Nonstenotic Carotid Plaque Research Articles

Overview and Future Direction of Embolic Stroke of Undetermined Source from the Insights of CHALLENGE ESUS/CS Registry.

Cryptogenic stroke (CS) accounts for approximately one-fourth of acute ischemic strokes, with most cases derived from embolic etiologies. In 2014, embolic stroke of undetermined source (ESUS) was advocated and the efficacy of anticoagulant therapy was anticipated. However, 3 large-scale clinical trials failed to demonstrate the superiority of direct oral anticoagulants (DOACs) over aspirin, potentially due to the heterogeneous and diverse pathologies of ESUS, including paroxysmal atrial fibrillation (AF), arteriogenic sources such as nonstenotic carotid plaque and aortic complicated lesion (ACL), patent foramen oval (PFO), and nonbacterial thrombotic endocarditis (NBTE) related to active cancer.Transesophageal echocardiography (TEE) is one of the most effective imaging modalities for assessing embolic sources in ESUS and CS. The Mechanisms of Embolic Stroke Clarified by Transesophageal Echocardiography for Embolic Stroke of Undetermined Source/Cryptogenic Stroke (CHALLENGE ESUS/CS) registry is a multicenter registry that enrolled consecutive patients with CS who underwent TEE at 8 hospitals in Japan between April 2014 and December 2016. Their mean age was 68.7±12.8 years, and 455 patients (67.2%) were male. The median National Institutes of Health Stroke Scale (NIHSS) score was 2. Since 7 analyses have been conducted from each institution to date, novel and significant insights regarding embolic origins and pathophysiologies of ESUS and CS were elucidated from this multicenter registry. This review discusses the diagnosis and treatment of ESUS and CS, tracing their past and future directions. Meaningful insights from the CHALLENGE ESUS/CS registry are also referenced and analyzed.

Sex-Specific Risk Factors of Nonstenotic Carotid Plaque in Embolic Stroke of Unknown Source: A Case-Control Study.

Many ischemic strokes are diagnosed as embolic strokes of undetermined source (ESUS). Recent evidence suggests that nonstenotic carotid plaque (nsCP) may be a substantial contributor to the risk for ESUS. We aimed to investigate the risk factor profile associated with nsCP in ESUS and defined stroke etiologies. In this retrospective case-control study, we investigated consecutive patients with acute ischemic stroke due to ESUS, small-vessel disease, or cardioembolism proven by magnetic resonance imaging. The association of vascular risk factors age, arterial hypertension, diabetes, dyslipoproteinemia, body mass index, alcohol consumption, tobacco use, kidney failure, and history of stroke with the presence of nsCP was investigated using binary logistic regression analysis and further stratified by stroke etiology and sex. In total, 609 patients (median age, 76 years; 46% women) who were treated from 2018 to 2020 were considered. In patients with ESUS, sex played a more important role for the prevalence of nsCP than in defined etiologies. Female patients with ESUS had lower odds of exhibiting nsCP compared with male patients with ESUS (adjusted odds ratio, 0.36 [95% CI, 0.15-0.86]). In male patients with ESUS, we observed that age (adjusted odds ratio per 10-year increase, 2.55 [95% CI, 1.26-5.17]) and hypertension (adjusted odds ratio, 2.49 [95% CI, 0.56-11.1]) were the main risk factors for nsCP, whereas in female patients with ESUS also tobacco use was particularly relevant (adjusted odds ratio, 3.71 [95% CI, 0.61-22.5]). These results were in line with a sensitivity analysis in nsCP located ipsilateral to the infarct. Sex differences play an important role in nsCP prevalence in patients with ESUS. These findings may have important implications for the management in targeted secondary prevention following ESUS.

Subcortical infarcts in patients with nonstenotic cervical atherosclerotic disease

BackgroundPrior studies have elucidated a relationship between nonstenotic plaque in patients with cryptogenic embolic infarcts with a largely cortical topology, however, it is unclear if nonstenotic cervical internal carotid artery (ICA) plaque is relevant in subcortical cryptogenic infarct patterns. MethodsA nested cohort of consecutive patients with anterior, unilateral, and subcortical infarcts without an identifiable embolic source were identified from a prospective stroke registry (September 2019 - June 2021). Patients with extracranial stenosis >50% or cardiac sources of embolism were excluded. Patients with computed tomography angiography were included and comparisons were made according to the infarct pattern being lacunar versus non-lacunar. Prevalence estimates for cervical internal carotid artery (ICA) plaque presence were estimated with 95% confidence intervals (CI), and differences in plaque thickness and features were compared between sides. ResultsOf the 1684 who were screened, 141 met inclusion criteria (n=80 due to small vessel disease, n=61 cryptogenic). The median age was 66y (interquartile range, IQR 58-73) and the National Institutes of Health Stroke Scale score was 3 (IQR 1-5). There was a higher probability of finding excess plaque ipsilateral to the stroke (41.1%, 95% CI 33.3-49.3%) than finding excess contralateral plaque (29.1%, 95% CI 22.2-37.1%; p=0.03), but this was driven by patients with non-lacunar infarcts (excess ipsilateral vs. contralateral plaque frequency of 49.2% vs. 14.8%, p<0.001) rather than lacunar infarcts (35.0% vs. 40.0%, p=0.51). ConclusionsThe probability of finding ipsilateral, nonstenotic carotid plaque in patients with subcortical cryptogenic strokes exceeds the probability of contralateral plaque and is driven by larger subcortical infarcts, classically defined as being cryptogenic. Approximately 1 in 3 unilateral anterior subcortical infarcts may be due to nonstenotic ICA plaque.

Abstract Number ‐ 239: Subcortical Infarcts in Patients with Nonstenotic Cervical Atherosclerotic Disease

Introduction Prior studies have elucidated a relationship between nonstenotic plaque in patients with cryptogenic embolic (cortical) infarcts, however it is unclear if nonstenotic carotid plaque is relevant in subcortical infarct patterns. Methods A nested cohort of consecutive patients with anterior, unilateral, subcortical infarcts without an identifiable embolic source were identified from a prospective stroke registry (September 2019 ‐ June 2021). Patients with extracranial stenosis &gt;50% were excluded. Patients with computed tomography angiography were included and comparisons made according to infarct pattern being lacunar (single lesion &lt; 1.5cm on computed tomography [CT] or &lt; 2.0cm on diffusion weighted imaging [DWI]) versus cryptogenic (≥ 1.5cm on CT or ≥ 2.0cm on DWI, or scattered subcortical lesions). Prevalence estimates for cervical internal carotid artery (ICA) plaque presence were estimated with 95% confidence intervals (CI), and differences in plaque thickness and features were compared between sides. Results Of the 1684 who were screened, 141 met inclusion criteria (n = 80 due to small vessel disease, n = 61 cryptogenic). The median age was 66y (interquartile range, IQR 58–73) and National Institutes of Health Stroke Scale score was 3 (IQR 1–5). There was a higher probability of finding excess plaque ipsilateral to the stroke (41.1%, 95%CI 33.3‐49.3%) than finding excess contralateral plaque (29.1%, 95%CI 22.2‐37.1%; p = 0.03), but this was driven by patients with cryptogenic infarcts (excess ipsilateral vs. contralateral plaque frequency of 49.2% vs. 14.8%, p&lt; 0.001) and not lacunar disease (35.0% vs. 40.0%, p = 0.51). Conclusions The probability of finding ipsilateral, nonstenotic carotid plaque in patients with subcortical cryptogenic strokes exceeds the probability of contralateral plaque and is driven by larger subcortical infarcts, classically defined as being cryptogenic. Approximately 1 in 3 unilateral anterior subcortical infarcts may be due to nonstenotic ICA plaque.

The Attributable Risk of Nonstenotic Cervical Carotid Plaque in Cryptogenic Embolic Stroke

Nonstenotic plaque (NSP) of a cervical artery feeding the territory of acute cerebral infarction is increasingly recognized as a cause of cryptogenic stroke. While these atherosclerotic lesions are not associated with significant luminal stenosis (&lt;50%), the probability of finding such plaque exceeds chance and is more common in parent vessels rather than vessels supplying brain regions remote from infarction. More than 20%–30% of patients with unilateral hemispheric embolic stroke of undetermined source may be attributable to cervical internal or common carotid NSP. For these patients, randomized clinical trials have not shown a significant benefit of revascularization (endarterectomy or stenting), and optimal secondary prevention strategies rely on risk factor modification and antiplatelet therapy. Heightened awareness of this subtle finding may inform second‐tier diagnostic testing recommendations for occult stroke mechanisms (eg, monitoring for paroxysmal atrial fibrillation or hypercoagulability testing). Furthermore, recognition of NSP as a culprit lesion may lead to more targeted pharmacologic strategies aimed at stabilizing plaque. Recent guidelines have also incorporated evidence of plaque vulnerability (eg, intraplaque hemorrhage or lipid‐rich necrotic core) in decision making regarding revascularization approaches. In this review, the epidemiology and management of NSP in patients with cryptogenic embolic infarction is summarized, with an emphasis on recognition of NSP such that future clinical trials can be designed to test novel interventional strategies against current medical management of embolic stroke of undetermined source.

Nonstenotic Carotid Plaques and Embolic Stroke of Undetermined Source: A Multimodality Review.

Symptomatic nonstenotic carotid artery disease has been increasingly recognized as a thromboembolic source in patients who would otherwise be classified as having embolic stroke of undetermined source. Evidence suggests that certain plaque features seen on sonography, CT, and MR imaging in nonstenotic carotid artery disease may predispose to recurrent stroke in patients with embolic stroke of undetermined source. We performed a focused literature review to further study plaque features in the context of embolic stroke of undetermined source and to determine which plaque features may be associated with ipsilateral ischemic events in such patients. Plaque thickness as seen on both ultrasound and CT appears to have a consistent association with ipsilateral stroke in patients with embolic stroke of undetermined source across multiple studies. Intraplaque hemorrhage as seen on MR imaging is now understood to have a strong association with ipsilateral stroke in patients with embolic stroke of undetermined source. Continued study of various plaque features as seen on different modalities is warranted to uncover other potential associations.

非狭窄性颈动脉斑块与前循环不明原因栓塞性卒中的相关性研究 Correlation of Non-Stenotic Carotid Plaque with Anterior Circulation Embolic Stroke of Undetermined Source

非狭窄性颈动脉斑块与前循环不明原因栓塞性卒中的相关性研究 Correlation of Non-Stenotic Carotid Plaque with Anterior Circulation Embolic Stroke of Undetermined Source

Etiologic reclassification of cryptogenic stroke after implantable cardiac monitoring and computed tomography angiography re-assessment

IntroductionDifferent mechanisms may underlie cryptogenic stroke, including subclinical atrial fibrillation (AF), nonstenotic carotid plaques (NCP), and aortic arch atherosclerosis (AAA). In a cohort of cryptogenic stroke patients, we aimed to: (1) evaluate the prevalence of subclinical AF, NCP, and AAA, and reclassify the etiology accordingly; (2) compare the clinical features of patients with reclassified etiology with those with confirmed cryptogenic stroke.MethodsData of patients hospitalized for cryptogenic stroke between January 2018 and February 2021 were retrospectively analyzed. Patients were included if they received implantable cardiac monitoring (ICM) to detect subclinical AF. Baseline computed tomography angiography (CTA) was re-evaluated to assess NCP and AAA. Since aortic plaques with ulceration/intraluminal thrombus were considered pathogenetic during the initial workup, only patients with milder AAA were included. Stroke etiology was reclassified as “cardioembolic”, “atherosclerotic”, or “mixed” based on the detection of AF and NCP/AAA. Patients with “true cryptogenic” stroke (no AF, ipsilateral NCP, or AAA detected) were compared with those with reclassified etiology.ResultsAmong 63 patients included, 21 (33%) were diagnosed with AF (median follow-up time of 15 months), 12 (19%) had ipsilateral NCP, and 6 (10%) had AAA. Stroke etiology was reclassified in 30 patients (48%): cardioembolic in 14 (22%), atherosclerotic in 9 (14%), and mixed in 7 (11%). Patients with true cryptogenic stroke were younger compared to those with reclassified etiology (p = 0.001).DiscussionOne or more potential covert stroke sources can be recognized in half of the patients with a cryptogenic stroke through long-term cardiac monitoring and focused CTA re-assessment.

Characteristics of non-stenotic carotid plaque in embolic stroke of undetermined source compared with cardiogenic embolism: a retrospective cross-sectional observational study

BackgroundNon-stenotic carotid plaque is considered an important etiology of embolic stroke of undetermined source (ESUS). However, only a few previous studies included a negative control group, and the characteristics of non-stenotic carotid plaque in ESUS have yet to be investigated. The objective of this study is to explore the clinical characteristics of ESUS and the correlation between non-stenotic carotid plaque and ESUS.MethodsThis is a single-center, retrospective cross-sectional observational study conducted to compare differences in clinical information among ESUS, CE, and large-artery atherosclerosis (LAA), as well as the prevalence of non-stenotic carotid plaque and non-stenotic carotid plaque with low echo between patients with ESUS and CE in Changzhou No.2 People’s Hospital from January 2020 to January 2022. Ultrasound was used to evaluate the characteristics of non-stenotic carotid plaque and vulnerable carotid plaque was defined as plaque with low echo. The binary logistic regression model was used to analyze the relationship between the characteristics of non-stenotic carotid plaque and ESUS. The receiver-operating characteristic curve was used to evaluate the diagnostic efficiency of the characteristics of non-stenotic carotid plaque for ESUS.ResultsWe had a final studying population of 280 patients including 81 with ESUS, 37 with CE, and 162 with LAA. There were no differences in clinical features between ESUS and LAA, but in the comparison of CE and ESUS, there were differences in age, smoking, hypertension, levels of triglyceride, total cholesterol, and low density lipoprotein cholesterol. In ESUS, the prevalence of non-stenotic carotid plaque was more common on the ipsilateral side of stroke than in CE [55 (67.90%) vs. 18 (48.65%), p = 0.046], so was the prevalence of non-stenotic carotid plaque with low echo [38 (46.91%) vs. 5 (13.51%), p < 0.001]. Logistic regression analysis showed that the prevalence of non-stenotic carotid plaque (OR: 4.19; 95% CI: 1.45–12.11; p = 0.008) and the prevalence of non-stenotic carotid plaque with low echo (OR: 5.12; 95% CI: 1.55–16.93; p = 0.007) were, respectively, the independent predictors of ESUS. The results receiver-operating characteristic (ROC) curve showed that the combination of age, hypertension, and ipsilateral non-stenotic carotid plaque with low echo had the best diagnostic efficiency for ESUS (0.811; 95%CI: 0.727–0.896; p < 0.001).ConclusionOur results suggest that ipsilateral vulnerable non-stenotic carotid plaque is associated with ESUS in anterior circulation infarction.

Features of non-stenotic carotid plaque on computed tomographic angiography in patients with embolic stroke of undetermined source.

PurposeEmbolic stroke of undetermined source (ESUS) is a subset of cryptogenic stroke constituting a large proportion of acute ischemic strokes. This study aimed to assess the features of non-stenotic carotid plaque (<50%) on computed tomographic angiography (CTA) and to evaluate the association between non-stenotic carotid plaque and ESUS.MethodsFrom January 1 to December 31, 2019, a total of 60 consecutive patients with primary unilateral ESUS and <50% carotid artery stenosis, as determined using screening ultrasonography, were hospitalized in the Department of Neurology of our hospital. All enrolled patients underwent CTA to determine the composition and morphological features of non-stenotic carotid plaques using consecutive sections in both carotid arteries. The features of these plaques with and without ipsilateral stroke in patients with ESUS were compared.ResultsSixty ESUS images were included in the study, with 85 plaques. Forty-five (52.9%) of these plaques were ipsilateral and 40 (47.1%) were contralateral to the stroke. Compared to that of the contralateral plaque group, the maximum carotid plaque thickness and plaque length of the ipsilateral group were greater (2.1 mm vs. 1.5 mm, p = 0.03; 20.8 mm vs. 12.1 mm, p = 0.02); however, there were no significant differences in the degree of luminal stenosis, presence of soft plaque and calcified plaque, and the number of ulcers on the plaque surface between the two groups. Similarly, the number of plaques with thickness >3 mm in the ipsilateral group was greater than in the contralateral group (30 vs. 13, p = 0.01). A lipid core was more common in individuals with ipsilateral strokes than in those with contralateral strokes (19 vs. 7, p = 0.02). Regression analysis showed that plaque lipid core area was an independent risk factor for ESUS (odds ratio, 1.92; 95% confidence interval, 1.22–3.04; p = 0.03).ConclusionsNon-stenotic carotid plaques could be an etiology of acute ischemic strokes classified as ESUS. The presence of a lipid core was a risk factor in individuals with non-stenotic carotid plaques.

Change of Heart: The Underexplored Role of Plaque Hemorrhage in the Evaluation of Stroke of Undetermined Etiology.

In the evaluation of embolic strokes of undetermined source, great emphasis is often placed on cardiovascular disease, namely on atrial fibrillation. Other pathophysiologic mechanisms, however, may also be involved. Carotid artery intraplaque hemorrhage (IPH)—the presence of blood components within an atheromatous plaque—has become increasingly recognized as a possible etiologic mechanism in some cryptogenic strokes. IPH is a marker of plaque instability and is associated with ipsilateral neurologic ischemic events, even in nonstenotic carotid plaques. As recognition of carotid IPH as an etiology of embolic strokes has grown, so too has the complexity with which such patients are evaluated and treated, particularly because overlaps exist in the risk factors for atrial fibrillation and IPH. In this article, we review what is currently known about carotid IPH and how this clinical entity should be approached in the context of the evaluation of embolic strokes of undetermined source.

Age Alters Prevalence of Left Atrial Enlargement and Nonstenotic Carotid Plaque in Embolic Stroke of Undetermined Source.

Nonstenotic carotid plaque and undetected atrial fibrillation are potential mechanisms of embolic stroke of undetermined source (ESUS), but it is unclear which is more likely to be the contributing stroke mechanism. We explored the relationship between left atrial enlargement (LAE) and nonstenotic carotid plaque across age ranges in an ESUS population. A retrospective multicenter cohort of consecutive patients with unilateral, anterior circulation ESUS was queried (2015 to 2021). LAE and plaque thickness were determined by transthoracic echocardiography and computed tomography angiography, respectively. Descriptive statistics were used to compare plaque features in relation to age and left atrial dimensions. Among the 4155 patients screened, 273 (7%) met the inclusion criteria. The median age was 65 years (interquartile range [IQR] 54-74), 133 (48.7%) were female, and the median left atrial diameter was 3.5 cm (IQR 3.1-4.1). Patients with any LAE more frequently had hypertension (85.9% versus 67.2%, P<0.01), diabetes (41.0% versus 25.6%, P=0.01), dyslipidemia (56.4% versus 40.0%, P=0.01), and coronary artery disease (22.8% versus 11.3%, P=0.02). Carotid plaque thickness was greater ipsilateral versus contralateral to the stroke hemisphere in the overall cohort (median 1.9 mm [IQR 0-3] versus 1.5 mm [IQR 0-2.6], P<0.01); however, this was largely driven by the subgroup of patients without any LAE (median 1.8 mm [IQR 0-2.9] versus 1.5 mm [IQR 0-2.5], P<0.01). Compared with patients ≥70 years, younger patients had more carotid plaque ipsilateral versus contralateral (mean difference 0.42 mm±1.24 versus 0.08 mm±1.54, P=0.047) and less moderate-to-severe LAE (6.3% versus 15.3%, P=0.02). Younger patients with ESUS had greater prevalence of ipsilateral nonstenotic plaque, while the elderly had more LAE. The differential effect of age on the probability of specific mechanisms underlying ESUS should be considered in future studies.

Association of Carotid Plaque Morphology and Glycemic and Lipid Parameters in the Northern Manhattan Study.

Low Gray-Scale Median (GSM) index is an ultrasonographic parameter of soft, lipid rich plaque morphology that has been associated with stroke and cardiovascular disease (CVD). We sought to explore the contribution of the modifiable and not-modifiable cardiovascular risk factors (RFs) to vulnerable plaque morphology measured by the low GSM index. A total of 1,030 stroke-free community dwelling individuals with carotid plaques present (mean age, 71.8 ± 9.1; 58% women; 56% Hispanic, 20% Non-Hispanic Black, 22% Non-Hispanic White) were assessed for minimum GSM (min GSM) using high-resolution B-mode carotid ultrasound. Multiple linear regression models were used to evaluate the association between RFs and minGSM after adjusting for sociodemographic characteristics. Within an individual, median plaque number was 2 (IQR: 1–3) and mean plaque number 2.3 (SD: 1.4). Mean minGSM was 78.4 ± 28.7 (IQR: 56–96), 76.3 ± 28.8 in men and 80 ± 28.5 in women; 78.7 ± 29.3 in Hispanics participants, 78.5 ± 27.2 in Non-Hispanic Black participants, and 78.2 ± 29 in Non-Hispanic white participants. In multivariable adjusted model, male sex (β = −5.78, p = 0.007), obesity BMI (β = −6.92, p = 0.01), and greater levels of fasting glucose (β = −8.02, p = 0.02) and LDL dyslipidemia (β = −6.64, p = 0.005) were positively associated with lower minGSM, while presence of glucose lowering medication resulted in a significant inverse association (β = 7.68, p = 0.04). Interaction (with p for interaction <0.1) and stratification analyses showed that effect of age on minGSM was stronger in men (β = −0.44, p = 0.03) than in women (β = −0.20, p = 0.18), and in individuals not taking glucose lowering medication (β = −0.33, p = 0.009). Our study has demonstrated an important contribution of glycemic and lipid metabolism to vulnerable, low density or echolucent plaque morphology, especially among men and suggested that use of glucose lowering medication was associated with more fibrose-stable plaque phenotype (greater GSM). Further research is needed to evaluate effects of medical therapies in individuals with vulnerable, low density, non-stenotic carotid plaques and how these effects translate to prevention of cerebrovascular disease.

Non-stenotic Carotid Plaques in Embolic Stroke of Unknown Source.

Embolic stroke of unknown source (ESUS) represents one in five ischemic strokes. Ipsilateral non-stenotic carotid plaques are identified in 40% of all ESUS. In this narrative review, we summarize the evidence supporting the potential causal relationship between ESUS and non-stenotic carotid plaques; discuss the remaining challenges in establishing the causal link between non-stenotic plaques and ESUS and describe biomarkers of potential interest for future research. In support of the causal relationship between ESUS and non-stenotic carotid plaques, studies have shown that plaques with high-risk features are five times more prevalent in the ipsilateral vs. the contralateral carotid and there is a lower incidence of atrial fibrillation during follow-up in patients with ipsilateral non-stenotic carotid plaques. However, non-stenotic carotid plaques with or without high-risk features often coexist with other potential etiologies of stroke, notably atrial fibrillation (8.5%), intracranial atherosclerosis (8.4%), patent foramen ovale (5–9%), and atrial cardiopathy (2.4%). Such puzzling clinical associations make it challenging to confirm the causal link between non-stenotic plaques and ESUS. There are several ongoing studies exploring whether select protein and RNA biomarkers of plaque progression or vulnerability could facilitate the reclassification of some ESUS as large vessel strokes or help to optimize secondary prevention strategies.

Nonstenotic Carotid Plaques in Ischemic Stroke: Analysis of the STRATIS Registry.

Few studies assess nonstenotic carotid plaques on CTA, and the causative role of these plaques in stroke is not entirely clear. We used CTA to determine the prevalence of nonstenotic carotid plaques (<50%), plaque features, and their association with ipsilateral strokes in patients with cardioembolic and cryptogenic strokes. Data were from the Systematic Evaluation of Patients Treated With Neurothrombectomy Devices for Acute Ischemic Stroke (STRATIS) registry, a prospective, nonrandomized registry of patients undergoing thrombectomy with the Solitaire device. The prevalence of nonstenotic carotid plaques ipsilateral and contralateral to the stroke was compared in patients with cryptogenic and cardioembolic strokes. Plaque features were further compared within both subgroups between patients with and without ipsilateral stroke. Adjusted associations among nonstenotic carotid plaque, plaque characteristics, and ipsilateral stroke in both subgroups were determined with logistic regression. Of the 946 patients in the data base, 226 patients with cardioembolic stroke (median age, 72 years) and 141 patients with cryptogenic stroke (median age, 69 years) were included in the analysis. The prevalence of nonstenotic carotid plaque in the cardioembolic and cryptogenic subgroups was 33/226 (14.6%) and 32/141 (22.7%), respectively. Bilateral nonstenotic carotid plaques were seen in 10/226 (4.4%) patients with cardioembolic and 13/141 (9.2%) with cryptogenic strokes. Nonstenotic carotid plaques were significantly associated with ipsilateral strokes in the cardioembolic stroke (adjusted OR = 1.91; 95% CI, 1.15-3.18) and the cryptogenic stroke (adjusted OR = 1.69; 95% CI, 1.05-2.73) groups. Plaque irregularity, hypodensity, and per-millimeter increase in plaque thickness were significantly associated with ipsilateral stroke in the cryptogenic subgroup. Nonstenotic carotid plaques were significantly associated with ipsilateral stroke in cardioembolic and cryptogenic stroke groups, and there was an association of plaque irregularity and hypodense plaque with ipsilateral stroke in the cryptogenic group, suggesting these plaques could be a potential cause of stroke in these patient subgroups.

Sex Differences in Carotid Plaque Composition in Patients With Embolic Stroke of Undetermined Source.

BackgroundWe examined sex differences in nonstenotic carotid plaque composition in patients with embolic stroke of undetermined source (ESUS).Methods and ResultsPatients with anterior circulation ischemic stroke imaged with neck computed tomographic angiography who met criteria for ESUS or had atrial fibrillation were identified. Patients with atrial fibrillation were included as a negative control. Semiautomated plaque quantification software analyzed carotid artery bifurcations. Plaque subcomponent (calcium, intraplaque hemorrhage [IPH], and lipid rich necrotic core) volumes were compared by sex and in paired analyses of plaque ipsilateral versus contralateral to stroke. Multivariate linear regressions tested for associations. Ninety‐four patients with ESUS (55% women) and 95 patients with atrial fibrillation (47% women) were identified. Men with ESUS showed significantly higher volumes of calcified plaque (63.9 versus 19.6 mm3, P<0.001), IPH (9.4 versus 3.3 mm3, P=0.008) and a IPH/lipid rich necrotic core ratio (0.17 versus 0.07, P=0.03) in carotid plaque ipsilateral to stroke side than women. The atrial fibrillation cohort showed no significant sex differences in plaque volumes ipsilateral to stroke. Multivariate analyses of the ESUS cohort showed male sex was associated with IPHipsi (β=0.49; 95% CI, 0.11–0.87) and calciumipsi (β=0.78; 95% CI, 0.33–1.23). Paired plaque analyses in men with ESUS showed significantly higher calcified plaque (63.9 versus 34.1 mm3, P=0.03) and a trend of higher IPHipsi (9.4 versus 7.5 mm3, P=0.73) and lipid rich necrotic coreipsi (59.0 versus 48.4 mm3, P=0.94) volumes.ConclusionsSex differences in carotid plaque composition in ESUS suggest the possibility of a differential contribution of nonstenosing carotid plaque as a stroke mechanism in men versus women.

Abstract P316: Non-Stenotic Carotid Plaques in Ischemic Stroke - Analysis of the STRATIS Registry

Objective: To determine the prevalence of non-stenotic carotid plaques (&lt;50%) and their association with ipsilateral strokes. Methods: Data was analyzed from the STRATIS registry (Systematic Evaluation of Patients Treated With Neurothrombectomy Devices for Acute Ischemic Stroke)—a prospective, nonrandomized study of patients undergoing thrombectomy with the Solitaire device. Prevalence of non-stenotic carotid plaques, ipsilateral and contralateral to the stroke was compared in patients with ESUS and cardioembolic strokes. Plaque features were further compared within both subgroups between patients with and without ipsilateral stroke. Uni- and multivariable logistic regression was performed to determine associations between non-stenotic carotid plaque, plaque characteristics, and ipsilateral stroke in both subgroups. Results: Of the 946 patients in the database, 226 patients with cardioembolic stroke (median age, 72 years) and 141 patients with ESUS (median age, 69 years) were included in the analysis.The prevalence of non-stenotic carotid plaque in the cardioembolic and ESUS subgroups was 33/226 (14.6%) and 32/141(22.7%) respectively. Bilateral non-stenotic carotid plaques were seen in 10/226(4.4%) cardioembolic and 13/141(9.2%) ESUS patients. Non-stenotic carotid plaques were significantly associated with ipsilateral strokes in cardioembolic stroke (aOR,1.91 [95% CI,1.15-3.18]) and in ESUS (aOR,1.69 [95% CI, 1.05-2.73]). Plaque irregularity, plaque hypodensity and increasing plaque thickness were significantly associated with ipsilateral stroke, only in the ESUS subgroup. Conclusion: Non-stenotic carotid plaques were significantly associated with ipsilateral stroke in cardioembolic and ESUS subgroups and there was increased association of hypodense plaque, increasing plaque thickness and plaque irregularity with ipsilateral stroke in the ESUS subgroup, suggesting these plaques could be a potential cause of stroke in these patient subgroups.

Abstract P372: Sex-Differences in Carotid Plaque Composition in Patients With Embolic Stroke of Undetermined Source

Introduction: Non-stenotic carotid plaque may be the cause of ischemic stroke in some patients with embolic stroke of undetermined source (ESUS). We examined sex-differences in carotid plaque composition in patients with ESUS. Methods: A retrospective cohort of anterior circulation acute ischemic stroke patients with CTA head/neck and meeting criteria for ESUS was identified. Carotid artery bifurcations (4cm segment) ipsilateral to the stroke were evaluated using a semi-automated segmentation software to measure total plaque volume and plaque subcomponents (calcium, intraplaque hemorrhage [IPH], and lipid rich necrotic core [LRNC]). Sex-differences in baseline vascular risk factors and plaque subcomponent volumes were tested by Mann-Whitney U tests or students t-tests for continuous variables and Fisher’s exact test for categorical variables. Associations of each plaque subcomponent were tested by multivariate linear regressions. Results: Of 94 patients, 55% were women. Mean age of the cohort was 65 years. Women had higher body mass indices than men (29.2 vs 26.3; p=0.02). There were no other significant differences in age or vascular risk factors between men and women. Overall plaque volume (p=0.001) was significantly greater in men as was the volume of calcification (p&lt;0.001) and IPH (p=0.008) in carotid arteries ipsilateral to the stroke (Figure). No significant difference was detected in LRNC volume by sex (p=0.84). In multivariate analysis, male sex (β=45.9, 95% CI 18.0-73.7, p=0.002) and older age (β=1.85, 95% CI 0.73-3.0, p=0.001) were significantly associated with calcified plaque volume, and male sex (β= 6.7, 95% CI 2.6-10.8, p=0.002) with IPH. Neither age nor sex was significantly associated with LRNC. Conclusions: Sex-differences in carotid plaque composition in ESUS suggest the possibility of a differential contribution of non-stenotic carotid plaque to stroke mechanism in men versus women.

Letter by Nastro Siniscalchi and Raffa Regarding Article, “Prevalence of Ipsilateral Nonstenotic Carotid Plaques on Computed Tomography Angiography in Embolic Stroke of Undetermined Source”

Letter by Nastro Siniscalchi and Raffa Regarding Article, “Prevalence of Ipsilateral Nonstenotic Carotid Plaques on Computed Tomography Angiography in Embolic Stroke of Undetermined Source”

Response by Ospel and Goyal to Letter Regarding Article, “Prevalence of Ipsilateral Nonstenotic Carotid Plaques on Computed Tomography Angiography in Embolic Stroke of Undetermined Source”

Response by Ospel and Goyal to Letter Regarding Article, “Prevalence of Ipsilateral Nonstenotic Carotid Plaques on Computed Tomography Angiography in Embolic Stroke of Undetermined Source”