| 1. |
- Pedersen, Annie, 1981, et al.
(författare)
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Fibrinogen concentrations predict long-term cognitive outcome in young ischemic stroke patients
- 2018
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Ingår i: Research and Practice in Thrombosis and Haemostasis. - : Elsevier BV. - 2475-0379. ; 2:2, s. 339-346
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Tidskriftsartikel (refereegranskat)abstract
- Background: Cognitive impairment is frequent after stroke, and young patients may live with this consequence for a long time. Predictors of cognitive outcomes after stroke represent a current gap of knowledge. Objectives: To investigate levels of three hemostatic biomarkers as predictors of long-term cognitive function after stroke. Methods: This longitudinal study included consecutively recruited patients with ischemic stroke at 18-69 years (n = 268). Blood was collected 3 months after index stroke and analyzed for plasma concentrations of fibrinogen, von Willebrand factor (VWF) and tissue-type plasminogen activator (t-PA) antigen. Cognitive function 7 years after index stroke was assessed by the Barrow Neurological Institute Screen for Higher Cerebral Functions (BNIS). Participants with stroke <50 years of age were also examined by the Trail Making Test A and B (n = 41). Associations between biomarker concentrations and cognitive scales were assessed in the whole group and in participants with stroke <50 years of age. Results: The hemostatic biomarkers fibrinogen, VWF and t-PA, were all correlated to total BNIS score, but these associations did not withstand adjustment for confounding factors in the whole group. However, in patients <50 years, we found an independent association between fibrinogen concentrations and total BNIS score (beta(std) = -.27, 95% confidence interval [CI], -0.47 to -0.07) and to performance on the Trail Making Test A (beta(std) = 31, 95% CI, 0.03-0.58). No such association was seen for the Trail Making Test B. Conclusion: High convalescent fibrinogen concentrations were associated with worse long-term cognitive outcomes in ischemic stroke <50 years of age. We propose further investigations of fibrinogen in relation to cognitive function in stroke in the young.
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| 2. |
- Pulit, SL, et al.
(författare)
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Loci associated with ischaemic stroke and its subtypes (SiGN): a genome-wide association study.
- 2016
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Ingår i: The Lancet. Neurology. - 1474-4465. ; 15:2, s. 174-84
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Tidskriftsartikel (refereegranskat)abstract
- The discovery of disease-associated loci through genome-wide association studies (GWAS) is the leading genetic approach to the identification of novel biological pathways underlying diseases in humans. Until recently, GWAS in ischaemic stroke have been limited by small sample sizes and have yielded few loci associated with ischaemic stroke. We did a large-scale GWAS to identify additional susceptibility genes for stroke and its subtypes.To identify genetic loci associated with ischaemic stroke, we did a two-stage GWAS. In the first stage, we included 16 851 cases with state-of-the-art phenotyping data and 32 473 stroke-free controls. Cases were aged 16 to 104 years, recruited between 1989 and 2012, and subtypes of ischaemic stroke were recorded by centrally trained and certified investigators who used the web-based protocol, Causative Classification of Stroke (CCS). We constructed case-control strata by identifying samples that were genotyped on nearly identical arrays and were of similar genetic ancestral background. We cleaned and imputed data by use of dense imputation reference panels generated from whole-genome sequence data. We did genome-wide testing to identify stroke-associated loci within each stratum for each available phenotype, and we combined summary-level results using inverse variance-weighted fixed-effects meta-analysis. In the second stage, we did in-silico lookups of 1372 single nucleotide polymorphisms identified from the first stage GWAS in 20 941 cases and 364 736 unique stroke-free controls. The ischaemic stroke subtypes of these cases had previously been established with the Trial of Org 10 172 in Acute Stroke Treatment (TOAST) classification system, in accordance with local standards. Results from the two stages were then jointly analysed in a final meta-analysis.We identified a novel locus (G allele at rs12122341) at 1p13.2 near TSPAN2 that was associated with large artery atherosclerosis-related stroke (first stage odds ratio [OR] 1·21, 95% CI 1·13-1·30, p=4·50 × 10(-8); joint OR 1·19, 1·12-1·26, p=1·30 × 10(-9)). Our results also supported robust associations with ischaemic stroke for four other loci that have been reported in previous studies, including PITX2 (first stage OR 1·39, 1·29-1·49, p=3·26 × 10(-19); joint OR 1·37, 1·30-1·45, p=2·79 × 10(-32)) and ZFHX3 (first stage OR 1·19, 1·11-1·27, p=2·93 × 10(-7); joint OR 1·17, 1·11-1·23, p=2·29 × 10(-10)) for cardioembolic stroke, and HDAC9 (first stage OR 1·29, 1·18-1·42, p=3·50 × 10(-8); joint OR 1·24, 1·15-1·33, p=4·52 × 10(-9)) for large artery atherosclerosis stroke. The 12q24 locus near ALDH2, which has previously been associated with all ischaemic stroke but not with any specific subtype, exceeded genome-wide significance in the meta-analysis of small artery stroke (first stage OR 1·20, 1·12-1·28, p=6·82 × 10(-8); joint OR 1·17, 1·11-1·23, p=2·92 × 10(-9)). Other loci associated with stroke in previous studies, including NINJ2, were not confirmed.Our results suggest that all ischaemic stroke-related loci previously implicated by GWAS are subtype specific. We identified a novel gene associated with large artery atherosclerosis stroke susceptibility. Follow-up studies will be necessary to establish whether the locus near TSPAN2 can be a target for a novel therapeutic approach to stroke prevention. In view of the subtype-specificity of the associations detected, the rich phenotyping data available in the Stroke Genetics Network (SiGN) are likely to be crucial for further genetic discoveries related to ischaemic stroke.US National Institute of Neurological Disorders and Stroke, National Institutes of Health.
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| 3. |
- Åberg, Daniel, 1973, et al.
(författare)
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Serum IGFBP-1 Concentration as a Predictor of Outcome after Ischemic Stroke—A Prospective Observational Study
- 2023
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Ingår i: International Journal of Molecular Sciences. - 1422-0067. ; 24:11
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Tidskriftsartikel (refereegranskat)abstract
- Insulin-like growth factor-binding protein-1 (IGFBP-1) regulates insulin-like growth factor- I (IGF-I) bioactivity, and is a central player in normal growth, metabolism, and stroke recovery. However, the role of serum IGFBP-1 (s-IGFBP-1) after ischemic stroke is unclear. We determined whether s-IGFBP-1 is predictive of poststroke outcome. The study population comprised patients (n = 470) and controls (n = 471) from the Sahlgrenska Academy Study on Ischemic Stroke (SAHLSIS). Functional outcome was evaluated after 3 months, 2, and 7 years using the modified Rankin Scale (mRS). Survival was followed for a minimum of 7 years or until death. S-IGFBP-1 was increased after 3 months (p < 0.01), but not in the acute phase after stroke, compared with the controls. Higher acute s-IGFBP-1 was associated with poor functional outcome (mRS score > 2) after 7 years [fully adjusted odds ratio (OR) per log increase 2.9, 95% confidence interval (CI): 1.4-5.9]. Moreover, higher s-IGFBP-1 after 3 months was associated with a risk of poor functional outcome after 2 and 7 years (fully adjusted: OR 3.4, 95% CI: 1.4–8.5 and OR 5.7, 95% CI: 2.5–12.8, respectively) and with increased mortality risk (fully adjusted: HR 2.0, 95% CI: 1.1–3.7). Thus, high acute s-IGFBP-1 was only associated with poor functional outcome after 7 years, whereas s-IGFBP-1 after 3 months was an independent predictor of poor long-term functional outcome and poststroke mortality.
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