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.

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.

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).

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.

Correlation between Mild Cognitive Impairment and Sarcopenia: The Prospective Role of Lipids and Basal Metabolic Rate in the Link.

There is evidence of correlation between mild cognitive impairment (MCI) and sarcopenia (SA). However, the influencing factors and the mechanism, such as age-related lipid redistribution, remain unknown. This study aimed to clarify the role of dietary fats and erythrocyte lipids profile combined with basal metabolic rate (BMR) in the link between MCI and SA. A total of 1050 participants aged 65 to 85 were divided into control, MCI, SA and MCI and SA groups. Bioelectrical impedance analysis was used to evaluate appendicular lean mass and BMR. Cognition and dietary nutrition were detected by neuropsychological tests and food frequency questionnaires. UHPLC-QExactive-MS/MS and UHPLC-Qtrap-MS/MS were used to conduct the lipidomics analysis. Lower dietary intake of different phospholipids, unsaturated fatty acids and kinds of choline were significantly associated with MCI and SA. Least absolute shrinkage and selection operator, multivariate logistic regression, receiver operating characteristic curve and validation tests provided evidence that specific phospholipids, unsaturated fatty acids and BMR might be the critical factors in the processing of MCI and SA, as well as in their link. The lipidomic analysis observed a clear discrimination of the lipid profiles in the individuals who are in MCI, SA, or MCI and SA, compared with the control. Lower expressions in certain phospholipid species, such as sphingomyelin and phosphatidylethanolamines, decreased phosphatidylcholine with more unsaturated double bonds, lower level of lipids with C20:5 and C20:4, higher level of lipids with C18:2 and lipids with a remodeled length of acyl chain, might be closely related to the link between MCI and SA. Inadequate dietary intake and lower concentrations of the erythrocyte lipid profile of phospholipids and unsaturated fatty acids with a lower level of BMR might be the key points that lead to progress in MCI and SA, as well as in their link. They could be used as the prospective biomarkers for the higher risk of cognitive decline and/or SA in elderly population.

Prognostic value of susceptibility-weighted imaging of prominent veins in acute ischemic stroke: A systematic review and meta-analysis.

Background: The prominent veins sign (PVS) on susceptibility-weighted imaging (SWI) has been suggested to be related to the prognosis of patients with acute ischemic stroke (AIS). This meta-analysis aims to clarify the association between PVS and the prognosis of patients with AIS. Methods: This meta-analysis was registered in PROSPERO (no. CRD42022343795). We performed systematic research in PubMed, Web of Science, EMBASE, and Cochrane Library databases for studies investigating the prognostic value of PVS. Based on the enrolled studies, patients were divided into two groups as follows: those with PVS cohort and those without PVS cohort. Outcomes were unfavorable functional outcome, early neurological deterioration (END), and hemorrhagic transformation (HT). The random-effects models were used for the meta-analytical pooled. Heterogeneity was estimated using Cochran's Q-test and I 2 value. Subgroup and sensitivity analyses were also performed to explore the potential sources of heterogeneity. Publication bias was assessed with funnel plots and using Begger's and Egger's tests. Results: A total of 19 studies with 1,867 patients were included. PVS was correlated with an unfavorable functional outcome in patients with AIS (risk ratio [RR] 1.61, 95% CI 1.28-2.02), especially in those receiving recanalization therapy (RR 2.00, 95% CI 1.52-2.63), but not in those treated conservatively (RR 1.33, 95% CI 0.87-2.04). Moreover, PVS was related to END (RR 2.77, 95% CI 2.21-3.46), while without an increased risk of HT (RR 0.97, 95% CI 0.64-1.47). Conclusion: PVS was associated with an unfavorable prognosis of patients with AIS and increased the risk of END, while not correlated with an increased risk of HT. PVS might be useful for predicting functional outcomes of patients with AIS as a novel imaging maker. Systematic review registration: https://www.crd.york.ac.uk/PROSPERO/, identifier: CRD42022343795.

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.

Safety and efficacy of tenecteplase versus alteplase in patients with acute ischaemic stroke (TRACE): a multicentre, randomised, open label, blinded-endpoint (PROBE) controlled phase II study.

BACKGROUND: Tenecteplase (TNK) possesses several pharmacological characteristics superior to conventional alteplase (rt-PA), with well-established safety and efficacy profile in Caucasians. There exists controversy over the optimal dose of intravenous rt-PA for East Asians with acute ischaemic stroke (AIS). Current study aimed to determine the safety dose range of recombinant human TNK tissue-type plasminogen activator (rhTNK-tPA) for patients with AIS in China. METHODS: This multicentre, prospective, randomised, open-label, blinded end-point, phase II study compared three tiers of 0.1, 0.25, 0.32 mg/kg rhTNK-tPA (to a maximum of 40 mg) with standard 0.9 mg/kg rt-PA (to a maximum of 90 mg) in patients who were eligible for intravenous thrombolysis. The safety outcome were symptomatic intracranial haemorrhage (sICH) within 36 hours. RESULTS: Between May 2018 and February 2020, 240 patients were randomly assigned to four group, 4 of whom did not receive study treatment. The intention-to-treat analysis included 236 patients. There was no difference in the improvement on National Institutes of Health Stroke Scale at day 14 in the 3 tiers and control group (63.3%, 77.2%, 66.7% vs 62.7%). The number of sICH was 3 of 60 (5.0%) in the 0.1 mg/kg group, none in the 0.25 mg/kg group, 2 of 60 (3.3%) in the 0.32 mg/kg group and 1 (1.7%) of 59 in the rt-PA group. There were no significant between-group differences in severe adverse events. CONCLUSIONS: Similar to the Caucasians, rhTNK-tPA was well tolerated in Chinese patients with AIS at all doses administered within 3 hours of symptom onset. The dose-efficacy profile of rhTNK-tPA needs to be established with future investigations. TRIAL REGISTRATION NUMBER: NCT04676659.

Analytical validation of GMEX rapid point-of-care CYP2C19 genotyping system for the CHANCE-2 trial.

BACKGROUND AND PURPOSE: Rapid genotyping is useful for guiding early antiplatelet therapy in patients with high-risk nondisabling ischaemic cerebrovascular events (HR-NICE). Conventional genetic testing methods used in CYP2C19 genotype-guided antiplatelet therapy for patients with HR-NICE did not satisfy the needs of the Clopidogrel in High-Risk Patients with Acute Nondisabling Cerebrovascular Events (CHANCE)-2 trial. Therefore, we developed the rapid-genotyping GMEX (point-of-care) system to meet the needs of the CHANCE-2 trial. METHODS: Healthy individuals and patients with history of cardiovascular diseases (n=408) were enrolled from six centres of the CHANCE-2 trial. We compared the laboratory-based genomic test results with Sanger sequencing test results for accuracy verification. Next, we demonstrated the accuracy, timeliness and clinical operability of the GMEX system compared with laboratory-based technology (YZY Kit) to verify whether the GMEX system satisfies the needs of the CHANCE-2 trial. RESULTS: Genotypes reported by the GMEX system showed 100% agreement with those determined by using the YZY Kit and Sanger sequencing for all three CYP2C19 alleles (*2, *3 and *17) tested. The average result's turnaround times for the GMEX and YZY Kit methods were 85.0 (IQR: 85.0-86.0) and 1630.0 (IQR: 354.0-7594.0) min (p<0.001), respectively. CONCLUSIONS: Our data suggest that the GMEX system is a reliable and feasible point-of-care system for rapid CYP2C19 genotyping for the CHANCE-2 trial or related clinical and research applications.

Association of Trimethylamine N-Oxide and Its Precursor With Cerebral Small Vessel Imaging Markers.

Background: High plasma levels of trimethylamine N-oxide (TMAO) and its precursor choline have been linked to stroke; however, their association with cerebral small vessel disease remains unclear. Here we evaluated the association of plasma levels of TMAO and choline with imaging markers of cerebral small vessel disease, including white matter hyperintensities, lacunes, and cerebral microbleeds. Methods: We performed a baseline cross-sectional analysis of a multicenter hospital-based cohort study from 2015 to 2018. The data were collected from 30 hospitals in China and included 1,098 patients with ischemic stroke/transient ischemic attack aged ≥18 years. White matter hyperintensities, lacunes, and cerebral microbleeds were evaluated with the patients' demographic, clinical, and laboratory information removed. White matter hyperintensities were rated using the Fazekas visual grading scale, while the degree of severity of the lacunes and cerebral microbleeds was defined by the number of lesions. Results: Increased TMAO levels were associated with severe white matter hyperintensities [adjusted odds ratio (aOR) for the highest vs. lowest quartile, 1.5; 95% confidence interval (CI), 1.0-2.1, p = 0.04]. High TMAO levels were more strongly associated with severe periventricular white matter hyperintensities (aOR for the highest vs. lowest quartile, 1.6; 95% CI, 1.1-2.3, p = 0.009) than deep white matter hyperintensities (aOR for the highest vs. lowest quartile, 1.3; 95% CI, 0.9-1.9, p = 0.16). No significant association was observed between TMAO and lacunes or cerebral microbleeds. Choline showed trends similar to that of TMAO in the association with cerebral small vessel disease. Conclusions: In patients with ischemic stroke or transient ischemic attack, TMAO and choline appear to be associated with white matter hyperintensities, but not with lacunes or cerebral microbleeds; TMAO and choline were associated with increased risk of a greater periventricular, rather than deep, white matter hyperintensities burden.

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.

Association of Brachial Ankle Pulse Wave Velocity With New Onset Stroke in Hypertensive Patients Aged Less Than 65 With Normal Fasting Glucose Among Chinese Community-Based Population.

Background: Previous studies have shown an association of stroke and brachial ankle pulse wave velocity (baPWV). However, due to limitations on total population size and small numbers of stroke cases, lack of power has prevented further detection among subgroups such as age and laboratory testing. Methods: A total of 19217 participants including 660 incident stroke patients were pooled in the present study. Participants were divided to 2 groups, aged less than 65 years [56.0 (50.0, 61.0)] and aged 65 years or more [70.0 (67.0, 74.0)]. Results: After adjustment for demographic, anthropometric, and laboratory parameters, the incident stroke was positively associated to baPWV in the group aged less than 65 years (OR, 1.16; 95% CI, 1.05-1.28), but not in the older group aged 65 or more. When baPWV was assigned as quartiles, a significant, increased risk of new-onset stroke was found in quartiles 3-4 compared with quartile 1. In addition, the predictive value of baPWV for incident stroke was modified by fasting glucose in participants aged less than 65 years (P-interaction = 0.010). An increase in baPWV was strongly, positively associated to new-onset stroke in the subgroup of normal fasting glucose (< 5.6 mmol/L) (OR, 1.34; 95% CI, 1.15 - 1.57), but no effect was seen in the impaired fasting glucose (5.6-7.0 mmol/L) or diabetic fasting glucose (> 7.0 mmol/L) subgroups. Conclusions: Increased baPWV was significantly associated with new-onset stroke in a hypertensive population aged less than 65 years. Particularly, it is of great importance to monitor baPWV for predicting incident stroke in "relatively healthy" hypertensive patients, i.e. aged less than 65 years with normal fasting glucose.

Implementation of regional Acute Stroke Care Map increases thrombolysis rates for acute ischaemic stroke in Chinese urban area in only 3 months.

BACKGROUND: The rate of intravenous thrombolysis for acute ischaemic stroke remains low in China. We investigated whether the implementation of a citywide Acute Stroke Care Map (ASCaM) is associated with an improvement of acute stroke care quality in a Chinese urban area. METHODS: The ASCaM comprises 10 improvement strategies and has been implemented through a network consisting of 20 tertiary hospitals. We identified 7827 patients with ischaemic stroke admitted from April to October 2017, and 506 patients underwent thrombolysis were finally included for analysis. RESULTS: Compared with 'pre-ASCaM period', we observed an increased rate of administration of tissue plasminogen activator within 4.5 hours (65.4% vs 54.5%; adjusted OR, 1.724; 95% CI 1.21 to 2.45; p=0.003) during 'ASCaM period'. In multivariate analysis models, 'ASCaM period' was associated with a significant reduction in onset-to-door time (114.1±55.7 vs 135.7±58.4 min, p=0.0002) and onset-to-needle time (ONT) (169.2±58.1 vs 195.6±59.3 min, p<0.0001). Yet no change was found in door-to-needle time. Clinical outcomes such as symptomatic intracranial haemorrhage, favourable functional outcome (modified Rankin Scale ≤2) and in-hospital mortality remained unchanged. CONCLUSION: The implementation of ASCaM was significantly associated with increased rates of intravenous thrombolysis and shorter ONT. The ASCaM may, in proof-of-principle, serve as a model to reduce treatment delay and increase thrombolysis rates in Chinese urban areas and possibly other highly populated Asian regions.

Measuring effects on intima-media thickness: an evaluation of rosuvastatin in Chinese subjects with subclinical atherosclerosis-design, rationale, and methodology of the METEOR-China study.

BACKGROUND: The beneficial effect of statins on atherosclerosis and cardiovascular outcomes has been well established. The Measuring Effects on intima media Thickness: an Evaluation Of Rosuvastatin (METEOR) global study demonstrated that a 2-year orally administered treatment with rosuvastatin 40 mg daily significantly slowed the progression of carotid intima-media thickness (CIMT) compared to placebo. The current METEOR-China study is designed to evaluate the effect of rosuvastatin 20 mg daily versus placebo on the progression of atherosclerosis measured by CIMT in asymptomatic Chinese subjects. METHODS: This is a phase 3, randomised, double-blind, placebo-controlled, multicentre parallel-group study. Asymptomatic Chinese subjects with a 10-year ischaemic cardiovascular disease (ICVD) risk < 10% will be recruited at 25 study sites. They will be treated with rosuvastatin 20 mg or placebo for 104 weeks. The primary endpoint is the annualised rate of change in CIMT measured by B-mode ultrasonography. Secondary endpoints include the annualised rate of change in CIMT at three different sections of the carotid artery and changes in the serum lipid profile. Safety parameters will also be assessed. CONCLUSION: The study will evaluate whether rosuvastatin 20 mg slows the progression of CIMT in asymptomatic Chinese subjects at low risk of ICVD. TRIAL REGISTRATION: ClinicalTrials.gov NCT02546323 . Registered on September 10, 2015.

Chinese Stroke Association guidelines for clinical management of cerebrovascular disorders: executive summary and 2019 update of the management of high-risk population.

AIM: Cerebrovascular disease is the leading cause of death and disability in China, causing a huge burden among patients and their families. Hence, stroke prevention is critical, especially in the high-risk population. Here, we present the evidence-based guideline suitable for the Chinese population. METHODS: Literature search of PubMed and Cochrane library (from January 1964 to June 2019) was done. After thorough discussion among the writing group members, recommendations were listed and summarised. This guideline was reviewed and discussed by the fellow writing committees of the Chinese Stroke Association's Stroke. RESULTS: This evidence-based guideline was written in three parts: controlling the risk factors of stroke, utilisation of antiplatelet agents and assessing the risks of first-ever stroke. All recommendations were listed along with the recommending classes and levels of evidence. CONCLUSIONS: This guideline provides recommendations for primary prevention of cerebrovascular disease among high-risk population in China. Controlling related risk factors, appropriately using antiplatelet agents, assessing the risk of developing first-ever stroke should help reduce the rate of cerebrovascular disease in China.

Combined impact of body mass index and glycemic control on the efficacy of clopidogrel-aspirin therapy in patients with minor stroke or transient ischemic attack.

BACKGROUND: A single index of body mass index (BMI) may not fully address its impact on anti-platelet therapy. We aimed to elucidate the combined impact of BMI and dysglycemia expressed by glycated albumin (GA) on efficacy of clopidogrel-aspirin therapy among minor stroke (MS) or transient ischemic attack (TIA) patients. RESULTS: Patients with overweight/obesity and low GA levels still benefited from clopidogrel-aspirin therapy for stroke recurrence (Hazard ratio [HR]: 0.48, 95 % confidence interval [CI]: 0.28-0.82), so did those with high GA levels but low/normal weight (HR: 0.67, 95 % CI: 0.45-0.99). However, patients with both overweight/obesity and high GA levels did not benefit from clopidogrel-aspirin therapy (HR: 0.89, 95 % CI: 0.59-1.33). CONCLUSIONS: Compared with aspirin alone, efficacy of clopidogrel-aspirin therapy for stroke still exists in overweight/obesity patients with normal glycemic control. METHODS: In Clopidogrel in High-Risk Patients with Acute Nondisabling Cerebrovascular Events trial, 3044 patients with available baseline GA were recruited. Low/normal weight and overweight/obesity were defined as BMI < 25 kg/m2 and ≥ 25 kg/m2, respectively. Elevated and low GA levels were defined as GA levels > 15.5 % and ≤ 15.5 %, respectively. The primary outcome was stroke recurrence during the 90-day follow-up.

Chinese Stroke Association guidelines for clinical management of cerebrovascular disorders: executive summary and 2019 update of clinical management of ischaemic cerebrovascular diseases.

AIM: Stroke is the leading cause of disability and death in China. Ischaemic stroke accounts for about 60%-80% of all strokes. It is of considerable significance to carry out multidimensional management of ischaemic cerebrovascular diseases. This evidence-based guideline aims to provide the latest detailed and comprehensive recommendations on the diagnosis, treatment and secondary prevention of ischaemic cerebrovascular diseases. METHODS: We had performed comprehensive searches of MEDLINE (via PubMed) (before 30 June 2019), and integrated the relevant information into charts and distributed to the writing group. Writing group members discussed and determined the recommendations through teleconference. We used the level of evidence grading algorithm of Chinese Stroke Association to grade each recommendation. The draft was reviewed by the Guideline Writing Committee of Chinese Stroke Association Stroke and finalised. This guideline is fully updated every 3 years. RESULTS: This evidence-based guideline is based on the treatment, care and prevention of ischaemic cerebrovascular diseases, which emphasises on pathogenesis evaluation, intravenous thrombolysis, endovascular therapy, antiplatelet therapy, prevention and treatment of complications, and risk factor management. CONCLUSIONS: This updated guideline presents a framework for the management of ischaemic cerebrovascular diseases. Timely first-aid measures, professional care in the acute stage, and proactive secondary prevention will be helpful to patients.

Thrombolysis with alteplase 3-4.5 hours after acute ischaemic stroke: the first multicentre, phase III trial in China.

BACKGROUND AND PURPOSE: Data on the efficacy and safety of alteplase for acute ischaemic stroke (AIS) administered 3-4.5 hours after the onset of stroke symptoms in Chinese patients is limited. We sought to determine whether AIS patients would benefit from thrombolysis with alteplase between 3 and 4.5 hours after the onset of stroke symptoms in a prospective, multicentre, single-arm trial in China. MATERIALS AND METHODS: Eligible AIS patients were given 0.9 mg/kg alteplase intravenously. The primary efficacy endpoint was a favourable outcome at 3 months, defined as a score of 0 or 1 on the modified Rankin Scale. Thresholds for the primary efficacy endpoint were determined to be 40% based on the literature review. The primary safety endpoint was symptomatic intracranial haemorrhage (sICH) according to the European Cooperative Acute Stroke Study III (ECASS III) trial definition. Post hoc analysis between this study and the ECASS III trial were compared using the propensity score matching (PSM) method. RESULTS: A total of 120 eligible AIS patients from 11 sites in China received thrombolysis therapy in this study. The median time from onset of symptoms to needle was 3 hours 54 min. The percentage of patients with a favourable outcome was 63.3% (95% CI 54.4 to 71.4), significantly higher than the predefined threshold (p<0.0001). Three patients (2.5%, 95% CI 0.5 to 7.1) had sICH, including two fatal sICH. Six patients died within 3 months after treatment. The post hoc PSM analysis showed a numerically higher rate of the primary efficacy endpoint in this study (63.3%) than the matched placebo arm (56.7%) in the ECASS III trial. CONCLUSIONS: Intravenous alteplase with a standard dose administered between 3 and 4.5 hours after onset of symptoms is effective and safe for Chinese AIS patients. TRIAL REGISTRATION NUMBER: NCT02930837.

Estimated glomerular filtration rate, anemia and outcomes in patients with ischemic stroke.

BACKGROUND: Anemia is highly prevalent in patients with low estimated glomerular filtration rate (eGFR). However, the combined effect of anemia and low eGFR on the prognosis of stroke has not been well studied. METHODS: Data of patients with acute ischemic stroke in the prospective cohort study of China National Stroke Registry was reviewed. According to the levels of eGFR and hemoglobin, patients were categorized into four groups: low eGFR (<60 mL/min per 1.73 m2) or normal eGFR (≥60 mL/min per 1.73 m2) with or without anemia. Multivariate logistic regression methods were used to analyze the association between eGFR with or without anemia and outcomes after stroke [the poor functional outcome (modified Rankin Scale, mRS 3-6), mortality and stroke recurrence] at 3 months and 1 year. RESULTS: This study included 8,303 stroke patients. After adjusting for the confounding factors, low eGFR with normal hemoglobin increased the risk of mortality at 1 year of follow-up [odds ratio (OR) =1.50; 95% confidence interval (95% CI), 1.14-1.97]. Anemia with normal eGFR was not associated with any poor outcome at 1-year of follow-up. In patients with both low eGFR and anemia, there was an increased risk of 1-year poor functional outcome (OR 1.73; 95% CI, 1.30-2.29), mortality (OR 2.64; 95% CI, 1.94-3.59) and stroke recurrence (OR 1.42; 95% CI, 1.06-1.91). Combined and interactive effects of the pattern of low eGFR and anemia on the poor functional outcome (P for interaction =0.02) and all-cause mortality (P for interaction =0.046) were observed. CONCLUSIONS: Ischemic stroke patients with concurrent low eGFR and anemia increased risks of poor functional outcome, mortality and stroke recurrence after 1-year follow-up.