Carotid Artery Plaque Calcifications: Lessons From Histopathology to Diagnostic Imaging

Stroke ◽  
2021 ◽  
Author(s):  
Luca Saba ◽  
Valentina Nardi ◽  
Riccardo Cau ◽  
Ajay Gupta ◽  
Hooman Kamel ◽  
...  
Keyword(s):  
Carotid Artery ◽  
Carotid Plaque ◽  
Intraplaque Hemorrhage ◽  
Calcium Deposition ◽  
Carotid Artery Plaque ◽  
Carotid Plaques ◽  
Novel Technologies ◽  
Carotid Artery Calcification ◽  
Wide Range

The role of calcium in atherosclerosis is controversial and the relationship between vascular calcification and plaque vulnerability is not fully understood. Although calcifications are present in ≈50% to 60% of carotid plaques, their association with cerebrovascular ischemic events remains unclear. In this review, we summarize current understanding of carotid plaque calcification. We outline the role of calcium in atherosclerotic carotid disease by analyzing laboratory studies and histopathologic studies, as well as imaging findings to understand clinical implications of carotid artery calcifications. Differences in mechanism of calcium deposition express themselves into a wide range of calcification phenotypes in carotid plaques. Some patterns, such as rim calcification, are suggestive of plaques with inflammatory activity with leakage of the vasa vasourm and intraplaque hemorrhage. Other patterns such as dense, nodular calcifications may confer greater mechanical stability to the plaque and reduce the risk of embolization for a given degree of plaque size and luminal stenosis. Various distributions and patterns of carotid plaque calcification, often influenced by the underlying systemic pathological condition, have a different role in affecting plaque stability. Modern imaging techniques afford multiple approaches to assess geometry, pattern of distribution, size, and composition of carotid artery calcifications. Future investigations with these novel technologies will further improve our understanding of carotid artery calcification and will play an important role in understanding and minimizing stroke risk in patients with carotid plaques.

Abstract 3482: Increased Matrix Metalloproteinase-9 Expression is Correlated with Carotid Intraplaque hemorrhage in a Swine Model

Stroke ◽  
2012 ◽  
Vol 43 (suppl_1) ◽  
Author(s):  
Zhong-Song Shi ◽  
Xiao-Bing Jiang ◽  
Jin-Shan Wang ◽  
Wei-Si Yuan ◽  
Dong-Hong Liu
Keyword(s):  
Carotid Artery ◽  
Matrix Metalloproteinase ◽  
Vulnerable Plaque ◽  
Carotid Plaque ◽  
Carotid Atherosclerosis ◽  
Intraplaque Hemorrhage ◽  
Swine Model ◽  
Carotid Plaques ◽  
Rete Mirabile ◽  
Atherosclerotic Changes

Purpose: The limited number of large animal carotid atherosclerotic models restricts the preclinical evaluation of endovascular therapies. Carotid intraplaque hemorrhage may be associated with a higher risk of ischemic stroke in patients with carotid disease. In this study, we assess the association of the lesional expression of matrix metalloproteinase (MMP)-9 with vulnerable atherosclerotic carotid plaque and intraplaque hemorrhage in a Swine model. Materials and Methods: Carotid atherosclerosis was induced in miniswines using the combination of partial ligation and high cholesterol diet, and a minimum 70% stenosis was confirmed by Doppler ultrasonography immediately post-ligation. Carotid artery sections were obtained for histopathological examination and immunohistochemical study for MMP-9 at three months. Distal embolism was determined by the presence of atheroemboli in the ipsilateral rete mirabile. Atherosclerotic changes were classified by AHA/Stary stage (type I to VI). The association of distal embolism in the rete mirabile with vulnerable carotid plaque was analyzed. The association of MMP-9 expression in the plaque with the vulnerable plaque and intraplaque hemorrhage was further analyzed. Results: One hundred ninety-one carotid segments from ten carotid artery models were assessed. Among 139 segments with atherosclerotic changes, 102 segments had vulnerable plaque (Stary IV to VI). Vulnerable atherosclerotic plaques were found more frequently in the vessel wall proximal to the partial ligation than distal ( P <0.0001). Distal embolism was found in all 10 rete mirabilis, and deemed to be from the ipsilateral vulnerable carotid plaques. Areas positive for MMP-9 tended to be greater in the vulnerable plaque than in the stable plaque (8.69 ± 0.73% vs. 7.04 ± 0.94%, p=0.35). Areas positive for MMP-9 were significantly greater in the plaque with intraplaque hemorrhage than in the plaque without intraplaque hemorrhage (11.84 ± 1.22% vs. 6.63 ± 0.59%, p<0.001). On multivariate analysis, positive expression of MMP-9 was an independent predictor of intraplaque hemorrhage (p=0.007). Conclusion: Vulnerable carotid plaques with distal embolism were created in a Swine model of carotid atherosclerosis. Increased expression of MMP-9 may be associated with vulnerable carotid plaques, especially having the feature of intraplaque hemorrhage.

Abstract 957: Elevated Levels of Neopterin are Associated with Carotid Complex Plaques in Patients with Stable Angina Pectoris

Circulation ◽  
2008 ◽  
Vol 118 (suppl_18) ◽  
Author(s):  
Kenichi Sugioka ◽  
Takahiko Naruko ◽  
Takeshi Hozumi ◽  
Shoichi Ehara ◽  
Takuhiro Okuyama ◽  
...  
Keyword(s):  
Angina Pectoris ◽  
Carotid Artery ◽  
Stable Angina ◽  
Carotid Plaque ◽  
Coronary Vessels ◽  
Surface Irregularity ◽  
Stable Angina Pectoris ◽  
Carotid Artery Plaque ◽  
Plaque Score ◽  
Carotid Plaques

Background: Neopterin is produced by activated macrophages and serves as an activation marker for monocytes/macrophages. Serum levels of neopterin have been shown to be associated with the presence of complex coronary lesions in unstable angina pectoris. However, the relationship between neopterin levels and complex carotid lesions is still unknown. We investigated the association between plasma neopterin levels and the characteristics of carotid plaques in patients with stable angina pectoris (SAP). Moreover, we immunohistochemically studied the presence of neopterin in carotid endarterectomy specimens. Methods: We studied 65 SAP patients who were scheduled coronary angiography. In all patients, plasma neopterin levels were measured and carotid ultrasound was performed for evaluation of carotid artery plaque score (PS) defined by the sum of plaque thickness, plaque number (PN) and plaque surface irregularity. Frozen tissue of 40 endarterectomy specimens for extracranial high-grade carotid stenosis were immunohistochemically examed with antibodies against macrophages and neopterin. Results: There was no significant correlation between plasma neopterin levels and PS (P=0.38) or PN (P=0.49). On the other hand, plasma neopterin levels were significantly higher in patients with carotid plaque surface irregularity compared with patients without it (25.4 ± 13.5 nmol/L vs.16.9 ± 6.5 nmol/L, P=0.0015). Carotid plaque irregularity was detected more frequently in patients with higher neopterin levels (>=18.5 nmol/L median) compared with those with lower neopterin levels (41.9% vs. 16.1%, P=0.025). Using multivariate analyses, nepopterin levels (OR, 1.11; 95%CI, 1.01 to 1.21; P=0.023) and the number of diseased coronary vessels (OR, 2.51; 95%CI, 1.01 to 6.22; P=0.047) are independently associated with carotid plaque irregularity. Immunohistochemical staining showed abundant neopterin-positive macrophages in the unstable carotid plaques. Conclusions: Neopterin levels are associated with carotid complex plaques rather than the severity of carotid atherosclerotic change. Neopterin can be considered as one of the significant markers of plaque destabilization in not only coronary artery but carotid artery atherosclerotic lesions.

Abstract WP122: Asymptomatic Moderate Carotid Artery Stenosis With Intraplaque Hemorrhage ∼ Progression of Degree of Stenosis and New Ischemic Stroke

Stroke ◽  
2016 ◽  
Vol 47 (suppl_1) ◽  
Author(s):  
Kiyofumi Yamada ◽  
Masanori Kawasaki ◽  
Shinichi Yoshimura ◽  
Shigehiro Nakahara ◽  
Yoshikazu Sato
Keyword(s):  
Ischemic Stroke ◽  
Carotid Artery ◽  
Carotid Stenosis ◽  
Carotid Artery Stenosis ◽  
Carotid Plaque ◽  
Intraplaque Hemorrhage ◽  
Progression Rate ◽  
Negative Group ◽  
Positive Group ◽  
Carotid Plaques

Background: Carotid artery stenosis is one of the major causes of ischemic stroke. Carotid intraplaque hemorrhage (IPH) plays a critical role in the progression of carotid atherosclerotic disease. Previous studies showed that IPH was associated with high intensity signal (HIS) on maximum intensity projection (MIP) images from routine three dimensional magnetic resonance imaging (3D-TOF MRA). The aim of this study was to evaluate the relationships among HIS, new ipsilateral ischemic stroke and a progression rate in carotid plaques with moderate stenosis. Materials and Methods: We included 45 carotid plaques with moderate stenosis (50% to 69%) in 45 patients who could be followed more than 12 months. Carotid IPH was defined as the presence of HIS in carotid plaque on MIP image from routine 3DTOF MRA using the criteria previously we published. We analyzed the relation between the presence of HIS in the plaques and new ischemic strokes and annual progression rate of carotid stenosis. Results: HIS in carotid plaque was present in 21 (47%) carotid arteries. Over a follow-up period of 24 ± 9 months, six ischemic strokes occurred ipsilateral to the index carotid artery. New ipsilateral ischemic stroke occurred more frequently in HIS positive group (6 of 21, 29%) than HIS negative group (0 of 24, 0%) (p=0.017). Annual progression rate of carotid stenosis is significantly higher in HIS positive group (+3.35%/year) than HIS negative group (-0.02%/year) (p= 0.0026). In multivariate regression analysis, HIS positive was an independent predictor for annual progression rate of carotid stenosis (p=0.003). Conclusions: HIS in carotid plaques on 3DTOF-MRA MIP images are associated with new ischemic stroke and higher annual progression rate of stenosis. Evaluation of HIS in asymptomatic moderate carotid stenosis can potentially provide risk stratification of new ipsilateral ischemic strokes.

Imaging of high-risk carotid artery plaques: current status and future directions

2014 ◽  
Vol 36 (1) ◽  
pp. E1 ◽  
Author(s):  
J. Kevin DeMarco ◽  
John Huston
Keyword(s):  
High Risk ◽  
Carotid Artery ◽  
Carotid Plaque ◽  
Treatment Strategies ◽  
Automated Analysis ◽  
Current Status ◽  
Intraplaque Hemorrhage ◽  
Carotid Artery Plaque ◽  
Future Directions

In this paper, the authors review the definition of high-risk plaque as developed by experienced researchers in atherosclerosis, including pathologists, clinicians, molecular biologists, and imaging scientists. Current concepts of vulnerable plaque are based on histological studies of coronary and carotid artery plaque as well as natural history studies and include the presence of a lipid-rich necrotic core with an overlying thin fibrous cap, plaque inflammation, fissured plaque, and intraplaque hemorrhage. The extension of these histologically identified high-risk carotid plaque features to human in vivo MRI is reviewed as well. The authors also assess the ability of in vivo MRI to depict these vulnerable carotid plaque features. Next, the ability of these MRI-demonstrated high-risk carotid plaque features to predict the risk of ipsilateral carotid thromboembolic events is reviewed and compared with the risk assessment provided by simple carotid artery stenosis measurements. Lastly, future directions of high-risk carotid plaque MRI are discussed, including the potential for increased clinical availability and more automated analysis of carotid plaque MRI. The ultimate goal of high-risk plaque imaging is to design and run future multicenter trials using carotid plaque MRI to guide individual patient selection and decisions about optimal atherosclerotic treatment strategies.

scholarly journals Ultrasound Elastography: another piece in the puzzle of carotid plaque vulnerability?

2021 ◽  
Author(s):  
Andjoli Davidhi ◽  
Vasileios Rafailidis ◽  
Evangelos Destanis ◽  
Panos Prassopoulos ◽  
Stefanos Foinitsis
Keyword(s):  
Shear Wave ◽  
Carotid Plaque ◽  
Diagnostic Yield ◽  
Imaging Modality ◽  
Shear Wave Elastography ◽  
Ultrasound Elastography ◽  
Intraplaque Hemorrhage ◽  
Plaque Vulnerability ◽  
Carotid Plaques ◽  
Increased Risk

Recent literature has shown that various carotid plaque features, other than stenosis, contribute to plaque vulnerability. Features such as surface morphology and plaque composition with distinct components (e.g. intraplaque hemorrhage, lipid core) have been associated with the increased risk of future cerebrovascular events. Ultrasonography constitutes the first line modality for the assessment of carotid disease and has traditionally been used to grade stenosis with high accuracy. Recenttechnological advances such as contrast-enhanced ultrasound and elastography increased the diagnostic yield of ultrasound in assessing the morphology of carotid plaques. The purpose of this review is to present the available literature on ultrasound elastography of the atherosclerotic carotid. Strain and shear wave elastography allow for the characterization of plaque components, thus indicating its nature and importantly, the plaque’s vulnerability. Shear wave elastography indices appear morerobust than Strain indices. Overall, elastography is a feasible method to distinguish vulnerable carotid plaques. There is, however, a need for larger and longer prospective controlled clinical studies in order to validate elastography as an imaging modality used for the detection of unstable carotid plaques.

scholarly journals The Role of the Carotid Artery Plaque: Pathogenesis of Cerebral Ischemia

1994 ◽  
Vol 22 (3) ◽  
pp. 235-240 ◽  
Author(s):  
Shigeharu FUKAO ◽  
Nobuo HASHIMOTO ◽  
Tetsuya TSUKAHARA ◽  
Jun OGATA ◽  
Chikao YUTANI ◽  
...  
Keyword(s):  
Cerebral Ischemia ◽  
Carotid Artery ◽  
Carotid Artery Plaque

Abstract P322: Association of Hiv Infection With Carotid Artery Plaque Echomorphology in the Women’s Interagency HIV Study (wihs)

Circulation ◽  
2020 ◽  
Vol 141 (Suppl_1) ◽  
Author(s):  
Claudio A Bravo ◽  
Jee-Young Moon ◽  
Jean Claude Uwamungu ◽  
Robert Kaplan ◽  
Kathryn Anastos ◽  
...  
Keyword(s):  
Cardiovascular Disease ◽  
Carotid Artery ◽  
Hiv Infection ◽  
Carotid Plaque ◽  
Cd4 Count ◽  
Morbidity And Mortality ◽  
Hiv Care ◽  
Carotid Artery Plaque ◽  
Hiv Women ◽  
Hiv Negative

Introduction: Cardiovascular disease is a major contributor to morbidity and mortality among women living with HIV (WLWH). We previously found HIV infection to be associated with carotid artery plaque, a marker of subclinical atherosclerosis. Plaque morphology and composition may predict plaque rupture and cardiovascular disease events. We characterized the association of HIV-related factors with carotid plaque echomorphology in the WIHS. Methods: Using B-mode ultrasound, we characterized plaque (focal intima-media thickness >1.5 mm) at 6 locations in the right carotid artery in 1,722 participants (1,230 HIV+, 492 HIV-) of the WIHS, a cohort study of women with or at risk for HIV at 6 US sites. Plaque echomorphologic features included relative echogenicity (>50% of plaque is echolucent vs >50% of plaque is echogenic) and surface morphology (smooth vs irregular, i.e., height variations along contour of plaque). We used multinomial logistic regression to assess the odds of each feature vs no plaque comparing HIV+ and HIV- women, adjusting for demographic (e.g., age, race/ethnicity, socioeconomic status), behavioral (e.g., drug/alcohol use, smoking, HCV infection, smoking), cardiometabolic (e.g., systolic blood pressure, BMI, lipids, diabetes) and HIV-related risk factors (e.g., antiretroviral therapy use, current CD4+ T-cell count, AIDS). We further stratified WLWH by CD4+ count (<200, 200-499, 500+ cells/uL) and HIV-1 RNA suppression. Results: Among 1,722 women (median age 40, IQR 33-46, 59% black, 29% Hispanic, 71% HIV+), 160 (9%) had at least one carotid plaque (128 HIV+, 32 HIV-). In unadjusted analyses, WLWH had more echolucent plaque (5.3% vs 2.6%, p=0.02) and plaques with smooth surface (2.7% vs 0.6%, p=0.005) than HIV-negative women. After covariate adjustment, HIV serostatus remained significantly associated with smooth plaque (odds ratio [OR] 3.45, 95% CI 1.12-10.62) but not with echolucent plaque (OR 1.60, 95% CI 0.84-3.05). Stratified by HIV viremia, WLWH with unsuppressed HIV viremia had significantly more smooth plaque (OR 3.34, 95% CI 1.26-8.87) than HIV- women, whereas suppressed WLWH did not (OR 1.79, 95% CI 0.55-5.83). In a dose-response manner, lower CD4+ count among WLWH was associated with smooth plaque (e.g., OR for <200 cells/uL compared with HIV-negative women 7.43, 95% CI 1.46-37.87), and this association was of greater magnitude than that with irregular plaque (OR 2.46, 95% CI 1.14-5.32). Low CD4+ count was also associated with both echolucent (OR 3.36 for <200 cells/uL vs HIV-negative, 95% CI 1.29-8.77) and echogenic plaque (OR 2.65, 95% CI 1.18-5.96). Conclusions: Unsuppressed viremia and low CD4+ count, which are markers of suboptimal HIV care, were associated with certain echomorphologic features of carotid plaque. Further work should assess whether these features differentially lead to cardiovascular morbidity and mortality in WLWH.

Do Carotid Plaque Ulcers Heal? Potential Detection of Carotid Artery Plaque Healing by Carotid Ultrasound Imaging

2020 ◽  
Author(s):  
Marialaura Simonetto ◽  
Sushrut Dharmadhikari ◽  
Ari Bennett ◽  
Nelly Campo ◽  
Negar Asdaghi ◽  
...  
Keyword(s):  
Carotid Artery ◽  
Ultrasound Imaging ◽  
Carotid Plaque ◽  
Carotid Ultrasound ◽  
Carotid Artery Plaque

scholarly journals Hemoglobin A1c as A Potential Indicator for Intraplaque Hemorrhage of Carotid Artery Atherosclerosis in Asymptomatic Adults

2021 ◽  
Author(s):  
Yu Wang ◽  
Runhua Zhang ◽  
Yong Jiang ◽  
Miaoxin Yu ◽  
Huiyu Qiao ◽  
...  
Keyword(s):  
Carotid Artery ◽  
Carotid Plaque ◽  
Hemoglobin A1c ◽  
Univariate Analysis ◽  
Intraplaque Hemorrhage ◽  
Stepwise Logistic Regression ◽  
Community Based ◽  
Stepwise Logistic Regression Analysis ◽  
Cross Sectional ◽  
High Hba1c

Abstract BackgroundTo investigate the association between hemoglobin A1c (HbA1c) and intraplaque hemorrhage (IPH) in carotid atherosclerotic plaque detected by high-resolution magnetic resonance imaging (HR-MRI) in a community-based population. MethodsIn this cross-sectional, community-based study, a total of 598 participants were recruited from May 2015 to September 2019. All participants underwent carotid artery HR-MRI. Data on demographics, medical history, and physical examinations were obtained through face-to-face interview, and fasting blood sample were collected. HbA1c was determined using high-performance liquid chromatographic analysis. Presence or absence of carotid plaque IPH was determined by HR-MRI. Multiple stepwise logistic regression analysis was performed to investigate the association between HbA1c levels and carotid plaque IPH. ResultsOf the 598 participants, 317 (53.0%) had atherosclerotic plaques, and 25 (4.2%) had IPH in carotid arteries. HbA1c was associated with the presence of IPH (OR, 1.94; 95% CI, 1.38-2.73) in the univariate analysis, and the association remained significant after adjustment for age, sex, traditional vascular factors, high-sensitivity C-reactive protein, and other potential confounders (OR, 1.70; 95% CI, 1.14-2.52).ConclusionsThis study showed that high HbA1c was associated with carotid plaque IPH detected by HR-MRI, which suggests that individuals with high HbA1c may have a higher risk of developing vulnerable carotid plaques.

scholarly journals Identification of Symptomatic Carotid Artery Plaque: A Three-Item Scale Combined Angiography With Optical Coherence Tomography

2021 ◽  
Vol 15 ◽  
Author(s):  
Qingwen Yang ◽  
Hongquan Guo ◽  
Xuan Shi ◽  
Xiaohui Xu ◽  
Mingming Zha ◽  
...  
Keyword(s):  
Optical Coherence Tomography ◽  
Carotid Plaque ◽  
Large Scale ◽  
Plaque Morphology ◽  
Optical Coherence ◽  
Carotid Artery Plaque ◽  
Carotid Plaques ◽  
Symptomatic Carotid ◽  
Oct Imaging ◽  
Item Scale

Introduction: Symptomatic carotid disease conveys a high risk of recurrent stroke. Plaque morphology and specific plaque characteristics are associated with the risk of stroke. This study aimed to evaluate the detailed plaque features by optical coherence tomography (OCT) and develop a simple scale combining clinical indicators, digital subtraction angiography (DSA), and OCT imaging markers to identify symptomatic carotid plaque.Methods: Carotid plaques from consecutive patients who underwent carotid OCT imaging between June 2017 and June 2021 were evaluated. Clinical characteristics, DSA, and OCT data were compared between the symptomatic and asymptomatic groups. Logistic regression was performed to identify the factors associated with symptomatic carotid plaque and to develop a scale. The area under the receiver operating characteristic curve (AUC) was used to evaluate the performance of the scale.Results: A total of 90 carotid plaques from 90 patients were included (symptomatic 35.6%, asymptomatic 64.4%). Three main factors were found to be associated with symptomatic carotid plaque: high-density lipoprotein cholesterol (HDL-C) &lt;0.925 mmol/L (OR, 4.708; 95% CI, 1.640 to 13.517; P = 0.004), irregular plaque (OR, 4.017; 95% CI, 1.250 to 12.910; P = 0.020), and white thrombus (OR, 4.594; 95% CI, 1.141 to 18.487; P = 0.032). The corresponding score of three items produced a scale with good discrimination (AUC, 0.768; 95% CI, 0.665 to 0.871). The optimal cutoff value of the scale was 1.5 points with 59.4% sensitivity and 84.5% specificity.Conclusion: The three-item scale comprising HDL-C &lt;0.925 mmol/L, angiographical irregular plaque, and white thrombus detected by OCT may provide information to identify symptomatic carotid plaque. Further large-scale studies are required to validate whether the symptomatic carotid plaque scale is clinically valuable in recognizing carotid atherosclerosis in the early stages.

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