenting

To assess the ability of transcutaneous ultrasound (US) to identify carotid atherosclerotic plaques at high risk for development of procedural strokes, the authors retrospectively analyzed the plaque echomorphology by means of gray-scale value (GSV). Both transcutaneous and intravascular US demonstrated a similar ability to characterize the atherosclerotic plaques. A case with embolic complication was proven to have had the lowest GSV in the studied cases. With computerized assessment of plaque echogenicity, pre-procedural transcutaneous US may be used to predict plaques that are associated with a high risk of distal embolization.

Increase in Echogenicity of Echolucent Carotid Plaques after Treatment with Total Triterpenic Fraction of Centella asiatica: A Prospective, Placebo-Controlled, Randomized Trial

The aim of this study was to evaluate whether total triterpenic fraction of Centella asiatica (TTFCA), was effective in modulating collagen production over 12 months, by producing an increase in echogenicity in echolucent carotid plaques. Part I was a pilot study aimed at evaluating the effects of TTFCA on different types of plaques. Part II was a prospective, randomized, placebo-controlled trial aimed at evaluating the effects of TTFCA on hypoechoic-echolucent plaques. The sonographic examination of carotid plaques was made with high-resolution ultrasound. Capturing, digital image processing, and normalization were standardized, interobserver, intrascanner, gain-level variability were standardized using as reference blood (black) for the most echolucent parts of the plaque and the adventitia (white) as the most echogenic part. Normalization of echo texture was obtained and plaque characterization differentiated echo-texture of plaque associated with events and those that did not cause embolization, thrombosis, or cardiovascular events. After identifying plaques at higher risk, patients were treated with TTFCA (oral tablets, 60 mg, thrice daily for 12 months) to evaluate whether this compound, by modulating collagen synthesis, could increase the echogenicity and therefore the stability of echolucent plaques. Part II was aimed at evaluating the effects of TTFCA on hypoechoic-echolucent plaques. Asymptomatic patients with echolucent plaques (GSM<18) were treated with TTFCA (60 mg, oral tablets three times daily for 12 months) or with comparable placebo after informed consent. All patients were also treated with antiplatelet agents. In part 1, at inclusion the GSC in the hypoechoic group was 15 (range, 12-18) while in the hyperechoic group it was 26 (range, 24-31); at 6 months it was increased in the hypoechoic group and at 12 months the increase was significant (19.5; p<0.05). There was a minor increase in GSM in the hyperechoic group (30; ns). In part II in the treatment group there was a significant difference in GSM (increase) at 12 months (p<0.05), improvement in texture (p<0.05) and a nonsignificant decrease in stenosis. No changes were observed in the placebo group. Events were observed in 6.5% of patients in the TTFCA group and in 11% in the control group (p<0.05). In conclusion these observations suggest a positive action of TTFCA on the stabilization of hypoechoic, low-density carotid plaques.