Cerebral Microbleeds and Chronic Kidney Disease in Acute Ischemic Stroke Patients with Atrial Fibrillation

Background: Cerebral microbleeds (CMBs) are associated with the risk of intracerebral hemorrhage in stroke patients with atrial fibrillation (AF). We investigated the association between CMBs and chronic kidney disease (CKD) in patients with acute ischemic stroke and AF. Methods: We retrospectively examined consecutive patients with acute ischemic stroke and AF who underwent brain gradient-echo T2*-weighted magnetic resonance imaging. The number and distribution (lobar, deep or infratentorial, and mixed) of CMBs were assessed. Kidney function was assessed according to the estimated glomerular filtration rate (eGFR), which was calculated using a modified version of the Modification of Diet in Renal Disease equation. Results: Of the 357 included patients, 105 (29.4%) had CMBs. CKD (eGFR < 60 mL/min/1.73 m²) was found in 131 (36.7%) patients. Patients with CKD showed a higher prevalence of any form of CMB (41.2% versus 22.6%, P < .001), deep or infratentorial CMBs (19.9% versus 9.3%, P < .01), and mixed CMBs (14.5% versus 5.3%, P < .01) than those without CKD. After adjusting for age and other confounding factors, CKD was found to be independently associated with the presence of any form of CMB (odds ratio 1.89, P = .02) and mixed CMBs (odds ratio 3.10, P < .01). Moreover, moderate to severe CKD (eGFR < 45 mL/min/1.73 m²) was independently associated with the presence of multiple CMBs (odds ratio 2.31, P = .04). Conclusions: CMBs and CKD are common in acute ischemic stroke patients with AF, and CKD may be a risk factor for CMBs. Further longitudinal studies are needed to evaluate whether maintaining kidney function can prevent the development of CMBs.     

急性缺血性卒中患者脑微出血相关因素分析

【摘要】
目的 探讨急性缺血性卒中患者合并脑微出血（cerebral microbleeds,CMB）的情况及其相关因素。
方法 本研究采用单中心、前瞻性研究方法,连续收集2011年1月～2012年6月于北京市第六医院神经内科住院的急性缺血性卒中患者302例,根据有无CMB将患者分为有CMB组（83例）和无CMB组（219例）,比较两组间一般临床资料、生化指标及影像学特点是否存在差异,并采用多因素逐步Logistic回归模型分析CMB发生的独立危险因素。
结果 302例患者中,合并有CMB者83例（27.5%）,其中年龄（t=3.67,P<0.001）、高血压（χ2=4.76,P=0.03）、卒中史（χ2=5.46,P=0.02）、纤维蛋白原（t=2.33,P=0.02）、腔隙性脑梗死数目（Z=-5.04,P<0.001）以及脑白质疏松程度评分（Z=-7.88,P<0.001）两组间比较差异具有显著性。Logistic回归分析显示,纤维蛋白原［比值比（odds ratio,OR）1.469,95%可信区间（confidence interval,CI）1.366～1.602;P=0.037］、腔隙性脑梗死数目（OR 1.636,95%CI 1.200～2.231;P=0.002）以及脑白质疏松程度评分（OR 1.700,95%CI 1.502～1.980;P<0.001）是急性缺血性卒中患者CMB发生的独立危险因素。
结论 CMB的发生与纤维蛋白原含量、腔隙性脑梗死数目以及脑白质疏松程度相关。     

Factors Associated with Thrombolysis Outcome in Ischemic Stroke Patients with Atrial Fibrillation

The outcome of early intravenous thrombolysis for ischemic stroke in patients with atrial fibrillation (AF) is worse than that without thrombosis. How to increase the efficacy of intravenous thrombolysis for AF-related ischemic stroke remains largely unknown. In this study, we investigated factors that influence the effect of intravenous thrombolysis in these patients. Our results showed that thrombolysis was independently associated with a favorable outcome (P < 0.001) and did not influence the mortality of AF-related ischemic stroke, although it increased the risk of hemorrhage within 24 h after treatment. Risk factors for a poor outcome at admission were: heart failure (P = 0.045); high systolic pressure (P = 0.039); high blood glucose (P = 0.030); and a high National Institutes of Health Stroke Scale (NIHSS) score (P < 0.001). Moreover, high systolic pressure at admission (P = 0.007), high blood glucose (P = 0.027), and a high NIHSS score (P < 0.001) were independent risk factors for mortality at 3 months. Besides thrombolysis, a high NIHSS score (P = 0.006) and warfarin taken within 48 h before stroke onset (P = 0.032) were also independent risk factors for symptomatic hemorrhage within 24 h after treatment. Ischemic stroke patients with AF benefited from intravenous thrombolysis with recombinant tissue plasminogen activator within 4.5 h after stroke.     

Cerebral Microbleeds are Associated with Higher Mortality Among Ischemic Stroke Patients

Background

Several studies have shown that cerebral microbleeds (CMBs) increase the risk of long-term stroke-related mortality. The purpose of this study was to determine if the existence and burden of CMBs are a predictor of in-hospital death among patients with acute ischemic stroke (AIS).

Pharmacotherapy for Patients with Atrial Fibrillation and Cerebral Microbleeds

Background: Patients with cerebral microbleeds have increased risk of intracranial hemorrhage and ischemic stroke. No trial specifically informs antithrombotic therapy for patients with cerebral microbleeds and atrial fibrillation. We investigated the safety of anticoagulation versus no anticoagulation with regard to cerebrovascular outcomes and mortality. Methods: All consecutive atrial fibrillation patients from 2015 to 2018 with MRI evidence of ≥1 cerebral microbleed at time of imaging were reviewed. Patients were treated with warfarin, direct oral anticoagulants, or neither. Primary outcome was all-cause mortality informed by National Death Registry and the composite of ischemic and hemorrhagic stroke. All statistical tests were 2-sided and significant at P < .05. Results: The median interval from patient identification until the end of electronic health record surveillance was 9.93 months (interquartile range, 2.83-19.17 months). We identified 308 atrial fibrillation patients with cerebral microbleeds; 128(41.6%) were on warfarin, 88(28.6%) on direct oral anticoagulants, and 92(29.9%) on neither. Over the surveillance interval, 87 deaths, 51 ischemic strokes, and 14 hemorrhagic strokes occurred. The estimated likelihoods of the composite stroke outcome and ischemic stroke only did not differ significantly among the 3 groups. However, patients taking direct oral anticoagulants had a significantly smaller likelihood of all-cause mortality than patients who were not anticoagulated (adjusted hazard ratio: .44[.23, .83], P=.012). Conclusions: In patients with coprevalent atrial fibrillation and cerebral microbleeds, we did not detect differences in subsequent ischemic stroke, hemorrhagic stroke, or both, comparing warfarin, direct oral anticoagulants, or neither. Patients treated with direct oral anticoagulants had better survival than nonanticoagulated patients.     

缺血性卒中患者脑内微出血特点及危险因素的研究

目的 探讨脑内微出血在缺血性卒中患者中的发生率及在脑内各区域的分布情况,观察缺血性卒中亚型之间微出血发生率的差异,初步分析其相关因素及其与腔隙性脑梗死、脑白质病变等微小血管病变程度之间的关系。方法 连续入选261例心源性栓塞型、大动脉粥样硬化型及小动脉闭塞型3个亚型的缺血性卒中患者。记录患者一般临床资料及实验室检查结果,应用头颅磁共振梯度回波T2*加权成像（gradient-echoT2*-weighted,GRE-T2*）观察脑内微出血的数目及部位,同时观察腔隙性脑梗死数目和部位以及脑白质病变程度。结果 80例患者（30.70%）存在脑内微出血,数目为1～109个。微出血最常见于皮质-皮质下区（46.09%）,其次位于基底节区（27.80%）。各亚型中小动脉闭塞型患者脑内微出血的发生率最高（53.30%）。高血压、腔隙性脑梗死数目及脑白质改变程度为缺血性卒中患者脑内微出血发生的独立危险因素,比值比（odds ratio,OR）分别为4.364、1.190和1.310;脑内微出血的分级与腔隙性梗死分级（r =0.519,P <0.001）及白质改变程度（r =0.437,P <0.001）显著相关。结论 微出血在缺血性卒中患者特别是小动脉闭塞患者中发生率较高,微出血与腔隙性脑梗死数目及脑白质改变明显相关。     

卒中合并脑微出血的影像学研究

目的 探讨ICH和脑梗死患者合并脑微出血（cerebral microbleeds，CMBs）数量分级及部位分布差异。 方法 连续选取2017年8月-2018年12月在北京市大兴区人民医院神经内科病房住院且资料完整的 卒中患者，分为ICH和脑梗死两组。收集患者发病2周内头颅MRI磁敏感加权成像影像，统计ICH与脑梗 死患者中CMBs数量分级及部位分布特点。 结果 共入组患者234例，其中ICH组79例，脑梗死组155例。ICH组合并CMBs 65例（82.3%），其中 CMBs＞5个的患者41例（51.9%）；脑梗死组合并CMBs 73例（47.1%），其中CMBs＞5个的患者21例 （13.6%），两组差异有统计学意义（P＜0.001）。ICH组中，CMBs同时累及脑叶和深部脑组织的患者40例 （50.6%）；脑梗死组中，CMBs同时累及脑叶和深部脑组织的患者25例（16.1%），两组差异有统计学意 义（P＜0.001）。 结论 CMBs病灶＞5个多见于ICH患者；CMBs同时累及脑叶及深部脑组织多见于ICH患者。     

Risk of Ischemic Stroke and Major Bleeding in Patients with Atrial Fibrillation and Cancer

Background: Atrial fibrillation (AF) is an important risk factor for ischemic stroke. Cancer may increase the risk both of ischemic stroke and of bleeding. Less is known about risk of ischemic stroke and bleeding among cancer patients with AF, complicating the prevention of ischemic stroke in these patients. Methods: Register based cohort study comprising all Swedish patients hospitalized with a primary diagnosis of AF from July 1, 2005 until December 31, 2014. Patients with cancer diagnosis were compared to the rest of the cohort. We repeated the analysis focusing on recent cancer diagnosis and on cancer types prone to thromboembolism. Associations between predictor and outcome variables were analyzed with Cox regression. Results: The cohort consisted of 294,989 AF patients including 71,882 with prior cancer diagnosis. After adjustments, neither cancer diagnosis overall, recent cancer diagnosis, or any subgroup of cancer were associated with increased risk of ischemic stroke. Several cancer forms were however associated with risk of major bleedings, including risk of intracranial hemorrhage for patients with prostate cancer and risk of gastrointestinal bleeds for patients with colorectal and pancreatic cancer, adjusted hazard ratios with 95% confidence intervals 1.31 (1.06-1.62), 1.74 (1.53-1.97), and 2.86 (1.80-4.55) respectively. Conclusion: Cancer diagnosis was not associated with increased risk of ischemic stroke but several cancer forms were associated with risk of major bleedings in this large, Swedish cohort of AF patients. The results may have implications for prevention of ischemic stroke in these patients.     

心房颤动合并急性缺血性脑卒中的溶栓及抗凝治疗研究进展

急性缺血性脑卒中是常见病、多发病。心房颤动(房颤)是临床上常见的心律失常,尤以非瓣膜性房颤为著。房颤合并急性缺血性脑卒中的患者临床常见,且病情重、出血转化率高、复发率高,给治疗带来一定的难度。重组组织型纤溶酶原激活剂是目前治疗急性缺血性脑卒中最有效的药物,可减少急性缺血性脑卒中患者的致残率;口服抗凝药可减少房颤相关急性缺血性脑卒中的复发;抗血小板治疗对房颤合并急性缺血性脑卒中患者也有一定的二级预防作用。鉴于房颤合并急性缺血性脑卒中所特有的临床特征,选择适宜的药物治疗至关重要。     

Anticoagulation Protocol for Secondary Prevention of Acute Ischemic Stroke Associated with Nonvalvular Atrial Fibrillation

ObjectivesThere is no clear evidence regarding when to initiate oral anticoagulants (OACs) for secondary prevention of recurrent stroke in patients with atrial fibrillation (AF). Therefore, this study aimed to evaluate the safety and efficacy of a novel OAC initiation protocol for secondary prevention of acute ischemic stroke associated with AF.Materials and methodsIn this multicenter prospective study 597 consecutive Japanese patients with acute ischemic stroke associated with nonvalvular AF received post-stroke OACs according to a protocol based on severity (clinical (NIHSS) and radiological (ASPECTS + W)), rt-PA use, reperfusion, and hemorrhagic transformation (HT). Primary outcomes of safety and efficacy, including symptomatic hemorrhage, cerebral stroke, and disability were evaluated at 14 and 90 days.ResultsMean OAC initiation time was 2.60±2.14 days from onset. The shortest and longest mean initiation times were 0.47±0.50 and 6.16±0.72 days, respectively. Following OAC administration, no ICH was observed within 90 days. A significantly higher incidence of acute recurrent ischemic events occurred 14 days prior to OAC (4.7%) compared with chronic recurrence within 90 days (0.8%) (P = 0.00013, McNemar's test) . Recurrence prior to OAC use was significantly correlated with days to treatment (P = 0.00224), severity (NIHSS, ASPECTS+W: P = 0.0223, P = 0.0393, respectively), and HAS-BLED (P = 0.0395) and there were no correlations with CHADS₂ (P = 0.277) or CHA₂DS₂-VASc (P = 0.246) (Wilcoxon rank sum-test).ConclusionsThis comprehensive OAC initiation protocol was relatively safe and effective for secondary prevention of stroke in patients with AF. Risk of acute recurrence was high, indicating that OACs should be started as early as possible. (clinical trial registration number: 15B 128)     

Prevalence and Risk Factors of Silent Cerebral Microbleeds in Patients with Coronary Artery Disease

ObjectivesCerebral microbleeds (CMBs), which can be detected by gradient-echo T2*-weighted magnetic resonance imaging (MRI), represent small chronic brain hemorrhages caused by structural abnormalities in cerebral small vessels. CMBs are known to be a potential predictor of future stroke, and are associated with age, various cardiovascular risk factors, cognitive impairment, and the use of antithrombotic drugs. Patients with coronary artery disease (CAD) are at potentially high risk of CMBs due to the presence of coexistent conditions. However, little is known about CMBs in patients with CAD. We aimed to identify the factors associated with the presence of CMBs among patients with CAD.MethodsWe evaluated 356 consecutive patients [mean age, 72 ± 10 years; men = 276 (78%)] with angiographically proven CAD who underwent T2*-weighted brain MRI. The brain MRI was assessed by researchers blinded to the patients’ clinical details.ResultsCMBs were found in 128 (36%) patients. Among 356 patients, 119 (33%) had previously undergone percutaneous coronary intervention (PCI), and 26 (7%) coronary artery bypass grafting (CABG). There was no significant relationship between CMBs and sex, hypertension, dyslipidemia, diabetes mellitus, anticoagulation therapy, antiplatelet therapy, or prior PCI. CMBs were significantly associated with advanced age, previous CABG, eGFR, non-HDL cholesterol, carotid artery disease, long-term antiplatelet therapy, and long-term dual antiplatelet therapy (DAPT) using univariate logistic regression analysis. The multivariate logistic regression analysis showed that long-term antiplatelet therapy (odds ratio, 1.73; 95% CI, 1.06 – 2.84; P = 0.03) or long-term DAPT (odds ratio, 2.92; 95% CI, 1.39 – 6.17; P = 0.004) was significantly associated with CMBs after adjustment for confounding variables.ConclusionsCMBs were frequently observed in patients with CAD and were significantly associated with long-term antiplatelet therapy, especially long-term DAPT.