Carotid Plaque Composition Assessed by CT Predicts Subsequent Cardiovascular Events among Subjects with Carotid Stenosis

Abstract Introduction According to the current guidelines the visualization of atherosclerotic plaques in the carotid arteries is the only option that carotid ultrasound provides for the assessment of cardiovascular risk (CVR). The direction devoted to the development and implementation of markers based on the quantification of atheroma, is promising. Purpose The aim of the study was to evaluate the prognostic value of various markers of carotid atherosclerosis (plaque, carotid total plaque area (cTPA) and carotid stenosis) in patients at high and very high CVR. Methods The study included patients aged 40–75 years at high and very high CVR. All patients underwent carotid duplex ultrasound. The presence of carotid plaque was assessed according to Mannheim consensus. The percentage of stenosis was measured planimetrically in the B-mode by the diameter in the cross section of the vessel. cTPA was estimated in the longitudinal position, which allows to achieve the best visualization of plaque, the area of plaque was measured in the manual trace mode. These measurements were performed for each rendered plaque, followed by the calculation of the total value. The combined endpoint was cardiovascular death, non-fatal myocardial infarction or unstable angina (which required hospitalization), non-fatal stroke, and coronary revascularization. Results The study included 100 patients at high and very high risk. The duration of the follow-up period was 24.4 (14.1–34.3) months. The events constituting the combined endpoint occurred in 34 (34%) patients: cardiovascular death was recorded in 7 (7%) patients; non-fatal myocardial infarction or stroke in 3 (3%) patients; unstable angina, which required hospitalization in 24 (24%) patients, while emergency coronary angiography was performed in 8 (8%) patients, coronary artery stenting was performed in 3 (3%) cases. The presence of carotid plaque in accordance with Cox regression after adjusting for factors such as sex, age, smoking, hypertension, BMI, eGFR, LDL-c and HbA1c, RR of adverse cardiovascular events was 10.5 (95% CI 1.27–86.5; p=0.008; see Figure 1). The optimal cut-off values of cTPA and carotid stenosis were determined by ROC-analysis. An increase in cTPA ≥69 mm2 corrected for sex, age, smoking, hypertension, BMI, eGFR, LDL-c, HbA1c, and the presence of carotid plaque was associated with an increase in the RR of adverse cardiovascular events by 5.86 times (95% CI 2.09–16.4; p=0.001; see Figure 1). Also, there were no statistically significant associations between carotid arteries stenosis and adverse cardiovascular events (RR 1.29; 95% CI 0.61–2.76; p=0.504). Kaplan–Meier curves for cTPA, stenosis Conclusion In patients at high and very high cardiovascular risk among carotid ultrasound parameters the presence of carotid plaque and cTPA, but not the degree of stenosis, had an independent predictive value regarding the development of adverse cardiovascular events.

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Sex Differences in Plaque Composition and Morphology Among Symptomatic Patients With Mild-to-Moderate Carotid Artery Stenosis

Stroke ◽

10.1161/strokeaha.121.036564 ◽

2022 ◽

Author(s):

Dianne H.K. van Dam-Nolen ◽

Nina C.M. van Egmond ◽

Kristine Dilba ◽

Kelly Nies ◽

Anja G. van der Kolk ◽

...

Keyword(s):

Sex Differences ◽

Carotid Stenosis ◽

Carotid Plaque ◽

Plaque Burden ◽

Multidetector Row Computed Tomography ◽

Plaque Composition ◽

Plaque Volume ◽

Men And Women ◽

Fibrous Cap ◽

Significant Difference

Background and Purpose: Incidence of ischemic stroke differs between men and women, with substantially higher rates in men. The underlying mechanism of this difference remains poorly understood but may be because of differences in carotid atherosclerosis. Using an in-depth imaging-based approach, we investigated differences between carotid plaque composition and morphology in male and female patients with stroke, taking into account differences in total plaque burden. Additionally, we investigated all possible within-artery combinations of plaque characteristics to explore differences between various plaque phenotypes. Methods: We included 156 men and 68 women from the PARISK (Plaque At Risk) study, a prospective cohort study of patients with recent ischemic cerebrovascular symptoms and <70% ipsilateral carotid stenosis. Plaque characteristics (intraplaque hemorrhage [IPH], lipid-rich necrotic core [LRNC], calcifications, thin-or-ruptured fibrous cap, ulcerations, total plaque volume) were assessed with magnetic resonance imaging and multidetector-row computed tomography angiography. We used multivariable logistic and linear regression analyses to assess sex differences in plaque characteristics. Results: We found significant difference in total plaque volume between men and women (β=22.9 mm 3 [95% CI, 15.4–30.5]; mean volume in men 1399±425 mm 3 , in women 1011±242 mm 3 ). Additionally, men were more likely to have IPH (odds ratio [OR]=2.8 [95% CI, 1.3–6.3]; IPH proportion in men 49%, in women 16%) and LRNC (OR=2.4 [95% CI, 1.2–4.7]; LRNC proportion in men 73%, in women 41%) even after adjustment for total plaque volume. We found no sex-specific differences in plaque volume-corrected volumes of IPH, LRNC, and calcifications. In terms of coexistence of plaque characteristics, we found that men had more often a plaque with coexistence of calcifications, LRNC, and IPH (OR=2.7 [95% CI, 1.2–7.0]), with coexistence of thin-or-ruptured fibrous cap/ulcerations, LRNC, and IPH (OR=2.4 [95% CI, 1.1–5.9]), and with coexistence of all plaque characteristics (OR=3.0 [95% CI, 1.2–8.6]). Conclusions: In symptomatic patients with mild-to-moderate carotid stenosis, men are more likely to have a high-risk carotid plaque with IPH and LRNC than women, regardless of total plaque burden. Men also have more often a plaque with multiple vulnerable plaque components, which could comprise an even higher stroke risk. REGISTRATION: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT01208025.

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Doppler Ultrasound Monitoring of Echogenicity in Asymptomatic Subcritical Carotid Stenosis and Assessment of Response to Oral Supplementation of Vitamin K2 (PLAK2 Randomized Controlled Trial)

Diagnostics ◽

10.3390/diagnostics11020229 ◽

2021 ◽

Vol 11 (2) ◽

pp. 229

Author(s):

Yamume Tshomba ◽

Domenico Baccellieri ◽

Niccolò Carta ◽

Giuseppe Cilli ◽

Vincenzo Ardita ◽

...

Keyword(s):

Randomized Controlled Trial ◽

Acetylsalicylic Acid ◽

Carotid Stenosis ◽

Standard Therapy ◽

Carotid Plaque ◽

Controlled Trial ◽

Vitamin K2 ◽

Plaque Composition ◽

Oral Supplementation ◽

Randomized Controlled

Background: Plaque composition may predict the evolution of carotid artery stenosis rather than its sole extent. The grey scale median (GSM) value is a reproducible and standardized value to report plaque echogenicity as an indirect measure of its composition. We monitored plaque composition in asymptomatic subcritical carotid stenosis and evaluated the effect of an oral modulating calcification factor (vitamin K2). Methods: Carotid plaque composition was assessed by GSM value. Monitoring the effects of standard therapy (acetylsalicylic acid and low–medium dosage statin) (acetylsalicylic acid (ASA) arm) or standard therapy plus vitamins K2 oral supplementation (ASA + K2 arm) over a 12 months period was conducted using an ultrasound scan in a prospective, open-label, randomized controlled trial (PLAK2). Results: Sixty patients on low–medium dosage statin therapy were enrolled and randomized (30 per arm) to either ASA + K2 or ASA alone. Thirty-seven patients (61.6%) showed at 12 months a stable plaque with a mean increase in the GSM value in respect to the baseline of 2.6% with no differences between the two study arms (p = 0.66). Fifteen patients (25%) showed an 8% GSM value reduction respect the baseline with no differences between the two study arms (p = 0.99). At multivariable analysis, the adjusted mean (95% confidence interval) GSM change per month from baseline was greater in the ASA + K2 arm (−0.55 points, p = 0.048) compared to ASA alone (−0.18 points, p = 0.529). Conclusions: Carotid plaque composition monitoring through GSM value represents a laborious procedure. Although its use may not be applied to everyday practice, a specific application consists in evaluating the effect of pharmacological therapy on plaque composition. This 12 months randomized trial showed that the majority of subcritical asymptomatic carotid plaque on treatment with low–medium dosage statin presented a stable or increased echogenicity. Although vitamin K2 beyond standard therapy did not determine a significant change in plaque composition, for those who presented with GSM reduction it did enhance a GSM monthly decline.

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The analysis of the connection between plaque morphology of the asymptomatic carotid stenosis and ischemic brain lesions

Vojnosanitetski pregled ◽

10.2298/vsp110519020m ◽

2013 ◽

Vol 70 (11) ◽

pp. 993-998 ◽

Cited By ~ 3

Author(s):

Djordje Milosevic ◽

Janko Pasternak ◽

Vladan Popovic ◽

Dragan Nikolic ◽

Pavle Milosevic ◽

...

Keyword(s):

Risk Factors ◽

Carotid Stenosis ◽

Carotid Plaque ◽

Brain Infarction ◽

Statistical Significance ◽

Brain Parenchyma ◽

Plaque Morphology ◽

Asymptomatic Carotid Stenosis ◽

Asymptomatic Carotid ◽

Silent Brain Infarction

Background/Aim. A certain percentage of patients with asymptomatic carotid stenosis have an unstable carotid plaque. For these patients it is possible to register by modern imaging methods the existence of lesions of the brain parenchyma - the silent brain infarction. These patients have a greater risk of ischemic stroke. The aim of this study was to analyze the connection between the morphology of atherosclerotic carotid plaque in patients with asymptomatic carotid stenosis and the manifestation of silent brain infarction, and to analyze the influence of risk factors for cardiovascular diseases on the occurrence of silent brain infarction and the morphology of carotid plaque. Methods. This retrospective study included patients who had been operated for high grade (> 70%) extracranial atherosclerotic carotid stenosis at the Clinic for Vascular and Transplantation Surgery of the Clinical Center of Vojvodina over a period of 5 years. The patients analyzed had no clinical manifestation of cerebrovascular insufficiency of the carotid artery territory up to the time of operation. The classification of carotid plaque morphology was carried out according to the Gray-Weale classification, after which all the types were subcategorized into two groups: stable and unstable. Brain lesions were verified using preoperative imaging of the brain parenchyma by magnetic resonance. We analyzed ipsilateral lesions of the size > or = 3 mm. Results. Out of a 201 patients 78% had stable plaque and 22% unstable one. Unstable plaque was prevalent in the male patients (male/female ratio = 24.8% : 17.8%), but without a statistically significant difference (p > 0.05). The risk factors (hypertension, nicotinism, hyperlipoproteinemia, and diabetes mellitus) showed no statistically significant impact on carotid plaque morphology and the occurrence of silent brain infarction. Silent brain infarction was detected in 30.8% of the patients. Unstable carotid plaque was found in a larger percentage of patients with silent brain infarction (36.4% : 29.3%) but without a significant statistical difference (p > 0.05). Conclusions. Even though silent brain infarction is more frequent in patients with unstable plaque of carotid bifurication, the difference is of no statistical significance. The effects of the number and type of risk factors bear no statistical significance on the incidence of morphological asymptomatic carotid plaque.

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Association between carotid plaque composition assessed by multidetector computed tomography and cerebral embolism after carotid stenting

Neuroradiology ◽

10.1007/s00234-011-0920-9 ◽

2011 ◽

Vol 54 (5) ◽

pp. 487-493 ◽

Cited By ~ 16

Author(s):

Naoyuki Uchiyama ◽

Kouichi Misaki ◽

Masanao Mohri ◽

Takuya Watanabe ◽

Yuichi Hirota ◽

...

Keyword(s):

Computed Tomography ◽

Multidetector Computed Tomography ◽

Carotid Plaque ◽

Carotid Stenting ◽

Cerebral Embolism ◽

Plaque Composition

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Hyperintense Carotid Plaque on T1-Weighted Turbo-Field Echo MRI in Symptomatic Patients with Low-Grade Carotid Stenosis and Carotid Occlusion

Cerebrovascular Diseases ◽

10.1159/000317182 ◽

2010 ◽

Vol 30 (3) ◽

pp. 221-229 ◽

Cited By ~ 1

Author(s):

Anja G. van der Kolk ◽

Gert J. de Borst ◽

Anne G. den Hartog ◽

M. Eline Kooi ◽

Willem P.T.M. Mali ◽

...

Keyword(s):

Carotid Stenosis ◽

Carotid Plaque ◽

Carotid Occlusion ◽

Low Grade ◽

Turbo Field Echo

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Abstract WP158: Validation of a Preliminary Prediction Model with MR Plaque Imaging to Estimate Risk for New Ischemic Brain Lesions after Carotid Endarterectomy or Stenting

Stroke ◽

10.1161/str.44.suppl_1.awp158 ◽

2013 ◽

Vol 44 (suppl_1) ◽

Author(s):

Kohkichi Hosoda ◽

Nobuyuki Akutsu ◽

Atsushi Fujita ◽

Eiji Kohmura

Keyword(s):

Prediction Model ◽

Carotid Stenosis ◽

Predictive Value ◽

Signal Intensity ◽

Carotid Plaque ◽

Brain Lesions ◽

Black Blood ◽

Training Set ◽

Ischemic Brain ◽

Validation Set

[Objective] Recently, we reported a preliminary prediction model with carotid plaque MRI to estimate risk for new ischaemic brain lesions after CEA or CAS. The objective of this study was to validate this model in new set of patients with carotid stenosis. [Methods] One hundred four patients with carotid stenosis undergoing treatment (63 CEA, 41 CAS) were used as a training set for construction of a preliminary prediction model to estimate risk for new ischemic brain lesions after CEA or CAS. T1 and T2 signal intensity of carotid plaque were measured on black-blood MRI. Associations among MRI findings, treatment, clinical factors, and occurrence of new ischemic lesions on DWI 1 day after treatment were studied by logistic regression. The validity of the prediction model was examined using a new set of patients with carotid stenosis (n = 43) as a validation set. [Results] In the training set, new DWI lesions after treatment were observed in 25 patients (24%). The model demonstrated that T1-signal intensity and CAS were positively associated with new lesions on post-treatment DWI scans, and T2 signal intensity was negatively associated (Fig. 1). The C-index was 0.79, which indicated some predictive value. In the validation set, new DWI lesions after treatment were observed in 10 patients (23%). However, C-index was 0.6 and positive predictive value was 33% (Fig. 2), which suggested overfitting of our model and/or differences in case-mix between the training set and validation set. [Conclusions] Our preliminary prediction model may provide some useful information for decision-making regarding treatment strategy, but needs further collection of patients to improve its predictive value.

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Abstract 18836: Integrative Pathway Analysis of Genome-wide Association Studies of Carotid Plaque Phenotypes

Circulation ◽

10.1161/circ.132.suppl_3.18836 ◽

2015 ◽

Vol 132 (suppl_3) ◽

Author(s):

Yuqi Zhao ◽

Sander M van der Laan ◽

Hester M den Ruijter ◽

Saskia Haitjema ◽

Gerard Pasterkamp ◽

...

Keyword(s):

Smooth Muscle ◽

Cardiovascular Events ◽

Association Studies ◽

Genome Wide Association ◽

Sphingolipid Metabolism ◽

Genome Wide Association Studies ◽

Plaque Composition ◽

Genetic Loci ◽

Genetic Components ◽

Genome Wide

Introduction: The composition of atherosclerotic plaques differs between individuals and contributes to the incidence of cardiovascular events. A better understanding of the biology underlying variability in plaque composition will provide insights into the progression of cardiovascular diseases. We carried out genome-wide association studies (GWAS) to investigate the genetic underpinnings of the plaque. Methods: We included carotid endarterectomy patients from the Athero-Express Biobank Study (n = 1,439). We quantified the percentage of macrophages and smooth muscle cells, the number of intraplaque vessels, the amount of collagen and calcification, the atheroma size, and the presence of plaque hemorrhage. GWAS was performed for all 9 plaque traits, and combined with summary level from GWAS consortia data on coronary artery disease (CAD), and ischemic stroke. Next, these data were integrated with data from human expression quantitative trait loci analyses, and pathway analyses of the plaque traits. Results: No individual locus reached genome-wide significance, likely due to the moderate sample size involved. However, it is plausible that perturbations of diverse pathways by a large number of genetic loci with small effects together contribute to the regulation of plaque composition. We identified 42-97 pathways significantly associated with each plaque phenotype, with many specific to each trait, supporting the presence of unique genetic components of individual plaque phenotypes. We also detected 39 pathways associated with at least four plaque phenotypes, among which were CAD-associated processes such as “extracellular matrix”, “complement and coagulation cascades” and stroke-associated pathways such as “Toll-like receptor signaling”. Interestingly, we found that smooth muscle cell percentage and atheroma size shared more genetic loci and pathways with intraplaque hemorrhage (such as “Sphingolipid metabolism”); the latter trait is associated with secondary cardiovascular events. Conclusion: There are genetic correlations among plaque phenotypes as well as between plaque phenotypes that provide mechanistic insight into the composition of the plaque and progression to secondary events.

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Elevated circulating metalloproteinase 7 predicts recurrent cardiovascular events in patients with carotid stenosis: a prospective cohort study

BMC Cardiovascular Disorders ◽

10.1186/s12872-020-01387-3 ◽

2020 ◽

Vol 20 (1) ◽

Cited By ~ 1

Author(s):

David Moreno-Ajona ◽

Pablo Irimia ◽

José Antonio Rodríguez ◽

María José García-Velloso ◽

Jesús López-Fidalgo ◽

...

Keyword(s):

Cohort Study ◽

Carotid Stenosis ◽

Prospective Cohort Study ◽

Prospective Cohort ◽

Cardiovascular Events

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3041Wall shear stress measurement by ultrafast vector flow imaging for atherosclerotic carotid stenosis

European Heart Journal ◽

10.1093/eurheartj/ehz745.0008 ◽

2019 ◽

Vol 40 (Supplement_1) ◽

Author(s):

G Goudot ◽

L Khider ◽

O Pedreira ◽

J M Poree ◽

P Julia ◽

...

Keyword(s):

Shear Stress ◽

Carotid Artery ◽

Wall Shear Stress ◽

Internal Carotid Artery ◽

Carotid Stenosis ◽

Common Carotid Artery ◽

Carotid Plaque ◽

Internal Carotid ◽

Plaque Vulnerability ◽

Wall Shear

Abstract Background Carotid plaque vulnerability assessment is an important factor in guiding the decision to treat significant carotid stenosis. Ultrafast Ultrasound Imaging (UF) offers the possibility of evaluating local flow velocities over an entire 2D image, allowing access to velocity measurements in contact with the arterial wall and to measure the wall shear stress (WSS). Purpose To evaluate the feasibility of WSS measurement in a prospective series of patients with carotid stenosis. Methods A 7.5 MHz linear probe of an Aixplorer scanner was used. UF acquisitions had 3 tilted plane waves transmits (−10; 0; 10°) and an effective frame rate of 5000Hz. We evaluated the flow velocity in 5 areas of the carotid wall: common carotid artery (1), plaque ascent (2), plaque peak (3), plaque descent (4), internal carotid artery (5) (Figure). WSS was computed with the vector field speed using the following formula, WSS=μ·δn·v with v the blood velocity, n the normal vector to the vessel wall and μ, the blood viscosity, calculated from the hematocrit value for each patient. WSS measurement method was first validated using a laminar flow phantom and known viscosity. And then, 33 patients were then prospectively evaluated, with a median carotid stenosis degree of 80% [75–85]. Results Significant correlation was found between in vitro measurement and the theoretical WSS values (R2=0.95; p<0.001).In patients,the maximum WSS value over the cardiac cycle follows the shape of the plaque with an increase during the ascend, reaching its maximum value of 3.57 Pa [2.47–4.45] at the peak of the plaque, and a fall after passing the peak (0.99 Pa [0.8–1.32]) lower than the WSS values in the non-stenotic areas (1.55 Pa [1.13–1.90] for the common carotid artery) (Table). Table 1 Wall's area Wall shear stress (Pa) Min Max Delta 1. Common carotid artery 0.14 [0.05–0.27] 1.55 [1.13–1.90] 0.73 [0.55–0.96] 2. Plaque's ascent 0.39 [0.24–0.59] 2.63 [1.89–3.28] 1.20 [0.89–1.79] 3. Plaque's peak 0.60 [0.32–0.89] 3.57 [2.47–4.45] 1.78 [1.44–2.46] 4. Plaque's descent 0.16 [0.13–0.22] 0.99 [0.80–1.32] 0.52 [0.34–0.73] 5. Internal carotid artery 0.17 [0.13–0.35] 1.37 [1.04–1.75] 0.72 [0.50–0.87] Results are median [25th–75th percentile]. Figure 1 Conclusion UF provide reliable WSS values. High WSS was present at the peak of the plaque, whereas lowest WSS values were found at the post-stenotic zone. WSS evaluation may help to better characterize the carotid plaque vulnerability.

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