Hao Li

China National Clinical Research Center for Neurological Diseases

BACKGROUND Although many studies have examined the influence of individual preexisting heart conditions on stroke outcomes, the combined effects of these conditions remain understudied. METHODS The data supporting this study's findings are available from the corresponding author upon reasonable request. Data on patients with acute ischemic stroke...

Ischemic stroke (IS) is a leading cause of adult disability that can severely compromise the quality of life for patients. Accurately predicting the IS functional outcome is crucial for precise risk stratification and effective therapeutic interventions. We developed a predictive model integrating genetic, environmental, and clinical factors using...

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 Cerebrovascul...

Although essential for cardiovascular therapy, the pleiotropic effects of statins on ischemic stroke lack clinical evidence. This study examined the effects of statins beyond low-density lipoprotein cholesterol (LDL-C) levels on mortality and stroke severity. A total of 825,874 patients with ischemic stroke were included in this study, of whom 125,...

Importance Tenecteplase is a bioengineered variant of alteplase with greater fibrin specificity and a longer half-life, allowing single-bolus administration. Evidence on the treatment effect of tenecteplase 0.25 mg/kg in Chinese patients with acute ischemic stroke (AIS) is limited. Objective To establish the noninferiority of tenecteplase to altep...

Peroxisome proliferator-activated receptor-γ ( PPARγ) plays a protective role against brain injury after stroke in mice. However, the relationship between PPARγ gene polymorphisms and the functional outcome of acute ischemic stroke (AIS) remains unknown. 8822 patients from The Third China National Stroke Registry (CNSR-III) after whole-genome seque...

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...

Background Previous research on ABO blood types and stroke has been controversial, predominantly suggesting heightened risk of stroke in non-O blood types. Nonetheless, investigations into the correlation and underlying mechanisms between ABO blood groups and stroke subtypes, especially within Chinese cohorts, remain limited. Methods The ABO blood...

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 hospital...

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...

Background: Alteplase is the standard agent used in early reperfusion therapy, but alternative thrombolytic agents are needed. The efficacy and safety of reteplase as compared with alteplase in patients with acute ischemic stroke are unclear. Methods: We randomly assigned patients with ischemic stroke within 4.5 hours after symptom onset in a 1:...

Background: Tenecteplase is an effective thrombolytic agent for eligible patients with stroke who are treated within 4.5 hours after the onset of stroke. However, data regarding the effectiveness of tenecteplase beyond 4.5 hours are limited. Methods: In a trial conducted in China, we randomly assigned patients with large-vessel occlusion of the...

BACKGROUND The atherosclerotic sources of embolism are a significant contributor to embolic stroke of undetermined source (ESUS). However, there is limited evidence for the efficacy of intensive dual antiplatelet therapy for ESUS. We conducted an investigation to determine whether gene-directed dual antiplatelet therapy could reduce the risk of rec...

Background and Purpose Non-high-density lipoprotein cholesterol (non-HDL-C), which represents the total cholesterol content of all pro-atherogenic lipoproteins, has recently been included as a new target for lipid-lowering therapy in high-risk atherosclerotic patients in multiple guidelines. Herein, we aimed to explore the relationship between non-...

BACKGROUND Mitochondrial DNA copy number (mtDNA-CN) is associated with the severity and mortality in patients with stroke, but the associations in different stroke subtypes remain unexplored. METHODS We conducted an observational prospective cohort analysis on patients with ischemic stroke or transient ischemic attack enrolled in the Third China N...

Introduction The angiotensin-converting enzyme-2 (ACE-2) and its shedding product [soluble ACE-2 (sACE-2)] are implicated in adverse cardiovascular outcomes. However, the relationship between sACE-2 and stroke recurrence is unknown. Herein, we examined the relationship of sACE-2 with stroke recurrence in patients with ischemic stroke or transient i...

Importance Evidence on the bleeding risk associated with low-density lipoprotein cholesterol (LDL-C) levels in patients receiving dual antiplatelet therapy (DAPT) remains sparse. Objective To investigate the association of LDL-C levels with bleeding risk in patients with minor ischemic stroke (MIS) or high-risk transient ischemic attack (HRTIA) re...

Aim The aim of the study was to analyze the association between inflammatory marker profiles and in‐hospital neurological deterioration (ND) in acute ischemic stroke (AIS) patients. Methods Data from patients with minor AIS from the Third China National Stroke Registry were analyzed. Inflammatory cytokine levels within 24 h of admission were measu...

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. M...

Aims: Studies showed that low-density lipoprotein cholesterol (LDL-C) to triglyceride (TG) ratio could be used as a predictive parameter of low-density lipoprotein oxidation in vivo and the level of small dense LDL-C. However, whether LDL-C/TG ratio is associated with stroke prognosis remains unclear. We investigated the associations of LDL-C/TG ra...

Background: Elevated homocysteine levels are associated with increased blood coagulation and platelet activity and may modulate the response to antiplatelet therapies. We aimed to investigate the effects of homocysteine levels on the efficacy and safety of ticagrelor-acetylsalicylic acid (ASA) versus clopidogrel-ASA among patients with minor strok...

The network nature of the brain is gradually becoming a consensus in the neuroscience field. A set of highly connected regions in the brain network called “rich‐club” are crucial high efficiency communication hubs in the brain. The abnormal rich‐club organization can reflect underlying abnormal brain function and metabolism, which receives increasi...

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...

Background and purpose: Recombinant human prourokinase (rhPro-UK) is a new generation of specific plasminogen activator, that is non-inferior to alteplase in acute ischemic stroke. We aimed to investigate the efficacy and safety of rhPro-UK compared with standard medical treatment in acute mild ischemic stroke within 4.5 hours of symptom onset. M...

Objectives Evidence of the optimal antiplatelet therapy for elderly patients who had a stroke is limited, especially those elder than 80 years. This study aimed to explore the efficacy and safety of dual antiplatelet therapy (DAPT) in old-old patients compared with younger patients in the ticagrelor or Clopidogrel with aspirin in High-risk patients...

Background and objectives: The Ticagrelor or Clopidogrel with Aspirin in High-Risk Patients with Acute Nondisabling Cerebrovascular Events II (CHANCE-2) trial showed that among Chinese patients with minor ischemic stroke or transient ischemic attack (TIA) who were carriers of CYP2C19 loss-of-function alleles, dual-antiplatelet therapy with ticagre...

Background The atherogenicity of remnant cholesterol (RC), a contributor to residual risk of cardiovascular events, has been underlined by recent guidelines. We aimed to evaluate the relationship between RC levels and the efficacy and safety of genotype-guided dual antiplatelet therapy in the CHANCE-2 trial. Methods This post-hoc study used data f...

BACKGROUND Reteplase is a more affordable new-generation thrombolytic with a prolonged half-life. We aimed to determine the safety dose range of reteplase for patients with acute ischemic stroke within 4.5 hours of onset. METHODS This is a multicenter, prospective, randomized controlled, open-label, blinded-end point phase 2 clinical trial. Patien...

Background Clonal hematopoiesis of indeterminate potential (CHIP) is a phenomenon that characterizes individuals with somatic mutations that are related to hematologic malignancy but without hematologic abnormalities. Presence of CHIP is associated with the atherosclerotic cardiovascular disease through the activation of the interleukin 6 (IL-6) pa...

Background and Objectives Female patients have been shown to experience worse clinical outcomes after acute ischemic stroke (AIS) compared with male patients. We aimed to estimate the temporal trends in the sex differences in stroke outcomes and identify risk factors contributing to the sex differences spanning 10 years in China. Methods This coho...

Background Insulin resistance is linked to atherosclerotic cardiovascular diseases and stroke, whereas less is known about adipose tissue specific insulin resistance and outcomes after ischemic stroke. This study aimed to estimate the association between adipose tissue specific insulin resistance and prognosis of nondiabetic patients with ischemic...

Introduction: Fibrinogen-to-albumin ratio (FAR) is implicated in prothrombotic states and is associated with an increased risk of acute ischemic stroke (AIS). However, studies investigating whether the prothrombotic effect of FAR is associated with long-term adverse outcomes in patients with AIS are lacking. Therefore, we aimed to investigate the...

Introduction: We utilized data from the Third China National Stroke Registry to investigate the prevalence of atrial cardiopathy markers in patients with embolic stroke of undetermined source (ESUS) and to assess their association with death and stroke recurrence. Methods: In China, patients experiencing transient ischemic attack or ischemic stroke...

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) t...

Background This is the first real-world study to estimate the direct costs and indirect costs of first-ever ischaemic stroke with 1-year follow-up in China, based on a nationally representative sample. Methods Patients were chosen from 20 geographically diverse sites from the nationally representative database China National Stroke Registry-III (C...

Objective:Acute embolic stroke has a high risk of recurrence, including artery-to-artery embolic, cardioembolism, and embolic stroke of undetermined source. Whether lipoprotein(a) contributes to stroke recurrence risk in embolic stroke patients remains unknown. Approach and Results:This prospective cohort biomarker sub-study included 8,076 patients...

Objectives: We sought to investigate whether the prognostic value of intracranial arterial stenosis (ICAS) is consistent across different risk stratifications using the Essen Stroke Risk score (ESRS). Methods: We derived data from the Clopidogrel in High-Risk Patients with Acute Nondisabling Cerebrovascular Events trial. Patients without complet...

Aims: Inflammation is associated with vascular events. We aimed to investigate the relationship between high-sensitivity C-reactive protein (hsCRP) levels with and without intracranial arterial stenosis (ICAS) and the prognosis of patients with minor stroke or transient ischemic attack. Methods: We used data from the Clopidogrel in High-Risk Patien...

Background Given the swift advancements in artificial intelligence (AI), the utilisation of AI-based clinical decision support systems (AI-CDSSs) has become increasingly prevalent in the medical domain, particularly in the management of cerebrovascular disease. Aims To describe the design, rationale and methods of a cluster-randomised multifaceted...

Background: It is unclear whether patients with different stroke/transient ischemic attack etiologies benefit differently from gene-directed dual antiplatelet therapy. This study explored the efficacy and safety of ticagrelor-aspirin versus clopidogrel-aspirin in transient ischemic attack or minor stroke with different causes in the CHANCE-2 trial...

Background Lack of high-quality national-level data on in-hospital ischaemic stroke hinders the development of tailored strategies for this subgroup's identification, treatment, and management. Methods We analyzed and compared clinical characteristics, in-hospital management measures, and outcomes, including death or discharge against medical advi...

Background and purpose Multiple factors play important roles in the occurrence and prognosis of stroke. However, the roles of monogenic variants in all-cause ischaemic stroke have not been systematically investigated. We aim to identify underdiagnosed monogenic stroke in an adult ischaemic stroke/transient ischaemic attack (TIA) cohort (the Third C...

The association between the fibrinogen-to-albumin ratio (FAR) and intracranial arterial stenosis (ICAS) in patients with acute ischemic stroke (AIS) has not yet been reported. In this large-scale investigation, 7894 AIS patients with ICAS-evaluation imaging data from the Third China National Stroke Registry were included. ICAS was defined as >50% s...

Ischemic stroke is a leading cause of global mortality and long-term disability. However, there is a paucity of whole-genome sequencing studies on ischemic stroke, resulting in limited knowledge of the interplay between genomic and phenotypic variations among affected patients. Here, we outline the STROMICS design and present the first whole-genome...

Background: Body mass index (BMI) may affect the response to platelet P2Y12 receptor inhibitors. We aimed to explore whether BMI influenced the efficacy and safety of ticagrelor and clopidogrel for secondary prevention of minor ischemic stroke or transient ischemic attack (TIA) among patients enrolled in the CHANCE-2 (Ticagrelor or Clopidogrel wit...

Objective Cognitive impairment after stroke/transient ischemic attack (TIA) has a high prevalence. Cystatin C (CysC) has been found as a novel biomarker of neurodegenerative diseases, such as dementia and Alzheimer’s disease. We aimed to explore the possible correlations of serum CysC level with cognitive impairment in patients who had mild ischemi...

Background In large-scale high-throughput sequencing projects and biobank construction, sample tagging is essential to prevent sample mix-ups. Despite the availability of fingerprint panels for DNA data, little research has been conducted on sample tagging of whole genome bisulfite sequencing (WGBS) data. This study aims to construct a pipeline and...

Aim Post‐stroke inflammation increases the risk of functional disability through enlarged cerebral infarct size directly and follow‐up stroke event indirectly. We aimed to use post‐stroke proinflammatory cytokine interleukin‐6 (IL‐6) as a marker of inflammatory burden and quantify post‐stroke inflammation's direct and indirect effect on functional...

Background: There is a close brain-kidney interaction following ischemic cerebrovascular disease. The new-onset kidney injury after stroke leads to severe neurological deficits and poor functional outcomes. We aimed to validate the Nelson equation for predicting the new-onset and long-term kidney function decline in patients with acute ischemic st...

Background: CYP2B6 (cytochrome P450 subfamily IIB polypeptide 6), encoded by the CYP2B6 gene, is a critical enzyme involved in clopidogrel metabolism. However, the association between CYP2B6 polymorphisms and the efficacy of clopidogrel in minor stroke or transient ischemic attack for secondary stroke prevention remains unclear. Methods: Based o...

Introduction: To investigate the impact of smoking on dual antiplatelet therapy in patients with minor stroke or transient ischemic attack (TIA) under different glycated albumin (GA) levels. Methods: We analyzed data from the Clopidogrel in High-risk patients with Acute Nondisabling Cerebrovascular Events (CHANCE) trial. A subgroup of 3044 patie...

Importance: Reperfusion therapy is the most effective treatment for acute ischemic stroke but remains underused in China. Objective: To evaluate the effect of a problem-oriented, culturally adapted, targeted quality improvement intervention on reperfusion therapy for patients with acute ischemic stroke in China. Design, setting, and participant...

Importance: The Clopidogrel With Aspirin in High-Risk Patients With Acute Nondisabling Cerebrovascular Events II (CHANCE-2) trial showed that ticagrelor-aspirin combination therapy reduced the risk of stroke compared with a clopidogrel-aspirin combination among carriers of CYP2C19 loss-of-function (LOF) alleles after a transient ischemic attack (T...

Acute ischemic stroke (AIS) is a major cause of disability and mortality worldwide. Non-cardioembolic ischemic stroke (NCIS), which constitutes the majority of AIS cases, is highly heterogeneous, thus requiring precision medicine treatments. This study aimed to investigate the molecular mechanisms underlying NCIS heterogeneity. We integrated data f...

Background and purpose Recombinant human TNK tissue-type plasminogen activator (rhTNK-tPA) was not inferior to alteplase for ischaemic stroke within 4.5 hours. Our study aimed to investigate the efficacy and safety of rhTNK-tPA in patients who had an ischaemic stroke due to large vessel occlusion (LVO) of anterior circulation beyond 4.5 hours. Met...

Background and purpose The ring finger protein 213 gene ( RNF213 ) p.R4810K variant increased the risk of acute ischaemic stroke (AIS) attributable to intracranial arterial stenosis (ICAS) in the Japanese and Korean populations. In this study, we aimed to examine the prevalence of the RNF213 p.R4810K variant in Chinese patients with AIS or transien...

During the acute stage of ischemic stroke, it remains unclear how to interpret the low low-density lipoprotein cholesterol (LDL-C) level. We aimed to evaluate the association between LDL-C levels, post-stroke infection, and all-cause mortality. 804,855 ischemic stroke patients were included. Associations between LDL-C levels, infection, and mortali...

Background: Anti-inflammatory therapy using colchicine has reduced recurrent vascular events in patients with coronary heart disease. Design: Colchicine in High-risk Patients with Acute Minor-to-moderate Ischemic Stroke or Transient Ischemic Attack (CHANCE-3) is a randomized, double-blind, placebo-controlled multicenter trial, in which 8,238 pat...

Background: Aspirin is recommended for secondary stroke prevention in patients with moderate-to-severe ischaemic stroke but can lead to gastrointestinal intolerance and bleeding. Indobufen is used as an alternative antiplatelet agent in some countries, despite an absence of large-scale clinical trials for this indication. We tested the hypothesis...

Aims The monocyte to high‐density lipoprotein cholesterol ratio (MHR) has emerged as a novel inflammatory biomarker of atherosclerotic cardiovascular disease. However, it has not yet been identified whether MHR can predict the long‐term prognosis of ischemic stroke. We aimed to investigate the associations of MHR levels with clinical outcomes in pa...

Objectives Our goal was to determine the risk conferred by elevated total homocysteine (tHcy) levels on recurrent stroke and cardiovascular disease (CVD) events after an ischemic stroke (IS), using data from the Chinese Stroke Center Alliance (CSCA). Methods The study consisted of 746,854 total participants with IS. Subjects were split into groups...

Objectives The aims of the study were to assess the management of low-density lipoprotein cholesterol (LDL-C) and the goal achievement, as well as to investigate the association between baseline LDL-C level, lipid-lowering treatment (LLT), and stroke recurrence in patients with ischaemic stroke or transient ischaemic attack (TIA). Design Our study...

Little is known about the role of high-sensitivity C-reactive protein (hsCRP) in the relationship between P-wave terminal force in lead V1 (PTFV1) and stroke prognosis. We aimed to investigate how hsCRP influences the effect of PTFV1 on ischemic stroke recurrence and mortality. In this study, patients enrolled in the Third China National Stroke Reg...

Elevated levels of high-sensitivity C-reactive protein (hsCRP) were associated with an increased risk of recurrent stroke. However, it is still unknown whether the predictive value of hsCRP differed according to the severity of cerebrovascular disease. We used the cohort of the prospective multicenter cohort study of the Third China National Stroke...

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...

Background: It is unclear whether infarct location affects stroke recurrence after index ischemic stroke. We aimed to compare the risk of stroke recurrence and the responses to dual antiplatelets with ticagrelor-aspirin versus clopidogrel-aspirin between patients with posterior circulation infarct (PCI) and those with anterior circulation infarct...

Background: Women with stroke differ from men in risk factors, treatment, and outcomes. However, previous inconsistent results in China hampered the development of tailored sex-specific strategies for ischemic stroke management. We performed a nationwide serial cross-sectional survey to obtain national-level estimates to assess the ten-year trends...