High-risk Carotid Plaque Research Articles

Predictors for High-Risk Carotid Plaque in Asymptomatic Korean Population.

Aims High-risk carotid plaque remains an important risk factor for atherosclerotic cardiovascular disease (ASCVD). We sought to evaluate the characteristics of carotid plaque and to find out the predictors for high-risk carotid plaque in asymptomatic Koreans. Methods Subjects (n = 801) without a history of ASCVD from 12 university hospitals in Korea underwent carotid ultrasound. The images were standardized at core laboratory. Morphologic characteristics of plaque were analyzed with laboratory and clinical characteristics. High-risk carotid plaque features included the highest quartile of carotid plaque score (cPS), irregular plaque surface, and hypoechoic and ulcerated plaque. Results The carotid plaque prevalence was 22.1% (177/801 persons, 293 plaques). The plaque was increased with age (p < 0.001) and conventional ASCVD risk estimator (p < 0.001) and the most frequently found in bulb (n = 190, 64.8%). The number of the highest quartile of cPS was 44/177 (24.9%). Irregular plaque was seen in 20.8% out of total plaque (61/293) and was more frequent in the high-risk 10-year ASCVD risk group than in the low-risk group (36.1% vs. 15.8%, p = 0.023). Hypoechoic and ulcerated plaques were seen in 14.3% (42/293) and 2% (6/293), respectively. The independent predictors for high-risk plaque were age (β = 0.052, p < 0.001), HbA1c (β = 0.182, p = 0.004), male (β = 0.118, p = 0.006), hypertension (β = 0.090, p = 0.032), and multiple plaques (OR: 4.810 (two plaques) and 8.621 (three plaques), all p < 0.001). Conclusions This study suggests that high-risk carotid plaque was seen in 12.4% (99/801). The high-risk plaque was associated with diabetes control status reflected by the HbA1c level as well as traditional risk factors in asymptomatic Korean population.

Identification of high-risk carotid plaque with MRI-based radiomics and machine learning.

We sought to build a high-risk plaque MRI-based model (HRPMM) using radiomics features and machine learning for differentiating symptomatic from asymptomatic carotid plaques. One hundred sixty-two patients with carotid stenosis were randomly divided into training and test cohorts. Multi-contrast MRI including time of flight (TOF), T1- and T2-weighted imaging, and contrast-enhanced imaging was done. Radiological characteristics of the carotid plaques were recorded and calculated to build a traditional model. After extracting the radiomics features on these images, we constructed HRPMM with least absolute shrinkage and selection operator algorithm in the training cohort and evaluated its performance in the test cohort. A combined model was also built using both the traditional and radiomics features. The performance of all the models in the identification of high-risk carotid plaque was compared. Intraplaque hemorrhage and lipid-rich necrotic core were independently associated with clinical symptoms and were used to build the traditional model, which achieved an area under the curve (AUC) of 0.825 versus 0.804 in the training and test cohorts. The HRPMM and the combined model achieved an AUC of 0.988 versus 0.984 and of 0.989 versus 0.986 respectively in the two cohorts. Both the radiomics model and combined model outperformed the traditional model, whereas the combined model showed no significant difference with the HRPMM. Our MRI-based radiomics model can accurately distinguish symptomatic from asymptomatic carotid plaques. It is superior to the traditional model in the identification of high-risk plaques. • Carotid plaque multi-contrast MRI stores other valuable information to be further exploited by radiomics analysis. • Radiomics analysis can accurately distinguish symptomatic from asymptomatic carotid plaques. • The radiomics model is superior to the traditional model in the identification of high-risk plaques.

Reclassification of Ischemic Stroke Etiological Subtypes on the Basis of High-Risk Nonstenosing Carotid Plaque.

Background and Purpose- Carotid artery plaque with <50% luminal stenosis may be an underappreciated stroke mechanism. We assessed how many stroke causes might be reclassified after accounting for nonstenosing plaques with high-risk features. Methods- We included patients enrolled in the Cornell Acute Stroke Academic Registry from 2011 to 2015 who had anterior circulation infarction, magnetic resonance imaging of the brain, and magnetic resonance angiography of the neck. High-risk plaque was identified by intraplaque hemorrhage ascertained from routine neck magnetic resonance angiography studies using validated methods. Infarct location was determined from diffusion-weighted imaging. Intraplaque hemorrhage and infarct location were assessed separately in a blinded fashion by a neuroradiologist. We used the McNemar test for matched data to compare the prevalence of intraplaque hemorrhage ipsilateral versus contralateral to brain infarction. We reclassified stroke subtypes by including large-artery atherosclerosis as a cause if there was intraplaque hemorrhage ipsilateral to brain infarction, regardless of the degree of stenosis. Results- Among the 1721 acute ischemic stroke patients registered in the Cornell Acute Stroke Academic Registry from 2011 to 2015, 579 were eligible for this analysis. High-risk plaque was more common ipsilateral versus contralateral to brain infarction in large-artery atherosclerotic (risk ratio [RR], 3.7 [95% CI, 2.2-6.1]), cryptogenic (RR, 2.1 [95% CI, 1.4-3.1]), and cardioembolic strokes (RR, 1.7 [95% CI, 1.1-2.4]). There were nonsignificant ipsilateral-contralateral differences in high-risk plaque among lacunar strokes (RR, 1.2 [95% CI, 0.4-3.5]) and strokes of other determined cause (RR, 1.5 [95% CI, 0.7-3.3]). After accounting for ipsilateral high-risk plaque, 88 (15.2%) patients were reclassified: 38 (22.6%) cardioembolic to multiple potential etiologies, 6 (8.5%) lacunar to multiple, 3 (15.8%) other determined cause to multiple, and 41 (20.8%) cryptogenic to large-artery atherosclerosis. Conclusions- High-risk carotid plaque was more prevalent ipsilateral to brain infarction across several ischemic stroke subtypes. Accounting for such plaques may reclassify the etiologies of up to 15% of cases in our sample.

P4389Effect of cigarette smoking on carotid artery atherosclerosis: a community-based cohort study

Abstract Background Cigarette smoking is closely associated with the development of cardiovascular diseases (CVD), and the European Society of Cardiology/European Atherosclerosis Society (ESC/EAS) guidelines recommend smoking bans.On the other hand, the relationship between cigarette smoking and subclinical atherosclerosis has not been fully studied. Carotid intima-media thickness (cIMT) is commonly used as a subclinical atherosclerosis marker, and a carotid plaque feature is also known to be an important predictor of cardiovascular diseases. Purpose We sought to clarify the association between cigarette smoking and subclinical atherosclerosis by evaluating carotid plaque including cIMT and carotid plaque features in general population. Methods and results Among 1,209 participants with no prior coronary artery disease who received a medical check-up with cardiovascular examination at our institution, 450 participants (37.2%) were smokers (including both past and current smokers). We defined carotid plaque as cIMT ≥1.1 mm and high-risk plaque as carotid plaque with hypoechoic dominant and/or plaque ulceration. The value of cIMT and the rate of carotid plaque were not different between smokers and never smokers (Figure A &amp; B). However, the rate of carotid high-risk plaque was significantly higher in participants with smokers than those with never smokers (29.7%, vs 23.5%, p=0.011) (Figure C). Even after adjustment with covariates including age, gender and traditional cardiovascular risk factors, cigarette smoking was independently associated with high-risk plaque formation (odds ratio 1.384, 95% CI 1.020–1.877; p=0.037). According to the subgroup analysis classified by age, cigarette smoking was associated with not only the development of high-risk plaque but also the increased value of cIMT in the subgroup over 60 years old, whereas only the rate of high-risk plaque was higher in smokers than never smokers in the subgroup under 60 years old. Carotid plaque and smoking Conclusion The development of high-risk carotid artery plaque may precede thickening of cIMT in cigarette smokers, suggesting that the novel insight for the pathological mechanism underlying cardiovascular events and cigarette smoking.

Association between low levels of serum miR-638 and atherosclerotic plaque vulnerability in patients with high-grade carotid stenosis.

Carotid artery atherosclerosis is a major cause of ischemic stroke. However, reliable criteria to identify patients with high-risk carotid plaques beyond the severity of stenosis are still lacking. Circulating microRNAs (miRNAs) are being postulated as biomarkers for a variety of vascular immune-inflammatory diseases. The authors investigated whether cell-free circulating miR-638, highly expressed in vascular smooth muscle cells and implicated in proliferative vascular diseases, is associated with vulnerable atherosclerotic plaques in high-risk patients with advanced carotid artery stenosis undergoing carotid endarterectomy (CEA). The authors conducted a prospective study in 22 consecutive symptomatic patients with high-grade carotid stenosis undergoing CEA and 36 age- and sex-matched patients without ischemic stroke history or carotid atherosclerosis (control group). In addition, they reviewed data from a historical group of 9 CEA patients who underwent long-term follow-up after revascularization. Total RNA was isolated from all serum samples, and relative miR-638 expression levels were detected by reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and compared among groups. A correlation analysis of serum miR-638 levels with vascular risk factors and treatments, and with plaque features, was performed. The ability of serum miR-638 to discriminate between the non-CEA control group and the different CEA groups was assessed by receiver operating characteristic evaluation. A logistic regression model was employed to examine the association between stratified CEA patients and serum miR-638 levels. Serum levels of miR-638 were significantly lower in symptomatic CEA patients (p = 0.009) and particularly in the subgroup of CEA patients who had experienced stroke (p = 0.0006) than in non-CEA controls. Discrimination of high-risk plaques was accurate (area under the curve [AUC] 0.66 for symptomatic CEA patients in general and 0.76 for those who had experienced stroke). When only patients with high cardiovascular risk were considered, the diagnostic value of serum miR-638 from symptomatic CEA patients and CEA patients who had experienced stroke improved (AUC 0.79 and 0.85). Moreover, serum miR-638 was negatively correlated with the occurrence of stroke, smoker status, presence of bilateral pathology, coronary artery disease, and cholesterol treatment; and with the high-risk fibroatheroma plaques extracted from CEA patients. Multivariate logistic regression analysis demonstrated that serum miR-638 was an independent predictor of plaque instability. Furthermore, serum miR-638 appeared to attain good discrimination for atherosclerotic stenosis in CEA patients based on analysis of blood samples obtained in the historical group before and 5 years after intervention (p = 0.04) (AUC = 0.79). According to this preliminary proof-of-concept study, serum miR-638 might constitute a promising noninvasive biomarker associated with plaque vulnerability and ischemic stroke, particularly in individuals with elevated cardiovascular risk.

Abstract WP72: Recurrent Cerebral Ischemic Events in Symptomatic Carotid Stenosis are Related to Plaque Inflammation

Background and Aims: Severity of symptomatic carotid stenosis often determines the treatment approach. However, severity explains only the regional hypoperfusion as the mechanism of cerebral ischemia. Artery-to-artery embolisation remains an important pathogenic mechanism in patients with high-risk carotid plaques. Inflammation is considered as the initiating event for plaque rupture and cerebral embolism. Using 18F-fluorodeoxyglucose positron-emission tomography (FDG-PET)/computed tomography (CT) and high-resolution magnetic resonance imaging (HR-MRI), we investigated the role of plaque imaging in stroke recurrence in our patients with recently symptomatic carotid stenosis. Methods: This prospective study included consecutive patients within 30-days of recent stroke and ipsilateral carotid stenosis (≥50%). FDG uptake was quantified as mean standardized uptake values (SUV, g/ml). The ratio of T1 hyperintensity of carotid plaque to the ipsilateral sternocleidomastoid muscle (SCM) was recorded on T1-weighted fat suppressed HR-MRI. Patients were followed-up for stroke recurrence within 90-days. Results: Of the 115 patients included in the study, 17 (15%) suffered from recurrent cerebral ischemic event in the stenosed carotid territory within 90-days. Compared to patients who remained asymptomatic, patients with recurrent cerebral ischemia showed higher mean T1 carotid-SCM ratio (2.19 versus 1.38; p&lt;0.0001) and higher mean SUV value in the carotid plaque (3.04g/ml versus 1.25g/ml; p&lt;0.0001). Higher T1 carotid-SCM ratio on HR-MRI (OR 3.215, 95%CI 1.304-5.927; p&lt;0.0001) and higher mean SUV on FDG-PET (OR 3.601, 95%CI 2.924-7.628; p=0.005) were independent predictors of recurrent cerebral ischemia. Conclusions: FDG-PET/CT and HR-MRI of carotid stenosis are useful tools for risk stratification and may aid in better therapeutic decision-making.

Association Between Incomplete Circle of Willis and Carotid Vulnerable Atherosclerotic Plaques.

Objective- Carotid high-risk plaque, characterized by intraplaque hemorrhage, fibrous cap rupture, and large lipid-rich necrotic core, is associated with cerebrovascular events. This study sought to investigate the relationship between high-risk carotid plaque and an incomplete circle of Willis (COW). Approach and Results- Patients were recruited from a multicenter study, Chinese Atherosclerosis Risk Evaluation (CARE-II) and underwent 3-dimensional time-of-flight magnetic resonance angiography for intracranial arteries and 2-dimensional multicontrast magnetic resonance vessel wall imaging for carotid arteries on a 3.0T magnetic resonance scanner. The integrity of the COW in anterior and posterior portions was evaluated. Characteristics of carotid plaques were assessed. Correlation between incomplete COW and carotid plaque features was determined. Of 482 eligible patients, patients with carotid intraplaque hemorrhage showed significantly higher prevalence of an incomplete anterior COW (52.7% versus 38.5%; P=0.022) compared with those without. An incomplete anterior COW was associated with intraplaque hemorrhage before (odds ratio, 1.781; 95% CI, 1.083-2.931; P=0.023) and after adjusted for clinical risk factors (odds ratio, 1.945; 95% CI, 1.139-3.321; P=0.015). The unilateral carotid artery stenosis showed no correlation with incomplete anterior COW and posterior COW (all P>0.025). No significant associations were found between other plaque features and any type of incomplete COW (all P>0.025). Conclusions- An incomplete COW is independently associated with intraplaque hemorrhage of carotid atherosclerotic plaques. Clinical Trial Registration- URL: http://www.clinicaltrials.gov . Unique identifier: NCT02017756.

Endothelial vascular cell adhesion molecule 1 is a marker for high-risk carotid plaques and target for ultrasound molecular imaging

BackgroundMolecular imaging of carotid plaque vulnerability to atheroembolic events is likely to lead to improvements in selection of patients for carotid endarterectomy (CEA). The aims of this study were to assess the relative value of endothelial inflammatory markers for this application and to develop molecular ultrasound contrast agents for their imaging. MethodsHuman CEA specimens were obtained prospectively from asymptomatic (30) and symptomatic (30) patients. Plaques were assessed by semiquantitative immunohistochemistry for vascular cell adhesion molecule 1 (VCAM-1), lectin-like oxidized low-density lipoprotein receptor 1, P-selectin, and von Willebrand factor. Established small peptide ligands to each of these targets were then synthesized and covalently conjugated to the surface of lipid-shelled microbubble ultrasound contrast agents, which were then evaluated in a flow chamber for binding kinetics to activated human aortic endothelial cells under variable shear conditions. ResultsExpression of VCAM-1 on the endothelium of CEA specimens from symptomatic patients was 2.4-fold greater than that from asymptomatic patients (P < .01). Expression was not significantly different between groups for P-selectin (P = .43), von Willebrand factor (P = .59), or lectin-like oxidized low-density lipoprotein receptor 1 (P = .99). Although most plaques from asymptomatic patients displayed low VCAM-1 expression, approximately one in five expressed high VCAM-1 similar to plaques from symptomatic patients. In vitro flow chamber experiments demonstrated that VCAM-1-targeted microbubbles bind cells that express VCAM-1, even under high-shear conditions that approximate those found in human carotid arteries, whereas binding efficiency was lower for the other agents. ConclusionsVCAM-1 displays significantly higher expression on high-risk (symptomatic) vs low-risk (asymptomatic) carotid plaques. Ultrasound contrast agents bearing ligands for VCAM-1 can sustain high-shear attachment and may be useful for identifying patients in whom more aggressive treatment is warranted.

Abstract 147: Plaque Inflammation is Associated With Early Cerebral Ischemic Events in Symptomatic Carotid Stenosis

Background and aims: Currently, the severity of the symptomatic carotid stenosis determines the treatment approach. However, it explains only the regional hypoperfusion as the mechanism of cerebral ischemia. Artery-to-artery embolisation remains an important pathogenic mechanism in patients with high-risk carotid plaques. Recently, inflammation has been proposed as the initiating event for plaque rupture and cerebral embolism. Using 18F-fluorodeoxyglucose positron-emission tomography (FDG-PET)/computed tomography (CT) and high resolution magnetic resonance imaging (HR-MRI), we investigated the role of plaque imaging and stroke recurrence in our cohort of patients with recently symptomatic carotid stenosis. Methods: This ongoing prospective study included consecutive patients within 30-days of recent stroke and ipsilateral carotid stenosis (≥50%). FDG uptake was quantified as mean standardized uptake values (SUV, g/ml). The ratio of T1 hyperintensity of carotid plaque to the ipsilateral sternocleidomastoid muscle (SCM) was recorded on T1-weighted fat suppressed HR-MRI. Patients were followed prospectively for stroke recurrence within 90-days. Results: Of the 70 patients included in the study, 11 (16%) suffered from recurrent cerebral ischemic event in the same vascular territory within 90-days. Compared to patients without subsequent cerebral ischemic events, patients with recurrent cerebral ischemia showed higher mean T1 carotid-SCM ratio (2.24 versus 1.46; p&lt;0.0001) and higher mean SUV value in the carotid plaque (3.26g/ml versus 1.28g/ml; p&lt;0.0001). Higher T1 carotid-SCM ratio on HR-MRI (OR 3.374, 95%CI 1.561-6.253; p&lt;0.0001), higher mean SUV on FDG-PET (OR 3.646, 95%CI 3.172-11.524; p=0.005) were independent predictors of recurrent cerebral ischemia. Conclusions: FDG-PET/CT and HR-MRI of carotid stenosis helps in identification of patients at higher risk of subsequent cerebral ischemic events and may aid in better therapeutic decision-making.

Association between Carotid Plaque Features on CTA and Cerebrovascular Ischemia: A Systematic Review and Meta-Analysis.

CTA is a widely available imaging examination that may allow the evaluation of high-risk carotid plaque features. Our aim was to evaluate the association between specific carotid plaque features on CTA and ipsilateral cerebrovascular ischemia. We performed a systematic review of Ovid MEDLINE, Ovid Embase, Scopus, and the Cochrane Library from inception to March 2016 for articles that evaluated the relationship between CTA-detected carotid plaque features and ischemic events, defined as ipsilateral ischemic stroke or transient ischemic attack. Sixteen studies were ultimately included after screening 12,557. Two readers recorded data from each study and assessed the study quality with all disagreements resolved by a third reader. A random-effects OR was used to evaluate the association between cerebrovascular ischemia and each of the evaluated plaque features. We found significant positive relationships with cerebrovascular ischemia for the presence of soft plaque (OR, 2.9; 95% CI, 1.4-6.0), plaque ulceration (OR, 2.2; 95% CI, 1.4-3.4), and increased common carotid artery wall thickness (OR, 6.2; 95% CI, 2.5-15.6). We found a significant negative relationship between calcified plaque and ipsilateral ischemia (OR, 0.5; 95% CI, 0.4-0.7). We found heterogeneity in the existing literature secondary to lack of standardized plaque features and clinical definitions. Soft plaque, plaque ulceration, and increased common carotid artery wall thickness on CTA are associated with ipsilateral cerebrovascular ischemia, while calcified plaque is negatively associated with downstream ischemic events.

Association between Snoring and High-Risk Carotid Plaque Features.

Objectives Previous studies have demonstrated an association between snoring and carotid disease independent of sleep apnea. The aim of this study was to quantify the association between self-reported snoring and high-risk carotid plaque features on magnetic resonance imaging (MRI) that predict stroke. Study Design Cross-sectional. Setting Tertiary care university hospital and affiliated county hospital. Methods We surveyed 133 subjects with asymptomatic carotid artery disease that had been previously evaluated with high-resolution MRI. The survey captured data on self-reported snoring (exposure) and covariates (age, sex, body mass index, and sleep apnea via the STOP-Bang questionnaire). A subset of patients underwent home sleep apnea testing. High-risk carotid plaque features were identified on the high-resolution MRI and included thin/ruptured fibrous cap and intraplaque hemorrhage (outcomes). We quantified the association between snoring and high-risk carotid plaque features with the chi-square test (unadjusted analysis) and multivariate logistic regression adjusting for the covariates. Results Of 133 subjects surveyed, 61 (46%) responded; 32 (52%) reported snoring. Significantly higher proportions of snorers than nonsnorers had a thin/ruptured fibrous cap (56% vs 25%, P = .01) and intraplaque hemorrhage (63% vs 29%, P < .01). In multivariate analysis, snoring was associated with thin/ruptured fibrous cap (odds ratio, 4.4; 95% CI, 1.1-16.6; P = .04) and intraplaque hemorrhage (odds ratio, 8.2; 95% CI, 2.1-31.6; P < .01) after adjusting for age, sex, body mass index, and sleep apnea. Conclusion This pilot study suggests a significant independent association between snoring and high-risk carotid plaque features on MRI. Further study is warranted to confirm these results in a larger cohort of subjects.

High-risk carotid plaque: lessons learned from histopathology

The pathophysiology and natural history of atherosclerotic carotid disease is predicated on a more extensive knowledge of lesion progression gained in the studies conducted in the coronary arteries, and these will be reviewed. While the precise sequence of lesion progression leading to carotid plaque vulnerability and cerebrovascular events remain less well understood, specific early and more advanced progressive lesion morphologies associated with stroke risk have been characterized. Of late, there has been a conscious effort for stroke prevention in symptomatic and asymptomatic patients to move beyond luminal stenosis as the only guidance to predict future cerebrovascular events. Driving this strategy are recent advances in medical imaging modalities to assess carotid atherosclerosis vulnerability particularly involving molecular imaging, which is now positioned at the forefront to provide a more detailed and mechanistic assessment of stroke risk. As such, we will spotlight the pathology of high-risk carotid plaques in patients with symptomatic and asymptomatic carotid disease with further reference into more recent mechanistic insights involving a recognized macrophage-mediated inflammatory change, intraplaque neoangiogenesis/hemorrhage, hypoxia, and microcalcification, as potential morphologic indicators of stroke risk.

Imaging of high-risk carotid plaques: ultrasound

Duplex ultrasonography has a well-established role in the assessment of the degree of stenosis caused by carotid atherosclerosis. This assessment is derived from Doppler velocity changes induced by the narrowing lumen of the artery. New research into the mechanisms for plaque rupture and atheroembolic stroke indicates that the degree of narrowing is an imperfect predictor of stroke risk, and that other factors, such as plaque composition and remodeling and biomechanical forces acting on the plaque, can play a role. New advances in ultrasound imaging technology have made it possible to investigate these measures of plaque vulnerability to identify pre-embolic unstable carotid plaques. Efforts have been made to quantify the morphologic appearance of the plaque in B-mode images and to correlate them with histology. Additional research has resulted in the first generation of clinically available 3-dimensional ultrasound transducers that reduce operator-dependence and variability. Finally, ultrasonography provides real-time imaging and physiologic information that can be utilized to measure disruptive forces acting on carotid plaques. We review some of these exciting developments in ultrasonography and discuss how these may impact clinical practice.

Transcranial Doppler monitoring for microemboli: a marker of a high-risk carotid plaque

In the United States, 90% of carotid intervention is being performed for asymptomatic carotid stenosis, even though 90% of patients would be better treated with intensive medical therapy. This is being justified by comparing risks of stroke or death with medical therapy during clinical trials completed decades ago (approximately 2% per year) with risks of intervention with carotid artery stenting (CAS) versus carotid endarterectomy in recent trials that did not have a medical arm. Such extrapolations are, simply put, invalid. Even though the two most recent papers comparing carotid endarterectomy with CAS reported that the long-term risk (after first deducting periprocedural risks) is similar to that with medical therapy (approximately 0.5% per year), when the periprocedural risks are considered (approximately 3% with stenting v 1.5% with CAS), most patients would be better treated with intensive medical therapy. Furthermore, it must be recognized that the low risks observed in clinical trials with highly selected surgeons and interventionalists are much lower than in real-world practice. It is therefore necessary to have ways to identify, among patients with asymptomatic carotid stenosis, the few (approximately 10% to 15%) who could benefit from intervention. Indicators of vulnerable plaque, such as ulceration, juxtaluminal lucent plaque, intraplaque hemorrhage on magnetic resonance imaging, and plaque inflammation on positron emission tomography/computed tomography are in development for that purpose. The best-validated approach is detection of microemboli on transcranial Doppler. A prospective single-center study of 468 patients showed that microemboli identified high-risk asymptomatic stenosis; this was validated by a prospective multicenter international study in 467 patients. Increased risk with microemboli persisted in the era of lower risks with intensive medical therapy. Patients with asymptomatic carotid stenosis should not be offered CAS or carotid endarterectomy without first being identified as high risk; percent stenosis does not do so. Currently, the best way to improve the risk to benefit ratio for intervention is transcranial Doppler embolus detection.

Imaging of the high-risk carotid plaque: magnetic resonance imaging

The emergence of the concept of high-risk atherosclerotic plaque has led to considerable interest in noninvasive imaging techniques to identify high-risk features before clinical sequelae. For plaques in the carotid arteries, magnetic resonance imaging has undergone considerable histologic validation to link imaging features to indicators of plaque instability, including plaque burden, intraplaque hemorrhage, fibrous cap disruption, lipid rich necrotic core, and calcification. Recently introduced imaging technologies, especially those focused on three-dimensional imaging sequences, are now poised for integration into the clinical workup of patients with suspected carotid atherosclerosis. The purpose of this article is to review the carotid plaque magnetic resonance imaging techniques that are most ready for integration into the clinic.

Predicting Stroke Risk in Patients with Carotid Artery Stenosis Using Contrast Enhanced Carotid Duplex Ultrasound to Quantify Plaque Vasa-Vasorum Volume: Results of a Pilot Study

Introduction: In selecting patients for carotid revascularization, relying solely on symptoms and/or degree of stenosis is not sufficient. Patients with severe stenosis often remain asymptomatic, while other patients with moderate stenosis experience stroke. In contemporary practice, surgery or intervention is carried out much more often in asymptomatic patients. With the advent of improved medical management, the indications for surgery or intervention in the asymptomatic have become unclear. We utilized a technique for measuring Plaque Vasavasorum Volume (PVV) using Contrast Enhanced Carotid Duplex Ultrasound (CECDU) as a novel method for identifying asymptomatic patients with carotid artery stenosis who are at highest risk for stroke and thus more likely to benefit from early revascularization. Objective: To establish the diagnostic accuracy and reliability of PVV measured by CE-CDU in identifying high risk carotid plaques and to identify a diagnostic cut-off point beyond which the risk of stroke exceeds the risk of surgery/intervention in asymptomatic patients with carotid stenosis. Methods: The Stroke Prevention with Plaque Vasa-vasorum in Carotid Stenosis Study (SPIVICS) is a two phase multi-center double blinded prospective study. The first phase is a cross-sectional study of patients who qualify for carotid endarterectomy per current guidelines (asymptomatic patients with >70% stenosis and symptomatic patients with >50% stenosis). End points are analyzed using standard univariate and multivariate regression, correlation and diagnostic analyses. Outcomes: Primary outcome relating to plaque morphology is the PVV volume. Clinical outcomes are neurologic symptoms (Amaurosis fugax, transient ischemic attack, and stroke) and asymptomatic events detected on imaging. Results: A total of 16 patients were examined in this pilot study. Three were leadin subjects and four of them had severe calcified plaque and VV was not visualized. For those who had a successful screen, Mean age was 69 (± 7) years, Five males and the mean plaque VVV was 0.29 (± 0.62) mm. Conclusion: Plaque Vasa-vasorum Volume is a promising predictor of stroke risk. By identifying patients who are truly at high risk for stroke, PVV measured by CECDU will establish more reliable criteria for patient selection for intervention. This in turn will help with stroke prevention, limit disability, save lives, and expend health care resources in a more selective manner.

Usefulness of Plaque Magnetic Resonance Imaging in Identifying High-Risk Carotid Plaques Irrespective of the Degree of Stenosis.

ObjectiveMeasurement of the degree of stenosis is not enough to decide on the treatment strategy for patients with carotid stenosis. Plaque morphology examination is needed for such a decision-making. Thus, we evaluated the usefulness of plaque magnetic resonance imaging (MRI) to decide on the modality of treatment for patients with carotid atherosclerotic plaques.Materials and MethodsFifteen patients presenting with carotid stenosis between 2014 and 2016 were included. They underwent angiography for measurement of the degree of stenosis. Carotid plaques were visualized using MRI.ResultsThere were six (40%) stable and nine (60%) unstable plaques. Seven symptomatic patients (77.7%) had unstable lesions and two symptomatic patients (33.3%) had stable lesions (p = 0.096). There were six (40%) intraplaque hemorrhage (IPH) cases. There were six symptomatic patients (100%) in the IPH group and three symptomatic patients (33.3%) in the non-IPH group (p = 0.013). The mean stenosis degree was 58.9% in the IPH group and 70.4% in the non-IPH group (p = 0.094). Symptoms occurred irrespective of the degree of the stenosis in the IPH groups. In the IPH group, the recurrent ischemic cerebrovascular event rate was 33.3%. Particularly, the recurrent ischemic cerebrovascular event rate was 66.7% in the IPH group with mild stenosis treated with medications.ConclusionIPH in plaque MRI is significantly associated with ischemic symptoms and has a high risk for subsequent ischemic cerebrovascular events irrespective of the degree of stenosis. Plaque MRI is a useful tool in predicting symptomatic risks for carotid stenosis irrespective of the degree of such stenosis.

High-risk carotid plaques identified by CT-angiogram can predict acute myocardial infarction.

Prior studies identified the incremental value of non-invasive imaging by CT-angiogram (CTA) to detect high-risk coronary atherosclerotic plaques. Due to their superficial locations, larger calibers and motion-free imaging, the carotid arteries provide the best anatomic access for the non-invasive characterization of atherosclerotic plaques. We aim to assess the ability of predicting obstructive coronary artery disease (CAD) or acute myocardial infarction (MI) based on high-risk carotid plaque features identified by CTA. We retrospectively examined carotid CTAs of 492 patients that presented with acute stroke to characterize the atherosclerotic plaques of the carotid arteries and examined development of acute MI and obstructive CAD within 12-months. Carotid lesions were defined in terms of calcifications (large or speckled), presence of low-attenuation plaques, positive remodeling, and presence of napkin ring sign. Adjusted relative risks were calculated for each plaque features. Patients with speckled (<3mm) calcifications and/or larger calcifications on CTA had a higher risk of developing an MI and/or obstructive CAD within 1 year compared to patients without (adjusted RR of 7.51, 95%CI 1.26-73.42, P = 0.001). Patients with low-attenuation plaques on CTA had a higher risk of developing an MI and/or obstructive CAD within 1 year than patients without (adjusted RR of 2.73, 95%CI 1.19-8.50, P = 0.021). Presence of carotid calcifications and low-attenuation plaques also portended higher sensitivity (100 and 79.17%, respectively) for the development of acute MI. Presence of carotid calcifications and low-attenuation plaques can predict the risk of developing acute MI and/or obstructive CAD within 12-months. Given their high sensitivity, their absence can reliably exclude 12-month events.

High-Risk Carotid Plaque Characteristics and Implications for Carotid Stenting

High-Risk Carotid Plaque Characteristics and Implications for Carotid Stenting

Serum vitamin D level is negatively associated with carotid atherosclerosis in Korean adults

The present study investigated the associations between serum vitamin D levels and carotid intima-media thickness (CIMT), carotid plaque and atherosclerosis in 71 Korean adults. CIMT and the presence of carotid plaque were assessed with a high-resolution B-mode ultrasound system, and carotid atherosclerosis was defined as a mean CIMT value >0.9 mm or the presence of carotid plaque. A vitamin D deficiency was associated with the presence of carotid plaque (adjusted odds ratio [aOR]: 9.25, 95% confidence interval [CI]: 1.52–56.3; p = 0.016). As serum vitamin D levels increased, the presence of high-risk carotid plaque decreased (aOR: 0.84, 95%CI: 0.72–0.99; p = 0.039). Serum vitamin D levels was negatively associated with carotid atherosclerosis (aOR: 0.86, 95%CI: 0.76–0.97; p = 0.018). Further studies are needed to investigate whether vitamin D supplementation would be effective for the prevention of atherosclerosis and cardiovascular diseases.