International Union of Angiology (IUA) consensus paper on imaging strategies in atherosclerotic carotid artery imaging: From basic strategies to advanced approaches - ScienceDirect

Atherosclerosis

Volume 354, August 2022, Pages 23-40

Atherosclerosis

https://doi.org/10.1016/j.atherosclerosis.2022.06.1014 Get rights and content

Highlights

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Carotid artery disease is a risk factor for ischemic stroke and a predictor of cardiovascular events.
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Imaging assessment of carotid artery disease is critical for surveillance, risk stratification, and patient management.
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A comprehensive assessment of carotid artery disease should aid physicians and surgeons in their decision-making.

Abstract

Cardiovascular disease (CVD) is the leading cause of mortality and disability in developed countries. According to WHO, an estimated 17.9 million people died from CVDs in 2019, representing 32% of all global deaths. Of these deaths, 85% were due to major adverse cardiac and cerebral events. Early detection and care for individuals at high risk could save lives, alleviate suffering, and diminish economic burden associated with these diseases.

Carotid artery disease is not only a well-established risk factor for ischemic stroke, contributing to 10%–20% of strokes or transient ischemic attacks (TIAs), but it is also a surrogate marker of generalized atherosclerosis and a predictor of cardiovascular events. In addition to diligent history, physical examination, and laboratory detection of metabolic abnormalities leading to vascular changes, imaging of carotid arteries adds very important information in assessing stroke and overall cardiovascular risk. Spanning from carotid intima-media thickness (IMT) measurements in arteriopathy to plaque burden, morphology and biology in more advanced disease, imaging of carotid arteries could help not only in stroke prevention but also in ameliorating cardiovascular events in other territories (e.g. in the coronary arteries).

While ultrasound is the most widely available and affordable imaging methods, computed tomography (CT), magnetic resonance imaging (MRI), positron emission tomography (PET), their combination and other more sophisticated methods have introduced novel concepts in detection of carotid plaque characteristics and risk assessment of stroke and other cardiovascular events. However, in addition to robust progress in usage of these methods, all of them have limitations which should be taken into account. The main purpose of this consensus document is to discuss pros but also cons in clinical, epidemiological and research use of all these techniques.

Graphical abstract

Section snippets

Targets of carotid imaging

Detailed imaging assessment of extracranial carotid artery disease is critical for appropriate risk stratification and management of those presenting with cerebrovascular ischemia as well as of selected asymptomatic individuals [1].

The degree of luminal stenosis in the carotid bifurcation has historically served as the primary imaging feature for determining ischemic stroke risk and the potential need for surgery. Contemporary multimodality imaging including ultrasound, magnetic resonance

Stenosis

Grading and stratification of carotid stenosis is manly based on multiparametric, hemodynamic criteria on Duplex ultrasound [4] (Table 2). The most important parameters are the measurement of the peak systolic and the end-diastolic flow velocity within the stenosis. The accuracy of Duplex ultrasound compared with angiography for detecting >50% and ≥70% stenosis, respectively, is very good, with a positive predictive value of >90% and a specificity of >85% [5]. Duplex ultrasound is recommended

Stenosis

CTA has evolved along with the technological advances of CT hardware and software. Modern CTA, performed with multidetector high-speed CT hardware and evaluated with 3D reformatting software, accurately and reliably depicts carotid disease and allows for direct quantification of carotid stenosis in millimeters [[66], [67], [68], [69], [70], [71], [72]].

CTA is an anatomic study of arteries, allowing for direct evaluation of carotid stenosis. CTA is fast, with images of the head and neck acquired

Stroke risk assessment and characterization of low-grade carotid atherosclerosis

Risk assessment of carotid atherosclerotic plaque for cerebrovascular ischemic events has historically relied on angiographic measures of stenosis, with thresholds for revascularization defined by randomized clinical trials that date back to the early 1990's [93,110,111]. The established threshold for SCS is 70%, although revascularization is often considered for stenosis beginning at 50% when symptomatic and 60% when asymptomatic [93,110,112,113]. Stenosis has worked well in these studies

PET

PET enables molecular imaging of biological and biochemical processes in vivo, whereas hybrid PET/CT [137] or PET/MRI [138,139] also provides additional information on plaque morphology. The glucose analogue 18F-Fluorodeoxyglucose (FDG) is taken up by cells with a high metabolic rate, such as macrophages within an atherosclerotic plaque, and therefore enables to quantify the inflammatory activity within carotid atherosclerotic plaques [140]. In order to correct for uptake of the tracer in the

Artificial intelligence

As stroke is the second leading cause of global mortality, this demonstrated the need for improved tools in the management of occlusive vascular disease [163,164]. Patients with cardiovascular disease leading to stroke often require significant medical imaging in the acute, sub-acute, and chronic settings, using a range of imaging modalities. Vascular imaging is then used as a key source of information in the determination of appropriate clinical management. In the era of modern medicine, AI is

Summary and conclusion

Ultrasonography is the first-line imaging modality for the evaluation of atherosclerotic carotid artery disease, as it is non-invasive, cost-effective, readily available, well-tolerated, and safe [213,214]. Anatomic information is provided with traditional B-mode (greyscale) ultrasound, while hemodynamic information is provided with color Doppler, power Doppler, and pulsed-wave Doppler technique [213,214].

The image quality provided by ultrasound can be enhanced by the use of a contrast agent [

CRediT authorship contribution statement

Luca Saba: Conceptualization, Methodology, Validation, Writing – review & editing. Pier Luigi Antignani: Conceptualization, Methodology, Validation, Writing – review & editing. Ajay Gupta: Conceptualization, Writing – original draft. Riccardo Cau: Conceptualization, Writing – original draft, Writing – review & editing. Kosmas I. Paraskevas: Methodology, Writing – original draft. Pavel Poredos: Methodology, Writing – original draft. Bruce A. Wasserman: Writing – original draft. Hooman Kamel:

Declaration of competing interest

The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Dr. Seemant Chaturvedi is on the executive committee of CREST 2 and ACT I and serves as an Associate Editor for Stroke. Dr. Luis Savastano is equity owner and CMO of VerAvanti Inc.

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Angiogenesis in atherosclerosis (AS) promotes plaque destabilization. miR-126 has a significant role in angiogenesis. Tetramethylpyrazine (TMP) and paeoniflorin (PF) have anti-atherosclerotic effects. However, the miR-126-related mechanisms of TMP and PF combination (TMP-PF) on angiogenesis in AS have not been understood. To explore the mechanism of TMP-PF on angiogenesis in AS targeting miR-126. Human umbilical vein endothelial cells (HUVECs) were assigned into the control, model, TMP-PF, TMP-PF + miR-126 inhibitor, and simvastatin groups. HUVECs were transfected with miR-126 inhibitor or negative control, incubated with oxidized low-density lipoprotein (ox-LDL) to establish AS model, and then treated with TMP-PF or simvastatin. Cell proliferation, migration, and tube formation assays are conducted, and the expression of angiogenesis-related factors were detected by enzyme-linked immunosorbent assay (ELISA) and Western blotting. The expression level of miR-126 was confirmed by polymerase chain reaction (PCR).
ox-LDL promoted HUVECs proliferation, migration, and tube formation, downregulated miR-126 expression, and increased the expression of VEGF, VEGFR2, bFGF, and FGFR1. TMP-PF inhibited proliferation, migration, and tube formation, upregulated miR-126 expression and decreased the expression of VEGF, VEGFR2, bFGF, and FGFR1 in ox-LDL-induced HUVECs. However, the effects of TMP-PF on angiogenesis and the expression of miR-126, VEGF, VEGFR2, and FGFR1 were abolished by miR-126 inhibitor. TMP-PF suppressed angiogenesis in AS by regulating miR-126/VEGF/VEGFR2 pathway, which might elucidate the underlying mechanism of TMP-PF in alleviating AS.
Carotid stenosis and cryptogenic stroke
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Cryptogenic stroke represents a type of ischemic stroke with an unknown origin, presenting a significant challenge in both stroke management and prevention. According to the Trial of Org 10,172 in Acute Stroke Treatment criteria, a stroke is categorized as being caused by large artery atherosclerosis only when there is >50% luminal narrowing of the ipsilateral internal carotid artery. However, nonstenosing carotid artery plaques can be an underlying cause of ischemic stroke. Indeed, emerging evidence documents that some features of plaque vulnerability may act as an independent risk factor, regardless of the degree of stenosis, in precipitating cerebrovascular events. This review, drawing from an array of imaging-based studies, explores the predictive values of carotid imaging modalities in the detection of nonstenosing carotid plaque (<50%), that could be the cause of a cerebrovascular event when some features of vulnerability are present.
Google Scholar, Scopus, and PubMed were searched for articles on cryptogenic stroke and those reporting the association between cryptogenic stroke and imaging features of carotid plaque vulnerability.
Despite extensive diagnostic evaluations, the etiology of a considerable proportion of strokes remains undetermined, contributing to the recurrence rate and persistent morbidity in affected individuals. Advances in imaging modalities, such as magnetic resonance imaging, computed tomography scans, and ultrasound examination, facilitate more accurate detection of nonstenosing carotid artery plaque and allow better stratification of stroke risk, leading to a more tailored treatment strategy.
Early detection of nonstenosing carotid plaque with features of vulnerability through carotid imaging techniques impacts the clinical management of cryptogenic stroke, resulting in refined stroke subtype classification and improved patient management. Additional research is required to validate these findings and recommend the integration of these state-of-the-art imaging methodologies into standard diagnostic protocols to improve stroke management and prevention.
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Objective: To investigate if there is an association between atherosclerosis and depression by using as imaging biomarker the carotid intima media thickness (cIMT), a surrogate marker for atherosclerosis.
Methods: PubMed/Medline, Embase and Cochrane databases were comprehensively searched to identify studies investigating the association between cIMT and depression. The results were pooled using a random-effects statistical model, appropriate for the expected high heterogeneity. Sensitivity and subgroup analyses were conducted where data was available.
Results: Overall, 22 and 13 studies met inclusion criteria for the qualitative and the quantitative synthesis, respectively, with a total of 4466 patients and 21,635 control participants. Results showed that cIMT is significantly higher in the depression, compared to the control groups with an overall mean difference of 0.07 mm (95% CI 0.04–0.10, p < 0.01). Subgroup analysis showed that diabetes could present as a confounding factor in patients with depression and an increased cIMT.
Conclusions: This study confirms a significantly increased cIMT in patients with depression, compared with controls and suggests a possible bidirectional link between atherosclerosis and depression. An early screening of cardiovascular disease in individuals suffering with depression should be considered.
Taking care of the clues already under our eyes: Early carotid plaque ultrasound detection may enlighten the age-old paradigm shift of glomerular hyperfiltration
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Maybe asymptomatic carotid disease is not as benign as we think
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^☆: J. Pitha was supported by Ministry of Health of the Czech Republic, grant No. NU22-02-00051.

© 2022 Elsevier B.V. All rights reserved.

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