Family history of stroke and death or vascular events within one year after ischemic stroke

ABSTRACT

Background and aims: The association between family history of stroke and clinical outcomes after ischemic stroke remains unclear.

Methods: A total of 3878 acute ischemic stroke patients from CATIS were included. The participants with ischemic stroke were divided into groups according to types of family history of stroke, stroke onset age and stroke subtypes. The primary outcome was a composite outcome of death and vascular events within 1 year after stroke. Multivariable Cox proportional hazard models were used to analyze the association between family history of stroke and other variables and clinical outcomes.

Results: Among 3878 ischemic stroke patients, 708 (18.26%) had a history of stroke in their first-degree relatives and 399 experienced a composite outcome (172 patients died and 227 experienced vascular events) within 1 year after stroke. Overall family history was not associated with the primary outcome (HR, 1.08; 95% CI, 0.37–3.19). However, the patients with maternal stroke history (HR, 1.87; 95% CI, 1.31–2.97), stroke onset age<55 years with family history (HR, 2.02; 95% CI, 1.08–3.80) and thrombotic stroke in the patients with family history (HR, 1.46; 95% CI, 1.00–2.12) were associated with primary outcome, death and vascular events, respectively.

Conclusion: This study suggests that maternal stroke history, age<55 years at stroke onset and thrombotic stroke in the patients with a family history are associated with poor outcomes after stroke. Further studies from other samples are needed to replicate our findings due to a reason for excluding some severe stroke patients in this study.     

Effect of Postural Hypotension on Recurrent Stroke: Secondary Prevention of Small Subcortical Strokes (SPS3) Study

Background: Orthostatic hypotension (OH) has been independently associated with increased risk of stroke and other cardiovascular events. We sought to investigate the relationship between OH at follow-up and recurrent stroke risk in SPS3 (Secondary Prevention of Small Subcortical Strokes) trial patient cohort. This is a retrospective cohort analysis. Methods: We included all SPS3 trial participants with blood pressure measurements in both sitting and standing position per protocol at baseline, with at least 1 follow-up visit to establish the relationship between OH at follow-up and recurrent stroke risk (primary outcome). Secondary outcomes included major vascular events, myocardial infarction, all-cause mortality, and, ischemic and hemorrhagic stroke subtypes. Participants were classified as having OH at baseline and at each follow-up visit based on a systolic BP decline ≥20 mm Hg or a diastolic BP decline ≥10 mm Hg on position change from sitting to standing. We used Cox proportional hazards regression modeling to compare the risk of outcomes among those with and without OH. Results: A total of 2275 patients were included with a mean follow up time 3.2 years (standard deviation = 1.6 years). 39% (881/2275) had OH at some point during their follow-up. Of these, 41% (366/881) had orthostatic symptoms accompanying the BP drop. In a fully adjusted model, those with OH had a 1.8 times higher risk of recurrent stroke than those without OH (95% confidence interval: 1.1-3.0). The risk of ischemic stroke, major vascular events, and all-cause mortality was similarly elevated among the OH group. Conclusion: OH was associated with increased recurrent stroke risk, vascular events, and all-cause death in this large cohort of lacunar stroke patients. Whether minimizing OH in the management of poststroke hypertension in patients with lacunar stroke reduces recurrent stroke risk deserves further study.     

Secondary Stroke Prophylaxis with Clopidogrel Produces Sufficient Antiplatelet Response

Background

Antiplatelet therapy is a cornerstone prevention strategy for secondary ischemic stroke (IS) and transient ischemic attack (TIA). Yet, a proportion of patients who receive antiplatelet therapy experience recurrent ischemic cerebrovascular events. A recent meta-analysis found an increased risk of recurrent stroke in clopidogrel- or aspirin-treated patients with ischemic stroke who had high on-treatment platelet reactivity (HTPR). Few studies have focused specifically on clopidogrel HTPR. Therefore, the aim of this study was to examine the relationship between clopidogrel HTPR and recurrent ischemic events in a population of Danish patients with IS.

Association of CYP3A4*1G and CYP3A5*3 With the 1-year Outcome of Acute Ischemic Stroke in the Han Chinese Population

Background and purpose: Previous studies have shown that common variants within CYP3A4 and CYP3A5 are associated with statin pharmacokinetics and the risk of cardiovascular disease. However, the association of variants in CYP3A4 and CYP3A5 with the prognosis of ischemic stroke remains undetermined. Therefore, we investigated this herein. Methods: Four hundred thirty-three consecutive patients with acute ischemic stroke were recruited. The outcome at the 1-year follow-up was assessed using the modified Rankin Scale (mRS). Two variants, CYP3A4*1G and CYP3A5*3, were genotyped by the improved Multiple Ligase Detection Reaction platform. Results: Binary logistic regression analysis showed that the CYP3A4*1G/*1G homozygote was associated with poor outcome at 1 year (mRS score ≥2) after adjustment for conventional factors in the additive model (odds ratio [OR] = 2.92; 95% confidence interval, 1.07-7.98; P = .037) and recessive model (OR = 3.37; 95% confidence interval, 1.26-9.04; P = .016). Subgroup analysis indicated that the CYP3A4*1G/*1G homozygote was associated with poor prognosis at 1 year among patients with stable high-intensity atorvastatin therapy (40-80 mg/d) after adjustment for conventional factors in the additive model (OR = 8.16; 95% confidence interval, 1.50-44.44; P = .015) and recessive model (OR = 9.06; 95% confidence interval, 1.72-47.64; P = .009). No significant association was identified between CYP3A5*3 and the 1-year outcome of patients with ischemic stroke. Conclusions: Our study findings suggest that the CYP3A4*1G/CYP3A4*1G genotype may be associated with poor prognosis at 1 year after acute ischemic stroke in the Han Chinese population.     

ADP‐induced platelet aggregation in acute ischemic stroke patients on aspirin therapy

Background and purpose: Aspirin is an important therapeutic regimen to prevent the recurrent ischemic events or death after acute ischemic stroke. In this study, we evaluated the relationship between the extent of adenosine diphosphate (ADP) ‐induced platelet aggregation and outcome in acute ischemic stroke patients on aspirin therapy. Methods: We selected 107 acute ischemic stroke patients who had been prescribed aspirin and evaluated platelet function test by using optic platelet aggregometer test after 5 days of taking it and investigated the prognosis 90 days after ischemic events. Kaplan–Meyer curve was used for survival analysis. Results: After stratification of the subjected patients by tertiles of ADP‐induced platelet aggregation, the events rates were 7.4%, 9.3% and 30.8% (P = 0.023). In multiple logistic regression analysis, old age over 70 years (OR, 13.7; 95% CI, 2.14–88.07; P = 0.001) and the increased ADP‐induced platelet aggregation had independent significance to the risk of primary end‐points after acute ischemic stroke (OR, 1.1; 95% CI 1.01 to 1.20; P = 0.026). Conclusions: This study showed that the increased ADP‐induced platelet aggregation under using aspirin is associated with poor outcome after acute ischemic stroke.     

Predictive utility of stress tests in the detection of asymptomatic coronary artery disease in atherosclerotic stroke patients

IntroductionWhether and how atherosclerotic ischemic stroke patients should be investigated for asymptomatic coronary artery disease (CAD) is controversial. Our aim was to carry out a prospective observational study to determine the frequency and predictors of functionally significant coronary stenosis in these patients as well as the predictors of major adverse cardiovascular events (MACE) during post-stroke follow-up.Material and methodsFrom January 2014 to June 2018, patients with atherosclerotic ischemic stroke were referred from the stroke unit to our cardiovascular department 3+/- 1 months after the acute event where they benefited from evaluation of cardiovascular risk factors, vascular and myocardial disease. Main outcome was defined as the prevalence of myocardial ischemia defined by perfusion stress echography 3 months after stroke. Secondary outcome (MACE) was defined as the incidence of stroke, transient ischemic attack (TIA), acute coronary syndrome, cardiovascular (CV) death or coronary or peripheral revascularization during a 3 year follow-up.ResultsThree hundred and twenty five patients (92% of strokes and 8% TIA) were included and median follow-up was 1075 days. At 3 months post-stroke, myocardial ischemia was found in 17 patients (5.2%). During the 3 year follow-up, 11 MACE occurred (3.4%, all in the non-ischemic group) of which 6 were recurrent strokes. In multivariate analysis, myocardial ischemia was significantly associated with the number of atheromatous vascular beds (OR 4.3; 95% CI, 1.7 to 10.6) and ECG signs of necrosis (OR 6.5; 95% CI, 1.9 to 21.9). MACE were also associated with ECG signs of necrosis (OR 3.5; 95% CI, 1.3 to 9.1), and unrelated to myocardial ischemia.ConclusionMyocardial ischemia and CV events were infrequent and both strongly associated with ECG signs of necrosis, suggesting a low yield of stress tests and the potential for a more straightforward algorithm in the choice of patients eligible to coronary angiogram or other coronary imaging in post-stroke setting.     

Rationale, design and baseline data of a randomized, double-blind, controlled trial comparing two antithrombotic regimens (a fixed-dose combination of extended-release dipyridamole plus ASA with clopidogrel) and telmisartan versus placebo in patients with strokes: the Prevention Regimen for Effectively Avoiding Second Strokes Trial (PRoFESS)

BACKGROUND: Individuals with transient ischemic attack and ischemic stroke have a high risk of recurrent stroke and death. While acetylsalicylic acid (ASA, aspirin) is proven and accepted as standard therapy in these patients, recent trials demonstrate that a combination of ASA and dipyridamole (DP) or clopidogrel may be superior to ASA. Blocking the renin-angiotensin system with angiotensin-converting enzyme inhibitors or angiotensin receptor blockers may also reduce recurrent stroke. The ongoing PRoFESS (Prevention Regimen for Effectively Avoiding Second Strokes) trial is designed to evaluate whether ASA + extended-release DP compared to clopidogrel, and whether telmisartan in addition to usual care in individuals after a stroke, will reduce the risk of further strokes. METHODS: PRoFESS is a multicenter, randomized, double-blind trial involving 695 sites from 35 countries or regions. Patients > or = 50 years presenting with an ischemic stroke < 120 days who were stable were randomized. The primary outcome for the trial is recurrent stroke, using a time-to-event analysis. The most important secondary outcome is the composite of stroke, myocardial infarction or vascular death. Other secondary outcomes include this composite + congestive heart failure, new-onset diabetes, other designated occlusive vascular events (pulmonary embolism, deep-vein thrombosis, peripheral arterial occlusion, transient ischemic attack, cerebral venous thrombosis or retinal vascular accident not classified as stroke), any death, stroke subtype by TOAST criteria and Mini Mental State Examination score. Safety is evaluated by assessing the risk of major hemorrhagic events. The comparison between ASA + DP and clopidogrel is based on an initial assessment of noninferiority, followed by evaluation of superiority, while for telmisartan, we will assess its superiority over placebo. RESULTS: With over 20,000 patients randomized, and utilizing a 2 x 2 factorial design, PRoFESS is the largest stroke trial to investigate the prevention of recurrent stroke. The mean age was 66.1 +/- 8.6 years, and 36.0% of the patients were females. The median time from qualifying event to randomization was 15 days with 39.9% of patients randomized within 10 days. According to the TOAST criteria, 28.5% of the strokes were due to large-vessel disease, 52.1% to small-vessel disease, 1.8% to cardioembolism, and 2.0% to other determined etiologies and 15.5% were of undetermined etiology. CONCLUSIONS: PRoFESS is the largest secondary stroke prevention trial to date and will directly compare two antiplatelet regimens as well as the benefit of telmisartan versus placebo.     

既往卒中病史对缺血性脑血管病患者卒中结局的影响研究

目的 探讨中国人群中首发和复发缺血性脑血管病患者的临床特征和卒中结局差异。 方法 本研究基于全国多中心前瞻性中国国家卒中登记研究Ⅲ（the third China national stroke regi stry,CNSR-Ⅲ）,连续纳入2015年8月-2018年3月急性缺血性卒中或TIA患者,收集人口学信息、血 管危险因素、既往用药史及病因分型系统（causative classification system,CCS）等临床资料,记录随 访3个月和1年时卒中结局。卒中结局包括卒中复发（缺血性卒中或出血性卒中）、联合血管事件（卒中、 心肌梗死及血管性死亡事件）、脑血管病源性死亡及不良功能结局（mRS＞2分）。依据患者既往是否 有卒中病史分为有卒中病史组和无卒中病史组,比较两组的临床特征及卒中结局差异,并分析卒中病 史与卒中结局间的关系。 结果 最终纳入15 166例患者,平均年龄62.2±11.3岁,其中女性4802例（31.7%）;有卒中病史患者 3355例,无卒中病史患者11 811例。有卒中病史组患者年龄,冠心病、高血压、脂代谢紊乱、糖尿病、心 房颤动比例,既往用药史比例、入院NIHSS评分、住院期间降糖和降压治疗比例均高于无卒中病史组, 目前吸烟和重度饮酒比例、入院时LDL-C水平及住院期间抗血小板治疗比例低于无卒中病史组,差 异均有统计学意义。两组CCS分型的分布差异有统计学意义,其中有卒中病史组大动脉粥样硬化型和 心源性栓塞型卒中比例高于无卒中病史组。多因素分析结果显示,卒中病史是随访3个月不良功能结 局（校正OR 1.25,95%CI 1.09～1.44,P =0.002）,随访1年卒中复发（校正HR 1.44,95%CI 1.25～1.67, P＜0.001）、联合血管事件（校正HR 1.43,95%CI 1.24～1.64,P＜0.001）、脑血管病源性死亡（校正 HR 1.42,95%CI 1.12～1.80,P =0.004）、不良功能结局（校正OR 1.63,95%CI 1.42～1.88,P＜0.001）的 危险因素。 结论 有无卒中病史的缺血性卒中患者的临床特征及随访结局差异较大,尽管患者进行卒中二级 预防治疗,卒中病史仍然是患者1年卒中复发、联合血管事件、脑血管病源性死亡及不良功能结局的 危险因素。     

锌指同源框3基因多态性与不同亚型缺血性卒中结局的特异性关联研究

目的 分析中国卒中人群中锌指同源框3（zinc finger homeobox 3，ZFHX3）基因单核苷酸变异（single nucleotide variant，SNV）位点对卒中结局的影响。 方法 本研究基于全国多中心前瞻性中国国家卒中登记研究Ⅲ，连续纳入2015年8月-2018年3月首 次发生急性缺血性卒中或TIA的患者，收集人口学信息、病史和卒中结局等相关临床资料。卒中结局 包括随访1年内卒中复发（缺血性卒中或出血性卒中）、联合血管事件（卒中、心肌梗死及血管性死亡 事件）及不良功能结局（mRS＞2分）。采用竞争性等位基因特异性PCR技术对3个SNV位点（rs7193343、 rs879324、rs12932445）进行基因分型。对于研究过程中的计量资料和计数资料，分别采用线性回归 或逻辑回归进行关联分析；对于卒中结局，分别采用Cox或逻辑回归进行关联分析。 结果 最终纳入7674例患者，平均年龄61.7±11.5岁，其中女性2438例（31.77%）。关联分析结果 显示，处于高度连锁不平衡状态（相关系数R 2=0.88）的rs879324和rs12932445位点与心房颤动、入 院时NIHSS评分及卒中亚型有关联。在不同卒中亚型中，3个SNV位点均与1年联合血管事件相关，在 校正年龄、性别及心房颤动协变量后关联性仍然显著。在心源性栓塞型卒中患者中，rs7193343位点 的T等位基因与卒中复发、联合血管事件的发生有关联（校正HR 1.92，95%CI 1.21～3.05；校正HR 1.95，95%CI 1.26～3.01）；rs879324位点的A等位基因和rs12932445位点的C等位基因与联合血管事 件有关联（校正HR 1.58，95%CI 1.10～2.27；校正HR 1.66，95%CI 1.16～2.38）。在原因未明型卒中患 者中，rs7193343位点的T等位基因与卒中复发和联合血管事件的发生有关联（校正HR 1.34，95%CI 1.09～1.64；校正HR 1.36，95%CI 1.11～1.66）。校正相关因素后未发现3个SNV位点与不良功能结局之 间存在关联。 结论 ZFHX3基因上的变异位点与特定卒中亚型的卒中复发及联合血管事件的发生风险存在关联， 但未发现与不良功能结局有关。     

Cardiovascular and cerebrovascular events in patients with intracerebral hemorrhage: Clinical characteristics and long-term predictors

Few studies have examined the long-term prognosis of Chinese patients with intracerebral hemorrhage (ICH). This study assessed the clinical characteristics and predictors of vascular events occurring within 5 years after ICH.We included consecutive patients diagnosed with first-ever ICH between June 2013 and December 2014. Based on follow-up data (collected until December 2019), we used multivariable logistic regression to examine the clinical characteristics and long-term predictors of vascular events (including recurrent ICH, ischemic stroke, and acute coronary syndrome) in patients who survived more than 30 days after ICH.Across the 307 patients in our analysis, the 5-year mortality rate was 28.01%. Within 5 years after ICH, major vascular events were observed in 62 patients (17.82%, 95% CI 13.78–21.82%). We observed high incidence of recurrent ICH (8.91%) and ischemic stroke (10.06%), but low incidence of acute coronary syndrome (1.15%). Most cases of recurrent ICH (80.65%) occurred within 3 years after ICH. Age ≥56 years and history of ischemic stroke or transient ischemic attack (TIA) were identified as predictors of cardiovascular and cerebrovascular events.ICH survivors are at high risk of both cardiovascular and cerebrovascular events, especially older patients (≥56 years) and those who experienced ischemic stroke or TIA prior to their first ICH. Recurrent ICH is more likely to occur within the first three years after first ICH than at later times. Clinicians should monitor patients closely for adverse events, particularly during the first three years after initial ICH.     

Lateralization of Insular Ischemic Stroke is Not Associated With Any Stroke Clinical Outcomes: The Athens Stroke Registry

Background: Controversial evidence suggests that right insular stroke may be associated with worse outcomes compared to the left insular ischemic lesion. Objectives: We investigated whether lateralization of insular stroke is associated with early and late outcome in terms of in-hospital complications, stroke recurrence, cardiovascular events, and death. Methods: Data were prospectively collected from the Athens Stroke Registry. Insular cortex involvement was identified based on brain CT scans or MRI images. Patients were followed up prospectively at 1, 3, 6 months after hospital discharge and yearly thereafter up to 5-years or until death. The assessed outcomes were in-hospital complications, functional outcome assessed by the modified Rankin Scale, stroke recurrence, cardiovascular events, and death. Cox-regression analysis was performed to estimate the cumulative probability of each outcome according to the lateralization of insular strokes. Results: Among the 1212 patients, 650 had left insular stroke involvement and 562 had right. New onset of in-hospital atrial fibrillation was similar between right and left insular strokes (11.6% versus 12.9%, P = .484). During the 5-year follow-up sudden death occurred in 21 (3.7%) patients with right insular compared to 30 (4.6%) with left insular stroke (P = .476). There was no difference between left and right insular strokes regarding mortality (adjusted odds ratio [OR]: .92, 95% confidence interval [CI]: .80-1.06), stroke recurrence (4.3% versus 4.9%; adjusted OR: .81 95% CI: .58-1.13), cardiovascular events, and sudden death (adjusted OR: .99, 95% CI: .76-1.29) and on death and dependency (adjusted OR: .88, 95% CI: .75-1.02) during a 5-year follow up. Conclusions: Lateralization of insular ischemic stroke involvement is not associated with stroke outcomes.     

Impact of CHADS2 Score on Neurological Severity and Long-Term Outcome in Atrial Fibrillation-Related Ischemic Stroke

Background and Purpose

The CHADS₂ (an acronym for congestive heart failure, hypertension, age ≥75 years, diabetes mellitus, and prior stroke or transient ischemic attack or thromboembolism) score is a widely used system for estimating the risk of stroke in patients with atrial fibrillation. However, how the CHADS₂ score is related to stroke severity and outcome in patients with strokes due to atrial fibrillation has not yet been elucidated.

Methods

We enrolled patients with atrial fibrillation who visited our stroke center within 7 days after the onset of acute ischemic stroke between October 2002 and September 2008. CHADS₂ scores were categorized into three groups: 0 points, low risk; 1 or 2 points, intermediate risk; and 3-6 points, high risk. Poor neurological state was defined as follows: a National Institutes of Health Stroke Scale (NIHSS) score of ≥2, and a modified Rankin Scale (mRS) score of ≥3 at discharge. Mortality information was ascertained as at December 2008.

Results

A cohort of 298 patients with atrial-fibrillation-related stroke was included in this study. A high-risk CHADS₂ score at admission was a powerful predictor of poor neurological outcome [for NIHSS: odds ratio (OR), 4.17; 95% confidence interval (CI), 1.76-9.87; for mRS: OR, 2.97; 95% CI, 1.23-7.16] after controlling for all possible confounders. In addition, a high-risk CHADS₂ score was an independent predictor of all causes of death during the follow-up [hazard ratio (HR), 3.01; 95% CI, 1.18-7.65] and vascular death (HR, 12.25; 95% CI, 1.50-99.90).

Conclusions

Although the CHADS₂ score was originally designed to distinguish patients with a future risk of stroke, our study shows that it may also be used to predict poor neurological outcome after atrial-fibrillation-related stroke.     

Temporal Trends in the Use of Acute Recanalization Therapies for Ischemic Stroke in Patients with Cancer

Objective: We sought to characterize the US nationwide temporal trends in recanalization therapy utilization for ischemic stroke among patients with and without cancer. Methods: We identified all acute ischemic stroke (AIS) hospitalizations in the National Inpatient Sample from January 1, 1998 to September 30, 2015. The primary exposure was solid or hematologic cancer. The primary outcome was use of intravenous thrombolysis. The secondary outcome was use of endovascular therapy (EVT). Results: Among 9,508,804 AIS hospitalizations, 503,510 (5.3%) involved cancer patients. Intravenous thrombolysis use among ischemic stroke patients with cancer increased from .01% (95% confidence interval [CI], .00%-.02%) in 1998 to 4.91% (95% CI, 4.33%-5.48%) in 2015, whereas intravenous thrombolysis use among ischemic stroke patients without cancer increased from .02% (95% CI, .01%-.02%) in 1998 to 7.22% (95% CI, 6.98%-7.45%) in 2015. The demographic- and comorbidity-adjusted odds ratio/year of receiving intravenous thrombolysis was similar in patients with cancer (1.21; 95% CI, 1.20-1.23) versus those without (1.20; 95% CI, 1.19-1.21). EVT use among ischemic stroke patients with cancer increased from .05% (95% CI, .02%-.07%) in 2006 to 1.90% (95% CI, 1.49%-2.31%) in 2015, whereas EVT use among ischemic stroke patients without cancer increased from .09% (95% CI, .00%-.18%) in 2006 to 1.88% (95% CI, 1.68%-2.09%) in 2015. Conclusions: Among 9.5 million AIS hospitalizations, patients with cancer received intravenous thrombolysis about two thirds as often as patients without cancer. This difference persisted over time despite increased utilization in both groups. EVT utilization was similar between cancer and non–cancer AIS patients.     

Intracranial Artery Calcium Burden Predicts Recurrent Cerebrovascular Events in Transient Ischaemic Attack Patients

Background: Patients with initial transient ischaemic attack (TIA) subsequently have a higher risk of recurrent TIA or acute ischemic stroke (AIS). The role of scoring intracranial arterial calcification (IAC) in predicting the prevalence of stroke remains unclear. We aim to evaluate if radiological CT calcium score measuring IAC burden could predict future ischemic events in a cohort of TIA patients. Methods: We studied consecutive patients from July 2014 to December 2015 who presented with first episode of TIA. All patients had noncontrasted CT or CT-angiogram of the brain on admission. CT calcium score (cm3) was quantified by measuring calcium deposition in the bilateral internal carotid arteries, middle cerebral arteries, and vertebrobasilar system. Patients were followed up for 2 years and ischemic events for either recurrent TIA or AIS were recorded. We compared patients in terms of clinical profile at presentation and CT calcium score using appropriate univariate and multivariable analyses. Results: Of 156 TIA patients studied, 22% (n = 35) had recurrent TIA or AIS within 2 years of follow-up. On univariate analyses, recurrent TIA/AIS was associated with gender (OR 0.61; 95%CI 0.40-0.95; P = .038), hypertension (mean difference 2.49; 95%CI 1.08-5.75; P = .030) and higher CT calcium score (mean difference 0.84 95%CI 0.16-1.52 P = .016). On multivariable logistic regression, a higher CT calcium score was significantly associated with recurrent TIA/AIS (adjusted OR 1.25 95%CI 1.01-1.55 P = .042). Conclusions: In TIA patients, higher IAC burden by measurement of a quantitative CT calcium score may be associated with recurrent ischemic events.     

Underweight predicts poststroke cardiovascular events in patients without atrial fibrillation

Background and purposeThe purpose of this study was to determine whether underweight is associated with poststroke cardiovascular events and whether such association is different according to the presence of atrial fibrillation (AF).MethodsPatients with acute stroke or transient ischemic attack who were prospectively registered in a multicenter stroke database from April 2008 to July 2020 were analyzed, excluding those aged 75 or older and those who were overweight. We prospectively captured major adverse cardiovascular events (MACE) within one year after stroke. Cox-proportional hazard regression analysis was conducted for each subgroup with or without AF after adjusting for predetermined vascular risk factors and potential confounders.ResultsAmong 30,912 patients, 1494 (4.8%) cases were underweight and 29,418 (95.2%) cases were normal weight. The cumulative event rate of 1-year MACE was higher in the underweight group (9.0%) than in the normal weight group (5.6%). In Cox-proportional regression, underweight was associated with significantly higher MACE (adjusted hazard ratio [HR]: 1.62, 95% confidence interval [CI]: 1.26–2.09) and recurrent stroke (adjusted HR: 1.42, 95% CI: 1.02–1.98) in all study patients. In patients with AF, the risk of MACE for the underweight group was not significantly increased. In contrast, in patients without AF, the underweight group had a consistently higher risk of MACE (adjusted HR: 1.66, 95% CI: 1.25–2.22) and recurrent stroke (adjusted HR: 1.50, 95% CI: 1.05–2.14).ConclusionsUnderweight increased the risk of MACE and recurrent stroke within one year after acute stroke, especially in stroke without AF.     

Osteoprotegerin Assessment Improves Prediction of Mortality in Stroke Patients

Background: Elevated circulating osteoprotegerin (OPG) level is associated with an increased risk of hospitalization for ischemic stroke and coronary artery disease. The aim of the present study was to analyze whether OPG assessment may improve the prediction of mortality in patients with stroke. Patients and Methods: Serum OPG, fetuin A, 25-OH-D₃, intact parathyroid hormone levels were assessed in serum samples which were left over after routine tests in a hospital laboratory. This assessment was conducted in 240 consecutive patients with acute ischemic stroke, admitted within 24hours after the onset of symptoms to the Stroke Unit. Mortality data were obtained from the local registry office. Results: The mean OPG serum level was 14.6 ± 6.0pmol/L (range: 3.7-43.4). There were no significant differences in the OPG values between men and women (13.9 ± 5.0 versus 15.1 ± 6.7 pmol/L; P = .12). Therefore, tertiles were calculated for the whole group. During the follow-up, 85 (35.4%) patients died and 92 (38.3%) died or had recurrent stroke. OPG level appeared a significant predictors of death and composite end-point (death/recurrent stroke), in addition to the well-established once (age, atrial fibrillation, diabetes RANKIN at admission and discharge, severity of stroke). In multivariable stepwise backward analyses, the OPG level persisted as a significant and independent predictor of death (hazard ratio [HR]?=?1.084 (95% confidence intervals: 1.036-1.134)] and composite and point (HR?=?1.082 [1.037-1.129]). Conclusions: OPG level may be considered as a predictor of mortality in stroke patients.     

Association of obesity with recurrent stroke and cardiovascular events

Background and purposeThe relation between obesity and stroke recurrence is still under debate. In this study, we investigated whether initial obesity was associated with recurrent stroke and major cardiovascular events over a long period of time.Materials and methodsFive-years follow-up data of the Ege Stroke Registry for stroke recurrence and cardiovascular events related to obesity were analyzed. Data include age, gender, stroke severity, neuroimaging studies, cardiovascular risk factors. Within the inclusion period, all of the included patients were followed until censoring (10th of December 2011) or readmission because of recurrent stroke, cardiovascular event or death, whichever came first. The Kaplan-Meier method was used for survival analysis. Cox proportional hazard model was applied to identify predictors of stroke and all major vascular events.ResultsOf 9285 eligible patients for evaluation, 5158 (56%) were male and 3068 (33%) with a prior stroke were obese at baseline. Among 2198 patients with recurrent stroke, 843 (38%) had obesity while 2229 (62%) had no obesity (HR, 1.36; 95% CI, 1.23–1.50; P < 0.001). Overall major vascular events (recurrent stroke, cardiovascular events, and death) occurred in 1464 obese patients (48%) and in 2182 non-obese patients (35%) (HR, 1.69; 95%CI, 1.55–1.84). Cox hazard model showed that being obese was associated with increased recurrent stroke risk compared with those without obesity (HR, 0.85; 95%CI, 0.76–0.94; P < 0.001), being obese was not associated with cardiovascular events (HR, 1.09; 95%CI, 0.95–1.26; P = 0.22).ConclusionsOur results showed that obesity is a significant risk factor for recurrent stroke, although obesity was not associated significantly with myocardial infarction and death after 5-years of first stroke. Further clinical goal-directed weight reduction outcome trials in this area will be critical to validate the most effective approaches and, ultimately, to guide policy is certainly needed.     

Post-stroke cognitive impairment and the risk of stroke recurrence and death in patients with insulin resistance

ObjectivePost-stroke cognitive impairment (PSCI) is associated with etiology, severity, and functional outcome of stroke. The risks of recurrent stroke and death in patients with PSCI and insulin resistance (IR) is unknown. The goal of this study was to determine whether global and domain-specific cognitive impairment after stroke in patients with IR was associated with recurrent stroke and death.Materials and MethodsWe studied patients with recent stroke or transient ischemic attack (TIA) and IR with a baseline Modified Mini-Mental State Examination (3MS) cognitive exam at median of 79 days after stroke. We considered a baseline score of ≤ 88 on the 3MS to indicate global cognitive impairment, and domain-specific summary scores in the lowest quartile to indicate language, attention, orientation, memory and visuospatial impairments. The primary endpoint was fatal or non-fatal recurrent stroke, and the secondary endpoints were all-cause mortality, and fatal or non-fatal myocardial infarction (MI).ResultsAmong studied n = 3,338 patients 13.6% had global cognitive impairment. During the median 4.96 years of follow-up, 7.4% patients experienced recurrent stroke, 3.5% MI, and 7.3% died. In the fully adjusted model, impairment in language (HR 1.35; 95% CI 1.01—1.81) and orientation (HR 1.41; 95% CI: 1.06—1.87) were associated with a higher risk of recurrent stroke, while attention impairment was associated with all-cause mortality (HR 1.34; 95% CI: 1.01—1.78).Discussion/ConclusionIn patients with recent stroke/TIA and IR, post-stroke language and orientation impairments independently predicted recurrent stroke, while attention deficit was associated with increased risk of all-cause mortality.     

The prognostic value of pulsatility index, flow velocity, and their ratio, measured with TCD ultrasound, in patients with a recent TIA or ischemic stroke

Wijnhoud AD, Koudstaal PJ, Dippel DWJ. The prognostic value of pulsatility index, flow velocity, and their ratio, measured with TCD ultrasound, in patients with a recent TIA or ischemic stroke.
Acta Neurol Scand: 2011: 124: 238–244.
© 2011 John Wiley & Sons A/S. Background – Increased flow velocities, and combinations of low mean flow velocity (MFV) and a high pulsatility index (PI) are associated with intracranial arterial disease. We investigated the association of MFV and the ratio of PI and MFV (PI–MFV ratio) in the middle cerebral artery (MCA) with recurrence of vascular events in patients with a transient ischemic attack (TIA) or minor ischemic stroke. Methods – Five hundred and ninety‐eight consecutive patients underwent TCD investigation. Outcome events were fatal or non‐fatal stroke and the composite of stroke, myocardial infarction, or vascular death (major vascular events). Hazard ratios (HR) were estimated with Cox proportional hazards multiple regression method, adjusted for age, gender, and vascular risk factors. Results – TCD registration was successful in 489 patients. Mean follow‐up was 2.1 years. Cumulative incidence was 9% for all stroke and 12% for major vascular events. MFV over 60.5 cm/s increased the risk for both stroke (HR 2.8; 95% CI: 1.3–6.0) and major vascular events (HR 2.6; 95% CI: 1.3–5.0). Each unit increase in PI–MFV ratio was associated with a HR 2.8 (95% CI: 1.7–4.8) for stroke and HR 2.2 (95% CI: 1.3–3.6) for major vascular events. Conclusion – In patients with a TIA or non‐disabling ischemic stroke, MFV and the PI–MFV ratio in the MCA are independent prognostic factors for recurrent vascular events.     

Statin treatment after a recent TIA or stroke: is effectiveness shown in randomized clinical trials also observed in everyday clinical practice?

Lingsma HF, Steyerberg EW, Scholte op Reimer WJM, van Domburg R, Dippel DWJ, the Netherlands Stroke Survey Investigators. Statin treatment after a recent TIA or stroke: is effectiveness shown in randomized clinical trials also observed in everyday clinical practice?
Acta Neurol Scand: 2010: 122: 15–20.
© 2009 The Authors Journal compilation © 2009 Blackwell Munksgaard. Aim and background – The benefit of statin treatment in patients with a previous ischemic stroke or transient ischemic attack (TIA) has been demonstrated in randomized clinical trials (RCT). However, the effectiveness in everyday clinical practice may be decreased because of a different patient population and less controlled setting. We aim to describe statin use in an unselected cohort of patients, identify factors related to statin use and test whether the effect of statins on recurrent vascular events and mortality observed in RCTs is also observed in everyday clinical practice. Methods – In 10 centers in the Netherlands, patients admitted to the hospital or visiting the outpatient clinic with a recent TIA or ischemic stroke were prospectively and consecutively enrolled between October 2002 and May 2003. Statin use was determined at discharge and during follow‐up. We used logistic regression models to estimate the effect of statins on the occurrence of vascular events (stroke or myocardial infarction) and mortality within 3 years. We adjusted for confounders with a propensity score that relates patient characteristics to the probability of using statins. Results – Of the 751 patients in the study, 252 (34%) experienced a vascular event within 3 years. Age, elevated cholesterol levels and other cardiovascular risk factors were associated with statin use at discharge. After 3 years, 109 of 280 (39%) of the users at discharge had stopped using statins. Propensity score adjusted analyses showed a beneficial effect of statins on the occurrence of the primary outcome (odds ratio 0.8, 95% CI: 0.6–1.2). Conclusion – In our study, we found poor treatment adherence to statins. Nevertheless, after adjustment for the differences between statin users and non‐statin users, the observed beneficial effect of statins on the occurrence of vascular events within 3 years, although not statistically significant, is compatible with the effect observed in clinical trials.