Carotid Plaque Echogenicity Research Articles

Adverse outcomes following carotid artery stenting in echolucent plaques: a systematic review and meta-analysis

Abstract Objective Conflicting evidence exists regarding carotid artery stenting (CAS) interventions on echolucent plaques and adverse outcomes. This meta-analysis aims to assess the relationship between carotid plaque echogenicity and adverse outcomes following CAS. Methods We conducted a systematic search of electronic databases (PubMed, MEDLINE, EMBASE and Cochrane Center Register) up to January 2024. Two researchers independently assessed the eligibility of studies that used ultrasound to assess carotid artery plaque echogenicity and its relationship with adverse outcomes after CAS. We used web-based systematic review production software RevMan to conduct the analysis. Results Eight studies including 810 patients’ data that have reported on in-stent restenosis, distal embolization and stroke after CAS were meta-analyzed. Mean age of the participants was 68±11 years and 43% were females. CAS performed on echolucent plaques demonstrated a higher frequency of association with distal microembolization OR=3.64 (95% CI 2.11-6.30, p<0.001), in-stent restenosis OR=2.87 (95% CI 1.84-4.47, p=0.003) and stroke OR=3.80 (95% CI 1.93-7.44, p<0.001). In the pooled analysis covering all adverse outcomes following CAS, the OR was 3.28 (95% CI 2.41-4.45, p<0.001, I2=25%). Conclusions Arterial stenting performed on echolucent carotid plaques was more frequently associated with adverse outcomes, such as stroke, distal microembolization, and in-stent restenosis.

Ultrasound diagnostic potential of carotid plaques in symptomatic and asymptomatic patients: Insights from quantitative gray-scale analysis

ObjectivesTo determine the ability of ultrasound gray-scale analysis to differentiate between carotid plaques in symptomatic and asymptomatic patients and to assess the reproducibility of carotid plaque gray-scale analysis. MethodsUltrasound B-mode images from patients with carotid plaques were retrospectively evaluated. Gray-scale mean and median values of carotid plaque echogenicity were determined via computer-assisted quantification using the histogram feature in Adobe Photoshop. Gray-scale values of the entire plaque obtained by the two observers were used to measure echogenicity. Receiver operating characteristic and independent t-test were used to determine potential cut-off for normalized gray-scale values, and whether there was a significant difference between the normalized gray-scale values of carotid plaques in symptomatic and asymptomatic patients, respectively. Inter-observer reproducibility of gray-scale values was assessed using intraclass correlation coefficient (ICC). ResultsEighty-seven carotid plaques (59 symptomatic and 28 asymptomatic) from 54 patients with carotid plaques were evaluated on ultrasound B-mode. Gray-scale mean and median cut-off values of 25 and 22 showed sensitivity of 75% (95% CI 56.6–87.3%) and specificity of 23.7% (95% CI 14.6–35.9%). Carotid plaques in symptomatic patients had significantly lower gray-scale mean (p = 0.03) and median (p = 0.04) values compared with asymptomatic patients. Inter-observer agreement for gray-scale mean and median was excellent, with ICC values of 0.998 and 0.997, respectively. ConclusionUltrasound gray-scale analysis is reproducible and represents a promising diagnostic additive tool to differentiate between carotid plaques in symptomatic and asymptomatic patients. Further research is needed to establish the clinical utility of ultrasound gray-scale analysis for carotid artery disease management.

Associations Between GGT/ALT Ratio and Carotid Plaque in Inpatients With Coronary Artery Disease: A RCSCD-TCM Study.

This study investigated the relationship between gamma-glutamyltransferase/alanine aminotransferase (GGT/ALT) ratio and carotid plaques in patients with coronary artery disease (CAD). This multicenter retrospective study included 8,255 patients with CAD who were divided according to GGT/ALT quartiles: Q1 (GGT/ALT ≤ 1.00), Q2 (1.00 < GGT/ALT ≤ 1.41), Q3 (1.41 < GGT/ALT ≤ 2.05), and Q4 (GGT/ALT > 2.05). Logistic regression was used to analyze the relationship between GGT/ALT, carotid plaques, and carotid plaque echogenicity. GGT/ALT ratio (odds ratio [OR]: 1.16; 95% confidence interval [CI]: 1.11-1.21; P < .001) was significantly associated with carotid plaque risk. The degree of relevance was higher in men (OR: 1.71; 95% CI: 1.35-2.15; P < .001) than in women (OR: 1.56; 95% CI: 1.28-1.91; P < .001). The ORs value of carotid plaque risk was higher in middle-aged patients (OR: 2.23; 95% CI: 1.78-2.80; P < .001) than in older patients (OR: 1.77; 95% CI: 1.44-2.18; P < .001). The GGT/ALT ratio was significantly associated with different carotid plaque echogenicity, and the highest OR values were for isoechoic plaques (OR: 1.18; 95% CI: 1.12-1.24; P < .001). These findings suggest that the GGT/ALT ratio might be associated with a high risk of developing carotid plaques and different types of plaque echoes and was more significantly associated with isoechoic plaques.

High-risk carotid plaques and incident ischemic stroke in patients with atrial fibrillation in the Cardiovascular Health Study.

Whether carotid artery disease could improve stroke risk stratification tools in patients with atrial fibrillation (AF) remains uncertain. This study was undertaken to investigate the risk of ischemic stroke associated with occlusive and nonocclusive carotid atheroscleroticdisease in patients with AF in the prospective population-based Cardiovascular Health Study. We included participants aged ≥65 years with AF. We used multivariable Cox regression analysis to explore the risk of ischemic stroke associated with the percentage of carotid stenosis, plaque irregularity, echogenicity, and vulnerability (markedly irregular, ulcerated, or hypoechoic plaques). A total of 1398 participants were included (55.2% female, 61.7% aged 65-74 years). The maximum carotid stenosis was <50%, 50%-99%, and 100% in 94.5%, 5%, and 0.5% of participants, respectively. High-risk plaques based on echogenicity and plaque irregularity were found in 25.6% and 8.9% of participants, respectively. After a median follow-up of 10.9 years (interquartile range = 7.5-15.6), 298 ischemic strokes were recorded. There was no difference in the incidence of ischemic stroke according to the degree of carotid artery stenosis (p = 0.44), plaque echogenicity (low vs. high risk, p = 0.68), plaque irregularity (low vs. high risk, p = 0.55), and plaque vulnerability (p = 0.86). The CHA₂DS₂-VASc score was associated with an increased risk of ischemic stroke (adjusted hazard ratio = 1.28, 95% confidence interval = 1.18-1.40, p < 0.001). Both maximum grade of stenosis and plaque vulnerability were not associated with incident ischemic stroke (all p > 0.05). Neither the degree of carotid stenosis nor the presence of vulnerable plaques was associated with incident ischemic stroke in this cohortof individuals with AF. This suggests that carotid disease was probably not a significant contributor to ischemic stroke in this population.

Enhanced Carotid Plaque Echolucency Is Associated with Reduced Cognitive Performance in Elderly Patients with Atherosclerotic Disease Independently on Metabolic Profile.

Vulnerable carotid atherosclerotic plaques are related to an increased risk of cognitive impairment and dementia in advanced age. In this study, we investigated the relationship between the echogenicity of carotid plaques and cognitive performance in patients with asymptomatic carotid atherosclerotic plaques. We enrolled 113 patients aged 65 years or more (72.4 ± 5.9 years) who underwent carotid duplex ultrasound to evaluate plaque echogenicity by grey-scale median (GSM) and neuropsychological tests to assess cognitive function. The GSM values at baseline were inversely correlated with the number of seconds required to complete Trail Makin Test (TMT) A (rho: -0.442; p < 0.0001), TMT B (rho: -0.460; p < 0.0001) and TMT B-A (rho: -0.333; p < 0.0001) and directly correlated with Mini Mental State Examination (MMSE) and Verbal Fluency Test (VFT) score (rho: 0.217; p = 0.021 and rho: 0.375; p < 0.0001, respectively) and the composite cognitive z-score (rho: 0.464; p < 0.0001). After a mean period of 3.5 ± 0.5 years, 55 patients were reevaluated according to the same baseline study protocol. Patients with baseline GSM value higher than the median value of 29 did not show any significant variation in the z-score. Instead, those with GSM ≤ 29 showed a significant worsening of z-score (-1.2; p = 0.0258). In conclusion, this study demonstrates the existence of an inverse relationship between the echolucency of carotid plaques and cognitive function in elderly patients with atherosclerotic carotid disease. These data suggest that the assessment of plaque echogenicity if used appropriately, might aid in identifying subjects at increased risk for cognitive dysfunction.

Association of HbA1c with carotid artery plaques in patients with coronary heart disease: a retrospective clinical study

Background and aims Haemoglobin A1c (HbA1c) levels have been shown to be related to carotid artery plaques. However, studies on the relationship between HbA1c levels and carotid artery plaques in patients with coronary heart disease (CHD) are limited and inconsistent. Our objective was to examine the correlation between HbA1c levels and carotid artery plaques in patients with CHD. Methods The study comprised 9275 Chinese adults with CHD from January 1, 2014, to September 30, 2020. HbA1c levels were assessed, and colour Doppler ultrasound was used to evaluate the carotid artery, including plaque presence, intima-media thickness, and plaque echo properties, to investigate the association between HbA1c and carotid plaque. A logistic regression model was used to assess the association between carotid artery plaques, carotid plaque echogenicity, and HbA1c. Results The HbA1c level of the plaque-present group was higher than that of the plaque-absent group [6.1 (5.6–7.2) vs. 5.8 (5.5–6.5), p < 0.001]. In multiple linear regression analysis, intima-media thickness was associated with HbA1c (p < 0.001). Logistic regression showed that a higher HbA1c level was associated with plaque incidence as well as hyperechoic and heterogeneous plaques (p < 0.001). These associations persist after adjusting for age, sex, blood pressure, lipid profiles, alcohol consumption, and tobacco exposure. Conclusion HbA1c levels are notably associated with carotid artery plaque incidence, intima-media thickness, and plaque echogenicity in patients with CHD. These findings show that different levels of HbA1c may be an indicator for carotid artery plaques and thus, should be observed in patients with CHD.

Echolucent Carotid Plaques Becomes More Echogenic over Time – A 3D Ultrasound Study

Despite the presence of only a few established risk factors, some patients will experience atherosclerotic events. Therefore, methods for improved risk stratification for atherosclerotic events are wanted. We aimed to detect changes in carotid artery atherosclerotic plaque volume and echogenicity over time in patients with an acute thromboembolic event and in patients with chronic atherosclerotic disease, both treated with statin, using a novel 3D ultrasound system. We included two cohorts of patients; 70 patients, naïve to statin treatment, admitted with acute, first-time myocardial infarction (aMI), and 69 patients who had been on statin treatment for a minimum of 6 months with chronic peripheral arterial disease (cPAD). 3D ultrasound examination was performed at baseline and after 3 and 12 months. Plaque volume was quantified in 3D ultrasound plaque acquisitions, and echogenicity was assessed using grayscale median (GSM) and normalized with adventitia as reference. The aMI group had darker plaques than the cPAD group at baseline (mean GSM: 60.98, standard deviation (SD): 24.09 vs. 71.75, SD: 21.55; P=0.006), 3 months (63.64, SD: 20.47 vs. 73.44, SD: 20.46; P=0.006) and at 12 months follow-up (59.25, SD: 18.07 vs. 71.02, SD: 22.31; P=0.004). The differences were not significant after adjusting for traditional risk factors. Dividing both groups by the median GSM, the darkest half of the aMI group's had an increase in GSM mainly within the first 3 months (10.49, CI 95%: 2.45 to 18.53; P=0.012) and hereafter remained unchanged at 12 months follow-up (-0.53, CI 95%: -7.28 to 6.22, P=0.875). In the darkest cPAD group GSM also increased within 3 months (8.14, CI 95%: 1.85-14.32, P=0.012) and hereafter stabilized till 12 months (-2.54, CI 95%: -9.62 to 4.53, P=0.475). Plaque volume did not change in the aMI group from baseline (median: 55.41mm3, interquartile range (IQR): 24.24-84.31) to 12 months (58.67mm3, IQR: 31.81-93.51) (P=0.220) whereas there was a small decrease in the cPAD group from baseline (71.63mm3, IQR: 40.12-135.61) to 12 months (67.73mm3, IQR: 31.00-122.38) (P=0.026). Echolucent carotid plaque, assessed with the novel 3D matrix ultrasound system, had increasing GSM within 3 months period, indicating stabilization of the more vulnerable plaques in aMI and cPAD patients. Plaque volume decreased over 12 months follow-up in a long-term statin-treated patient with cPAD, but not during the first 12months statin therapy in patients with aMI.

The Association of Arterial Stiffness With Significant Carotid Atherosclerosis and Carotid Plaque Vulnerability.

Arterial stiffness and its valid index, the cardio-ankle vascular index (CAVI), have emerged as predictors of adverse cardiovascular outcomes. We investigated the relationship of the CAVI with significant carotid stenosis (> 50%) and the related cerebrovascular symptoms or carotid plaque echogenicity, assessed by ultrasound gray-scale median (GSM) score, at baseline and after carotid artery stenting (CAS). We prospectively enrolled 113 patients with carotid stenosis (70-99% for asymptomatic and > 50% for symptomatic participants) eligible for CAS. Age- and sex-matched individuals (n = 38) served as controls (CON). Clinical data, CAVI, and biochemical profile were obtained at baseline. Clinical assessment and CAVI measurement were performed 6 months after CAS. Compared with the CON group, the CAS group had a higher incidence of co-morbidities (diabetes, hypertension, and hyperlipidemia), higher CAVI values (9.94 ± 2.14 vs 7.85 ± .97 m/sec, P < .001), but a better lipid profile due to increased prescription of statins. The symptomatic CAS subgroup showed higher CAVI (P < .001), high-sensitivity C-reactive protein (P = .048), and osteoprotegerin (P = .002) levels than the asymptomatic one. In multivariate analysis, CAVI at baseline was independently associated with the presence of significant carotid atherosclerosis (β = .695, P < .001), cerebrovascular events (β = .474, P < .001), and GSM score (β = -.275, P = .042). Raised CAVI values were independently associated with significant carotid stenosis and plaque vulnerability.

Multilevel Strip Pooling-Based Convolutional Neural Network for the Classification of Carotid Plaque Echogenicity

Carotid plaque echogenicity in ultrasound images has been found to be closely correlated with the risk of stroke in atherosclerotic patients. The automatic and accurate classification of carotid plaque echogenicity is of great significance for clinically estimating the stability of carotid plaques and predicting cardiovascular events. Existing convolutional neural networks (CNNs) can provide an automatic carotid plaque echogenicity classification; however, they require a fixed-size input image, while the carotid plaques are of varying sizes. Although cropping and scaling the input carotid plaque images is promising, it will cause content loss or distortion and hence reduce the classification accuracy. In this study, we redesign the spatial pyramid pooling (SPP) and propose multilevel strip pooling (MSP) for the automatic and accurate classification of carotid plaque echogenicity in the longitudinal section. The proposed MSP module can accept arbitrarily sized carotid plaques as input and capture a long-range informative context to improve the accuracy of classification. In our experiments, we implement an MSP-based CNN by using the visual geometry group (VGG) network as the backbone. A total of 1463 carotid plaques (335 echo-rich plaques, 405 intermediate plaques, and 723 echolucent plaques) were collected from Zhongnan Hospital of Wuhan University. The 5-fold cross-validation results show that the proposed MSP-based VGGNet achieves a sensitivity of 92.1%, specificity of 95.6%, accuracy of 92.1%, and F1-score of 92.1%. These results demonstrate that our approach provides a way to enhance the applicability of CNN by enabling the acceptance of arbitrary input sizes and improving the classification accuracy of carotid plaque echogenicity, which has a great potential for an efficient and objective risk assessment of carotid plaques in the clinic.

Patients with Unstable Atherosclerosis Have More Echolucent Carotid Plaques Compared with Stable Atherosclerotic Patients: A 3-D Ultrasound Study

Using a novel 3-D ultrasound system, we aimed to determine differences in carotid plaque size and echogenicity in two atherosclerotic groups. Seventy patients admitted with acute myocardial infarction (aMI) and 69 patients known with chronic peripheral arterial disease (cPAD) were included. The cPAD group had larger plaque volumes (median: 70.24 mm3, interquartile range [40.12–135.61] vs. 55.41 mm3 [4.24–84.31], p = 0.004), thicker plaques (2.45 mm [1.85–3.25] vs. 1.99 mm [1.55 – 2.64], p = 0.005) and higher gray-scale medians (GSMs) (mean: 71.75, standard deviation: 21.55 vs. 60.99 [24.09], p = 0.006) than the aMI group. After adjustment for traditional risk factors, the difference persisted for thickness and volume. The difference in GSM persisted after adjustment for volume only. Patients with stable atherosclerotic disease had larger and brighter carotid plaques compared with unstable atherosclerotic patients. 3-D ultrasound may prove useful in identifying thromboembolic risk.

436 Prognostic value of calcium scoring in changes of echogenicity in carotid plaques

Abstract Background Atherosclerosis is a dynamic process, in which the characteristics of the plaques evaluated by imaging methods could represent the degree of inflamatory activity of the disease. Purpose Assess the value of the coronary calcium score in the changes of echogenicity of carotid plaques in a population with low-intermediate cardiovascular risk. Methods Patients with no cardiovascular history and low and intermediate Framingham risk score were evaluated. Patients attended at our institute for a preventive cardiovascular control between January 2012 and April 2013, and then a subsequent follow-up was made until January 2019. They were screened for coronary calcium scoring (CCS) and carotid plaque by ultrasound at first visit. Then the changes of carotid atherosclerotic disease were evaluated through new carotid ultrasound exam at follow up. A carotid artery plaque was defined as a localized protrusion of the vessel wall, which 1) extended into the lumen ≥ 1.5 mm, or 2) had a thickness exceeding the intima-media thickness (IMT) of the adjacent portion of the vessel wall by &amp;gt;50%. Plaque morphology was defined in terms of its echogenicity. Results 121 patients that have carotid atherosclerotic disease at first carotid ultrasound exam were included. The mean age was 61 ± 9 years, 72 (59%) male patients. Cardiovascular risk factors: hypertension: 68 (56%), dyslipidemia: 46 (38%), sedentary lifestyle: 24 (20%), overweight: 17 (14%), smoking: 29 (24%) and diabetes: 15 (12%). Median distribution of CCS was 192 (percentile distribution 25-75%: 8 – 224) Agatston units. Medium follow-up: 5 ± 1 year. At first ultrasonography study, 47 patients (39%) presented hypoechoic plaques, 61 patients (50%) isoechoic plaques and hyperechoic plaques in 13 patients (11%). After the follow-up, the distribution of the plates according to their sonographic characteristics was: hypoechoic plaques in 23 patients (19%), isoechoic plaques in 55 patients (45%) and hyperechoic plaques in 42 patients (36%). The incidence of the progression of sonographic changes of the carotid plaques varies according to CCS: 0-100:29%, 101-400: 54%, &amp;gt;401:53% (p &amp;lt; 0,001) Figure 1. The value of CCS was associated with the progression of carotid atherosclerotic plaque regardless of the use of statins and angiotensin-converting enzyme inhibitors or angiotensin 2 receptor blockers (Cox model p &amp;lt;0.001). Conclusions This study shows that there is an association between coronary calcium score and progression of carotid disease. Even in populations with low and intermediate cardiovascular risk, the higher the severity of the calcium score, the greater changes in the structure of the carotid plaque manifested in our work as changes in the echogenicity; regardless of the use of statins. These findings could be useful to assess the progression of atherosclerotic disease at a median follow up. Abstract 436 Figure. folow up

P121 Background of the Development of Carotid and Femoral Atherosclerotic Plaques in Twins

IntroductionDevelopment of carotid and femoral atherosclerotic plaques proved to be heritable in previous studies. However, no comprehensive ultrasonographic evaluation of the volume and types of plaque has been performed.MethodsComprehensive carotid and femoral arterial ultrasound examination (Samsung RS85, arterial analysis, 15 MHz probe) was performed in 92 Hungarian twins (54 monozygotic, MZ and 38 dizygotic, DZ twin pairs, mean age 54 ± 13 years). The volume of plaques was automatically measured, and the plaque type was grouped according to echogenicity. Raw heritability was evaluated using the Falconer formula.ResultsNo heritability of the total number of carotid and femoral plaques and total plaque volume was detected. Although the number of carotid plaques themselves has been found to be hereditary (h2 = 0.492), the volume of carotid and femoral plaques as well as the number of femoral plaques were not heritable. More MZ twin pairs were discordant in the presence of soft plaques in the carotid artery as DZ twin pairs, but greater similarity in femoral plaques was not detected between MZ twins, which does not indicate a genetic background. The presence of calcified and mixed echogenic carotid plaques in the MZ twins was more concordant as in DZ twins, indicating inheritance.ConclusionThe total number and volume of carotid and femoral plaques are influenced by the environment. Different plaque types have different backgrounds: while calcified and mixed echogenic carotid plaques are more affected by genetics, soft carotid and femoral plaques are more affected by the environment.

Statin Naïve Patients with Myocardial Infarction have more Echolucent Plaques Compared to Long-term Statin Treated Chronic Atherosclerotic Patients – A 3D Ultrasound Study

Introduction: Size and morphology of carotid atherosclerotic plaques can be quantified by ultrasound (US) imaging. Carotid artery plaque size and gray-scale median (GSM) have been identified as risk markers for both cardiovascular events and stroke ADDIN EN.CITE ADDIN EN.CITE.DATA (1, 2). Unstable plaques have a thin fibrotic cap and a lipid or hemorrhagic core ADDIN EN.CITE ADDIN EN.CITE.DATA (3-6). A higher amount of lipid and hemorrhage have been observed in echolucent carotid plaques presenting as lower GSM compared to echogenic carotid plaques containing fibrotic tissue and calcification ADDIN EN.CITE ADDIN EN.CITE.DATA (7-10). Classic cardiovascular risk scores such as Framingham score lack precision ADDIN EN.CITE ADDIN EN.CITE.DATA (11, 12). Information about atherosclerotic plaque characteristics and development can potentially improve risk stratification. Methods: : Two patient populations were included prospectively; a group admitted with first-time myocardial infraction and naive to statin treatment and a group followed for peripheral arterial disease on stable statin treatment for more than six months, all being ≤65 years old. Both carotid arteries were scanned with 3D ultrasound by the same sonographer. All plaques were analyzed using a semiautomated software. Gray-scale readings were normalized with adventitia as reference and GSM recorded. In patients with bilateral carotid artery plaques the thickest plaque was used for data analyses. Results: In the statin treated patients (n=70 , 64% male, mean age 60 (range 40-65)) compared to the statin naive patients (n= 70, 79% male, mean age 57 (range 38-65)) we found an increased plaque thickness (difference 0.65 mm, P=0.001), a larger plaque volume (difference 31.98 mm3, P=0.001) as well as a higher GSM (difference 9.46, 95% confidence interval: 1.59 - 17.33, P=0.019) (figure 1). The differences in thickness and volume disappeared after adjustment for age, gender, smoking, hypertension and diabetes mellitus (P= 0.066 and 0.050, respectively). The differences in GSM persisted after adjusting for volume (difference of 9.05, CI95%: 0.90 - 17.21, P=0.030). There was no correlation between volume and GSM (P=0.16). Conclusion: .By 3D US we detected differences in carotid plaque thickness, volume and morphology between two different atherosclerotic populations. The statin treated group with known clinical atherosclerotic disease, had larger plaques indicating a more advanced stage of disease as the difference diminished when adjusting for atherosclerotic risk factors. Also, this group had more echogenic plaques (higher GSM) which indicate less vulnerability, or a more stable stage of disease as compared to the statin naive group. Carotid 3D US imaging may prove clinically useful for identification and assessment of treatment response in high-risk patients with vulnerable plaques Disclosure: Co-author H. Sillesen has received research grants from Philips Ultrasound.

Decreased bone mineral density and osteoporotic fractures are associated with the development of echogenic plaques in the carotid arteries over a 10-year follow-up period: The Japanese Population-based Osteoporosis (JPOS) Cohort Study

ObjectivesTo investigate whether low bone mineral density (BMD) and history of fracture at baseline are associated with the development of echogenic carotid plaques over a 10-year follow-up period. Study designA prospective cohort study. Main outcome measuresDevelopment of echogenic plaques identified by ultrasonography of the carotid arteries. MethodsAmong 1048 women aged 40 or more who completed the baseline survey of the Japanese Population-based Osteoporosis (JPOS) cohort study, 500 women who completed the first decade of follow-up and 267 women who completed the second decade of follow-up were included. We identified history and incidence of clinical osteoporotic fracture during the follow-up through medical interviews, and determined vertebral fractures by morphometry of absorptiometric images. ResultsWe identified 67 (13.4%) and 31 (11.6%) women with echogenic plaques at the end of first and second decade of follow-up, respectively. Participants with echogenic plaques were significantly older, exhibited lower spine BMD, and had a higher prevalence of osteoporotic fracture, diabetes, and hypertension. A generalized estimating equation analysis was used to combine the participants from the two follow-up periods into a single cohort, and showed that osteoporotic BMD and osteoporotic fractures were significantly associated with the development of echogenic plaques, after adjusting for atherosclerosis risk factors (odds ratio (OR): 2.15, 95% confidence interval (95% CI): 1.04, 4.44; OR: 1.84, 95% CI: 1.03, 3.28, respectively). ConclusionOsteoporotic BMD and osteoporotic fracture history were significantly, and independently, associated with an increased occurrence of echogenic plaques. Ultrasonographic screening of the carotid artery may benefit patients with osteoporosis.

Intra-Plaque Vessels on Contrast-Enhanced Ultrasound Sonography Predict Carotid Plaque Histology

Background and Purpose: Although the echogenicity of carotid plaques on carotid enhanced ultrasound (CEUS) was reported to correlate with the historological density of intra-plaque neovessels, it is unclear whether the intra-plaque vessel size is associated with carotid plaque vulnerability. We evaluated the relationship of size of intra-plaque vessels on CEUS with carotid plaque histology. Methods: We prospectively registered patients with carotid stenosis who were hospitalized to receive carotid endarterectomy between 2012 and 2016. CEUS was performed by ultrasound specialists using a 7-MHz linear transducer (GE LOGIQ7; GE Healthcare, Milwaukee, WN, USA). Sonazoid® was used for conducting CEUS. The sizes of microbubbles inside the plaques were scored at 0, 1, 3, and 5 min after the injection of contrast agent, and were categorized according to our defined vascular score (Vas-S; 0: the effect of contrast was not recognized; 1: the microbubbles were visible, but so blurred and vague that their shape could not be recognized; 2: dot or string-like microbubbles with movement, localized in part or the whole site of the plaque). At histological examination, we simplified the modified American Heart Association classification and defined as an atherosclerotic category (Ath-cat; 1: unruptured plaque; 2: ruptured plaque; 3: healed plaque). We then assessed the correlation of Vas-S with Ath-cat, which describes the process of rupture and restoration of carotid plaques. Results: A total of 97 patients were included in this study. A higher Ath-cat was significantly associated with higher Vas-S at any time. Spearman signed-rank test indicated that Vas-S at 1 min was most strongly correlated with Ath-cat (ρ = 0.43, p = 0.001). Receiver operating curve analysis indicated that a Vas-S of 0 at 1 min was significantly associated with an unruptured plaque (area under curve [AUC] 0.72, p = 0.006), while a Vas-S of 2 at 1 min was significantly associated with a healed plaque (AUC 0.72, p = 0.001). Conclusion: Vas-S values of 0 and 2 at 1 min indicated unruptured and healed plaques respectively. Thus, a Vas-S of 1 at 1 min is an indicator of a ruptured plaque. The intra-plaque vessel size on CEUS was significantly associated with carotid plaque histology, and may predict the process of plaque rupture and restoration.

Abstract 627: Combined Plaque Evaluation by Ultrasound and Microarrays Reveals Bclaf1 as a Novel Regulator of Smooth Muscle Cell Transdifferentiation in Atherosclerosis

Objective: Understanding molecular processes behind carotid plaque instability is necessary to develop methods that can identify patients and lesions at risk of stroke. Here, we investigated molecular signatures in human plaques stratified by echogenicity as assessed by duplex ultrasound (US). Results: Plaque echogenicity measured by US was correlated to microarray profiles from lesions retrieved at surgery (n=96). Pathway analyses highlighted enrichment of cell apoptosis and proliferation, and BCLAF1 (BCL2 associated factor 1) as the most significantly dysregulated gene (adjusted p&lt;0.0001). BCLAF1 was strongly downregulated in plaques vs. control tissues, positively correlated to markers of cell proliferation and negatively to apoptosis, at both transcriptomic and proteomic level. Immunohistochemistry showed that BCLAF1 was localized in smooth muscle cells (SMCs) nuclei and repressed early during atherogenesis, but reappeared in CD68+ cells in advanced plaques. Proximity ligation assay demonstrated interaction of BCLAF1 with previously reported interaction partners THRAP3 and BCL2, in normal arteries and plaques. In vitro , stimulation of SMCs with pro-survival factors EGF, bFGF, PDGFB resulted in induction of BCLAF1, while it was suppressed by macrophage-conditioned medium. Moreover, BCLAF1 silencing in SMCs led to downregulation of BCL2 and SMC markers, and a decrease in proliferation and adhesion (p&lt;0.0001). Transdifferentiation of SMCs using oxLDL, confirmed by CD68 upregulation and MYH11 repression, was accompanied by upregulation of BCLAF1. However, a combination of oxLDL exposure and BCLAF1 silencing, resulted in preserved expression of MYH11 and prevented transdifferentiation. Finally, BCLAF1 expression in CD68+/BCL2+ cells of SMC origin, was verified in plaques from MYH11-lineage tracing atherosclerotic mice. Conclusions: Carotid plaque echogenicity correlated with enrichment of molecular pathways associated with cell survival and apoptosis and identified BCLAF1, previously not described in atherosclerosis, as the most dysregulated gene. Functionally, BCLAF1 appeared to promote SMC survival by transdifferentiation into macrophage-like phenotype, by interacting with BCL2 and THRAP3.

Carotid Plaque Stiffness Measured with Supersonic Shear Imaging and Its Correlation with Serum Homocysteine Level in Ischemic Stroke Patients.

ObjectiveTo ascertain the feasibility of using shear wave velocity (SWV) in assessing the stiffness of carotid plaque by supersonic shear imaging (SSI) and explore preliminary clinical value for such evaluation.Materials and MethodsSupersonic shear imaging was performed in 142 patients with ischemic stroke, including 76 males and 66 females with mean age of 66 years (range, 45–80 years). The maximum, minimum, and mean values of SWV were measured for 129 carotid plaques. SWVs were compared between echolucent and echogenic plaques. Correlations between SWVs and serum homocysteine levels were investigated. Based on neurological symptom, the surrogate marker of vulnerable plaque (VP), binary logistic regression was performed and area under curve (AUC) of homocysteine only and homocysteine combing SWVmean was calculated respectively.ResultsEchogenic plaques (n = 51) had higher SWVs than echolucent ones (n = 78) (SWVmin 3.91 [3.24–4.17] m/s vs. 1.51 [1.04–1.94] m/s; SWVmean, 4.29 [3.98–4.57] m/s vs. 2.09 [1.69–2.41] m/s; SWVmax, 4.67 [4.33–4.86] m/s vs. 2.62 [2.32–3.31] m/s all p values < 0.01). Pearson correlation analysis showed that stiffness of plaques was negatively correlated with homocysteine level. R values for SWVmin, SWVmean, and SWVmax were −0.205, −0.213, and −0.199, respectively. Binary logistic regression analysis showed that sex (p = 0.008), low-density lipoprotein (p = 0.015), triglycerides (p = 0.011), SWVmean (p = 0.004), and hyper-homocysteinemia (p = 0.010) were significantly associated with symptomatic ischemic stroke. Receiver operating characteristic curves revealed that SWVmean combing serum homocysteine level (AUC = 0.67) presented better diagnostic value than serum homocysteine only (AUC = 0.60) for symptomatic ischemic stroke.ConclusionSupersonic shear imaging could be used to quantitatively evaluate stiffness of both echolucent and echogenic carotid plaques. More importantly, SWVs of plaques were not only correlated to serum homocysteine level, but also associated with symptomatic ischemic stroke, suggesting that SSI might be useful for understanding more about VP.

Evaluation of carotid plaque echogenicity based on the integral of the cumulative probability distribution using gray-scale ultrasound images.

ObjectiveCarotid plaque echogenicity is associated with the risk of cardiovascular events. Gray-scale median (GSM) of the ultrasound image of carotid plaques has been widely used as an objective method for evaluation of plaque echogenicity in patients with atherosclerosis. We proposed a computer-aided method to evaluate plaque echogenicity and compared its efficiency with GSM.MethodsOne hundred and twenty-five carotid plaques (43 echo-rich, 35 intermediate, 47 echolucent) were collected from 72 patients in this study. The cumulative probability distribution curves were obtained based on statistics of the pixels in the gray-level images of plaques. The area under the cumulative probability distribution curve (AUCPDC) was calculated as its integral value to evaluate plaque echogenicity.ResultsThe classification accuracy for three types of plaques is 78.4% (kappa value, κ = 0.673), when the AUCPDC is used for classifier training, whereas GSM is 64.8% (κ = 0.460). The receiver operating characteristic curves were produced to test the effectiveness of AUCPDC and GSM for the identification of echolucent plaques. The area under the curve (AUC) was 0.817 when AUCPDC was used for training the classifier, which is higher than that achieved using GSM (AUC = 0.746). Compared with GSM, the AUCPDC showed a borderline association with coronary heart disease (Spearman r = 0.234, p = 0.050).ConclusionsOur experimental results suggest that AUCPDC analysis is a promising method for evaluation of plaque echogenicity and predicting cardiovascular events in patients with plaques.

Echogenic carotid plaques are associated with asymptomatic intracranial atherosclerotic disease in an employee health screening database

Background: Intracranial atherosclerotic disease (ICAD) is highly prevalent in Asians than Westerners. Although the association between metabolic syndrome (MetS) and ICAD has been implicated, the reason for this ethnic difference remains unclear.

Differential associations of systolic and diastolic time rate of blood pressure variation with carotid atherosclerosis and plaque echogenicity.

In the current study, the authors sought to assess whether the time rate of systolic and diastolic blood pressure variation is associated with advanced subclinical stages of carotid atherosclerosis and plaque echogenicity assessed by gray scale median. The authors recruited 237 consecutive patients with normotension and hypertension who underwent 24-hour ambulatory blood pressure monitoring and carotid artery ultrasonography. There was an independent association between low 24-hour systolic time rate and increased echogenicity of carotid plaques (adjusted odds ratio for highest vs lower tertiles of gray scale median, 0.470; 95% confidence interval, 0.245-0.902 [P = .023]). Moreover, increased nighttime diastolic time rate independently correlated with the presence (adjusted odds ratio, 1.328; P = .015) and number of carotid plaques (adjusted odds ratio, 1.410; P = .003). These results indicate differential associations of the systolic and diastolic components of time rate of blood pressure variation with the presence, extent, and composition of carotid plaques and suggest that when blood pressure variation is assessed, both components should be considered.