Optimal Management of Asymptomatic Carotid Stenosis in 2021: The Jury is Still Out. An International, Multispecialty, Expert Review and Position Statement.

OBJECTIVES: The recommendations of international guidelines for the management of asymptomatic carotid stenosis (ACS) often vary considerably and extend from a conservative approach with risk factor modification and best medical treatment (BMT) alone, to a more aggressive approach with a carotid intervention plus BMT. The aim of the current multispecialty position statement is to reconcile the conflicting views on the topic. MATERIALS AND METHODS: A literature review was performed with a focus on data from recent studies. RESULTS: Several clinical and imaging high-risk features have been identified that are associated with an increased long-term ipsilateral ischemic stroke risk in patients with ACS. Such high-risk clinical/imaging features include intraplaque hemorrhage, impaired cerebrovascular reserve, carotid plaque echolucency/ulceration/ neovascularization, a lipid-rich necrotic core, a thin or ruptured fibrous cap, silent brain infarction, a contralateral transient ischemic attack/stroke episode, male patients < 75 years and microembolic signals on transcranial Doppler. There is growing evidence that 80-99% ACS indicate a higher stroke risk than 50-79% stenoses. CONCLUSIONS: Although aggressive risk factor control and BMT should be implemented in all ACS patients, several high-risk features that may increase the risk of a future cerebrovascular event are now documented. Consequently, some guidelines recommend a prophylactic carotid intervention in high-risk patients to prevent future cerebrovascular events. Until the results of the much-anticipated randomized controlled trials emerge, the jury is still out regarding the optimal management of ACS patients.

Activation of calpain-1 in human carotid artery atherosclerotic lesions.

BACKGROUND: In a previous study, we observed that oxidized low-density lipoprotein-induced death of endothelial cells was calpain-1-dependent. The purpose of the present paper was to study the possible activation of calpain in human carotid plaques, and to compare calpain activity in the plaques from symptomatic patients with those obtained from patients without symptoms. METHODS: Human atherosclerotic carotid plaques (n = 29, 12 associated with symptoms) were removed by endarterectomy. Calpain activity and apoptosis were detected by performing immunohistochemical analysis and TUNEL assay on human carotid plaque sections. An antibody specific for calpain-proteolyzed alpha-fodrin was used on western blots. RESULTS: We found that calpain was activated in all the plaques and calpain activity colocalized with apoptotic cell death. Our observation of autoproteolytic cleavage of the 80 kDa subunit of calpain-1 provided further evidence for enzyme activity in the plaque samples. When calpain activity was quantified, we found that plaques from symptomatic patients displayed significantly lower calpain activity compared with asymptomatic plaques. CONCLUSION: These novel results suggest that calpain-1 is commonly active in carotid artery atherosclerotic plaques, and that calpain activity is colocalized with cell death and inversely associated with symptoms.

A 3-D ultrasound-based framework to characterize the echo morphology of carotid plaques.

Carotid atherosclerosis is the main cause of brain stroke, which is the most common life-threatening neurological disease. Nearly all methods aiming at assessing the risk of plaque rupture are based on its characterization from 2-D ultrasound images, which depends on plaque geometry, degree of stenosis, and echo morphology (intensity and texture). The computation of these indicators is, however, usually affected by inaccuracy and subjectivity associated with data acquisition and operator-dependent image selection. To circumvent these limitations, a novel and simple method based on 3-D freehand ultrasound is proposed that does not require any expensive equipment except the common scanner. This method comprises the 3-D reconstruction of carotids and plaques to provide clinically meaningful parameters not available in 2-D ultrasound imaging, namely diagnostic views not usually accessible via conventional techniques and local 3-D characterization of plaque echo morphology. The labeling procedure, based on graph cuts, allows us to identify, locate, and quantify potentially vulnerable foci within the plaque. Validation of the characterization method was made with synthetic data. Results of plaque characterization with real data are encouraging and consistent with the results from conventional methods and after inspection of surgically removed plaques.