The FAITHS2 Model Predicts Functional Disability in Patients With Acute Ischemic Stroke.

The present study aimed to develop a model to predict functional disability at 3 months in patients with acute ischemic stroke (AIS) (n = 5,406). The primary outcome was functional disability (modified Rankin Scale [mRS] >2) at 3 months. A prediction model including blood biomarkers was developed based on a multivariable logistic regression model, which was internally validated by the 100-time bootstrap method. A nomogram and a web-based calculator were developed for usage in clinical practice. At 3 months, 11% (638/5,406) of the patients had functional disability. Seven independent predictors of functional disability at 3 months were incorporated into the FAITHS2 model (fasting plasma glucose, age, interleukin-6, stroke history, National Institute of Health Stroke Scale [NIHSS] at admission, sex, and systolic blood pressure). The Area Under Curves (AUCs) were 0.814 (95% confidence interval [CI] 0.796-0.832) and 0.808 (95% CI 0.806-0.810), and the Brier scores were 0.088 ± 0.214 and 0.089 ± 0.003 for the derivation cohort and internal validation, respectively, showing optimal performance of the model. The FAITHS2 model has excellent potential to be a dependable application for individualized clinical decision making.

Inflammatory marker profiles and in-hospital neurological deterioration in patients with acute minor ischemic stroke.

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 measured. The primary outcome was in-hospital ND (an increase in National Institutes of Health Stroke Scale score ≥4 from admission to discharge). Associations were evaluated using odds ratios (ORs) and 95% confidence intervals (CIs) derived from logistic regression models. Net reclassification improvement (NRI) and integrated discrimination improvement (IDI) were used to evaluate incremental predictive values. RESULTS: A total of 4031 patients (1246 women, 30.9%) with a median age of 62 years were included. In-hospital ND occurred in 121 patients (3%). Each standard-deviation increase in interleukin (IL)-6 (OR, 1.17 [95% CI, 1.06-1.31]) and high-sensitivity C-reactive protein (hsCRP) (OR, 1.43 [95% CI, 1.24-1.66]) levels was associated with increased in-hospital ND risk. Incremental predictive values for adding IL-6 (IDI, 0.012; NRI, 0.329) but not hsCRP levels to the conventional risk factors were found. CONCLUSION: In minor AIS, hsCRP and IL-6 levels were associated with in-hospital ND, including IL-6 levels in prognostic models improved risk classification.

Predictors of dysphagia screening and pneumonia among patients with intracerebral haemorrhage in China: a cross-sectional hospital-based retrospective study.

OBJECTIVES: This study aimed to investigate factors associated with undergoing dysphagia screening (DS) and developing pneumonia, as well as the relationship between DS and pneumonia in patients with intracerebral haemorrhage (ICH). DESIGN: Our study was a cross-sectional hospital-based retrospective study. STUDY DESIGN AND SETTINGS: We derived data from the China Stroke Centre Alliance, a nationwide clinical registry of ICH from 1476 participating hospitals in mainland China. To identify predictors for pneumonia, multivariable logistic regression models were used to identify patient characteristics that were independently associated with DS and pneumonia. PARTICIPANTS: We included 31 546 patients in this study with patient characteristics, admission location, medical history, hospital characteristics and hospital grade from August 2015 to July 2019. PRIMARY AND SECONDARY OUTCOME MEASURES: The primary outcomes were DS and pneumonia during acute hospitalisation. RESULTS: In total, 25 749 (81.6%) and 7257 (23.0%) patients with ICH underwent DS and developed pneumonia. Compared with patients without pneumonia, those who developed pneumonia were older and had severe strokes (Glasgow Coma Scale 9-13: 52.7% vs 26.9%). Multivariable analyses revealed that a higher pneumonia risk was associated with dysphagia (OR, 4.34; 95% CI, 4.02 to 4.68), heart failure (OR, 1.85; 95% CI, 1.24 to 2.77) and smoking (OR, 1.12; 95% CI, 1.12 to 0.20). DS was associated with lower odds of pneumonia (OR, 0.65; 95% CI, 0.44 to 0.95). CONCLUSION: Our findings further confirm that dysphagia is an independent risk factor for pneumonia; one-fifth of patients with ICH did not undergo DS. However, comprehensive dysphagia evaluation and effective management are crucial. Nursing processes ensure the collection of complete and accurate information during evaluation of patients. There is a need to increase the rate of DS in patients with ICH, especially those with severe stroke or older. Further, randomised controlled trials are warranted to determine the effectiveness of DS on clinical outcomes.

Associations between admission levels of multiple biomarkers and subsequent worse outcomes in acute ischemic stroke patients.

The modified Rankin Scale change score (ΔmRS) is useful for evaluating acute poststroke functional improvement or deterioration. We investigated the relationship between multiple biomarkers and ΔmRS by analyzing data on 6931 patients with acute ischemic stroke (average age 62.3 ± 11.3 years, 2174 (31.4%) female) enrolled from the Third China National Stroke Registry (CNSR-III) and 15 available biomarkers. Worse outcomes at 3 months were defined as ΔmRS3m-discharge ≥1 (ΔmRS3m-discharge = mRS3m-mRSdischarge). Adjusted odds ratios (aORs) and their 95% confidence intervals (CIs) were calculated from logistic regression models. At 3-months poststroke, 1026 (14.8%) patients experienced worse outcomes. The highest quartiles of white blood cells (WBCs) (aOR [95%CI],1.37 [1.12-1.66]), high-sensitivity C-reactive protein (hs-CRP) (1.37 [1.12-1.67]), interleukin-6 (IL-6) (1.43 [1.16-1.76]), interleukin-1 receptor antagonist (IL-1Ra) (1.46 [1.20-1.78]) and YKL-40 (1.31 [1.06-1.63]) were associated with an increased risk of worse outcomes at 3 months. Results remained stable except for YKL-40 when simultaneously adding multiple biomarkers to the basic traditional-risk-factor model. Similar results were observed at 6 and 12 months after stroke. This study indicated that WBCs, hs-CRP, IL-6, IL-1Ra, and YKL-40 were significantly associated with worse outcomes in acute ischemic stroke patients, and all inflammatory biomarkers except YKL-40 were independent predictors of worse outcomes at 3 months.

Clinical characteristics, in-hospital management, and outcomes of patients with in-hospital vs. community-onset ischaemic stroke: a hospital-based cohort study.

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 advice (DAMA), major adverse cardiovascular events (MACEs), disability at discharge, and in-hospital complications between in-hospital and community-onset ischaemic stroke enrolled in the Chinese Stroke Center Association registry from August 2015 to December 2022. Findings: The cohort comprised 14,948 in-hospital and 1,366,898 community-onset ischaemic stroke patients. In-hospital ischaemic stroke exhibited greater stroke severity, higher prevalence of comorbidities, more pre-admission medications, and had suboptimal management measures, for example, the onset-to-needle time within 4.5 h (83.3% vs. 93.1%; difference, -9.8% [-11.4% to -8.3%]), and antithrombotics at discharge (78.6% vs. 90.0%; difference, -11.4% [95% CI, -12.1% to -10.7%]). After adjusting for covariates, in-hospital ischaemic stroke remains associated with higher risks of unfavorable outcomes, including in-hospital death/DAMA (13.9% vs. 8.6%; adjusted risk difference [aRD], 2.2% [95% CI, 1.8%-2.7%]; adjusted odds ratio [aOR], 1.35 [95% CI, 1.25-1.45]), MACE (12.6% vs. 6.5%; aRD, 4.1% [95% CI, 3.5%-4.7%]; aOR, 1.68 [95% CI, 1.52-1.85]), and complications (23.7% vs. 12.1%; aRD, 6.5% [95% CI, 5.1%-7.9%]; aOR, 1.72 [95% CI, 1.64-1.80]), except for disability at discharge (41.1% vs. 33.1%; aRD, 0.4% [95% CI, -1.7% to 2.5%]; aOR, 0.99 [95% CI, 0.88-1.11]). Interpretation: In-hospital ischaemic stroke demonstrated more severe strokes, worse vascular risk profiles, suboptimal management measures, and worse outcomes compared to community-onset ischaemic stroke. This emphasizes the urgent need for improved hospital systems of care and targeted quality improvement initiatives for better outcomes in in-hospital ischaemic stroke. Funding: National Key R&D Programme of China and Beijing Hospitals Authority.

Assessment of rehabilitation following subarachnoid haemorrhage in China: findings from the Chinese Stroke Center Alliance.

BACKGROUND: Rehabilitation improves functional recovery in subarachnoid hemorrhage (SAH) patients, and assessing patients for rehabilitation is the first step in this process. However, little is known about clinical practice in China regarding the assessment and provision of rehabilitation for patients with SAH. METHODS: To identify patients hospitalized with SAH and to analyze rehabilitation assessment rates, we used data for 11,234 SAH patients admitted to 861 hospitals from the China Stroke Center Alliance from August 2015 to July 2019. We examined factors for rehabilitation assessment and analyzed the relationship between rehabilitation assessment and outcomes in these patients. RESULTS: Among 11,234 patients with SAH, 6,513 (58.0%) were assessed for rehabilitation. Assessed patients had an increased length of stay (mean ± SD days: 17.3 ± 12.5 versus 11.6 ± 10.5, P = 49.4), a higher Glasgow Coma Scale (GCS) score on admission (mean ± SD GCS score: 12.3 ± 3.8 versus 11.8 ± 4.4, P = 12.2), and were more likely to be admitted to the stroke unit (19.6% versus 13.8%, P = 15.6). In multivariable analysis, factors associated with an increased likelihood of a rehabilitation assessment (p < 0.05) included a longer length of stay (odds ratio [OR], 1.04; 95% confidence interval (CI), 1.04 to 1.05) and care such as dysphagia screening (OR, 1.88; 95% CI, 1.73 to 2.04), DVT prophylaxis (OR, 1.56; 95% CI, 1.41 to 1.72) and vessel evaluation (OR, 1.80; 95% CI, 1.63 to 1.98). For the multivariate analysis of outcomes, patients undergoing rehabilitation assessment had a longer length of stay (OR, 1.96; 95% CI, 1.81 to 2.12), a higher modified Rankin Scale (mRS) score at discharge (OR, 1.49; 95% CI, 1.36 to 1.64), and higher rates of discharge to a rehabilitation center (OR, 3.23; 95% CI, 1.81-5.75). CONCLUSION: More than two-fifths of SAH patients were not assessed for rehabilitation. Rates vary considerably among hospital grades, and there is a need to improve adherence to recommended care for SAH patients.

Mediation effect of stroke recurrence in the association between post-stroke interleukin-6 and functional disability.

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 disability. METHODS: We analyzed patients with acute ischemic stroke admitted to 169 hospitals in the Third China National Stroke Registry. Blood samples were collected within 24 h of admission. Stroke recurrence and functional outcome measured by the modified Rankin scale (mRS) were assessed via face-to-face interviews at 3 months. Functional disability was defined as an mRS score ≥2. Mediation analyses under the counterfactual framework were performed to examine the potential causal chain in which stroke recurrence may mediate the relationship between IL-6 and functional outcome. RESULTS: Among the 7053 analyzed patients, the median (interquartile range [IQR]) NIHSS score was 3 (1-5), and the median (IQR) level of IL-6 was 2.61 (1.60-4.73) pg/mL. Stroke recurrence was observed in 458 (6.5%) patients, and functional disability was seen in 1708 (24.2%) patients at the 90-day follow-up. Per stand deviation (4.26 pg/mL) increase in the concentration of IL-6 was associated with an increased risk of stroke recurrence (adjusted odds ratio [aOR], 1.19; 95% CI, 1.09-1.29) and disability (aOR, 1.22; 95% CI, 1.15-1.30) within 90 days. Mediation analyses revealed that 18.72% (95% CI, 9.26%-28.18%) of the relationship between IL-6 and functional disability was mediated by stroke recurrence. CONCLUSIONS: Stroke recurrence mediates less than 20% of the association between IL-6 and functional outcome at 90 days among patients with acute ischemic stroke. In addition to typical secondary prevention strategies for preventing stroke recurrence, more attention should be paid to novel anti-inflammatory therapy to improve functional outcomes directly.

U-shaped association between low-density lipoprotein cholesterol levels and risk of all-cause mortality mediated by post-stroke infection in acute ischemic stroke.

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 mortality risk were estimated by multivariate logistic regression models and displayed by restricted cubic spline curves. Mediation analysis was performed under counterfactual framework to elucidate the mediation effect of post-stroke infection. The association between LDL-C and mortality risk was U-shaped. The nadir in LDL-C level with the lowest mortality risk was 2.67 mmol/L. Compared with the group with LDL-C = 2.50-2.99 mmol/L, the multivariable-adjusted odds ratio for mortality was 2.22 (95% confidence intervals (CI): 1.77-2.79) for LDL-C <1.0 mmol/L and 1.22 (95% CI: 0.98-1.50) for LDL-C ≥5.0 mmol/L. The association between LDL-C and all-cause mortality was 38.20% (95% CI: 5.96-70.45, P = 0.020) mediated by infection. After stepwise excluding patients with increasing numbers of cardiovascular risk factors, the U-shaped association between LDL-C and all-cause mortality and the mediation effects of infection remained consistent with the primary analysis, but the LDL-C interval with the lowest mortality risk increased progressively. The mediation effects of infection were largely consistent with the primary analysis in subgroups of age ≥65 years, female, body mass index <25 kg/m2, and National Institutes of Health Stroke Scale ≥16. During the acute stage of ischemic stroke, there is a U-shaped association between LDL-C level and all-cause mortality, where post-stroke infection is an important mediating mechanism.

Effectiveness of a Quality Improvement Intervention on Reperfusion Treatment for Patients With Acute Ischemic Stroke: A Stepped-Wedge Cluster Randomized Clinical Trial.

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 Participants: In this stepped-wedge cluster randomized clinical trial, patients from 16 secondary and 33 tertiary hospitals in China with acute ischemic stroke within 6 hours of symptom onset were consecutively recruited between July 1, 2018, and June 30, 2020. Interventions: Hospitals were randomly assigned to 1 of 3 sequences to receive the targeted quality improvement intervention (n = 5689), in which workflow reconstruction was promoted to reduce in-hospital reperfusion treatment delays, or usual care (n = 6443), in which conventional stroke care was left to the discretion of the stroke team. Main Outcomes and Measures: The primary outcome was the reperfusion therapy rate, a composite outcome of intravenous recombinant tissue plasminogen activator (IV rtPA) or endovascular thrombectomy (EVT) for eligible patients who arrived within 3.5 or 4.5 hours of symptom onset. Secondary outcomes were the IV rtPA administration rate among eligible patients who arrived within 3.5 hours of symptom onset, the EVT rate among eligible participants who arrived within 4.5 hours of symptom onset, the proportion of patients with door-to-needle time within 60 minutes, the proportion of patients with door-to-puncture time within 90 minutes, in-hospital mortality, and 3-month disability as measured by a modified Rankin Scale score greater than 2. Results: All 12 132 eligible patients (mean [SD] age, 66 [12.1] years; 7759 male [64.0%]) completed the trial. The reperfusion rate was 53.5% (3046 of 5689) for the eligible patients in the intervention period and 43.9% (2830 of 6443) in the control period. No significant improvement in primary outcomes was found for the intervention after adjusting for cluster, period, and imbalanced baseline covariates (adjusted risk difference [ARD], 5.5%; 95% CI, -8.0% to 19.0%; adjusted odds ratio [AOR], 1.26; 95% CI, 0.72-2.21) or for the secondary outcomes. However, significant improvements were found in secondary hospitals for reperfusion therapy (1081 of 1870 patients [57.8%] vs 945 of 2022 patients [42.9%]; ARD, 19.0%; 95% CI, 6.4%-31.6%; AOR, 2.24; 95% CI, 1.29-3.88), IV rtPA administration (1062 of 1826 patients [58.2%] vs 916 of 2170 patients [42.2%]; ARD, 20.3%; 95% CI, 7.4%-33.1%; AOR, 2.37; 95% CI, 1.34-4.19), and EVT (51 of 231 patients [22.1%] vs 37 of 259 patients [14.3%]; ARD, 13.6%; 95% CI, 1.0%-26.3%; AOR, 3.03; 95% CI, 1.11-8.25) in subgroup analyses. Conclusions and Relevance: In this stepped-wedge cluster randomized clinical trial of patients with acute ischemic stroke in China, the use of a targeted quality improvement intervention compared with usual care did not improve the reperfusion therapy rate. However, the intervention may be effective in secondary hospitals. Trial Registration: ClinicalTrials.gov Identifier: NCT03578107.

Lipid management in ischaemic stroke or transient ischaemic attack in China: result from China National Stroke Registry III.

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 was a post hoc analysis of the Third China National Stroke Registry (CNSR-III). SETTING: We derived data from the CNSR-III - a nationwide clinical registry of ischaemic stroke and TIA based on 201 participating hospitals in mainland China. PARTICIPANTS: 15,166 patients were included in this study with demographic characteristics, etiology, imaging, and biological markers from August 2015 to March 2018. PRIMARY AND SECONDARY OUTCOME MEASURES: The primary outcome was a new stroke, LDL-C goal (LDL-C<1.8mmol/L and LDL-C<1.4mmol/L, respectively) achievement rates, and LLT compliance within 3, 6, and 12 months. The secondary outcomes included major adverse cardiovascular events (MACE) and all caused death at 3 and 12 months. RESULTS: Among the 15,166 patients, over 90% of patients received LLT during hospitalization and 2 weeks after discharge; the LLT compliance was 84.5% at 3 months, 75.6% at 6 months, and 64.8% at 12 months. At 12 months, LDL-C goal achievement rate for 1.8mmol/L and 1.4mmol/L was 35.4% and 17.6%, respectively. LLT at discharge was associated with reduced risk of ischemic stroke recurrence (HR=0.69, 95% CI: 0.48-0.99, p=0.04) at 3 months. The rate of LDL-C reduction from baseline to 3-month follow-up was not associated with a reduced risk of stroke recurrence or major adverse cardiovascular events (MACE) at 12 months. Patients with baseline LDL-C ≤1.4mmol/L had a numerically lower risk of stroke, ischemic stroke and MACE at both 3 months and 12 months. CONCLUSIONS: The LDL-C goal achievement rate has increased mildly in the stroke and TIA population in mainland China. Lowered baseline LDL-C level was significantly associated with a decreased short- and long-term risk of ischemic stroke among stroke and TIA patients. LDL-C<1.4mmol/L might be a safe standard for this population.

Elevated levels of total homocysteine after ischemic stroke: a potential marker for in-hospital outcomes.

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 as well as quartiles according to tHcy level. Groups included a hyperhomocysteinemia (HHcy) group with tHcy ≥15 µmol/l and a normohomocysteinemia group (nHcy) with tHcy <15 µmol/l. The determined groups and quartiles underwent multiple logistic regression models with nHcy or quartile 1 as reference groups, respectively. The information from these analyses was adjusted for potential covariates and used to investigate the association between blood tHcy and in-hospital outcomes. Information collected at discharge included in-hospital stroke recurrence and CVD events. RESULTS: The mean [SD] age of participants was 66.2 [12.0] and 37.4% (n = 279,571) were female. The median hospital duration was 11.0 days (interquartile range, 8.0-14.0 days) and 343,346 (46.0%) patients were identified as HHcy cases (tHcy ≥15 µmol/). According to the tHcy quartile, the cumulative rates of stroke recurrence (from lowest quartile to highest) were 5.2%, 5.6%, 6.1%, and 6.6% (P < 0.0001). Similarly, those of CVD events were 5.8%, 6.1%, 6.7%, and 7.2% (P < 0.0001). Compared with the nHcy group, the HHcy group was associated with increased risks of in-hospital stroke recurrence (21912 [6.4%] vs. 22048 [5.5%], with the adjusted odds ratio (OR) 1.08, 95% CI: 1.05 to 1.10) as well as CVD events (24001 [7.0%] vs. 24236 [6.0%], with the adjusted OR: 1.08, 95% CI: 1.06 to 1.10) among patients with IS in the fully adjusted model. CONCLUSION: HHcy was associated with increased in-hospital stroke recurrence and CVD events among patients with IS. In low-folate regions, tHcy levels may potentially predict in-hospital outcomes after IS.

Ten-year trends in sex differences in cardiovascular risk factors, in-hospital management, and outcomes of ischemic stroke in China: Analyses of a nationwide serial cross-sectional survey from 2005 to 2015.

BACKGROUND: Women with stroke differ from men in terms of 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 10-year trends in sex differences in cardiovascular risk factors, in-hospital management, and outcomes in China from 2005 to 2015. METHODS: We used a two-stage random sampling design, economic-geographical region-stratified random sampling for hospitals first and then systematic sampling for patients, to obtain a nationally representative sample of ischemic strokes in China in 2005, 2010, and 2015. We extracted data on clinical characteristics, management measures (diagnostic tests, interventions, and secondary prevention treatments), in-hospital outcomes (all-cause in-hospital mortality, discharge against medical advice [DAMA], and a composite outcome of in-hospital death and DAMA), and comorbidities. We applied weights proportional to the inverse sampling fraction of hospitals within each stratum and the inverse sampling fraction of patients within each hospital. RESULTS: A total of 26,900 ischemic stroke admissions were analyzed. Compared to men, women had a much lower prevalence of current smokers and a slightly higher prevalence of hypertension, diabetes, dyslipidemia, and atrial fibrillation at admission. Prevalence differences between sex in these cardiovascular risk factors were stable except for atrial fibrillation (decreased from 3.7% [95% CI: 1.8% to 5.7%] to 1.3% [95% CI: 0.5% to 2.0%]) and current smoker (increased from -18.0 [95% CI: -20.2% to -15.9%] to -25.6% [95% CI: -26.6% to -24.6%]). From 2005 to 2015, in-hospital management and outcomes were improved both for women and men, and sex differences in cerebrovascular assessment, cervical vessels assessment, and transthoracic echocardiography/transesophageal echocardiography were improved as well. However, women increased more slowly than men in the administration of clopidogrel (from 0.3% [95% CI: -0.9% to 1.4%) to -7.3% [95% CI: -8.7% to -6.0%]) and aspirin plus clopidogrel (0.3% [95% CI: -5.0% to 1.1%] to -5.0% [95% CI: -6.2% to -3.9%]). CONCLUSION: Compared to men, women patients with ischemic stroke had a steadily higher prevalence of cardiovascular risk factors, a slower increase rate in the administration of key secondary prevention drugs, and comparable in-hospital outcomes. More effort should be paid to the treatment and control of cardiovascular risk factors and also to the prescription of antiplatelets at discharge for women.

Low estimated glomerular filtration rate explains the association between hyperhomocysteinemia and in-hospital mortality among patients with ischemic stroke/transient ischemic attack or intracerebral hemorrhage: Results from the Chinese Stroke Center Alliance.

OBJECTIVES: To investigate the association between hyperhomocysteinemia (HHcy) and in-hospital mortality following ischemic stroke (IS), transient ischemic attack (TIA), or intracerebral hemorrhage (ICH). METHODS: Data on patients with ischemic cerebrovascular disease (IS/TIA) or ICH enrolled in the Chinese Stroke Center Alliance (CSCA) from 2015 to 2019 were extracted. Patient characteristics and in-hospital mortality were analyzed and multiple adjusted logistic regression analyses performed to investigate the association between blood tHcy (total homocysteine) and in-hospital mortality in patients with HHcy (tHcy ⩾ 15 µmol) and patients with normohomocysteinemia (nHcy) (tHcy < 15 µmol). RESULTS: A total of 823,622 participants were included. Mean (SD) age was 65.9 (12.1), and 62.5% (n = 514,888) were male. A total of 379,807 (46.0%) patients were identified as having HHcy, and 70,364 (8.5%) patients had an estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73 m2. An eGFR < 60 mL/min/1.73 m2 was the strongest independent risk factor for HHcy in both patients with IS/TIA (adjusted odds ratio (aOR) 2.67, 95% confidence interval (CI): 2.49-2.86), and those with ICH (2.94, 2.46-3.50). On multivariable logistic regression, after adjusting for potential confounding factors, HHcy was associated with in-hospital mortality (aOR: 1.25, 95% CI: 1.13-1.37 for patients with IS/TIA; aOR: 1.40, 95% CI: 1.12-1.76 for patients with ICH). However, after additionally adjusting for eGFR, this association disappeared among patients with both IS/TIA (aOR: 1.09, 95% CI: 0.99-1.20) and those with ICH (aOR: 1.17, 9% CI: 0.96-1.43). CONCLUSION: HHcy was associated with in-hospital mortality among the patients with IS/TIA or ICH but this association disappeared after controlling for eGFR, suggesting HHcy was acting as a marker of poor renal function which itself was the predictor of poor outcome. Our results suggest the prevention and management of renal impairment may be an important measure in the reduction of mortality in patients with HHcy after IS/TIA or ICH.

Short-term effect of PM2.5 on stroke in susceptible populations: A case-crossover study.

BACKGROUND: Fine particulate matter (PM2.5) is a risk factor for stroke, and patients with pre-existing diseases appear to be particularly susceptible. We conducted a case-crossover study to examine the association between short-term exposure to fine particulate matter (PM2.5) and hospital admission for stroke in individuals with atrial fibrillation (AF), hypertension, diabetes, or hyperlipidemia. METHODS: Patients diagnosed with acute ischemic stroke (AIS) were recruited from 2015 to 2017 in Chinese Stroke Center Alliances. We estimated daily PM2.5 average exposures with a spatial resolution of 0.1° using a data assimilation approach combining satellite measurements, air model simulations, and monitoring values. Conditional logistic regression was used to assess PM2.5-related stroke risk in patients with pre-existing medical co-morbidities. RESULTS: A total of 155,616 patients diagnosed with AIS were admitted. Patients with a history of AF (n = 15,430), hypertension (n = 138,220), diabetes (n = 43,737), or hyperlipidemia (n = 16,855) were assessed separately. A 10 µg/m3 increase in daily PM2.5 was associated with a significant increase in AIS for individuals with AF at lag 4 (odds ratio (OR), 1.008; 95% confidence interval (CI), 1.002-1.014), and with hypertension (OR, 1.008; 95% CI, 1.006-1.010), diabetes (OR, 1.006; 95% CI, 1.003-1.010), and hyperlipidemia (OR, 1.007; 95% CI, 1.001-1.012) at lags 0-7. Elderly (⩾ 65 years old) and female patients with AF had significantly higher associations at lag 5 (OR, 1.009; 95% CI, 1.002-1.015) and lag 5 (OR, 1.010; 95% CI, 1.002-1.018), respectively. CONCLUSION: Short-term exposure to PM2.5 is significantly associated with hospital admission for stroke in individuals with pre-existing medical histories, especially in older or female patients with AF. Preventive measures to reduce PM2.5 concentrations are particularly important in individuals with other medical co-morbidities.

Assessment of rehabilitation following intracerebral hemorrhage in China: findings from the Chinese stroke center alliance.

OBJECTIVES: Evidence shows that rehabilitation is the most effective strategy to reduce the disability rate of patients with stroke. However, there is limited understanding about the factors associated with rehabilitation assessment among patients with intracerebral hemorrhage (ICH) in China. We aimed to investigate the factors associated with rehabilitation assessment in patients with ICH and the relationship between rehabilitation assessment and hospitalization outcomes. METHODS: Data from 85,664 patients with ICH admitted to 1,312 hospitals between 1 August 2015 and 31 July 2019 were analyzed. A multivariable logistic regression model accounting for in-hospital clustering was used to identify patient and hospital factors associated with rehabilitation assessment during acute hospitalization. RESULTS: A total of 62,228 (72.6%) patients with ICH underwent rehabilitation assessments. In multivariable analyses, factors associated with an increased likelihood of undergoing a rehabilitation assessment (P < .05) included a higher Glasgow Coma Scale score on admission, a history of hypertension, a history of peripheral vascular disease, dysphagia screening, carotid vessel imaging, and a longer length of hospital stay. Conversely, patients admitted to the intensive care unit and tertiary-grade hospitals were less likely to undergo rehabilitation assessments during hospitalization for ICH. DISCUSSION: This study showed that the rate of rehabilitation assessment was 74.2%, which is low. Rehabilitation assessment was associated with longer hospital stays and lower mortality. Therefore, patients with acute cerebral haemorrhage should undergo comprehensive and professional rehabilitation assessment.

External validation of ABCD series scores for predicting early stroke events following transient ischemic attack in a large nationwide registry.

Introduction: In the context of modern guideline-based strategies, new validations of prognostic scores for predicting early stroke risk are needed. We aimed to compare the validity of the ABCD series scores and assess the incremental values of risk components for predicting in-hospital stroke events in patients with transient ischemic attack (TIA). Patients and methods: We abstracted data from the Chinese Stroke Center Alliance (CSCA), a nationwide registry with 68,433 TIA patients admitted within 7 days of symptom onset from 1476 hospitals. TIA was defined by time-based criteria according to the World Health Organization (WHO). The discrimination of ABCD, ABCD2, ABCD2-I, and ABCD3 scores for predicting in-hospital stroke events was assessed by the area under the receiver-operating characteristics curves (AUC). The incremental predictive values of added risk predictor were determined by net reclassification improvement (NRI) and integrated discrimination improvement (IDI). Results: A total of 29,286 TIA patients were included, of whom 1466 (5.0%) had in-hospital stroke events. Compared with ABCD2-I score (AUC 0.79, 95% confidence interval [CI] 0.77-0.80), ABCD (AUC 0.58, 95% CI 0.57-0.60), ABCD2 (AUC 0.58, 95% CI 0.56-0.59), and ABCD3 (AUC 0.58, 95% CI 0.56-0.60) had lower predictive utility. An incremental value was observed when adding infarction on DWI (IDI = 0.0597, NRI = 1.1036) into ABCD2 score to be ABCD2-I. Conclusion: The traditional scales utilizing medical history (ABCD, ABCD2, and ABCD3 scores) show fair ability for predicting in-hospital stroke events after TIA, but the ABCD2-I score, which adds infarction on DWI, improves the predictive ability.

Pre-stroke dementia and in-hospital outcomes in the Chinese Stroke Center Alliance.

Background: Little is known about the impact of prevalent dementia on in-hospital outcomes of patients with incident stroke in China. Using data from the Chinese Stroke Center Alliance (CSCA), we aim to quantify the prevalence of pre-stroke dementia and whether this group is at higher risk of adverse in-hospital outcomes compared to those without pre-stroke dementia. Methods: We used multivariable logistic regression models to assess the associations between pre-stroke dementia and ambulation by day 2, in-hospital mortality, in-hospital complications, and being discharged home. Covariates included age, sex, comorbidities [dyslipidemia, atrial fibrillation, peripheral vascular disease (PVD), smoking, and alcohol use], medication history (antiplatelet drugs or lipid-lowering drugs), stroke severity [measured by the National Institute of Health Stroke Scale (NIHSS)], administration of intravenous tissue plasminogen activator (IV tPA) within 4.5 hours of stroke onset, and receipt of deep vein thrombosis (DVT) prophylaxis if indicated. Results: In the final analytic sample of 559,070 ischemic stroke patients with no prior stroke history enrolled across 1,476 hospitals, those with pre-stroke dementia (n=1,511; 0.3%) were older and more likely to be female. Despite having received similar treatment, patients with pre-stroke dementia had lower odds of ambulating by day 2 [odds ratio (OR) =0.69; 95% confidence interval (CI): 0.62-0.78], higher odds of in-hospital mortality (OR =2.01; 95% CI: 1.35-2.99) or complications (OR =2.17; 95% CI: 1.93-2.44), and lower odds of being discharged home compared to those without pre-stroke dementia (OR =0.71; 95% CI: 0.62-0.83). Conclusions: Worse in-hospital outcomes among patients with pre-stroke dementia may be explained by pre-existing cognitive impairment that limited their ability to advocate for care needs. Further research is needed to determine whether a different care pathway or additional attention from clinicians is necessary for patients with pre-stroke dementia.

Thrombolysis, time-to-treatment and in-hospital outcomes among young adults with ischaemic stroke in China: findings from a nationwide registry study in China.

BACKGROUND AND PURPOSE: We aimed to determine whether young adults (<50 years) with acute ischaemic stroke (AIS) are more likely to receive intravenous tissue plasminogen activator (IV tPA) and have shorter time to treatment than older patients with stroke. METHODS: We analysed data from the Chinese Stroke Center Alliance registry for patients with AIS hospitalised between August 2015 and July 2019. Patients were classified into two groups according to age: young adults (<50 years of age) and older adults (≥50 years of age). RESULTS: Of 793 175 patients with AIS admitted to 1471 hospitals, 9.1% (71 860) were young adults. Compared with older adults, a higher proportion of young adults received IV tPA among patients without contraindicaitons (7.2% vs 6.1%, adjusted OR (aOR) 1.13, 95% CI 1.10 to 1.17) and among patients without contraindications and with onset-to-door time ≤3.5 hours (23.6% vs 19.3%, aOR 1.20, 95% CI 1.15 to 1.24). We did not observe differences in onset-to-needle time (median hours 2.7 hours) or door-to-needle time (DNT) (median minutes 60 min) between young and older adults. The proportion of DNT ≤30 min, DNT ≤45 min and DNT ≤60 min in young and older IV tPA-treated patients were 16.9% vs 18.8%, 30.2% vs 32.8% and 50.2% vs 54.2%, respectively. Compared with older adults, young adults treated with IV tPA had lower odds of in-hospital mortality (0.5% vs 1.3%, aOR 0.54, 95% CI 0.35 to 0.82) and higher odds of independent ambulation at discharge (61.0% vs 53.6%, aOR 1.15, 95% CI 1.08 to 1.22), and the associations may be partly explained by stroke severity measured by the National Institutes of Health Stroke Scale score. CONCLUSION: Young adults with AIS were more likely to receive IV tPA than older adults, although there was no difference between the two groups in time to treatment. Compared with older adults, young adults may had better in-hospital outcomes.

Association between high-sensitivity C-reactive protein, functional disability, and stroke recurrence in patients with acute ischaemic stroke: A mediation analysis.

BACKGROUND: Post-stroke inflammation biomarker high-sensitivity C-reactive protein (hsCRP) increases cerebral infarct size and results in functional disability directly, it also contributes to the formation and maturation of atherosclerotic plaques, which increase the risk of stroke recurrence and results in functional disability indirectly. However, no study has quantified how much functional disability was mediated by stroke recurrence. METHODS: Patients with acute ischaemic stroke within 7 days and admitted to 169 hospitals in the Third China National Stroke Registry were analyzed. Blood samples were collected within 24 h of admission. Stroke recurrence and functional disability (defined as a modified Rankin scale score ≥ 2) were assessed via face-to-face interviews at three months. Mediation analysis under the counterfactual framework was performed to examine the potential causal chain in which stroke recurrence may mediate the relationship between hsCRP and functional outcome. Sensitivity analyses were performed across different subgroups and on different scales of hsCRP measurement. FINDINGS: Of the 7603 analyzed patients (mean [SD] age, 62.3 [11.3] years; 2392 [31.5%] women), the median (interquartile range [IQR]) of NIHSS score was 3.0 (1.0-6.0). The median (IQR) level of hsCRP was 1.73 (0.81-4.38) mg/L. A total of 496 (6.5%) cases of stroke recurrence and 1884 (24.8%) cases of functional disability were observed at the 90-day follow-up. Each SD increase in the concentration of hsCRP was associated with an increased risk of stroke recurrence (adjusted odds ratio [aOR], 1.11; 95% CI, 1.04-1.18) and disability (aOR, 1.14; 95% CI, 1.08-1.20) within 90 days. Of 1884 functionally disabled patients, only 16.0 % (n = 302) of patients experienced stroke recurrence before functional disability. Stroke recurrence during follow-up explained 16.52% (95% CI, 5.79%-27.25%) of the relationship between hsCRP and functional disability. Sensitivity analyses in different subgroups and on different scales of hsCRP measurement showed comparable results. INTERPRETATION: Stroke recurrence mediates less than 20% of the association between hsCRP and functional disability at 90 days among patients with acute ischaemic stroke. In addition to typical secondary prevention strategies for preventing stroke recurrence, more attention should be paid to novel anti-inflammatory therapy to improve functional outcomes. FUNDING: Beijing Natural Science Foundation, the National Key R&D Program of China, the National Natural Science Foundation of China, and the Beijing Municipal Science & Technology Commission.

Prognosis and antiplatelet therapy of small single subcortical infarcts in penetrating artery territory: a post hoc analysis of the Third China National Stroke Registry.

Background: Small single subcortical infarction (SSSI) may be classified as parent artery disease-related or only branch involved according to the stenosis of parent artery. The study aimed to evaluate short-term and long-term prognoses and the effectiveness of antiplatelet therapy in SSSI. Methods: We prospectively enrolled 2890 patients with SSSI from the Third China National Stroke Registry (CNSR-III) database from August 2015 to March 2018. We assessed clinical outcomes and antiplatelet treatment effects in patients with SSSI with and without parent artery stenosis (PAS) identified by magnetic resonance angiography. Results: Among 2890 patients with SSSI in the perforator territory of the middle cerebral artery and the basilar artery, there were 680 (23.53%) patients with PAS and 2210 (76.47%) patients without PAS, respectively. After adjusting for potential confounders, the PAS group had a greater initial stroke severity (OR 1.262, 95% CI 1.058 to 1.505; p=0.0097) and a higher risk of ischaemic stroke recurrence at 3 months (OR 2.266, 95% CI 1.631 to 3.149; p<0.0001) and 1 year (OR 2.054, 95% CI 1.561 to 2.702; p<0.0001), as well as composite vascular events at 3 months (OR 2.306, 95% CI 1.674 to 3.178; p<0.0001) and 1 year (OR 1.983, 95% CI 1.530 to 2.570; p<0.0001), compared with the non-PAS group. In both groups, dual antiplatelet therapy was not superior to single antiplatelet therapy in preventing stroke recurrence, composite vascular events and disability. Conclusion: PAS related to significantly higher rates of short-term and long-term stroke recurrence and composite vascular events, suggesting heterogeneous mechanisms in SSSI subgroups. The effectiveness of antiplatelet therapy for SSSI needs further investigation.