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Background The aim of this study was to investigate the efficacy and safety of tenecteplase versus alteplase in patients with acute ischemic stroke, considering their diabetes history and admission hyperglycemia status. Methods and Results This was a post hoc analysis of the TRACE‐2 (Tenecteplase Reperfusion Therapy in Acute Ischemic Cerebrovascular Events‐2) randomized clinical trial that enrolled patients in China between June 2021 and May 2022. Eligible patients with acute ischemic stroke for standard intravenous thrombolysis, but ineligible for endovascular thrombectomy, were randomly assigned (1:1) to tenecteplase or alteplase within 4.5 hours of symptom onset. Admission hyperglycemia was defined as plasma glucose >7.8 mmol/L. The primary efficacy and safety outcome were excellent functional outcome at 90 days (modified Rankin Scale score of 0–1) and symptomatic intracranial hemorrhage within 36 hours, respectively. The Cochran–Mantel–Haenszel χ2 test was used for the outcomes. Of the 1382 patients included, 369 (26.7%) had a history of diabetes, and 482 (34.9%) experienced admission hyperglycemia. The primary efficacy outcome, comparing tenecteplase to alteplase, was achieved in 93 (56.7%) versus 97 (48.3%) among patients with a history of diabetes (P=0.11) and 335 (64.6%) versus 300 (62.2%) among those without diabetes (P=0.45), respectively. The primary efficacy outcome for tenecteplase versus alteplase was comparable among patients with and without admission hyperglycemia (57.5% versus 53.9%, P = 0.44; 65.4% versus 60.4%, P=0.12, respectively). No significant difference in the risk of symptomatic intracranial hemorrhage within 36 hours was observed between tenecteplase and alteplase, regardless of diabetes history or admission hyperglycemia. Conclusions This study demonstrated that intravenous tenecteplase exhibits similar clinical outcomes compared with alteplase, irrespective of the patient's glucose metabolism status. Registration URL: https://clinicaltrials.gov; Unique identifier: NCT04797013.

Abstract Background and Aim Glycated albumin (GA) is a biomarker monitoring glycemia 2–4 weeks before stroke onset. This study was designed to explore the association between GA levels with poststroke outcomes in patients with acute ischemic stroke or transient ischemic attack (TIA). Method Participants with ischemic stroke or TIA who had a baseline GA measurement were included in the Third China National Stroke Registry study. The effect of GA on stroke recurrence, poor functional outcomes, and combined vascular events was examined during the 1‐year follow‐up period. Multivariate Cox and logistic regression models were performed to evaluate the association. Discrimination tests were used to examine the incremental predictive value of GA when incorporating it into the conventional model. Results A total of 3861 participants were enrolled. At the 3‐month follow‐up, the elevated GA level was associated with an increased risk of poor functional outcomes (adjusted odds ratio [OR], 1.45; 95% confidence interval [CI], 1.01–2.09). A similar increase was observed for stroke recurrence (adjusted hazard ratio [HR], 1.56; 95% CI, 1.09–2.24), poor functional outcomes (adjusted OR, 1.62; 95% CI, 1.07–2.45), and combined vascular events (adjusted HR, 1.55; 95% CI, 1.09–2.20) at the 1‐year follow‐up. In nondiabetic patients, the association between GA and poor functional outcomes was more pronounced (adjusted OR, 1.62; 95% CI, 1.05–2.50). Adding GA into the conventional model resulted in slight improvements in predicting poor functional outcomes (net reclassification improvement [NRI]: 12.30% at 1 year). Conclusion This study demonstrated that elevated GA levels in serum were associated with stroke adverse outcomes, including stroke recurrence, poor functional outcomes, and combined vascular events, in patients with ischemic stroke or TIA.

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 (

Abstract Somatic mutations related to clonal hematopoiesis of indeterminate potential (CHIP) are risk factors for stroke. The impact of DNMT3A, the most mutated gene in CHIP, on clinical functional outcomes of acute ischemic stroke (AIS) remains unclear. In a well‐characterized cohort of 8524 ischemic stroke patients, we demonstrated that DNMT3A‐driven CHIP was significantly associated with neurological disability in these patients. With a stroke mouse model of transient middle cerebral artery occlusion (tMCAO), we demonstrated that DNMT3A protein levels in the brain penumbra increased. The DNMT3A inhibitor RG108 administration amplified neutrophil proliferation in the blood, promoted neutrophil infiltration into the brain penumbra, and exaggerated proinflammatory activation in tMCAO male mice. DNMT3A inhibition also significantly increased infarct volume and worsened neurobehavioral function in tMCAO male mice. In conclusion, DNMT3A somatic mutations are associated with worsened neurological disability in some patients with AIS, potentially through increased neutrophil proliferation and infiltration in the ischemic brain region. These findings suggest a possible mechanism for proinflammatory activation and tissue damage in the affected brain tissue, highlighting the need for further research in this area.

Background Tenecteplase, a bioengineered variant of alteplase, is a new alternative thrombolytic agent. The ORIGINAL study aims to evaluate the efficacy and safety of tenecteplase versus standard care in Chinese patients with acute ischemic stroke within 4.5 hours of symptom onset. Methods This is a multicenter phase III study that employs a randomized (1:1), active‐controlled, parallel‐group, prospective, open‐label, blinded–end point design. Adult participants (aged ≥18 years) with acute ischemic stroke who are eligible for intravenous thrombolysis within 4.5 hours of symptom onset according to current guideline recommendations are recruited from ≈55 neurology clinics/stroke centers throughout China. Results The primary objective of the ORIGINAL study is to demonstrate the noninferiority of tenecteplase (0.25 mg/kg) to alteplase (0.9 mg/kg) on the basis of the proportion of patients who achieve a modified Rankin Scale score of 0 or 1 on day 90, that is, a favorable functional outcome. The prespecified noninferiority risk ratio margin is 0.937. Secondary end points include other functional outcomes and the following safety end points: adjudicated symptomatic intracerebral hemorrhage (up to 36 hours after the end of study drug administration) based on the European Cooperative Acute Stroke Study III definition; all‐cause death within 90 days; and the proportion of patients with a modified Rankin Scale score of 5 or 6 on day 90. Conclusions It is anticipated that the results of this study will contribute to the growing body of evidence for the noninferiority of tenecteplase to alteplase given within 4.5 hours of acute ischemic stroke symptom onset and support a new indication for tenecteplase in China. Clinical Trial Registration Information NCT04915729 (https://clinicaltrials.gov/study/NCT04915729)

Background We aim to identify the distinct lesion patterns and regions associated with functional outcome and inflammation in patients with acute ischemic stroke, and investigate whether the association between lesion patterns and functional outcome was mediated by inflammation. Methods and Results We performed nonnegative matrix factorization to derived low‐dimensional lesion patterns (atoms), and Bayesian linear regression models were applied to explore the associations of lesion patterns with inflammatory factors including high‐sensitivity C‐reactive protein and interleukin‐6, as well as functional outcome (defined as modified Rankin Scale score at 3 months). The difference distribution mean and 95% highest probability density interval (HPDI) were calculated. Mediation analysis was used to examine the mediating effects of inflammation on the relationships between lesion patterns and functional outcome. Seven lesion patterns were derived from 5914 patients with acute ischemic stroke. Lesion patterns distributed in the cortical regions were associated with inflammatory response, including atom 1 (interleukin‐6: mean, 0.113 [95% HPDI, 0.073–0.162]; high‐sensitivity C‐reactive protein: mean, 0.082 [95% HPDI, 0.038–0.123]) and atom 4 (interleukin‐6: mean, 0.113 [95% HPDI, 0.071–0.167]; high‐sensitivity C‐reactive protein: mean, 0.108 [95% HPDI, 0.058–0.165]). These lesion patterns were also significantly associated with functional outcome (atom 1: mean, 1.958 [95% HPDI, 1.538–2.383]; atom 4: mean, 2.245 [95% HPDI, 1.773–2.741]). Mediation analysis suggested that interleukin‐6 explained 15.34% and 7.47% in the association of atom 1 and atom 4 with functional outcome, respectively. Conclusions Certain lesion patterns that are associated with both inflammation and functional outcome of acute ischemic stroke, especially cortical infarction, may play a role in functional outcome through modulating inflammatory reactions.

Background Elevated white blood cell count, fibrinogen levels, and lower levels of albumin signify higher systemic inflammatory response, hypercoagulable state, and poorer nutritional status, respectively. However, a consistent conclusion could not be drawn on whether the association between inflammatory markers and cardiovascular disease was affected by the presence of chronic kidney disease (CKD). We aimed to explore the association between inflammation and adverse outcomes in patients with acute ischemic stroke (AIS), as well as whether this association differs due to the presence of CKD. Methods and Results This research was based on the Third China National Stroke Registry. The main adverse outcomes were poor functional outcome, stroke recurrence, and combined vascular event after 1 year. Inflammation was defined as the worst quartile of at least 2 of the aforementioned 3 markers. Finally, 8493 patients with AIS were enrolled in this study. The adjusted odds ratios/hazard ratios and 95% CIs of inflammation were 1.58 (1.34–1.86) for poor functional outcomes, 1.25 (1.06–1.47) for stroke recurrence, and 1.25 (1.06–1.46) for combined vascular event. The association between inflammation and adverse outcomes existed only in patients with AIS without CKD, although the interaction between CKD and inflammation was not statistically significant. (P for interaction >0.05). Conclusions Inflammation, which was defined as a combination of fibrinogen, white blood cell count, and albumin, was associated with all 1‐year adverse outcomes among patients with AIS. Routine assessment of these biomarkers could become a potential part of the clinical evaluation for patients with AIS, especially those without CKD, aiding clinicians in risk stratification and treatment decision‐making.

Background Risk of recurrence after minor ischemic stroke is usually reported with transient ischemic attack. No previous meta‐analysis has focused on minor ischemic stroke alone. The objective was to evaluate the pooled proportion of 90‐day stroke recurrence for minor ischemic stroke, defined as a National Institutes of Health Stroke Scale severity score of ≤5. Methods and Results Published papers found on PubMed from 2000 to January 12, 2021, reference lists of relevant articles, and experts in the field were involved in identifying relevant studies. Randomized controlled trials and observational studies describing minor stroke cohort with reported 90‐day stroke recurrence were selected by 2 independent reviewers. Altogether 14 of 432 (3.2%) studies met inclusion criteria. Multilevel random‐effects meta‐analysis was performed. A total of 6 randomized controlled trials and 8 observational studies totaling 45 462 patients were included. The pooled 90‐day stroke recurrence was 8.6% (95% CI, 6.5–10.7), reducing by 0.60% (95% CI, 0.09–1.1; P=0.02) with each subsequent year of publication. Recurrence was lowest in dual antiplatelet trial arms (6.3%, 95% CI, 4.5–8.0) when compared with non‐dual antiplatelet trial arms (7.2%, 95% CI, 4.7–9.6) and observational studies 10.6% (95% CI, 7.0–14.2). Age, hypertension, diabetes, ischemic heart disease, or known atrial fibrillation had no significant association with outcome. Defining minor stroke with a lower National Institutes of Health Stroke Scale threshold made no difference – score ≤3: 8.6% (95% CI, 6.0–11.1), score ≤4: 8.4% (95% CI, 6.1–10.6), as did excluding studies with n

Background Insulin resistance as a significant vascular risk factor has been studied in relation to cerebral small vessel disease (SVD). Evidence suggests that insulin resistance might trigger high blood pressure (BP). Therefore, we aimed to investigate whether insulin resistance impacts SVD with a mediating effect of BP in nondiabetic subjects. Methods and Results PRECISE (Polyvascular Evaluation for Cognitive Impairment and Vascular Events) study participants underwent brain and vascular imaging techniques and metabolomic risk factors measurements. Insulin resistance was evaluated by the insulin sensitivity index and the Homeostatic Model Assessment for Insulin Resistance based on the standard oral glucose tolerance test. On average, 2752 nondiabetic subjects (47.1% men) aged 60.9 years were included. The multivariable logistic regression model and linear regression model tested the association of insulin resistance with BP components (including systolic BP [SBP], diastolic BP (DBP), and pulse pressure [PP]) and SVD, and of BP components with SVD. In the mediation analysis, SBP, DBP, and PP were found to partially mediate the detrimental effect of insulin resistance (assessed by the insulin sensitivity index) on lacunes (mediation percentage: SBP, 31.15%; DBP, 34.21%; PP, 10.43%), white matter hyperintensity (mediation percentage: SBP, 37.34%; DBP, 44.15%; PP, 9.80%), and SVD total burden (mediation percentage: SBP, 42.07%; DBP, 49.29%; PP, 11.71%) (all P

Background Acute ischemic stroke is a major cause of mortality and disability worldwide, with approximately 7.4% to 7.7% recurrence within the first 3 months. This study aimed to identify potential biomarkers for predicting stroke recurrence. Methods and Results We conducted a nested case–control study using a hospital‐based cohort from the Third China National Stroke Registry selecting 214 age‐ and sex‐matched patients with ischemic stroke with hypertension and no history of diabetes or heart disease. Using data‐independent acquisition for discovery and multiple reaction monitoring for quantitative validation, we identified 26 differentially expressed proteins in large‐artery atherosclerosis (Causative Classification of Ischemic Stroke [CCS]1), 16 in small‐artery occlusion (CCS3), and 25 in undetermined causes (CCS5) among patients with recurrent stroke. In the CCS1 and CCS3 subgroups, differentially expressed proteins were associated with platelet aggregation, neuronal death/cerebroprotection, and immune response, whereas differentially expressed proteins in the CCS5 subgroup were linked to altered metabolic functions. Validated recurrence predictors included proteins associated with neutrophil activity and vascular inflammation (TAGLN2 [transgelin 2], ITGAM [integrin subunit α M]/TAGLN2 ratio, ITGAM/MYL9 [myosin light chain 9] ratio, TAGLN2/RSU1 [Ras suppressor protein 1] ratio) in the CCS3 subgroup and proteins associated with endothelial plasticity and blood–brain barrier integrity (ITGAM/MYL9 ratio and COL1A2 [collagen type I α 2 chain]/MYL9 ratio) in the CCS3 and CCS5 subgroups, respectively. Conclusions These findings provide a foundation for developing a blood‐based biomarker panel, using causative classifications, which may be used in routine clinical practice to predict stroke recurrence.

Abstract In deep coal mining, the high temperature and humidity environment are one of the main disasters threatening workers and equipment. To predict the temperature and humidity of airflow in the airway accurately, this study establishes a numerical calculation model of the surrounding rock temperature, airflow temperature, and humidity under the conditions of considering the moisture evaporation and heat absorption of the airway wall, the condensation and heat release of supersaturated water vapor in the airflow, and the influence of air compression or expansion. Combined with the two‐dimensional (2D) heat conduction model (considering the influence of the axial surrounding rock heat conduction of the airway), the axial strip partial moisture calculation model of the airway is proposed, and then the uniform moist wall model and the axial strip partial moist wall model are established. The influence of different parameters on the temperature and humidity of airflow is discussed by analyzing the results of numerical simulation of the uniform wet surface model (UWSM) and partly wet surface model (PWSM) of the airway wall. The results show that the surrounding rock temperature, especially the temperature distribution of the airway wall, calculated by using the 2D heat conduction model under the local humid airway conditions, is more realistic. The increment of airflow temperature decreases with the increase of wet area ratio, airflow temperature at the entrance and airway radius, and increases with relative humidity at the entrance. The calculation accuracy of temperature and humidity prediction for large ventilation networks can be further improved by using the equivalent humidity of the UWSM to replace the correction coefficient of the wet area ratio of the PWSM.

Background This study aimed to investigate the efficacy and safety of ticagrelor–aspirin versus clopidogrel–aspirin in Chinese patients by the presence and clinical presentation of intracranial artery stenosis (ICAS) using randomized trial data from the CHANCE‐2 (Clopidogrel in High‐Risk Patients With Acute Nondisabling Cerebrovascular Events‐II) trial. Methods and Results A total of 6412 patients with minor stroke or transient ischemic attack who carried CYP2C19 loss‐of‐function alleles were randomized to either the ticagrelor–aspirin or clopidogrel–aspirin group. Patients without imaging of the intracranial artery were excluded from the nonprespecified subgroup analysis of CHANCE‐2. All patients included were classified into the following groups: without ICAS, symptomatic ICAS, or asymptomatic ICAS. The primary efficacy outcome was new strokes within 90 days. There were 5893 patients (median age, 64.8 years; 33.9% women) included, and 172 (4.9%), 171 (10.5%), and 57 (7.7%) cases of new strokes occurred within 90 days in the without ICAS, with symptomatic ICAS, and with asymptomatic ICAS groups, respectively. Ticagrelor–aspirin was associated with reduced risk of new stroke in patients without ICAS (62 [3.5%] versus 110 [6.3%]; hazard ratio [HR], 0.57 [95% CI, 0.41–0.78]) but not in those with symptomatic ICAS (HR, 0.77 [95% CI, 0.56–1.05]) or in those with asymptomatic ICAS (HR, 0.77 [95% CI, 0.43–1.38]) compared with clopidogrel–aspirin (P for interaction=0.14). There were no significant differences in the proportion of severe or moderate bleeding events among different ICAS groups. Conclusions Patients without ICAS received a significantly greater benefit from ticagrelor–aspirin than clopidogrel–aspirin after minor ischemic stroke or transient ischemic attack, and there was no statistically significant difference between treatments in patients with symptomatic ICAS or asymptomatic ICAS. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT04078737.

Abstract Background The relationship between single nucleotide polymorphisms (SNPs) and ovarian cancer (OC) risk remains controversial. This systematic review and network meta‐analysis was aimed to determine the association between SNPs and OC risk. Methods Several databases (PubMed, EMBASE, China National Knowledge Infrastructure, Wanfang databases, China Science and Technology Journal Database, and China Biology Medicine disc) were searched to summarize the association between SNPs and OC published throughout April 2021. Direct meta‐analysis was used to identify SNPs that could predict the incidence of OC. Ranking probability resulting from network meta‐analysis and the Thakkinstian’s algorithm was used to select the most appropriate gene model. The false positive report probability (FPRP) and Venice criteria were further tested for credible relationships. Subgroup analysis was also carried out to explore whether there are racial differences. Results A total of 63 genes and 92 SNPs were included in our study after careful consideration. Fok1 rs2228570 is likely a dominant risk factor for the development of OC compared to other selected genes. The dominant gene model of Fok1 rs2228570 (pooled OR = 1.158, 95% CI: 1.068–1.256) was determined to be the most suitable model with a FPRP

Abstract Little is known about the relationship between baseline systolic blood pressure (SBP) and subsequent clinical events in patients with different lesion patterns on diffusion weighted imaging (DWI). We analyzed the Acute Non‐disabling Cerebrovascular Events (CHANCE) trial dataset. Patients were categorized into negative DW imaging (no detectable lesions), lacunar infarction (single lesion ≤15 mm) and non‐lacunar infarction (single lesion >15 mm or multiple lesions) based on lesion patterns on DWI. The primary outcome was recurrent stroke within 90 days. Cox proportional hazards models were used to assess the association between SBP levels and stroke outcomes in patients with different lesion patterns. A total of 1089 patients were analyzed. We found 258 cases (23.7%) with negative DW imaging, 392 (36.0%) with lacunar infarction and 439 (40.3%) with non‐lacunar infarction. Patients with non‐lacunar infarction had the highest incidence of stroke at 90‐day (P

Background Smoking is a well‐established risk factor for the development of acute ischemic stroke (AIS). However, the “smoker's paradox” suggests that it is associated with favorable clinical outcomes following stroke. We aimed to reevaluate the association between smoking and in‐hospital outcomes in patients with AIS in contemporary practice. Methods and Results A total of 649 610 inpatients with AIS from 1476 participating hospitals in the Chinese Stroke Center Alliance were included. In‐hospital outcomes measurement included all‐cause mortality, discharge against medical advice, and complications. Multivariable logistic regression models adjusting for baseline characteristics, clinical profiles at presentation, and in‐hospital management were used to evaluate the association between smoking and in‐hospital outcomes. A propensity score–matched analysis was also conducted. Of these patients with AIS, 36.8% (n=238 912) were smokers. Smokers were younger, had fewer comorbidities, and had slightly lower rates of adverse in‐hospital outcomes than nonsmokers (all‐cause death or discharge against medical advice: 6.0% versus 6.1%; in‐hospital complications: 14.5% versus 15.1%). Multivariable analysis revealed that smoking was associated with higher risk of adverse in‐hospital outcomes (all‐cause death or discharge against medical advice: odds ratio [OR], 1.05 [95% CI, 1.02–1.08]; P

Abstract Cognitive impairment after stroke/transient ischemic attack (TIA) has a high prevalence. The authors aimed to explore the risk factors for declined cognitive function with Montreal Cognitive Assessment (MoCA)‐Beijing in patients with stroke/TIA at acute phase. Total 2283 patients with acute stroke/TIA without a history of dementia were assessed at 2 weeks of onset. Patients were assessed by MoCA‐Beijing on day 14 and at 3 months follow‐ups. Cognitive impairment was defined as MoCA‐Beijing ≤22. Patients’ cognitive status was considered as declined if there were a reduction of ≥2 points in MoCA‐Beijing score and patients were considered to have improved if there were an increase of ≥2 points. The score of MoCA‐Beijing was considered to be stable if there were an increase or decrease of 1 point. Most patients were in 60 s (60.96 ± 10.75 years old) with a median (interquartile range) National Institute of Health Stroke Scale score of 3.00 (4.00) and greater than primary school level of education, and 1657 participants (72.58%) were male. Cognitive evaluation was conducted in 2283 of 2625 patients (82.70%) with MoCA‐Beijing at baseline. Total 292 (12.79%) patients have a cognitive decline at 3 months, 786 (34.42%) patients were stable and 1205 (52.78%) patients were improved. In the logistic regression, a history of hypertension was associated with cognitive deterioration from baseline to 3‐month. Patients with a history of hypertension have a higher risk for cognitive deterioration from baseline to 3‐month after stroke/TIA.

Abstract Introduction A high residual risk of subsequent stroke suggested that the predictive ability of Stroke Prognosis Instrument‐II (SPI‐II) and Essen Stroke Risk Score (ESRS) may have changed over the years. Aim To explore the predictive values of the SPI‐II and ESRS for 1‐year subsequent stroke risk in a pooled analysis of three consecutive national cohorts in China over 13 years. Results In the China National Stroke Registries (CNSRs), 10.7% (5297/50,374) of the patients had a subsequent stroke within 1 year; area under the curve (AUC) of SPI‐II and ESRS was .60 (95% confidence interval [CI]: .59–.61) and .58 (95% CI: .57–.59), respectively. For SPI‐II, the AUC was .60 (95% CI: .59–.62) in CNSR‐I, .60 (95% CI: .59–.62) in CNSR‐II, and .58 (95% CI: .56–.59) in CNSR‐III over the past 13 years. The declining trend was also found in ESRS scale (CNSR‐I: .60 [95% CI: .59–.61]; CNSR‐II: .60 [95% CI: .59–.62]; and CNSR‐III: .56 [95% CI: .55–.58]). Conclusions The predictive power of the traditional risk scores SPI‐II and ESRS was limited and gradually decreased over the past 13 years, thus the scales may not be useful for current clinical practice. Further derivation of risk scales with additional imaging features and biomarkers may be warranted.

Abstract Objective Deep medullary veins (DMVs) were not considered a typical marker of cerebral small vessel disease (CSVD) due to limited understanding of their involvement in pathology of CSVD. This study aimsto investigate potential vascular risk factors for DMVs and their associations with CSVD. Methods In total, 1909 community‐dwelling participants were included in this analysis. Demographic, clinical, laboratory, and imaging data were collected. DMV scores (0–18) werecalculated as the sum of bilateral frontal, parietal, and occipital regional scores using a semiquantitative visual scale (0–3). The presence, total burden, and imaging markers of CSVD were assessed. Linear regression analyses were conducted to explore potential vascular factors for DMV scores. Binary and ordinal logistic regression analyses were performed to investigate the associations of DMV scores with CSVD and its markers. Results Mean age was 61.8 (SD 6.5) years, and 1027 (53.8%) of participants were men. The median DMV scores were14 (IQR 12–16). DMV scores wererelated to age, male sex, body mass index, diastolic blood pressure, hypercholesterolaemia, atrial fibrillation, current drinking, total cholesterol, triglycerides, low‐density lipoprotein, hemoglobin A1c, leukocytes, lymphocytes, hemoglobin, and platelets (p

Ischemic strokes (IS) and transient ischemic attacks (TIA) account for approximately 80% of all strokes and are leading causes of death worldwide. Assessing the risk of recurrence or functional impairment in IS and TIA patients is essential to both acute phase treatment and secondary prevention. Current risk prediction systems that rely on clinical parameters alone without leveraging imaging data have only modest performance. Herein, a deep learning‐based risk prediction system (RPS) is developed to predict the probability of stroke recurrence or disability (i.e., deep‐learning stroke recurrence risk score, SRR score). Then, Kaplan–Meier analysis to evaluate the ability of SRR score to stratify patients at stroke recurrence risk is discussed. Using 15 166 Third China National Stroke Registry (CNSR‐III) cases, the RPS's receiver operating characteristic curve (AUC) values of 0.850 for 14 day TIA recurrence prediction and 0.837 for 3 month IS disability prediction are used. Among patients deemed high risk by SRR score, 22.9% and 24.4% of individuals with TIA and IS respectively have stroke recurrence within 1 year, which are significantly higher than the rates in low‐risk individuals. Deep learning‐based RPS can outperform conventional risk scores and has the potential to assist accurate prognostication in stroke patients to optimize management.

Abstract Purpose Resting metabolic rate (RMR) could represent metabolic health status. This study aims to examine the association of the predicted RMR with 1‐year poor functional outcome and all‐cause mortality in patients with ischemic stroke as a proxy of metabolic profile. Methods A total of 15,166 patients with ischemic stroke or transient ischemic attack (TIA) from the Third China National Stroke Registry (CNSR‐III) were enrolled in this study. The Harris–Benedict equation based on sex, age, weight, and height was used to predict RMR. The primary endpoints were poor functional outcome defined as ≥3 modified Rankin Scale (mRS) score and all‐cause mortality within 1 year. The association between predicted RMR and prognosis was assessed by multivariable regression analysis. Besides that, subgroup analysis of age, sex, and body mass index (BMI) with predicted RMR was also performed. Results 12.85% (1657) individuals had poor functional outcome and 2.87% (380) died of whatever causes within 1 year. An inverse association was found between predicted RMR with poor functional outcome and all‐cause mortality. Compared to the lowest quartile, the highest quartile was significantly associated with lower risk of poor functional outcome (adjusted odds ratio [OR], 0.43 [95% confidence interval (CI) 0.33–0.56]) and all‐cause mortality (adjusted hazard ratio [HR], 0.44 [95% CI 0.28–0.71]). No significant interaction was between predicted RMR and specified subgroup. Conclusions Predicted RMR by the Harris–Benedict equation seems to be an independent protective predictor of poor functional outcome and all‐cause mortality after ischemic stroke as a metabolic proxy.

Abstract The heart rate (HR) trajectory is a dynamic metric that shows how HR changes over time. Previous studies have demonstrated that elevated HR is associated with stroke events. However, little research has been done on the influence of shifting HR throughout the acute period on clinical outcomes. This study aims to investigate the effect of HR trajectories on functional outcomes in patients with acute ischemic stroke (AIS). A total of 981 AIS patients were included in the study. A latent mixture model was used to assess HR trends over the first 7 days following disease onset. The patients were divided into four groups based on different HR trajectories: markedly decreasing in 48 h (T1), mildly decreasing in 48 h (T2), sustained moderate in 7 days (T3), and sustained high in 7 days (T4). Poor outcome was defined as a modified Rankin Scale (mRS) score of ≥3 in 3 months. Logistic regression was used to analyze the correlation between different HR trajectories and outcomes. The incidence of poor outcomes was 9.02%, 10.80%, 11.79%, 16.36% in T1 (n = 133), T2 (n = 352), T3 (n = 441), and T4 (n = 55) groups, respectively. Compared with T1 group, T4 group was significantly associated with a higher risk of poor outcome at 3 months (odds ratio = 3.00, 95% confidence interval = 1.06–8.54, p value = .0392). This suggests that in AIS patients, a sustained high HR trajectory is linked to a greater likelihood of poor functional outcome than a markedly decreasing HR trajectory. HR trajectories demonstrate the utility of repeated HR measurements for outcome assessment.

Abstract Background Osteoporosis is a metabolic disease, and osteoporotic fracture (OPF) is one of its most serious complications. It is often ignored that the influence of the muscles surrounding the fracture on the healing of OPF. We aimed to clarify the role of skeletal muscle satellite cells (SMSCs) in promoting OPF healing by β‐catenin, to improve our understanding of SMSCs, and let us explore its potential as a therapeutic target. Methods Skeletal muscles were obtained from control non‐OPF or OPF patients for primary SMSCs culture (n = 3, 33% females, mean age 60 ± 15.52). Expression of SMSCs was measured. In vivo, 3‐month‐old female C57BL/6 mice underwent OVX surgery. Three months later, the left tibia fracture model was again performed. The control and the treatment group (n = 24, per group, female). The treatment group was treated with an agonist (osthole). Detection of SMSCs in muscles and fracture healing at 7, 14, and 28 three time points (n = 8, 8, 8, female). To further clarify the scientific hypothesis, we innovatively used Pax7‐CreERT2/+;β‐cateninfx/fx transgenic mice (n = 12, per group, male). Knock out β‐catenin in SMSC to observe the proliferation and osteogenic differentiation of SMSCs, and OPF healing. In vitro primary cells of SMSCs from 3‐month‐old litter‐negative β‐cateninfx/fx transgenic mice. After adenovirus‐CRE transfection, the myogenic and osteogenic differentiation of SMSC was observed. Results We find that human SMSCs reduced proliferation and osteogenic differentiation in patients with OPF (−38.63%, P

Abstract Nocturnal trough systolic blood pressure (NTSBP) and Time Point of Nocturnal Trough Systolic Blood Pressure (T‐NTSBP) were important parameters of nocturnal blood pressure, the predictive values of which are unclear for stroke outcome. This study aimed to examine the relationship between NTSBP/T‐NTSBP and stroke outcome. The authors used data from a nationwide ambulatory blood pressure monitoring cohort study conducted in China, which recruited 2348 ischemic stroke and transient ischemic attack (TIA) patients. NTSBP was defined as the lowest SBP during nighttime (22:00–6:00), and T‐NTSBP was defined as the corresponding time point of NTSBP. The associations between NTSBP/T‐NTSBP and stroke outcome (stroke recurrence and combined vascular event [CVE]) at 90 days or 1 year were analyzed using cox regression models. According to NTSBP classified by quartile, hazard ratio (HR) with 95% confidence interval (CI) for NTSBP quartile 4 (>129 mm Hg) was 2.727 (1.148–6.478) for CVE at 90‐day, compared with quartile 1 (≤102 mm Hg). However, an attenuated association between NTSBP and CVE was observed at 1 year. In addition, we observed the group of T‐NTSBP at 4:00–6:00 had a lowest CVE incidence at 90 days among four groups (22:00–23:59, 00:00–1:59 2:00–3:59, 4:00–6:00). After multivariable adjustment, T‐NTSBP was significantly associated with CVE incidence at 90 days (T‐NTSBP at the 4:00–6:00 versus the 22:00–23:59 group: HR, 0.433; 95%CI, 0.190–0.986), independent of NTSBP and average nocturnal SBP. Both of NTSBP and T‐NTSBP were important predictors for short‐term cardiovascular risk in ischemic stroke and TIA patients.

Abstract Background and purpose The impact of sex and age on prognosis in patients with intracerebral hemorrhage (ICH) in the Chinese population remains unclear. Our study aimed to investigate the relationship between sex and age of Chinese ICH patients and adverse prognosis. Methods We used the Chinese Stroke Center Alliance database with in‐hospital mortality as the primary outcome and hospital complications as the secondary outcome. Patients were divided into four groups by sex and age. Logistic regression analyses were performed to assess the association between sex and age and the prognosis of ICH patients. Results We enrolled 60,911 ICH patients, including 22,284 young and middle‐aged males, 15,651 older males, 11,948 young and middle‐aged females, and 11,028 older females. After adjusting for variables, older male patients had a higher mortality rate (OR = 1.21, 95% CI 1.01–1.45), combined with more frequent hematoma expansion (OR = 1.14, 95% CI 1.03–1.26), pneumonia (OR = 1.91, 95% CI 1.81–2.03), and hydrocephalus (OR = 1.28, 95% CI 1.04–1.59). Young and middle‐aged female patients had a lower mortality rate (OR = 0.74, 95% CI 0.58–0.95) and less frequent combined pneumonia (OR = 0.81, 95% CI 0.75–0.87). In‐hospital mortality was not significantly different in older females compared with young and middle‐aged males, but the odds of deep vein thrombosis, swallowing disorders, urinary tract infections, and gastrointestinal bleeding were significantly higher. Conclusion Among young and middle‐aged patients, females are related to a lower in‐hospital mortality rate from ICH. Older patients are at an increased risk of ICH complications, with higher in‐hospital mortality in older men.

Abstract Cognitive function following acute ischemic stroke (AIS) is critical to prognosis and quality of life. Hypertension is a risk factor for stroke and is associated with post stroke cognitive impairment (PSCI). However, the optimal blood pressure parameters after AIS is unknown. This is a sub‐study of the Impairment of CognitiON and Sleep after acute ischemic stroke or transient ischemic attack in Chinese patients (ICONS) study conducted between August 2015 and March 2018. Cognition was assessed at two‐week (2w), three‐month (3 m), and twelve‐month (12 m) by Montreal Cognitive Assessment (MoCA). A total of 682 participants who met the inclusion criteria were enrolled. The primary outcome was cognitive changes after 3 and 12 months post stroke. Among 682 participants, the mean age was 59.35 ± 10.40 years and 72.29% were men. PSCI patients with high systolic blood pressure (SBP ≥140 mm Hg) at 3 m not only had worse cognition as evidenced by MoCA scores at 3 m but also predicted worse scores at 12 m. When participants were stratified into cognitively stable/improved (MoCA score ≥0, 2w vs. 12 m) and cognitively impaired (MoCA score ≤‐2, 2w vs. 12 m), those with high SBP were more likely to be cognitively impaired (OR 2.17, 95%CI 1.12–4.21, p

Background Oxidized low‐density lipoprotein (oxLDL) and hs‐CRP (high‐sensitivity C‐reactive protein) plays an important role in cardiovascular diseases though inflammation and oxidative stress, etc. However, evidence on their combined effects on stroke prognosis is still limited. We aimed to explore the joint association of oxLDL and hs‐CRP with outcomes of minor stroke or transient ischemic attack. Methods and Results A subgroup of 3019 patients from the CHANCE trial (Clopidogrel in High‐Risk Patients With Acute Nondisabling Cerebrovascular Events) were analyzed. Baseline oxLDL and hs‐CRP levels were measured. The primary outcome was any stroke within 90 days. The secondary outcomes included any stroke within 1 year, and ischemic stroke, combined vascular events, and poor functional outcomes (modified Rankin Scale 2–6 or 3–6) at 90 days and 1 year. Vascular events outcomes were analyzed with Cox proportional hazards and poor functional outcomes with logistic models. Elevated oxLDL (>28.81 μg/dL) and hs‐CRP (>4.20 mg/L) was observed in 624 (20.67%) of the 3019 patients. Patients with oxLDL >28.81 μg/dL and hs‐CRP >4.20 mg/L had a higher risk of recurrent stroke within 90 days (adjusted hazard ratio, 1.52; 95% CI, 1.17–1.97), compared with those with oxLDL ≤28.81 μg/dL and hs‐CRP ≤4.20 mg/L, after adjusting relevant confounding factors (P=0.002). Similar results were observed for secondary outcomes (P

Background Trimethylamine N‐oxide (TMAO) contributes to cardiovascular disease through its prothrombotic, proatherothrombotic, and proinflammatory effects. We aimed to evaluate whether residual risk of recurrent stroke of TMAO and its precursor choline remain among patients who received dual‐antiplatelet therapy and intensive lipid‐lowering therapy and with a low inflammation level (high‐sensitivity C‐reactive protein

Abstract Background Little is known about the distribution of the intracranial arteries that are responsible for noncardiogenic posterior circulation stroke (PCS) in the Chinese population. Furthermore, few studies have compared the imaging manifestations and outcomes across PCS due to the disease of different intracranial arteries. Therefore, our aim was to demonstrate the distribution of the intracranial arteries that were responsible for noncardiogenic PCS and to compare the imaging manifestations and outcome across PCS due to the disease of different intracranial arteries. Methods We prospectively enrolled 690 patients from 22 Chinese centers with noncardiogenic PCS due to intracranial artery disease. Intracranial artery disease was classified as intracranial vertebral artery disease (IVAD) and intracranial nonvertebral artery disease (INVAD). Clinical‐radiologic patterns and outcomes were compared between IVAD and INVAD. Results INVAD was more frequent than IVAD. Compared to the INVAD group, the IVAD group more frequently had hypertension, coronary heart disease, multiple infarcts, border zone infarcts, territorial infarcts, small cortical infarcts, multilevel infarcts, multisector infarcts, and more often had severe stenosis of the responsible artery, more often presented with decreased alertness, gaze palsy, bilateral limb weakness, ataxia, dysphagia, diplopia, vertigo, and headache. In addition, the IVAD group had a higher National Institutes of Health stroke scale score and modified Rankin Scale score at discharge and more deaths and recurrent ischemic cerebrovascular disease within 1 year of onset. Multivariable Cox regression identified IVAD as an independent predictor of recurrent ischemic cerebrovascular disease. Conclusions PCS due to INVAD was more common in the Chinese population. However, PCS due to IVAD had more serious clinical‐radiologic patterns and worse outcomes.

Abstract Background and purpose Diabetes mellitus is a strong independent risk factor for stroke recurrence. However, the association between diabetes duration and the prognosis of stroke remains uncertain. We aimed to characterize whether an association exists between diabetes duration and stroke outcomes in patients with ischemic stroke or transient ischemic attack (TIA). Methods Between 2015 and 2018, 14,674 patients with ischemic stroke or TIA within 7 days and older than 18 years from the Third China National Stroke Registry (CNSR‐III) were included in this analysis. Diabetes duration at baseline was collected by face‐to‐face interviews and further categorized into groups of without diabetes, diabetes

Background The aim of this study was to investigate the association between hsCRP (high‐sensitivity C‐reactive protein) and prognosis over time after stroke onset. Methods and Results In this prespecified prospective substudy of the Third China National Stroke Registry, a total of 9438 patients with acute ischemic stroke or transient ischemic attack and measured hsCRP were included. Patients were categorized into 3 groups according to the sampling time after index onset (

Abstract Background Ischemic stroke (IS) caused by middle cerebral artery (MCA) disease is the most common type of IS caused by intracranial artery disease in the Chinese population. Hypertension and diabetes mellitus are the common risk factors of cerebral small vessel disease and large artery atherosclerosis (LAA). However, little is known about whether hypertension and diabetes mellitus had different correlations with the small artery occlusion (SAO) and LAA etiology of MCA disease. Therefore, our aim was to identify the predictors of the etiology of MCA disease. Methods We consecutively enrolled 967 patients with noncardiogenic IS in unilateral MCA territory. Vascular risk factors and the clinical–radiologic features of IS were analyzed. The etiology of IS were classified as SAO or LAA according to the Stop Stroke Study Trial of Org 10172 in Acute Stroke Treatment classification criteria. Multivariable logistic regression was used to identify the differences in the predictors between SAO and LAA etiology of MCA disease. Results Multivariable logistic regression identified male and hypertension as the predictors of the SAO etiology of MCA disease, however diabetes mellitus, repeated transient ischemic attack before the stroke, gaze palsy, aphasia, headache at admission, and disability at discharge as the predictors of the LAA etiology of MCA disease. Conclusion Hypertension and diabetes mellitus are related with the different etiology of MCA disease.

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

Background The serum uric acid/serum creatinine ratio (SUA/SCr), which represents renal function‐normalized SUA, is associated with diverse adverse outcomes. The aim of this study was to investigate the association between SUA/SCr and cardiovascular disease (CVD), and determine whether and to what extent this association is mediated by cardiometabolic factors. Methods and Results This prospective study enrolled 96 378 participants from the Kailuan study without stroke and myocardial infarction at baseline (2006). Cox proportional hazard models were used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs). Mediation analyses were conducted to separately explore the mediating effects of cardiometabolic factors on the association between SUA/SCr and CVD. During median follow up of 11.01 years, 6315 (6.55%) individuals developed incident CVD. After adjustment for potential confounders, the highest quartile of SUA/SCr was associated with the highest risk of CVD (HR, 1.15; 95% CI, 1.07–1.23), stroke (HR, 1.16; 95% CI, 1.07–1.26), ischemic stroke (HR, 1.12; 95% CI, 1.02–1.22), and hemorrhagic stroke (HR, 1.36; 95% CI, 1.11–1.65), but not with myocardial infarction (HR, 1.07; 95% CI, 0.92–1.25). The association was consistent across different degrees of kidney function and glucose tolerance statuses. Additionally, the association between high SUA/SCr and CVD was partially mediated by triglycerides (30.74%), body mass index (BMI) (19.52%), total cholesterol (15.06%), hs‐CRP (high‐sensitivity C‐reactive protein) (13.06%), diastolic blood pressure (11.75%), and blood glucose (−16.38%). Conclusions SUA/SCr and CVD were positively associated. Furthermore, this association was partially mediated through blood lipids, BMI, blood pressure, hs‐CRP, and blood glucose.

Background Trimethyllysine, a trimethylamine N‐oxide precursor, has been identified as an independent cardiovascular risk factor in acute coronary syndrome. However, limited data are available to examine the role of trimethyllysine in the population with stroke. We aimed to examine the relationship between plasma trimethyllysine levels and stroke outcomes in patients presenting with ischemic stroke or transient ischemic attack. Methods and Results Data of 10 027 patients with ischemic stroke/transient ischemic attack from the CNSR‐III (Third China National Stroke Registry) and 1‐year follow‐up data for stroke outcomes were analyzed. Plasma levels of trimethyllysine were measured with mass spectrometry. The association between trimethyllysine and stroke outcomes was analyzed using Cox regression models. Mediation analysis was performed to examine the mediation effects of risk factors on the associations of trimethyllysine and stroke outcomes. Elevated trimethyllysine levels were associated with increased risk of cardiovascular death (quartile 4 versus quartile 1: adjusted hazard ratio [HR], 1.72; 95% CI, 1.03–2.86) and all‐cause mortality (quartile 4 versus quartile 1: HR, 1.97; 95% CI, 1.40–2.78) in multivariate Cox regression model. However, no associations were found between trimethyllysine and nonfatal stroke recurrence or nonfatal myocardial infarction. Trimethyllysine was associated with cardiovascular death independent of trimethylamine N‐oxide. Both estimated glomerular filtration rate and hs‐CRP (high‐sensitivity C‐reactive protein) had significant mediation effects on the association of trimethyllysine with cardiovascular death, with a mediation effect of 37.8% and 13.4%, respectively. Conclusions Elevated trimethyllysine level is associated with cardiovascular death among patients with ischemic stroke/transient ischemic attack. Mediation analyses propose that trimethyllysine contributes to cardiovascular death through inflammation and renal function, suggesting a possible pathomechanistic link.

Background Anemia or low hemoglobin can increase the risk of stroke. However, the association between hemoglobin and outcomes after stroke is uncertain. In this study, we aimed to investigate the association between hemoglobin and clinical outcomes, including mortality, poor functional outcome, stroke recurrence, and composite vascular events at 1 year. Methods and Results We included the patients diagnosed with acute ischemic stroke or transient ischemic attack from the Third China National Stroke Registry. We used the Cox model for mortality, stroke recurrence, and composite vascular events and the logistic model for the poor functional outcome to examine the relationship between hemoglobin and clinical outcomes. In addition, we used the restricted cubic spline to evaluate the nonlinear relationship. This study included 14 159 patients with acute ischemic stroke or transient ischemic attack. After adjusted for potential cofounders, both anemia and high hemoglobin were associated with the higher risk of mortality (hazard ratio [HR], 1.73; 95% CI, 1.39–2.15; HR, 2.71; 95% CI, 1.95–3.76) and poor functional outcome (odds ratio [OR], 1.36; 95% CI, 1.18–1.57; OR, 1.42; 95% CI, 1.07–1.87). High hemoglobin, but not anemia, increased the risk of stroke recurrence (HR, 1.37; 95% CI, 1.05–1.79) and composite vascular events (HR, 1.41; 95% CI, 1.08–1.83). There was a U‐shaped relationship between hemoglobin and mortality and poor functional outcome. Conclusions Abnormal hemoglobin was associated with a higher risk of all‐cause mortality, poor functional outcome, stroke recurrence, and composite vascular events. More well‐designed clinical studies are needed to confirm the relationship between hemoglobin and clinical outcomes after stroke.

Background To investigate whether collateral status could modify the associations between post‐thrombectomy blood pressure (BP) measures and outcomes. Methods and Results Patients with anterior‐circulation large‐vessel‐occlusion successfully recanalized in a multicenter endovascular thrombectomy registry were enrolled. Pretreatment collateral status was graded and dichotomized (good/poor) in angiography. Maximum, minimum, and mean systolic BP (SBP) and BP variability (assessed by the SD, coefficient of variation) during the initial 24 hours after endovascular thrombectomy were obtained. The primary outcome was unfavorable 90‐day outcome (modified Rankin Scale score 3–6). Secondary outcomes included symptomatic intracranial hemorrhage and 90‐day mortality. Adjusted odds ratios (aOR) of BP parameters over the outcomes were obtained in all patients and in patients with good/poor collaterals. Among 596 patients (mean age 66 years; 59.9% males), 302 (50.7%) patients had unfavorable 90‐day outcome. In multivariable analyses, higher mean SBP (aOR, 1.59 per 10 mm Hg increment; 95% CI, 1.26–2.02; P140 mm Hg (versus ≤120 mm Hg; aOR, 4.27; 95% CI, 1.66–10.97; P=0.002), and higher SBP SD (aOR, 1.08 per 1‐SD increment; 95% CI, 1.01–1.16; P=0.02) were respectively associated with unfavorable 90‐day outcome in patients with poor collateral but not in those with good collateral. A marginal interaction between SBP coefficient of variation tertiles and collaterals on 90‐day functional outcome (P for interaction, 0.09) was observed. A significant interaction between SBP coefficient of variation tertiles and collaterals on 90‐day mortality (P for interaction, 0.03) was observed. Conclusions Higher postprocedural BP is associated with 90‐day unfavorable outcomes after successful endovascular thrombectomy in patients with poor collateral. Registration URL: https://www.chictr.org.cn; Unique identifier: ChiCTR1900022154.

Background D‐dimer is involved in poor outcomes of stroke as a coagulation biomarker. We aimed to investigate the associations of the level and increase in D‐dimer between baseline and 90 days with all‐cause death or poor functional outcome in patients after ischemic stroke or transient ischemic attack. Methods and Results We collected data from the CNSRIII (Third China National Stroke Registry) study. The present substudy included 10 518 patients within 7 days (baseline) of ischemic stroke or transient ischemic attack and 6268 patients at 90 days. Poor functional outcome at 1 year was assessed on the basis of the modified Rankin Scale (≥3). Multivariable Cox regression or logistic regression was used to assess the association of D‐dimer levels with all‐cause death or poor functional outcome. D‐dimer levels at 90 days were lower than those at baseline (1.4 µg/mL versus 1.7 µg/mL; P

Abstract Background and purpose We performed a retrospective analysis of the “Thrombolysis Implementation and Monitor of Acute Ischemic Stroke in China (TIMS‐China)” registry to explore the benefit and risk of intravenous thrombolysis (IVT) followed by intravenous heparin (IVH) in acute ischemic stroke (AIS) patients. Methods In the TIMS‐China database, the patients who received IVH immediately after IVT (Early IVH group) and those who initiated antithrombotic therapy (ATT) until 24 hr after IVT (Standard ATT group) were screened for this comparison. Propensity score (PS) matching was performed between both groups. The logistic regression analysis was performed in the matched population to compare all the efficacy and safety outcomes. Results Of 1,437 patients in this study, 119 received early IVH and 1,318 cases initiated standard ATT. After PS matching (1:2), 117 pairs were identified. The early IVH group had higher proportions of neurological improvement at 24 hr (OR = 2.24, 95% CI = 1.42–3.53) and 7 days (OR = 1.92, 95% CI = 1.22–3.03), better chance of excellent recovery (OR = 1.69, 95% CI = 1.07–2.67) and functional independence (OR = 1.77, 95% CI = 1.13–2.78) at 90 days, and a lower 90‐day mortality (OR = 0.44, 95% CI = 0.21–0.92) than standard ATT group. Additionally, early IVH did not increase the risk of symptomatic intracranial hemorrhage (OR = 0.92, 95% CI = 0.34–2.48). Conclusions IVH immediately after thrombolysis seems to be safe and potentially more effective as compared with standard ATT delay of 24 hr for a subset of AIS patients.

Background Proteinuria often changes and is known as a “time‐dependent exposure.” The effect of time‐dependent proteinuria on the risk of future stroke remains unclear. Proteinuria is often detected in patients with diabetes mellitus. The present study was designed to evaluate the association between time‐dependent proteinuria and the risk of stroke in a patient cohort with different glucose tolerance status. Methods and Results A total of 82 938 participants, who were free of myocardial infarction or stroke and underwent fasting blood glucose and urinary protein measurements at baseline in the Kailuan study, were enrolled. Proteinuria was determined using urine dipstick tests at baseline and subsequent follow‐ups. Time‐dependent proteinuria was defined as the status of urine protein updated through the follow‐up examinations, separately. Time‐dependent Cox regression models were used to analyze the relationship between time‐dependent proteinuria and the risk of stroke. During a median follow‐up of 8.37 years, 2538 participants developed stroke. After adjusting for confounding factors, the hazard ratio (95% CI) for stroke in time‐dependent proteinuria among all participants, and the normoglycemia, prediabetes, and diabetes mellitus populations were 1.68 (1.49–1.89), 1.73 (1.47–2.05), 2.15 (1.70–2.72), and 1.30 (1.03–1.65), respectively. There were interaction effects in patients with normoglycemia and prediabetes compared with those with diabetes mellitus. Findings were similar for ischemic and hemorrhagic strokes and were confirmed in sensitivity analyses. Conclusions Time‐dependent proteinuria is an independent risk factor of stroke, especially in the normoglycemia and prediabetes populations.

Background Atrial fibrillation (AF) has been shown to be associated with an increased risk of dementia as well as Alzheimer disease in observational studies. Whether this association reflects causal association is still unclear. The purpose of this study was to examine the causal association of AF with Alzheimer disease. Methods and Results We used a 2‐sample Mendelian randomization approach to evaluate the causal effect of AF on Alzheimer disease. Summary data on the association of single nucleotide polymorphisms with AF were obtained from a recently published genome‐wide association study with up to 1 030 836 individuals and data on single nucleotide polymorphism‐Alzheimer disease association from another genome‐wide association study with up to 455 258 individuals. AF was mainly diagnosed according to International Classification of Diseases, Ninth Revision (ICD‐9 or ICD‐10) and Alzheimer disease was mainly diagnosed according to clinical criteria (eg, National Institute of Neurological and Communicative Disorders and Stroke and the Alzheimer's Disease and Related Disorders Association [NINCDS‐ADRDA] criteria). Effect estimates were calculated using the inverse‐variance weighted method. The Mendelian randomization analysis showed nonsignificant association of genetically predicted AF with risk of Alzheimer disease (odds ratio=1.002, 95% CI: 0.996–1.009, P=0.47) using 93 single nucleotide polymorphisms as the instruments. Mendelian randomization‐Egger indicated no evidence of genetic pleiotropy (intercept=0.0002, 95% CI: −0.001 to 0.001, P=0.70). Conclusions This Mendelian randomization analysis found no evidence to support causal association between AF and Alzheimer disease.