Large Artery Atherosclerosis Stroke Research Articles

Lipoprotein (a) concentration as a risk factor for ischaemic stroke and its subtypes.

To investigate the relationship between serum lipoprotein (a) [Lp(a)] concentration and the risk of ischaemic stroke (IS) and its subtypes. Lp(a) plays a role in atherogenic, pro-thrombotic, and antifibrinolytic processes. Elevated plasma Lp(a) is a strong independent risk factor for the development and progression of atherosclerotic disease. The association between lipoproteins and IS is more complex than that reported for cardiovascular diseases, with inconsistent and contradictory results from epidemiological studies. 231 patients with acute IS (defined as cases) and 163 age- and sex-matched control subjects were included in this prospective case-control study. Demographic and clinical variables (i.e. age, sex, smoking, presence of chronic diseases and concomitant medication) and laboratory data (i.e. concentrations of total cholesterol, high-density lipoprotein-cholesterol, low-density lipoprotein-cholesterol, triglycerides, Lp(a), apolipoprotein A1, apolipoprotein B) were recorded. The mean age and the percentage of men did not significantly differ between groups. Compared to controls, there was a significantly higher percentage of cases reported with concomitant diseases: diabetes mellitus, myocardial infarction, ischaemic heart disease, peripheral arterial disease, and atrial fibrillation. The study showed a significantly higher serum Lp(a) concentration in cases than in control subjects (81.81 nmol/L [c.32.7 mg/dL] vs. 59.75 nmol/L [c.23.9 mg/dL]; p = 0.036) and found an association between Lp(a) levels stratified by quartiles and the risk for ischaemic stroke (Q1 [Lp(a) < 13 nmol/L] vs. Q4 [Lp(a) > 117 nmol/L]: OR 2.23; 95% CI 1.23-4.03; p = 0.008). A subgroup analysis based on the TOAST classification of IS also showed a significant association between Lp(a) value of more than 75 nmol/L (30 mg/dL) and the risk of large-artery atherosclerosis stroke compared to the controls (OR 2.4; 95% CI 1.39-3.93; p = 0.001), as well as a statistically non-significant association with other subtypes of IS. The influence of Lp(a) remained significant even after adjusting for established risk factors for IS (OR 1.99; 95% CI 1.05-3.76; p = 0.04; respectively for the large-artery atherosclerotic subtype: OR 2.54; 95% CI 1.39-4.67; p = 0.003). We found that Lp(a) is an independent risk factor for ischaemic stroke, and for the large-artery atherosclerotic subtype of ischaemic stroke.

Stroke recurrence and osteoporotic conditions in postmenopausal patients with atherosclerotic ischemic stroke

Recurrence after stroke is common, and associated with a high mortality rate. Degradation of the elastic tissue in the arterial wall has been shown to aggravate atherosclerosis in blood vessels. Considering that type 1 collagen is present in both bone and vascular smooth muscle cells, we explored whether osteoporotic conditions affect the likelihood of stroke recurrence in postmenopausal women following atherosclerotic ischemic stroke. To determine actual bone mineral density (BMD), the Hounsfield unit values in the frontal skull were evaluated using brain computed tomography (CT) scans taken at admission. A multivariate Cox regression analysis was also performed to examine if osteoporosis could independently predict stroke recurrence in postmenopausal patients with large artery atherosclerosis (LAA) or small vessel occlusion (SVO) stroke. This study included 2130 consecutive patients (both males and females aged 50 and older) with acute LAA or SVO strokes. After adjusting for all covariates, hypothetical osteoporosis was identified as an independent predictor of stroke recurrence in female patients ≥50 years with acute LAA or SVO stroke (hazard ratio, 1.84; 95 % confidence interval, 1.05 to 3.24; p = 0.034). Our findings showed that osteoporosis could potentially affect the recurrence of ischemic stroke in postmenopausal patients with LAA or SVO stroke.

The predictive value of serum F-actin on the severity and early neurological deterioration of acute ischemic stroke: Predictive value of F-actin in stroke

BackgroundF-actin is involved in the progression of ischemic stroke and is associated with the disruption of the blood-brain barrier. In this article, we evaluated serum F-actin as a biomarker in stroke severity and early neurological deterioration (END) in acute ischemic stroke. MethodsIn this study, serum F-actin was measured in consecutively collected 140 AIS patients and 144 healthy controls matched in gender and age by ELISA. Early neurological deterioration (END) was defined as the deterioration of neurological dysfunction within 72 hours of admission, with an increase of ≥ 4 points in the NIHSS score. Severe stroke was defined as a NIHSS score>8 at admission. ResultsThe serum F-actin level in AIS was significantly higher than healthy controls (p = 0.041). In large-artery atherosclerosis stroke and cardioembolic stroke, serum F-actin were significantly higher than that in small artery occlusion stroke (padjust = 0.019, padjust < 0.001, respectively).F-actin level above the critical value (>1.37 µg/L) was significantly associated with severe stroke (OR, 3.015; 95 %CI, 1.014–8.963; p = 0.047) . In addition, elevated level of F-actin was significantly associated with END (OR, 1.323; 95 % CI, 1.001-1.747, p = 0.049). When the level of F-actin was above the critical value (>2.17 µg/L), its association with END remained significant (OR, 6.303; 95 %CI, 2.160-18.394; p < 0.001) . ConclusionF-actin is an important blood biomarker in the early stage of AIS, and high levels of F-actin are valuable in determining the severity of stroke and predicting early neurological deterioration.

Single-nucleotide polymorphism rs2910829 in PDE4D is related to stroke susceptibility in Chinese populations: The results of a meta-analysis.

Stroke is a debilitating condition that often leads to disability and death. The increasing prevalence of stroke has drawn worldwide attention. Extensive evidence indicates a crucial role of genetic determinants in the occurrence and perpetuation of stroke. An Icelandic study identified a significant correlation of the phosphodiesterase 4D (PDE4D) single-nucleotide polymorphism (SNP) rs2910829 with stroke susceptibility. However, subsequent studies reported in Chinese populations were contradictory. We implemented a meta-analysis to inspect whether SNP rs2910829 is related to stroke susceptibility in Chinese populations and subsequently performed an in silico analysis to predict its potential functions. Finally, we analysed data from 24 studies comprising 7,484 Chinese stroke patients and 7,962 control individuals. Compared with the CC genotype, the TT genotype was associated with increased susceptibility to stroke (pooled odds ratio [OR] 1.28, 95% confidence interval [CI] 1.13-1.46, P < 0.001), whereas the CT genotype was not. Correspondingly, a significant association was detected under the recessive model (TT vs CT + CC: OR 1.30, 95% CI 1.15-1.47, P < 0.001). Similar results were obtained in large artery atherosclerosis (LAA) stroke but not in small vessel stroke. Bioinformatics analysis also revealed that SNP rs2910829 and its linked SNPs might be implicated in transcriptional regulation. This meta-analysis reveals significant relationships between the PDE4D SNP rs2910829 and susceptibility to stroke and subtype-LAA stroke in Chinese individuals, and further investigations are warranted to evaluate this effect.

Remnant cholesterol traits and risk of stroke: A multivariable Mendelian randomization study.

Observational epidemiological studies have reported a relationship between remnant cholesterol and stroke. However, the results are inconclusive, and causality remains unclear due to confounding or reverse causality. Our objective in this study was to investigate the causal relevance of remnant cholesterol and the risk of stroke and its subtypes using the Mendelian randomization (MR) approach. Genome-wide association studies (GWASs) including 115,082 European individuals (UK Biobank) were used to identify instruments for remnant cholesterol, including intermediate-density lipoprotein (IDL) cholesterol and very-low-density lipoprotein (VLDL) cholesterol. Summary-level data for total stroke, intracerebral hemorrhage, subarachnoid hemorrhage, ischemic stroke (IS), and IS subtypes were obtained from GWAS meta-analyses conducted by the MEGASTROKE consortium. Univariable and multivariable MR analyses were performed. The GWAS identified multiple single-nucleotide polymorphisms after clumping for remnant cholesterol (n = 52), IDL cholesterol (n = 62), and VLDL cholesterol (n = 67). Assessed individually using MR, remnant cholesterol (weighted median: odds ratio [OR] 1.32 per 1-SD higher trait; 95% CI: 1.04-1.67; P = 0.024) had effect estimates consistent with a higher risk of LAS-IS, driven by IDL cholesterol (OR 1.32; 95% CI: 1.04-1.68; P = 0.022). In multivariable MR, IDL cholesterol (OR 1.46; 95% CI: 1.10-1.93; P = 0.009) retained a robust effect on LAS-IS after controlling for VLDL cholesterol and high-density lipoprotein cholesterol. The MR analysis did not indicate causal associations between remnant cholesterol and other stroke subtypes. This study suggests that remnant cholesterol is causally associated with the risk of LAS-IS driven by IDL cholesterol.

Association between clonal hematopoiesis-related gene mutations and unfavorable functional outcome in patients with large-artery atherosclerotic stroke

BackgroundClonal hematopoiesis of indeterminate potential (CHIP) is a phenomenon that characterizes individuals with somatic mutations that are related to hematologic malignancy but without hematologic abnormalities. Presence of CHIP is associated with the atherosclerotic cardiovascular disease through the activation of the interleukin 6 (IL-6) pathway; however, its role on unfavorable functional outcomes in different etiologies of ischemic stroke remains unclear. We aimed to investigate the association between CHIP-related gene mutations and unfavorable functional outcomes of ischemic stroke with different etiologies.MethodsWe prospectively studied a cohort of 3396 stroke patients with identified etiologies, and identified CHIP and the presence of the IL6R variant (IL6R p.Asp358Ala) by whole-genome sequencing. The IL6R p.Asp358Ala coding mutation was used as a genetic inhibition for IL-6 signaling. The primary outcome was unfavorable functional outcome [(Modified Rankin Scale), mRS 2–6] at 3 months.ResultsOf the 3396 patients, 110 (3.2%) were CHIP carriers and the median age was 62 years (IQR, 54.0–69.0). The CHIP increased the risk of unfavorable functional outcome among patients with hyper-inflammation status of high-sensitivity C-reactive protein (hsCRP) > median levels in patients with large-artery atherosclerosis (LAA) (OR 2.45, 95% CI 1.00–5.98, p = 0.049, pinteraction = 0.01). Presence of IL6R variant (IL6R p.Asp358Ala) could attenuate the risk of unfavorable functional outcome only in patients with CHIP (OR 0.30, 95%CI 0.12–0.76, p = 0.01, pinteraction = 0.02), and especially in LAA patients with CHIP (OR 0.1, 95%CI 0.02–0.42, p = 0.002; pinteraction = 0.001).ConclusionCHIP is associated with unfavorable functional outcomes in patients with LAA stroke and hyper-inflammation. Genetic IL-6 signaling inhibition might attenuate the risk of unfavorable functional outcomes in CHIP carriers, especially in LAA stroke patients.

Fibrinogen-to-Albumin Ratio and Clinical Outcomes in Patients With Large Artery Atherosclerosis Stroke.

A high fibrinogen-to-albumin ratio (FAR), a novel inflammatory marker, is considered to be a prognostic marker in vascular diseases. However, the association of FAR with large artery atherosclerosis (LAA) stroke is still unknown. This study was conducted to evaluate the association between FAR levels and clinical outcomes in patients with acute LAA stroke. A total of 809 patients within 72 hours of LAA stroke were included and followed up to 1 year. FAR was calculated as fibrinogen (g/L)/albumin (g/L). The associations of FAR with clinical outcomes were assessed by multivariate Cox regression or logistic regression analysis. Clinical outcomes included stroke recurrence, all-cause death, poor functional outcome (modified Rankin Scale score 3-6), and dependence (modified Rankin Scale score 3-5). Among the 809 patients with acute LAA stroke, the median FAR was 0.075 (interquartile range, 0.064-0.087). At 1 year, 103 (12.7%) patients had stroke recurrence, 105 (13.0%) had poor functional outcome, 76 (9.8%) had dependence, and 29 (3.6%) had died. After adjusting for all confounding risk factors, a high FAR level was associated with stroke recurrence (hazard ratio, 2.57 [95% CI, 1.32-5.02]), poor functional outcome (odds ratio, 3.30 [95% CI, 1.57-6.94]), and dependence (odds ratio, 3.49 [95% CI, 1.49-8.19]). A high FAR level was associated with an increased risk of stroke recurrence, poor functional outcome, and dependence in patients with acute LAA stroke.

Association between ApoB/ApoA-I ratio and post-stroke cognitive impairment in large artery atherosclerosis stroke

Association between ApoB/ApoA-I ratio and post-stroke cognitive impairment in large artery atherosclerosis stroke

Association between metabolic syndrome and outcomes of large-artery atherosclerosis stroke treated with reperfusion therapy

Association between metabolic syndrome and outcomes of large-artery atherosclerosis stroke treated with reperfusion therapy

The diagnostic tests and functional outcomes of acute ischemic stroke or transient ischemic attack in young adults: A 4-year hospital-based observational study.

Ischemic strokes in young adults have been a significant concern due to various potential etiologies and had substantial clinical and public health impacts. We aimed to study the diagnostic tests, etiologies, and functional outcomes of acute ischemic stroke (AIS) and transient ischemic attack (TIA) in young adult patients. The data were retrieved from the Chiang Mai University Hospital Stroke Registry between January 2018 and December 2021. Consecutive AIS or TIA patients were included if they were 18-50 years and had no stroke mimics. Study outcomes were proportions of positive diagnostic tests, and 90-day modified Rankin Scale (mRS). Of 244 enrolled patients, 59.0% (n = 144) were male, and 38.1% (n = 93) were aged 18-40, classified as the younger age group. There was a high incidence of diabetes (24.5%) and dyslipidemia (54.3%) among patients aged 41-50, associated with small-vessel occlusion and large-artery atherosclerosis stroke classification in this age group. Patients aged 18-40 years had more other determined etiologies (39.8%), with hypercoagulability (8.2%), arterial dissection (7.8%), and cardiac sources (6.6%) being the first three causes, which were associated with higher anticoagulant treatment. The cerebrovascular study, cardiac evaluation using echocardiography, and antiphospholipid syndrome testing were commonly performed, of which computed tomography angiography provided a high proportion of positive results (80.3%). 76.3% of young adult patients had excellent functional outcomes (mRS 0-1) with a median mRS of 0 (interquartile range 0-1) at 90-day follow-up. Stroke of other determined etiology remained the common cause of stroke in young adults, and most affected individuals had excellent clinical outcomes. Blood tests for arterial hypercoagulability and noninvasive vascular and cardiac evaluations are encouraged in selected patients to determine the stroke etiology and guide for appropriate preventive strategies.

Association between vertebrobasilar artery geometry and vertebrobasilar stenosis, recurrence, and death in posterior circulation stroke and transient ischemic attack

BackgroundIntracranial atherosclerosis is one of the primary causes of posterior circulation stroke and transient ischemic attack (TIA), particularly in people of South and East Asian heritage. Focal vessel geometry may play a role in atherosclerosis progression. Thus, we investigated the relevance of vertebrobasilar artery (VBA) geometry and vertebrobasilar atherosclerotic stenosis, recurrence, and death in posterior circulation stroke and TIA. MethodsFour hundred and twenty patients with posterior circulation ischemic stroke or TIA were included. The VBA geometric features, comprising the geometric configurations (Tuning fork, Walking, Lambda, and No confluence), vascular bends (multi-bending and oligo-bending), and VBA stenosis degrees, were defined based on computed tomography angiography (CTA) images. Recurrence of stroke or TIA and death were assessed through a 1-year follow-up. Additionally, the relationship between VBA geometric features, VBA stenosis, and prognosis were analyzed. ResultsWalking type and vascular multi-bending showed significant associations with more severe VBA stenosis and distribution, and these were also more frequently observed in patients with large-artery atherosclerosis (LAA) stroke (all P < 0.05). Sixty-four patients exhibited recurrent stroke or TIA, and 31 died during the 1-year follow-up. In the binary logistic regression analysis, Walking type (P = 0.018), Lambda type (P = 0.021), and multi-bending type (P = 0.004) were found to be independently associated with stroke recurrence, while No confluence type was independently associated with death (P = 0.010). ConclusionsThe geometric characteristics of the VBA are associated with vertebrobasilar stenosis, LAA stroke, 1-year recurrence, and death in posterior circulation stroke and TIA. VBA geometry may be used to stratify the risk of stroke and TIA in the posterior circulation.

Update on Biomarkers Associated with Large-Artery Atherosclerosis Stroke.

Intracranial and extracranial large-artery atherosclerosis (LAA) are a main cause of ischemic stroke. Biomarkers may aid in the diagnosis of LAA and help to stratify patients' risk of stroke. We performed a narrative review of the literature, mainly published in the last five years, with the aim of identifying biomarkers associated either with intracranial or extracranial LAA in humans. Several potential biomarkers of LAA, mainly related to lipidic pathways and inflammation, have been studied. Diagnostic biomarkers of LAA were evaluated by measuring biomarkers levels in patients with LAA stroke and other stroke etiologies. Some biomarkers were associated with the functional prognosis of LAA stroke patients. Increased levels of IL-6 and sLOX-1 were associated with a risk of progression of carotid atherosclerotic disease. Findings support the notion that the immune system plays a central role in the pathogenesis of LAA. Overall, in most studies, results were not externally validated. In the future, biomarkers could be useful for the selection of patients for clinical trials. To adopt these biomarkers in clinical practice, we will need robust multicentric studies proving their reproducibility and a clear practical applicability for their use.

Exploring the Causality of Type 1 Diabetes and Stroke Risk: A Mendelian Randomization Study and Meta-analysis.

Type II diabetes was causally related to stroke, which is a risk factor for stroke. However, the causal relationship between type I diabetes(T1D) and stroke, especially its subtypes, remains unclear. To determine whether T1D has a genetic causal link to stroke and its subtypes, we undertook this mendelian randomization (MR) study. The genome-wide association studies (GWAS) of T1D was the source of exposure. The outcomes were strokes and their subtypes, including ischemic stroke (IS), small vessel stroke (SVS), cardioembolic stroke (CES), large artery atherosclerosis stroke (LAS), intracerebral hemorrhage (ICH), lobar intracerebral hemorrhage (LICH), and non-lobar intracerebral hemorrhage (NLICH). We used outcome GWAS conducted by ISGC consortium for the initial phase and GWAS from MEGASTROKE consortium as the data for the replication phase to confirm the causal association. Besides, we conducted a meta-analysis of the causal association from ISGC and MEGASTROKE databases to confirm robust causality. Inverse-variance weighting (IVW) was utilized as the primary method to estimate the causality between T1D and stroke. The Cochran's Q test and the MR-PRESSO global test were used to examine the sensitivity. We discovered the causal relationship between T1D and SVS (OR = 1.17, 95% CI: 1.07-1.28, p = 6.0 × 10- 4), CES (OR = 1.11, 95%CI: 1.03-1.21, p = 0.0080) in initial stage. The replication phase validated T1D has a causal relationship with SVS (OR = 1.12, 95% CI: 1.06-1.18, p = 4.0 × 10- 5), but not with stroke and other subtypes. The meta-analysis of initial and replication stage again supported the causal link between T1D and SVS (OR = 1.13, 95% CI: 1.08-1.18, p < 0.05). However, no causal relationship was found between T1D and other stroke subtypes. The sensitivity analysis also supported the robust of these results. In conclusion, T1D was causally associated with SVS, but not with other subtypes of stroke. More investigation is needed to understand the underlying biology mechanism.

Poststroke neutrophil count is predictive of the outcomes of large-artery atherosclerotic stroke and associated with craniocervical atherosclerosis

Elevation of the neutrophil count is detrimental to the outcome of patients with stroke. The effect of poststroke neutrophil count on the outcome of patients with large-artery atherosclerosis (LAA) stroke is unclear. This study aims to explore the relationship of poststroke neutrophil count with the functional outcome of patients with LAA stroke, and the relationship of poststroke neutrophil count and craniocervical atherosclerotic stenosis (AS) number in these patients. The AS was defined as ≥ 50% stenosis or occlusion attributed to atherosclerosis on craniocervical large arteries. A total of 297 participants were enrolled in the cohort. In multivariable analyses, neutrophil count [adjusted relative risk (aRR) = 1.23, 95% confidence interval (CI) 1.09–1.40, p = 0.001] was an independent predictor of 90-day poor functional outcome [modified Rankin Scale (mRS) > 2 points]. The neutrophil count was significantly associated with the craniocervical AS number in a multivariable ordinal logistic regression analysis [adjusted odds ratio (aOR) = 1.41, 95% CI 1.16–1.72, p = 0.001]. The poststroke neutrophil count is a valuable predictor of 90-day poor functional outcome of patients with LAA stroke. The poststroke neutrophil count is positively correlated with the craniocervical AS number in these patients.

Increased plasma levels of circPTP4A2 and circTLK2 are associated with stroke injury.

Accumulating studies have shown that circulating circular RNAs (circRNAs) represent novel biomarkers for many human diseases. We investigated whether plasma circPTP4A2 and circTLK2 levels are associated with stroke severity, infarct volume, stroke etiology, and functional outcome in acute ischemic stroke (AIS) patients. We applied quantitative real-time PCR (qPCR) to measure plasma circPTP4A2 and circTLK2 levels of 236 AIS patients within 72 h of symptoms onset and 136 healthy controls. We further assessed the National Institutes of Health Stroke Scale (NIHSS), infarct size, the Trial of Org 10172 in Acute Stroke Treatment (TOAST) classification and the 90-day modified Rankin scale (mRS) for each patient. At admission, plasma circPTP4A2 and circTLK2 levels in patients with moderate to severe stroke were significantly higher compared to those with mild stroke. Logistic regression and receiver-operating characteristic (ROC) curve analyses indicated that they might function as predictive biomarkers for moderate to severe stroke. We also observed a medium positive correlation between these two circRNAs and NIHSS. Plasma circPTP4A2 and circTLK2 levels were slight positively correlated with cerebral infarct volume only in anterior circulation infarction (ACI) patients. Levels of both circPTP4A2 and circTLK2 were closely related with large artery atherosclerosis (LAA) stroke. Moreover, changes within 7 days after admission in circPTP4A2 and circTLK2 were able to predict unfavorable clinical outcome 90 days after AIS. These results demonstrate that plasma circPTP4A2 and circTLK2 strongly correlated with severity, subtypes and prognosis of AIS, and they could serve as promising biomarkers.

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.

Co-existing intracranial and extracranial carotid atherosclerosis predicts large-artery atherosclerosis stroke recurrence: a single-center prospective study utilizing combined head-and-neck vessel wall imaging.

Intracranial and extracranial plaque features on high-resolution vessel wall imaging (HR-VWI) are associated with large-artery atherosclerosis (LAA) stroke recurrence. However, most studies have focused on a single vascular bed, and the prognostic value of combined intracranial and extracranial plaque features has yet to be studied. This study aimed to investigate the roles of plaque features, plaque number, and co-existing atherosclerosis in predicting stroke recurrence, utilizing combined head-and-neck HR-VWI. From September 2016 to March 2020, participants with acute LAA ischemic strokes were prospectively enrolled and underwent combined head-and-neck HR-VWI. The participants were followed for stroke recurrence for at least 12months or until a subsequent event occurred. The imaging features at baseline, including conventional and histogram plaque features, plaque number, and co-existing atherosclerosis, were evaluated. Univariable Cox regression analysis and the least absolute shrinkage and selection operator (lasso) method were used for variable screening. Multivariable Cox regression analyses were used to determine the independent risk factors of stroke recurrence. A total of 97 participants (59 ± 12years, 63 men) were followed for a median of 30.9months, and 21 participants experienced recurrent strokes. Multivariable Cox analysis identified co-existing intracranial high signal on T1-weighted fat-suppressed images (HST1) and extracranial carotid atherosclerosis (HR, 6.12; 95% CI, 2.52-14.82; p = 0.001) as an independent imaging predictor of stroke recurrence. Co-existing intracranial HST1 and extracranial carotid atherosclerosis independently predicted LAA stroke recurrence. Combined head-and-neck HR-VWI is a promising technique for atherosclerosis imaging. This prospective study using combined head-and-neck HR-VWI highlighted the necessity of both intracranial culprit plaque evaluation and multi-vascular bed assessment, adding value to the prediction of stroke recurrence. • This study highlighted the necessity of both intracranial culprit plaque evaluation and multi-vascular bed assessment, adding value to the prediction of stroke recurrence. • This prospective study using combined head-and-neck HR-VWI found co-existing intracranial HST1 and extracranial carotid atherosclerosis to be independent predictors of stroke recurrence.

Twenty-four-hour ambulatory blood pressure variability and association with ischemic stroke subtypes in the subacute stage.

Blood pressure (BP) variability (BPV) increases the risk of cerebral disease in both hemorrhagic and ischemic strokes. However, whether BPV is associated with different types of ischemic stroke remains unclear. In this study, we explored the relationship between BPV and ischemic stroke subtypes. We enrolled consecutive patients aged 47-95 years with ischemic stroke in the subacute stage. We categorized them into four groups based on their artery atherosclerosis severity, brain magnetic resonance imaging markers, and disease history: large-artery atherosclerosis, branch atheromatous disease, small-vessel disease, and cardioembolic stroke. Twenty-four-hour ambulatory blood pressure monitoring was performed, and the mean systolic blood pressure/diastolic blood pressure, standard deviation, and coefficient of variation were calculated. A multiple logistic regression model and random forest were used to test the relationship between BP and BPV in the different types of ischemic stroke. A total of 286 patients, including 150 men (73.0 ± 12.3 years) and 136 women (77.8 ± 9.6 years) were included in the study. Of these, 86 (30.1%) patients had large-artery atherosclerosis, 76 (26.6%) had branch atheromatous disease, 82 (28.7%) had small-vessel disease, and 42 (14.7%) had cardioembolic stroke. There were statistically significant differences in BPV between subtypes of ischemic stroke in 24-h ambulatory blood pressure monitoring. The random forest model showed that BP and BPV were important features associated with ischemic stroke. Multinomial logistic regression analysis demonstrated that systolic blood pressure levels; systolic blood pressure variability at 24 h, daytime and nighttime; and nighttime diastolic blood pressure were independent risk factors for large-artery atherosclerosis after adjustment for confounders. When compared to branch atheromatous disease and small-vessel disease, nighttime diastolic blood pressure and standard deviation of diastolic blood pressure were significantly associated with patients in the cardioembolic stroke group. However, a similar statistical difference was not seen in patients with large-artery atherosclerosis. The results of this study indicate a discrepancy in blood pressure variability among different ischemic stroke subtypes during the subacute stage. Higher systolic blood pressure and systolic blood pressure variability during the 24 h, daytime, and nighttime, and nighttime diastolic blood pressure were independent predictors for large-artery atherosclerosis stroke. Increased nighttime diastolic BPV was an independent risk factor for cardioembolic stroke.

Targeted Metabolomic Biomarkers for Stroke Subtyping.

Ischemic stroke is a heterogeneous disease with various etiologies. The current subtyping process is complicated, time-consuming, and costly. Metabolite-based biomarkers have the potential to improve classification and deliver optimal treatments. We here aimed to identify novel, targeted metabolomics-based biomarkers to discriminate between large-artery atherosclerosis (LAA) and cardioembolic (CE) stroke. We acquired serum samples and clinical data from a hospital-based acute stroke registry (ischemic stroke within 3 days from symptom onset). We included 346 participants (169 LAA, 147 CE, and 30 healthy older adults) and divided them into training and test sets. Targeted metabolomic analysis was performed using quantitative and quality-controlled liquid chromatography with tandem mass spectrometry. A multivariate regression model using metabolomic signatures was created that could independently distinguish between LAA and CE strokes. The training set (n = 193) identified metabolomic signatures that were different in patients with LAA and CE strokes. Six metabolomic biomarkers, i.e., lysine, serine, threonine, kynurenine, putrescine, and lysophosphatidylcholine acyl C16:0, could discriminate between LAA and CE stroke after adjusting for sex, age, body mass index, stroke severity, and comorbidities. The enhanced diagnostic power of key metabolite combinations for discriminating between LAA and CE stroke was validated using the test set (n = 123). We observed significant differences in metabolite profiles in LAA and CE strokes. Targeted metabolomics may provide enhanced diagnostic yield for stroke subtypes. The pathophysiological pathways of the identified metabolites should be explored in future studies.

Abstract 93: Effect Of Intravenous Tirofiban Following Successful Endovascular Thrombectomy On Functional Outcomes In Large Artery Atherosclerotic Stroke: Secondary Analysis Of A Randomized Clinical Trial

Background: Incomplete reperfusion contributes to reduced neurological recovery of patients with acute large vessel occlusion and successful reperfusion after endovascular thrombectomy. Intravenous tirofiban might enhance macrocirculatory and microcirculatory reperfusion in these patients, especially in those with large artery atherosclerotic stroke. We aimed to investigate whether treatment with adjunct intravenous tirofiban is associated improved outcomes following successful reperfusion in patients with acute large artery atherosclerotic stroke. Methods: In this subgroup analysis of RESCUE BT trial, patients with intracranial large artery atherosclerotic stroke and an expanded Treatment in Cerebral Ischemia angiographic score of 2b50 to 3 were included. The primary outcome was the difference in proportion of independent functional outcome, defined as a modified Rankin score of 0 to 2 at 90 days. Safety outcomes included the rates of symptomatic intracranial hemorrhage and 90-day mortality. Results: Among the 382 patients with intracranial large artery atherosclerosis stroke and successful reperfusion (median [IQR] age, 65 (55-72) years; 105 [27.5%] women), 175 patients (45.8%) were treated with intravenous tirofiban and 207 (54.2%) with placebo. The proportion of patients with independent functional outcome at 90 days was 54.3% (95/175) with tirofiban and 44.0% (91/207) with placebo (adjusted odds ratio [aOR], 1.59; 95% CI, 1.03-2.45; P = 0.04). Intravenous tirofiban was not significantly associated with an increased risk of symptomatic intracranial hemorrhage within 48 hours (12/175 [6.9%] vs. 11/207 [5.3%]; aOR, 1.41; 95% CI, 0.59-3.34; P = 0.44) or 90-day mortality (21/175 [12.0] vs. 34/207 [16.4%]; aOR, 0.71; 95% CI, 0.38-1.31; P = 0.27). Conclusions: Among patients with acute large artery atherosclerotic stroke and successful reperfusion following endovascular thrombectomy, adjunct intravenous tirofiban was associated with a higher rate of independent functional outcome, without higher rates of symptomatic intracranial hemorrhage or mortality. Confirmatory randomized trials in these patients are desirable.