Plaque Echogenicity Research Articles

Contrast-Enhanced Ultrasound Imaging of Intraplaque Neovascularization in Carotid Arteries: Correlation With Histology and Plaque Echogenicity

This study was designed to evaluate contrast-enhanced ultrasound imaging of carotid atherosclerosis as a clinical tool to study intraplaque neovascularization. Plaque neovascularization is associated with plaque vulnerability and symptomatic disease; therefore, imaging of neovascularization in carotid atherosclerosis may represent a useful tool for clinical risk stratification and monitoring the efficacy of antiatherosclerotic therapies. Thirty-two patients with 52 carotid plaques were studied by standard and contrast-enhanced ultrasound imaging. In 17 of these patients who underwent endarterectomy, the surgical specimen was available for histological determination of microvessel density by CD31/CD34 double staining. Plaque echogenicity and degree of stenosis at standard ultrasound imaging were evaluated for each lesion. Contrast-agent enhancement within the plaque was categorized as absent/peripheral (grade 1) and extensive/internal (grade 2). In the surgical subgroup, plaques with higher contrast-agent enhancement showed a greater neovascularization at histology (grade 2 vs. grade 1 contrast-agent enhancement: median vasa vasorum density: 3.24/mm(2) vs. 1.82/mm(2), respectively, p = 0.005). In the whole series of 52 lesions, echolucent plaques showed a higher degree of contrast-agent enhancement (p < 0.001). Stenosis degree was not associated with neovascularization at histology or with the grade of contrast-agent enhancement. Carotid plaque contrast-agent enhancement with sonographic agents correlates with histological density of neovessels and is associated with plaque echolucency, a well-accepted marker of high risk lesions, but it is unrelated to the degree of stenosis. Contrast-enhanced carotid ultrasound imaging may provide valuable information for plaque risk stratification and for assessing the response to antiatherosclerotic therapies, beyond that provided by standard ultrasound imaging.

The Role of Carotid Plaque Vulnerability and Inflammation in the Pathogenesis of Acute Ischemic Stroke

Increasing evidences show that disruption of carotid plaque followed by arterio-arterial thromboembolism is an important mechanism in the generation of ischemic stroke. Inflammatory mechanisms play a key role in transforming structurally vulnerable plaques into functionally unstable ones. The purpose of the present study is to evaluate the roles of carotid plaque vulnerability and inflammation in the pathogenesis of acute ischemic stroke. Fifty-two patients with acute ischemic stroke affecting the anterior circulation (stroke group) and 44 with asymptomatic carotid stenosis (asymptomatic group) were investigated. Duplex ultrasonography was used to evaluate the characteristics of carotid plaque and grading the degree of carotid stenosis. Plaque echogenicity was assessed as echolucent, predominantly echolucent, predominantly echogenic, or echogenic. Plaque surface was classified as smooth, irregular, or ulcerated. All subjects had duplex-determined 50% to 99% carotid stenosis. Serum levels of matrix metalloproteinase-9 (MMP-9), tissue inhibitors of metalloproteinases (TIMP-1), soluble CD40 ligand (sCD40L) and high-sensitivity C-reactive protein (hsCRP) were measured. Plaques in the stroke group were echolucent or predominantly echolucent, whereas those of the asymptomatic group were predominantly echogenic or echogenic plaques (P<0.05). Irregular and ulcerated plaques were frequently found in stroke patients, while smooth plaques were frequently detected in asymptomatic patients (P<0.05). Serum levels of MMP-9, sCD40L, hsCRP were higher in stroke than in asymptomatic patients. By contrast, serum TIMP-1 levels were significantly higher in the asymptomatic than in the stroke group. The results suggest that inflammation plays a crucial role in carotid plaque vulnerability and, together with carotid plaque morphology, in the pathogenesis of acute ischemic stroke.

Intravascular ultrasound tissue characterization. I like the rainbow but... what's behind the colours?

Intravascular ultrasound (IVUS) remains the gold standard for, precise, high-quality visualization of atherosclerotic plaque on the vessel wall.1 Conventional grey-scale IVUS provides unique insights into the underlying substrate of atherosclerotic disease, and classical studies have demonstrated that plaque echogenicity correlated with its histological composition. However, despite its ability to provide direct insight on plaque composition, grey-scale IVUS has been unable to identify vulnerable plaques.2 The reason for this appears to be multifaceted. First, the current resolution of the technique is unable to define some subtle characteristics of these plaques, including the thickness of the fibrous cap. Secondly, ‘thrombotic-prone’ plaques have several pathological substrates apart from the classical ‘vulnerable plaque’ (i.e. thin cap fibroateroma) and, phenotypically, constitute a moving target. Thirdly, further accuracy to identify better the distinct histological components of atherosclerotic plaques with IVUS is clearly required. Some technological developments have attempted to overcome the limitations of conventional IVUS to elucidate plaque components.2–6 All of them rely on sophisticated mathematical analyses of the raw radiofrequency signal, aim to obtain real-time clinically meaningful tissue characterization, and provide a “ rainbow ” of appealing colours encoding different plaque components.2–6 Direct use of radiofrequency data avoids signal alterations induced by automated processing and gain adjustments. Integrated backscatter IVUS (IB-IVUS) uses the fast Fourier transformation to analyse frequencies within the signal and provides colour-coded tissue maps of plaque components (lipid, fibrous, and calcified) enabling tissue characterization with a good correlation with histological and angioscopic findings.3 Some provocative preliminary studies have even suggested that IB-IVUS may allow the detection of changes in plaque characteristics induced by lipid-lowering drugs and could also help to predict future coronary events.2,4 Alternative modalities of tissue characterization, namely wavelet analysis of radiofrequency signals, have also been validated to … *Corresponding author. Email: falf{at}hotmail.com

In-vivo imaging of carotid plaque neoangiogenesis with contrast-enhanced harmonic ultrasound

We describe a case where a mild carotid atherosclerotic plaque was assessed by contrast enhanced harmonic ultrasonography and image analysis. Quantitative indices of plaque echogenicity were determined prior and after the injection of microbubbles. Changes in plaque echogenicity were detected possibly due to the flow of microbubbles through vasa vasorum within the plaque and at the plaque base at the adventitial level. Future histological studies remain to be done to link the presence and the extent of plaque and adventitial neovascularization with the visual and quantitative findings derived by contrast enhanced harmonic ultrasound and image analysis.

Prevalence of Micro-Emboli in Symptomatic High Grade Carotid Artery Disease: A Transcranial Doppler Study

Background and purpose: Echolucent carotid plaques, as well as downstream micro-embolisation, may be associated with an increased risk of stroke. However, the relationship between carotid plaque ultrasound characteristics and micro-embolic signals (MES) detected in the middle cerebral artery (MCA) is still controversial. The purpose of this study was to investigate the prevalence of MES in patients with symptomatic high-grade internal carotid artery (ICA) stenosis and to identify predisposing factors, such as plaque echogenicity and intra stenotic blood flow velocity pattern. Methods: 197 patients (mean age 69.5 ± 8.6, 161 males) with confirmed symptomatic high-grade ICA stenosis and anti-platelet treatment underwent bilateral MES monitoring for 30 minutes within the anterior circulation, using Power M-mode transcranial Doppler techniques (TCD). Carotid artery plaques were characterized by Gray-Weale scaling. Results: In 32.0% of the patients, we detected MES by TCD within the MCA on the symptomatic side, but the same finding was made in only 4.5% on the corresponding asymptomatic site (p < 0.0001). The presence or absence of MES was associated with neither ultrasonic plaque characteristics nor the intrastenotic blood flow velocities at peak systole and end diastole. The median time since the last ischemic event symptoms was shorter in the patient group with MES [+] than in MES [−] (p = 0.013). Conclusions: Despite optimum standard anti-platelet therapy, cerebral micro-embolisation occurs in 30% of patients with symptomatic carotid artery disease, which might therefore be a possible risk factor for recurrent neurological symptoms. However, the presence of MES is independent of intrastenotic blood flow disturbances and grey scale ultrasound plaque characteristics. The presence of MES as an indicator of unstable plaque and thereby a possible risk factor for stroke should be evaluated prospectively using various algorithms for plaque classifications.

Statin Therapy Increases Carotid Plaque Echogenicity in Hypercholesterolemic Patients

Stabilization of carotid artery plaques by pharmacologic intervention is a promising strategy for the prevention of ischemic stroke. In this study, we examined the effect of 12 months of statin therapy on carotid plaque echogenicity. This study included 81 hypercholesterolemic patients with carotid atherosclerotic plaques. Echogenicity of the largest plaque in each patient was evaluated by ultrasound with integrated backscatter analysis. All patients underwent dietary modification. Forty patients were treated with simvastatin (10 mg/day, n = 24) or atorvastatin (5 mg/day, n = 16) according to the choice by each attending physician. Carotid plaques were monitored by measuring plaque thickness and echogenicity during a 12-month follow-up period. Levels of serum high-sensitivity CRP (hs-CRP), interleukin (IL)-6 and IL-18 were determined in all patients. Total cholesterol, triglyceride, hs-CRP and IL-18 were significantly decreased after 12 months of statin therapy. The change in IL-6 level was not significant. Significant increases in echogenicity of carotid plaques and decreases in plaque thickness were noted after statin therapy. In the 41 patients without statin therapy, carotid plaque echogenicity, plaque thickness and serum levels of inflammatory markers were not significantly altered. Our results suggest that statin therapy in hypercholesterolemic patients for 12 months increases carotid plaque echogenicity and decreases plaque thickness, in addition to lowering serum levels of lipids and inflammatory markers. (E-mail: kitagawa@medone.med.osaka-u.ac.jp).

Intensive Lipid-lowering Therapy Ameliorates Novel Calcification Markers and GSM Score in Patients with Carotid Stenosis

Carotid plaque echogenicity quantified by the Gray-Scale Median (GSM) score has been associated with plaque vulnerability. The aim of this study was to assess whether intensive lipid-lowering treatment with atorvastatin in patients with carotid artery stenosis ameliorates novel vascular calcification inhibitors, such as osteopontin (OPN) and osteoprotegerin (OPG), and improves GSM score. Ninety-seven patients with carotid stenosis (>40%), but without indication for intervention, were treated for 6 months with atorvastatin (10mg-80mg) to target LDL<100mg/dl. Fifty-two age-and sex-matched healthy individuals served as the control group. Blood samples and GSM were obtained at the beginning and after 6 months. Systolic blood pressure, hsCRP, fibrinogen, OPN and OPG levels differed significantly between patients with carotid stenosis and healthy controls at baseline (p<0.05). Atorvastatin treatment improved lipid profile and significantly reduced hsCRP (p=0.002), WBC count (p=0.041), OPN (p<0.001) and OPG levels (p<0.001). GSM score increased considerably after atorvastatin therapy (from 58.33+/-24.38 to 79.33+/-22.3; p<0.001) and that effect appeared related to OPN (p=0.001), OPG (p=0.013) and LDL (p=0.01) reduction. In patients with carotid stenosis, intensive lipid-lowering therapy with statins attenuates serum OPN and OPG levels and enhances carotid plaque echogenicity, outlining their beneficial effects on plaque stability.

Circulating matrix metalloproteinase 9 levels in relation to sampling methods, femoral and carotid atherosclerosis

To examine whether circulating levels of matrix metalloproteinase 9 (MMP-9) were associated with ultrasound-assessed intima-media thickness (IMT) and echolucent plaques in the carotid and femoral arteries. To examine preanalytical sources of variability in MMP-9 concentrations related to sampling procedures. Plasma and serum MMP-9 levels were compared with ultrasound assessed measures of femoral and carotid atherosclerosis, in a cross-sectional study of 61-year-old men (n = 473). Preanalytical sources of variability in MMP-9 levels were examined in 10 healthy subjects. Main outcome measures were circulating levels of MMP-9 in serum and plasma, IMT of the carotid and femoral arteries, and plaque status based on size and echolucency. Research unit at university hospital. Plasma concentrations of total and active MMP-9 were associated with femoral artery IMT independently of traditional cardiovascular risk factors, and were higher in subjects with moderate to large femoral plaques. Plasma MMP-9 concentration was higher in men with echolucent femoral plaques (P = 0.006) compared with subjects without femoral plaques. No similar associations were found for carotid plaques. MMP-9 concentrations were higher in serum than in plasma, and higher when sampling was performed with Vacutainer than with syringe. MMP-9 levels in serum were more strongly associated with peripheral neutrophil count compared with MMP-9 levels in plasma. Plasma MMP-9 levels were associated with atherosclerosis in the femoral artery, and total MMP-9 concentration was higher in men with echolucent femoral plaques. The choice of sample material and sampling method affect the measurements of circulating MMP-9 levels.

Delayed Metabolism of Postprandial Triglyceride‐Rich Lipoproteins in Subjects with Echolucent Carotid Plaques

Subjects with echolucent carotid plaques have an increased risk of ischemic cerebrovascular events independent of degree of stenosis. Low plasma lipoprotein lipase (LPL) activity promotes a proatherogenic lipid profile, and delayed chylomicron clearance is a risk factor for atherosclerosis. This study was conducted to determine plasma LPL activity and postprandial metabolism of triglycerides in relation to carotid plaque morphology. Plaque echogenicity was assessed by B-mode ultrasound and analysis of the grey scale median (GSM). Echolucent plaques were defined as GSM < or = 63 (the median) and echogenic plaques as GSM > 63, and 57 subjects with carotid plaques and 38 subjects without carotid plaques were recruited. Blood samples were collected before and at 2-h interval for 8 h after a standard high fat meal. LPL activity and mass was determined before and after heparin administration. Postheparin LPL activity was decreased in subjects with echolucent plaques compared to subjects with echogenic plaques (P = 0.06) and to controls (P = 0.04). Plaque echogenicity increased linearly with increasing levels of postheparin LPL activity (P = 0.02) and mass (P = 0.03). Subjects with echolucent plaques had delayed postprandial clearance of chylomicron triglycerides compared to controls (P = 0.04). Low postheparin LPL activity due to attenuated mobilization of LPL from capillary endothelium may play an important role in the formation of echolucent plaques by modulation of postprandial lipids and subsequent fat accumulation in the arterial wall.

Prevalence of Micro-Emboli in Symptomatic High Grade Carotid Artery Disease: A Transcranial Doppler Study

Echolucent carotid plaques, as well as downstream micro-embolisation, may be associated with an increased risk of stroke. However, the relationship between carotid plaque ultrasound characteristics and micro-embolic signals (MES) detected in the middle cerebral artery (MCA) is still controversial. The purpose of this study was to investigate the prevalence of MES in patients with symptomatic high-grade internal carotid artery (ICA) stenosis and to identify predisposing factors, such as plaque echogenicity and intra stenotic blood flow velocity pattern. 197 patients (mean age 69.5+/-8.6, 161 males) with confirmed symptomatic high-grade ICA stenosis and anti-platelet treatment underwent bilateral MES monitoring for 30 minutes within the anterior circulation, using Power M-mode transcranial Doppler techniques (TCD). Carotid artery plaques were characterized by Gray-Weale scaling. In 32.0% of the patients, we detected MES by TCD within the MCA on the symptomatic side, but the same finding was made in only 4.5% on the corresponding asymptomatic site (p<0.0001). The presence or absence of MES was associated with neither ultrasonic plaque characteristics nor the intrastenotic blood flow velocities at peak systole and end diastole. The median time since the last ischemic event symptoms was shorter in the patient group with MES [+] than in MES [-] (p=0.013). Despite optimum standard anti-platelet therapy, cerebral micro-embolisation occurs in 30% of patients with symptomatic carotid artery disease, which might therefore be a possible risk factor for recurrent neurological symptoms. However, the presence of MES is independent of intrastenotic blood flow disturbances and grey scale ultrasound plaque characteristics. The presence of MES as an indicator of unstable plaque and thereby a possible risk factor for stroke should be evaluated prospectively using various algorithms for plaque classifications.

The prevalence of hypoechoic carotid plaques is greater in peripheral than in coronary artery disease and is related to the neutrophil count

Previous reports indicate that the prevalence and severity of carotid stenoses is greater in peripheral artery disease (PAD) than in coronary artery disease (CAD). To date, no study has compared these two populations with respect to plaque echogenicity, which is an independent risk factor for cerebrovascular events. In 43 PAD patients without CAD and in 43 CAD patients without PAD, carotid plaques were studied with high-resolution B-mode ultrasound and by computerized measurement of the gray-scale median. At visual analysis, the prevalence of hypoechoic plaques was 39.5% in PAD and 18.6% in CAD (P = .033). The corresponding values for gray-scale median analysis were 34.9% and 14.0% (P = .024). At multivariate analysis, PAD patients showed a greater risk of having hypoechoic plaques than CAD patients at visual (odds ratio [OR], 4.39, 95% confidence interval [CI] 1.21-15.92, P = .025) and gray-scale median analysis (OR, 5.13; 95% CI, 1.27-20.67; P = .021). This association was no longer significant when neutrophil number was included among the covariates. In this model, only an increased neutrophil count was associated with hypoechoic plaques (P < .01 for both visual and gray-scale median analysis). Indeed, neutrophil count was greater in PAD than in CAD (4.4 +/- 1.0 vs 3.9 +/- 1.2 10(9)/L, P = .030). The concordance between visual typing of carotid plaques and gray-scale median measurement was good (rho = 0.714, P < .01). Compared with CAD patients, those with PAD, in addition to a greater atherosclerotic burden, may have characteristics of instability of carotid plaques that, in turn, may result in cerebrovascular events. Prospective studies are needed to assess specifically whether the greater prevalence of hypoechoic plaques in PAD vs CAD patients is associated with a greater risk of cerebrovascular events.

A three-dimensional ultrasonographic quantitative analysis of non-ulcerated carotid plaque morphology in symptomatic and asymptomatic carotid stenosis

Background and purpose Studies evaluating the association between carotid plaque composition and occurrence of ischemic cerebrovascular disease reveal inconsistent results. This study correlates the carotid echomorphology with the degree of stenosis in symptomatic and asymptomatic patients. Methods We included consecutive patients with hemispheric stroke or asymptomatic carotid artery stenosis assessed with 2D ultrasound. The echomorphology was assessed with mean gray value (MGV) of the three-dimensional (3D) volume. We used the free-hand approach for 3D image and volume acquisition. Analyses of the stored carotid plaque volumes were carried out offline using the Virtual Organ Computer-aided Analysis (VOCAL™) program. Results We studied 110 symptomatic and 104 asymptomatic atherosclerotic carotid plaques. MGV was lower in symptomatic carotid plaques causing <70% stenosis compared to plaques causing ≥70% stenosis (25.95 ± 7.40 vs. 32.16 ± 11.35, p = 0.002). There was no difference in MGV between plaques producing <60% and those with ≥60% in asymptomatic patients (32.08 ± 8.36 vs. 31.46 ± 9.25, p = 0.724). There were significant differences in MGV between symptomatic and asymptomatic plaques causing <60 or <70% stenosis; MGV was lower in symptomatic patients. Conclusions Lower plaque echogenicity is observed in symptomatic than in asymptomatic patients with moderate degree of carotid stenosis, indicating that it is a significant factor for the production of cerebral ischemia. Our method could be useful in assessing the risk of cerebral ischemia and the response of carotid artery atherosclerosis to medical therapies.

Associations of Insulin-Like Growth Factor (IGF)-I, IGF-II, IGF Binding Protein (IGFBP)-2 and IGFBP-3 with Ultrasound Measures of Atherosclerosis and Plaque Stability in an Older Adult Population

Circulating IGF-I is inversely associated with ischemic heart disease incidence. Whether this association relates to alterations in plaque growth or stability, and the role of IGF-II and the major binding proteins [IGF binding protein (IGFBP)-2 and -3], is unclear. Our objective was to test the hypothesis that circulating IGF-I is inversely, and IGF-II is positively, associated with subclinical atherosclerosis and plaque stability. This was a cross-sectional analysis based on 310 participants in the United Kingdom-based Boyd Orr cohort who were aged 63-82 yr. Cohort members from Aberdeen, Bristol, Dundee, Wisbech, and London were invited to clinics for fasted venepuncture and arterial ultrasound examination. Arterial intima-media thickness, arterial plaque prevalence, and computerized assessment of plaque echogenicity (a measure of stability), undertaken using the gray scale median, were calculated. In total, 269 of 310 (86.8%) participants had at least one carotid or femoral plaque. In models controlling for IGFBP-3, there was a 44% (95% confidence interval 12-64%) reduction in the odds of any plaque and a 28% lower (0-48%) odds of echolucent (unstable) plaques per sd increase in IGF-I. IGFBP-3 was positively associated with plaque instability (odds ratio: 1.38; 0.99-1.93). IGF-II was positively associated (0.05-mm increase per sd; 95% confidence interval 0.01-0.09), and IGFBP-2 was inversely associated, with carotid bifurcation intima-media thickness. Neither IGF-II nor IGFBP-2 was associated with plaque prevalence or echogenicity. High-circulating IGF-I levels may promote arterial plaque stability. IGF-II and IGFBP-2 do not appear to play a role in plaque development or stability.

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.

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.

Associations of IGF-I, IGF-II, IGFBP-2 and IGFBP-3 with ultrasound measures of atherosclerosis and plaque stability in an older adult population.

Context: Circulating IGF-I is inversely associated with ischemic heart disease incidence. Whether this association relates to alterations in plaque growth or stability, and the role of IGF-II and the major binding proteins [IGF binding protein (IGFBP)-2 and -3], is unclear. Objective: Our objective was to test the hypothesis that circulating IGF-I is inversely, and IGF-II is positively, associated with subclinical atherosclerosis and plaque stability. Design, Setting, and Participants: This was a cross-sectional analysis based on 310 participants in the United Kingdom-based Boyd Orr cohort who were aged 63-82 yr. Cohort members from Aberdeen, Bristol, Dundee, Wisbech, and London were invited to clinics for fasted venepuncture and arterial ultrasound examination. Main Outcomes: Arterial intima-media thickness, arterial plaque prevalence, and computerized assessment of plaque echogenicity (a measure of stability), undertaken using the gray scale median, were calculated. Results: In total, 269 of 310 (86.8%) participants had at least one carotid or femoral plaque. In models controlling for IGFBP-3, there was a 44% (95% confidence interval 12-64%) reduction in the odds of any plaque and a 28% lower (0-48%) odds of echolucent (unstable) plaques per sd increase in IGF-I. IGFBP-3 was positively associated with plaque instability (odds ratio: 1.38; 0.99-1.93). IGF-II was positively associated (0.05-mm increase per sd; 95% confidence interval 0.01-0.09), and IGFBP-2 was inversely associated, with carotid bifurcation intima-media thickness. Neither IGF-II nor IGFBP-2 was associated with plaque prevalence or echogenicity. Conclusion: High-circulating IGF-I levels may promote arterial plaque stability. IGF-II and IGFBP-2 do not appear to play a role in plaque development or stability.

The relationship between serum levels of vascular calcification inhibitors and carotid plaque vulnerability

Osteopontin (OPN) and osteoprotegerin (OPG) are well-known vascular calcification inhibitors, which have been recently demonstrated to correlate with inflammation and cardiovascular events incidence. The aim of this cross-sectional study is to survey whether OPN and OPG are involved in carotid plaque vulnerability. For this reason, we assessed serum OPN and OPG levels in patients with carotid stenosis, and we explored their relationship with carotid plaque echogenicity and subsequent cerebrovascular ischemic events. A total of 164 Whites were selected from a large cohort of 297 subjects to participate. In particular, 114 patients (61 men, 53 women), aged 55 to 80, had recently-diagnosed ICA stenosis higher than 50%. A group of 50 age-, sex-, and body mass index (BMI)-matched healthy individuals served as healthy controls. Patients with renal failure, hypothyroidism, osteoporosis, and lipid-lowering therapy were excluded. Images of both carotids were obtained from all participants using a high-resolution color duplex ultrasound and the gray-scale median (GSM) score was calculated. Brain computed tomography (CT), and magnetic resonance imaging (MRI) scans when CT was questionable, were performed on all patients with carotid stenosis. Clinical parameters, lipid and glycemic indexes, hsCRP, fibrinogen, white blood cells (WBC) count, OPN, and OPG were measured. Independent t test, one-way ANOVA, Pearson correlation, and multiple regression analysis were used for statistical analysis. Among patients with carotid stenosis, 60 had history of ipsilateral stroke or TIA and positive CT or MRI findings (group A), while 54 had no neurological symptoms and negative CT and MRI scan (group B). Overall, patients with carotid stenosis showed worse lipid profile and increased waist circumference, blood pressure, hsCRP, fibrinogen, WBC count, OPN, and OPG levels compared with healthy subjects (group C) (P <.05). Statistical analysis revealed that group A had significantly lower levels of GSM than group B (57.41 +/- 38.19 vs 76.32 +/- 36.72; P = .008) and higher levels of hsCRP, OPN, and OPG than groups B and C (P < .05). Concerning the latter, biochemical markers group B showed only elevated OPG levels compared with group C (P = .038). Notably, GSM was considerably associated with serum OPN and OPG and waist circumference in patients with carotid atherosclerosis in univariate (r = -0.333; P = .032, r = -0.575; P < .001, r = -0.590; P =.006, respectively) and multiple regression analysis (R(2) = 0.445; P =.006). The present study demonstrated elevated serum OPN and OPG levels in patients with carotid stenosis and documented an independent association between these biochemical markers, GSM and carotid-induced symptomatology. Therefore bone-matrix proteins combined with GSM could be potential markers for vulnerable carotid plaques.

Gray-scale median of the atherosclerotic plaque can predict success of lumen re-entry during subintimal femoral-popliteal angioplasty

This study assessed whether the duplex ultrasound (DUS)-derived gray-scale median (GSM) of the most six distal portion of the occluded femoral-popliteal arterial segment can predict success of lumen re-entry for subintimal angioplasty. During the last 3 years, 108 patients (62% men) with a mean age of 73 +/- 10 years underwent 116 primary attempted DUS-guided subintimal angioplasties of the femoral-popliteal segment. Preprocedural B-mode DUS images of the plaque at the most distal occlusion segment were digitalized and normalized using Photoshop (Adobe, San Jose, Calif) software and standard criteria (gray level, 0 to 5 for lumen blood and 185 to 190 for the adventitia on a linear scale of 0 to 255). Overall GSM of the plaque segment about 2 cm long, immediately before the planned re-entry point to the true arterial lumen, was used for retrospective correlation with procedure success and other clinical indicators. Mean plaque GSM for all cases was 22.5 +/- 12.6 (range, 3 to 60). The overall success rate of subintimal angioplasty procedures was 85%. Mean plaque GSM for 99 successful cases (18.4 +/- 7.8) was significantly lower than for 17 cases (46.4 +/- 8.1) where we failed (P < .0001). We failed in 90% of 19 cases with GSM >35, in 71% of 24 cases with GSM >20, and in 50% of 34 cases with GSM >25. There was no statistically significant difference (P = .45) between plaque GSM in 64 patients with diabetes (23.3 +/- 13.5) compared with 52 nondiabetic patients (21.5 +/- 11.4). Similarly, plaque GSM was not statistically different (P = .9) in 52 patients with renal insufficiency (22.7 +/- 13.2) compared with 64 patients with normal creatinine levels (22.4 +/- 12.2). At the 6-month follow-up, no statistically significant difference was found between mean GSM (17.8 +/- 7.8) in 47 stenosis-free cases compared with mean GSM (18 +/- 6.8) in 22 cases where severe restenosis (>70%) or reocclusion was identified by DUS scan (P = .4). Plaque echogenicity represented by DUS-derived GSM can be used to predict the success of primary subintimal femoral-popliteal angioplasties.

Carotid Atherosclerosis Is a Stronger Predictor of Myocardial Infarction in Women Than in Men

Ultrasound of carotid arteries provides measures of intima media thickness (IMT) and plaque, both widely used as surrogate measures of cardiovascular disease. Although IMT and plaques are highly intercorrelated, the relationship between carotid plaque and IMT and cardiovascular disease has been conflicting. In this prospective, population-based study, we measured carotid IMT, total plaque area, and plaque echogenicity as predictors for first-ever myocardial infarction (MI). IMT, total plaque area, and plaque echogenicity were measured in 6226 men and women aged 25 to 84 years with no previous MI. The subjects were followed for 6 years and incident MI was registered. During follow-up, MI occurred in 6.6% of men and 3.0% of women. The adjusted relative risk (RR; 95% CI) between the highest plaque area tertile versus no plaque was 1.56 (1.04 to 2.36) in men and 3.95 (2.16 to 7.19) in women. In women, there was a significant trend toward a higher MI risk with more echolucent plaque. The adjusted RR (95% CI) in the highest versus lowest IMT quartile was 1.73 (0.98 to 3.06) in men and 2.86 (1.07 to 7.65) in women. When we excluded bulb IMT from analyses, IMT did not predict MI in either sex. In a general population, carotid plaque area was a stronger predictor of first-ever MI than was IMT. Carotid atherosclerosis was a stronger risk factor for MI in women than in men. In women, the risk of MI increased with plaque echolucency.

The use of Speckle Reduction Imaging (SRI) Ultrasound in the characterization of carotid artery plaques

Background and purpose Speckle Reduction Imaging is a new algorithm that improves the image quality of B-mode scanning by reducing the reverberation artifacts. In the present study the value of this method for the characterization of atherosclerotic plaques in the internal carotid artery was investigated. Methods Two hundred and twenty two patients (161 men, 61 women; mean age 73 years) referred for carotid ultrasound evaluation were included in the study. Patients with plaques of the internal carotid artery as identified by conventional B-mode scanning were investigated also with the addition of Speckle Reduction Imaging (SRI) with the use of a 4–11-MHz wide band linear transducer. Plaque morphology was rated according to a standardized protocol by two independent observers. Results For the determination of plaque echogenicity, the reproducibility of SRI ( κ = 0.83) was higher than that of conventional B-mode ultrasound ( κ = 0.68). The interobserver agreement for plaque surface characterization was also higher for SRI ( κ = 0.8) than for conventional B-mode ( κ = 0.61). At the evaluation of the image quality through a semiquantitative analysis, SRI was rated superior in the plaque texture resolution, plaque borders determination, vessel wall demarcation and fibrous cap depiction. In addition, the level of “speckle” was reduced with the use of SRI. Conclusions SRI is a technique that shows good general agreement with high-resolution B-mode and can be used for the characterization of atherosclerotic plaques in the carotid artery. Furthermore, because this advanced technique allows reduction of ultrasound artifacts, it improves the image quality allowing more precise visualization of plaque morphological details.