Tenecteplase versus alteplase in acute ischaemic cerebrovascular events (TRACE-2): a phase 3, multicentre, open-label, randomised controlled, non-inferiority trial.

BACKGROUND: There is increasing interest in replacing alteplase with tenecteplase as the preferred thrombolytic treatment for patients with acute ischaemic stroke. We aimed to establish the non-inferiority of tenecteplase to alteplase for these patients. METHODS: In this multicentre, prospective, open-label, blinded-endpoint, randomised controlled, non-inferiority trial, adults with an acute ischaemic stroke who were eligible for standard intravenous thrombolysis but ineligible for endovascular thrombectomy were enrolled from 53 centres in China and randomly assigned (1:1) to receive intravenous tenecteplase (0·25 mg/kg, maximum dose of 25 mg) or intravenous alteplase (0·9 mg/kg, maximum dose of 90 mg). Participants had to be able to receive treatment within 4·5 h of stroke, have a modified Rankin Scale (mRS) score of no more than 1 before enrolment, and have a National Institutes of Health Stroke Scale score of 5-25. Patients and treating clinicians were not masked to group assignment; clinicians evaluating outcomes were masked to treatment type. The primary efficacy outcome was the proportion of participants who had a mRS score of 0-1 at 90 days, assessed in the modified intention-to-treat population (all randomly assigned participants who received the allocated thrombolytic), with a non-inferiority margin of 0·937 for the risk ratio (RR). The primary safety outcome was symptomatic intracranial haemorrhage within 36 h, assessed in all participants who received study drug and had a safety assessment available. The trial is registered with ClinicalTrials.gov, NCT04797013, and has been completed. FINDINGS: Between June 12, 2021, and May 29, 2022, 1430 participants were enrolled and randomly assigned to tenecteplase (n=716) or alteplase (n=714). Six patients assigned to tenecteplase and seven to alteplase did not receive study product, and five participants in the tenecteplase group and 11 in the alteplase group were lost to follow-up at 90 days. The primary outcome in the modified intention-to-treat population occurred in 439 (62%) of 705 in the tenecteplase group versus 405 (58%) of 696 in the alteplase group (RR 1·07, 95% CI 0·98-1·16). The lower limit of the RR's 95% CI was greater than the non-inferiority margin. Symptomatic intracranial haemorrhage within 36 h was observed in 15 (2%) of 711 in the tenecteplase group and 13 (2%) of 706 in the alteplase group (RR 1·18, 95% CI 0·56-2·50). Mortality within 90 days occurred in 46 (7%) individuals in the tenecteplase group versus 35 (5%) in the alteplase group (RR 1·31, 95% CI 0·86-2·01). INTERPRETATION: Tenecteplase was non-inferior to alteplase in people with ischaemic stroke who were eligible for standard intravenous thrombolytic but ineligible for or refused endovascular thrombectomy. FUNDING: National Science and Technology Major Project, Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences, National Natural Science Foundation of China, and China Shijiazhuang Pharmaceutical Company Recomgen Pharmaceutical (Guangzhou).

Rosuvastatin Slows Progression of Carotid Intima-Media Thickness: The METEOR-China Randomized Controlled Study.

BACKGROUND: Atherosclerosis is the leading cause of cardiovascular disease worldwide, including in China. Primary prevention, through lipid-lowering, could avert development of atherosclerosis. Carotid intima-media thickness (CIMT) is a well-validated measure of atherosclerosis used in intervention studies as the primary outcome and alternative end point for cardiovascular disease events. METHODS: This randomized, double-blind, placebo-controlled, multicenter, parallel-group study assessed the effects of rosuvastatin 20 mg/d compared with placebo on progression of CIMT over 104 weeks in Chinese people with subclinical atherosclerosis. The primary end point was the annualized rate of change in mean of the maximum CIMT measurements taken 7× over the study period from each of 12 carotid artery sites (near and far walls of the right and left common carotid artery, carotid bulb, and internal carotid artery). Secondary end points included CIMT changes at different artery sites and lipid-parameter changes. Safety was also assessed. RESULTS: Participants were randomized (1:1) to receive rosuvastatin (n=272) or placebo (n=271). Baseline characteristics were well balanced between groups. The change in mean of the maximum CIMT of the 12 carotid sites was 0.0038 mm/y (95% CI, -0.0023-0.0100) for the rosuvastatin group versus 0.0142 mm/y (95% CI, 0.0080-0.0204) for the placebo group, with a difference of -0.0103 mm/y (95% CI, -0.0191 to -0.0016; P=0.020). For the CIMT secondary end points, the results were generally consistent with the primary end point. There were clinically relevant improvements in lipid parameters with rosuvastatin. We observed an adverse-event profile consistent with the known safety profile of rosuvastatin. CONCLUSIONS: Rosuvastatin 20 mg/d significantly reduced the progression of CIMT over 2 years in Chinese adults with subclinical atherosclerosis and was well tolerated. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT02546323.

Edaravone Dexborneol Versus Edaravone Alone for the Treatment of Acute Ischemic Stroke: A Phase III, Randomized, Double-Blind, Comparative Trial.

BACKGROUND AND PURPOSE: Edaravone dexborneol, comprised of 2 active ingredients, edaravone and (+)-borneol, has been developed as a novel neuroprotective agent with synergistic effects of antioxidant and anti-inflammatory in animal models. The present clinical trial aimed at testing the effects of edaravone dexborneol versus edaravone on 90-day functional outcome in patients with acute ischemic stroke (AIS). METHODS: A multicenter, randomized, double-blind, comparative, phase III clinical trial was conducted at 48 hospitals in China between May 2015 and December 2016. Inclusion criteria included patients diagnosed as AIS, 35 to 80 years of age, National Institutes of Health Stroke Scale Score between 4 and 24, and within 48 hours of AIS onset. AIS patients were randomized in 1:1 ratio into 2 treatment arms: 14-day infusion of edaravone dexborneol or edaravone injection. The primary end point was the proportion of patients with modified Rankin Scale score ≤1 on day 90 after randomization. RESULTS: One thousand one hundred sixty-five AIS patients were randomly allocated to the edaravone dexborneol group (n=585) or the edaravone group (n=580). The edaravone dexborneol group showed significantly higher proportion of patients experiencing good functional outcomes on day 90 after randomization, compared with the edaravone group (modified Rankin Scale score ≤1, 67.18% versus 58.97%; odds ratio, 1.42 [95% CI, 1.12-1.81]; P=0.004). The prespecified subgroup analyses indicated that a greater benefit was observed in female patients than their male counterparts (2.26, 1.49-3.43 versus 1.14, 0.85-1.52). CONCLUSIONS: When edaravone dexborneol versus edaravone was administered within 48 hours after AIS, 90-day good functional outcomes favored the edaravone dexborneol group, especially in female patients. Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT02430350.

Low- versus Standard-Dose Intravenous Tissue-Type Plasminogen Activator for Acute Ischemic Stroke: An Updated Meta-Analysis.

BACKGROUND: We performed a meta-analysis to compare the efficacy and safety between low- and standard-dose intravenous (IV) tissue-type plasminogen activator (tPA) for acute ischemic stroke (AIS) patients within 4.5 hours of symptom onset. METHODS: We searched PubMed and EMBASE for relevant studies from inception to June1, 2017. Cohort or randomized controlled studies for AIS within 4.5 hours of symptom onset with comparison between low-dose and standard-dose tPA were included. The primary efficacy end point was favorable functional outcome (modified Rankin scale scores [mRS] of 0-1) at 90 days. The primary safety end point was the incidence rate of symptomatic intracerebral hemorrhage (sICH). The secondary end points were independent functional outcome (mRS scores of 0-2) and mortality. RESULTS: A total of 11 studies were pooled in this meta-analysis. The low-dose strategy appeared to be as effective as standard-dose tPA (43.4% versus 45.4%; odds ratio [OR] = 0.93, 95% confidence interval [CI]: 0.78-1.10; P = .38) in primary efficacy outcome. The secondary efficacy outcome produced similar results (57.3% versus 57.0%; OR = 0.95, 95% CI: 0.86-1.05; P= .33). There was no evidence of statistical difference for sICH (4.2% versus 4.9%; OR = 1.02 [0.66-1.55]; P = .94) and mortality (9.0% versus 10.6%; OR = 0.99 [0.74-1.31]; P = .92) at 90 days between low- and standard-dose therapy. In a subgroup analysis by ethnicity, there was no significant difference between patients of Asian and non-Asian descent for any of the end points. CONCLUSIONS: This study showed that AIS patients receiving low-dose IV-tPA had comparably efficacy and safety to those receiving standard-dose IV-tPA. However, the effect is especially pronounced within the Asian population, which limits the generalizability of these results.

Prognosis of Intracerebral Hemorrhage with Newly Diagnosed Diabetes Mellitus According to Hemoglobin A1c Criteria.

OBJECTIVES: Hemoglobin A1c (HbA1c) has been recommended for diagnosing diabetes mellitus (DM). We aimed to assess the prevalence of newly diagnosed diabetes mellitus (NDDM) in patients with intracerebral hemorrhage (ICH) using HbA1c criteria and to investigate the long-term prognosis of patients with ICH with NDDM. MATERIALS AND METHODS: Data of patients with ICH without a DM history were derived from the Abnormal Glucose Regulation in Patients with Acute Stroke across China. NDDM was defined as a fasting plasma glucose (FPG) level of 7.0 mmol/L or higher, a 2-hour oral glucose tolerance test (OGTT) result of 11.1 mmol/L or higher, or an HbA1c level of 6.5% or higher. The prevalence of NDDM with different screening methods was assessed. The association between NDDM and 1-year prognosis (mortality, stroke recurrence, and poor functional outcome [modified Rankin scale score of 3-6]) was estimated. RESULTS: There were 357 patients with ICH included in the analysis, and 131 (36.7%) were diagnosed as NDDM using the new criteria. NDDM was present in 31 (8.7%), 98 (27.5%), and 68 (19.0%) patients with ICH, based on FPG, 2-hour OGTT, and HbA1c criteria, respectively. NDDM was independently associated with 1-year poor functional outcome (odds ratio 1.93; 95% confidence interval, 1.10-3.38, P = .02). Nevertheless, NDDM showed no significant association with 1-year death and stroke recurrence (P > .05 for both). CONCLUSIONS: More than one third of patients with ICH without a history of DM were diagnosed NDDM using the new criteria. NDDM by the new criteria was an independent risk factor of poor functional outcome, but not of death and stroke recurrence at 1 year after ICH onset.

Insulin Resistance and Prognosis of Nondiabetic Patients With Ischemic Stroke: The ACROSS-China Study (Abnormal Glucose Regulation in Patients With Acute Stroke Across China).

BACKGROUND AND PURPOSE: Insulin resistance was common in patients with stroke. This study investigated the association between insulin resistance and outcomes in nondiabetic patients with first-ever acute ischemic stroke. METHODS: Patients with ischemic stroke without history of diabetes mellitus in the ACROSS-China registry (Abnormal Glucose Regulation in Patients With Acute Stroke Across China) were included. Insulin resistance was defined as a homeostatis model assessment-insulin resistance (HOMA-IR) index in the top quartile (Q4). HOMA-IR was calculated as fasting insulin (µU/mL)×fasting glucose (mmol/L)/22.5. Multivariable logistic regression or Cox regression was performed to estimate the association between HOMA-IR and 1-year prognosis (mortality, stroke recurrence, poor functional outcome [modified Rankin scale score 3-6], and dependence [modified Rankin scale score 3-5]). RESULTS: Among the 1245 patients with acute ischemic stroke enrolled in this study, the median HOMA-IR was 1.9 (interquartile range, 1.1-3.1). Patients with insulin resistance were associated with a higher mortality risk than those without (adjusted hazard ratio, 1.68; 95% confidence interval, 1.12-2.53; P=0.01), stroke recurrence (adjusted hazard ratio, 1.57, 95% confidence interval, 1.12-2.19; P=0.008), and poor outcome (adjusted odds ratio, 1.42; 95% confidence interval, 1.03-1.95; P=0.03) but not dependence after adjustment for potential confounders. Higher HOMA-IR quartile categories were associated with a higher risk of 1-year death, stroke recurrence, and poor outcome (P for trend =0.005, 0.005, and 0.001, respectively). CONCLUSIONS: Insulin resistance was associated with an increased risk of death, stroke recurrence, and poor outcome but not dependence in nondiabetic patients with acute ischemic stroke.

Pancreatic ß-Cell Function and Prognosis of Nondiabetic Patients With Ischemic Stroke.

BACKGROUND AND PURPOSE: Pancreatic ß-cell dysfunction is an important factor in the development of type 2 diabetes mellitus. This study aimed to estimate the association between ß-cell dysfunction and prognosis of nondiabetic patients with ischemic stroke. METHODS: Patients with ischemic stroke without a history of diabetes mellitus in the ACROSS-China (Abnormal Glucose Regulation in Patients with Acute Stroke across China) registry were included. Disposition index was estimated as computer-based model of homeostatic model assessment 2-ß%/homeostatic model assessment 2-insulin resistance based on fasting C-peptide level. Outcomes included stroke recurrence, all-cause death, and dependency (modified Rankin Scale, 3-5) at 12 months after onset. RESULTS: Among 1171 patients, 37.2% were women with a mean age of 62.4 years. At 12 months, 167 (14.8%) patients had recurrent stroke, 110 (9.4%) died, and 184 (16.0%) had a dependency. The first quartile of the disposition index was associated with an increased risk of stroke recurrence (adjusted hazard ratio, 3.57; 95% confidence interval, 2.13-5.99) and dependency (adjusted hazard ratio, 2.30; 95% confidence interval, 1.21-4.38); both the first and second quartiles of the disposition index were associated with an increased risk of death (adjusted hazard ratio, 5.09; 95% confidence interval, 2.51-10.33; adjusted hazard ratio, 2.42; 95% confidence interval, 1.17-5.03) compared with the fourth quartile. Using a multivariable regression model with restricted cubic spline, we observed an L-shaped association between the disposition index and the risk of each end point. CONCLUSIONS: In this large-scale registry, ß-cell dysfunction was associated with an increased risk of 12-month poor prognosis in nondiabetic patients with ischemic stroke.

High On-Treatment Platelet Reactivity to Adenosine Diphosphate Predicts Ischemic Events of Minor Stroke and Transient Ischemic Attack.

BACKGROUND: This study aimed to evaluate the relationship between thromboelastography adenosine diphosphate maximum amplitude (TEG-ADPMA) and recurrent ischemic events in patients with minor ischemic stroke or high-risk transient ischemic attack (TIA). METHODS: A total of 265 patients received dual antiplatelet therapy were consecutively enrolled. High on-treatment platelet reactivity (HTPR) to ADP was assessed by TEG-ADPMA and detected the CYP2C19 genotype; recurrent ischemic events were followed up for 90 days after onset. The difference of recurrent ischemic events was analyzed with or without HTPR to ADP by the Kaplan-Meier, and further to determine the difference of recurrent ischemic events in each group according to TEG-ADPMA-based tertile distribution. RESULTS: A total of 23 (8.6%) patients had recurrent ischemic events. TEG-ADPMA greater than or equal to 48 mm had good predictive value. Whether these patients were divided into 2 groups or 3 groups, the HTPR to ADP group had higher risk of recurrent ischemic events than the normal on-treatment platelet reactivity to ADP group by the Kaplan-Meier (all, P < .05). The tertile distribution map showed that the results of recurrent ischemic events were statistically significant in the third tertile group compared with the other two groups (all, P < .03); also, the third tertile group had a higher rate of carriers of at least 1 CYP2C19 reduced-function allele than the other two groups (P < .05). CONCLUSIONS: In patients with minor ischemic stroke and high-risk TIA, the TEG-ADPMA could predict recurrent ischemic events and has auxiliary effect on clinical decision-making.

Prognosis of Ischemic Stroke With Newly Diagnosed Diabetes Mellitus According to Hemoglobin A1c Criteria in Chinese Population.

BACKGROUND AND PURPOSE: Hemoglobin A1c (HbA1c) was recommended to diagnose diabetes mellitus, but whether newly diagnosed diabetes mellitus (NDDM) according to the new criteria was associated with stroke prognosis was unclear. We aimed to investigate the prognosis of ischemic stroke with NDDM according to the new criteria. METHODS: Ischemic stroke without a diabetes mellitus history in the survey on Abnormal Glucose Regulation in Patients With Acute Stroke Across China were included in the analysis. NDDM was defined as fasting plasma glucose ≥7.0 mmol/L, 2-hour oral glucose tolerance test ≥11.1 mmol/L, or HbA1c ≥6.5%, and NDDM was divided into group 1, diagnosed by glucose criteria (fasting plasma glucose ≥7.0 mmol/L or 2-hour oral glucose tolerance test ≥11.1 mmol/L with/without HbA1c ≥6.5%), or group 2, diagnosed by single high HbA1c (fasting plasma glucose <7.0 mmol/L, 2-hour oral glucose tolerance test <11.1 mmol/L, and HbA1c ≥6.5%). The association between NDDM and 1-year prognosis (mortality, stroke recurrence, and poor functional outcome [modified Rankin scale score 3-6]) was estimated. RESULTS: Among 1251 ischemic stroke patients, 539 were NDDM and 141 of NDDM with single high HbA1c. NDDM was an independent risk factor for 1-year mortality (hazard ratio, 1.12; 95% confidence interval, 1.001-1.26), stroke recurrence (hazard ratio, 1.14; 95% confidence interval, 1.01-1.28), and poor functional outcome (odds ratio, 2.58; 95% confidence interval, 1.95-3.43) compared with non-diabetes mellitus. Nevertheless, NDDM with single high HbA1c was not significantly associated with 1-year prognosis for all end points (P>0.05 for all). CONCLUSIONS: NDDM by new criteria was associated with poor prognosis at 1 year after ischemic stroke; however, NDDM with single high HbA1c did not predict a poor prognosis.

Smoking-Thrombolysis Relationship Depends on Ischemic Stroke Subtype.

BACKGROUND AND PURPOSE: The relationship between smoking and the outcome in patients received thrombolysis is undetermined. The outcome could be influenced by different stroke subtypes. This study aimed to explore whether smoking had any impact on the outcome in patients with stroke of different subtypes who received intravenous thrombolysis. METHODS: All patients who received intravenous thrombolysis within 4.5 hours after symptom onset from the Thrombolysis Implementation and Monitor of Acute Ischemic Stroke in China (TIMS-China) database were eligible to be entered into this analysis. Smokers were considered if they smoked at least 1 cigarette/d for >6 months before stroke. Ischemic stroke subtype was classified by using the Trial of Org 10172 in Acute Stroke Treatment criteria. Outcome measurements included post-intravenous thrombolysis symptomatic intracranial hemorrhage within 7 days, mortality, and functional independence at 90 days. The relationship between smoking and thrombolysis was analyzed by using univariate and multivariate logistic regression models. RESULTS: Of 1118 patients enrolled, we identified 454 smokers and 664 nonsmokers. After stratifying for ischemic stroke subtypes, multivariate analysis revealed a significant relationship between smoking and functional independence in patients with noncardioembolism stroke subtypes (large artery atherosclerosis: odds ratio [OR], 1.452; 95% confidence interval [CI], 1.053-2.264; small artery occlusion: OR, 4.275; 95% CI, 1.098-16.649; other: OR, 3.120; 95% CI, 1.162-8.373). Furthermore, smoking was specially related to lower rates of symptomatic intracranial hemorrhage (OR, 0.316; 95% CI, 0.120-0.832) and mortality (OR, 0.272; 95% CI, 0.128-0.577) in patients with large artery atherosclerosis subtype. CONCLUSIONS: In patients treated with intravenous thrombolysis, smoking could be related to a better chance of functional independence if their subtype of stroke was noncardioembolic, and a lower risk of symptomatic intracranial hemorrhage and mortality in those with large artery atherosclerosis.

A Validation of the Essen Stroke Risk Score in Outpatients with Ischemic Stroke.

BACKGROUND: Little is known about the predictive accuracy of the Essen Stroke Risk Score (ESRS) for Chinese stroke outpatients. Our goal was to perform an external validation of the ESRS using a large multicenter cohort of outpatients with ischemic stroke (IS). METHODS: We estimated the 1-year cumulative event rates for both recurrent stroke and combined vascular events for patients in different ESRS categories using data from a prospective cohort of 3316 outpatients with IS admitted to 18 hospitals in China. In addition, we evaluated the predictive accuracy of the ESRS for both recurrent stroke and combined vascular events using C statistic. RESULTS: In the nonatrial fibrillation IS outpatients, the cumulative 1-year event rate was 2.47% (95% confidence interval [CI], 1.97%-3.06%) for recurrent stroke and 4.32% (95% CI, 3.65%-5.06%) for combined vascular events. The event rates were significantly higher in patients in higher ESRS categories. The ESRS had a predictive accuracy of .63 (.57-.69) for recurrent stroke and .63 (.58-.68) for combined vascular events. CONCLUSION: Among the Chinese outpatients with IS, the ESRS was able to stratify the risk of both recurrent stroke and combined vascular events equally well. A prediction model suitable for Chinese IS populations is needed.

Factors for short-term outcomes in patients with a minor stroke: results from China National Stroke Registry.

BACKGROUND: Stroke recurrence and disability in patients with a minor stroke is one of the most depressing medical situations. In this study, we aimed to identify which factors were associated with adverse outcomes of a minor stroke. METHODS: The China National Stroke Registry (CNSR) is a nationwide prospective registry for patients presented to hospitals with acute cerebrovascular events between September 2007 and August 2008. The 3-month follow-up was completed in 4669 patients with a minor stroke defined as the initial neurological severity lower than 4 in the National Institutes of Health Stroke Scale (NIHSS). Multivariate model was used to determine the association between risk factors and clinical outcomes. RESULTS: Of 4669 patients with a minor stroke during 3-month follow-up, 459 (9.8 %) patients experienced recurrent stroke, 679 (14.5 %) had stroke disability and 168 (3.6 %) died. Multivariate model identified hypertension, diabetes mellitus, atrial fibrillation, coronary heart disease and previous stroke as independent predictors for the recurrent stroke. Age, diabetes mellitus, atrial fibrillation, previous stroke and time from onset to admission < 24 h were independent predictors for stroke disability. The independent predictors for the all-caused death were age, atrial fibrillation, and coronary heart disease. CONCLUSIONS: The short-term risk of poor clinical outcome in Chinese patients with a minor stroke was substantial. Therefore, patients with a minor stroke should be given expeditious assessment and urgent aggressive intervention.

Impaired glucose regulation predicted 1-year mortality of Chinese patients with ischemic stroke: data from abnormal glucose regulation in patients with acute stroke across China.

BACKGROUND AND PURPOSE: It remains uncertain if impaired glucose regulation (IGR) as a predictor for stroke outcomes. This study aimed at observing the effect of IGR on the 1-year outcomes in Chinese patients with ischemic stroke. METHODS: Patients with acute ischemic stroke were recruited consecutively in multihospitals across China. Oral glucose tolerance test was performed to identify IGR. Cox proportion hazard model was performed to investigate the effect of IGR on 1-year mortality or stroke recurrence in patients with ischemic stroke. RESULTS: The study recruited 2639 patients with ischemic stroke. IGR was shown as an independent risk factor for the mortality of patients with ischemic stroke (hazard ratio [95% confidence interval], 3.088 [1.386-6.884]; P=0.006). However, IGR showed no significant effects on the dependency or stroke recurrence of patients (P=0.540 and 0.618, respectively). CONCLUSIONS: IGR was an independent predictor for the mortality of patients with ischemic stroke. IGR should be highlighted and intervened actively in the patients with ischemic stroke.

Remnant cholesterol is associated with unstable carotid plaque in a neurologically healthy population.

BACKGROUND: Remnant cholesterol (RC) is considered to be one of the most significant and important risk factors for atherosclerotic cardiovascular disease (ASCVD). Nonetheless, the association between RC and unstable carotid plaque remains unclear. Our primary objective is to ascertain whether RC exhibits an independent and significant association with unstable carotid plaque in a neurologically healthy population. METHODS: In the cross-sectional study, we enrolled neurologically healthy participants who visited our centre for health checkups between 2021 and 2022. All eligible participants underwent a standardised questionnaire, physical examinations and laboratory testing. The carotid plaque was evaluated with a standard carotid ultrasound and an advanced ultrasound imaging technique called superb microvascular imaging. The correlation between lipids and unstable carotid plaque was primarily assessed utilising univariate and multivariate logistic regression. RESULTS: The study totally enrolled 1100 participants who had an average age of 57.00 years (IQR: 49.00-63.00), with 67.55% being men. Among the participants, 321 (29.18%) had unstable carotid plaque. In the multivariate logistic regression analysis, higher RC had an independent association with an elevated incidence of unstable carotid plaque compared with the lowest concentrations of RC (OR=1.673, 95% CI 1.113 to 2.515, p=0.0134), but not other lipids. In addition, apolipoprotein A1 was negatively related to unstable carotid plaque (OR=0.549, 95% CI 0.364 to 0.830, p=0.0045). CONCLUSIONS: Elevated concentrations of RC are independently and excellently correlated with unstable carotid plaque within a neurologically healthy population.

Exploring the link between brain topological resilience and cognitive performance in the context of aging and vascular risk factors: A cross-ethnicity population-based study.

Brain aging is typically associated with a significant decline in cognitive performance. Vascular risk factors (VRF) and subsequent atherosclerosis (AS) play a major role in this process. Brain resilience reflects the brain's ability to withstand external perturbations, but the relationship of brain resilience with cognition during the aging process remains unclear. Here, we investigated how brain topological resilience (BTR) is associated with cognitive performance in the face of aging and vascular risk factors. We used data from two cross-ethnicity community cohorts, PolyvasculaR Evaluation for Cognitive Impairment and Vascular Events (PRECISE, n = 2220) and Sydney Memory and Ageing Study (MAS, n = 246). We conducted an attack simulation on brain structural networks based on k-shell decomposition and node degree centrality. BTR was defined based on changes in the size of the largest subgroup of the network during the simulation process. Subsequently, we explored the negative correlations of BTR with age, VRF, and AS, and its positive correlation with cognitive performance. Furthermore, using structural equation modeling (SEM), we constructed path models to analyze the directional dependencies among these variables, demonstrating that aging, AS, and VRF affect cognition by disrupting BTR. Our results also indicated the specificity of this metric, independent of brain volume. Overall, these findings underscore the supportive role of BTR on cognition during aging and highlight its potential application as an imaging marker for objective assessment of brain cognitive performance.

Outcomes associated to the time to treatment with intravenous tenecteplase for acute ischaemic stroke: subgroup analysis of the TRACE-2 randomised controlled clinical trial.

BACKGROUND: The benefit of intravenous alteplase in acute ischaemic stroke (AIS) is time-dependent. Tenecteplase is non-inferior to alteplase among patients with AIS. We aimed to delineate the association of the stroke onset to treatment time (OTT) with tenecteplase compared with alteplase on therapeutic benefit and clinical risks. METHODS: This is a post hoc analysis of the Tenecteplase Reperfusion therapy in Acute ischaemic Cerebrovascular Events-2 an open-label, randomised, controlled, non-inferior trial. A total of 1430 AIS within 4.5 hours onset at 53 sites in China from 12 June 2021 to 29 May 2022 were randomly assigned (1:1) to receive either tenecteplase 0.25 mg/kg or alteplase 0.9 mg/kg. The primary efficacy outcome was the proportion of participants with a modified Rankin Scale score of 0-1 at 90 days. A post hoc subgroup analysis was conducted with the OTT divided into three intervals (0-90 min, 91-180 min and 181-270 min). The primary safety outcome was symptomatic intracranial haemorrhage within 36 hours post-thrombolytic treatment. RESULTS: Treatment was initiated within 270 min of stroke onset in 1412 patients who were randomly allocated to either tenecteplase (n=707) or alteplase (n=705). The OR of primary efficacy outcome was similar as OTT increased (p=0.84). Adjusted odds of an excellent functional outcome were 0.99 (95% CI 0.37 to 2.67) for 0-90 min, 1.23 (95% CI 0.88 to 1.71) for 91-180 min and 1.21 (95% CI 0.88 to 1.65) for 181-270 min. All were in favour of the tenecteplase group. Meta-analysis of 2949 patients yielded a pooled risk difference of 5.54 (95% CI -0.18 to 11.26; p=0.82) in favour of tenecteplase for more than 180 min and 1.77 (95% CI -2.66 to 6.20; p=0.58) for 0-180 min. CONCLUSIONS: In AIS patients who were treated with either tenecteplase or alteplase within 4.5 hours onset, there was no difference observed in the efficacy and safety between the two groups at the three different OTT time intervals.

Colchicine in patients with acute ischaemic stroke or transient ischaemic attack (CHANCE-3): multicentre, double blind, randomised, placebo controlled trial.

OBJECTIVES: To assess the efficacy and safety of colchicine versus placebo on reducing the risk of subsequent stroke after high risk non-cardioembolic ischaemic stroke or transient ischaemic attack within the first three months of symptom onset (CHANCE-3). DESIGN: Multicentre, double blind, randomised, placebo controlled trial. SETTING: 244 hospitals in China between 11 August 2022 and 13 April 2023. PARTICIPANTS: 8343 patients aged 40 years of age or older with a minor-to-moderate ischaemic stroke or transient ischaemic attack and a high sensitivity C-reactive protein ≥2 mg/L were enrolled. INTERVENTIONS: Patients were randomly assigned 1:1 within 24 h of symptom onset to receive colchicine (0.5 mg twice daily on days 1-3, followed by 0.5 mg daily thereafter) or placebo for 90 days. MAIN OUTCOME MEASURES: The primary efficacy outcome was any new stroke within 90 days after randomisation. The primary safety outcome was any serious adverse event during the treatment period. All efficacy and safety analyses were by intention to treat. RESULTS: 4176 patients were assigned to the colchicine group and 4167 were assigned to the placebo group. Stroke occurred within 90 days in 264 patients (6.3%) in the colchicine group and 270 patients (6.5%) in the placebo group (hazard ratio 0.98 (95% confidence interval 0.83 to 1.16); P=0.79). Any serious adverse event was observed in 91 (2.2%) patients in the colchicine group and 88 (2.1%) in the placebo group (P=0.83). CONCLUSIONS: The study did not provide evidence that low-dose colchicine could reduce the risk of subsequent stroke within 90 days as compared with placebo among patients with acute non-cardioembolic minor-to-moderate ischaemic stroke or transient ischaemic attack and a high sensitivity C-reactive protein ≥2 mg/L. TRIAL REGISTRATION: ClinicalTrials.gov, NCT05439356.

External validation of the ASTRAL score to predict 3- and 12-month functional outcome in the China National Stroke Registry.

BACKGROUND AND PURPOSE: The ASTRAL score was recently introduced as a prognostic tool for acute ischemic stroke. It predicts 3-month outcome reliably in both the derivation and the validation European cohorts. We aimed to validate the ASTRAL score in a Chinese stroke population and moreover to explore its prognostic value to predict 12-month outcome. METHODS: We applied the ASTRAL score to acute ischemic stroke patients admitted to 132 study sites of the China National Stroke Registry. Unfavorable outcome was assessed as a modified Rankin Scale score >2 at 3 and 12 months. Areas under the curve were calculated to quantify the prognostic value. Calibration was assessed by comparing predicted and observed probability of unfavorable outcome using Pearson correlation coefficient. RESULTS: Among 3755 patients, 1473 (39.7%) had 3-month unfavorable outcome. Areas under the curve for 3 and 12 months were 0.82 and 0.81, respectively. There was high correlation between observed and expected probability of unfavorable 3- and 12-month outcome (Pearson correlation coefficient: 0.964 and 0.963, respectively). CONCLUSIONS: ASTRAL score is a reliable tool to predict unfavorable outcome at 3 and 12 months after acute ischemic stroke in the Chinese population. It is a useful tool that can be readily applied in clinical practice to risk-stratify acute stroke patients.

FLAIR vascular hyperintensity combined with asymmetrical prominent veins in acute anterior circulation ischemic stroke: prediction of collateral circulation and clinical outcome.

BACKGROUND: To investigate the value of fluid-attenuated inversion recovery vascular hyperintensity (FVH) within asymmetrical prominent veins sign (APVS) on susceptibility-weighted imaging predicting collateral circulation and prognosis in patients with acute anterior circulation ischemic stroke. METHOD: Patients with severe stenosis or occlusion of ICA or MCA M1, who underwent MRI within 72 h from stroke onset were reviewed. The Alberta Stroke Program Early CT Score was used to evaluate the volume of infarction on DWI, the degree of FVH and APVS. Spearman correlation analysis was used to evaluate the correlation between FVH and APVS. All patients were divided into the good prognosis group and the poor prognosis group according to the score of the modified ranking scale (mRS) 90 days after the stroke. Logistic regression analysis was used to explore the relationship between FVH and APVS and functional prognosis, while receiver operating characteristic (ROC) curves were plotted to assess the value of FVH and APVS in predicting prognosis. RESULTS: Spearman correlation analysis revealed moderate positive correlations between FVH and APVS (r = 0.586, P < 0.001). The poor prognosis group had a higher rate of a history of atrial fibrillation, a larger cerebral infarction volume, a higher NIHSS score at admission, and a higher FVH and APVS score compared with the good prognosis group (all P < 0.05). A further logistic regression indicated that the NIHSS score, cerebral infarction volume, FVH and APVS were independent risk factors for a poor functional prognosis. In terms of FVH, APVS, alone and their combination for the diagnosis of poor prognosis, the sensitivity, specificity, area under the ROC curve (AUC), and 95% confidence interval (CI) were 86.8%, 83.3%, 0.899 (95% CI 0.830-0.968); 60.5%, 93.7%, 0.818 (95% CI 0.723-0.912); 86.8%, 89.6%, 0.921 (95% CI 0.860-0.981), respectively. CONCLUSION: The presence of FVH and APVS can provide a comprehensive assessment of collateral circulation from the perspective of veins and arteries, and the correlation between the two is positively correlated. Both of them were independent risk factors for poor prognosis, their combination is complementary and can improve the predictive value.

Increased Resting-State Functional Connectivity as a Compensatory Mechanism for Reduced Brain Volume in Prediabetes and Type 2 Diabetes.

OBJECTIVE: To investigate the contribution of alterations in brain structure and function to cognitive function and their interactions in individuals with diabetes and patients with type 2 diabetes mellitus (T2DM). RESEARCH DESIGN AND METHODS: This population-based study included 2,483 participants who underwent structural MRI (n = 569 with normal glucose metabolism [NGM], n = 1,353 with prediabetes, and n = 561 with T2DM) and cognitive testing. Of these, 2145 participants also underwent functional MRI (n = 496 NGM, n = 1,170 prediabetes, and n = 479 T2DM). Multivariate linear regression models were used to assess the association of brain volume and functional connectivity with cognition, as well as the association of brain volume and functional connectivity. RESULTS: Compared with NGM participants, those with T2DM had lower brain volume in a wide range of brain regions and stronger functional connectivity between the bilateral thalamus and brain functional network (visual network and default mode network), and those with prediabetes had lower brain volume in specific local regions (subcortical gray matter volume and subcortical subregions [bilateral thalamus, bilateral nucleus accumbens, and right putamen]) and stronger functional connectivity between the right thalamus and visual network. Cognition was associated with greater right thalamus volume and lower functional connectivity between the right thalamus and visual network. Functional connectivity between the right thalamus and visual network was associated with lower right thalamus volume. CONCLUSIONS: Cognition was associated with greater brain volume and lower functional connectivity in T2DM. Increased functional connectivity may indicate a compensatory mechanism for reduced brain volume that begins in the prediabetic phase.