Independent Predictive Value of Elevated YKL-40 in Ischemic Stroke Prognosis: Findings from a Nationwide Stroke Registry.

INTRODUCTION: Elevated circulatory concentrations of YKL-40 have been reported in patients with ischemic stroke. This study further investigated the association of plasma YKL-40 concentrations at admission and short, long-term prognosis after ischemic stroke. METHODS: Based on a prospective, nationwide multicenter registry focusing consecutive patients of ischemic stroke and transient ischemic attack, plasma YKL-40 levels were detected by enzyme-linked immunosorbent assay at admission, and patients were stratified into percentile according to the plasma YKL-40 concentrations. The multivariate Cox or logistic regression model was used to investigate the association of YKL-40 concentration with death and functional outcomes at 3 months, 6 months, and 12 months after ischemic stroke, with potential confounders adjusted. RESULTS: A total of 8,006 first-ever ischemic stroke patients, with the age of 61.7 ± 11.5, were included in this study. The mortality of 0-33%, 34-66%, 67-90%, and 91-100% groups at 12 months follow-up was 0.9%, 2.2%, 4.4%, and 9.4%, respectively (p < 0.0001), and the modified Rankin Scale 3-6 ratio was 6.8%, 10.5%, 15.7%, and 24.0%, respectively (p < 0.0001). In the multivariate regression, after adjusting for potential confounders, 91-100% group had higher risk of death (hazard ratio 2.99, 95% confidence interval 1.75-5.11)and modified Rankin Scale 3-6 (odds ratio 1.42, 95% confidence interval 1.08-1.88) at 12 months since onset of ischemic stroke compared to the 0-33% group. CONCLUSIONS: The elevated YKL-40 at admission can potentially help predict death, functional prognosis after ischemic stroke, which may help further studies to explore the potential physiological and pathological mechanism including the effects of vulnerable plaque and collateral circulation.

Association between haemoglobin A1c and cerebral microbleeds in community-based stroke-free individuals: A cross-sectional study.

AIMS: The association between haemoglobin A1c (HbA1c) and cerebral microbleeds (CMBs) remains unclear. We aimed to investigate the association between HbA1c and CMBs in community-based individuals without stroke or transient ischaemic attack (TIA) and whether the association differs between individuals with and without diabetes mellitus (DM). MATERIALS AND METHODS: All individuals were recruited from a community in Beijing, China, from January 2015 to September 2019. All individuals completed a questionnaire and underwent blood tests and brain magnetic resonance imaging. A susceptibility-weighted imaging sequence was acquired to detect CMBs, which were defined as small, round and low-signal lesions with <10 mm diameter. The association between HbA1c and CMBs was analysed using multivariable logistic regression adjusted for demographics, medical history and blood sample test results. Subgroup analyses stratified by history of DM were performed. RESULTS: Of 544 recruited individuals, 119 (21.88%) had CMBs. HbA1c was independently associated with CMBs (odds ratio [OR], 1.51; 95% confidence interval [CI], 1.03-2.22). In 87 individuals with DM, multivariable logistic analysis showed that HbA1c was significantly associated with CMBs (OR, 1.67; 95% CI, 1.04-2.69), whereas in individuals without DM, no significant association was observed between HbA1c and CMBs (OR, 1.07; 95% CI, 0.50-2.30). CONCLUSIONS: HbA1c was associated with CMBs in individuals without stroke or TIA, particularly in individuals with DM, suggesting that the status of glycaemic control warrants attention for the prevention of CMBs. It would be beneficial to manage HbA1c specifically to control the risk of CMBs, especially in individuals with DM.

Carotid atherosclerotic plaque predicts progression of intracranial artery atherosclerosis: A MR imaging-based community cohort study.

PURPOSE: Intracranial artery atherosclerosis (ICAS) progression is associated with stroke. However, the association of carotid plaque with ICAS progression among stroke-free participants is still unclear. This study aimed to evaluate the association between carotid plaque and ICAS progression in stroke-free participants. METHOD: Stroke-free participants were recruited from a community-based cohort study. All participants underwent questionnaire interviews, blood tests, and high-resolution vessel wall magnetic resonance (MR) imaging at baseline and follow-up for around three years. The atherosclerotic plaque was defined as eccentric wall thickening on MR imaging. The presence, location, total number, and burden (maximum wall thickness, length, and stenosis) of carotid and intracranial plaque were evaluated. ICAS progression was defined as the number increased or plaque burden (maximum wall thickness, length, or stenosis increase) increased by ≥ 20 %. The association between carotid plaque and ICAS progression was evaluated using multivariable logistic regression. RESULTS: Of the 312 participants (mean age at baseline: 59.85 ± 13.04 years; 136 males) who completed baseline and follow-up studies with a mean time interval of 3.15 ± 0.59 years, 85 (27.24 %) had progression of ICAS during follow-up. At least one carotid plaque was detected at baseline in 167 (53.53 %) participants. In the multivariable logistic analysis, carotid plaque was a significant predictor for the progression of ICAS (odds ratio, 2.04; 95 % confidence interval, 1.06-3.92; P = 0.032). CONCLUSIONS: Carotid plaque is associated with intracranial artery atherosclerosis progression in stroke-free population. Our findings suggest that carotid plaque may be an effective predictor for intracranial artery atherosclerosis progression.

Association of the coexistence of intracranial atherosclerotic disease and cerebral small vessel disease with acute ischemic stroke.

PURPOSE: Whether the coexistence of intracranial atherosclerotic disease (ICAD) and cerebral small vessel disease (CSVD) is an effective indicator for acute ischemic stroke (AIS) is unclear. This study aimed to investigate the association of coexistence of ICAD and CSVD with AIS. METHODS: Patients with symptomatic ICAD were recruited from a multicenter study. All patients underwent intracranial artery vessel wall and brain magnetic resonance (MR) imaging at 3.0 T. The characteristics of T1 hyperintensity, plaque enhancement, and surface irregularity of the ICAD were assessed. The types of CSVD including enlarged perivascular space, white matter hyperintensity and lacune, and AIS were also analyzed. Logistic regressions were used to evaluate the associations of coexistence of ICAD and CSVD with AIS. RESULTS: Of 122 recruited patients (mean age: 56.69 ± 11.07 years; 70 males), 69 (56.56%) had AIS. Coexistence of ICAD and CSVD was more likely found in patients with AIS compared to those without AIS (all P < 0.05). After full adjustment, coexistences of surface irregularity and EPVS (odds ratio [OR], 12.770; 95% confidence interval [CI], 2.163-75.380; P = 0.005), surface irregularity and lacune (OR, 8.450; 95% CI, 2.028-35.213; P = 0.003), enhancement and lacune (OR, 13.888; 95% CI, 2.888-66.786; P = 0.001), surface irregularity and WMH (OR, 3.692; 95% CI, 1.264-10.786; P = 0.017), and enhancement and WMH (OR, 7.899; 95% CI, 2.357-26.475; P = 0.001) were significantly associated with AIS. CONCLUSION: Coexistence of intracranial atherosclerosis and cerebral small vessel disease might be a stronger indicator for acute ischemic stroke than each alone.

Associations between cerebral blood flow and progression of white matter hyperintensity in community-dwelling adults: a longitudinal cohort study.

Background: White matter hyperintensity (WMH) is prevalent in elderly populations. Ischemia is characterized by a decline in cerebral blood flow (CBF) and may play a key role in the pathogenesis of WMH. However, the association between CBF reduction and WMH progression remains controversial. This study aimed to investigate the association between CBF and the progression of WMH at a 2-year follow-up of community-based, asymptomatic adults in a longitudinal cohort study across the lifespan. Methods: Asymptomatic adults who participated in a community-based study were recruited and underwent brain structural and perfusion magnetic resonance imaging (MRI) at baseline and at a 2-year follow-up visit. The CBF was measured on pseudo-continuous arterial spin-labeling (pCASL) MRI. The WMH was evaluated on T2-weighted fluid-attenuated inversion recovery (T2-FLAIR) images. Tissue segmentation was conducted on T1-weighted (T1W) images to derive binary masks of gray matter and normal-appearing white matter. Linear mixed effect models were conducted to analyze the cross-sectional and longitudinal associations between CBF and WMH. Results: A total of 229 adults (mean age 57.3±12.6 years; 94 males) were enrolled at baseline, among whom 84 participants (mean age 54.1±11.9 years; 41 males) completed a follow-up visit with a mean time interval of 2.77±0.44 years. At baseline, there was a decreasing trend in gray matter (GM) CBF with an increase of WMH burden (P=0.063), but this association was attenuated after adjusting for age (P=0.362). In the longitudinal analysis, baseline WMH volume was significantly associated with the reduction of perfusion in GM [coefficient =-1.96, 95% confidence interval (CI): -3.25 to -0.67; P=0.004] and normal appearing white matter (coefficient =-0.99, 95% CI: -1.66 to -0.31; P=0.005) during follow-up. On the contrary, neither baseline CBF in GM (P=0.888) nor normal appearing white matter (P=0.850) was associated with WMH progression. In addition, CBF changes within WMH were significantly associated with both baseline (coefficient =-0.014, 95% CI: -0.025 to -0.003; P=0.017) and progression (coefficient =-1.01, 95% CI: -1.81 to -0.20; P=0.015) of WMH volume. Conclusions: A WMH burden was not found to be directly associated with cortex perfusion at baseline due to the effects of age on both CBF and WMH. However, baseline WMH volume could predict the reduction of perfusion.

Segmentation and differentiation of periventricular and deep white matter hyperintensities in 2D T2-FLAIR MRI based on a cascade U-net.

Background: White matter hyperintensities (WMHs) are a subtype of cerebral small vessel disease and can be divided into periventricular WMHs (pvWMHs) and deep WMHs (dWMHs). pvWMHs and dWMHs were proved to be determined by different etiologies. This study aimed to develop a 2D Cascade U-net (Cascade U) for the segmentation and differentiation of pvWMHs and dWMHs on 2D T2-FLAIR images. Methods: A total of 253 subjects were recruited in the present study. All subjects underwent 2D T2-FLAIR scan on a 3.0 Tesla MR scanner. Both contours of pvWMHs and dWMHs were manually delineated by the observers and considered as the gold standard. Fazekas scale was used to evaluate the burdens of pvWMHs and dWMHs, respectively. Cascade U consisted of a segmentation U-net and a differentiation U-net and was trained with a combined loss function. The performance of Cascade U was compared with two other U-net models (Pipeline U and Separate U). Dice similarity coefficient (DSC), Matthews correlation coefficient (MCC), precision, and recall were used to evaluate the performances of all models. The linear correlations between WMHs volume (WMHV) measured by all models and the gold standard were also conducted. Results: Compared with other models, Cascade U exhibited a better performance on WMHs segmentation and pvWMHs identification. Cascade U achieved DSC values of 0.605 ± 0.135, 0.517 ± 0.263, and 0.510 ± 0.241 and MCC values of 0.617 ± 0.122, 0.526 ± 0.263, and 0.522 ± 0.243 on the segmentation of total WMHs, pvWMHs, and dWMHs, respectively. Cascade U exhibited strong correlations with the gold standard on measuring WMHV (R2 = 0.954, p < 0.001), pvWMHV (R2 = 0.933, p < 0.001), and dWMHV (R2 = 0.918, p < 0.001). A significant correlation was found on lesion volume between Cascade U and gold standard (r > 0.510, p < 0.001). Conclusion: Cascade U showed competitive results in segmentation and differentiation of pvWMHs and dWMHs on 2D T2-FLAIR images, indicating potential feasibility in precisely evaluating the burdens of WMHs.

Risk Factors for Asymptomatic and Symptomatic Intracranial Atherosclerosis Determined by Magnetic Resonance Vessel Wall Imaging in Chinese Population: A Case-Control Study.

BACKGROUND AND PURPOSE: The association between risk factors and intracranial atherosclerosis disease (ICAD) determined by magnetic resonance (MR) vessel wall imaging in Chinese population has not been investigated. The aim of this study was to investigate the associations of conventional vascular risk factors with asymptomatic and symptomatic ICAD using MR vessel wall imaging in Chinese population. METHODS: The study population was recruited from two cohort studies of ICASMAP and CAMERA comprised 104 symptomatic ICAD subjects (57.1 ± 11.1 years; 35.6% females), 51 asymptomatic ICAD subjects (70.1 ± 8.4 years; 50.0% females) and 418 controls (58.0 ± 13.3 years; 61.0% females) defined as asymptomatic subjects without ICAD on MR vessel wall imaging. We compared the vascular risk factors between the three groups using a multivariate logistic regression analysis. RESULTS: Compared with controls, there was a significant positive association between age (OR: 1.07, 95% CI: 1.03-1.10, p < 0.001) and hypertension (OR: 3.03, 95% CI: 1.45-6.36, p = 0.003) and asymptomatic ICAD. There was a positive association of smoking (OR: 3.41, 95% CI: 1.57-7.42, p = 0.001), hypertension (OR: 7.43, 95% CI: 3.81-14.49, p < 0.001) and diabetes (OR: 3.54, 95% CI: 1.93-6.49, p < 0.001) and an inverse association of high-density lipoprotein (HDL) (p < 0.017) with symptomatic ICAD. Compared to asymptomatic ICAD, there was a significant inverse association of age (OR: 0.86, 95% CI: 0.81-0.92, p < 0.001) and HDL (p < 0.001) with symptomatic ICAD. CONCLUSION: Old age and hypertension are associated with asymptomatic ICAD and smoking, hypertension, diabetes and lower HDL are associated with an increased risk of symptomatic ICAD in Chinese population. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT03417063.

Association between antiplatelet medication and cerebral microbleeds in stroke-free population.

BACKGROUND: Cerebral microbleeds (CMBs) may increase the risk of future intracerebral hemorrhage and ischemic stroke. However, It is unclear whether antiplatelet medication is associated with CMBs. This study aimed to investigate the association between antiplatelet medication and CMBs in a community-based stroke-free population. METHODS: In this cross-sectional study, stroke-free participants aged 18-85 years were recruited from a community in Beijing, China. Demographic, clinical, and antiplatelet medication data were collected through a questionnaire, and all participants underwent blood tests and brain magnetic resonance imaging at 3.0T. The presence, count, and location of CMBs were evaluated using susceptibility-weighted imaging. The association between antiplatelet medication and the presence of CMBs was analyzed using multivariable logistic regression. The associations between antiplatelet medication and CMBs by location (lobar, deep brain or infratentorial, and mixed regions) were also analyzed using multinomial logistic regression. A linear regression analysis was conducted to determine the association between antiplatelet medication and the log-transformed number of CMBs. RESULTS: Of the 544 participants (mean age: 58.65 ± 13.66 years, 217 males), 119 participants (21.88%) had CMBs, and 64 participants (11.76%) used antiplatelet medication. Antiplatelet medication was found to be associated with CMBs at any location [odds ratio (OR) = 2.39, 95% CI: 1.24-4.58] and lobar region (OR = 2.83, 95% CI: 1.36-5.86), but not with the number of CMBs (ß = 0.14, 95% CI: -0.21-0.48). Among antiplatelet medications, aspirin use was found to be associated with any CMB (OR = 3.17, 95% CI: 1.49-6.72) and lobar CMBs (OR = 3.61, 95% CI: 1.57-8.26). CONCLUSIONS: Antiplatelet medication was associated with CMBs in stroke-free participants, particularly lobar CMBs. Among antiplatelet medications, aspirin use was associated with any CMB and lobar CMBs. Our findings suggest that it might be essential to optimize the management of antiplatelet medication in the stroke-free population with a higher burden of vascular risk factors to reduce the potential risk of CMBs.

Association between short-term exposure to ambient air pollution and hospital admissions for transient ischemic attacks in Beijing, China.

Numerous studies have examined the associations between air pollution and stroke. However, little is known about the associations between air pollution and transient ischemic attack (TIA). In this study, we aimed to conduct a time-series study to systematically examine the associations between hospital admissions for TIA and air pollutants. Admissions for TIA (ICD-10: G45) from 1 January 2014 to 31 December 2016 were identified based on the primary diagnosis from 134 hospitals in Beijing, China. Hourly measurements of air pollutants were obtained from the National Air Pollution Monitoring System. Generalized additive models with quasi-Poisson regression were used to determine the associations for each pollutant. Additionally, stratified analysis was implemented to examine whether age, gender, temperature, and season were the potential effect modifiers. Restricted cubic spline was applied to investigate the exposure-response curve. In total, 109,975 hospital admissions for TIA were included. The positive associations were detected between PM2.5, PM10, SO2, NO2, and CO and hospital admissions for TIA. The effects of PM2.5 and PM10 in men are stronger than in women. Additionally, the effects of PM2.5, PM10, SO2, and O3 are more pronounced on warm days than cool days. From exposure-response curves, we observe a nearly linear relationship for PM2.5, PM10, CO, and NO2. Further studies are needed to verify the association. This research contributes evidence on the association between air pollution and admissions for TIA in the low- and middle-income countries and may promote related public health policy development.

Stroke History is an Independent Risk Factor for Poor Prognosis in Ischemic Stroke Patients: Results from a Large Nationwide Stroke Registry.

BACKGROUND: There is some controversy whether stroke history is an independent risk factor for poor prognosis of stroke or not. This study aimed to investigate the difference of mortality, disability and recurrent rate of ischemic stroke patients without and with stroke history, as well as to explore the effect of stroke history on stroke prognosis. METHODS: We analyzed patients with ischemic stroke enrolled in the China National Stroke Registry which was a nationwide, multicenter, and prospective registry of consecutive patients with acute cerebrovascular events from 2007 to 2008. Multivariable logistic regression was performed to assess the risk of worse prognosis of stroke history in patients with ischemic stroke. RESULTS: A total of 8181(65.9%) patients without stroke history and 4234(34.1%) patients with stroke history were enrolled in the study. The mortality, recurrence, modified Rankin Scale (mRS) 3-6 rate was 11.4%, 14.7% and 28.5% respectively at 1 year for patients without stroke history, which was significantly lower than that of 17.3%, 23.6%, 42.1% in patients with stroke history, respectively. Multivariable analysis showed that patients with stroke history had higher risk of death [odds ratio (OR) 1.34,95% confidence interval (CI) 1.17-1.54], recurrence (OR 1.47, 95 % CI 1.31-1.65) and mRS 3-6 (OR 1.49,95% CI 1.34-1.66) at 1 year. CONCLUSION: After adjusting for the potential confounders, stroke history was still an independent risk factor for poor prognosis of ischemic stroke, which further emphasizes the importance of secondary prevention of ischemic stroke. The specific causes of poor prognosis in patients with history of stroke need to be furtherly investigated.

Worldwide 1-month case fatality of ischaemic stroke and the temporal trend.

BACKGROUND: The 1-month case fatality of ischaemic stroke is an essential epidemiological metric. Whereas the case fatality after ischaemic stroke and the temporal trend is uncertain. We aimed to estimate the 1-month case fatality of ischaemic stroke and its temporal trend, as well as its regional variation. METHODS: We searched PubMed and Embase to identify the studies for 1-month case fatality of ischaemic stroke . The population-based studies were included. Two investigators extracted the data and assessed the quality independently. One-month case fatality of ischaemic stroke was estimated using a random effects model. The temporal trend was evaluated using a mixed-effect meta-regression model. RESULTS: A total of 59 articles with 77 time periods were included. The worldwide 1-month case fatality of ischaemic stroke was 13.5% (95% CI 12.3% to 14.7%). The case fatality was 10.8% (95% CI 8.3% to 13.5%) in Asia, 14.2% (95% CI 12.6% to 15.9%) in Europe, 14.0% (95% CI 11.2% to 17.1%) in South America and Caribbean, 14.0% (95% CI 9.5% to 19.1%) in North America and 12.5% (95% CI 11.1% to 13.9%) in Australia and New Zealand. Overall, there was a non-significant decrease of 0.1% per year in case fatality. It decreased significantly in Europe (-0.2% annually, 95% CI -0.4% to -0.01%) and North America (-0.2% annually, 95% CI -0.4% to -0.04%), increased significantly in Australia and New Zealand (0.2% annually, 95% CI 0.1% to 0.4%), while no evidence of change in other regions. CONCLUSION: The 1-month case fatality of ischaemic stroke and its temporal trend were divergent across regions. Further studies are needed to address the reason of the regional difference, which will be helpful to guide the effort of reducing stroke burden.

Characteristics of Non-linguistic Cognitive Impairment in Post-stroke Aphasia Patients.

Background: Non-linguistic cognitive training has been suggested to improve the communication skills of patients with post-stroke aphasia (PSA). However, the association between language and non-linguistic cognitive functions is not fully understood. In this study, we used the Loewenstein Occupational Therapy Cognitive Assessment (LOTCA) to evaluate the characteristics of non-linguistic cognitive impairments in Chinese PSA patients. Methods: A total of 86 stroke patients were recruited in this study. Language and non-linguistic cognitive impairments were evaluated by the Western Aphasia Battery (WAB) and LOTCA, respectively. The patients were divided into two groups (PSA and non-PSA), and the Chinese norm (the data came from 44 Chinese individuals without neurological disorders in a previous study) was used as the control group. The LOTCA scores were compared among the three groups. Patients in the PSA group were subdivided into the fluent aphasia group (FAG) and the non-FAG according to the Chinese aphasia fluency characteristic scale. The LOTCA scores were also compared between the PSA subdivisions. Potential confounders were adjusted in the analysis of covariance. Partial correlation analysis between the subscores of WAB and LOTCA was also performed. Results: The total LOTCA scores in the PSA group (75.11 ± 17.08) were significantly lower compared with scores in the non-PSA (96.80 ± 7.75, P < 0.001) and the control group (97.65 ± 16.24, P < 0.001). The PSA group also had lower orientation, visual perception (VP), spatial perception (SP), visuomotor organization, thinking operation, and attention scores. The total LOTCA, orientation, VP, SP, and MP scores were lower in the non-FAG (69.24 ± 18.06, 8.62 ± 5.09, 12.76 ± 2.47, 7.48 ± 3.01, and 9.62 ± 2.25, respectively) compared with the FAG (80.36 ± 14.07, 12.14 ± 3.99, 14.09 ± 1.93, 9.68 ± 3.01, 10.55 ± 1.63, respectively, P's < 0.05). The aphasia quotient was positively correlated with the total score of LOTCA and scores of orientation, VP, SP, and MP (r = 0.710, 0.744, 0.565, 0.597, and 0.616; P < 0.001). Conclusion: Compared with stroke patients without aphasia, patients with PSA often have more extensive and serious non-linguistic cognitive impairments. Patients with non-fluent aphasia often present with serious cognitive impairments than those with fluent aphasia, especially the impairments of orientation and SP. Non-linguistic cognitive impairments correlate with language impairments in aphasia.