| 1. |
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| 2. |
- Anderson, Christopher D., et al.
(författare)
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Genetic variants in CETP increase risk of intracerebral hemorrhage
- 2016
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Ingår i: Annals of Neurology. - : Wiley. - 1531-8249 .- 0364-5134. ; 80:5, s. 730-740
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: In observational epidemiologic studies, higher plasma high-density lipoprotein cholesterol (HDL-C) has been associated with increased risk of intracerebral hemorrhage (ICH). DNA sequence variants that decrease cholesteryl ester transfer protein (CETP) gene activity increase plasma HDL-C; as such, medicines that inhibit CETP and raise HDL-C are in clinical development. Here, we test the hypothesis that CETP DNA sequence variants associated with higher HDL-C also increase risk for ICH.METHODS: We performed 2 candidate-gene analyses of CETP. First, we tested individual CETP variants in a discovery cohort of 1,149 ICH cases and 1,238 controls from 3 studies, followed by replication in 1,625 cases and 1,845 controls from 5 studies. Second, we constructed a genetic risk score comprised of 7 independent variants at the CETP locus and tested this score for association with HDL-C as well as ICH risk.RESULTS: Twelve variants within CETP demonstrated nominal association with ICH, with the strongest association at the rs173539 locus (odds ratio [OR] = 1.25, standard error [SE] = 0.06, p = 6.0 × 10(-4) ) with no heterogeneity across studies (I(2) = 0%). This association was replicated in patients of European ancestry (p = 0.03). A genetic score of CETP variants found to increase HDL-C by ∼2.85mg/dl in the Global Lipids Genetics Consortium was strongly associated with ICH risk (OR = 1.86, SE = 0.13, p = 1.39 × 10(-6) ).INTERPRETATION: Genetic variants in CETP associated with increased HDL-C raise the risk of ICH. Given ongoing therapeutic development in CETP inhibition and other HDL-raising strategies, further exploration of potential adverse cerebrovascular outcomes may be warranted. Ann Neurol 2016;80:730-740.
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| 3. |
- Antonenko, Kateryna, et al.
(författare)
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Sex-related differences in risk factors, type of treatment received and outcomes in patients with atrial fibrillation and acute stroke: Results from the RAF-study (Early Recurrence and Cerebral Bleeding in Patients with Acute Ischemic Stroke and Atrial Fibrillation)
- 2017
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Ingår i: European Stroke Journal. - : SAGE Publications. - 2396-9873 .- 2396-9881. ; 2:1, s. 46-53
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: Atrial fibrillation is an independent risk factor of thromboembolism. Women with atrial fibrillation are at a higher overall risk for stroke compared to men with atrial fibrillation. The aim of this study was to evaluate for sex differences in patients with acute stroke and atrial fibrillation, regarding risk factors, treatments received and outcomes. Methods: Data were analyzed from the ‘‘Recurrence and Cerebral Bleeding in Patients with Acute Ischemic Stroke and Atrial Fibrillation’’ (RAF-study), a prospective, multicenter, international study including only patients with acute stroke and atrial fibrillation. Patients were followed up for 90 days. Disability was measured by the modified Rankin Scale (0–2 favorable outcome, 3–6 unfavorable outcome). Results: Of the 1029 patients enrolled, 561 were women (54.5%) (p<0.001) and younger (p<0.001) compared to men. In patients with known atrial fibrillation, women were less likely to receive oral anticoagulants before index stroke (p¼0.026) and were less likely to receive anticoagulants after stroke (71.3% versus 78.4%, p¼0.01). There was no observed sex difference regarding the time of starting anticoagulant therapy between the two groups (6.411.7 days for men versus 6.512.4 days for women, p¼0.902). Men presented with more severe strokes at onset (mean NIHSS 9.26.9 versus 8.17.5, p<0.001). Within 90 days, 46 (8.2%) recurrent ischemic events (stroke/TIA/systemic embolism) and 19 (3.4%) symptomatic cerebral bleedings were found in women compared to 30 (6.4%) and 18 (3.8%) in men (p¼0.28 and p¼0.74). At 90 days, 57.7% of women were disabled or deceased, compared to 41.1% of the men (p<0.001). Multivariate analysis did not confirm this significance. Conclusions: Women with atrial fibrillation were less likely to receive oral anticoagulants prior to and after stroke compared to men with atrial fibrillation, and when stroke occurred, regardless of the fact that in our study women were younger and with less severe stroke, outcomes did not differ between the sexes.
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| 4. |
- Debette, Stéphanie, et al.
(författare)
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Common variation in PHACTR1 is associated with susceptibility to cervical artery dissection
- 2015
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 47, s. 78-83
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Tidskriftsartikel (refereegranskat)abstract
- Cervical artery dissection (CeAD), a mural hematoma in a carotid or vertebral artery, is a major cause of ischemic stroke in young adults although relatively uncommon in the general population (incidence of 2.6/100,000 per year)1. Minor cervical traumas, infection, migraine and hypertension are putative risk factors1–3, and inverse associations with obesity and hypercholesterolemia are described3,4. No confirmed genetic susceptibility factors have been identified using candidate gene approaches5. We performed genome-wide association studies (GWAS) in 1 1,393 CeAD cases and 1 14,416 controls. The rs9349379[G] allele (PHACTR1) was associated with lower CeAD risk (odds ratio (OR) = 0.75, 95% confidence interval (CI) = 0.69–0.82; P = 4.46 × 1 10−10), with confirmation in independent follow-up samples (659 CeAD cases and 2,648 controls; P = 3.91 1 × 1 10−3; combined P = 1 1.00 × 1 10−1111). The rs9349379[G] allele was previously shown to be associated with lower risk of migraine and increased risk of myocardial infarction6–9. Deciphering the mechanisms underlying this pleiotropy might provide important information on the biological underpinnings of these disabling conditions.
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| 5. |
- Paciaroni, Maurizio, et al.
(författare)
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Early recurrence in paroxysmal versus sustained atrial fibrillation in patients with acute ischaemic stroke.
- 2019
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Ingår i: European stroke journal. - : SAGE Publications. - 2396-9881 .- 2396-9873. ; 4:1, s. 55-64
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Tidskriftsartikel (refereegranskat)abstract
- The relationship between different patterns of atrial fibrillation and early recurrence after an acute ischaemic stroke is unclear.In a prospective cohort study, we evaluated the rates of early ischaemic recurrence after an acute ischaemic stroke in patients with paroxysmal atrial fibrillation or sustained atrial fibrillation which included persistent and permanent atrial fibrillation.In patients with acute ischaemic stroke, atrial fibrillation was categorised as paroxysmal atrial fibrillation or sustained atrial fibrillation. Ischaemic recurrences were the composite of ischaemic stroke, transient ischaemic attack and symptomatic systemic embolism occurring within 90 days from acute index stroke.A total of 2150 patients (1155 females, 53.7%) were enrolled: 930 (43.3%) had paroxysmal atrial fibrillation and 1220 (56.7%) sustained atrial fibrillation. During the 90-day follow-up, 111 ischaemic recurrences were observed in 107 patients: 31 in patients with paroxysmal atrial fibrillation (3.3%) and 76 with sustained atrial fibrillation (6.2%) (hazard ratio (HR) 1.86 (95% CI 1.24-2.81)). Patients with sustained atrial fibrillation were on average older, more likely to have diabetes mellitus, hypertension, history of stroke/ transient ischaemic attack, congestive heart failure, atrial enlargement, high baseline NIHSS-score and implanted pacemaker. After adjustment by Cox proportional hazard model, sustained atrial fibrillation was not associated with early ischaemic recurrences (adjusted HR 1.23 (95% CI 0.74-2.04)).After acute ischaemic stroke, patients with sustained atrial fibrillation had a higher rate of early ischaemic recurrence than patients with paroxysmal atrial fibrillation. After adjustment for relevant risk factors, sustained atrial fibrillation was not associated with a significantly higher risk of recurrence, thus suggesting that the risk profile associated with atrial fibrillation, rather than its pattern, is determinant for recurrence.
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| 6. |
- Cancelloni, Virginia, et al.
(författare)
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Reperfusion therapies in patients with acute ischaemic stroke and atrial fibrillation: data on safety and effectiveness from a multi-centre cohort study
- 2024
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Ingår i: NEUROLOGICAL SCIENCES. - 1590-1874 .- 1590-3478.
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Tidskriftsartikel (refereegranskat)abstract
- Background Intravenous thrombolysis (IVT) and/or endovascular therapy (EVT) are currently considered best practices in acute stroke patients. Data regarding the efficacy and safety of reperfusion therapies in patients with atrial fibrillation (AF) are conflicting as regards haemorrhagic transformation, mortality, and functional outcome. This study sought to investigate for any differences, in terms of safety and effectiveness, between AF patients with acute ischaemic stroke (AIS) treated and untreated with reperfusion therapies.Methods Data from two multicenter cohort studies (RAF and RAF-NOACs) on consecutive patients with AF and AIS were analyzed to compare patients treated and not treated with reperfusion therapies (IVT and/or EVT). Multivariable logistic regression analysis was performed to identify independent predictors for outcome events: 90-day good functional outcome and mortality. A propensity score matching (PSM) analysis compared treated and untreated patients.Results Overall, 441 (25.4%) were included in the reperfusion-treated group and 1,295 (74.6%) in the untreated group. The multivariable model suggested that reperfusion therapies were significantly associated with good functional outcome. Rates of mortality and disability were higher in patients not treated, especially in the case of higher NIHSS scores. In the PSM comparison, 173/250 patients (69.2%) who had received reperfusion therapies had good functional outcome at 90 days, compared to 146/250 (58.4%) untreated patients (p = 0.009, OR: 1.60, 95% CI:1.11-2.31).Conclusions Patients with AF and AIS treated with reperfusion therapies had a significantly higher rate of good functional outcome and lower rates of mortality compared to those patients with AF and AIS who had undergone conservative treatment.
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| 7. |
- Cheng, Yu-Ching, et al.
(författare)
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Genome-Wide Association Analysis of Young-Onset Stroke Identifies a Locus on Chromosome 10q25 Near HABP2.
- 2016
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Ingår i: Stroke; a journal of cerebral circulation. - 1524-4628. ; 47:2, s. 307-16
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Tidskriftsartikel (refereegranskat)abstract
- Although a genetic contribution to ischemic stroke is well recognized, only a handful of stroke loci have been identified by large-scale genetic association studies to date. Hypothesizing that genetic effects might be stronger for early- versus late-onset stroke, we conducted a 2-stage meta-analysis of genome-wide association studies, focusing on stroke cases with an age of onset <60 years.
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| 8. |
- Cole, John W, et al.
(författare)
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Genetics of the thrombomodulin-endothelial cell protein C receptor system and the risk of early-onset ischemic stroke.
- 2018
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Ingår i: PloS one. - : Public Library of Science (PLoS). - 1932-6203. ; 13:11
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Tidskriftsartikel (refereegranskat)abstract
- Polymorphisms in coagulation genes have been associated with early-onset ischemic stroke. Here we pursue an a priori hypothesis that genetic variation in the endothelial-based receptors of the thrombomodulin-protein C system (THBD and PROCR) may similarly be associated with early-onset ischemic stroke. We explored this hypothesis utilizing a multi-stage design of discovery and replication.Discovery was performed in the Genetics-of-Early-Onset Stroke (GEOS) Study, a biracial population-based case-control study of ischemic stroke among men and women aged 15-49 including 829 cases of first ischemic stroke (42.2% African-American) and 850 age-comparable stroke-free controls (38.1% African-American). Twenty-four single-nucleotide-polymorphisms (SNPs) in THBD and 22 SNPs in PROCR were evaluated. Following LD pruning (r2≥0.8), we advanced uncorrelated SNPs forward for association analyses. Associated SNPs were evaluated for replication in an early-onset ischemic stroke population (onset-age<60 years) consisting of 3676 cases and 21118 non-stroke controls from 6 case-control studies. Lastly, we determined if the replicated SNPs also associated with older-onset ischemic stroke in the METASTROKE data-base.Among GEOS Caucasians, PROCR rs9574, which was in strong LD with 8 other SNPs, and one additional independent SNP rs2069951, were significantly associated with ischemic stroke (rs9574, OR = 1.33, p = 0.003; rs2069951, OR = 1.80, p = 0.006) using an additive-model adjusting for age, gender and population-structure. Adjusting for risk factors did not change the associations; however, associations were strengthened among those without risk factors. PROCR rs9574 also associated with early-onset ischemic stroke in the replication sample (OR = 1.08, p = 0.015), but not older-onset stroke. There were no PROCR associations in African-Americans, nor were there any THBD associations in either ethnicity.PROCR polymorphisms are associated with early-onset ischemic stroke in Caucasians.
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| 9. |
- Cotlarciuc, Ioana, et al.
(författare)
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Towards the genetic basis of cerebral venous thrombosis-the BEAST Consortium: a study protocol.
- 2016
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Ingår i: BMJ open. - : BMJ. - 2044-6055. ; 6:11
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Tidskriftsartikel (refereegranskat)abstract
- Cerebral venous thrombosis (CVT) is a rare cerebrovascular condition accounting for <1% of all stroke cases and mainly affects young adults. Its genetic aetiology is not clearly elucidated.To better understand the genetic basis of CVT, we have established an international biobank of CVT cases, Biorepository to Establish the Aetiology of Sinovenous Thrombosis (BEAST) which aims to recruit highly phenotyped cases initially of European descent and later from other populations. To date we have recruited 745 CVT cases from 12 research centres. As an initial step, the consortium plans to undertake a genome-wide association analysis of CVT using the Illumina Infinium HumanCoreExome BeadChip to assess the association and impact of common and low-frequency genetic variants on CVT risk by using a case-control study design. Replication will be performed to confirm putative findings. Furthermore, we aim to identify interactions of genetic variants with several environmental and comorbidity factors which will likely contribute to improve the understanding of the biological mechanisms underlying this complex disease.BEAST meets all ethical standards set by local institutional review boards for each of the participating sites. The research outcomes will be published in international peer-reviewed open-access journals with high impact and visibility. The results will be presented at national and international meetings to highlight the contributions into improving the understanding of the mechanisms underlying this uncommon but important disease. This international DNA repository will become an important resource for investigators in the field of haematological and vascular disorders.
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| 10. |
- Ekker, Merel, et al.
(författare)
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Global Outcome Assessment Life-long after stroke in young adults initiative-the GOAL initiative: study protocol and rationale of a multicentre retrospective individual patient data meta-analysis.
- 2019
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Ingår i: BMJ open. - : BMJ. - 2044-6055. ; 9:11
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Tidskriftsartikel (refereegranskat)abstract
- Worldwide, 2 million patients aged 18-50 years suffer a stroke each year, and this number is increasing. Knowledge about global distribution of risk factors and aetiologies, and information about prognosis and optimal secondary prevention in young stroke patients are limited. This limits evidence-based treatment and hampers the provision of appropriate information regarding the causes of stroke, risk factors and prognosis of young stroke patients.The Global Outcome Assessment Life-long after stroke in young adults (GOAL) initiative aims to perform a global individual patient data meta-analysis with existing data from young stroke cohorts worldwide. All patients aged 18-50 years with ischaemic stroke or intracerebral haemorrhage will be included. Outcomes will be the distribution of stroke aetiology and (vascular) risk factors, functional outcome after stroke, risk of recurrent vascular events and death and finally the use of secondary prevention. Subgroup analyses will be made based on age, gender, aetiology, ethnicity and climate of residence.Ethical approval for the GOAL study has already been obtained from the Medical Review Ethics Committee region Arnhem-Nijmegen. Additionally and when necessary, approval will also be obtained from national or local institutional review boards in the participating centres. When needed, a standardised data transfer agreement will be provided for participating centres. We plan dissemination of our results in peer-reviewed international scientific journals and through conference presentations. We expect that the results of this unique study will lead to better understanding of worldwide differences in risk factors, causes and outcome of young stroke patients.
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| 11. |
- Jacob, Mina A, et al.
(författare)
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Global Differences in Risk Factors, Etiology, and Outcome of Ischemic Stroke in Young Adults: A Worldwide Meta-analysis: The GOAL-Initiative.
- 2022
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Ingår i: Neurology. - 1526-632X. ; 98:6
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Tidskriftsartikel (refereegranskat)abstract
- There is a worldwide increase in the incidence of stroke in young adults, with major regional and ethnic differences. Advancing knowledge of ethnic and regional variation in causes and outcomes will be beneficial in implementation of regional healthcare services. To study the global distribution of risk factors, causes and 3-month mortality of young ischemic stroke patients, by performing a patient data meta-analysis form different cohorts worldwide.We did a pooled analysis of individual patient data from cohort studies which included consecutive ischemic stroke patients aged 18-50 years. We studied differences in prevalence of risk factors and causes between different ethnic and racial groups, geographic regions and countries with different income levels. We investigated differences in 3-month mortality by mixed-effects multivariable logistic regression.We included 17,663 patients from 32 cohorts in 29 countries. Hypertension and diabetes were most prevalent in Blacks (hypertension, 52.1%; diabetes, 20.7%) and Asians (hypertension 46.1%, diabetes, 20.9%). Large vessel atherosclerosis and small vessel disease were more often cause of stroke in high-income countries (HICs; both p<0.001), whereas ''other determined stroke'' and ''undetermined stroke'' were higher in low and middle-income countries (LMICs; both p<0.001). Patients in LMICs were younger, had less vascular risk factors, and despite this, more often died within 3 months than those from HICs (OR 2.49; 95% CI 1.42-4.36).The ethnoracial and regional differences in risk factors and causes of stroke at young age provide an understanding of ethnic and racial, and regional differences in incidence of ischemic stroke. Our results also visualize the dissimilarities in outcome after stroke in young adults that exist between LMICs and HICs, which should serve as call to action to improve healthcare facilities in LMICs.
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| 12. |
- Marto, João Pedro, et al.
(författare)
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Safety and Outcome of Revascularization Treatment in Patients With Acute Ischemic Stroke and COVID-19: The Global COVID-19 Stroke Registry.
- 2023
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Ingår i: Neurology. - 1526-632X. ; 100:7
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Tidskriftsartikel (refereegranskat)abstract
- COVID-19-related inflammation, endothelial dysfunction, and coagulopathy may increase the bleeding risk and lower the efficacy of revascularization treatments in patients with acute ischemic stroke (AIS). We aimed to evaluate the safety and outcomes of revascularization treatments in patients with AIS and COVID-19.This was a retrospective multicenter cohort study of consecutive patients with AIS receiving intravenous thrombolysis (IVT) and/or endovascular treatment (EVT) between March 2020 and June 2021 tested for severe acute respiratory syndrome coronavirus 2 infection. With a doubly robust model combining propensity score weighting and multivariate regression, we studied the association of COVID-19 with intracranial bleeding complications and clinical outcomes. Subgroup analyses were performed according to treatment groups (IVT-only and EVT).Of a total of 15,128 included patients from 105 centers, 853 (5.6%) were diagnosed with COVID-19; of those, 5,848 (38.7%) patients received IVT-only and 9,280 (61.3%) EVT (with or without IVT). Patients with COVID-19 had a higher rate of symptomatic intracerebral hemorrhage (SICH) (adjusted OR 1.53; 95% CI 1.16-2.01), symptomatic subarachnoid hemorrhage (SSAH) (OR 1.80; 95% CI 1.20-2.69), SICH and/or SSAH combined (OR 1.56; 95% CI 1.23-1.99), 24-hour mortality (OR 2.47; 95% CI 1.58-3.86), and 3-month mortality (OR 1.88; 95% CI 1.52-2.33). Patients with COVID-19 also had an unfavorable shift in the distribution of the modified Rankin score at 3 months (OR 1.42; 95% CI 1.26-1.60).Patients with AIS and COVID-19 showed higher rates of intracranial bleeding complications and worse clinical outcomes after revascularization treatments than contemporaneous non-COVID-19 patients receiving treatment. Current available data do not allow direct conclusions to be drawn on the effectiveness of revascularization treatments in patients with COVID-19 or to establish different treatment recommendations in this subgroup of patients with ischemic stroke. Our findings can be taken into consideration for treatment decisions, patient monitoring, and establishing prognosis.The study was registered under ClinicalTrials.gov identifier NCT04895462.
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| 13. |
- Nordanstig, Annika, 1974, et al.
(författare)
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EndoVAscular treatment and ThRombolysis for Ischemic Stroke Patients (EVA-TRISP) registry: basis and methodology of a pan-European prospective ischaemic stroke revascularisation treatment registry.
- 2021
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Ingår i: BMJ open. - : BMJ. - 2044-6055. ; 11:8
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Tidskriftsartikel (refereegranskat)abstract
- The Thrombolysis in Ischemic Stroke Patients (TRISP) collaboration was a concerted effort initiated in 2010 with the purpose to address relevant research questions about the effectiveness and safety of intravenous thrombolysis (IVT). The collaboration also aims to prospectively collect data on patients undergoing endovascular treatment (EVT) and hence the name of the collaboration was changed from TRISP to EVA-TRISP. The methodology of the former TRISP registry for patients treated with IVT has already been published. This paper focuses on describing the EVT part of the registry.All centres committed to collecting predefined variables on consecutive patients prospectively. We aim for accuracy and completeness of the data and to adapt local databases to investigate novel research questions. Herein, we introduce the methodology of a recently constructed academic investigator-initiated open collaboration EVT registry built as an extension of an existing IVT registry in patients with acute ischaemic stroke (AIS).Currently, the EVA-TRISP network includes 20 stroke centres with considerable expertise in EVT and maintenance of high-quality hospital-based registries. Following several successful randomised controlled trials (RCTs), many important clinical questions remain unanswered in the (EVT) field and some of them will unlikely be investigated in future RCTs. Prospective registries with high-quality data on EVT-treated patients may help answering some of these unanswered issues, especially on safety and efficacy of EVT in specific patient subgroups.This collaborative effort aims at addressing clinically important questions on safety and efficacy of EVT in conditions not covered by RCTs. The TRISP registry generated substantial novel data supporting stroke physicians in their daily decision making considering IVT candidate patients. While providing observational data on EVT in daily clinical practice, our future findings may likewise be hypothesis generating for future research as well as for quality improvement (on EVT). The collaboration welcomes participation of further centres willing to fulfill the commitment and the outlined requirements.
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| 14. |
- Pfeiffer, Dorothea, et al.
(författare)
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Genetic Imbalance Is Associated With Functional Outcome After Ischemic Stroke
- 2019
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Ingår i: Stroke. - 1524-4628. ; 50:2, s. 298-304
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Tidskriftsartikel (refereegranskat)abstract
- Background and Purpose- We sought to explore the effect of genetic imbalance on functional outcome after ischemic stroke (IS). Methods- Copy number variation was identified in high-density single-nucleotide polymorphism microarray data of IS patients from the CADISP (Cervical Artery Dissection and Ischemic Stroke Patients) and SiGN (Stroke Genetics Network)/GISCOME (Genetics of Ischaemic Stroke Functional Outcome) networks. Genetic imbalance, defined as total number of protein-coding genes affected by copy number variations in an individual, was compared between patients with favorable (modified Rankin Scale score of 0-2) and unfavorable (modified Rankin Scale score of ≥3) outcome after 3 months. Subgroup analyses were confined to patients with imbalance affecting ohnologs-a class of dose-sensitive genes, or to those with imbalance not affecting ohnologs. The association of imbalance with outcome was analyzed by logistic regression analysis, adjusted for age, sex, stroke subtype, stroke severity, and ancestry. Results- The study sample comprised 816 CADISP patients (age 44.2±10.3 years) and 2498 SiGN/GISCOME patients (age 67.7±14.2 years). Outcome was unfavorable in 122 CADISP and 889 SiGN/GISCOME patients. Multivariate logistic regression analysis revealed that increased genetic imbalance was associated with less favorable outcome in both samples (CADISP: P=0.0007; odds ratio=0.89; 95% CI, 0.82-0.95 and SiGN/GISCOME: P=0.0036; odds ratio=0.94; 95% CI, 0.91-0.98). The association was independent of age, sex, stroke severity on admission, stroke subtype, and ancestry. On subgroup analysis, imbalance affecting ohnologs was associated with outcome (CADISP: odds ratio=0.88; 95% CI, 0.80-0.95 and SiGN/GISCOME: odds ratio=0.93; 95% CI, 0.89-0.98) whereas imbalance without ohnologs lacked such an association. Conclusions- Increased genetic imbalance was associated with poorer functional outcome after IS in both study populations. Subgroup analysis revealed that this association was driven by presence of ohnologs in the respective copy number variations, suggesting a causal role of the deleterious effects of genetic imbalance.
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| 15. |
- Putaala, Jukka, et al.
(författare)
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Searching for Explanations for Cryptogenic Stroke in the Young : Revealing the Triggers, Causes, and Outcome (SECRETO): Rationale and design
- 2017
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Ingår i: European Stroke Journal. - : SAGE Publications. - 2396-9873 .- 2396-9881. ; 2:2, s. 116-125
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Tidskriftsartikel (refereegranskat)abstract
- Background: Worldwide, about 1.3 million annual ischaemic strokes (IS) occur in adults aged <50 years. Of these early-onset strokes, up to 50% can be regarded as cryptogenic or associated with conditions with poorly documented causality like patent foramen ovale and coagulopathies. Key hypotheses/aims: (1) Investigate transient triggers and clinical/sub-clinical chronic risk factors associated with cryptogenic IS in the young; (2) use cardiac imaging methods exceeding state-of-the-art to reveal novel sources for embolism; (3) search for covert thrombosis and haemostasis abnormalities; (4) discover new disease pathways using next-generation sequencing and RNA gene expression studies; (5) determine patient prognosis by use of phenotypic and genetic data; and (6) adapt systems medicine approach to investigate complex risk-factor interactions. Design: Searching for Explanations for Cryptogenic Stroke in the Young: Revealing the Etiology, Triggers, and Outcome (SECRETO; NCT01934725) is a prospective multi-centre case–control study enrolling patients aged 18–49 years hospitalised due to first-ever imaging-proven IS of undetermined etiology. Patients are examined according to a standardised protocol and followed up for 10 years. Patients are 1:1 age- and sex-matched to stroke-free controls. Key study elements include centralised reading of echocardiography, electrocardiography, and neurovascular imaging, as well as blood samples for genetic, gene-expression, thrombosis and haemostasis and biomarker analysis. We aim to have 600 patient–control pairs enrolled by the end of 2018. Summary: SECRETO is aiming to establish novel mechanisms and prognosis of cryptogenic IS in the young and will provide new directions for therapy development for these patients. First results are anticipated in 2019.
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| 16. |
- Ranjan, Redoy, et al.
(författare)
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Coma in adult cerebral venous thrombosis: The BEAST study
- 2024
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Ingår i: EUROPEAN JOURNAL OF NEUROLOGY. - 1351-5101 .- 1468-1331. ; 31:8
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Tidskriftsartikel (refereegranskat)abstract
- Background and purpose: Coma is an independent predictor of poor clinical outcomes in cerebral venous thrombosis (CVT). We aimed to describe the association of age, sex, and radiological characteristics of adult coma patients with CVT. Methods: We used data from the international, multicentre prospective observational BEAST (Biorepository to Establish the Aetiology of Sinovenous Thrombosis) study. Only positively associated variables with coma with <10% missing data in univariate analysis were considered for the multivariate logistic regression model. Results: Of the 596 adult patients with CVT (75.7% women), 53 (8.9%) patients suffered coma. Despite being a female-predominant disease, the prevalence of coma was higher among men than women (13.1% vs. 7.5%, p = 0.04). Transverse sinus thrombosis was least likely to be associated with coma (23.9% vs. 73.3%, p < 0.001). The prevalence of superior sagittal sinus thrombosis was higher among men than women in the coma sample (73.6% vs. 37.5%, p = 0.01). Men were significantly older than women, with a median (interquartile range) age of 51 (38.5-60) versus 40 (33-47) years in the coma (p = 0.04) and 44.5 (34-58) versus 37 (29-48) years in the non-coma sample (p < 0.001), respectively. Furthermore, an age- and superior sagittal sinus-adjusted multivariate logistic regression model found male sex (odds ratio = 1.8, 95% confidence interval [CI] = 1.0-3.4, p = 0.04) to be an independent predictor of coma in CVT, with an area under the receiver operating characteristic curve of 0.61 (95% CI = 0.52-0.68, p = 0.01). Conclusions: Although CVT is a female-predominant disease, men were older and nearly twice as likely to suffer from coma than women.
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| 17. |
- Scheitz, Jan F, et al.
(författare)
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Cohort profile: Thrombolysis in Ischemic Stroke Patients (TRISP): a multicentre research collaboration.
- 2018
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Ingår i: BMJ open. - : BMJ. - 2044-6055. ; 8:9
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Tidskriftsartikel (refereegranskat)abstract
- The ThRombolysis in Ischemic Stroke Patients (TRISP) collaboration aims to address clinically relevant questions about safety and outcomes of intravenous thrombolysis (IVT) and endovascular thrombectomy. The findings can provide observational information on treatment of patients derived from everyday clinical practice.TRISP is an open, investigator-driven collaborative research initiative of European stroke centres with expertise in treatment with revascularisation therapies and maintenance of hospital-based registries. All participating centres made a commitment to prospectively collect data on consecutive patients with stroke treated with IVT using standardised definitions of variables and outcomes, to assure accuracy and completeness of the data and to adapt their local databases to answer novel research questions.Currently, TRISP comprises 18 centres and registers >10000IVT-treated patients. Prior TRISP projects provided evidence on the safety and functional outcome in relevant subgroups of patients who were excluded, under-represented or not specifically addressed in randomised controlled trials (ie, pre-existing disability, cervical artery dissections, stroke mimics, prior statin use), demonstrated deficits in organisation of acute stroke care (ie, IVT during non-working hours, effects of onset-to-door time on onset-to-needle time), evaluated the association between laboratory findings on outcome after IVT and served to develop risk estimation tools for prediction of haemorrhagic complications and functional outcome after IVT.Further TRISP projects to increase knowledge of the effect and safety of revascularisation therapies in acute stroke are ongoing. TRISP welcomes participation and project proposals of further centres fulfilling the outlined requirements. In the future, TRISP will be extended to include patients undergoing endovascular thrombectomy.
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| 18. |
- Traenka, Christopher, et al.
(författare)
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Artery occlusion independently predicts unfavorable outcome in cervical artery dissection.
- 2020
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Ingår i: Neurology. - 1526-632X. ; 94:2
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Tidskriftsartikel (refereegranskat)abstract
- To assess the impact of dissected artery occlusion (DAO) on functional outcome and complications in patients with cervical artery dissection (CeAD).We analyzed combined individual patient data from 3 multicenter cohorts of consecutive patients with CeAD (the Cervical Artery Dissection and Ischemic Stroke Patients [CADISP]-Plus consortium dataset). Patients with data on DAO and functional outcome were included. We compared patients with DAO to those without DAO. Primary outcome was favorable functional outcome (i.e., modified Rankin Scale [mRS] score 0-1) measured 3-6 months from baseline. Secondary outcomes included delayed cerebral ischemia, major hemorrhage, recurrent CeAD, and death. We performed univariate and multivariable binary logistic regression analyses and calculated odds ratios (OR) with 95% confidence intervals (CI), with adjustment for potential confounders.Of 2,148 patients (median age 45 years [interquartile range (IQR) 38-52], 43.6% women), 728 (33.9%) had DAO. Patients with DAO more frequently presented with cerebral ischemia (84.6% vs 58.5%, p < 0.001). Patients with DAO were less likely to have favorable outcome when compared to patients without DAO (mRS 0-1: 59.6% vs 80.1%, punadjusted < 0.001). After adjustment for age, sex, and initial stroke severity, DAO was independently associated with less favorable outcome (mRS 0-1: OR 0.65, CI 0.50-0.84, p = 0.001). Delayed cerebral ischemia occurred more frequently in patients with DAO than in patients without DAO (4.5% vs 2.9%, p = 0.059).DAO independently predicts less favorable functional outcome in patients with CeAD. Further research on vessel patency, collateral status and effects of revascularization therapies particularly in patients with DAO is warranted.
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| 19. |
- Traenka, Christopher, et al.
(författare)
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Cervical artery dissection in patients ≥60 years: Often painless, few mechanical triggers.
- 2017
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Ingår i: Neurology. - 1526-632X. ; 88:14, s. 1313-1320
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Tidskriftsartikel (refereegranskat)abstract
- In a cohort of patients diagnosed with cervical artery dissection (CeAD), to determine the proportion of patients aged ≥60 years and compare the frequency of characteristics (presenting symptoms, risk factors, and outcome) in patients aged <60 vs ≥60 years.We combined data from 3 large cohorts of consecutive patients diagnosed with CeAD (i.e., Cervical Artery Dissection and Ischemic Stroke Patients-Plus consortium). We dichotomized cases into 2 groups, age ≥60 and <60 years, and compared clinical characteristics, risk factors, vascular features, and 3-month outcome between the groups. First, we performed a combined analysis of pooled individual patient data. Secondary analyses were done within each cohort and across cohorts. Crude and adjusted odds ratios (OR [95% confidence interval]) were calculated.Among 2,391 patients diagnosed with CeAD, we identified 177 patients (7.4%) aged ≥60 years. In this age group, cervical pain (ORadjusted 0.47 [0.33-0.66]), headache (ORadjusted 0.58 [0.42-0.79]), mechanical trigger events (ORadjusted 0.53 [0.36-0.77]), and migraine (ORadjusted 0.58 [0.39-0.85]) were less frequent than in younger patients. In turn, hypercholesterolemia (ORadjusted 1.52 [1.1-2.10]) and hypertension (ORadjusted 3.08 [2.25-4.22]) were more frequent in older patients. Key differences between age groups were confirmed in secondary analyses. In multivariable, adjusted analyses, favorable outcome (i.e., modified Rankin Scale score 0-2) was less frequent in the older age group (ORadjusted 0.45 [0.25, 0.83]).In our study population of patients diagnosed with CeAD, 1 in 14 was aged ≥60 years. In these patients, pain and mechanical triggers might be missing, rendering the diagnosis more challenging and increasing the risk of missed CeAD diagnosis in older patients.
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