A novel risk score to predict deep vein thrombosis after spontaneous intracerebral hemorrhage.

Background and purpose: Studies showed that patients with hemorrhagic stroke are at a higher risk of developing deep vein thrombosis (DVT) than those with ischemic stroke. We aimed to develop a risk score (intracerebral hemorrhage-associated deep vein thrombosis score, ICH-DVT) for predicting in-hospital DVT after ICH. Methods: The ICH-DVT was developed based on the Beijing Registration of Intracerebral Hemorrhage, in which eligible patients were randomly divided into derivation (60%) and internal validation cohorts (40%). External validation was performed using the iMCAS study (In-hospital Medical Complication after Acute Stroke). Independent predictors of in-hospital DVT after ICH were obtained using multivariable logistic regression, and ß-coefficients were used to generate a scoring system of the ICH-DVT. The area under the receiver operating characteristic curve (AUROC) and the Hosmer-Lemeshow goodness-of-fit test were used to assess model discrimination and calibration, respectively. Results: The overall in-hospital DVT after ICH was 6.3%, 6.0%, and 5.7% in the derivation (n = 1,309), internal validation (n = 655), and external validation (n = 314) cohorts, respectively. A 31-point ICH-DVT was developed from the set of independent predictors including age, hematoma volume, subarachnoid extension, pneumonia, gastrointestinal bleeding, and length of hospitalization. The ICH-DVT showed good discrimination (AUROC) in the derivation (0.81; 95%CI = 0.79-0.83), internal validation (0.83, 95%CI = 0.80-0.86), and external validation (0.88; 95%CI = 0.84-0.92) cohorts. The ICH-DVT was well calibrated (Hosmer-Lemeshow test) in the derivation (P = 0.53), internal validation (P = 0.38), and external validation (P = 0.06) cohorts. Conclusion: The ICH-DVT is a valid grading scale for predicting in-hospital DVT after ICH. Further studies on the effect of the ICH-DVT on clinical outcomes after ICH are warranted.

MicroRNA Expression in Circulating Leukocytes and Bioinformatic Analysis of Patients With Moyamoya Disease.

Objective: MicroRNAs (miRNAs) in exosomes had been implicated differentially expressed in patient with moyamoya disease (MMD), but the miRNAs expression in circulating leukocytes remains unclear. This study was investigated on the differential expression of miRNAs in peripheral leukocytes between MMD patients and healthy adults, and among patients with subtypes of MMD. Materials and methods: A total of 30 patients with MMD and 10 healthy adults were enrolled in a stroke center from October 2017 to December 2018. The gene microarray was used to detect the differential expression profiles of miRNA in leukocytes between MMD patients and controls, and the differentially expressed miRNAs were verified by the method of real-time PCR. The Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) were used to explore the key signaling pathways and possible pathogenesis of MMD. Results: The microarray results showed 12 differentially expressed miRNAs in leukocytes of MMD patients compared with controls (fold change >2.0, p < 0.05 and FDR <0.05), of which 8 miRNAs were upregulated (miRNA-142-5p, miRNA-29b-3p, miRNA-424-5p, MiRNA-582-5p, miRNA-6807-5p, miRNA-142-3p, miRNA-340-5p, miRNA-4270), and 4 miRNAs were downregulated (miRNA-144-3p, miRNA-451a, miRNA-486-5p, miRNA-363-3p). The real-time PCR confirmed seven differentially expressed miRNAs (p < 0.05), of which 4 miRNAs (miRNA-29b-3p, miRNA-142-3p, miRNA-340-5p, miRNA-582-5p) were upregulated, and 3 miRNAs (miRNA-363-3p, miRNA-451a and miRNA-486-5p) were downregulated. Both GO and KEGG analysis suggested that the Wnt signaling pathway may be involved in the pathogenesis of MMD. In addition, miRNAs were also differentially expressed among patients with subtypes of MMD. Conclusion: This study indicated that miRNAs are differentially expressed in peripheral leukocytes between MMD patients and healthy adults, and among patients with subtypes of MMD. The Wnt signaling pathway is probably involved in the pathogenesis of MMD.

Comparison of clinical scores for predicting stroke-associated pneumonia after intracerebral hemorrhage (ICH): potential tools for personalized care and clinical trials for ICH.

Background: This study aimed to systematically compare the discrimination and calibration of 5 clinical scores for stroke-associated pneumonia (SAP) after intracerebral hemorrhage (ICH). Methods: We derived a validation cohort from the Beijing Registration of Intracerebral Hemorrhage. SAP was then diagnosed according to the Center for Disease Control and Prevention's criteria for hospital-acquired pneumonia. The area under the receiver operating characteristic curve (AUROC) and Hosmer-Lemeshow goodness-of-fit test were used to assess model discrimination and calibration. Results: A total of 1964 patients were enrolled in the study. The mean age was 56.8±14.4 years, and 67.6% were male. The median National Institutes of Health Stroke Scale (NIHSS) score at admission was 11 [interquartile range (IQR), 3-21], while the median length of stay (LOS) was 16 days (IQR, 8-22 days). A total of 575 (29.2%) patients were diagnosed with in-hospital SAP after ICH. The AUROC of the 5 clinical scores ranged from 0.732 to 0.800. In comparing these scores, we found that the ICH-associated pneumonia score-B (ICH-APS-B 0.800; 95% CI: 0.780-0.820; P<0.001) showed a statistically better discrimination than did the other risk models (all P<0.001). Furthermore, all clinical scores performed better in patients with an LOS >72 h. The ICH-APS-B (0.827; 95% CI: 0.806-0.848; P<0.001) still showed statistically better discrimination than did the other risk models in patients with an LOS longer than 72 hours. The Hosmer-Lemeshow test also revealed that the ICH-APS-B. had the largest Cox and Snell R2 result for in-hospital SAP after ICH. Conclusions: Among the 5 models for predicting SAP after ICH, the ICH-APS-B showed the best predictive performance, suggests it may be a useful tool for implementing the personalized care of patients and conducting clinical trials of SAP after ICH.

Correlation analysis of Trial of Org 10172 in acute stroke treatment classification and National Institutes of Health Stroke Scale score in acute cerebral infarction with risk factors.

OBJECTIVE: The aim of this study was to investigate the correlation between the Trial of Org 10172 in acute stroke treatment classification and the National Institutes of Health Stroke Scale score of acute cerebral infarction as well as acute cerebral infarction's risk factors. METHODS: The clinical data of 3,996 patients with acute cerebral infarction hospitalized in Hebei Renqiu Kangjixintu Hospital from January 2014 to November 2018 were analyzed retrospectively. According to Trial of Org 10172 in acute stroke treatment, they were divided into five groups: arteriosclerosis, cardio cerebral embolism, arterial occlusion, other causes, and unknown causes. Through questionnaire design, routine physical examination, and physical and chemical analysis of fasting venous blood samples, the risk factors were evaluated, and the correlation between Trial of Org 10172 in acute stroke treatment classification and National Institutes of Health Stroke Scale classification was analyzed using multivariate logistic regression. In addition, the relationship between National Institutes of Health Stroke Scale score and risk factors in different groups was compared, and the correlation between Trial of Org 10172 in acute stroke treatment classification and National Institutes of Health Stroke Scale score was analyzed. RESULTS: Multivariate logistic regression analysis showed that diabetes, atrial fibrillation or stroke history, age, and education level were related to Trial of Org 10172 in acute stroke treatment classification. In the National Institutes of Health Stroke Scale comparison, the scores of the cardio cerebral embolism group were significantly higher than those of the other four groups, and patients with diabetes, atrial fibrillation, or stroke history had a high share, especially atrial fibrillation (33.06%). CONCLUSIONS: The nerve function defect is more serious after acute cerebral infarction with cardiogenic cerebral embolism, indicating a poor prognosis.

Correlation analysis of Trial of Org 10172 in acute stroke treatment classification and National Institutes of Health Stroke Scale score in acute cerebral infarction with risk factors

SUMMARY OBJECTIVE: The aim of this study was to investigate the correlation between the Trial of Org 10172 in acute stroke treatment classification and the National Institutes of Health Stroke Scale score of acute cerebral infarction as well as acute cerebral infarction's risk factors. METHODS: The clinical data of 3,996 patients with acute cerebral infarction hospitalized in Hebei Renqiu Kangjixintu Hospital from January 2014 to November 2018 were analyzed retrospectively. According to Trial of Org 10172 in acute stroke treatment, they were divided into five groups: arteriosclerosis, cardio cerebral embolism, arterial occlusion, other causes, and unknown causes. Through questionnaire design, routine physical examination, and physical and chemical analysis of fasting venous blood samples, the risk factors were evaluated, and the correlation between Trial of Org 10172 in acute stroke treatment classification and National Institutes of Health Stroke Scale classification was analyzed using multivariate logistic regression. In addition, the relationship between National Institutes of Health Stroke Scale score and risk factors in different groups was compared, and the correlation between Trial of Org 10172 in acute stroke treatment classification and National Institutes of Health Stroke Scale score was analyzed. RESULTS: Multivariate logistic regression analysis showed that diabetes, atrial fibrillation or stroke history, age, and education level were related to Trial of Org 10172 in acute stroke treatment classification. In the National Institutes of Health Stroke Scale comparison, the scores of the cardio cerebral embolism group were significantly higher than those of the other four groups, and patients with diabetes, atrial fibrillation, or stroke history had a high share, especially atrial fibrillation (33.06%). CONCLUSIONS: The nerve function defect is more serious after acute cerebral infarction with cardiogenic cerebral embolism, indicating a poor prognosis.

Head-to-head comparison of prognostic models of spontaneous intracerebral hemorrhage: tools for personalized care and clinical trial in ICH.

To systematically compare 27 ICH models with regard to mortality and functional outcome at 1-month, 3-month and 1-year after ICH. The validation cohort was derived from the Beijing Registration of Intracerebral Hemorrhage. Poor functional outcome was defined as modified Rankin Scale score (mRS) ≥3 at 1-month, 3-month and 1-year after ICH, respectively. The area under the receiver operating characteristic curve (AUROC) and Hosmer-Lemeshow goodness-of-fit test were used to assess model discrimination and calibration. A total number of 1575 patients were included. The mean age was 57.2 ± 14.3 and 67.2% were male. The median NIHSS score on admission was 11 (IQR: 3-21). For predicting mortality at 3-month after ICH, AUROC of 27 ICH models ranged from 0.604 to 0.856. In pairwise comparison, the ICH-FOS (0.856, 95%CI = 0.835-0.878, P < 0.001) showed statistically better discrimination than other models for mortality at 3-month after ICH (all P < 0.05). For predicting poor functional outcome (mRS≥3) at 3-month after ICH, AUROC of 27 ICH models ranged from 0.602 to 0.880. In pairwise comparison with other prediction models, the ICH-FOS was superior in predicting poor functional outcome at 3-month after ICH (all P < 0.001). The ICH-FOS showed the largest Cox and Snell R-square. Similar results were verified for mortality and poor functional outcome at 1-month and 1-year after ICH. Several risk models are externally validated to be effective for risk stratification and outcome prediction after ICH, especially the ICH-FOS, which would be useful tools for personalized care and clinical trial in ICH.

Higher Cerebral Blood Flow Predicts Early Hematoma Expansion in Patients With Intracerebral Hemorrhage: A Clinical Study.

The early hematoma expansion of intracerebral hemorrhage (ICH) indicates a poor prognosis. This paper studies the relationship between cerebral blood flow (CBF) around the hematoma and hematoma expansion (HE) in the acute stage of intracerebral hemorrhage. A total of 50 patients with supratentorial cerebral hemorrhage were enrolled in this study. They underwent baseline whole-brain CTP within 6 h after intracerebral hemorrhage, and non-contrast CT within 24 h. Absolute hematoma growth and relative hematoma growth were calculated, respectively. A relative growth of Hematoma volume >33% was considered to be hematoma expansion. The Ipsilateral peri-edema CBF and Ipsilateral edema CBF were calculated by CTP maps in patients with and without hematoma expansion, respectively. In this study the incidence of hematoma expansion in the early stage of supratentorial cerebral hemorrhage was 32%; The CBF of the hematoma expansion group was higher than that of the patients without hematoma expansion (23.5 ± 12.5 vs. 15.1 ± 7.4, P = 0.004). After adjusting for age, gender, Symptom onset to NCCT and Baseline hematoma volume, ipsilateral peri-edema CBF was still an independent risk factor for early HE (or = 1.095, 95% CI = 1.01-1.19, P = 0.024). Here, we concluded that higher cerebral blood flow predicts early hematoma expansion in patients with intracerebral hemorrhage.

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.

In-hospital complications affect short-term and long-term mortality in ICH: a prospective cohort study.

BACKGROUND: Medical complications strongly affected the mortality of patients with stroke. However, only limited research has studied the effect of in-hospital medical complications on the mortality of patients with spontaneous intracerebral haemorrhage (ICH) globally. Using the China National Stroke Registry, the effect was prospectively and systematically investigated in patients with spontaneous ICH during their hospitalisation, at 3, 6 and 12 months after disease onset. METHODS: This study collected data on patients over 18 years old with spontaneous ICH from 132 Chinese clinical centres across 32 provinces and four municipalities (Hong Kong included), from September 2007 to August 2008. Data on patient complications, death and other information were acquired through paper-based registry forms. Using multivariable logistic regression, the association of medical complications with stroke outcomes was evaluated. RESULTS: Of 3255 patients with spontaneous ICH, 878 (26.97%) had in-hospital medical complications. In-hospital medical complications were independent risk factors for death during the hospitalisation (adjusted OR 4.41, 95% CI 3.18 to 6.12), at 3 months (adjusted OR 2.18, 95% CI 1.70 to 2.80), 6 months (adjusted OR 1.84, 95% CI 1.45 to 2.34) and 12 months (adjusted OR 1.59, 95% CI 1.26 to 2.01) after spontaneous ICH. CONCLUSION: The results revealed that the short-term and long-term mortality of patients with spontaneous ICH in China was significantly associated with their in-hospital medical complications.

Gastrointestinal bleeding during acute ischaemic stroke hospitalisation increases the risk of stroke recurrence.

OBJECTIVE: Gastrointestinal (GI) bleeding in patients who had a stroke is strongly associated with a higher risk of death and loss of independence. However, it is unknown whether GI bleeding increases risk for recurrence of stroke. In this study, we assess the potential relationship between GI bleeding and stroke recurrence in patients within 12 months of an acute ischaemic stroke (AIS), using the China National Stroke Registry (CNSR). METHODS: This study included 22 216 patients who had an ischaemic stroke included in the CNSR from 2007 to 2008. We analysed baseline patient characteristics, GI bleeding and outcomes of patients who had an AIS, specifically stroke recurrence at 3, 6 and 12 months. We used multivariable logistic regression to evaluate a possible association between GI bleeding and stroke recurrence. RESULTS: Of the 12 415 patients included in our study, 12.3%, 15.5% and 17.7% had a stroke recurrence at 3, 6 and 12 months, respectively. GI bleeding was an independent stroke recurrence risk factor in patients after ischaemic stroke at 3 months (adjusted OR 1.481, 95% CI 1.118 to 1.962), 6 months (adjusted OR 1.448, 95% CI 1.106 to 1.896) and 12 months (adjusted OR 1.350; 95% CI 1.034 to 1.763). CONCLUSION: GI bleeding was associated with the increased risk of stroke recurrence after an AIS.

Clinical and Radiological Outcomes After Revascularization of Hemorrhagic Moyamoya Disease.

Objective: To evaluate clinical and radiological outcomes after revascularization of hemorrhagic moyamoya disease (MMD). Materials and Methods: We retrospectively collected patients with hemorrhagic MMD who received revascularization from January 2011 to June 2018 at a high-volume stroke center. Rebleeding, ischemic stroke, modified Rankin Scale (mRS) and death after revascularization were used to evaluate long-term clinical outcome. Poor neurological outcome was defined as a mRS>2. The changes of original and revascularization collaterals were used to evaluate radiological outcome. The clinical and radiological outcomes between patients with different surgical revascularization were compared. Results: A total of 312 patients (319 hemispheres) were recruited, including 133 hemispheres (41.7%) with indirect revascularization and 186 hemispheres (58.3%) with direct revascularization. In 308 hemispheres with clinical follow-up data, Postoperative rebleeding, ischemic stroke, poor neurological outcome and death occurred in 13.0% (40/308), 2.6% (8/308), 12.0% (37/308), and 6.2% (19/308) of the hemispheres, respectively. The rates of postoperative rebleeding (8.5 vs. 19.1%, P = 0.006) and poor neurological outcome (8.5 vs. 16.8%, P = 0.026) were lower in hemispheres with direct revascularization than those with indirect revascularization. However, there was no statistically significant difference in the rates of postoperative ischemic stroke (1.1 vs. 4.6%, P = 0.129) and death (4.5 vs. 8.4%, P = 0.162) between the two groups. Multivariate logistic regression analysis indicated that the risk of postoperative rebleeding was higher in those with untreated aneurysms, repetitive bleeding episodes, normal perfusion status, and indirect revascularization (P < 0.05). In 78 hemispheres with radiological follow-up data, the regression of moyamoya vessels, anterior choroidal artery (AchA), posterior communicating artery (PcomA) and aneurysms were present in 44.9, 47.4, 25.6, and 11.5% of the hemispheres, respectively. The regression of original collaterals and establishment of revascularization collaterals were more significant in hemispheres with direct revascularization than those with indirect revascularization (P < 0.05). Conclusion: Direct revascularization may be superior to indirect revascularization for prevention of rebleeding and poor neurological outcome in adults with hemorrhagic MMD. The risk of postoperative rebleeding was higher in those with untreated aneurysms, repetitive bleeding episodes, normal perfusion status, and indirect revascularization. The regression of original collaterals and establishment of revascularization collaterals after revascularization were more significant in hemispheres with direct revascularization than those with indirect revascularization.

Uric Acid and Clinical Outcomes Among Intracerebral Hemorrhage Patients: Results From the China Stroke Center Alliance.

Background and Purpose: The effect of uric acid (UA) levels on severity and prognosis of spontaneous intracerebral hemorrhage (ICH) remains controversial. We aimed to explore the association of admission UA levels with stroke severity and outcomes in ICH patients. Materials and Methods: The patients enrolled in this study were from the China Stroke Center Alliance study (CSCA). Patients were divided into four groups (Q1-Q4) according to the quartiles of UA levels at admission. The primary outcome was in-hospital mortality. The secondary outcomes included stroke severity, in-hospital complications, and discharge disposition. Multivariate logistic regression was adopted to explore the association of UA levels with outcomes after ICH. Results: Patients (84,304) with acute ICH were included in the final analysis; the median (interquartile range) of UA was 277 (210, 354) µmol/L. The four groups were defined as follows: Q1 ≤ 210 µmol/L, 210 µmol/L < Q2 ≤ 277 µmol/L, 277 µmol/L < Q3 ≤ 354 µmol/L, Q4 > 354 µmol/L. There was no significant evidence indicating that UA levels were correlated with the discharge disposition and in-hospital mortality after ICH. However, compared to Q1, the patients with higher UA levels had decreased odds of severe stroke (NIHSS ≥ 16) at admission (OR 0.89, 95% CI 0.86-0.92). An L-shaped association was found between UA and severe stroke. Among in-hospital complications, decrease in pneumonia, poor swallow function, gastrointestinal bleeding, and deep vein thrombosis (DVT) were significantly associated with higher UA levels compared to Q1 (P for trend < 0.0001). Conclusions: UA was a protective factor for stroke severity and in-hospital complications such as pneumonia, poor swallow function, gastrointestinal bleeding, and DVT. However, no significant evidence indicated that UA levels were predictive of the discharge disposition and in-hospital mortality after ICH.

The Third China National Stroke Registry (CNSR-III) for patients with acute ischaemic stroke or transient ischaemic attack: design, rationale and baseline patient characteristics.

Background and purpose: Stroke is the leading cause of mortality and disability in China. Precise aetiological classification, imaging and biological markers may predict the prognosis of stroke. The Third China National Stroke Registry (CNSR-III), a nationwide registry of ischaemic stroke or transient ischaemic attack (TIA) in China based on aetiology, imaging and biology markers, will be considered to clarify the pathogenesis and prognostic factors of ischaemic stroke. Methods: Between August 2015 and March 2018, the CNSR-III recruited consecutive patients with ischaemic stroke or TIA from 201 hospitals that cover 22 provinces and four municipalities in China. Clinical data were collected prospectively using an electronic data capture system by face-to-face interviews. Patients were followed for clinical outcomes at 3 months, 6 months and 1-5 year annually. Brain imaging, including brain MRI and CT, were completed at baseline. Blood samples were collected and biomarkers were tested at baseline. Results: A total of 15 166 stroke patients were enrolled, among which 31.7% patients were women with the average age of 62.2±11.3 years. Ischaemic stroke was predominant (93.3%, n=14 146) and 1020 (6.7%) TIAs were enrolled. Conclusions: CNSR-III is a large scale nationwide registry in China. Data from this prospective registry may provide opportunity to evaluate imaging and biomarker prognostic determinants of stroke.

Higher risk of deep vein thrombosis after hemorrhagic stroke than after acute ischemic stroke.

Patients with stroke are at particularly increased risk of developing deep vein thrombosis (DVT) during hospitalization. In this study, we aimed to compare the potential risk of in-hospital DVT by stroke subtypes. This study is based on a prospective cohort (in-hospital medical complication after acute stroke [iMCAS] registry) enrolling patients with acute ischemic stroke (AIS), intracerebral hemorrhage (ICH), and subarachnoid hemorrhage (SAH). In-hospital DVT was diagnosed by clinical manifestations and verified by compression Doppler ultrasound. A logistic regression analysis was performed to assess the association between stroke subtypes and occurrence of DVT. A total number of 1,771 patients were enrolled in the iMCAS. The mean age was 57.1 ± 12.9 years, and 27.5% were female patients. The median length of stay was 14 days (interquartile range [IQR], 11-16). The median National Institutes of Health Stroke Scale score on admission for patients with AIS, ICH, and SAH was 4 (IQR: 2-8), 4 (IQR:1-10), and 0 (IQR:0-0), respectively. In-hospital DVT after AIS, ICH, and SAH was 1.9%, 5.7%, and 7.9%, respectively. The median time from stroke onset to DVT formation after AIS, ICH, and SAH was 10.5 days (IQR: 3.8-14.5), 7.5 days (IQR:4.0-9.5), and 7.0 days (IQR:5.0-12.5), respectively. After adjusting for potential confounders, patients with ICH (odds ratio = 7.350; 95% confidence interval = 2.411-22.13; P < .001) and SAH (odds ratio = 11.92; 95% confidence interval = 5.192-27.38; P < .001) had significantly higher risk of in-hospital DVT than those patients with AIS. In conclusion, patients with hemorrhagic stroke (ICH and SAH) have significantly higher risk of in-hospital DVT than patients with AIS. Further studies on pathophysiologic mechanisms are warranted.

Reduced Ischemic Lesion Growth with Heparin in Acute Ischemic Stroke.

OBJECTIVE: The role of heparin in acute ischemic stroke is controversial. We investigated the effect of heparin on ischemic lesion growth. METHODS: Data were analyzed on nonthrombolyzed ischemic stroke patients in whom diffusion-weighted imaging (DWI)/perfusion-weighted imaging (PWI) MRI was performed less than 12 hours of last known well and showed a PWI-DWI lesion mismatch, and who underwent follow-up neuroimaging at least 4 days after admission. Lesion growth was assessed by (1) absolute lesion growth and (2) percentage mismatch lost (PML). Univariate and multivariate regression analysis, and propensity score matching, were used to determine the effects of heparin on ischemic lesion growth. RESULTS: Of the 113 patients meeting study criteria, 59 received heparin within 24 hours. Heparin use was associated with ∼5-fold reductions in PML (3.5% versus 19.2%, P = .002) and absolute lesion growth (4.7 versus 20.5 mL, P = .009). In multivariate regression models, heparin independently predicted reduced PML (P = .04) and absolute lesion growth (P = .04) in the entire cohort, and in multiple subgroups (patients with and without proximal artery occlusion; DWI volume greater than 5 mL; cardio-embolic mechanism; DEFUSE-3 target mismatch). In propensity score matching analysis where patients were matched by admission NIHSS, DWI volume and proximal artery occlusion, heparin remained an independent predictor of PML (P = .048) and tended to predict absolute lesion growth (P = .06). Heparin treatment did not predict functional outcome at discharge or 90 days. CONCLUSION: Early heparin treatment in acute ischemic stroke patients with PWI-DWI mismatch attenuates ischemic lesion growth. Clinical trials with careful patient selection are warranted to investigate the potential ischemic protective effects of heparin.

ECAS progression score: a web-based model to predict progression of extracranial carotid artery stenosis.

BACKGROUND AND PURPOSE: To develop and validate a risk model (Extracranial Carotid Artery Stenosis progression score, ECAS-PS) and to predict risk of ECAS progression. METHODS: The ECAS-PS was developed based on the Renqiu Stroke Screening Study (RSSS), in which eligible participants were randomly divided into derivation (60%) and validation (40%) cohorts. ECAS at baseline and follow-up was diagosed by carotid duplex ultrasound according to the published criteria. ECAS progression was defined as an increase in ECAS to≥50% for those with a baseline of <50% or as an increase to a higher category of stenosis if the baseline stenosis was ≥50%. Independent predictors of ECAS progression were obtained using multivariable logistic regression. The area under the receiver operating characteristic curve (AUROC) and the Hosmer-Lemeshow test were used to assess model discrimination and calibration. RESULTS: A total of 4111 participants were included and the mean age was 64.3. A total number of 29 (0.7%), 24 (0.6%) and 48 (1.2%) patients progressed during 2-year follow-up for left, right and bilateral (either left or right) carotid artery, respectively. The ECAS-PS was developed from a set of predictors of ECAS progression. The ECAS-PS demonstrated good discrimination in both the derivation and validation cohorts (AUROC range: 0.824-0.917). The Hosmer-Lemeshow tests of ECAS progression score were not significant in the derivation and validation cohorts (all P > 0.05). CONCLUSION: The ECAS progression score is a valid model for predicting the risk of ECAS progression. Further validation of the ECAS-PS in different populations and larger samples is warranted.

ECAS score: a web-based risk model to predict moderate and severe extracranial carotid artery stenosis.

Background and purpose To develop and validate a risk model (Extracranial Carotid Artery Stenosis score, ECAS score) to predict moderate and severe ECAS. Furthermore, we compared discrimination of the ECAS score and three existing models with regard to both moderate and severe ECAS. Methods The ECAS score was developed based on the Renqiu Stroke Screening Study (RSSS), in which eligible patients were randomly divided into derivation (60%) and validation (40%) cohorts. ECAS was diagnosed by carotid duplex ultrasound according to the published criteria. Independent predictors of moderate (≥50%) and severe (≥70%) ECAS were obtained using multivariable logistic regression. The area under the receiver operating characteristic curve (AUROC) and the Hosmer-Lemeshow test were used to assess model discrimination and calibration. Results A total of 5010 participants were included and the mean age was 64.3. The proportion of ECAS of < 50%, 50-69%, 70-99% and occlusion was 4.4, 0.5, 0.4, and 0.4%, respectively. The ECAS score was developed from sets of predictors of moderate and severe ECAS. The ECAS score demonstrated good discrimination in the derivation and validation cohorts (AUROC range: 0.785-0.846). The Hosmer-Lemeshow tests of ECAS score for moderate and severe ECAS were not significant in the derivation and validation cohorts (all P > 0.05). When compared to the three existing models, the ECAS score showed significantly better discrimination for both moderate and severe ECAS (all P < 0.001). Conclusion The ECAS score is a valid model for predicting moderate and severe ECAS. Further validation of the ECAS score in different populations and larger samples is warranted.

Current smoking is associated with extracranial carotid atherosclerotic stenosis but not with intracranial large artery disease.

BACKGROUND: Accumulating evidence has shown that cigarette smoking is an important risk factor for ischemic stroke. However, it is not clear about the potential mechanisms through which cigarette smoking affects stroke risk. In the study, we aimed to investigate the relationship between cigarette smoking and the occurrence of extracranial (ECAS) and intracranial atherosclerotic stenosis (ICAS). METHODS: We analyzed patients enrolled in the Chinese intracranial atherosclerosis (CICAS), which was a prospective, multicenter, hospital-based cohort study. Smoking status was classified into never, former and current smoking. For those patients with current smoking, data on time duration (year) and extent (the number of cigarette smoked per day) was recorded and pack year of smoking was calculated. ICAS was evaluated with 3-dimentional time-of-flight MRA and ECAS was evaluated with cervical ultrasonography or contrast-enhanced MRA. Multivariable Logistic regression was performed to identify the association between smoking status and the occurrence of ECAS and ICAS. RESULTS: A total of 2656 patients (92.7%) of acute ischemic stroke and 208 (7.3%) of transient ischemic attack were analyzed. The mean age was 61.9 ± 11.2 and 67.8% were male. There were 141 (4.9%) patients had only ECAS, 1074 (37.5%) had only ICAS, and 261 (9.1%) had both ECAS and ICAS. Current smoking was significantly associated with the occurrence of ECAS (adjusted OR = 1.47, 95% CI = 1.09-1.99, P < 0.01). In addition, with 1 year of smoking increment, the risk of ECAS increased by 1.1% (adjusted OR = 1.011; 95% CI = 1.003-1.019; P = 0.005); with one cigarette smoked per day increment, the risk of ECAS increased by 1.0% (adjusted OR = 1.010; 95% CI = 1.001-1.020; P = 0.03); and with one pack year of smoking increment, the risk of ECAS increased by 0.7% (adjusted OR = 1.007; 95% CI = 1.002-1.012; P < 0.01). However, no significant association was found between smoking status and the occurrence of ICAS. CONCLUSION: A dose-response relationship was identified between cigarette smoking and the occurrence of ECAS, but not ICAS. Further studies on molecular mechanisms were warranted.