Residual inflammatory risk and vulnerable plaque in the carotid artery in patients with ischemic stroke.

Objective: Inflammation is a central driver of atherogenesis and eventual plaque rupture. This study aimed to evaluate the association between residual inflammatory risk (RIR) and vulnerable plaques in the carotid artery in patients with ischemic stroke. Methods: Patients with acute ischemic stroke were enrolled from January 2021 to July 2022. They were divided into four groups: RIR only (LDL-C <2.6 mmol/L and hsCRP ≥2 mg/L), residual cholesterol risk (RCR) only (LDL-C ≥2.6 mmol/L and hsCRP <2 mg/L), both risk or residual cholesterol and inflammatory risk (RCIR) (LDL-C ≥2.6 mmol/L and hsCRP ≥2 mg/L), and neither risk (LDL-C <2.6 mmol/L and hsCRP <2 mg/L). Vulnerable plaques were determined if it had a low attenuated plaque CT value of <35 Hounsfield Units (HU) and a remodeling index of >1.1, which indicated a positive remodeling. Results: Out of the 468 enrolled patients, 157 (33.5%) were detected to have vulnerable plaques. The proportion of patients with neither risk, RIR, RCR, and RCIR were 32.9%, 28.6%, 18.8%, and 19.7%, respectively. Patients with vulnerable plaques exhibited a higher prevalence of hyperlipidemia (P = 0.026), higher proportion of RIR (P = 0.015), a higher ratio of stroke subtypes of large artery atherosclerosis (P = 0.012), and high leukocyte counts (P < 0.001). The logistic regression analysis detected that RIR was associated with vulnerable plaques after adjusted for major confounding factors (OR 1.98, 95% CI 1.13-3.45, P = 0.016), especially in the large artery atherosclerosis subtype (OR 2.71, 95% CI 1.08-6.77, P = 0.034). Conclusions: In patients with ischemic stroke, RIR is associated with the vulnerability of carotid plaques, especially for those with the large artery atherosclerosis subtype. Therefore, further studies investigating the interventions to modulate inflammation in these patients may be warranted.

Prognostic factors for acute vertebrobasilar artery occlusion-reperfusion: a multicenter retrospective cohort study.

BACKGROUND: This study aimed to analyze the long-term prognostic factors in acute vertebrobasilar artery occlusion (VBAO) patients treated with endovascular treatment (EVT). METHODS: This study was performed using the acute posterior circulation ischemic stroke registry database from 21 stroke centers in 18 cities in China and retrospectively included consecutive patients aged 18 years or older with an acute, symptomatic, radiologically confirmed VBAO who were treated with EVT between December 2015 and December 2018. Favorable clinical outcomes were evaluated by machine-learning methods. A clinical signature was constructed in the training cohort using the least absolute shrinkage and selection operator regression and was validated in the validation cohort. RESULTS: From 28 potential factors, 7 variables were independent prognostic factors and were included in the model: Modified Thrombolysis in Cerebral Infarction (M) [odds ratio (OR): 2.900; 95% confidence interval [CI]: 1.566-5.370], age (A) (OR, 0.977; 95% CI: 0.961-0.993), National Institutes of Health Stroke Scale (N) (13-27 vs. ≤12: OR, 0.491; 95% CI: 0.275-0.876; ≥28 vs. ≤12: OR, 0.148; 95% CI: 0.076-0.289), atrial fibrillation (A) (OR, 2.383; 95% CI: 1.444-3.933), Glasgow Coma Scale (G) (OR, 2.339; 95% CI: 1.383-3.957), endovascular stent-retriever thrombectomy (E) (stent-retriever vs. aspiration: OR, 0.375; 95% CI: 0.156-0.902), and estimated time of onset of the occlusion to groin puncture (Time) (OR, 0.950; 95% CI: 0.909-0.993) (abbreviated as MANAGE Time). In the internal validation set, this model was well calibrated with good discrimination [C-index (95% CI)=0.790 (0.755-0.826)]. A calculator based on the model can be found online ( http://ody-wong.shinyapps.io/1yearFCO/ ). CONCLUSION: Our results indicate that optimizing for EVT, along with specific risk stratification, may improve long-term prognosis. However, a larger prospective study is needed to confirm the findings.

Effects of admission systemic inflammatory indicators on clinical outcomes in patients with vertebrobasilar artery occlusion: insight from the PERSIST registry.

BACKGROUND: Few studies have focused on the effect of systemic inflammation in vertebrobasilar artery occlusion (VBAO). The aim of this study was to investigate the relationship between inflammatory indicators and the prognosis of VBAO patients receiving endovascular treatment (EVT). METHOD: Patients with VBAO who were treated with EVT within 24 hours of the estimated occlusion time were included in this study. Multivariate logistic regression and elastic net regularization were performed to analyze the effects of inflammatory indicators on the prognosis of patients with VBAO. The primary outcome was unfavorable outcome (a modified Rankin Scale score of 4-6) at 90 days. Secondary outcomes included symptomatic intracranial hemorrhage, in-hospital mortality, 90 day mortality, 1 year unfavorable outcome, and mortality. RESULTS: 560 patients were included in the study. Multivariate analysis showed that white blood cells (W), neutrophils (N), neutrophil to lymphocyte ratio (NLR), platelet to neutrophil ratio, platelet to white blood cell ratio, and NLR to platelet ratio were associated with the primary outcome. Elastic net regularization indicated that W, N, and NLR were the major inflammatory predictors of unfavorable outcome at 90 days. For long term prognosis, we found that the inflammatory indicators that predicted 1 year outcomes were consistent with those that predicted 90 day outcomes. CONCLUSION: Inflammatory indicators, especially W, N, and NLR, were associated with moderate and long term prognosis of patients with VBAO treated with EVT.

The ACORNS grading scale: a novel tool for the prediction of malignant brain edema after endovascular thrombectomy.

BACKGROUND: To develop and validate a novel tool for predicting the development of malignant brain edema (MBE) in large vessel occlusion stroke patients after endovascular thrombectomy (EVT). METHODS: We used a prospectively registered population of EVT patients from three comprehensive stroke centers. The population was randomly divided into two subsets (7:3): a training cohort and an internal validation cohort. External validation was performed using the Endovascular Treatment for Acute Anterior Circulation Ischemic Stroke Registry in China (ACTUAL) database. MBE was defined as (1) hypodense parenchyma in at least 50% of the middle cerebral artery and signs of local brain swelling, and (2) a midline shift of ≥5 mm at the septum pellucidum or pineal gland with obliteration of the basal cisterns. The model was constructed using logistic regression analysis. The performance of the model was examined in terms of discrimination and calibration. RESULTS: After adjusting for other confounders, baseline National Institutes of Health Stroke Scale (NIHSS) and Alberta Stroke Program Early CT (ASPECT) scores, a clinical history of hypertension, collateral status, intravenous thrombolysis before thrombectomy, fasting blood glucose, reperfusion status, and occlusion site were found to be independent predictors of MBE. These variables were combined to create the ACORNS grading scale. The areas under the curve in receiver operating curve analysis were 0.850 (95% CI 0.816 to 0.884), 0.874 (95% CI 0.821 to 0.926), and 0.785 (95% CI 0.740 to 0.829) for the training, internal validation, and external validation cohorts, respectively, indicating good discriminative performance in the validation cohorts. CONCLUSIONS: The ACORNS grading scale is an accurate and easily applicable model for the prediction of the development of MBE after EVT.

Effects of perioperative glycemic indicators on outcomes of endovascular treatment for vertebrobasilar artery occlusion.

Objective: Endovascular treatment (EVT) is, to date, the most promising treatment of vertebrobasilar artery occlusion (VBAO). The study aimed to determine the influence of perioperative glucose levels on clinical outcomes in patients with acute VBAO treated with EVT. Methods: We retrospectively collected consecutive VBAO patients received EVT in 21 stroke centers in China. The associations between perioperative glycemic indicators (including fasting blood glucose[FBG], admission hyperglycemia, stress hyperglycemia ratio [SHR] and short-term glycemic variability [GV]) and various clinical outcomes were analyzed in all patients and subgroups stratified by diabetes mellitus (DM). Results: A total of 569 patients were enrolled. Admission hyperglycemia significantly correlated with increased risk of symptomatic intracranial hemorrhage (sICH) (odds ratio [OR] 3.24, 95% confidence interval [CI]: 1.40-7.46), poor functional outcomes at 90 days (OR 1.91, 95%CI: 1.15-3.18) and 1 year (OR 1.96, 95%CI: 1.20-3.22). Similar significant correlations exist between FBG, SHR, GV and all the adverse outcomes except higher levels GV was not associated with increased risk of sICH (OR 1.04, 95% CI: 0.97-1.12). Subgroup analyses showed that admission hyperglycemia, FBG and SHR were significantly associated with adverse outcomes in non-diabetic patients, but not in DM patients. While, GV was associated with poor functional outcomes regardless of diabetes history. Conclusions: Admission hyperglycemia, FBG, SHR and short-term GV in VBAO patients treated with EVT were associated with adverse outcomes. The results suggested that comprehensive evaluation and appropriate management of perioperative glucose might be important for patients with VBAO and treatment with EVT.

Initial symptoms of vertebrobasilar artery occlusions and the outcomes after endovascular treatment.

BACKGROUND: Acute vertebrobasilar artery occlusion (VBAO) is a devastating disease in stroke patients. This study was aimed to identify the initial symptoms of patients with acute VBAO receiving endovascular treatment and determine its associations with clinical outcomes. METHODS: Patients with VBAO receiving endovascular treatment at 21 stroke centres in China were recruited for this derivation cohort A data-driven approach of latent class analysis was applied to identify distinct symptom typologies of VBAO patients. Multivariable binary and ordinary logistic regressions were used to evaluate the associations between symptom subtypes and clinical outcomes. RESULTS: A total of 548 patients were analysed in this study. Four distinct subgroups were defined: the vestibular symptom group (32.8%), anterior circulation mimic group (26.5%), non-specific symptom group (14.8%) and severe VBAO symptom group (25.9%). Compared with severe VBAO symptoms, non-specific symptoms were independently associated with higher rates of favourable outcome and functional independence at the 3 months [odds ratio (OR) 2.46, 95% confidence interval (CI) 1.15-5.28; OR 3.46, 95% CI 1.54-7.79]and 1 year follow-up (OR 2.25, 95% CI 1.05-4.82; OR 2.69, 95% CI 1.22-5.92), and better functional improvement (shift in mRS score) at the 3 months (OR 2.05, 95% CI 1.15-3.67). CONCLUSION: We identified four distinctive subtypes based on the initial symptoms of VBAO patients. Severe VBAO symptoms were associated with poor outcomes while non-specific and vestibular symptoms were indicators of a favourable outcome.

A Dynamic Nomogram for 3-Month Prognosis for Acute Ischemic Stroke Patients After Endovascular Therapy: A Pooled Analysis in Southern China.

Cerebral edema (CDE) is a common complication in patients with acute ischemic stroke (AIS) and can reduce the benefit of endovascular therapy (EVT). To determine whether certain risk factors are associated with a poor prognosis mediated by CDE after EVT. The 759 patients with anterior circulation stroke treated by EVT at three comprehensive stroke centers in China from January 2014 to October 2020 were analyzed. Patients underwent follow-up for 3 months after inclusion. The primary endpoint was a measure of a poor prognosis (modified Rankin Scale score ≥ 3) at 3 months assessed in all patients receiving EVT. Least absolute shrinkage and selection operator and multivariate logistic regression were used to select variables for the prognostic nomogram. Based on these variables, the nomogram was established and validated. In addition, structural equation modeling was used to explore the pathways linking CDE and a poor prognosis. Seven predictors were identified, namely, diabetes, age, baseline Alberta Stroke Program Early CT score, modified Thrombolysis in Cerebral Infarction score, early angiogenic CDE, National Institutes of Health Stroke Scale score, and collateral circulation. The nomogram consisting of these variables showed the best performance, with a large area under the curve in both the internal validation set (0.850; sensitivity, 0.737; specificity, 0.887) and external validation set (0.875; sensitivity, 0.752; specificity, 0.878). In addition, CDE (total path coefficient = 0.24, P < 0.001) served as a significant moderator. A nomogram for predicting a poor prognosis after EVT in AIS patients was established and validated with CDE as a moderator.

Blood Pressure After Endovascular Thrombectomy and Malignant Cerebral Edema in Large Vessel Occlusion Stroke.

Background: Elevated blood pressure (BP) can cause blood-brain barrier disruption and facilitates brain edema formation. We aimed to investigate the association of BP level after thrombectomy with the development of malignant cerebral edema (MCE) in patients treated with endovascular thrombectomy (EVT). Methods: Consecutive patients who underwent EVT for an anterior circulation ischemic stroke were enrolled from three comprehensive stroke centers. BP was measured hourly during the first 24 h after thrombectomy. MCE was defined as swelling causing a midline shift on the follow-up imaging within 5 days after EVT. Associations of various BP parameters, including mean BP, maximum BP (BPmax), and BP variability (BPV), with the development of MCE were analyzed. Results: Of the 498 patients (mean age 66.9 ± 11.7 years, male 58.2%), 97 (19.5%) patients developed MCE. Elevated mean systolic BP (SBP) (OR, 1.035; 95% CI, 1.006-1.065; P = 0.017) was associated with a higher likelihood of MCE. The best SBPmax threshold that predicted the development of MCE was 165 mmHg. Additionally, increases in BPV, as evaluated by SBP standard deviation (OR, 1.061; 95% CI, 1.003-1.123; P = 0.039), were associated with higher likelihood of MCE. Interpretation: Elevated mean SBP and BPV were associated with a higher likelihood of MCE. Having a SBPmax > 165 mm Hg was the best threshold to discriminate the development of MCE. These results suggest that continuous BP monitoring after EVT could be used as a non-invasive predictor for clinical deterioration due to MCE. Randomized clinical studies are warranted to address BP goal after thrombectomy.

Obesity and Poststroke Fatigue: A 2-Year Longitudinal Study.

INTRODUCTION: Obesity is associated with fatigue in many diseases, but the correlation between obesity and poststroke fatigue (PSF) is unclear. The study aimed to investigate the relationship between body mass index (BMI) and the occurrence of and recovery from PSF. METHODS: Within 3 days of the onset of ischemic stroke, patients were consecutively recruited. We assessed PSF at admission and at 6, 12, and 24 months with the Fatigue Severity Scale (FSS). Multivariable logistic regression and restricted cubic spline function were used to explore the relationships between baseline BMI and the risk of PSF at different time points. The correlation between baseline BMI and the dynamic changes in the natural logarithm transformation of the FSS (lnFSS) score during the follow-up period was analyzed by the piecewise linear mixed-effects model. RESULTS: A total of 1026 stroke patients were included. Multivariable analyses indicated that obesity was associated with a decreased risk of early PSF (fatigue diagnosed at baseline) [odds ratio (OR) 0.61, 95% confidence interval (CI) 0.41-0.93] but an increased risk of late PSF (fatigue diagnosed 6 months after the index stroke) (OR 1.63, 95% CI 1.06-2.50 for 6 months; OR 1.87, 95% CI 1.18-2.96 for 12 months; OR 2.11, 95% CI 1.28-3.49 for 24 months). Longitudinal analyses indicated that in the late stage of fatigue, the higher the BMI category, the slower the rate of decrease was for the FSS score. CONCLUSION: Obese patients are less likely to develop fatigue in the acute stage of ischemic stroke. However, they are more prone to late fatigue and exhibit a slower decline in the FSS score in the long term.

Corrigendum: Learning Curve for Endovascular Treatment of Anterior Circulation Large Vessel Occlusion at a Single Center.

[This corrects the article DOI: 10.3389/fneur.2020.587409.].

Blood pressure variability and outcomes after mechanical thrombectomy based on the recanalization and collateral status.

BACKGROUND: Blood pressure (BP), recanalization status, and collateral circulation are important factors for cerebral autoregulation after stroke. We aimed to investigate the association of various BP variability (BPV) parameters with clinical outcomes after mechanical thrombectomy (MT) according to recanalization and collateral status. METHODS: We included 502 consecutive patients who underwent MT due to anterior circulation large vessel occlusion stroke at three comprehensive stroke centers. BPV parameters were standard deviation (SD), maximum/minimum BP, coefficient of variation (CV) and successive variation (SV). The clinical outcomes included 90-day functional outcome assessed by modified Rankin Scale score and symptomatic intracranial hemorrhage (sICH). RESULTS: Among the included patients, 219 (43.6%) achieved good functional outcomes and 59 (11.8%) developed sICH. After adjusting for confounders, higher systolic BP (SBP) variability [CV (odds ratio (OR), 1.089, p = 0.035), SV (OR, 1.082, p = 0.004). and SD (OR, 1.074, p = 0.027)] was associated with a lower likelihood of a favorable outcome. In addition, higher SBP [CV (OR, 1.156, p = 0.001) and SD (OR, 1.118, p = 0.001)] were significantly associated with increased odds of sICH. Moreover, the relationship between BPV and the outcomes depended on recanalization status. However, regardless of collateral status, a higher BPV after MT was associated with worse outcomes. CONCLUSIONS: Higher SBP SD and CV during the first 24 h after MT was a powerful predictor of worse clinical outcomes, regardless of the collateral status. However, the effects of BPV on outcomes were more substantial among patients with successful reperfusion.

Essen Stroke Risk Score Predicts Carotid Atherosclerosis in Chinese Community Populations.

BACKGROUND: Carotid atherosclerosis (CA) is closely related to stroke, and Framingham Risk Score (FRS) has been used for CA risk evaluation. However, FRS could only be used for subjects of up to 74 years old. The present study was to determine if Essen Stroke Risk Score (ESRS) could be used to estimate CA risk in community populations without age limits. METHODS: In the present prospective multi-community screening study, we evaluated the prevalence of CA using high-resolution ultrasound in 521 males and 1039 females (35 to 91 years old). Both FRS and ESRS were calculated for the subjects. Multivariate logistic regression analysis was used to determine the predictive values of FRS and ESRS for CA in these subjects. RESULTS: Ultrasound data showed that CA was present in 56.2% of the participants (total of 1560). Multivariate logistic regression analysis showed that ESRS was associated with CA with odds ratio (OR): 1.34 (95% confidence interval (CI), 1.12-1.60, p=0.001). Central obesity (OR: 1.40, CI: 1.07-1.83, p=0.015), female (OR: 0.55, CI: 0.39-0.77, p <0.001) and age (OR: 2.63, CI: 2.27-3.06, p <0.001) were also associated with CA. Based on the estimated area under curve (AUC), FRS (AUC 0.775) was better than ESRS (AUC 0.693) (z statistic 6.774, p <0.001) for CA prediction for individuals of ≤74 years old. However, receiver operating characteristic analysis showed ESRS was a good CA predictor for all subjects (AUC of 0.715). CONCLUSION: ESRS could be used as an alternative to FRS to predict CA in community population of all age.

Effect of matrine on JAK2/STAT3 signaling pathway and brain protection in rats with cerebral ischemia-reperfusion.

BACKGROUND: Ischemic encephalopathy is a common clinical disease. The main treatment goal is to achieve vascular recanalization. However, after vascular recanalization, the reperfusion of fresh blood can change local cell metabolism, thus adversely affecting cell structure and function, which can result in reperfusion injury. OBJECTIVES: To explore the effect of matrine intervention of different concentrations on JAK2/STAT3 signaling pathway and brain protection in rats with cerebral ischemia-reperfusion. MATERIAL AND METHODS: Healthy male Sprague Dawley rats were divided into a blank control group (20 rats), a model group (80 rats) and a sham group (20 rats). In the model group, the middle cerebral artery was occluded with suture method to establish cerebral ischemia-reperfusion model rats, which were subdivided into cerebral ischemia-reperfusion group, and 5, 10 and 20 mg/kg matrine groups, with 20 rats in each group. Indicators including neurological function score, brain infarct size, brain water content, lactic dehydrogenase activity, protein expressions of p-JAK2 and p-STAT3, as well as superoxide dismutase activity and malondialdehyde content were evaluated. RESULTS: Compared with cerebral ischemia-reperfusion group, all the indicators were significantly improved in the 3 matrine treatment groups in a dose-dependent manner, and protein expressions of p-JAK2 and p-STAT3 in the brain tissue and brain cell apoptosis rate were decreased with the increase of matrine concentration (all p < 0.05). CONCLUSIONS: Matrine can significantly ameliorate the neurological function and brain edema of rats with cerebral ischemia-reperfusion, and improve superoxide dismutase, malondialdehyde and lactic dehydrogenase levels in the brain tissue and brain cell apoptosis rate. The mechanism of matrine may be related to the inhibition of abnormal JAK2/STAT3 signaling pathway activation.

Learning Curve for Endovascular Treatment of Anterior Circulation Large Vessel Occlusion at a Single Center.

Background and purpose: Data concerning the learning curve for endovascular treatment (EVT) of anterior circulation large vessel occlusion are scarce. This study aimed to investigate the relationship between operator experience and the outcome of EVT and to further identify the number of cases needed to acquire the ability to perform successful reperfusion. Materials and methods: Four hundred and thirty-four patients who underwent EVT by seven operators at a single center from January 2016 to September 2019 were enrolled. Procedural experience was defined by the number of cases performed by each operator. Multivariable backward regression analyses were used to investigate the association between procedural experience and functional independence (defined as a modified Rankin Scale score of 0-2), 90-days mortality, successful reperfusion (defined as a modified Thrombolysis in Cerebral Infarction score of 2b-3), and puncture-to-reperfusion time after adjusting for covariates. A risk-adjusted cumulative sum (RA-CUSUM) chart was utilized to identify the number of caseloads needed to overcome the learning curve effect. Results: Procedural experience was independently associated with functional independence, 90-days mortality, successful reperfusion, and puncture-to-reperfusion time reduction (per 10-case increment: OR 1.219, 95% CI: 1.079-1.383, P < 0.001; OR 0.847, 95% CI: 0.738-0.968, P = 0.016; OR 1.553, 95% CI: 1.332-1.830, P < 0.001 and ß 8.087 min, 95% CI: 6.184-9.991, P < 0.001, respectively). The RA-CUSUM chart indicated that at least 29 cases were required to overcome the learning curve effect. Conclusions: There was a dose-response relationship between operator case volume and clinical outcome, procedure time, and successful reperfusion. The experience needed for successful EVT was at least 29 cases.

Influence of procedure time on outcome and hemorrhagic transformation in stroke patients undergoing thrombectomy.

BACKGROUND AND PURPOSE: Data on procedure time (PT) for mechanical thrombectomy (MT) are scarce. Moreover, the relationship among PT, postprocedural hemorrhagic transformation (HT), and functional outcomes in MT patients remains unclear. We investigated whether postprocedural HT mediated the relationship between PT and functional outcomes in patients with stent-retriever thrombectomy. METHODS: We retrospectively analyzed consecutive patients who underwent MT at two comprehensive stroke centers. PT was defined as the time from puncture to first successful recanalization or to abortion of the procedure if successful recanalization was not achieved. A favorable outcome was defined as a 90-day modified Rankin Scale score of 0-2. HT was classified using the European Cooperative Acute Stroke Study definition. RESULTS: Among 283 patients (mean age, 67.2 ± 11.9 years; male, 53.7%), 124 (43.8%) patients had a favorable outcome and 27 (9.5%) patients experienced symptomatic intracranial hemorrhage (sICH). Whether in the overall cohort or in the successful recanalization cohort, extended PT was an independent predictor for a poor outcome (per 30 min: OR 1.433, 95% CI 1.062-1.865, p = 0.019; OR 1.522, 95% CI 1.062-2.159, p = 0.020, respectively) and sICH (per 30 min: OR 1.391, 95% CI 1.030-1.865, p = 0.029; OR 1.716, 95% CI 1.161-2.648, p = 0.009, respectively). Moreover, postprocedural HT might partially explain the worse function outcomes in patients with an extended PT (the regression coefficient was changed by 28.2% and 28.1%, respectively). CONCLUSIONS: The PT is an independent predictor for 90-day outcomes in stent-retriever thrombectomy patients. Postprocedural HT was partially responsible for the worse outcome in patients who experienced a longer PT.

Anterior Borderzone Angle for Hemodynamic Collateral Metric in Patients with Symptomatic Middle Cerebral Artery Stenosis.

BACKGROUND AND AIMS: We aimed to introduce a parameter of anterior borderzone angle (ABZA) to quantitatively evaluate the ACA-MCA leptomeningeal collaterals for middle cerebral artery stenosis (MCAS). METHODS: Two hundred seventy-five patients with 50-100% MCAS and 100 controls were included. The 95% reference range of ABZA was obtained from the controls. ABZAtrans was defined as "ABZA/the 95% upper limit." Relationships between ABZA and MCAS, -ABZAtrans and the TICI grade, the American Society of Interventional and Therapeutic Neuroradiology/Society of Interventional Radiology (ASITN/SIR) collateral grade were analyzed. An ABZA grade model for the ACA leptomeningeal collaterals was tentatively developed. RESULTS: The 95% reference range of ABZA was 0.0º-23.0º. ABZA was significantly associated with MCAS by a function of the fourth power (R2 = 0.723, p < 0.001), and could predict hemodynamic MCAS (≥70%) with an AUC of 0.928 (95% CI 0.903-0.953). ABZAtrans was negatively correlated with the TICI grade (rho = -0.752, p < 0.001) and positively with the ASITN/SIR grade (rho = 0.921, p < 0.001). The ABZA grade was created by rounding -ABZAtrans to a nearest integer, and was closely associated with the ASITN/SIR grade (rho = 0.894, p < 0.001). CONCLUSIONS: ABZA can be used as a hemodynamic parameter to quantitatively evaluate ACA leptomeningeal collaterals.

From clinical to tissue-based dual TIA: Validation and refinement of ABCD3-I score.

OBJECTIVE: To investigate whether dual tissue-defined ischemic attacks, defined as multiple diffusion-weighted imaging lesions of different age and/or arterial territory (dual DWI), are an independent and stronger predictor of 90-day stroke than dual clinical TIAs (dual TIA). METHODS: Consecutive patients with clinically defined TIA were enrolled and assessed clinically and by MRI within 3 days. The predictive ability of the ABCD clinical factors, dual TIA, and dual DWI was evaluated by means of multivariate logistic regression. RESULTS: Among 658 patients who were included in the study and completed 90 days of follow-up, a total of 70 patients (10.6%) experienced subsequent stroke by 90 days. Multivariate logistic regression indicated that dual DWI was an independent predictor for subsequent stroke (odds ratio 4.64, 95% confidence interval 2.15-10.01), while dual TIA was not (odds ratio 1.18, 95% confidence interval 0.69-2.01). C statistics was higher when the item of dual TIA in ABCD3-I score was replaced by dual DWI (0.759 vs 0.729, p = 0.035). The net reclassification value for 90-day stroke risk was also improved (continuous net reclassification improvement 0.301, p = 0.017). CONCLUSION: Dual DWI independently predicted future stroke in patients with TIA. A new ABCD3-I score with dual DWI instead of dual clinical TIA may improve risk stratification for early stroke risk after TIA.

Variant recurrent risk among stroke patients with different CYP2C19 phenotypes and treated with clopidogrel.

Polymorphisms of CYP2C19 have been associated with variant risk of subsequent cardiovascular events in survivors of myocardial infarction (MI) receiving clopidogrel. This study evaluated the impacts of CYP2C19 polymorphisms on stroke recurrence and other vascular events in a cohort of Chinese patients receiving clopidogrel. From Nanjing Stroke Registry Program, 625 consecutive patients with ischemic stroke were enrolled between May 2008 and April 2010. CYP2C19 variants (*2, *3, and *17) were genotyped. Clinical outcomes were determined with three monthly follow-up. The primary endpoint was a composite of vascular death, non-fatal ischemic stroke, and non-fatal MI. The second endpoint was bleeding events. The median exposure to clopidogrel was 13.2 (interquartile range, 8.9-18.0) months. Primary endpoint was observed in 85 (13.6%) patients and secondary endpoint in 13 (2.1%) patients. Frequencies of CYP2C19*1, *2, *3, and *17 alleles were 61.2, 34.0, 3.8, and 1.0%, respectively, in this patient cohort. CYP2C19 loss-of-function allele (*2 and *3, LOF) carriers were observed with higher risk of subsequent vascular events compared with non-carriers (17.2 versus 8.1%, HR = 2.16, 95% CI: 1.31-3.56, p = 0.003). After adjusted for age, sex, major cardiovascular risk factors, and drug agent, CYP2C19 LOF carrier was independently associated with primary endpoint (HR = 2.31, 95% CI: 1.39-3.84, p = 0.001). No significant association between CYP2C19 gain-of-function (*17, GOF) and clinical events was detected. In Chinese stroke survivors treated with clopidogrel, carriers of CYP2C19 LOF allele may have increased risk of recurrence.

Association of heme oxygenase-1 gene rs2071746 polymorphism with vascular outcomes in patients with atherosclerotic stroke.

As an inducible isoform of heme oxygenase (HO), HO-1 was suggested to have an anti-oxidative stress, anti-inflammatory, anti-apoptotic and anti-proliferative effect. It was regarded as an important cytoprotective enzyme. We undertook this study to investigate whether HO-1 gene rs2071746 polymorphism was associated with clinical outcomes in atherosclerosis ischemic stroke patients. Between December 2009 and October 2012, consecutive atherosclerosis ischemic stroke patients were enrolled. The primary endpoint was the composite of vascular death, nonfatal ischemic stroke and myocardial infarct. A total of 961 patients were enrolled. After an average follow-up of 15.13 (SD=7.42) months, 89 patients (9.26%) had the primary endpoint. The cumulative incidence of the primary endpoint was significantly lower in A carriers (AT+AA) than TT genotype (7.9% vs. 12.2%, HR=0.648, 95% CI: 0.425-0.988, P=0.044). After adjustment for age, sex and other cardiovascular risk factors, we found that A carrier was an independent protective factor for atherosclerosis ischemic stroke (HR=0.646, 95% CI: 0.420-0.994, P=0.047). Age (HR=1.023, P=0.028) and low level of HDL (HR=1.772, P=0.012) were independent risk factors for the primary endpoint. In conclusion, HO-1 gene rs2071746 A allele carrier might be a protective factor for patients with atherosclerotic stroke.

Impacts of COX-1 gene polymorphisms on vascular outcomes in patients with ischemic stroke and treated with aspirin.

As the key point of function for aspirin to educe anti-platelet effects, cyclooxygenase-1 (COX-1) gene polymorphisms have long been suspected as a potential cause for aspirin nonresponsiveness. But this hypothesis has not been confirmed by large longitudinal studies. This study prospectively evaluated the impacts of COX-1 gene polymorphisms on stroke recurrence and other vascular events in a large cohort of Chinese patients with ischemic stroke and treated with aspirin. Between December 2009 and October 2012, consecutive patients with ischemic stroke and treated with aspirin were enrolled. Polymorphisms of four alleles (rs1330344, rs10306114, rs3842788 and rs5788) in COX-1 gene were determined at baseline. The primary endpoint was a composite of nonfatal ischemic stroke, myocardial infarction, and death from cardiovascular causes. Impacts of COX-1 gene polymorphisms on vascular outcomes were evaluated with multivariate analysis. A total of 859 patients were included in data analysis. The minor allele frequencies of rs1330344, rs10306114, rs3842788 and rs5788 were 38.53%, 0.12%, 6.64% and 5.53%, respectively. During 14.64 ± 7.44 months of follow-up, primary endpoint was observed in 67 (7.80%) patients. Incidence of primary endpoint was higher in patients with CC genotype of rs1330344 than in patients with CT or TT genotype (HR=1.916, 95% CI: 1.126-3.260, P=0.016). After being adjusted for potential confounding factors, rs1330344 CC genotype was still independently associated with incidence of primary endpoint (HR=1.958, 95% CI: 1.151-3.332, P=0.013). The impacts of other three tested polymorphisms on primary endpoint were unremarkable. In conclusion, in Chinese patients with ischemic stroke and treated with aspirin, CC genotype of rs1330344 may increase the risk of subsequent vascular events.