Large-artery Atherosclerosis Group Research Articles

Outcome Comparison of Endovascular Treatment for Acute Large Vessel Occlusion Due to Large Artery Atherosclerosis and Cardioembolism in the Chinese Population: Data from the ANGEL Registry.

Studies on outcome comparison after endovascular treatment (EVT) for large vessel occlusion (LVO) between large artery atherosclerosis (LAA) and cardioembolism (CE) in the Asian population are scarce. We aimed to compare the baseline characteristics and clinical outcomes after EVT for anterior circulation LVO with LAA and CE in the Chinese population. Patients were selected from the ANGEL registry and divided into LAA and CE groups. The primary outcome was the 90-day modified Rankin Scale (mRS) 0-2. The secondary outcomes were 90-day mRS distribution, 90-day mRS 0-1, 90-day mRS 0-3, and early neurological improvement. The safety outcomes included death, symptomatic intracranial hemorrhage, and any intracranial hemorrhage. We conducted logistic regression models with adjustments to compare the outcomes. A total of 632 patients were included, of whom, 488 were in the LAA group and 144 were in the CE group. No significant difference in 90-day mRS 0-2 was observed between LAA and CE groups (55.7%vs.43.1%, odds ratio[OR] 1.19, 95% confidence interval(CI), 0.92-1.53, P=0.190). The LAA group exhibited a higher frequency of mRS 0-3 compared to the CE group (69.1% vs 32.6%, OR1.32, 95% CI 1.02-1.72, P=0.038). However, the incidence of death within 90 days did not significantly differ between the LAA and CE groups (10.9%vs.24.3%, OR0.91, 95% CI0.66-1.25, P=0.545), nor did the occurrences of symptomatic intracranial hemorrhage(SICH) (4.5%vs.9.7%,OR1.08, 95% CI 0.65-1.78, P=0.779) or intracranial hemorrhage(ICH) (21.9%vs.30.6%, OR 0.94, 95% CI0.71-1.25, P=0.680). Moreover, no significant disparities were detected in other outcomes between the two groups (All P>0.05). In the ANGEL registry, a higher prevalence of patients undergoing EVT for acute anterior circulation LVO with LAA was found than those with CE. However, our study revealed that the efficacy and safety of EVT remained consistent regardless of the stroke's etiology such as LAA or CE.

Abstract WMP90: Outcomes of Endovascular Treatment versus Best Medical Treatment for Acute Basilar-Artery Occlusion: Impacts of Etiology in the ATTENTION Randomized Trial

Objective: This study aimed to evaluate the efficacy and safety of endovascular treatment versus best medical treatment strategies in acute basilar artery occlusion with different stroke etiologies. Methods: The study was a post-hoc analysis of the Trial of Endovascular Treatment of Acute Basilar-artery Occlusion (ATTENTION), which was a multicenter, randomized trial at 36 centers in China from February 2021 to September 2022. Patients with acute basilar artery occlusion were classified into three groups according to stroke etiology: large-artery atherosclerosis (LAA), cardioembolism (CE), and undetermined/other determined cause (UC/ODC). The primary outcome was favorable outcome (modified Rankin scale 0-3) at 90 days. Safety outcomes included symptomatic intracranial hemorrhage and 90-day mortality. Results: A total of 340 patients were included. Compared with best medical treatment, endovascular treatment was associated with higher rates of favorable outcome at 90 days in the LAA group (49.1% vs 23.8%; adjusted odds ratio [aOR] 2.79; 95% confidence interval [CI] 1.16-6.71), CE group (52.2% vs 30.8%; aOR 3.68; 95%CI 1.04-12.97), and UC/ODC group (37.5% vs 17.4%; aOR 5.73, 95%CI 1.99-16.48). The rate of symptomatic intracranial hemorrhage in patients receiving endovascular treatment with LAA, CE and UC/ODC was 8.3%, 2.2%, and 3.2%, respectively, and none of the best medical treatment patients. Endovascular treatment led to lower 90-day mortality than best medical treatment in LAA patients (33.3% vs 57.1%; aOR 0.41; 95% CI 0.19-0.91). Among patients receiving endovascular treatment, a better functional outcomes of CE etiology was found than the UC/ODC etiology (52.2% vs 37.5%; aOR 2.68; 95% CI 1.07-6.70); there was no differences in symptomatic intracranial hemorrhage and 90-day mortality among the three etiology subtypes. Conclusion: Endovascular treatment was associated with better outcomes than the best medical treatment in acute basilar artery occlusion patients regardless of stroke etiologies, but the benefits-risk ratios were different among etiologies. The stroke etiology might be an important factor in predicting the prognosis of thrombectomy in acute basilar artery occlusion.

Abstract WP276: Large Artery Atherosclerosis and Young Stroke

Introduction: It is known that past the age of 35, the prevalence of large artery atherosclerosis (LAA) related strokes increases with a cardiovascular risk factor (CVRF) profile beginning to resemble that of elderly patients. However, LAA-related strokes still only account for <10% of all young strokes over the age of 35. Further, there is limited data regarding the location, intracranial or extracranial, of LAA in this patient population. Methods: We conducted a retrospective review of stroke patients between the ages of 18 to 50 years presenting to our Young Stroke Center between April 2022 through August 2023. For each case, data including basic demographics and medical history were collected, and stroke etiology was determined by a vascular neurologist. Patients with LAA as the stoke etiology were compared to all non-LAA stroke etiologies. The two groups were analyzed with respect to baseline demographics and CVRFs. Analysis was performed with logistic regression adjusting for age, sex, and race. Results: Of 179 patients in the registry, 15 patients had LAA compared with 164 patients with non-LAA as their stroke etiology. Only one patient had extracranial carotid stenosis, with the rest of the LAA patients having intracranial atherosclerotic disease. There was a significant difference in age at time of stroke (42.9 ± 5.0 vs. 38.2 ± 8.0 years; OR [95% CI]: 1.11 [1.01-1.21]) between LAA and non-LAA groups, respectively. There was no significant difference in sex (66.7% vs. 62.8% female) and race (46.7% vs. 54.9% Black). A significantly larger proportion of patients with LAA had baseline CVRFs including hypertension (80.0% vs. 44.5%; 5.0 [1.2-20.3]), dyslipidemia (66.7% vs. 31.7%; 4.3 [1.3-14.1]), and obesity (33.3% vs. 12.2%; 5.6 [1.5-20.7]). There was also a trend toward increased rates of smoking (40.0% vs. 20.7%; 2.82 [0.9-9.0]) and diabetes (26.7% vs. 18.9%; 1.3 [0.3-4.7]). Conclusion: In the young stroke population, stroke due to LAA is more likely due to intracranial disease rather than extracranial disease and is associated with traditional CVRFs including hypertension, dyslipidemia, and obesity. These findings reinforce the importance of early intervention of modifiable risk factors for primary prevention of stroke in the young.

The Untargeted Metabolomics Reveals Differences in Energy Metabolism in Patients with Different Subtypes of Ischemic Stroke.

Ischemic stroke (IS) is the most common subtype of stroke. The risk factors and pathogenesis of IS are complex and varied due to different subtypes. Therefore, we used metabolomics technology to investigate the biomarkers and potential pathophysiological mechanisms of different subtypes of IS. We included 126 IS patients and divided them into two groups based on the TOAST classification: large-artery atherosclerosis (LAA) group (n = 87) and small-vessel occlusion (SVO) group (n = 39). Plasma metabolomics analysis was performed using liquid chromatography-high-resolution mass spectrometry (LC-HRMS) to identify metabolic profiles in LAA and SVO subtype IS patients and to determine metabolic differences between patients with the two subtypes of IS. We identified 26 differential metabolites between LAA and SVO subtype IS. A multiple prediction model based on the plasm metabolites had good predictive ability for IS subtyping (AUC = 0.822, accuracy = 77.8%), with 12,13-DHOME being the most important differential metabolite in the model. The differential metabolic pathways between the two subtypes of IS patients included tricarboxylic acid (TCA) cycle, alanine, aspartate and glutamate metabolism, and pyruvate metabolism, mainly focused on energy metabolism. 12,13-DHOME emerged as the primary discriminatory metabolite between LAA and SVO subtypes of IS. In LAA subtype IS patients, energy metabolism, encompassing pyruvate metabolism and the TCA cycle, exhibited lower activity levels when compared to patients with the SVO subtype IS. The utilization of targeted metabolomics holds the potential to improve diagnostic accuracy for distinguishing stroke subtypes.

An isolated pontine infarct extending to the basal pontine surface has a higher abnormal ankle-brachial index

Patients with ischemic stroke and branch atheromatous disease (BAD) have worse neurological deficits and prognoses than those with small vessel occlusion (SVO). However, both disorders are forms of deep brain infarctions. This study aimed to investigate an MRI-based etiological classification for isolated pontine infarctions and assess differences in vascular risk factors and peripheral arterial disease among etiological subtypes. Consecutive data of patients admitted for acute ischemic stroke or transient ischemic attack between August 2016 and July 2019 were reviewed. Acute isolated pontine infarcts were classified into 3 groups: BAD, SVO, and large-artery atherosclerosis (LAA), according to basilar or vertebral artery steno-occlusion and the extent of the infarct lesion on the basal pontine surface as displayed on magnetic resonance imaging and angiography. Vascular risk factors, ankle-brachial index (ABI), and brachial-ankle pulse wave velocity were analyzed in the 3 groups. Among 64 enrolled patients, BAD was the most common cause of isolated pontine infarct. The BAD group had a higher frequency of abnormal ABI and hypertension than the SVO group. The BAD group had abnormal ABI and hyperlipidemia more frequently than the LAA group. No significant difference was found in diabetes or brachial-ankle pulse wave velocity incidence between the BAD and SVO groups. ABI and vascular risk factors in the BAD group were more similar to those in the LAA group than to those in the SVD group. This finding suggests that pontine lesions extending to the basal pontine surface have an atherosclerotic mechanism in BAD, requiring potent antiplatelet therapy for the secondary prevention of ischemic stroke.

Effect of Dual- versus Single-Antiplatelet Therapy on Early Neurological Deterioration in Minor Stroke of Undetermined Cause

Background. There is insufficient evidence about the suitability of dual-antiplatelet therapy (DAPT) for different stroke subtypes. We aimed to determine the relationship between DAPT and early neurological deterioration (END) in patients with minor stroke of undetermined cause. Methods. We retrospectively collected data on patients with minor stroke treated with aspirin alone or in combination with clopidogrel and aspirin. Efficacy was the incidence of END defined as the National Institutes of Health Stroke Scale score increase of ≥2 within 7 days after admission. Safety was defined as the rate of any bleeding event. These were investigated in subtypes including the stroke of undetermined cause (SUC), large artery atherosclerosis (LAA), cardioembolism (CE), and small artery occlusion (SAO). Results. 442 patients were assigned to the SUC ( n = 91 ), LAA ( n = 157 ), CE ( n = 30 ), and SAO ( n = 164 ) groups. The incidences of END were not significantly different between patients treated with dual- versus single-antiplatelet therapy in any stroke subtypes: LAA, 17.6% vs. 12.1% ( P = 0.348 ); CE, 0% vs. 20.0% ( P = 0.224 ); SAO, 8.8% vs. 2.4% ( P = 0.093 ); and SUC, 13.6% vs. 2.1% ( P = 0.053 ). Multivariable analysis showed that after adjusting for confounding factors, DAPT was the independent factor associated with END (odds ratio 13.39, 95% confidence interval (1.16-154.81), P = 0.038 ) in the SUC group, rather than the LAA, CE, and SAO groups. Conclusion. Combined clopidogrel and aspirin is a risk factor for the rate of END only in minor stroke patients with the SUC subtype. This suggests that cryptogenic stroke may not be suitable for DAPT in the acute phase.

Correlation Between MMP9 Promoter Methylation and Transient Ischemic Attack/Mild Ischemic Stroke with Early Cognitive Impairment.

Dyskinesia caused by transient ischemic attack (TIA) and mild ischemic stroke (MIS) is mild and short-lived; however, cognitive impairment (CI) can occur in the acute phase and be easily overlooked. DNA methylation is an epigenetic phenomenon that can affect gene expression through gene silencing. Blood levels of matrix metalloproteinase (MMP) 9 are elevated in ischemic stroke patients and is associated with the destruction of the blood-brain barrier and the occurrence of CI. No studies have investigated the relationship between MMP9 gene methylation and TIA/MIS with early cognitive impairment (ECI). As such, the purpose of the present study was to investigate the correlation between MMP9 gene methylation and TIA/MIS with ECI. Data from 112 subjects were collected, including 84 with TIA/MIS (National Institutes of Health Stroke Scale <5 points) and 28 non-stroke control subjects. Patients were evaluated within 7 days of TIA/MIS onset according to four single-domain cognitive scales. Whole blood DNA methylation was detected using MethylTarget sequencing technology. Comparison of MMP9 gene methylation levels among subgroups was performed using statistical methods. The site S33-79 in the TIA/MIS group was hypomethylated compared with the control group, and sites S33-25 and S33-30 in TIA/MIS with ECI was hypomethylated compared with TIA/MIS without ECI. Compared with the small artery occlusion group, MMP9 gene, S33-25, 30, 39, 53, 58, 73, 79, 113 and 131 sites in the large artery atherosclerosis group were hypomethylated. MMP9 gene hypomethylation sites were associated with TIA/MIS and TIA/MIS with ECI, and there was a strong correlation between MMP9 gene hypomethylation and atherosclerotic TIA/MIS. MMP9 gene methylation can reflect the severity of TIA/MIS. MMP9 gene hypomethylation sites may be used as potential biomarkers and therapeutic targets for TIA/MIS and TIA/MIS with ECI.

The value of serum Lp-PLA2 combined with MPO in the diagnosis of cerebral infarction caused by large artery atherosclerosis

ObjectiveTo explore the value of serum lipoprotein-associated phospholipase A2（Lp-PLA2）combined with myeloperoxidase（MPO）for the diagnosis of large artery atherosclerosis(LAA) cerebral infarction. MethodsBaseline data were collected from patients with first-ever acute cerebral infarction, serum Lp-PLA2 and MPO levels were measured. The etiology of cerebral infarction was classified according to the Chinese Ischemic Stroke Subtype Classification Standard. The risk factors associated with LAA cerebral infarction were identified by univariate and multivariate regression analysis. The diagnostic value of serum Lp-PLA2 and MPO for LAA cerebral infarction was assessed by the area under the receiver-operating characteristic (ROC) curve. ResultsOverall 368 patients were involved, 148 patients (40.22 %) were LAA. The serum La-PLA2 and MPO levels were higher in the LAA group than those in non-LAA group (23.06 ± 3.39 ng/mL versus 17.48 ± 3.26 ng/mL; 93.60 ± 9.58 ng/mL versus 75.98 ± 15.53 ng/mL; P < 0.001 for both). Multivariate analysis showed that elevated levels of serum Lp-PLA2 (OR 1.742, 95 %CI 1.499–2.025; P < 0.001) and MPO (OR 1.060, 95 % CI 1.026–1.096; P = 0.001) were the independent risk factors of LAA cerebral infarction. The area under curve of the serum Lp-PLA2 combined with MPO for the diagnosis of LAA cerebral infarction was 0.896 [0.866 ∼ 0.927] (P < 0.001). ConclusionSerum Lp-PLA2 combined with MPO could be valued as a predictor of acute cerebral infarction caused by large artery atherosclerosis.

A Study on the Efficacy of Thrombectomy in Patients with Atherosclerotic and Cardioembolic Basilar Artery Occlusion.

Background Studies on basilar artery occlusion are relatively few compared with those of anterior circulation stroke. The aim of the present study was to compare the efficacy of endovascular therapy (EVT) in patients with basilar artery occlusion classified as large artery atherosclerosis (LAA) and cardioembolism (CE), and to analyze the independent risk factors affecting the prognosis of EVT. Methods A total of 123 people were assigned to the LAA and CE groups (97 to the LAA and 26 to the CE). The primary outcome was a modified Rankin Scale (mRS) score of 2 or lower at 90 days. The primary safety outcome was mortality at 90 days. Secondary safety endpoints included the rates of symptomatic intracranial hemorrhage and reinfarction. Multiple logistic regression was used to screen out independent risk factors for EVT prognosis of the LAA and CE groups. Results In the analysis, the patients with LAA stroke had better collateral circulation (American Society of Interventional and Therapeutic Neuroradiology/Society of Interventional Radiology [SIR] score of 2-4; 61.9 vs. 19.2%, p = 0.000), and higher angioplasty rate (32.0 vs. 3.8%, p = 0.002). The proportions of patients with a 90-day mRS score of 0 to 2 and 90-day mortality were not found to be statistically significant between the two groups. Multivariate logistic regression analysis indicated that age, SIR, white blood cell, blood glucose, and modified thrombolysis in cerebral infarction were independent risk factors for the poor prognosis of EVT in the LAA group. Conclusion Although there were differences in clinical characteristics and imaging features between LAA and CE, there was no evidence of a significant difference in prognosis after EVT. In addition, the National Institutes of Health Stroke Scale score was not among the independent risk factors affecting the prognosis of the LAA group.

Exploration of the etiology of single small subcortical infarctions using high-resolution vessel wall MRI.

We aimed to explore imaging indicators for diagnosing the etiology of single small subcortical infarctions (SSI) using high-resolution vessel wall imaging (HR-VWI). Patients with acute isolated subcortical cerebral infarction were prospectively enrolled and classified as having large artery atherosclerosis (LAA), stroke of undetermined etiology (SUD), or small artery disease (SAD). The infarct information, the cerebral small vessel disease (CSVD) score, morphological characteristics of the lenticulostriate arteries (LSAs), and plaque characteristics were compared between the three groups. Seventy seven patients were enrolled (30 LAA, 28 SUD, and 19 SAD). The total CSVD score of the LAA (P = 0.001) and SUD groups (P = 0.017) was significantly lower than that of the SAD group. The number and total length of LSA branches in the LAA and SUD groups were shorter than in the SAD group. Moreover, the total length laterality index (LI) of the LSAs in the LAA and SUD groups was greater than in the SAD group. The total CSVD score and LI of total length were independent predictors for the SUD and LAA groups. The remodeling index of the SUD group was significantly higher than that of the LAA group (P = 0.002); positive remodeling was dominant in the SUD group (60.7%), whereas remodeling in the LAA group was primarily non-positive (83.3%). SSI with and without plaques on the carrier artery may have different modes of pathogenesis. Patients with plaques may also have a coexisting mechanism of atherosclerosis.

Plasma lncRNA LIPCAR Expression Levels Associated with Neurological Impairment and Stroke Subtypes in Patients with Acute Cerebral Infarction: A Prospective Observational Study with a Control Group.

This prospective observational study with a control group aimed to compare the plasma levels of long non-coding RNA (lncRNA) LIPCAR between patients with acute cerebral infarction (ACI) and healthy controls, and to assess the prognostic abilities of LIPCAR for adverse outcomes of patients with ACI at 1-year follow-up. Eighty patients with ACI, of whom 40 had large artery atherosclerosis (LAA) and 40 had cardioembolism (CE) and who were hospitalized at Xi'an No. 1 Hospital from July 2019 to June 2020, were selected as the case group. Age- and sex-matched non-stroke patients from the same hospital throughout the same time period were chosen as the control group. Real-time quantitative reverse transcription polymerase chain reaction was used to measure the levels of plasma lncRNA LIPCAR. The correlations of LIPCAR expression among the LAA, CE, and control groups were assessed using Spearman's correlation analysis. Curve fitting and multivariate logistic regression were used to analyze the LIPCAR levels and 1-year adverse outcomes of patients with ACI and its subtypes. The expression of plasma LIPCAR in the case group was noticeably higher than that of the control group (2.42±1.49 vs. 1.00±0.47, p<0.001). Patients with CE had considerably higher levels of LIPCAR expression than those with LAA. The National Institute of Health Stroke Scale score and modified Rankin scale score on admission were significantly positively correlated with LIPCAR expression in patients with CE and LAA. Furthermore, the correlation was stronger in patients with CE than in those with LAA, with correlation coefficients of 0.69 and 0.64, respectively. Curve fitting revealed a non-linear correlation between LIPCAR expression levels, 1-year recurrent stroke, all-cause mortalities, and poor prognoses, with a cut-off value of 2.2. The expression level of lncRNA LIPCAR may play a potential role in the identification of neurological impairment and CE subtype in patients with ACI. Increased 1-year risk of adverse outcomes may be associated with high levels of LIPCAR expression.

Effects of Different Etiologies of Anterior Circulation Tandem Lesions on Short-term Prognosis of Acute Ischemic Stroke.

The prognosis of anterior circulation tandem lesions caused by carotid artery dissection (CAD) and large artery atherosclerosis (LAA) after mechanical thrombectomy is controversial. By analyzing the clinical data of different etiologies, we explored the best treatment plan. Clinical data of patients with anterior circulation tandem lesions admitted to the Second Affiliated Hospital of Soochow University from April 2018 to October 2021 were retrospectively collected. The Modified Rankin Scale was used as the standard to evaluate the functional prognosis of patients at 3 months. Safety assessment included symptomatic intracranial hemorrhage (sICH) and mortality. The technical evaluation of interventional procedures included operation time, successful recanalization, and times of pass. 74 patients were enrolled, 59 in the LAA group and 15 in the CAD group. The two groups were similar regarding the proportion of successful recanalization, the bridge treatment and the choice of surgical instruments. The puncture to recanalization time and the onset of symptoms to successful recanalization time had no significant difference (p > 0.05). There were no significant differences in hemorrhage transformation (p = 0.26), sICH (p > 0.999), good functional prognosis (p = 0.054), and mortality (p = 0.181) between the two groups. We found a trend toward a better functional outcome at 3 months in the CAD group (p = 0.054). The tandem lesions of anterior circulation caused by CAD tend to have a good functional prognosis in 3 months. The proportion of successful recanalization and surgical safety was similar between the two groups.

Multiple chronic lacunes predicting early neurological deterioration and long-term functional outcomes according to TOAST classification in acute ischemic stroke.

Studies regarding multiple chronic lacunes (MCLs) and clinical outcome according to stroke etiology are scarce. We sought to evaluate the association between MCL and short-term/long-term clinical outcomes according to stroke etiology. We analyzed a prospectively collected stroke registry of acute ischemic stroke patients over 4years. The enrolled patients were classified as having large artery atherosclerosis (LAA), small vessel occlusion (SVO), cardioembolic (CE) stroke, and other etiology. The early neurological deterioration (END) and favorable outcome at 3months were assessed. A total of 1070 patients were enrolled. Patients with MCL had significantly more END compared to those without MCL both in total population (adjusted odds ratio (OR), 1.7; 95% confidence interval [CI], 1.1-2.5; p = 0.013*) and in the LAA group (adjusted OR, 2.3; 95% CI, 1.3-4.2, p < 0.006). Patients with MCL had a significantly lower OR for favorable outcome at 3months compared to those without MCL both in total population (adjusted OR, 0.7; 95% CI, 0.5-1.0, p = 0.035) and in the LAA group (adjusted OR, 0.6; 95% CI, 0.3-1.0, p = 0.043). However, MCL was not associated with END or long-term functional outcome in patients with SVO, CE, or other etiology. The presence of MCL was an independent predictive factor for END as well as long-term poor functional outcome in acute ischemic stroke patients. These associations were only observed in patients with LAA, not in those with SVO, CE, or other etiology.

Endovascular treatment for acute basilar artery occlusion due to different stroke etiologies of large artery atherosclerosis and cardioembolism.

Stroke etiology may affect the prognosis of acute basilar artery occlusion (BAO). This study aimed to estimate the efficacy and safety of endovascular treatment (EVT) in BAO strokes due to the underlying stroke etiologies of large artery atherosclerosis (LAA) and cardioembolism (CE). Patients with LAA and CE subtypes from the registry EVT for Acute Basilar Artery Occlusion Study (BASILAR) were selected for this analysis. We estimated the EVT treatment effect relative to standard medical treatment (SMT) in these patients by using a propensity score approach with inverse probability of treatment weighted estimation. Outcomes included 90-day favorable functional outcomes (modified Rankin scale (mRS) 0-3), functional independence (mRS 0-2), all-cause mortality, and symptomatic intracranial hemorrhage (sICH). A total of 744 patients were included in the final analysis. After weighting with inverse probability of treatment estimation, the patients who, based on their characteristics, were treated with EVT rather than SMT, demonstrated higher rates of favorable functional outcomes in both the LAA (29.2% vs 11.7%, adjusted OR with 95% CI: 4.34 [2.15-8.78], p < 0.001) and the CE subtype (36.0% vs 8.1%, adjusted OR with 95% CI: 9.14 [1.96-42.55], p = 0.005). A similar finding was also observed for functional independence. EVT patients also demonstrated lower rates of mortality than SMT. Among EVT patients, no significant difference was observed in mortality or sICH between LAA and CE groups, but LAA patients had lower rates of favorable functional outcome and functional independence (29.2% vs 37% and 24.2% vs 32.9%, respectively), where the latter remained significant after adjustment for imbalances in baseline data (p = 0.04). In acute BAO strokes, both LAA and CE patients who, based on their characteristics, were treated with EVT rather than SMT, demonstrated better outcomes. Among EVT patients, LAA and CE subtypes displayed important baseline and treatment differences, and LAA patients were less likely to achieve functional independence at 3 months, but mortality and sICH were similar between LAA or CE subtypes. These results need to be confirmed in future clinical trials.

Association of Systolic Blood Pressure and Cerebral Collateral Flow in Acute Ischemic Stroke by Stroke Subtype.

Background and PurposeCollateral flow in acute ischemic stroke is known as a predictor of treatment outcome and long-term prognosis. However, factors determining the initial collateral flow remain unclear. We investigated factors related to collateral flow in patients with acute ischemic stroke caused by large vessel occlusion (AIS-LVO) and further analyzed the results according to stroke etiology.MethodsThis was a retrospective study using prospective stroke registry data from a single university hospital from October 2014 to May 2021. AIS-LVO with middle cerebral artery M1 occlusion identified by pre-treatment multiphasic computed tomography angiography was included. Collateral flow score was graded on a 6-point ordinal scale according to pial arterial filling.ResultsA total of 74 patients [cardioembolism (CE): 57; large artery atherosclerosis (LAA): 17] was included. The mean age of all patients was 72.2 ± 11.7 years, and 37.8 % (n = 28) were men. Multivariate regression analysis showed that initial SBP [odds ratio (OR): 0.994; 95% confidence interval (CI): 0.990–0.998; p = 0.002] and stroke etiology (OR: 0.718; 95% CI: 0.548–0.940; p = 0.019) were independent factors of the collateral flow grade. Collateral flow grade was independently associated with initial SBP in the CE group (OR: 0.993; 95% CI: 0.989–0.998; p = 0.004) but not in the LAA group (OR: 0.992; 95% CI: 0.980–1.004; p = 0.218). Initial SBP was significantly correlated with NIHSS score in the CE group but not in the LAA group (r2= 0.091, p = 0.023; r2 = 0.043, p = 0.426, respectively).ConclusionsElevated initial SBP was associated with poor cerebral collateral flow and more severe symptoms in the CE group, but not in the LAA group in patients with AIS-LVO. These findings suggest differential effects of initial SBP elevation on collateral flow by stroke subtypes.

The Relationship Between Atrial Cardiopathy Biomarkers and Prognosis of Patients With Embolic Stroke of Undetermined Source.

ObjectiveTo compare the proportion of atrial cardiopathy in patients with embolic stroke of undetermined source (ESUS) and other non-cardiac strokes, and to evaluate the prognostic value of atrial cardiopathy biomarkers in patients with ESUS.MethodsThis retrospective study enrolled patients with ischemic stroke from January 2018 to April 2020 in a single stroke center, and compared the proportion of atrial cardiopathy in (1) ESUS group, (2) large artery atherosclerosis (LAA) group, and (3) small-vessel occlusion (SVO) group. Then, it compared the baseline characteristics between ESUS patients with atrial cardiopathy and cardioembolism (CE) group. In addition, the relationship was compared between the biomarkers of atrial cardiopathy and prognosis in patients with ESUS.ResultsIn total, 316 patients with ischemic stroke were included that included 105 (33.23%) ESUS, 84 (26.58%) LAA, 73 (23.10%) SVO, and 54 (17.09%) CE. Among these patients, patients with ESUS were younger, and had lower triglyceride, lower low-density lipoprotein than non-ESUS group. The proportion of atrial cardiopathy in ESUS group was higher than LAA group or SVO group (42.86 vs. 17.86 vs. 8.22%, p < 0.001). Compared with non-atrial cardiopathy group, patients with atrial cardiopathy were older, had lower EF value, larger left ventricular diameter, and longer PR interval. Among 105 patients with ESUS, 11 (10.78%) cases died, 32 (31.37%) cases had poor functional outcome (mRS >2). In the multivariable model, the risk factor associated with the death risk of patients with ESUS was N-terminal pro-B-type natriuretic peptide (NT-proBNP) >250 pg/ml [p = 0.025, hazard ratio (HR) = 4.626, 95% CI: 1.212–17.652] after a 1-year follow-up.ConclusionsAtrial cardiopathy is more common in patients with ESUS, and the characteristics of ESUS patients with atrial cardiopathy are similar to those in patients with CE. NT-proBNP >250 pg/ml is related to the risk of death in patients with ESUS.

Plasma Concentration of Tumor Necrosis Factor-Stimulated Gene-6 as a Novel Diagnostic and 3-Month Prognostic Indicator in Non-Cardioembolic Acute Ischemic Stroke.

BackgroundTumor necrosis factor-stimulated gene-6 (TSG-6) is a multifunctional, anti-inflammatory, and protective protein, while the association between TSG-6 and acute ischemic stroke (AIS) remains unclear in humans. This study aims to investigate the potential diagnostic and short-term prognosis predictive values of TSG-6 in non-cardioembolic AIS.MethodsA total of 134 non-cardioembolic AIS patients within 24 h after AIS onset and 40 control subjects were recruited. Using an AIS dataset from the Gene Expression Omnibus database and setting the median expression level of TNFAIP6 as the cutoff point, data were divided into TNFAIP6-high and TNFAIP6-low expression groups. Differently expressed genes (DEGs) were extracted to perform gene enrichment analysis and protein–protein interaction (PPI) network. Baseline data were analyzed in a four-group comparison plotted as plasma TSG-6 concentration median and 25th/75th percentiles. The correlative factors of 3-month outcome were evaluated by logistic regression. TSG-6 concentrations and TSG-6-to-interleukin-8 ratios were compared in a block design. A receiver-operating characteristic curve was used to analyze the detective value of TSG-6 and 3-month prognosis predictive values of TSG-6 and TSG-6-to-interleukin-8 ratio.ResultsNon-cardioembolic AIS patients had significantly higher plasma TSG-6 levels than control subjects (P < 0.0001). The large-artery atherosclerosis group had significantly higher TSG-6 levels than the small-artery occlusion group (P = 0.0184). Seven hundred and eighty-two DEGs might be both AIS-related and TNFAIP6-correlated genes, and 17 targets were deemed AIS-related being closely relevant to TNFAIP6. Interleukin-8 was selected for further study. The National Institutes of Health Stroke Scale and the Acute Stroke Registry and Analysis of Lausanne scores at admission, lesion volume, neutrophil count, neutrophil-to-lymphocyte ratio, and interleukin-8 level were positively correlated with TSG-6 level, respectively (P < 0.0001). The unfavorable outcome group had meaningfully higher TSG-6 levels (P < 0.0001) and lower TSG-6-to-interleukin-8 ratios (P < 0.0001) than the favorable outcome group. After adjusting for confounding variables, elevated TSG-6 levels remained independently associated with 3-month poor prognosis of non-cardioembolic AIS (P = 0.017). In non-cardioembolic AIS, the cutoff values of TSG-6 concentration for detection and 3-month prognosis prediction and the TSG-6-to-interleukin-8 ratio for the 3-month prognosis prediction were 8.13 ng/ml [AUC, 0.774 (0.686–0.861); P < 0.0001], 10.21 ng/ml [AUC, 0.795 (0.702–0.887); P < 0.0001], and 1.505 [AUC, 0.873 (0.795–0.951); P < 0.0001].ConclusionsPlasma TSG-6 concentration was a novel indicator for non-cardioembolic AIS diagnosis and 3-month prognosis. Elevated TSG-6-to-interleukin-8 ratio might suggest a 3-month favorable outcome.

Abstract TP210: Stroke Subtype-specific Association Of Systemic Blood Pressure And Cerebral Collateral Flow In Acute Ischemic Stroke With Large Vessel Occlusion

Introduction: Collateral flow in acute ischemic stroke is known as a predictor of acute treatment outcome and long-term prognosis. However, studies on the factors which determine the degree of initial collateral flow are not well known. We investigated the factors related to collateral degree in acute ischemic stroke caused by large vessel occlusion (AIS-LVO) and further analyzed the results according to stroke subtype. Methods: This was a retrospective cohort using prospective stroke registry data from October 2014 to May 2021. Patients admitted within 48 hours of symptom onset with middle cerebral artery M1 occlusion on multiphasic CT angiography were included. Collateral score was graded on a six-point scale according to pial arterial filling. Results: A total of 74 patients was enrolled (mean age=72.2±11.7 years; men=37.8%). Of whom 57 (77%) were in the cardioembolism (CE) group and 17 (23%) were in the large artery atherosclerosis (LAA) group. In ordinary logistic regression analysis, initial systolic blood pressure (SBP) was associated with the score of collateral flow (odds ratio [OR]=0.982; 95% confidence interval [CI]=0.968-0.997; p=0.017). Considering multivariate models adjusted for age, sex, and atrial fibrillation, initial SBP was an independent predictor of the score of collateral flow (OR=0.977; 95% CI=0.961-0.992; p=0.011). In subgroup analysis, the lower score of collateral flow was independently associated with increased initial SBP in CE group (OR=0.965; 95% CI=0.945-0.983; p&lt;0.001) but not in LAA group (OR=1.009; 95% CI=0.978-1.043; p=0.578). Echocardiographic parameters and anatomical variations of circle of Willis did not show significant association. Conclusions: Poor cerebral collaterals in AIS-LVO was associated with increased initial SBP. Subgroup analysis revealed the association was significant in CE group, but not in LAA group. Mechanism underlying differential effects of SBP on stroke subtypes may need further study.

Abstract WMP114: Putrescine And Kynurenine Are Associated With Large Artery Atherosclerosis Stroke: Targeted Metabolomics Study

Background: Ischemic stroke is a diversified disease with various mechanisms. However, the current subtyping process is complicated and time-consuming. Metabolite-based biomarkers have promising potential to improve classification and profound understanding of the disease. We aimed to identify novel targeted metabolomics-based biomarkers that are clinically relevant to the diagnosis of large-artery atherosclerosis (LAA) stroke. Methods and Results: We acquired serum samples and clinical data from a hospital-based acute stroke registry. Patients experiencing ischemic stroke within a week of symptoms onset were recruited. Finally, 238 acute ischemic stroke participants (97 LAA patients and 141 non-LAA patients) were included. A targeted quantitative and quality-controlled liquid chromatography with tandem mass spectrometry metabolomics analysis was performed, several metabolomic signatures which showed statistically significant differences between LAA and non-LAA groups were selected. A multivariate regression model was created to independently predict the LAA stroke. We obtained 55 serum metabolomics signatures, and of these, 2 biogenic amines (putrescine and kynurenine) were selected as independent discriminants for LAA (odds ratio [OR], 0.0004; 95% confidence interval [CI], 4.819x10 -07 -0.3601 for putrescine; OR, 0.4325; 95% CI, 0.2232-0.8381 for kynurenine) after adjustment for patients’ sex, age, body mass index, stroke severity, and comorbidities. Conclusions: Targeted metabolomics approach provided an enhanced understanding of LAA stroke pathogenesis. We have identified putrescine and kynurenine as novel biomarkers for LAA stroke.

Effect of stroke etiology on endovascular thrombectomy with or without intravenous alteplase: a subgroup analysis of DIRECT-MT

BackgroundStroke etiology might influence the clinical outcomes in patients with large vessel occlusion receiving endovascular treatment (EVT) with or without thrombolysis.ObjectiveTo examine whether stroke etiology resulted in different efficacy and...