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Serum erythropoietin and outcome after ischaemic stroke: a prospective study.

ABSTRACT: Erythropoietin (EPO), which is inversely associated with blood haemoglobin (Hb), exerts neuroprotective effects in experimental ischaemic stroke (IS). However, clinical treatment trials have so far been negative. Here, in patients with IS, we analysed whether serum EPO is associated with (1) initial stroke severity, (2) recovery and (3) functional outcome.Prospective. Controls available at baseline.A Swedish hospital-initiated study with outpatient follow-up after 3 months.Patients (n=600; 64% males, mean age 56 years, controls n=600) were included from the Sahlgrenska Academy Study on IS (SAHLSIS).In addition to EPO and Hb, initial stroke severity was assessed by the Scandinavian Stroke Scale (SSS) and compared with SSS after 3 months (follow-up) as a measure of recovery. Functional outcome was evaluated using the modified Rankin Scale (mRS) at follow-up. Serum EPO and SSS were divided into quintiles in the multivariate regression analyses.Serum EPO was 21% and 31% higher than in controls at the acute phase of IS and follow-up, respectively. In patients, acute serum EPO was 19.5% higher in severe versus mild IS. The highest acute EPO quintile adjusted for sex, age and Hb was associated with worse stroke severity quintile (OR 1.70, 95% CI 1.00 to 2.87), better stroke recovery quintile (OR 1.93, CI 1.09 to 3.41) and unfavourable mRS 3-6 (OR 2.59, CI 1.15 to 5.80). However, the fourth quintile of EPO increase (from acute to follow-up) was associated with favourable mRS 0-2 (OR 3.42, CI 1.46 to 8.03). Only the last association withstood full adjustment.The crude associations between EPO and worse stroke severity and outcome lost significance after multivariate modelling. However, in patients in whom EPO increased, the association with favourable outcome remained after adjustment for multiple covariates.

SUBMITTER: Aberg ND

PROVIDER: S-EPMC4769431 | biostudies-other | 2016 Feb

REPOSITORIES: biostudies-other

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Project description:ObjectiveWe report on: (1) the proportion of patients with known atrial fibrillation (AF); and (2) demographic, clinical or radiological differences between patients with known AF (and not treated) and patients with newly diagnosed AF, in a cohort of patients who presented with ischaemic stroke or transient ischaemic attack (TIA) not previously treated with anticoagulation.DesignWe reviewed cross-sectional baseline demographic and clinical data from a prospective observational cohort study, (CROMIS-2).SettingPatients were recruited from 79 hospital stroke centres throughout the UK and one centre in the Netherlands.ParticipantsPatients were eligible if they were adults who presented with ischaemic stroke or TIA and AF and had not been previously treated with oral anticoagulation.Main outcome measuresProportion of patients with known AF before index ischaemic stroke or TIA from a cohort of patients who have not been previously treated with oral anticoagulation. Secondary analysis includes the comparison of CHA2DS2-VASc and HAS-BLED scores and other demographics and risk factors between those with newly diagnosed AF and those with previously known AF.ResultsOf 1470 patients included in the analysis (mean age 76 years (SD 10)), 622 (42%) were female; 999 (68%) patients had newly diagnosed AF and 471 (32%) patients had known AF. Of the 471 patients with known AF, 68% had a strong indication for anticoagulation and 89% should have been considered for anticoagulation based upon CHA2DS2-VASc score. Patients with known AF were more likely to have a prior history of dementia (4% vs 2%, p=0.02) and had higher HAS-BLED scores (median 3 vs 2). CHA2DS2-VASc, other risk factors and demographics were similar.ConclusionsAbout 1/3 of patients who present with stroke and have AF who have not been treated with oral anticoagulation have previously known AF. Of these patients, at least 68% were not adequately treated with oral anticoagulation.Trial registration numberNCT02513316.

Project description:IntroductionNeuropsychiatric distubance is a common clinical manifestation in acute ischemic stroke. However, it is frequently overlooked by clinicians. This study aimed to explore the possible aetiology and pathogenesis of neuropsychiatric disturbances following ischaemic stroke (NDIS) from an anatomical and functional perspective with the help of neuroimaging methods.Method and analysisCONNECT is a prospective cohort study of neuroimaging and its functional outcome in NDIS. We aim to enrol a minimum of 300 individuals with first-ever stroke. The neuropsychological disturbances involved in this study include depression, anxiety disorder, headache, apathy, insomnia, fatigue and cognitive impairment. Using scales that have been shown to be effective in assessing the above symptoms, the NDIS evaluation battery requires at least 2 hours at baseline. Moreover, all patients will be required to complete 2 years of follow-up, during which the NDIS will be re-evaluated at 3 months, 12 months and 24 months by telephone and 6 months by outpatient interview after the index stroke. The primary outcome of our study is the incidence of NDIS at the 6-month mark. Secondary outcomes are related to the severity of NDIS as well as functional rehabilitation of patients. Functional imaging evaluation will be performed at baseline and 6-month follow-up using specific sequences including resting-state functional MRI, diffusion tensor imaging, T1-weighted imaging, T2-weighted imaging, diffusion-weighted imaging, arterial spin labelling, quantitative susceptibility mapping and fluid-attenuated inversion recovery imaging. In addition, we collect haematological information from patients to explore potential biological and genetic markers of NDIS through histological analysis.Ethics and disseminationThe CONNECT Study was approved by the Ethics Review Committee of the First Hospital of the University of Science and Technology of China (2021-ky012) and written informed consent will be obtained from all participants. Results will be disseminated via a peer-reviewed journal.Trial registration numberChiCTR2100043886.

Project description:BackgroundA third of transient ischaemic attacks (TIAs) and ischaemic strokes are of undetermined cause (ie, cryptogenic), potentially undermining secondary prevention. If these events are due to occult atheroma, the risk-factor profile and coronary prognosis should resemble that of overt large artery events. If they have a cardioembolic cause, the risk of future cardioembolic events should be increased. We aimed to assess the burden, outcome, risk factors, and long-term prognosis of cryptogenic TIA and stroke.MethodsIn a population-based study in Oxfordshire, UK, among patients with a first TIA or ischaemic stroke from April 1, 2002, to March 31, 2014, we compared cryptogenic events versus other causative subtypes according to the TOAST classification. We compared markers of atherosclerosis (ie, risk factors, coronary and peripheral arterial disease, asymptomatic carotid stenosis, and 10-year risk of acute coronary events) and of cardioembolism (ie, risk of cardioembolic stroke, systemic emboli, and new atrial fibrillation [AF] during follow-up, and minor-risk echocardiographic abnormalities and subclinical paroxysmal AF at baseline in patients with index events between 2010 and 2014).FindingsAmong 2555 patients, 812 (32%) had cryptogenic events (incidence of cryptogenic stroke 0·36 per 1000 population per year, 95% CI 0·23-0·49). Death or dependency at 6 months was similar after cryptogenic stroke compared with non-cardioembolic stroke (23% vs 27% for large artery and small vessel subtypes combined; p=0·26) as was the 10-year risk of recurrence (32% vs 27%; p=0·91). However, the cryptogenic group had fewer atherosclerotic risk factors than the large artery disease (p<0·0001), small vessel disease (p=0·001), and cardioembolic (p=0·008) groups. Compared with patients with large artery events, those with cryptogenic events had less hypertension (adjusted odds ratio [OR] 0·41, 95% CI 0·30-0·56; p<0·0001), diabetes (0·62, 0·43-0·90; p=0·01), peripheral vascular disease (0·27, 0·17-0·45; p<0·0001), hypercholesterolaemia (0·53, 0·40-0·70; p<0·0001), and history of smoking (0·68, 0·51-0·92; p=0·01), and compared with small vessel and cardioembolic subtypes, they had no excess risk of asymptomatic carotid disease (adjusted OR 0·64, 95% CI 0·37-1·11; p=0·11) or acute coronary events (adjusted hazard ratio [HR] 0·76, 95% CI 0·49-1·18; p=0·22) during follow-up. Compared with large artery and small vessel subtypes combined, patients with cryptogenic events also had no excess of minor-risk echocardiographic abnormalities (cryptogenic 37% vs 45%; p=0·18) or paroxysmal AF (6% vs 10%; p=0·17) at baseline or of new AF (adjusted HR 1·23, 0·78-1·95; p=0·37) or presumed cardioembolic events (1·16, 0·62-2·17; p=0·64) during follow-up.InterpretationThe clinical burden of cryptogenic TIA and stroke is substantial. Although stroke recurrence rates are comparable with other subtypes, cryptogenic events have the fewest atherosclerotic markers and no excess of cardioembolic markers.FundingWellcome Trust, Wolfson Foundation, UK Stroke Association, British Heart Foundation, Dunhill Medical Trust, National Institute for Health Research, Medical Research Council, and the NIHR Oxford Biomedical Research Centre.

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Serum erythropoietin and outcome after ischaemic stroke: a prospective study.

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