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Background: Recent Mendelian randomization and meta-analysis highlight the relevance of MCP-1 (monocyte chemoattractant protein-1) in stroke. We aimed to investigate the associations between MCP-1 and clinical outcomes in patients with ischemic stroke or transient ischemic attack and test whether inflammation mediates or jointly contributes to the relationships., Methods and Results: A total of 10 700 patients from the Third China National Stroke Registry study were included. Multivariable Cox regression was used for recurrent stroke and all-cause death, and logistic regression was used for poor functional outcome. Mediation analyses were performed to clarify whether inflammation mediates the associations. After adjusting for potential confounders, low MCP-1 level (<337.6 pg/mL) was associated with a reduced risk of all-cause death (hazard ratio [HR], 0.65 [95% CI, 0.51-0.82]) and poor functional outcome (odds ratio, 0.81 [95% CI, 0.70-0.94]) but was not associated with recurrent stroke (HR, 1.10 [95% CI, 0.95-1.27]), compared with high MCP-1 level (≥337.6 pg/mL). The association between MCP-1 and all-cause death was partially mediated by highly sensitive C-reactive protein, interleukin-6, and YKL-40 (Chitinase-3-like protein 1; mediated proportion: 7.4%, 10.5%, and 7.4%, respectively). The corresponding mediated proportion for poor functional outcome was 9.9%, 17.1%, and 7.1%, respectively. Patients with combined high levels of MCP-1 and inflammatory biomarkers had the highest risks of all-cause death and poor functional outcome., Conclusions: Low plasma MCP-1 level was associated with decreased risks of all-cause mortality and poor functional outcome after ischemic stroke or transient ischemic attack. Inflammation partially mediated and jointly contributed to the associations.

Aims: Studies showed that low-density lipoprotein cholesterol (LDL-C) to triglyceride (TG) ratio could be used as a predictive parameter of low-density lipoprotein oxidation in vivo and the level of small dense LDL-C. However, whether LDL-C/TG ratio is associated with stroke prognosis remains unclear. We investigated the associations of LDL-C/TG ratio with outcomes in patients with acute ischaemic stroke (AIS) or transient ischaemic attacks (TIA) and explored whether it produced more predictive value than LDL-C and TG., Methods: Data were derived from the Third China National Stroke Registry (CNSR-III). Multivariable Cox regression for stroke recurrence, composite vascular events and all-cause death and logistic regression for the poor functional outcome (modified Rankin Scale score 3-6) were used., Results: A total of 14123 patients were included. After adjusting for confounding factors, quartile 4 of LDL-C/TG ratio was associated with an increased risk of recurrent stroke (hazard ratio [HR], 1.27; 95% confidence interval [CI], 1.03-1.56), composite vascular events (HR,1.23; 95% CI, 1.00-1.52), death (HR,1.70; 95% CI, 1.13-2.54) and poor functional outcome (odds ratio, 1.34; 95% CI, 1.12-1.61) at 3 months follow-up compared with quartile 1. We also found that quartile 4 of LDL-C and TG was positively and negatively associated with poor functional outcome at 3 months, respectively. LDL-C/TG ratio performed better than LDL-C or TG in predicting clinical outcomes., Conclusions: LDL-C/TG ratio was associated with the risk of stroke recurrence, composite vascular events, death and poor functional outcome in patients with AIS or TIA.

Background: Frequent incidence of futile recanalization decreases the benefit of endovascular treatment (EVT) in acute ischemic stroke. We hypothesized that the inflammation and immune response after ischemic are associated with futile recanalization. We aimed to investigate the correlation of admission systemic immune-inflammation index (SII) with futile recanalization post EVT., Methods: Patients with successful recanalization (modified Thrombolysis in Cerebral Ischemia angiographic score 2b-3) and maintained artery recanalized after 24 h of EVT were chosen from a prospective nationwide registry study. Futile recanalization was defined as a poor functional outcome (modified Rankin Scale score 3-6) at 90 days, irrespective of a successful recanalization. At admission, SII was calculated as (platelet count × neutrophil count)/lymphocyte count/100. Logistic regression analysis helped to test the relationship of SII with futile recanalization., Results: Among the 1,002 patients included, futile recanalization occurred in 508 (50.70%). No matter whether tested as quartiles or continuous variables, SII was significantly associated with futile recanalization (P < 0.05), and for every one standard deviation increase of SII, the risk of futile recanalization elevated by 22.3% (odds ratio 1.223, 95% confidence interval 1.053-1.444, P = 0.0093). Moreover, no significant interactions could be observed between SII or SII quartiles and age, baseline National Institutes of Health Stroke Scale scores, onset-to-recanalization time, and modified Thrombolysis in Cerebral Ischemia angiographic scores (all P for interaction > 0.05)., Conclusions: Early SII elevation was associated with an increased risk of futile recanalization among patients with EVT. Our results indicated that therapeutic drug targeting hyperreactive immune-inflammation response might be helpful for reducing the incidence of futile recanalization., (© 2024. Springer Science+Business Media, LLC, part of Springer Nature and Neurocritical Care Society.)

Background: Upper limb motor dysfunction is a major problem in the rehabilitation of patients with stroke. Brain-computer interface (BCI) is a kind of communication system that converts the "ideas" in the brain into instructions and has been used in stroke rehabilitation. This study aimed to investigate the efficacy and safety of BCI in rehabilitation training on upper limb motor function among patients with ischemic stroke., Methods: This was an investigator-initiated, multicenter, randomized, open-label, blank-controlled clinical trial with blinded outcome assessment conducted at 17 centers in China. Patients were assigned in a 1:1 ratio to the BCI group or the control group based on traditional rehabilitation training. The primary efficacy outcome is the difference in improvement of the Fugl-Meyer Assessment upper extremity (FMA-UE) score between two groups at month 1 after randomization. The safety outcomes were any adverse events within 3 months., Findings: A total of 296 patients with ischemic stroke were enrolled and randomly allocated to the BCI group (n = 150) and the control group (n = 146). The primary efficacy outcomes of FMA-UE score change from baseline to 1 month were 13.17 (95% confidence interval [CI], 11.56-14.79) in the BCI group and 9.83 (95% CI, 8.19-11.47) in the control group (mean difference between groups was 3.35; 95% CI, 1.05-5.65; p = 0.0045). Adverse events occurred in 33 patients (22.00%) in the BCI group and in 31 patients (21.23%) in the control group., Conclusions: BCI rehabilitation training can further improve upper limb motor function based on traditional rehabilitation training in patients with ischemic stroke. This study was registered at ClinicalTrials.gov: NCT04387474., Funding: This work was supported by the National Key R&D Program of China (2018YFC1312903), the National Key Research and Development Program of China (2022YFC3600600), the Training Fund for Open Projects at Clinical Institutes and Departments of Capital Medical University (CCMU2022ZKYXZ009), the Beijing Natural Science Foundation Haidian original innovation joint fund (L222123), the Fund for Young Talents of Beijing Medical Management Center (QML20230505), and the high-level public health talents (xuekegugan-02-47)., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Ginkgo diterpene lactone meglumine (GDLM) could improve the functional outcome in patients with acute ischemic stroke (AIS). This study aimed to investigate the efficacy of GDLM on cognitive function in patients with AIS., Methods: This is a predefined exploratory analysis of the Efficacy and Safety of Ginkgo Diterpene Lactone Meglumine in Acute Ischemic Stroke trial, which was primarily designed to investigate the efficacy and safety of GDLM versus placebo on functional outcome at 100 centers in China. Cognitive function was measured using the Montreal Cognitive Assessment (MoCA) test. The primary outcomes were changes of MoCA from baseline to Day 14 and Day 90 after randomization., Results: A total of 3163 patients with completed data on MoCA were enrolled. There was statistically significant difference of changes in MoCA scores between the GDLM group and the placebo group from baseline to Day 14 (mean difference, 0.31; 95% confidence interval [CI], 0.08-0.53; P = 0.007) and to Day 90 after randomization (mean difference, 0.47; 95% CI, 0.22-0.72; P < 0.001). Additionally, GDLM was associated with a higher proportion of patients who reached a clinically significant level of improvement in MoCA from baseline to Day 14 (odds ratio [OR], 1.25; 95% CI, 1.08-1.44; P = 0.002) and Day 90 after randomization (OR, 1.21; 95% CI, 1.03-1.41; P = 0.02). Specially, GDLM could significantly improve the scores of visuo-spatial and executive function and language., Conclusions: In this predefined analysis of patients with AIS, GDLM could improve the 14-day and 90-day cognitive function compared with the placebo., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany.)

Rationale & Objective: Metabolic dysfunction-associated fatty liver disease (MAFLD), a risk factor for stroke and all-cause mortality, is highly prevalent among patients with chronic kidney disease (CKD), but it is unclear whether the association of MAFLD with stroke and all-cause mortality differs within and outside of the setting of CKD., Study Design: Prospective cohort study., Setting & Participants: We enrolled 95,353 participants from the Kailuan Cohort Study, among whom 35,749 had CKD at baseline or developed CKD during the follow-up period, and 59,604 individuals who had no CKD at baseline or during the follow-up period., Exposure: MAFLD., Outcome: Stroke (ischemic stroke, hemorrhagic stroke), all-cause mortality., Analytical Approach: Adjusted Cox regression models were used to estimate the influence of MAFLD on stroke outcomes within the subgroups defined by the presence of CKD., Results: After a median follow-up of 12.8 years, 6,140 strokes (6.4%) and 11,975 deaths from any cause (12.6%) occurred. After adjusting for potential confounders, MAFLD was associated with an increased incidence of stroke among the participants with CKD (HR, 1.34 [95% CI, 1.23-1.45]) but not among those without CKD (HR, 1.05 [95% CI, 0.97-1.15]; P interaction <0.001). This association was principally related to ischemic stroke (HR, 1.38 [95% CI, 1.26-1.51]) and not hemorrhagic stroke (HR, 1.04 [95% CI, 0.85-1.26]). No association was found between MAFLD and all-cause mortality in the participants with CKD (HR,1.04 [95% CI, 0.98-1.10]) or those without CKD (HR,1.03 [95% CI, 0.97-1.09]). Among the participants with CKD, compared with non-MAFLD, MAFLD with diabetes (HR,1.36 [95% CI, 1.23-1.50]) or overweight/obesity (HR,1.30 [95% CI, 1.14-1.50]) was associated with a higher risk of stroke whereas MAFLD without overweight/obesity or diabetes was not associated with a higher risk (HR,1.08 [95% CI, 0.81-1.43])., Limitations: This was an observational study and included individuals with CKD who had a relatively high estimated glomerular filtration rate., Conclusions: MAFLD was associated with an increased risk of stroke in individuals with CKD but not in those without CKD., Plain-Language Summary: Metabolic dysfunction-associated fatty liver disease (MAFLD), which is recognized as a risk factor for stroke in the general population, is highly prevalent among individuals with chronic kidney disease (CKD). However, the impact of MAFLD on the risk of stroke in patients with CKD remains uncertain. We investigated the association of MAFLD with stroke in individuals with and without CKD. Our analysis revealed that MAFLD was associated with a significantly increased risk of stroke in individuals with CKD, and the magnitude of this increased risk was greater in the setting of CKD. These findings highlight the need for increased attention to MAFLD in patients with CKD and emphasize that addressing and preventing MAFLD in this population may contribute to reduced morbidity from stroke., (Copyright © 2023 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.)

Background: Urine ketone bodies may appear in different states in the acute stage of stroke. We aimed to examine the association between urine ketone bodies and recurrent stroke in patients with acute ischemic stroke (AIS) or transient ischemic attack (TIA) in this study., Methods: In Third China National Stroke Registry (CNSR-III), 14,015 patients with AIS or TIA were screened for urine ketone bodies. The outcomes were any stroke, ischemic stroke and combined vascular events within 1 year. The association of urine ketone bodies with recurrent stroke were analyzed by Cox proportional hazards., Results: During 1 year of follow-up, 1,335 (9.53%) participants experienced recurrent stroke. After adjustment for conventional confounding factors, patients with urine ketone bodies test positive had a higher risk of recurrent stroke (hazard ratio [HR], 1.43; 95% confidence interval [CI], 1.13-1.82), compared to those were negative. The correlation between positive urine ketone bodies and recurrent stroke were consistent in patient with (HR, 1.45; 95% CI, 1.00-2.12) and without (HR, 1.40; 95% CI, 1.02-1.94) diabetes. No significant interaction between urine ketone bodies and diabetes were observed., Conclusions: Positive ketone bodies in urine was independently associated with recurrent stroke in patients with AIS or TIA., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier Ltd.)

Background: Evidence on the longitudinal associations between serum uric acid (SUA) and stroke was limited and yielded inconsistent conclusions. We aimed to investigate the associations of cumulative SUA (cumSUA), incorporating the time course of cumSUA accumulation, with the risk of stroke., Methods: The prospective cohort study enrolled 50 871 participants from Kailuan, China. CumSUA from 2006 to 2010 was derived by calculating the means of SUA values between consecutive examinations and multiplying by time intervals between visits. Time course of cumSUA accumulation was categorized as the slope of SUA versus time or by splitting the overall accumulation into an early (cumSUA 06-08 ) and late accumulation (cumSUA 08-10 ). Participants were classified by cumSUA quartiles, SUA slope (negative versus positive), and the combined median cumSUA (1105.21 μmol/L×year) with SUA slope, respectively. The associations with incident stroke between 2010 and 2019 were evaluated with competing risk model., Results: During a median follow-up of 9.02 years, 2217 cases of incident stroke were identified. In the multivariable-adjusted model, a higher risk of stroke was observed in participants with the highest quartile versus the lowest quartile of cumSUA (subdistribution hazard ratio, 1.15 [95% CI, 1.01-1.31]), and those with a negative versus positive SUA slope (subdistribution hazard ratio, 1.09 [95% CI, 1.01-1.19]). Consistently, a later accumulation of SUA was not associated with the risk of stroke after adjustment for an early accumulation, indicating early accumulation may contribute more to the risk of stroke than later accumulation. When cumSUA was incorporated with its time course, those with changes in cumSUA suggesting early accumulation had elevated risk of stroke (subdistribution hazard ratio, 1.17 [95% CI, 1.03-1.33]). Similar results were observed for ischemic stroke., Conclusions: Incident stroke risk was associated with cumulative exposure to SUA and its accumulation time course. Early SUA accumulation resulted in a greater risk compared with later accumulation, underscoring the importance of early control of SUA to an optimal level., Competing Interests: Disclosures None.

Importance: Ginkgo diterpene lactone meglumine (GDLM) has attracted much attention because of its potential neuroprotective properties in ischemic stroke. The efficacy of GDLM in patients with acute ischemic stroke (AIS) needs to be verified by well-designed randomized clinical trials., Objective: To assess the efficacy and safety of GDLM in patients with AIS., Design, Setting, and Participants: This multicenter, randomized, double-blind, placebo-controlled, parallel-group trial involved 3448 patients who had AIS, were aged 18 to 80 years, had a clinically diagnosed AIS symptom within 48 hours of onset, had a modified Rankin Scale (mRS) score of 0 or 1 prior to onset, and had a National Institutes of Health Stroke Scale score ranging from 4 to 24. The trial took place at 100 centers in China from February 1, 2016, to May 1, 2018. The mRS is a global stroke disability scale with scores ranging from 0 (no symptoms or completely recovered) to 6 (death). The National Institutes of Health Stroke Scale is a tool used by clinicians to quantify impairment caused by stroke (range, 0-42, with higher scores indicating greater severity). Data were analyzed from January 2019 to December 2022., Interventions: Patients were randomized to receive GDLM or placebo once daily via intravenous infusion in a 1:1 ratio. The treatment was dispensed within 48 hours after symptoms and continued for 14 days. Interventions of thrombolysis and thrombectomy were not permitted during the treatment., Main Outcomes and Measures: The primary outcome was the proportion of patients with an mRS of 0 or 1 on day 90 after randomization. Safety outcomes included adverse events and serious adverse events., Results: A total of 3448 patients were randomized, with 1725 patients assigned to the GDLM group and 1723 patients assigned to the placebo group. The median (IQR) age of the patients was 63 (55-71) years, and 1232 (35.7%) were women. The primary outcome on day 90 occurred in 877 patients (50.8%) in the GDLM group, and 759 patients (44.1%) in the placebo group (risk difference, 6.79%; 95% CI, 3.46%-10.10%; odds ratio, 1.31; 95% CI, 1.15-1.50; relative risk, 1.15; 95% CI, 1.08-1.24; P < .001). Adverse events occurred relatively equally between the 2 groups (303 [17.6%] vs 298 [17.3%]; risk difference, 0.27%; 95% CI, -2.26% to 2.80%; odds ratio, 1.02; 95% CI, 0.85-1.21; relative risk, 1.02; 95% CI, 0.88-1.17; P = .83)., Conclusions and Relevance: Among patients with AIS in this randomized clinical trial, GDLM improved the proportion of patients achieving favorable clinical outcomes at 90 days compared with placebo., Trial Registration: ClinicalTrials.gov Identifier: NCT02526225.

Background: Body mass index (BMI) may affect the response to platelet P2Y 12 receptor inhibitors. We aimed to explore whether BMI influenced the efficacy and safety of ticagrelor and clopidogrel for secondary prevention of minor ischemic stroke or transient ischemic attack (TIA) among patients enrolled in the CHANCE-2 (Ticagrelor or Clopidogrel with Aspirin in High-Risk Patients with Acute Nondisabling Cerebrovascular Events II) trial., Methods: In a multicentre, randomized, double-blind, placebo-controlled trial, conducted in China, we randomized patients with minor stroke or TIA who carried the CYP2C19 loss-of-function allele to receive either ticagrelor-acetylsalicylic acid (ASA) or clopidogrel-ASA. We classified patients into obese (BMI ≥ 28) or nonobese (BMI < 28) groups. The primary efficacy outcome was stroke within 90 days, and the primary safety outcome was severe or moderate bleeding within 90 days., Results: Among 6412 patients, 876 were classified as obese and 5536 were classified as nonobese. Compared with clopidogrel-ASA, ticagrelor-ASA was associated with a significantly lower rate of stroke within 90 days among patients with obesity (25 [5.4%] v. 47 [11.3%]; hazard ratio [HR] 0.51, 95% confidence interval [CI] 0.30-0.87), but not among those in the nonobese group (166 [6.0%] v. 196 [7.0%]; HR 0.84, 95% CI 0.69-1.04) The interaction of treatment and BMI group was significant ( p for interaction = 0.04). We did not observe any difference by BMI group in rates of severe or moderate bleeding (9 [0.3%] v. 10 [0.4%] in the nonobese group; 0 [0.0%] v. 1 [0.2%] in the obese group; p for interaction = 0.99)., Interpretation: In this secondary analysis of a randomized controlled trial involving patients with minor ischemic stroke or TIA, compared with clopidogrel-ASA, patients with obesity received more clinical benefit from ticagrelor-ASA therapy than those without obesity., Trial Registration: Clinicaltrials.gov, no. NCT04078737., Competing Interests: Competing interests: None declared., (© 2023 CMA Impact Inc. or its licensors.)

Aims: The monocyte to high-density lipoprotein cholesterol ratio (MHR) has emerged as a novel inflammatory biomarker of atherosclerotic cardiovascular disease. However, it has not yet been identified whether MHR can predict the long-term prognosis of ischemic stroke. We aimed to investigate the associations of MHR levels with clinical outcomes in patients with ischemic stroke or transient ischemic attack (TIA) at 3 months and 1 year., Methods: We derived data from the Third China National Stroke Registry (CNSR-III). Enrolled patients were divided into four groups by quartiles of MHR. Multivariable Cox regression for all-cause death and stroke recurrence and logistic regression for the poor functional outcome (modified Rankin Scale score 3-6) were used., Results: Among 13,865 enrolled patients, the median MHR was 0.39 (interquartile range, 0.27-0.53). After adjustment for conventional confounding factors, the MHR level in quartile 4 was associated with an increased risk of all-cause death (hazard ratio [HR], 1.45; 95% confidence interval [CI], 1.10-1.90), and poor functional outcome (odd ratio [OR], 1.47; 95% CI, 1.22-1.76), but not with stroke recurrence (HR, 1.02; 95% CI, 0.85-1.21) at 1 year follow-up, compared with MHR level in quartile 1. Similar results were observed for outcomes at 3 months. The addition of MHR to a basic model including conventional factors improved predictive ability for all-cause death and poor functional outcome validated by the C-statistic and net reclassification index (all p < 0.05)., Conclusions: Elevated MHR can independently predict all-cause death and poor functional outcome in patients with ischemic stroke or TIA., (© 2023 The Authors. CNS Neuroscience & Therapeutics published by John Wiley & Sons Ltd.)

Background: Serum albumin to globulin ratio (A/G) has been widely used as a representative biomarker for assessing inflammation and nutrition status. However, in patients with acute ischemic stroke (AIS), the predictive value of serum A/G has rarely been reported. We aimed to evaluate whether serum A/G is associated with prognosis in stroke., Methods: We analyzed data from the Third China National Stroke Registry. The patients were categorized into quartile groups according to the serum A/G at admission. Clinical outcomes included poor functional outcomes (modified Rankin Scale [mRS] score of 3-6 or 2-6) and all-cause mortality at 3 months and1 year. Multivariable logistic regressions and Cox proportional hazards regressions were used to evaluate the association of serum A/G with the risk of poor functional outcomes and all-cause mortality., Results: A total of 11, 298 patients were included in this study. After adjustment for confounding factors, patients in the highest serum A/G quartile had a lower proportion of mRS score 2-6 (odds ratio [OR], 0.87; 95% confidence interval [CI], 0.76-1.00) and mRS score 3-6 (OR, 0.87; 95% CI, 0.73-1.03) at 3 months follow-up. At 1 year follow-up, there was a significant association between higher serum A/G and mRS score 3-6 (OR, 0.68; 95% CI, 0.57-0.81). We also found that the highest serum A/G was related to decreased risk of all-cause mortality (hazard ratio [HR], 0.58; 95% CI, 0.36-0.94) at 3 months follow-up. Similar results were found at 1-year follow-up., Conclusions: Lower serum A/G levels were associated with poor functional outcomes and all-cause mortality at 3 months and 1-year follow-up in patients with acute ischemic stroke., (© 2023 The Authors. CNS Neuroscience & Therapeutics published by John Wiley & Sons Ltd.)

Aim: The association between magnesium and outcomes after stroke is uncertain. We aimed to investigate the association of serum magnesium with all-cause mortality and poor functional outcome., Methods: We included patients with acute ischemic stroke (AIS) or transient ischemic attack (TIA) from the China National Stroke Registry III. We used Cox proportional hazards model for all-cause mortality and logistic regression model for poor functional outcome (modified Rankin Scale [mRS] 2-6/3-6) to examine the relationships., Results: Among the 6483 patients, the median (interquartile range) magnesium was 0.87 (0.80-0.93) mmol/L. Patients in the first quartile had a higher risk of mRS score 3-6/2-6 at 3 months (adjusted odds ratio [OR]: 1.30; 95% confidence interval [CI]: 1.02, 1.64; adjusted OR: 1.29; 95% CI: 1.04-1.59) compared with those in the fourth quartile. Similar results were found for mRS score 26 at 1 year. The age- and sex-adjusted hazard ratio (HR) with 95% CI in first quartile magnesium was 1.40 (1.02-1.93) for all-cause mortality within 1 year, but became insignificant (HR: 1.03; 95% CI: 0.71-1.50) after adjusting for potential variables., Conclusions: Low serum magnesium was associated with a high risk of poor functional outcome in patients with AIS or TIA., (© 2022 The Authors. CNS Neuroscience & Therapeutics published by John Wiley & Sons Ltd.)

Medical treatment and endovascular therapy are widely used for intracranial atherosclerotic stenosis, but the best treatment strategy remains uncertain. The goal of this study was to compare the safety and effectiveness of medical treatment, stenting, and primary balloon angioplasty (PBA). We searched PubMed, MEDLINE, and EMBASE for trials comparing these three treatments for intracranial stenosis up to December 24, 2020. We performed a network meta-analysis with random-effects models. The primary outcome was any stroke or death during a long-term follow-up. Secondary outcomes included ischemic stroke, intracranial hemorrhage, and death. This network meta-analysis included 14 trials with 1520 participants. No significant difference was found between the three groups in the primary outcome, while PBA was probably the best treatment according to the ranking plot. Medical treatment had significantly lower rate of any stroke or death (odds ratio (OR), 0.31; 95% CI, 0.17-0.56), ischemic stroke (OR, 0.43; 95% CI, 0.23-0.81), and intracranial hemorrhage (OR, 0.12; 95% CI, 0.02-0.71) within 30 days than stenting but did not differ from PBA. The ranking plot demonstrated that PBA was also most likely to rank the highest for ischemic stroke during the long-term follow-up and beyond 30 days, although no significant difference was identified. Medical treatment had lower risk of any stroke or death within 30 days than stenting but did not differ from PBA. All the treatments had similar effects on the prevention of long-term stroke, while PBA had the highest probability of being the most effective., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Main Problem: The prognostic value of soluble lectin-like oxidized low-density lipoproteinreceptor-1 (sLOX-1) for stroke was unclearly. This study aimed to investigate the association between sLOX-1 and recurrent stroke in patients with acute ischemic stroke (AIS) or transient ischemic attack (TIA)., Methods: Data were obtained from the Third China National Stroke Registry. Eligible cases consisted of 400 patients who developed recurrent stroke within 1-year follow-up, 800 controls were selected using age- and sex-matched with a 1:2 case-control ratio. Conditional logistic regressions were used to evaluate the association between sLOX-1 and recurrent stroke., Results: Among 1200 patients included in this study, the median (interquartile range) of sLOX-1 was 247.12 (132.81-413.58) ng/L. After adjustment for conventional confounding factors, the odds ratio with 95% confidence interval in the highest tertile versus the lowest tertile was 2.23 (1.61-3.08) for recurrent stroke, 2.31 (1.64-3.24) for ischemic stroke, 2.30 (1.66-3.19) for combined vascular events within 1-year follow-up. Furthermore, the addition of sLOX-1 to a conventional risk model had an incremental effect on predictive value for recurrent stroke (C-statistics 0.76, p < 0.0001; integrated discrimination improvement 13.38%, p < 0.0001; net reclassification improvement 55.39%, p < 0.0001). Similar results were observed when the timepoint was set up as 3 months. Subgroup analysis showed the association between higher sLOX-1 and recurrent stroke was more pronounced in patients with a history of stroke (p for interaction = 0.0062)., Conclusions: sLOX-1 was positively associated with the risk of recurrent stroke, which may be a candidate biomarker to improve risk stratification of recurrent stroke., (© 2022 The Authors. CNS Neuroscience & Therapeutics published by John Wiley & Sons Ltd.)

Background and Purpose: The role of serum uric acid (SUA) in prognosis is controversial because SUA levels largely depend on renal clearance function. This study aimed to investigate the association between renal function-normalized SUA (SUA to serum creatinine [SCr] ratio [SUA/SCr ratio]) and poor functional outcomes in patients with acute ischemic stroke (AIS)., Methods: All patients were recruited from the Third China National Stroke Registry. Poor functional outcomes were defined by modified Rankin Scale (mRS) scores of 3-6 or 2-6 at 3 months and 1 year., Results: Among 8169 enrolled patients, the median (interquartile range) SUA/SCr ratio was 4.19 (3.47-5.08). Compared with patients in the fourth quintile group, those in the first quintile group had higher proportions of mRS scores 3-6 (odds ratio [OR] 1.55, 95% confidence interval [CI] 1.24-1.93) and mRS scores 2-6 (OR 1.28, 95% CI 1.08-1.53) at 3 months. The addition of SUA/SCr ratio to the conventional risk model had a greater incremental value than the addition of either SUA or SCr alone. Subgroup analysis showed that the association was only significant in patients with normal kidney function (p for interaction&lt;0.05). Similar results were found for outcomes at 1 year., Conclusions: A lower SUA/SCr ratio was associated with poor functional outcomes in patients with AIS at 3 months and at 1 year, suggesting the potential use of SUA/SCr ratio in clinical practice as a preferable marker for stroke outcomes., (© 2022 European Academy of Neurology.)

Elevated aspartate aminotransferase-to-alanine aminotransferase ratio (AAR) has been associated with cardiovascular diseases and mortality. The clinical significance of AAR in the prognosis of stroke has yet to be established. We aimed to investigate the associations between AAR levels and clinical outcomes in acute ischemic stroke (AIS) or transient ischemic attack (TIA). Patients with AIS or TIA in the Third China National Stroke Registry (CNSR-III) were divided into four groups by quartiles of AAR, and two groups according to AAR < 1 and AAR ≥ 1. Multivariable Cox regression for all-cause mortality and logistic regression for poor functional outcome (modified Rankin Scale, mRS 3-6/2-6) were adopted to explore the associations between AAR and clinical outcomes at 3 months and 1 year. Among 10,877 included patients, the median AAR was 1.06 (interquartile range [IQR], 0.82 to 1.36). In the multivariable-adjusted model, patients in the fourth AAR quartile had higher risk of all-cause mortality within 3 months and 1 year (hazard ratio [HR] 2.08, 95% confidence interval [CI] 1.25 to 3.47; HR 2.26, 95% CI 1.55 to 3.27), and mRS 3-6/2-6 at 1 year (odds ratio [OR] 1.29, 95% CI 1.07 to 1.55; OR 1.20, 95% CI 1.02 to 1.42), compared with those in the first quartile. Similar associations were also observed when AAR ≥ 1 compared with AAR < 1. Elevated AAR was associated with higher risk of all-cause mortality and poor functional outcome after AIS or TIA, and should be carefully assessed after admission., (© 2022. The Author(s), under exclusive licence to Società Italiana di Medicina Interna (SIMI).)

Aims: Gamma-glutamyl transferase (GGT) is considered a marker of oxidative stress in vivo. In this study, we aimed to examine the association of serum GGT levels with 3-month and 1-year stroke recurrence in patients with acute ischemic stroke or transient ischemic attack (TIA)., Methods: We conducted a large and multicenter cohort study. Participants with ischemic stroke or TIA who had a baseline GGT measurement were enrolled in the China National Stroke Registry-3 study from August 2015 to March 2018. They were divided into four groups according to sex-specific quartiles of GGT levels. The effect of GGT on stroke recurrence and other vascular events was examined during the 1-year follow-up period. Multivariate Cox regression models were performed to evaluate the association. Discrimination tests were used to examine the degree to which incorporating GGT into the conventional model predicted stroke adverse outcomes., Results: A total of 12,504 patients were enrolled. At both the 3-month and 1-year follow-ups, patients in the highest quartile group of GGT levels exhibited a higher risk of stroke recurrence [HR 1.32 (95% CI 1.07-1.63), HR 1.34 (95% CI 1.13-1.60)], ischemic stroke [HR 1.37 (95% CI 1.10-1.71), HR 1.37 (95% CI 1.14-1.64)], and combined vascular events [HR 1.34 (95% CI 1.09-1.65), HR 1.34 (95% CI 1.13-1.59)] than those in the lowest quartile group. Moreover, the Kaplan-Meier curves revealed that the incidence rates of stroke adverse outcomes were quite different in the four groups. The highest quartile group showed the highest cumulative incidence, while the lowest quartile group showed the lowest cumulative incidence. After applying discrimination tests, adding GGT into the conventional model resulted in slight improvements in predicting stroke adverse outcomes (NRI: 10%-14%)., Conclusion: This study demonstrated that elevated GGT levels were positively associated with an increased risk of stroke adverse outcomes, namely, recurrence, ischemic stroke, and combined vascular events., (© 2022 The Authors. CNS Neuroscience & Therapeutics published by John Wiley & Sons Ltd.)

Air pollution and ischemic stroke (IS) are both vital factors affecting the health of Beijing citizens. This study aims at exploring the associations between air pollution, meteorology, and the hospital admission of IS (IS HA). Information on 476,659 IS inpatients in secondary and higher hospitals in Beijing from 2013 to 2018 were collected. A time-stratified case-crossover design with the generalized additive model and the distributed lag nonlinear model were used. In the single-pollutant models, an inter-quartile range increase in O 3, SO 2 , CO, and NO 2 resulted in a significant highest increase in IS HA by 2.23% (95% CI: 1.56%, 2.90%), 1.53% (95% CI: 1.12%, 1.95%), 1.05% (95% CI: 0.70%, 1.40%), and 0.51% (95% CI: 0.24%, 0.79%) on the day of pollution, so did PM 2.5 and PM 10 by 1.13% (95% CI: 0.68%, 1.59%) and 1.19% (95% CI: 0.74%, 1.64%) at a lag of 0-5 days. There was a nonlinear relationship between meteorology and IS HA. In the multivariate model, the cumulative relative risks with a maximum lag time of 21 days of PM 2.5 and NO 2 were 1.11 (95% CI: 1.04, 1.19) and 0.88 (95% CI: 0.82, 0.94), while the effects of SO 2 , O 3 , and meteorology were insignificant. The findings suggested that particulate pollutants could increase the risk of IS, and the elderly were more sensitive to it, while the results of gaseous pollutants are still discordant. The control of air pollution and the protection of susceptible populations should receive higher attention from policymakers., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Air pollutants' effect on ischemic stroke (IS) has been widely reported. But the effect of high-level concentrations during people's outdoor periods among hypertension patients was unknown. Peak-hour concentrations were defined considering air pollutants' high concentrations as well as people's outdoor periods. We conducted a time-series study and used the generalized additive model to analyze peak-hour concentrations' acute effect. A total of 315,499 IS patients comorbid with hypertension were admitted to secondary and above hospitals in Beijing from 2014 to 2018. A 10 µg/m 3 (CO: 1 mg/m 3 ) increase of the peak-hour concentrations was positively associated with IS hospital admissions among hypertension patients. The maximum effect sizes were as follows: for PM 2.5 , 0.17% (95% confidence interval [CI]: 0.10-0.24%) at Lag0 and 0.22% (95% CI: 0.12-0.33%) at Lag0-5; for PM 10 , 0.09% (95% CI: 0.05-0.13%) at Lag5 and 0.17% (95% CI: 0.09-0.26%) at Lag0-5; for SO 2 , 0.87% (95% CI: 0.46-1.29%) at Lag5; for NO 2 , 0.83% (95% CI: 0.62-1.04%) at Lag0 and 0.86% (95% CI: 0.59-1.13%) at Lag0-1; for CO 1.23% (95% CI: 0.66-1.80%) at Lag0 and 1.33% (95% CI: 0.33-2.35%) at Lag0-5; for O 3 0.23% (95% CI: 0.12-0.35%) at Lag0 and 0.20% (95% CI: 0.05-0.34%) at Lag0-1. The effect sizes of PM 2.5 , NO 2 , and O 3 remained significant after adjusting daily mean. Larger effect sizes were observed for PM 2.5 and PM 10 in cool season and for O 3 in warm season. As significant exposure indicators of air pollution, peak-hour concentrations exposure increased the risk of IS hospital admissions among hypertension patients and it is worthy of consideration in relative environmental standard. It is suggested for hypertension patients to avoid outdoor activity during peak hours. More relevant searches are required to further illustrate air pollutant's effect on chronic disease population., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: This study aimed to investigate whether the relationship of prediabetes with the risk of stroke and its subtypes differed among individuals with or without hypertension., Methods: This prospective study included 85,763 participants without diabetes or a history of stroke at the baseline from the Kailuan study (2006). Prediabetes was defined as a fasting plasma glucose concentration between 5.6 and 6.9 mmol/L. We performed multiplicative and additive interaction analyses to assess the interaction effect between prediabetes and hypertension on the risk of incident stroke., Results: We found that 47.13% of all participants had no prediabetes or hypertension, 11.45% had prediabetes alone, 30.12% had hypertension alone, and 11.31% had both prediabetes and hypertension at baseline. During a median follow-up period of 11.05 years, we documented 3972 events of incident stroke. We found that hypertension modified the relationship of prediabetes with total stroke and ischaemic stroke (p for interaction <0.05). After adjustment for potential confounders, prediabetes was significantly associated with the risk of total stroke (hazard ratio [HR] 1.33, 95% confidence interval [CI] 1.18-1.52], p for interaction = 0.0147) and ischaemic stroke (HR 1.33, [95% CI 1.16-1.54], p for interaction = 0.0413) among participants without hypertension, but not among participants with hypertension. However, no interaction effect of the association between prediabetes and hypertension was observed on the risk of haemorrhagic stroke., Conclusions: Hypertension modified the association between prediabetes and risk of total and ischaemic stroke. Prediabetes was associated with an increased risk of total and ischaemic stroke only in the non-hypertension population., (© 2022 John Wiley & Sons Ltd.)

Background Many patients after stroke are found to have elevated serum creatine kinase (CK). This study aimed to investigate the associations between serum CK levels and clinical outcomes in patients with acute ischemic stroke or transient ischemic attack. Methods and Results The study included 8910 patients with acute ischemic stroke or transient ischemic attack from the CNSR-III (Third China National Stroke Registry). Baseline serum CK levels after admission were measured. The associations between CK and clinical outcomes (stroke recurrence, death, and disability, defined as modified Rankin scale score 3-6 or 2-6) were analyzed. Patients with elevated CK levels had higher risks of recurrent stroke (hazard ratio [HR], 1.53; 95% CI, 1.21-1.93), death (HR, 1.68; 95% CI, 1.10-2.58), and disability (modified Rankin scale score, 3-6; odds ratio, 1.57; 95% CI, 1.29-1.90) at 3 months after adjusting confounding factors. Similar results were found at 1 year. The effects of CK on death and disability were more significant in male patients than female patients ( P value for interaction <0.05). Elevated CK-MB levels were not associated with clinical outcomes in this study. Conclusions Elevated serum CK after ischemic stroke or transient ischemic attack is associated with higher risks of recurrent stroke, death, and disability at 3 months and 1 year. Serum CK may act as a useful predictor for recurrent stroke and poor functional outcomes in patients with acute ischemic stroke or transient ischemic attack. Sex modifies the relationship between elevated CK and disability or death.

Objective: This study was undertaken to identify the risk of bleeding events and potential risk factors within 90 days in patients who carried CYP2C19 loss-of-function alleles and received dual antiplatelet therapy after minor stroke or transient ischemic attack., Methods: A total of 6,412 patients were enrolled from the CHANCE-2 (Clopidogrel with Aspirin in High-Risk Patients with Acute Non-disabling Cerebrovascular Events II) trial. The main outcome was any bleeding within 90 days defined by the criteria from GUSTO (Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Coronary Arteries)., Results: A total of 250 (3.9%) bleeding events were reported, which occurred mainly within the 21 days of dual antiplatelet therapy (200 cases, 3.1%). Minor bleeding of the skin bruises, epistaxis, and gum bleeding were most frequent. Multivariate analysis showed that treatment with ticagrelor-aspirin compared with clopidogrel-aspirin was associated with increased bleeding (hazard ratio [HR] = 2.21, 95% confidence interval [CI] = 1.68-2.89, p < 0.001). Current smoking was associated with a lower risk of bleeding (HR = 0.70, 95% CI = 0.52-0.95, p = 0.02). Additionally, ticagrelor-aspirin compared with clopidogrel-aspirin was associated with higher risk of bleeding in patients aged <65 years (HR = 2.87, 95% CI = 1.95-4.22) and those without diabetes mellitus (HR = 2.65, 95% CI = 1.88-3.73; p for interaction = 0.04 and 0.03, respectively)., Interpretation: Bleeding events mostly occurred within the 21-day dual antiplatelet therapy stage and were generally mild. The risk of bleeding was greater in nonsmoking patients, and was associated with treatment with ticagrelor-aspirin compared with clopidogrel-aspirin, particularly in patients aged <65 years and nondiabetic patients. ANN NEUROL 2022;91:380-388., (© 2021 American Neurological Association.)

Introduction: Serum potassium abnormality is a risk factor of incident stroke, but whether it is associated with recurrent stroke in patients with acute ischemic stroke (AIS) or transient ischemic attack (TIA) remains unknown. This study aimed to investigate the association of serum potassium with the risk of recurrent stroke in patients with AIS or TIA., Methods: We included 12,425 patients from the China National Stroke Registry III. Patients were classified into 3 groups according to tertiles of potassium. The outcomes were recurrence of stroke and combined vascular events at 1 year. Cox proportional hazards regression was adopted to explore the associations by calculating hazard ratios (HRs) and their 95% confidence intervals (CIs)., Results: Among 12,425 enrolled patients, the median (interquartile range) of potassium was 3.92 (3.68-4.19) mmol/L. Compared with the highest tertile, after adjusted for confounding factors, the lowest tertile potassium was associated with increased risk of recurrent stroke at 1 year. The adjusted HR with 95% CI was 1.21 (1.04-1.41). There was an independent, linear association between serum potassium and stroke recurrence. Per 1 mmol/L decrease of potassium was associated with 19% higher risk of recurrent stroke (HR, 1.19; 95% CI, 1.04-1.37). Similar trends were found in ischemic stroke and combined vascular events., Conclusions: Lower serum potassium level was independently associated with elevated risk of recurrent stroke in patients with AIS or TIA. The finding suggested that monitoring serum potassium may help physicians to identify patients at high risk of recurrent stroke and to stratify risk for optimal management., (© 2021 S. Karger AG, Basel.)

Background: Previous studies found that lactate dehydrogenase (LDH) levels predicted poor outcomes in hemorrhagic stroke, but the prognostic role of LDH in ischemic stroke (IS) remains unclear. The aim of this study is to investigate the association between LDH and adverse clinical outcomes in patients with acute ischemic stroke (AIS) or transient ischemic attack (TIA)., Methods: All patients were enrolled from the Third China National Stroke Registry (CNSR-III). Adverse outcomes included all-cause death and poor functional outcomes [defined as modified Rankin Scale (mRS) score 3-6 and 2-6] at 3 months and 1 year. Multivariable Cox proportional hazards models and logistic regressions were used to evaluate the association of LDH with risk of all-cause death and poor functional outcomes, respectively., Results: Among 9,796 included patients, the median [interquartile range (IQR)] of LDH was 175.00 (151.00-205.40) U/L. After adjustment for confounding factors, patients in the highest LDH quartile had a higher risk of all-cause death [hazard ratio (HR), 2.23; 95% confidence interval (CI), 1.27-3.90], and a higher proportion of mRS score 3-6 [odds ratio (OR), 1.54; 95% CI, 1.26-1.90] and mRS score 2-6 (OR, 1.56; 95% CI, 1.32-1.84) at 3 months. We also observed a J-shaped association between LDH and risk of each outcome. Consistent results were found at 1 year., Conclusions: Higher LDH levels are independently associated with adverse outcomes in patients with AIS or TIA.

Background: The prognostic value of serum bilirubin in stroke is controversial, since bilirubin has both neuroprotective and neurotoxic properties. We aimed to investigate the association between serum bilirubin, including total bilirubin (TBIL), direct bilirubin (DBIL) and indirect bilirubin (IBIL) and poor functional outcomes in patients with acute ischemic stroke (AIS) or transient ischemic attack (TIA)., Methods: All patients with AIS or TIA were recruited from the Third China National Stroke Registry. The poor functional outcomes included modified Rankin Scale (mRS) score 2-6 and 3-6 at 3 months and 1 year. Multivariable logistic regression was used to investigate the associations of TBIL, DBIL, and IBIL with poor functional outcomes., Results: Among 11,121 enrolled patients, the median (interquartile range) of TBIL, DBIL, and IBIL was 13.30 (9.90-17.70), 3.80 (2.70-5.30), and 9.30 (6.70-12.80) µmol/L. After adjustment for conventional confounding factors, patients in the highest TBIL quartile had the highest proportion of mRS score 2-6 at 3 months (odds ratio [OR], 1.37; 95 % confidence interval [CI], 1.19-1.59) and 1 year (OR, 1.31; 95 % CI, 1.13-1.52), and mRS score 3-6 at 3 months (OR, 1.33; 95 % CI, 1.11-1.59) and 1 year (OR, 1.28; 95 % CI, 1.07-1.53), when compared to patients in the lowest TBIL quartile. Similar results were observed for DBIL and IBIL. We also found J-shaped associations between serum bilirubin levels and each outcome., Conclusions: Elevated levels of serum bilirubin were significantly associated with poor functional outcomes in patients with AIS or TIA at 3 months and 1 year., (© 2021. The Author(s).)

Background and Aims: Ideal cardiovascular health (CVH) metrics was associated with stroke, but the causal pathway was poorly investigated. Arterial stiffness was a major factor associated with both ideal CVH metrics and stroke. This study aimed to investigate whether the effect of ideal CVH metrics on stroke was mediated and enhanced by arterial stiffness., Methods and Results: A total of 15,297 participants were included in current study. Arterial stiffness was measured by brachial-ankle pulse wave velocity (baPWV). Causal mediation analyses were used to separate the overall effects of ideal CVH metrics on stroke into indirect effects (mediated by arterial stiffness) and direct effects (mediated through pathways other than arterial stiffness). After a median follow-up of 5.88 years, 324 total stroke events (292 ischemic stroke and 31 hemorrhagic stroke) occurred. Mediation analysis showed 23.94% of the relation between ideal CVH and total stroke was mediated by baPWV (95% confidence interval [CI] of the indirect effect: 0.93-0.95). Further analysis showed the ideal CVH < median combined with baPWV ≥1400 cm/s was associated with the highest risk of total stroke (hazard ratio: 5.62; 95% CI, 3.53-8.96), compared with CVH ≥ median combined with baPWV < 1400 cm/s. Similar results were observed for ischemic stroke, but not for hemorrhagic stroke., Conclusions: Arterial stiffness played a mediating role in the associations between ideal CVH metrics and risk of total and ischemic stroke. Combined ideal CVH metrics and baPWV is a reasonable and useful tool for the assessment and prevention of stroke., Competing Interests: Declaration of competing interest The authors have nothing to disclose., (Copyright © 2021 The Italian Diabetes Society, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.)

Background and Purpose: The clinical significance of carbon dioxide combining power (CO 2 CP) in ischaemic cerebrovascular disease is not well established, and the role of CO 2 CP in the prognosis of acute ischaemic stroke (AIS) or transient ischaemic attack (TIA) has not been reported. The objective of the study was to investigate the associations between CO 2 CP and clinical outcomes in patients with AIS or TIA., Methods: Data were derived from the China National Stroke Registry III. Patients were classified into five groups by quintiles of CO 2 CP levels and three groups according to the normal range of CO 2 CP (23-29 mmol/L). Multivariable Cox and logistic regressions were adopted to explore the associations of CO 2 CP levels with all-cause death and poor functional outcomes (modified Rankin Scale (mRS) 3-6/2-6) at 3 months and 1 year., Results: Among 9531 patients included in the study, the median (IQR) CO 2 CP was 24.9 (23.0-27.0) mmol/L. After adjustment for potential confounders, patients in the first CO 2 CP quintile (21.1-23.3 mmol/L) had higher risk of all-cause death and poor functional outcomes (mRS score of 3-6/2-6) (HR or OR with 95% CI 2.37 (1.32 to 4.25), 1.49 (1.20 to 1.83) and 1.21 (1.03 to 1.42), respectively) compared with those in the fourth quintile. Similar results were found for outcomes at 1 year. Furthermore, all associations were also significant when CO 2 CP was <23 mmol/L compared with CO 2 CP of 23-29 mmol/L., Conclusions: Decreased CO 2 CP was associated with high risk of all-cause death and poor functional outcomes in patients with AIS or TIA., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Introduction: As a neuroprotective medication, butylphthalide (NBP) may help protect against cerebral ischaemic injury. However, evidence on whether NBP influences the outcomes of patients who had acute ischaemic stroke who are receiving revascularisation treatment is limited. This study aims to evaluate whether additional NBP therapy can improve the functional outcome of patients who receive intravenous recombinant tissue plasminogen activator and/or endovascular treatment (EVT)., Methods and Analysis: The study will be a randomised, double-blind, placebo-controlled, multiple-centre, parallel group trial. The sample size is estimated at 1200 patients. Eligible patients will be randomised at a 1:1 ratio to receive either NBP or placebo daily for 90 days, which will include 14 days of injections and 76 days of capsules. The first use of NBP/placebo will be started within 6 hours of onset of ischaemic stroke. The primary outcome is the functional outcome as assessed by the 90-day modified Rankin Scale, adjusted for baseline scores on the National Institutes of Health Stroke Scale. The primary safety outcome is the percentage of serious adverse events during the 90 days of treatment. This trial will determine whether NBP medication benefits patients who had acute ischaemic stroke who receive intravenous thrombolysis or EVT., Ethics and Dissemination: The protocol was written according to the general ethical guidelines of the Declaration of Helsinki and approved by the Institutional Review Board/Ethics Committee of Beijing Tiantan Hospital, Capital Medical University with approval number KY 2018-003-02. Ethics committees of all participating sites have approved the study . Results of the study will be published in peer-reviewed scientific journals and shared in scientific presentations., Trial Registration Number: NCT03539445., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Triglyceride-glucose (TyG) index was recently suggested to be a reliable surrogate marker of insulin resistance. We aim to investigate the associations between baseline and long-term TyG index with subsequent stroke and its subtypes in a community-based cohort., Methods: A total of 97,653 participants free of history of stroke in the Kailuan Study were included. TyG index was calculated as ln (fasting triglyceride [mg/dL] × fasting glucose [mg/dL]/2). Baseline TyG index was measured during 2006-2007. Updated cumulative average TyG index used all available TyG index from baseline to the outcome events of interest or the end of follow up. The outcome was the first occurrence of stroke, including ischemic stroke, intracerebral hemorrhage and subarachnoid hemorrhage. The associations of TyG index with outcomes were explored with Cox regression., Results: During a median of 11.02 years of follow-up, 5122 participants developed stroke of whom 4277 were ischemic stroke, 880 intracerebral hemorrhage, and 144 subarachnoid hemorrhage. After adjusting for confounding variables, compared with participants in the lowest quartile of baseline TyG index, those in the third and fourth quartile were associated with an increased risk of stroke (adjusted hazard ratio [HR] 1.22, 95% confidence interval [CI] 1.12-1.33, and adjusted HR 1.32, 95% CI 1.21-1.44, respectively, P for trend < 0.001). We also found a linear association between baseline TyG index with stroke. Similar results were found for ischemic stroke. However, no significant associations were observed between baseline TyG index and risk of intracranial hemorrhage. Parallel results were observed for the associations of updated cumulative average TyG index with outcomes., Conclusions: Elevated levels of both baseline and long-term updated cumulative average TyG index can independently predict stroke and ischemic stroke but not intracerebral hemorrhage in the general population during an 11-year follow-up.

Background: Elevated homocysteine levels are associated with increased blood coagulation and platelet activity and may modulate the response to antiplatelet therapies. We aimed to investigate the effects of homocysteine levels on the efficacy and safety of ticagrelor–acetylsalicylic acid (ASA) versus clopidogrel–ASA among patients with minor stroke or transient ischemic attack who carried CYP2C19 loss-of-function alleles. Methods: We conducted a post hoc analysis of the CHANCE-2 (The Clopidogrel in High-risk Patients with Acute Nondisabling Cerebrovascular Events–II) trial. Participants were randomly assigned to treatment with ticagrelor–ASA or clopidogrel–ASA. We categorized participants into groups with elevated and non-elevated homocysteine levels, based on the median level. The primary efficacy outcome was recurrent stroke within 90-day follow-up. The primary safety outcome was severe or moderate bleeding within 90 days. Results: A total of 2740 participants were randomly assigned to receive ticagrelor–ASA and 2700 to receive clopidogrel–ASA. Use of ticagrelor–ASA was associated with a reduced risk of recurrent stroke among participants with elevated homocysteine levels (74 [5.3%] v. 119 [8.5%]; hazard ratio [HR] 0.60, 95% confidence interval [CI] 0.45–0.81), but not among those with non-elevated levels (86 [6.4%] v. 87 [6.7%]; HR 0.97, 95% CI 0.71–1.32; p = 0.04 for interaction). When analyzed as a continuous variable, the benefits of ticagrelor–ASA with regard to recurrent stroke increased as homocysteine levels increased (p = 0.04 for interaction). No significant interaction between homocysteine levels and treatment with regard to severe or moderate bleeding was observed (p = 0.7 for interaction). We found a significant interaction between homocysteine levels and therapy with regard to recurrent stroke in females (p = 0.04 for interaction) but not males. Interpretation: In comparison with clopidogrel–ASA, ticagrelor–ASA conferred more benefit to patients with elevated homocysteine levels, particularly to female patients, in this secondary analysis of a randomized controlled trial involving patients with minor ischemic stroke or TIA. Trial registration: ClinicalTrials.gov, no. NCT04078737 [ABSTRACT FROM AUTHOR]

Background: Body mass index (BMI) may affect the response to platelet P2Y12 receptor inhibitors. We aimed to explore whether BMI influenced the efficacy and safety of ticagrelor and clopidogrel for secondary prevention of minor ischemic stroke or transient ischemic attack (TIA) among patients enrolled in the CHANCE-2 (Ticagrelor or Clopidogrel with Aspirin in High-Risk Patients with Acute Nondisabling Cerebrovascular Events II) trial. Methods: In a multicentre, randomized, double-blind, placebo-controlled trial, conducted in China, we randomized patients with minor stroke or TIA who carried the CYP2C19 loss-of-function allele to receive either ticagrelor–acetylsalicylic acid (ASA) or clopidogrel–ASA. We classified patients into obese (BMI ≥ 28) or nonobese (BMI < 28) groups. The primary efficacy outcome was stroke within 90 days, and the primary safety outcome was severe or moderate bleeding within 90 days. Results: Among 6412 patients, 876 were classified as obese and 5536 were classified as nonobese. Compared with clopidogrel–ASA, ticagrelor–ASA was associated with a significantly lower rate of stroke within 90 days among patients with obesity (25 [5.4%] v. 47 [11.3%]; hazard ratio [HR] 0.51, 95% confidence interval [CI] 0.30–0.87), but not among those in the nonobese group (166 [6.0%] v. 196 [7.0%]; HR 0.84, 95% CI 0.69–1.04) The interaction of treatment and BMI group was significant (p for interaction = 0.04). We did not observe any difference by BMI group in rates of severe or moderate bleeding (9 [0.3%] v. 10 [0.4%] in the nonobese group; 0 [0.0%] v. 1 [0.2%] in the obese group; p for interaction = 0.99). Interpretation: In this secondary analysis of a randomized controlled trial involving patients with minor ischemic stroke or TIA, compared with clopidogrel–ASA, patients with obesity received more clinical benefit from ticagrelor–ASA therapy than those without obesity. Trial registration: Clinicaltrials.gov, no. NCT04078737. [ABSTRACT FROM AUTHOR]

Background: Evidence on the risk-benefit ratio of dual antiplatelet therapies among patients with stroke and impaired renal function is limited and inconsistent.Objective: To investigate the effect of renal function on the efficacy and safety of ticagrelor-aspirin versus clopidogrel-aspirin treatment.Design: Post hoc analysis of a multicenter, randomized, double-blind, placebo-controlled trial. (ClinicalTrials.gov: NCT04078737).Setting: 202 centers in China.Patients: CYP2C19 loss-of-function allele carriers with minor stroke or transient ischemic attack.Intervention: Ticagrelor-aspirin and clopidogrel-aspirin.Measurements: Renal function was evaluated by estimated glomerular filtration rate (eGFR) levels. The primary efficacy and safety outcomes were recurrent stroke and severe or moderate bleeding within 90 days, respectively.Results: Among 6378 patients, 4050 (63.5%) had normal (eGFR ≥90 mL/min/1.73 m2), 2010 (31.5%) had mildly decreased (eGFR 60 to 89 mL/min/1.73 m2), and 318 (5.0%) had moderately to severely decreased (eGFR <60 mL/min/1.73 m2) renal function. The corresponding differences in recurrent stroke between ticagrelor-aspirin and clopidogrel-aspirin for normal, mildly decreased, and moderately to severely decreased renal function was -2.8 percentage points (95% CI, -4.4 to -1.3 percentage points) (hazard ratio [HR], 0.63 [CI, 0.49 to 0.81]), -0.2 percentage point (CI, -2.4 to 2.0 percentage points) (HR, 0.98 [CI, 0.69 to 1.39]), and 3.7 percentage points (CI, -2.3 to 10.1 percentage points) (HR, 1.31 [CI, 0.48 to 3.55]), respectively. Rates of severe or moderate bleeding did not substantially differ by treatment assignments across eGFR categories.Limitation: Renal function was only evaluated by using eGFR, and the proportion of patients with severely decreased renal function was low.Conclusion: Patients with normal, rather than impaired, renal function received greater benefit from ticagrelor-aspirin versus clopidogrel-aspirin.Primary Funding Source: Ministry of Science and Technology of the People's Republic of China. [ABSTRACT FROM AUTHOR]

Background: Cerebral small vessel disease (SVD) is common in the aging population. The study aimed to evaluate the effect of SVD on functional outcomes in patients with acute ischemic stroke (AIS) receiving endovascular treatment (EVT). Methods: From a prospective registry, we selected patients with AIS receiving EVT. SVD features, including white matter hyperintensities (WMH), lacunes and brain atrophy, were assessed on MRI and a validated SVD score was calculated to reflect the total SVD burden. Results: Among 137 patients included, 106 had none-mild SVD burden and 31 had moderate-severe SVD burden. The moderate-severe SVD burden group showed a significantly higher modified Rankin Scale score at 90 d (median, 4 versus 1 points, adjusted common odds ratio 0.32 [95% CI, 0.14–0.69], P < 0.01) and a significantly smaller improvement of NIHSS at 24 h (median, –3 versus –3 points, adjusted β coefficient 4.02 [95% CI, 0.57–7.48], P = 0.02) and 7 days (median, –4 versus –6 points, adjusted β coefficient 4.71 [95% CI, 1.06–8.36], P = 0.01) than the none-mild group. There was no significant difference in successful recanalization, death within 90 days, symptomatic intracranial hemorrhage within 24 h between two groups (all P > 0.05). Additionally, for each single SVD feature, brain atrophy and WMH, but not lacunes, were associated with the functional outcome. Conclusion: Moderate-severe SVD burden was associated with poor early and late functional outcomes in patients with AIS receiving EVT. Our results suggest that SVD score may act as a good predictor of outcomes in these patients. [ABSTRACT FROM AUTHOR]

Background and Aims: The role of serum uric acid (SUA) in stroke remains controversial and analyses of changes in SUA and stroke are limited. The objective of the study was to investigate the associations of changes in SUA with stroke and its subtypes (ischemic and hemorrhagic stroke).Methods and Results: A total of 51 441 participants (mean age 52.69 ± 11.71 years) without history of myocardial infarction or stroke were enrolled. Participants were divided into four groups based on SUA level changes during 2006 and 2010: stable low, increasing, decreasing, and stable high. SUA score was quantified on a 3-point scale with 1 point awarded for hyperuricemia at either year 2006, 2008 or 2010. Multivariate Cox proportion models were used to calculated hazard ratios (HRs) and their 95% confidence intervals (CIs). During 7.03-year follow up, 1611 stroke (1410 ischemic stroke, 199 hemorrhagic stroke, and 47 subarachnoid hemorrhage) were identified. Participants with stable high SUA had higher risk of hemorrhagic stroke, the HR was 1.93 (95% CI: 1.06-3.51), compared to those with stable low SUA. Furthermore, cumulative high SUA exposure also increased the risk of hemorrhagic stroke, the HR (95%CI) was 2.99 (1.55-5.74), compared with cumulative low SUA exposure. However, no significant evidence indicated changes in SUA was associated with the risk of total and ischemic stroke, the HRs (95% CIs) were 0.98 (0.74-1.29) and 0.88 (0.65-1.19), respectively.Conclusions: Stable high SUA was positively associated with the risk of hemorrhagic stroke, but not with total and ischemic stroke risk. [ABSTRACT FROM AUTHOR]