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Low LDL-C level and intracranial haemorrhage risk after ischaemic stroke: a prospective cohort study. 低LDL-C水平与缺血性脑卒中后颅内出血风险:一项前瞻性队列研究
IF 5.9 1区 医学 Q1 CLINICAL NEUROLOGY Pub Date : 2023-04-01 DOI: 10.1136/svn-2022-001612
Jie Xu, Zimo Chen, Meng Wang, Jinglin Mo, Jing Jing, Gulbahram Yalkun, Liye Dai, Xia Meng, Hao Li, Zixiao Li, Yongjun Wang

Background and purpose: The Treat Stroke to Target trial has confirmed the benefit of targeting low-density lipoprotein cholesterol (LDL-C) of <1.8 mmol/L in patients who had an ischaemic stroke (IS). However, haemorrhagic risk brought by this target level (<1.8 mmol/L) or even lower level (<1.4 mmol/L) of LDL-C should also be concerned. In this study, we aimed to demonstrate whether low LDL-C could increase the intracranial haemorrhage risk following IS.

Methods: Patients who had an IS from China Stroke Center Alliance programme with complete baseline information were prospectively enrolled. 793 572 patients who had an IS were categorised into 6 groups according to LDL-C level (<1.40 mmol/L, 1.40-1.79 mmol/L, 1.80-2.59 mmol/L, 2.60-2.99 mmol/L, 3.00-4.89 mmol/L, ≥4.90 mmol/L). The study outcome was defined as intracranial haemorrhage identified during hospitalisation. Logistic regression model was used to examine the association between different LDL-C levels and risk of intracranial haemorrhage.

Results: Compared with patients of LDL-C=1.80-2.59 mmol/L, both subgroups of LDL-C<1.40 mmol/L and LDL-C=1.40-1.79 mmol/L showed significantly higher risk of intracranial haemorrhage (OR=1.26, 95% CI=1.18 to 1.35; OR=1.22, 95% CI=1.14 to 1.30, respectively). Interaction effect was found to exist between the subgroups of intravenous thrombolytic therapy (p=0.04), rather than the subgroups of age, sex and body mass index. Moreover, the sensitivity analyses indicated that even patients who had an IS with minor stroke still suffered from the increased intracranial haemorrhage risk related to low LDL-C level.

Conclusions: Among patients who had an IS, the low LDL-C level (<1.4 mmol/L or <1.8 mmol/L) at baseline is associated with increased risk of intracranial haemorrhage during acute stage. While actively lowering LDL-C level for patients who had an IS, clinicians should also concern about the haemorrhagic risk associated with low LDL-C level.

背景和目的:卒中靶向治疗试验证实了靶向治疗低密度脂蛋白胆固醇(LDL-C)的益处。方法:前瞻性纳入来自中国卒中中心联盟项目的具有完整基线信息的IS患者。将793 572例IS患者根据LDL-C水平分为6组(结果:与LDL-C=1.80 ~ 2.59 mmol/L的患者相比,两个亚组LDL-C水平均较低)。
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引用次数: 0
Associations of HDL-C/LDL-C with myocardial infarction, all-cause mortality, haemorrhagic stroke and ischaemic stroke: a longitudinal study based on 384 093 participants from the UK Biobank. HDL-C/LDL-C与心肌梗死、全因死亡率、出血性卒中和缺血性卒中的关系:一项基于英国生物银行384 093名参与者的纵向研究。
IF 5.9 1区 医学 Q1 CLINICAL NEUROLOGY Pub Date : 2023-04-01 DOI: 10.1136/svn-2022-001668
Shiqi Yuan, Xiaxuan Huang, Wen Ma, Rui Yang, Fengshuo Xu, Didi Han, Tao Huang, MIn Peng, Anding Xu, Jun Lyu

Objective: To explore the correlations of high-density lipoprotein cholesterol (HDL-C)/low-density lipoprotein cholesterol (LDL-C) with myocardial infarction (MI), all-cause mortality, haemorrhagic stroke and ischaemic stroke, as well as the joint association of genetic susceptibility and HDL-C/LDL-C with the MI risk.

Methods and results: This study selected 384 093 participants from the UK Biobank (UKB) database. First, restricted cubic splines indicated non-linear associations of HDL-C/LDL-C with MI, ischaemic stroke and all-cause mortality. Second, a Cox proportional-hazards model indicated that compared with HDL-C/LDL-C=0.4-0.6, HDL-C/LDL-C<0.4 and >0.6 were correlated with all-cause mortality (HR=0.97 for HDL-C/LDL-C<0.4, 95% CI=0.939 to 0.999, p<0.05; HR=1.21 for HDL-C/LDL-C>0.6, 95% CI=1.16 to 1.26, p<0.001) after full multivariable adjustment. HDL-C/LDL-C<0.4 was correlated with a higher MI risk (HR=1.36, 95% CI=1.28 to 1.44, p<0.05) and ischaemic stroke (HR=1.12, 95% CI=1.02 to 1.22, p<0.05) after full multivariable adjustment. HDL-C/LDL-C>0.6 was associated with higher risk haemorrhagic stroke risk after full multivariable adjustment (HR=1.25, 95% CI=1.03 to 1.52, p<0.05). Third, after calculating the coronary heart disease Genetic Risk Score (CHD-GRS) of each participant, the Cox proportional-hazards model indicated that compared with low CHD-GRS and HDL-C/LDL-C=0.4-0.6, participants with a combination of high CHD-GRS and HDL-C/LDL-C<0.4 were associated with the highest MI risk (HR=2.45, 95% CI=2.15 to 2.8, p<0.001). Participants with HDL-C/LDL-C<0.4 were correlated with a higher MI risk regardless of whether they had a high, intermediate or low CHD-GRS.

Conclusion: In UKB participants, HDL-C/LDL-C ratio of 0.4-0.6 was correlated with lower MI risk, all-cause mortality, haemorrhagic stroke and ischaemic stroke. Participants with HDL-C/LDL-C<0.4 were correlated with a higher MI risk regardless of whether they had a high, intermediate or low CHD-GRS. The clinical significance and impact of HDL-C/LDL-C need to be further verified in future studies.

目的:探讨高密度脂蛋白胆固醇(HDL-C)/低密度脂蛋白胆固醇(LDL-C)与心肌梗死(MI)、全因死亡率、出血性卒中和缺血性卒中的相关性,以及遗传易感性和HDL-C/LDL-C与MI风险的联合关系。方法和结果:本研究从UK Biobank (UKB)数据库中选择384093名参与者。首先,受限三次样条曲线表明HDL-C/LDL-C与心肌梗死、缺血性卒中和全因死亡率呈非线性关联。其次,Cox比例风险模型显示,与HDL-C/LDL-C=0.4-0.6相比,HDL-C/LDL-C0.6与全因死亡率相关(HDL-C/LDL-C0.6的HR=0.97, 95% CI=1.16 ~ 1.26, p0.6与全多变量调整后的出血性卒中风险较高相关(HR=1.25, 95% CI=1.03 ~ 1.52, p0.6)。结论:在UKB参与者中,HDL-C/LDL-C比值0.4-0.6与较低的心肌梗死风险、全因死亡率、出血性卒中和缺血性卒中相关。HDL-C/LDL-C患者
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引用次数: 13
Measures of intracranial compartments in acute intracerebral haemorrhage: data from the Rapid Intervention with Glyceryl Trinitrate in Hypertensive Stroke-2 Trial (RIGHT-2). 急性脑出血颅内室室的测量:来自高血压卒中快速干预试验的数据(右2)。
IF 5.9 1区 医学 Q1 CLINICAL NEUROLOGY Pub Date : 2023-04-01 DOI: 10.1136/svn-2021-001375
Kailash Krishnan, Zhe Kang Law, Lisa J Woodhouse, Rob A Dineen, Nikola Sprigg, Joanna M Wardlaw, Philip M Bath

Background and purpose: Intracerebral haemorrhage volume (ICHV) is prognostically important but does not account for intracranial volume (ICV) and cerebral parenchymal volume (CPV). We assessed measures of intracranial compartments in acute ICH using computerised tomography scans and whether ICHV/ICV and ICHV/CPV predict functional outcomes. We also assessed if cistern effacement, midline shift, old infarcts, leukoaraiosis and brain atrophy were associated with outcomes.

Methods: Data from 133 participants from the Rapid Intervention with Glyceryl Trinitrate in Hypertensive Stroke-2 Trial trial were analysed. Measures included ICHV (using ABC/2) and ICV (XYZ/2) (by independent observers); ICHV, ICV and CPV (semiautomated segmentation, SAS); atrophy (intercaudate distance, ICD, Sylvian fissure ratio, SFR); midline shift; leukoaraiosis and cistern effacement (visual assessment). The effects of these measures on death at day 4 and poor functional outcome at day 90 (modified Rankin scale, mRS of >3) was assessed.

Results: ICV was significantly different between XYZ and SAS: mean (SD) of 1357 (219) vs 1420 (196), mean difference (MD) 62 mL (p<0.001). There was no significant difference in ICHV between ABC/2 and SAS. There was very good agreement for ICV measured by SAS, CPV, ICD, SFR, leukoaraiosis and cistern score (all interclass correlations, n=10: interobserver 0.72-0.99, intraobserver 0.73-1.00). ICHV/ICV and ICHV/CPV were significantly associated with mRS at day 90, death at day 4 and acute neurological deterioration (all p<0.05), similar to ICHV. Midline shift and cistern effacement at baseline were associated with poor functional outcome but old infarcts, leukoaraiosis and brain atrophy were not.

Conclusions: Intracranial compartment measures and visual estimates are reproducible. ICHV adjusted for ICH and CPV could be useful to prognosticate in acute stroke. The presence of midline shift and cistern effacement may predict outcome but the mechanisms need validation in larger studies.

背景和目的:颅内出血量(ICHV)对预后有重要意义,但不能解释颅内体积(ICV)和脑实质体积(CPV)。我们使用计算机断层扫描评估急性脑出血患者颅内室室的测量,以及ICHV/ICV和ICHV/CPV是否预测功能结局。我们还评估了脑池淡化、中线移位、陈旧性梗死、白质变和脑萎缩是否与预后相关。方法:对高血压性卒中2期快速干预试验133例参与者的资料进行分析。测量包括ICHV(使用ABC/2)和ICV (XYZ/2)(由独立观察员);ICHV、ICV和CPV(半自动分割,SAS);萎缩(尾间距离,ICD, Sylvian裂隙比,SFR);中线移位;白质变和脑池淡化(目测)。评估这些措施对第4天死亡和第90天功能不良结局的影响(修正Rankin量表,mRS >3)。结果:XYZ和SAS之间的ICV有显著差异:平均(SD)为1357 (219)vs 1420(196),平均差(MD)为62 mL(结论:颅内间隔测量和视觉估计是可重复的。脑出血和脑脊液电位调整后的脑脊液电位可用于预测急性脑卒中患者的预后。中线移位和蓄水池消失的存在可以预测结果,但其机制需要在更大规模的研究中得到验证。
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引用次数: 0
Cilostazol and isosorbide mononitrate for the prevention of progression of cerebral small vessel disease: baseline data and statistical analysis plan for the Lacunar Intervention Trial-2 (LACI-2) (ISRCTN14911850). 西洛他唑和单硝酸异山梨酯预防脑血管疾病进展:腔隙干预试验-2 (LACI-2) (ISRCTN14911850)的基线数据和统计分析计划。
IF 5.9 1区 医学 Q1 CLINICAL NEUROLOGY Pub Date : 2023-04-01 DOI: 10.1136/svn-2022-001816
Philip M Bath, Iris Mhlanga, Lisa J Woodhouse, Fergus Doubal, Katherine Oatey, Alan A Montgomery, Joanna M Wardlaw

Background: Cerebral small vessel disease (SVD) causes lacunar strokes (25% of all ischaemic strokes), physical frailty and cognitive impairment and vascular and mixed dementia. There is no specific treatment to prevent progression of SVD.

Methods: The LACunar Intervention Trial-2 is an investigator-initiated prospective randomised open-label blinded-endpoint phase II feasibility study assessing cilostazol and isosorbide mononitrate for preventing SVD progression. We aimed to recruit 400 patients with clinically evident lacunar ischaemic stroke and randomised to cilostazol, isosorbide mononitrate, both or neither, in addition to guideline secondary ischaemic stroke prevention, in a partial factorial design. The primary outcome is feasibility of recruitment and adherence to medication; key secondary outcomes include: drug tolerability; recurrent vascular events, cognition and function at 1 year after randomisation; and safety (bleeding, falls, death). Data are number (%) and median (IQR).

Results: The trial commenced on 5 February 2018 and ceased recruitment on 31 May 2021 with 363 patients randomised, with the following baseline characteristics: average age 64 (56.0, 72.0) years, female 112 (30.9%), stroke onset to randomisation 79.0 (27.0, 244.0) days, hypertension 267 (73.6%), median blood pressures 143.0 (130.0, 157.0)/83.0 (75.0, 90.0) mm Hg, current smokers 67 (18.5%), educationally achieved end of school examinations (A-level) or higher 118 (32.5%), modified Rankin scale 1.0 (0.0, 1.0), National Institutes Health stroke scale 1.0 (1.4), Montreal Cognitive Assessment 26.0 (23.0, 28.0) and total SVD score on brain imaging 1.0 (0.0, 2.0). This publication summarises the baseline data and presents the statistical analysis plan.

Summary: The trial is currently in follow-up which will complete on 31 May 2022 with results expected in October 2022.

Trial registration number: ISRCTN14911850.

背景:脑血管病(SVD)可导致腔隙性卒中(占所有缺血性卒中的25%)、身体虚弱和认知障碍以及血管性和混合性痴呆。没有特定的治疗方法来防止SVD的进展。方法:LACunar干预试验-2是一项由研究者发起的前瞻性随机开放标签盲终点II期可行性研究,评估西洛他唑和单硝酸异山梨酯预防SVD进展的可行性。我们的目的是招募400名临床明显的腔内缺血性卒中患者,并在部分因子设计中随机分配到西洛他唑,单硝酸异山梨酯,两者都使用或不使用,此外还有指导方针的继发性缺血性卒中预防。主要结局是招募的可行性和药物依从性;主要次要结局包括:药物耐受性;随机分组后1年血管事件复发、认知和功能;还有安全(流血、摔倒、死亡)。数据为数字(%)和中位数(IQR)。结果:该试验于2018年2月5日开始,并于2021年5月31日停止招募,随机分配了363例患者,具有以下基线特征:平均年龄64岁(56.0,72.0)岁,女性112岁(30.9%),卒中发作时间为79.0(27.0,244.0)天,高血压267(73.6%),中位血压143.0 (130.0,157.0)/83.0 (75.0,90.0)mm Hg,当前吸烟者67(18.5%),教育程度达到学校毕业考试(A-level)或更高118(32.5%),修改Rankin量表1.0(0.0,1.0),国立卫生研究院卒中量表1.0(1.4),蒙特利尔认知评估26.0(23.0,28.0)和脑成像SVD总分1.0 (0.0,1.0),2.0)。本出版物总结了基线数据并提出了统计分析计划。摘要:该试验目前正在进行后续工作,将于2022年5月31日完成,预计将于2022年10月取得结果。试验注册号:ISRCTN14911850。
{"title":"Cilostazol and isosorbide mononitrate for the prevention of progression of cerebral small vessel disease: baseline data and statistical analysis plan for the Lacunar Intervention Trial-2 (LACI-2) (ISRCTN14911850).","authors":"Philip M Bath,&nbsp;Iris Mhlanga,&nbsp;Lisa J Woodhouse,&nbsp;Fergus Doubal,&nbsp;Katherine Oatey,&nbsp;Alan A Montgomery,&nbsp;Joanna M Wardlaw","doi":"10.1136/svn-2022-001816","DOIUrl":"https://doi.org/10.1136/svn-2022-001816","url":null,"abstract":"<p><strong>Background: </strong>Cerebral small vessel disease (SVD) causes lacunar strokes (25% of all ischaemic strokes), physical frailty and cognitive impairment and vascular and mixed dementia. There is no specific treatment to prevent progression of SVD.</p><p><strong>Methods: </strong>The LACunar Intervention Trial-2 is an investigator-initiated prospective randomised open-label blinded-endpoint phase II feasibility study assessing cilostazol and isosorbide mononitrate for preventing SVD progression. We aimed to recruit 400 patients with clinically evident lacunar ischaemic stroke and randomised to cilostazol, isosorbide mononitrate, both or neither, in addition to guideline secondary ischaemic stroke prevention, in a partial factorial design. The primary outcome is feasibility of recruitment and adherence to medication; key secondary outcomes include: drug tolerability; recurrent vascular events, cognition and function at 1 year after randomisation; and safety (bleeding, falls, death). Data are number (%) and median (IQR).</p><p><strong>Results: </strong>The trial commenced on 5 February 2018 and ceased recruitment on 31 May 2021 with 363 patients randomised, with the following baseline characteristics: average age 64 (56.0, 72.0) years, female 112 (30.9%), stroke onset to randomisation 79.0 (27.0, 244.0) days, hypertension 267 (73.6%), median blood pressures 143.0 (130.0, 157.0)/83.0 (75.0, 90.0) mm Hg, current smokers 67 (18.5%), educationally achieved end of school examinations (A-level) or higher 118 (32.5%), modified Rankin scale 1.0 (0.0, 1.0), National Institutes Health stroke scale 1.0 (1.4), Montreal Cognitive Assessment 26.0 (23.0, 28.0) and total SVD score on brain imaging 1.0 (0.0, 2.0). This publication summarises the baseline data and presents the statistical analysis plan.</p><p><strong>Summary: </strong>The trial is currently in follow-up which will complete on 31 May 2022 with results expected in October 2022.</p><p><strong>Trial registration number: </strong>ISRCTN14911850.</p>","PeriodicalId":22021,"journal":{"name":"Stroke and Vascular Neurology","volume":"8 2","pages":"134-143"},"PeriodicalIF":5.9,"publicationDate":"2023-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/6c/e8/svn-2022-001816.PMC10176977.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9561352","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 1
Deep white matter hyperintensity is spatially correlated to MRI-visible perivascular spaces in cerebral small vessel disease on 7 Tesla MRI. 在7特斯拉MRI上,脑小血管病变的深部白质高强度与MRI可见血管周围间隙在空间上相关。
IF 5.9 1区 医学 Q1 CLINICAL NEUROLOGY Pub Date : 2023-04-01 DOI: 10.1136/svn-2022-001611
Yajing Huo, Yilin Wang, Cen Guo, Qianyun Liu, Lili Shan, Mingyuan Liu, Haibo Wu, Guanwu Li, Huihui Lv, Lingdan Lu, Yintin Zhou, Jianfeng Feng, Yan Han

Background: The association between perivascular space (PVS) and white matter hyperintensity (WMH) has been unclear. Normal-appearing white matter (NAWM) around WMH is also found correlated with the development of focal WMH. This study aims to investigate the topological connections among PVS, deep WMH (dWMH) and NAWM around WMH using 7 Tesla (7T) MRI.

Methods: Thirty-two patients with non-confluent WMHs and 16 subjects without WMHs were recruited from our department and clinic. We compared the PVS burden between patients with and without WMHs using a 5-point scale. Then, the dilatation and the number of PVS within a radius of 1 cm around each dWMH were compared with those of a reference site (without WMH) in the contralateral hemisphere. In this study, we define NAWM as an area within the radius of 1 cm around each dWMH. Furthermore, we assessed the spatial relationship between dWMH and PVS.

Results: Higher PVS scores in the centrum semiovale were found in patients with >5 dWMHs (median 3) than subjects without dWMH (median 2, p = 0.014). We found there was a greater dilatation and a higher number of PVS in NAWM around dWMH than at the reference sites (p<0.001, p<0.001). In addition, 79.59% of the dWMHs were spatially connected with PVS.

Conclusion: dWMH, NAWM surrounding WMH and MRI-visible PVS are spatially correlated in the early stage of cerebral small vessel disease. Future study of WMH and NAWM should not overlook MRI-visible PVS.

背景:血管周围间隙(PVS)与白质高强度(WMH)之间的关系尚不清楚。WMH周围的正常白质(NAWM)也被发现与局灶性WMH的发展有关。本研究旨在利用7特斯拉(7T) MRI研究PVS、深度WMH (dWMH)和WMH周围NAWM之间的拓扑联系。方法:从我科和临床选取32例非合流性腰痛患者和16例非合流性腰痛患者。我们使用5分制比较了有和没有wmh患者的PVS负担。然后,与对侧半球参考部位(无WMH)比较每个dWMH周围1 cm半径内的扩张和PVS数量。在本研究中,我们将NAWM定义为每个dWMH周围1厘米半径内的区域。此外,我们还评估了dWMH与PVS之间的空间关系。结果:>5个dWMH患者(中位数为3)比无dWMH患者(中位数为2,p = 0.014)半膈中心PVS评分更高。我们发现,与参考部位相比,dWMH周围的NAWM扩张更大,PVS数量更多(p结论:dWMH、WMH周围的NAWM和mri可见的PVS在早期脑血管病中具有空间相关性。未来对WMH和NAWM的研究不应忽视mri可见pv。
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引用次数: 1
NOTCH2NLC expanded GGC repeats in patients with cerebral small vessel disease. NOTCH2NLC在脑血管疾病患者中扩增GGC重复序列。
IF 5.9 1区 医学 Q1 CLINICAL NEUROLOGY Pub Date : 2023-04-01 DOI: 10.1136/svn-2022-001631
Yun-Chao Wang, Yu Fan, Wen-Kai Yu, Si Shen, Jia-Di Li, Yuan Gao, Yan Ji, Yu-Sheng Li, Lu-Lu Yu, Zi-Chen Zhao, Shan-Shan Li, Yao Ding, Chang-He Shi, Yu-Ming Xu

Objective: GGC repeat expansions in the human-specific NOTCH2NLC gene have been reported as the cause of neuronal intranuclear inclusion disease (NIID). Given the clinical overlap of cognitive impairment in NIID and cerebral small vessel disease (CSVD), both diseases have white matter hyperintensity on T2-fluid-attenuated inversion recovery sequences of brain MRI, and white matter hyperintensity is a primary neuroimaging marker of CSVD on MRI. Therefore, we hypothesised that the GGC repeat expansions might also contribute to CSVD. To further investigate the relationship between NOTCH2NLC GGC repeat expansions and CSVD, we performed a genetic analysis of 814 patients with the disease.

Methods: We performed a comprehensive GGC repeat expansion screening in NOTCH2NLC from 814 patients with sporadic CSVD. Their Fazekas score was greater than or equal to 3 points. Repeat-primed PCR and fluorescence amplicon length analyses were performed to identify GGC repeat expansions, and whole-exome sequencing was used to detect any pathogenic mutation in previously reported genes associated with CSVD.

Results: We identified nine (1.11%) patients with pathogenic GGC repeat expansions ranging from 41 to 98 repeats. The minor allele frequency of expanded GGC repeats in NOTCH2NLC was 0.55%.

Conclusion: Our findings suggest that intermediate-length and longer-length GGC repeat expansions in NOTCH2NLC are associated with sporadic CSVD. This provides new thinking for studying the pathogenesis of CSVD.

目的:人类特异性NOTCH2NLC基因的GGC重复扩增已被报道为神经元核内包涵病(NIID)的原因。鉴于NIID与脑血管病(CSVD)认知功能障碍的临床重叠,两种疾病在脑MRI t2 -液体衰减反转恢复序列上均表现为白质高信号,白质高信号是CSVD的主要神经影像学标志物。因此,我们假设GGC重复扩增也可能导致CSVD。为了进一步研究NOTCH2NLC GGC重复扩增与CSVD之间的关系,我们对814例CSVD患者进行了遗传分析。方法:我们对814例散发性CSVD患者的NOTCH2NLC进行了全面的GGC重复扩展筛查。他们的法泽卡得分大于等于3分。重复引物PCR和荧光扩增子长度分析用于鉴定GGC重复扩增,全外显子组测序用于检测先前报道的与CSVD相关基因的任何致病性突变。结果:我们发现9例(1.11%)患者具有致病性GGC重复扩增,范围从41到98个重复。NOTCH2NLC扩增GGC重复序列的次要等位基因频率为0.55%。结论:我们的研究结果表明,NOTCH2NLC中中长度和较长长度的GGC重复扩增与散发性CSVD有关。这为研究心血管疾病的发病机制提供了新的思路。
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引用次数: 4
Correction: Cilostazol and isosorbide mononitrate for the prevention of progression of : baseline data and statistical analysis plan for the Lacunar Intervention Trial-2 (LACI-2) (ISRCTN14911850). 校正:西洛他唑和单硝酸异山梨酯预防:腔隙干预试验-2 (LACI-2) (ISRCTN14911850)的基线数据和统计分析计划。
IF 5.9 1区 医学 Q1 CLINICAL NEUROLOGY Pub Date : 2023-04-01 DOI: 10.1136/svn-2022-001816corr1
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引用次数: 1
Circulating endothelial microvesicles and their carried miR-125a-5p: potential biomarkers for ischaemic stroke. 循环内皮微泡及其携带的miR-125a-5p:缺血性卒中的潜在生物标志物
IF 5.9 1区 医学 Q1 CLINICAL NEUROLOGY Pub Date : 2023-04-01 DOI: 10.1136/svn-2021-001476
Xiaotang Ma, Xiaorong Liao, Jiehong Liu, Yan Wang, Xiang Wang, Yanfang Chen, Xiaojian Yin, Qunwen Pan
Background Endothelial microvesicles (EMVs) are closely associated with the status of endothelial cells (ECs). Our earlier study has shown that EMVs could exert protective roles in ECs by transferring their carried miR-125a-5p. However, whether circulating EMVs and their carried miR-125a-5p can be used as biomarkers in ischaemic stroke (IS) are remain unknown. Methods We recruited 72 subjects with IS, 60 subjects with high stroke risk and 56 age-matched controls. The circulating EMVs and their carried miR-125a-5p (EMV-miR-125a-5p) levels were detected. We used microRNA (miR) array to study expression changes of miRs in plasma EMVs samples of three IS patients and three matched healthy controls. Transient middle cerebral artery occlusion (tMCAO) was used to establish IS mouse model. Results EMVs level was obviously elevated in IS patients, with the highest level in acute stage, and was positively related to carotid plaque, carotid intima–media thickness (IMT), National Institutes of Health Stroke Scale (NIHSS), infarct volume. On the contrary, we observed that EMV-miR-125a-5p level was obviously reduced in IS, with the lowest level in acute stage, and was negatively correlated with carotid plaque, IMT, NIHSS scores, infarct volume. EMVs and EMV-miR-125a-5p levels were closely related with large artery atherosclerosis subgroup. Importantly, EMVs and EMV-miR-125a-5p levels could serve as independent risk factors, and receiver operating characteristic curve achieved an area under curve (AUC) of 0.720 and 0.832 for IS, respectively, and elevated to 0.881 after their combination. In IS mouse model, control EMVs or n-EMVs administration could decrease the infarct volume and neurological deficit score, while increase the cerebral blood flow of IS mice compared with vehicle group, while IS EMVs or oxygen and glucose deprivation (OGD)-EMVs administration aggravated the tMCAO induced ischaemic injury. In addition, we observed that OGD EMVmiR-125a-5p could partially ameliorate the OGD EMVs induced brain injury after IS. Conclusions These findings demonstrate that circulating EMVs and EMV-miR-125a-5p are closely related with the occurrence, progress, subtypes and severity of IS, and they can serve as innovative biomarkers and therapeutic targets for IS, especially when they are combined.
背景:内皮微泡(emv)与内皮细胞(ECs)的状态密切相关。我们早期的研究表明,emv可以通过转移其携带的miR-125a-5p在ECs中发挥保护作用。然而,循环emv及其携带的miR-125a-5p是否可以作为缺血性卒中(IS)的生物标志物仍然未知。方法:我们招募了72名IS患者,60名卒中高危患者和56名年龄匹配的对照组。检测循环emv及其携带的miR-125a-5p (EMV-miR-125a-5p)水平。我们使用microRNA (miR)阵列研究了3例IS患者和3例匹配的健康对照的血浆emv样本中miR的表达变化。采用短暂性大脑中动脉闭塞(tMCAO)建立IS小鼠模型。结果:IS患者emv水平明显升高,以急性期最高,且与颈动脉斑块、颈动脉内膜-中膜厚度(IMT)、美国国立卫生研究院卒中量表(NIHSS)、梗死体积呈正相关。相反,我们观察到EMV-miR-125a-5p水平在IS中明显降低,急性期最低,且与颈动脉斑块、IMT、NIHSS评分、梗死体积呈负相关。emv和EMV-miR-125a-5p水平与大动脉粥样硬化亚组密切相关。重要的是,emv和EMV-miR-125a-5p水平可以作为独立的危险因素,IS的受试者工作特征曲线的曲线下面积(AUC)分别为0.720和0.832,两者联合后升高至0.881。在IS小鼠模型中,与对照组相比,对照emv或n- emv给药可降低IS小鼠梗死面积和神经功能缺损评分,增加脑血流量,而IS emv或氧葡萄糖剥夺(OGD)- emv给药可加重tMCAO诱导的缺血损伤。此外,我们观察到OGD EMVmiR-125a-5p可以部分改善IS后OGD emv诱导的脑损伤。结论:这些研究结果表明,循环emv和EMV-miR-125a-5p与IS的发生、进展、亚型和严重程度密切相关,它们可以作为IS的创新生物标志物和治疗靶点,特别是当它们联合使用时。
{"title":"Circulating endothelial microvesicles and their carried miR-125a-5p: potential biomarkers for ischaemic stroke.","authors":"Xiaotang Ma,&nbsp;Xiaorong Liao,&nbsp;Jiehong Liu,&nbsp;Yan Wang,&nbsp;Xiang Wang,&nbsp;Yanfang Chen,&nbsp;Xiaojian Yin,&nbsp;Qunwen Pan","doi":"10.1136/svn-2021-001476","DOIUrl":"https://doi.org/10.1136/svn-2021-001476","url":null,"abstract":"Background Endothelial microvesicles (EMVs) are closely associated with the status of endothelial cells (ECs). Our earlier study has shown that EMVs could exert protective roles in ECs by transferring their carried miR-125a-5p. However, whether circulating EMVs and their carried miR-125a-5p can be used as biomarkers in ischaemic stroke (IS) are remain unknown. Methods We recruited 72 subjects with IS, 60 subjects with high stroke risk and 56 age-matched controls. The circulating EMVs and their carried miR-125a-5p (EMV-miR-125a-5p) levels were detected. We used microRNA (miR) array to study expression changes of miRs in plasma EMVs samples of three IS patients and three matched healthy controls. Transient middle cerebral artery occlusion (tMCAO) was used to establish IS mouse model. Results EMVs level was obviously elevated in IS patients, with the highest level in acute stage, and was positively related to carotid plaque, carotid intima–media thickness (IMT), National Institutes of Health Stroke Scale (NIHSS), infarct volume. On the contrary, we observed that EMV-miR-125a-5p level was obviously reduced in IS, with the lowest level in acute stage, and was negatively correlated with carotid plaque, IMT, NIHSS scores, infarct volume. EMVs and EMV-miR-125a-5p levels were closely related with large artery atherosclerosis subgroup. Importantly, EMVs and EMV-miR-125a-5p levels could serve as independent risk factors, and receiver operating characteristic curve achieved an area under curve (AUC) of 0.720 and 0.832 for IS, respectively, and elevated to 0.881 after their combination. In IS mouse model, control EMVs or n-EMVs administration could decrease the infarct volume and neurological deficit score, while increase the cerebral blood flow of IS mice compared with vehicle group, while IS EMVs or oxygen and glucose deprivation (OGD)-EMVs administration aggravated the tMCAO induced ischaemic injury. In addition, we observed that OGD EMVmiR-125a-5p could partially ameliorate the OGD EMVs induced brain injury after IS. Conclusions These findings demonstrate that circulating EMVs and EMV-miR-125a-5p are closely related with the occurrence, progress, subtypes and severity of IS, and they can serve as innovative biomarkers and therapeutic targets for IS, especially when they are combined.","PeriodicalId":22021,"journal":{"name":"Stroke and Vascular Neurology","volume":"8 2","pages":"89-102"},"PeriodicalIF":5.9,"publicationDate":"2023-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/12/86/svn-2021-001476.PMC10176997.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9561334","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 2
Somatic mutation contributing to clonal haematopoiesis is a risk factor of recurrent stroke in first-ever acute ischaemic stroke: a prospective cohort study. 体细胞突变促进克隆造血是首次急性缺血性卒中复发的危险因素:一项前瞻性队列研究。
IF 5.9 1区 医学 Q1 CLINICAL NEUROLOGY Pub Date : 2023-04-01 DOI: 10.1136/svn-2022-001756
Xin Qiu, Yalun Dai, Si Cheng, Hong-Qiu Gu, Yong Jiang, Xia Meng, Yilong Wang, Xingquan Zhao, Yingyu Jiang, Zhe Xu, Xinying Huang, Meng Wang, Tian Jie Lyu, Yubo Wang, Jiaxu Weng, Lingyun Cui, Yi Shangguan, Hao Li, Yongjun Wang, Zixiao Li

Background: Somatic mutation contributes to clonal haematopoiesis of indeterminate potential (CHIP) is related to age and associated with a higher risk of stroke and atherosclerotic cardiovascular disease. Here, we investigated the prognostic significance of CHIP in a large first-ever acute ischaemic stroke (AIS) cohort and explored the underlying mechanisms.

Methods: We studied a prospective cohort of 6016 patients who had a first-ever AIS in China. Whole-genome sequencing was performed to identify CHIP. High-sensitivity C reactive protein (hs-CRP) levels above 3 mg/L at baseline were defined as hyperinflammation. Recurrent stroke during the 3-month follow-up was the primary outcome.

Results: Among the 6016 patients who had a first-ever AIS, with a median age was 62 years (IQR, 54.0‒70.0), 3.70% were identified as CHIP carriers. The most common mutations occurred in the DNMT3A (30.0%) and TET2 (11.4%) genes. During a follow-up of 3 months, the presence of CHIP was associated with recurrent stroke (HR 1.62, 95% CI 1.04 to 2.51, p=0.03), recurrent ischaemic stroke (HR 1.64, 95% CI 1.04 to 2.58, p=0.03) and combined vascular events (HR 1.58, 95% CI 1.02 to 2.44, p=0.04) after adjusting for hsCRP levels at baseline in patients who had a first-ever AIS. Subgroup analysis demonstrated that CHIP was only associated with recurrent stroke when patients under hyperinflammation (OR 3.10, 95% CI 1.92 to 5.00, p<0.001) but not in those without hyperinflammation (OR 0.18, 95% CI 0.03 to 1.04, p=0.06, Pinteraction=0.002).

Conclusion: Our results suggest that somatic mutations contributing to CHIP increase the risk of short-term recurrent stroke in patients who had a first-ever AIS. Hyperinflammation may be important in the relationship between CHIP and recurrent stroke.

背景:体细胞突变导致克隆性不确定潜能造血(CHIP)与年龄有关,并与卒中和动脉粥样硬化性心血管疾病的高风险相关。在这里,我们研究了CHIP在首次急性缺血性卒中(AIS)队列中的预后意义,并探讨了其潜在机制。方法:我们研究了6016例中国首次AIS患者的前瞻性队列。全基因组测序鉴定CHIP。高敏C反应蛋白(hs-CRP)在基线水平高于3mg /L被定义为高炎症。3个月随访期间卒中复发是主要结局。结果:6016例首次AIS患者中,年龄中位数为62岁(IQR, 54.0-70.0), 3.70%为CHIP携带者。最常见的突变发生在DNMT3A(30.0%)和TET2(11.4%)基因。在3个月的随访中,CHIP的存在与卒中复发(HR 1.62, 95% CI 1.04 - 2.51, p=0.03)、缺血性卒中复发(HR 1.64, 95% CI 1.04 - 2.58, p=0.03)和合并血管事件(HR 1.58, 95% CI 1.02 - 2.44, p=0.04)相关,在首次AIS患者中调整基线hsCRP水平后。亚组分析显示,CHIP仅与高脂血症患者的卒中复发相关(OR 3.10, 95% CI 1.92 ~ 5.00, p互作=0.002)。结论:我们的研究结果表明,在首次AIS患者中,导致CHIP的体细胞突变增加了短期复发性卒中的风险。在CHIP与卒中复发之间的关系中,高炎症可能是重要的。
{"title":"Somatic mutation contributing to clonal haematopoiesis is a risk factor of recurrent stroke in first-ever acute ischaemic stroke: a prospective cohort study.","authors":"Xin Qiu,&nbsp;Yalun Dai,&nbsp;Si Cheng,&nbsp;Hong-Qiu Gu,&nbsp;Yong Jiang,&nbsp;Xia Meng,&nbsp;Yilong Wang,&nbsp;Xingquan Zhao,&nbsp;Yingyu Jiang,&nbsp;Zhe Xu,&nbsp;Xinying Huang,&nbsp;Meng Wang,&nbsp;Tian Jie Lyu,&nbsp;Yubo Wang,&nbsp;Jiaxu Weng,&nbsp;Lingyun Cui,&nbsp;Yi Shangguan,&nbsp;Hao Li,&nbsp;Yongjun Wang,&nbsp;Zixiao Li","doi":"10.1136/svn-2022-001756","DOIUrl":"https://doi.org/10.1136/svn-2022-001756","url":null,"abstract":"<p><strong>Background: </strong>Somatic mutation contributes to clonal haematopoiesis of indeterminate potential (CHIP) is related to age and associated with a higher risk of stroke and atherosclerotic cardiovascular disease. Here, we investigated the prognostic significance of CHIP in a large first-ever acute ischaemic stroke (AIS) cohort and explored the underlying mechanisms.</p><p><strong>Methods: </strong>We studied a prospective cohort of 6016 patients who had a first-ever AIS in China. Whole-genome sequencing was performed to identify CHIP. High-sensitivity C reactive protein (hs-CRP) levels above 3 mg/L at baseline were defined as hyperinflammation. Recurrent stroke during the 3-month follow-up was the primary outcome.</p><p><strong>Results: </strong>Among the 6016 patients who had a first-ever AIS, with a median age was 62 years (IQR, 54.0‒70.0), 3.70% were identified as CHIP carriers. The most common mutations occurred in the <i>DNMT3A</i> (30.0%) and <i>TET2</i> (11.4%) genes. During a follow-up of 3 months, the presence of CHIP was associated with recurrent stroke (HR 1.62, 95% CI 1.04 to 2.51, p=0.03), recurrent ischaemic stroke (HR 1.64, 95% CI 1.04 to 2.58, p=0.03) and combined vascular events (HR 1.58, 95% CI 1.02 to 2.44, p=0.04) after adjusting for hsCRP levels at baseline in patients who had a first-ever AIS. Subgroup analysis demonstrated that CHIP was only associated with recurrent stroke when patients under hyperinflammation (OR 3.10, 95% CI 1.92 to 5.00, p<0.001) but not in those without hyperinflammation (OR 0.18, 95% CI 0.03 to 1.04, p=0.06, P<sub>interaction</sub>=0.002).</p><p><strong>Conclusion: </strong>Our results suggest that somatic mutations contributing to CHIP increase the risk of short-term recurrent stroke in patients who had a first-ever AIS. Hyperinflammation may be important in the relationship between CHIP and recurrent stroke.</p>","PeriodicalId":22021,"journal":{"name":"Stroke and Vascular Neurology","volume":"8 2","pages":"103-110"},"PeriodicalIF":5.9,"publicationDate":"2023-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/9d/03/svn-2022-001756.PMC10176982.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9929030","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 1
ADVISING score: a reliable grading scale based on injury and response for intracerebral haemorrhage. 建议评分:基于损伤和脑出血反应的可靠分级量表。
IF 5.9 1区 医学 Q1 CLINICAL NEUROLOGY Pub Date : 2023-04-01 DOI: 10.1136/svn-2022-001707
Yan Wan, Hongxiu Guo, Shaoli Chen, Jiang Chang, David Wang, Rentang Bi, Man Li, Ke Shi, Zhaowei Wang, Daokai Gong, Jingwen Xu, Quanwei He, Bo Hu

Background: Intracerebral haemorrhage (ICH) is the most devastating form of stroke causing high morbidity and mortality. We aimed to develop a novel clinical score incorporating multisystem markers to predict functional dependence at 90 days after ICH.

Methods: We analysed data from Chinese Cerebral Hemorrhage: Mechanism and Intervention study. Multivariable logistic regression analysis was used to identify the factors associated with 90-day functional dependency (the modified Rankin Scale ≥3) after ICH and develop the ADVISING scoring system. To test the scoring system, a total of 2111 patients from Hubei province were included as the training cohort, and 733 patients from other three provinces in China were included as an external validation cohort.

Results: We found nine variables to be significantly associated with functional dependency and included in the ADVISING score system: age, deep location of haematoma, volume of haematoma, National Institutes of Health Stroke Scale, aspartate transaminase, international normalised ratio, neutrophil-lymphocyte ratio, fasting blood glucose and glomerular filtration rate. Individuals were divided into 12 different categories by using these nine potential predictors. The proportion of patients who were functionally dependent increased with higher ADVISING scores, which showed good discrimination and calibration in both the training cohort (C-statistic, 0.866; p value of Hosmer-Lemeshow test, 0.195) and validation cohort (C-statistic, 0.884; p value of Hosmer-Lemeshow test, 0.853). The ADVISING score also showed better discriminative performance compared with the other five existing ICH scores (p<0.001).

Conclusions: ADVISING score is a reliable tool to predict functional dependency at 90 days after ICH.

背景:脑出血(ICH)是最具破坏性的中风形式,具有高发病率和死亡率。我们的目标是开发一种包含多系统标记物的新型临床评分,以预测脑出血后90天的功能依赖。方法:对《中国脑出血:机制与干预研究》资料进行分析。采用多变量logistic回归分析,确定ICH后90天功能依赖(修正Rankin量表≥3)的相关因素,并制定advice评分系统。为了对评分系统进行检验,我们将来自湖北省的2111名患者作为训练队列,并将来自中国其他三个省份的733名患者作为外部验证队列。结果:我们发现9个变量与功能依赖显著相关,并包括在advice评分系统中:年龄、血肿深度位置、血肿体积、美国国立卫生研究院卒中量表、天冬氨酸转氨酶、国际正常化比率、中性粒细胞-淋巴细胞比率、空腹血糖和肾小球滤过率。通过使用这9个潜在的预测因子,将个体分为12个不同的类别。建议评分越高,功能依赖患者的比例越高,这在训练队列中都显示出良好的辨别和校准(C-statistic, 0.866;Hosmer-Lemeshow检验的p值为0.195)和验证队列(c统计量为0.884;Hosmer-Lemeshow检验p值为0.853)。与其他五种现有的脑出血评分相比,建议评分也显示出更好的判别性能(结论:建议评分是预测脑出血后90天功能依赖的可靠工具。
{"title":"ADVISING score: a reliable grading scale based on injury and response for intracerebral haemorrhage.","authors":"Yan Wan,&nbsp;Hongxiu Guo,&nbsp;Shaoli Chen,&nbsp;Jiang Chang,&nbsp;David Wang,&nbsp;Rentang Bi,&nbsp;Man Li,&nbsp;Ke Shi,&nbsp;Zhaowei Wang,&nbsp;Daokai Gong,&nbsp;Jingwen Xu,&nbsp;Quanwei He,&nbsp;Bo Hu","doi":"10.1136/svn-2022-001707","DOIUrl":"https://doi.org/10.1136/svn-2022-001707","url":null,"abstract":"<p><strong>Background: </strong>Intracerebral haemorrhage (ICH) is the most devastating form of stroke causing high morbidity and mortality. We aimed to develop a novel clinical score incorporating multisystem markers to predict functional dependence at 90 days after ICH.</p><p><strong>Methods: </strong>We analysed data from Chinese Cerebral Hemorrhage: Mechanism and Intervention study. Multivariable logistic regression analysis was used to identify the factors associated with 90-day functional dependency (the modified Rankin Scale ≥3) after ICH and develop the ADVISING scoring system. To test the scoring system, a total of 2111 patients from Hubei province were included as the training cohort, and 733 patients from other three provinces in China were included as an external validation cohort.</p><p><strong>Results: </strong>We found nine variables to be significantly associated with functional dependency and included in the ADVISING score system: age, deep location of haematoma, volume of haematoma, National Institutes of Health Stroke Scale, aspartate transaminase, international normalised ratio, neutrophil-lymphocyte ratio, fasting blood glucose and glomerular filtration rate. Individuals were divided into 12 different categories by using these nine potential predictors. The proportion of patients who were functionally dependent increased with higher ADVISING scores, which showed good discrimination and calibration in both the training cohort (C-statistic, 0.866; p value of Hosmer-Lemeshow test, 0.195) and validation cohort (C-statistic, 0.884; p value of Hosmer-Lemeshow test, 0.853). The ADVISING score also showed better discriminative performance compared with the other five existing ICH scores (p<0.001).</p><p><strong>Conclusions: </strong>ADVISING score is a reliable tool to predict functional dependency at 90 days after ICH.</p>","PeriodicalId":22021,"journal":{"name":"Stroke and Vascular Neurology","volume":"8 2","pages":"111-118"},"PeriodicalIF":5.9,"publicationDate":"2023-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/29/d8/svn-2022-001707.PMC10176996.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9557095","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 1
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Stroke and Vascular Neurology
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