Missense Variants in Hypoxia-Induced VEGFA/VEGFR2 Signaling Predict the Outcome of Large Artery Atherosclerotic Stroke.

Collateral density variations are a major determinant of stroke outcome. Here, we explored the association of missense variants in hypoxia-induced VEGFA/VEGFR2 signaling and stroke outcome. We recruited 683 large artery atherosclerotic (LAA) stroke patients as the training set from Nanjing Stroke Registry Program between August 2013 and January 2016. To validate the findings from the training set, we recruited an additional 333 LAA stroke patients between February 2016 and January 2017 as the validation set. Genotyping of target SNPs (rs11549465 [HIF-1α], rs11549467 [HIF-1α], rs1870377 [VEGFR2], and rs2305948 [VEGFR2]) was conducted using a SNPscan method. Unfavorable outcome was defined as a modified Rankin Scale (mRS) score > 2 at three months after index event. In the training set, the AA genotype of rs1870377 led to a decreased risk of unfavorable outcomes in the recessive model (AA vs. TA + TT, OR 0.60, 95% CI 0.38-0.95, P = 0.031). This was confirmed in the validation set (OR 0.43, 95% CI 0.21-0.86, P = 0.017) and the combined set (OR 0.54, 95% CI 0.36-0.79, P = 0.002). We also found that A allele was a protective factor for stroke outcome in both validation set and combined set (OR 0.70, 95% CI 0.49-0.99, P = 0.044 and OR 0.77, 95% CI 0.63-0.94, P = 0.012, respectively). In silico analysis indicated that the rs1870377 variant led to structural alterations in VEGFR2 that may influence its activity. Our findings demonstrate that the rs1870377 in the hypoxia-induced VEGFA/VEGFR2 axis predicts the 3-month outcome of patients with LAA stroke.

Leukoaraiosis and earlier neurological outcome after mechanical thrombectomy in acute ischemic stroke.

BACKGROUND AND PURPOSE: The aim of the study was to evaluate whether leukoaraiosis (LA) severity is associated with earlier neurological outcome in acute stroke patients undergoing mechanical thrombectomy. MATERIALS AND METHODS: In this retrospective multicenter study, we evaluated 273 acute stroke patients treated with mechanical thrombectomy. LA severity was graded as 0-2 (absent-to-moderate) versus 3-4 (severe) according to the van Swieten scale. The main clinical outcome was the proportion of early neurological improvement and early neurological deterioration. Early neurological improvement was defined as a decrease of≥4 points on the NIHSS, or an NIHSS score of zero 24hours after baseline assessment. Early neurological deterioration was defined as an increase of≥4 points on the NIHSS 24hours after baseline assessment. RESULTS: There was a significantly lower early neurological improvement rate (17.1% versus 39.2%; P=0.006) and non-significantly higher early neurological deterioration rate (29.3% versus 17.7%; P=0.084) in patients with severe LA (sLA) compared with patients with absent-to-moderate LA. In multivariable analysis, sLA was inversely associated with early neurological improvement (OR, 0.31; 95% CI, 0.13-0.78; P=0.012). There was no significant association of sLA with early neurological deterioration. However, in patients without symptomatic intracranial hemorrhage, sLA was an independent predictor of early neurological deterioration (OR, 2.65; 95% CI, 1.09-6.45; P=0.032). CONCLUSIONS: sLA is a significant negative predictor of early neurological improvement and is an independent predictor of early neurological deterioration in patients without symptomatic intracranial hemorrhage.

Safety of Intra-Arterial Tirofiban Administration in Ischemic Stroke Patients after Unsuccessful Mechanical Thrombectomy.

PURPOSE: To assess the safety of low-dose intra-arterial (IA) tirofiban bolus after unsuccessful mechanical thrombectomy in patients with ischemic stroke due to large artery occlusion in anterior cerebral circulation. MATERIALS AND METHODS: Patients with ischemic stroke who were treated with mechanical thrombectomy were enrolled in a multicenter registry. Low-dose tirofiban was injected into the residual arterial thrombus in patients after unsuccessful mechanical thrombectomy. The major safety measurement was defined as symptomatic intracranial hemorrhage (SICH). The functional outcome at 90 days was assessed with the modified Rankin Scale, and a score of 0-2 was defined as favorable. RESULTS: Of the 632 enrolled patients, 154 (24.4%) received IA tirofiban treatment. The SICH rate was 13.6% (21/154) in patients with tirofiban and 16.7% (80/478) in patients without tirofiban (P = .361). IA tirofiban was not associated with increased risk of SICH (odds ratio [OR], 0.69; 95% confidence interval [CI], 0.36-1.31; P = .26). IA tirofiban treatment did not increase the risk of mortality at 90 days of the index stroke (OR, 0.66; 95% CI, 0.36-1.31; P = .15). Patients with large artery atherosclerosis stroke who were treated with tirofiban were associated with decreased risk of death (OR, 11.3% vs 23.4%; P = .042) compared to patients who were not treated with tirofiban. CONCLUSIONS: Low-dose IA tirofiban administration may be relatively safe in patients with ischemic stroke after unsuccessful recanalization.

A GWAS-supported variant interacting with diabetes predicts risk of atherothrombotic stroke in Han Chinese population.

BACKGROUND: A recent genome-wide association study has identified that rs4376531 variant conferred risk of atherothrombotic stroke (AS) in a Japanese population. This study was to explore the association in Han Chinese population. METHODS: A total of 1036 cases and 643 healthy controls were enrolled. We genotyped rs4376531 variant with SNPscan. Multivariate logistic regression analysis was used to determine the association of genetic variation with risk of AS. Interaction analysis was examined by SNPStats web tool. RESULTS: After adjusting for gender, age, body mass index (BMI), hypertension, diabetes and smoking, compared with CC genotype, we observed that GC and GG/GC genotypes were associated with a significantly decreased risk of AS (OR = 0.76, 95% CI = 0.58-0.99 and OR = 0.76, 95% CI = 0.58-0.98, respectively). The decreased risk was more obvious among subgroups with high BMI (OR = 0.63, 95% CI = 0.45-0.88), no hypertension (OR = 0.66, 95% CI = 0.46-0.94), diabetes (OR = 0.33, 95% CI = 0.17-0.64), and smoking (OR = 0.65, 95% CI = 0.44-0.95) in the dominant model (GG/GC vs CC). Interaction analysis also revealed that compared with non-diabetic patients with CC genotype, diabetic patients with CC genotype had a 4.48-fold (OR = 4.48; 95% CI = 2.98-6.72) increased risk of AS. CONCLUSION: Our data suggested that GC and GG/GC of rs4376531 contributed to a decreased risk of AS while CC genotype, interacting with diabetes, increased the stroke risk in Han Chinese population.

Combined effect of ASPECTS and age on outcome of patients with large core infarction treated with mechanical thrombectomy.

BACKGROUND: Despite the remarkable effectiveness of endovascular treatment (EVT), recent randomized controlled trials indicate that up to half of patients with large core infarction have a very poor outcome (modified Rankin Scale score 5-6 at 90 days). This study investigates the combined effect of Alberta Stroke Program Early CT Score (ASPECTS) and age on very poor outcome in patients with large core infarction treated with EVT. METHODS: This subanalysis of the MAGIC registry, which is a prospective, multicenter cohort study of early treatment in acute stroke, focused on patients with ASPECTS ≤5 presenting within 24 hours of stroke onset and receiving CT followed by EVT from November 1, 2021 to February 8, 2023. Multivariable logistic regression was used to investigate the independent and joint association of ASPECTS and age with very poor outcome. RESULTS: Among the 490 patients (57.3% men; median (IQR) age 69 (59-78) years), very poor outcome occurred more frequently in those with lower ASPECTS (65.2% in ASPECTS 0-2 vs 43.4% in ASPECTS 3-5; P<0.001). The predictive value of successful recanalization for very poor outcome was significant in patients with ASPECTS 3-5 (P=0.010), but it diminished in those with ASPECTS 0-2 (P=0.547). Compared with patients with ASPECTS 3-5 and age ≤69 years, the risk of a very poor outcome increased incrementally in those with lower ASPECTS, advanced age, or both (P<0.05). Graphical plot analysis showed a significantly lower probability of very poor outcome in younger patients (≤69 years) compared with older patients (>69 years) across all ASPECTS points. CONCLUSION: These findings suggest prioritizing young patients as candidates for EVT in those with ASPECTS 0-2.

Magnitude of systolic blood pressure reduction following endovascular treatment and clinical outcomes in acute large artery occlusion stroke.

BACKGROUND: The impact of lowering systolic blood pressure (SBP) following endovascular treatment (EVT) in acute large vessel occlusion stroke (LVOS) patients remains unclear. We aimed to explore the effect of the magnitude of SBP reduction (SBPr) after EVT on outcomes in LVOS patients. METHODS: We consecutively registered patients at three comprehensive stroke centres who had experienced EVT as a result of acute anterior circulation LVOS. SBPr was calculated as follows: (baseline SBP-mean SBP/baseline SBP)×100%. The 90-day modified Rankin Scale score ranging from 0 to 2 was defined as a favourable functional outcome. Based on CT scans obtained within 24 hours after procedure, symptomatic intracranial haemorrhage (sICH) was assessed according to the criteria of the European Cooperative Acute Stroke Study III. RESULTS: We enrolled 1080 patients, of which 908 (84.1%) had successful recanalisation. In the overall cohort, SBPr was correlated with lower odds of sICH (SBPr±10% as a reference, 20%-30%: OR 0.460; 95% CI: 0.245 to 0.864; p=0.016; >30%: OR 0.304; 95% CI 0.123 to 0.749; p=0.010). In patients who achieved successful reperfusion, SBPr>30% was correlated with higher odds of a poor outcome (SBPr±10% as a reference, OR 2.150; 95% CI 1.268 to 3.645; p=0.004) and SBPr has a similar tendency towards reducing the incidence of sICH. In the subgroup analyses, baseline Alberta Stroke Programme Early CT (ASPECT) score (pinteract=0.024) modified the effect of SBPr on the 90-day outcome. CONCLUSION: Among patients with EVT, a significant drop in SBP may be related to a poor functional outcome and a reduced incidence of sICH. Baseline ASPECT score may be an important interacting factor in the association of SBPr with the 90-day outcome. This study provides new insights for individualised BP management in patients with EVT.

CRP as a potential predictor of outcome in acute ischemic stroke.

Ischemic stroke is one of the major causes of death and long-term disability worldwide. C-reactive protein (CRP) as a potential biomarker for functional outcome after acute ischemic stroke remains controversial. The aim of the present study was to examine the association between the level of CRP and functional outcome of stroke. A total of 218 consecutive patients with acute ischemic stroke within 24 h after onset were recruited for the study. Poor functional outcome was defined as a modified Rankin scale score of >2 at 3 months after stroke. The retrospective analysis was performed to investigate whether CRP within 24 h after stroke is associated with poor functional outcome at 3 months. Multivariate logistic regression analysis indicated that the CRP level (odds ratio=1.146, 95%CI: 1.012-1.297, P=0.031) was an independent risk factor for poor outcome. The receiver operating characteristics curve analysis revealed that the optimal cut-off value of CRP to distinguish favorable from poor outcome was 6.34 (area under the curve=0.829, 95%CI: 0.772-0.887, P<0.001), with 68.2% sensitivity and 85.7% specificity. Spearman correlation analysis indicated that the CRP level was positively related to the baseline National Institutes of Health Stroke Scale (NIHSS) score (r=0.551, P<0.001), fasting glucose (r=0.301, P<0.001) and age (r=0.252, P<0.001). In conclusion, a high level of CRP within 24 h after onset was associated with a poor functional outcome after the acute ischemic event. The elevation of CRP may be correlated with the baseline NIHSS score, fasting glucose and age.

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.

Pre-Existing Non-Disabling Encephalomalacia Confers Risk to Stroke Outcomes After Endovascular Treatment.

BACKGROUND: Patients with previous stroke episodes tend to have poor outcomes after an endovascular treatment (EVT). Encephalomalacia (EM) is an objective indicator of previous strokes but has not been systematically investigated. The fundamental aim of this exploration is to investigate the effects of a pre-existing non-disabling EM on clinical outcomes after EVT. METHODS: Consecutive patients undergoing an EVT due to the anterior circulation large vessel occlusion (LVO) strokes were enrolled in the study. The pre-existing EM was defined as the focal hypodense lesions (≥ 3 mm in maximum diameter) on a non-contrast cranial CT using axial images before EVT. The primary outcome was the 90-day functional assessment using the modified Rankin Scale (mRS) score. The safety outcome was the incidence of symptomatic intracranial hemorrhage (sICH) defined as any hemorrhage within 24 h after an EVT, which is responsible for an increase of ≥ 4 points in the score of National Institutes of Health Stroke Scale (NIHSS). RESULTS: Of the 433 patients analyzed in this investigation, a pre-existing non-disabling EM was observed in 106 (24.5%) patients. After adjusting for potential confounding factors, patients with contralateral EM (OR = 2.68, 95% CI = 1.13-6.31; P = 0.025) and with an EM+ > 20 mm in maximum diameter (OR = 2.21, 95% CI = 1.01-4.85; P =0.048) were substantially associated with unfavorable outcomes (mRS > 2). For the sICH, we did not observe any association with the pre-existing EM (P > 0.05). CONCLUSIONS: A pre-existing non-disabling EM is common and safe in patients undergoing EVT. However, a contralateral EM and the large size of EM may predict an unfavorable outcome at 90 days, which should receive more attention before EVT.

Time Course and Clinical Relevance of Neurological Deterioration After Endovascular Recanalization Therapy for Anterior Circulation Large Vessel Occlusion Stroke.

Neurological deterioration (ND) is a devastating complication for patients with ischemic stroke after endovascular recanalization therapy (EVT). We aimed to investigate the time course and clinical relevance of ND after EVT. Consecutive patients with acute ischemic stroke who underwent EVT for large arterial occlusions of the anterior cerebral circulation were enrolled. The National Institutes of Health Stroke Scale (NIHSS) scores were assessed before EVT, at the end of EVT, at 24 h (d1), on day 3 (d3), on day 15 (d15), at discharge and anytime when ND was indicated. ND was defined as an increase of ≥ 4 points in the NIHSS score and was divided into acute ND (AD, within 24 h), subacute ND (SD, d1-d3), and delayed ND (DD, d3-d15 or discharge). Using multivariable logistic regression analysis, we explored predictors and outcomes of ND at different time periods. As a result, of 343 patients, 129 (37.6%) experienced ND, including 90 (26.2%) with AD, 27 (7.9%) with SD and 12 (3.5%) with DD. Multivariable logistic regression analysis revealed that history of hypertension, cardioembolic stroke, lower Alberta Stroke Program Early Computed Tomography Score (ASPECTS), and poor collaterals were significantly associated with an increased risk of AD; history of hypertension, lower ASPECTS, poor collaterals, and unsuccessful recanalization, with SD; and high admission NIHSS score, with DD. In addition, patients who experienced AD (OR = 10.22, P < 0.001), SD (OR = 15.89, P = 0.004), or DD (OR = 8.31, P = 0.015) were more likely to have poor outcomes. ND was a strong predictor of poor stroke outcomes. Management of related risk factors at different ND time periods might improve the prognosis of EVT.

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.

TNFRSF11B polymorphisms predict poor outcome after large artery atherosclerosis stroke.

Osteoprotegerin is involved in the progression of atherosclerosis. This study aimed to determine whether TNFRSF11B polymorphisms are associated with prognosis of large artery atherosclerosis (LAA) stroke. Three TNFRSF11B polymorphisms (rs2073617, rs2073618 and rs3134069) were genotyped in 1010 patients with LAA stroke. Short-term outcome was evaluated using the modified Rankin Scale score at 3-month after stroke onset. Long-term outcome was assessed using the stroke recurrence. We found that rs2073617G was associated with an increased risk of poor outcome of LAA stroke (additive model: odds ratio (OR) = 1.35, 95% confidence interval (CI) = 1.06-1.73). This association was also observed in rs3134069C (additive model: OR = 1.53, 95% CI = 1.10-2.12). Furthermore, when we combined these two polymorphisms according to the numbers of risk alleles (rs2073617G and rs3134069C), we found that the patients with 3-4 risk alleles were statistically significantly associated with an increased risk of poor outcome of LAA stroke (OR = 1.90, 95% CI = 1.10-3.28) compared with 0-2 risk alleles, and this increased risk was more evident among those with hypertension (OR = 2.02, 95% CI = 1.04-3.91), those without diabetes (OR = 2.02, 95% CI = 1.02-4.01) and those with smoking (OR = 2.43, 95% CI = 1.09-5.42). In silico analysis showed that rs2073617 and rs3134069 are located in various histone modification marked regions, DNase I hypersensitive sites and can change the binding of regulatory motifs. Moreover, rs2073617 is also located in the binding site of transcription factors. Our findings suggested that TNFRSF11B polymorphisms may be associated with an increased risk of short-term poor outcome of LAA stroke.

Severe Stroke Patients With Left-Sided Occlusion of the Proximal Anterior Circulation Benefit More From Thrombectomy.

Background and Purpose: Endovascular thrombectomy improves the functional independence of patients with proximal anterior circulation occlusion. However, a subset of patients fail to benefit from thrombectomy procedures, the reasons for which remain poorly defined. In this study, we investigated whether the effectiveness of thrombectomy was affected by left- or right-sided occlusion among patients with similar stroke severities. Methods: Patients with proximal anterior circulation occlusion (internal carotid or M1 of middle cerebral artery) treated with the Solitaire stent retriever within 8 h of the onset of acute ischemic stroke were enrolled from the Yijishan Hospital of Wannan Medical College. Stroke severity was measured using the National Institutes of Health Stroke Scale (NIHSS) on admission. The functional outcomes were assessed using the modified Rankin scale (mRS) at 90 days. Results: We enrolled 174 patients including 90 left-sided occlusion and 84 right-sided occlusion. The NIHSS scores on admission were higher in the left-sided (median, 19; interquartile range, 16 to 20) compared to the right-sided occlusion group (median, 15, interquartile range, 13 to 18) (P < 0.001). Following adjustment for potential risk factors, patients with left-sided occlusion had higher rates of functional independence (mRS ≤ 2) and lower rates of mortality (mRS = 6) compared to the right-sided occlusion patients (39.5 vs. 19.6% and 28.9 vs. 47.8%, respectively) in the severe stroke group (NIHSS ≥ 15). Conclusions: In severe stroke patients with proximal anterior circulation occlusion, stent retriever thrombectomy within 8 h of the onset of symptoms provides more benefits to left-sided occlusion.

Chromosome 10q25 polymorphism is associated with susceptibility to large artery atherosclerotic stroke.

BACKGROUND AND AIMS: A recent genome-wide association study (GWAS) reported an association between a single nucleotide polymorphism (SNP) rs11196288 and risk of early-onset large artery atherosclerotic (LAA) stroke in European population. The interaction between genetic and environmental factors such as age has also received increasing attention. We performed this study to investigate the association between the rs11196288A > G polymorphism and LAA stroke risk in the Chinese Han population and test whether age interacts rs11196288 to influence LAA stroke risk. METHODS: Genotyping of rs11196288 was performed in 1066 LAA stroke patients and 1167 healthy controls. Multivariate logistic regression analyses were applied to assess the effect of the rs11196288A > G polymorphism on susceptibility and short-term outcome of LAA stroke. Nomograms were performed to estimate probability of risk for an individual patient. RESULTS: A significant decrement of LAA stroke risk was found in co-dominant (AG vs. AA, OR = 0.76, 95% CI = 0.64-0.91, P = 0.003; GG vs. AA, OR = 0.65, 95% CI = 0.50-0.85, P = 0.002), dominant (AG/GG vs. AA, OR = 0.74, 95% CI = 0.62-0.87, P < 0.001) and recessive models (GG vs. AA/AG, OR = 0.76, 95% CI = 0.59-0.97, P = 0.028) of rs11196288. However, the interaction between age and genotypes of rs11196288 was not statistically significant, and no significant association was observed between the rs11196288A > G polymorphism and short-term outcome of LAA stroke (P > 0.05). CONCLUSIONS: In the southeastern Chinese population, the rs11196288A > G polymorphism is associated with decreased risk of LAA stroke.

Leukoaraiosis severity and outcomes after mechanical thrombectomy with stent-retriever devices in acute ischemic stroke.

BACKGROUND AND PURPOSE: The aim of the study was to evaluate whether leukoaraiosis severity is associated with outcome in acute stroke patients undergoing mechanical thrombectomy with stent-retriever devices. METHODS: In this retrospective multicenter study, we evaluated 251 acute stroke patients (pretreatment National Institutes of Health Stroke Scale score ≥8) treated with stent-retriever devices. Leukoaraiosis severity was graded as 0-2 (absent-to-moderate) versus 3-4 (severe) according to the van Swieten scale. The main clinical outcome was the proportion of good functional outcome, defined as a modified Rankin Scale of 0-2 at 90 days. RESULTS: Significantly fewer patients in the severe LA group than in the absent-to-moderate LA group achieved a good functional outcome (18.4% vs 50.2%, P<0.001). In multivariable analysis, severe leukoaraiosis was a significant negative predictor of good functional outcome at 90 days (OR, 0.27; 95% CI 0.10-0.77; P=0.014). CONCLUSIONS: The severity of leukoaraiosis is independently associated with 90-day functional outcome in acute stroke patients undergoing mechanical thrombectomy with stent-retriever devices.

Neutrophil to Lymphocyte Ratio as a Predictor of Restenosis After Angioplasty and Stenting for Asymptomatic Carotid Stenosis.

The inflammatory response plays a vital role in the development of in-stent restenosis (ISR) after carotid angioplasty and stenting (CAS). The neutrophil to lymphocyte ratio (NLR) has been suggested as a sensitive inflammatory marker. We explored the association between NLR and ISR in CAS patients. A total of 427 patients who underwent CAS were enrolled. Neutrophil to lymphocyte ratio was measured before the procedure. Clinical examination and radiographic evaluation were performed at 6 months and annually after the procedure. In-stent restenosis was defined as ≥50% stenosis in the treated lesion. Cox regression was used to identify predictors of ISR after CAS. Of the 459 arteries (in 427 patients) with CAS, 72 (15.7%) were identified with ISR during a mean follow-up of 14.6 (19.1) months (range, 0.7-120.7 months). Increased NLR (≥2.13) was significantly related to ISR in patients with asymptomatic stenosis ( P = .001). However, significance was not observed in symptomatic stenosis. On multivariate analysis, baseline NLR ≥ 2.13 (hazard ratio [HR], 2.74; 95% confidence interval [CI], 1.46-5.14), smoking (HR, 1.99; 95% CI, 1.11-3.58), residual stenosis (HR, 1.12; 95% CI, 1.09-1.15), and baseline glucose level (HR, 1.01; 95% CI, 1.01-1.02) were associated with ISR. Elevated NLR may be a predictor of ISR after CAS for asymptomatic stenosis.

HDAC9 Polymorphisms Predict Susceptibility, Severity, and Short-Term Outcome of Large Artery Atherosclerotic Stroke in Chinese Population.

Recently, a genome-wide association study (GWAS) detected two histone deacetylase 9 (HDAC9) polymorphisms (rs2074633 and rs28688791) which may be associated with risk of large artery atherosclerotic (LAA) stroke. This study aimed to investigate whether these two polymorphisms were associated with susceptibility, severity, and short-term outcome of LAA stroke in a southern Chinese Han population. rs2074633 and rs28688791 were genotyped using SNPscan technology in 1011 LAA stroke patients and 1121 healthy controls. Stroke severity on admission and short-term outcome were, respectively, assessed by the National Institute of Health Stroke Scale (NIHSS) score on admission and modified Rankin Scale score at 3 months after stroke onset. rs2074633 (P = 0.039) and rs28688791 (P = 0.025) were associated with risk of LAA stroke. In subgroup analysis according to sex and age, this increased risk was only found in males (P = 0.029 for rs2074633; P = 0.013 for rs28688791) and adults aged < 60 years (P = 0.009 for rs2074633; P = 0.003 for rs28688791). Moreover, we detected significant interactions between these two polymorphisms and age (Pinteraction = 0.027 for rs2074633; Pinteraction = 0.044 for rs28688791). The CC genotype of rs28688791 (P = 0.037) was also associated with moderate and severe stroke (NIHSS ≥ 6). Additionally, the CC genotype of rs2074633 and rs28688791 (rs2074633, P = 0.019; rs28688791, P = 0.023) showed significant association with unfavorable short-term outcome of LAA stroke. Our results indicated that HDAC9 polymorphisms may be used as biomarkers for susceptibility, severity, and short-term outcome of LAA stroke.

Effects of mechanical thrombectomy for acute stroke patients with etiology of large artery atherosclerosis.

AIMS: Atherosclerosis is more prevalent in Asian population. This distinct etiology of stroke might disadvantage Asian patients when applying. mechanical thrombectomy (MT). The purpose of this research was to evaluate the efficacy and safety of MT in a cohort of Chinese patients with acute ischemic stroke. due to large artery atherosclerosis (LAA). METHODS AND RESULTS: A total of 649 patients treated with MT were included. Patients were classified according to etiology of stroke as LAA and cardioembolism ones. Successful revascularization was defined as modified Thrombolysis in Cerebral Infarction (mTICI) grade ≥ 2b. Favorable outcome was defined as modified Rankin Scale (mRS) score ≤ 2 at 90 days. Logistic regression was used to identify predictors for functional outcomes. The patients with stroke of LAA etiology had significantly higher rate of favorable functional outcome (50.2% vs 36.5%, p < .001) and good collateral (grade of ASITN/SIRI: 2-3) (58.8% versus 43.2%, p < .001), and lower median baseline National Institutes of Health Stroke Scale score (NIHSS) (15.6 versus 18.2, p < .001), compared to patients with stroke of cardioembolism etiology. There was no significant difference in the rate of successful postprocedural mTICI between groups (84.5% versus 83.2%, p = .671). Rates of symptomatic intracranial hemorrhage (20.0% versus 11.7%, p = .004) and mortality (31.8% versus 18.8%, p < .001) within 3 months were notably higher in the cardioembolism group than that in the LAA group. CONCLUSION: Mechanical thrombectomy may be more efficacious in treating acute ischemic stroke of LAA etiology than that of cardioembolism etiology.

Genetic variants in ALDH2 predict risk of ischemic stroke in a Chinese population.

BACKGROUND AND PURPOSE: Genome-wide association studies discovered a novel correlation between chromosome 12q24 and ischemic stroke in European populations. This study aimed to determine whether two genetic variants (rs10744777 and rs886205) on chromosome 12q24 can modify the risk of ischemic stroke in Chinese population. METHODS: We recruited 1195 patients with ischemic stroke and 642 healthy Chinese individuals. The rs10744777 and rs886205 polymorphisms in aldehyde dehydrogenase2 (ALDH2) was genotyped and compared using multivariate logistic regression. RESULTS: The genotype of rs10744777 (CT/TT) was associated with risk of ischemic stroke in males (OR = 1.99, 95% CI = 1.15-3.42, P = 0.013). In contrast, no significant correlation was found in females. Haplotype analysis indicated that haplotype "TA" was associated with increased ischemic stroke risk (OR = 1.85, 95% CI = 1.10-3.12, P = 0.042). Further subtype analysis demonstrated that the rs10744777 (CT/TT) genotype was strongly associated with large artery atherosclerosis subtype in males (OR = 2.27, 95% CI = 1.30-3.95, P = 0.004). After three months follow-up, we found a poorer functional outcome of ischemic stroke associated with the rs886205 GA genotype (OR = 1.76, 95% CI 1.03-3.00, P = 0.057) in males. CONCLUSIONS: Genetic polymorphisms in ALDH2 modified ischemic stroke risk and outcome in Chinese males, but not in females.