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| 62. |
- Jood, Katarina, 1966
(author)
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Risk factors in ischemic stroke
- 2005
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Doctoral thesis (other academic/artistic)abstract
- Ischemic stroke is a complex disease in which environmental and genetic factors make about equal contributions to the etiology. However, knowledge regarding the molecular basis of the genetic influence and the impact of specific lifestyle factors is limited. Hypertension, diabetes, and smoking have been identified as major risk factors, but data for the different ischemic stroke subtypes are incomplete. Potential novel vascular risk factors, such as hemostasis, have mainly been investigated in relation to coronary heart disease, and associations to stroke remain to be established. The aim of the present thesis was therefore to study risk factors for ischemic stroke with focus on genetics, fibrinolysis, and lifestyle.The Sahlgrenska Academy Study on Ischemic Stroke (SAHLSIS) was designed for genetic association studies. Six hundred patients with ischemic stroke before the age of 70 years, and 600 matched population controls were recruited. Great emphasize was put on classification of ischemic stroke subtypes, as we hypothesized that their risk factor profiles may differ. Accordingly, we found that the associations for established risk factors differed by subtype. Furthermore, family history of stroke was independently associated with overall ischemic stroke, large vessel disease (LVD), small vessel disease (SVD), and cryptogenic stroke, but not with cardioembolic (CE) stroke. Lifestyle factors were investigated prospectively in a cohort of 7,402 men. After 28 years of follow-up, we found an independent association between increased body mass index and ischemic stroke. Self-perceived psychological stress showed independent association with total stroke (i.e. ischemic and hemorrhagic stroke combined), but no significant association was found when the two stroke types were analyzed separately. Self-perceived psychological stress was further investigated in SAHLSIS. An independent association with overall ischemic stroke, LVD, SVD, cryptogenic stroke, but not with CE stroke was found. The importance of endogenous fibrinolysis was investigated using genetic markers for the expression of tissue-type plasminogen activator (t-PA) and plasminogen activator inhibitor type 1 (PAI-1), i.e. the t-PA -7,351C>T and the PAI-1 -675 4G>5G polymorphism. When analyzed as independent covariates, neither of the two genetic variants showed significant association with ischemic stroke. However, a protective effect for the t-PA CC/PAI-1 4G4G genotype combination (i.e. corresponding to high t-PA and high PAI-1 expression) was observed. We also investigated the pattern of acute t-PA release in a smaller experimental study. Compared to controls, patients with ischemic stroke showed a preserved, but delayed, acute t-PA release.In conclusion, we found distinct differences in risk factor patterns for the ischemic stroke subtypes. This was true for both established and novel risk factors, which highlights the importance of subtype characterization in stroke research. Regarding the fibrinolytic system, we found a protective effect of the t-PA CC/PAI-1 4G4G genotype combination, suggesting a gen-gen interaction and a complex role for t-PA and PAI-1 during brain ischemia.
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| 63. |
- Jood, Katarina, 1966, et al.
(author)
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Self-perceived psychological stress and ischemic stroke: a case-control study.
- 2009
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In: BMC medicine. - : Springer Science and Business Media LLC. - 1741-7015. ; 7
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Journal article (peer-reviewed)abstract
- BACKGROUND: A growing body of evidence suggests that psychological stress contributes to coronary artery disease. However, associations between stress and stroke are less clear. In this study, we investigated the possible association between ischemic stroke and self-perceived psychological stress, as measured by a single-item questionnaire, previously reported to be associated with myocardial infarction. METHODS: In the Sahlgrenska Academy Study on Ischemic Stroke (SAHLSIS), 600 consecutive patients with acute ischemic stroke (aged 18 to 69 years) and 600 age-matched and sex-matched population controls were recruited. Ischemic stroke subtype was determined according to Trial of Org 10172 in Acute Stroke Treatment (TOAST) criteria. Self-perceived psychological stress preceding stroke was assessed retrospectively using a single-item questionnaire. RESULTS: Permanent self-perceived psychological stress during the last year or longer was independently associated with overall ischemic stroke (multivariate adjusted odds ratio (OR) 3.49, 95% confidence interval (CI) 2.06 to 5.93). Analyses by stroke subtype showed that this association was present for large vessel disease (OR 3.91, 95% CI 1.58 to 9.67), small vessel disease (OR 3.20, 95% CI 1.64 to 6.24), and cryptogenic stroke (OR 4.03, 95% CI 2.34 to 6.95), but not for cardioembolic stroke (OR 1.48, 95% CI 0.64 to 3.39). CONCLUSION: In this case-control study, we found an independent association between self-perceived psychological stress and ischemic stroke. A novel finding was that this association differed by ischemic stroke subtype. Our results emphasize the need for further prospective studies addressing the potential role for psychological stress as a risk factor for ischemic stroke. In such studies ischemic stroke subtypes should be taken into consideration.
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| 64. |
- Jood, Katarina, 1966
(author)
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Stroke hos yngre
- 2007
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In: Vårdalinstitutets tematiska rum: Stroke-vård, omsorg och rehabilitering. - : Vårdalinstitutet.
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Other publication (other academic/artistic)abstract
- Elektronisk artikel: www.vardalinstitutet.net
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| 65. |
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| 66. |
- Jood, Katarina, 1966, et al.
(author)
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The psychosocial work environment is associated with risk of stroke at working age
- 2017
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In: Scandinavian Journal of Work Environment & Health. - : Scandinavian Journal of Work, Environment and Health. - 0355-3140 .- 1795-990X. ; 43:4, s. 367-374
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Journal article (peer-reviewed)abstract
- Objective The aim of this study was to explore the relation between the risk of first-ever stroke at working age and psychological work environmental factors. Methods A consecutive multicenter matched 1:2 case control study of acute stroke cases (N=198, age 30-65 years) who had been working full-time at the time of their stroke and 396 sex- and age-matched controls. Stroke cases and controls answered questionnaires on their psychosocial situation during the previous 12 months. The psychosocial work environment was assessed using three different measures: the job control demand model, the effort reward imbalance (ERI) score, and exposures to conflict at work. Results Among 198 stroke cases and 396 controls, job strain [odds ratio (OR) 1.30, 95% confidence interval (95% CI) 1.05-1.62], ERI (OR 1.28, 95% CI 1.01-1.62), and conflict at work (OR 1.75, 95% CI 1.07-2.88) were independent risk factors of stroke in multivariable regression models. Conclusions Adverse psychosocial working conditions during the past 12 months were more frequently observed among stroke cases. Since these factors are presumably modifiable, interventional studies targeting job strain and emotional work environment are warranted.
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| 67. |
- Karlsson, Adrian, et al.
(author)
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Extended treatment in cerebral ischemia score 2c or 3 as goal of successful endovascular treatment is associated with clinical benefit.
- 2024
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In: Journal of neuroradiology = Journal de neuroradiologie. - 0150-9861. ; 51:2, s. 190-195
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Journal article (peer-reviewed)abstract
- Successful reperfusion, defined as a modified treatment in cerebral ischemia (mTICI) score 2b or 3, is an important goal for endovascular treatment (EVT) of stroke. Recently, an extension of the mTICI score with an additional grade 2c indicating near-complete reperfusion (expanded TICI, eTICI) and a revised definition of success as eTICI 2c or 3 were proposed. We evaluate whether eTICI 2c translates into improved clinical outcome compared to eTICI 2b.Consecutive patients with large vessel occlusion in the anterior circulation who underwent EVT between December 2013 and December 2020 were included. Clinical outcome measures were favorable functional outcome at 90 days (modified Rankin Scale [mRS] scores 0 to 2 or return to pre-stroke mRS) and early neurological improvement (National Institutes of Health Stroke Scale [NIHSS] improvement ≥4 points or a score of 0-1 at 24h).Of 1282 included patients (median age 76, median NIHSS 16), reperfusion was classified as eTICI 2b in 410 (32%), eTICI 2c in 242 (19%) and eTICI 3 in 464 (36%). eTICI 2c differed significally from 2b with respect to early neurological improvement (aOR=1.49, 95% CI=1.01-2.19). No statistically significant difference in favorable functional outcome at 90 days was found (eTICI 2c vs 2b, aOR=1.31, 95% CI=0.88-2.00).Our study indicates early clinical benefit at 24h of achieving eTICI 2c compared to eTICI 2b, but no significant difference was seen in favorable functional outcome at 90 days. Our results support eTICI 2c and 3 as the goal of a successful thrombectomy but do not exclude eTICI 2b as an acceptable result.
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| 68. |
- Karlsson, Adrian, et al.
(author)
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Stent retriever versus aspiration based thrombectomy: impact on first pass reperfusion, procedure time, and clinical outcomes in large vessel occlusion. Nationwide registry based cohort study
- 2024
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In: JOURNAL OF NEUROINTERVENTIONAL SURGERY. - 1759-8478 .- 1759-8486.
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Journal article (peer-reviewed)abstract
- Background First pass reperfusion (FPR), defined as near complete reperfusion (extended Treatment in Cerebral Ischemia (eTICI) score 2c/3) in a single attempt without rescue therapy has been proposed as a quality metric. However, it remains unclear if the thrombectomy method influences clinical outcome and FPR rate. This study evaluates whether stent retriever and aspiration based thrombectomy differ in FPR rate, technical and clinical outcomes in FPR, and multiple pass reperfusion (MPR).Methods This retrospective, nationwide, multicenter registry study included consecutive patients with proximal anterior or posterior circulation stroke, treated between 2018 and 2021 in Sweden. Outcome measures were FPR rate, procedure time, early neurological improvement (>= 4 points on National Institutes of Health Stroke Scale (NIHSS) or a score of 0-1 at 24 hours), favorable functional outcome (modified Rankin Scale score of 0-2 or no decline at 90 days), and mortality at 90 days.Results Of 3309 patients (median age 75, median NIHSS 16), 1990 underwent stent retriever and 1319 aspiration based thrombectomy as the firstline method. No difference in FPR rate was observed. Aspiration based thrombectomy showed a shorter procedure time in the FPR group (crude OR (cOR) 6.4 min (95% CI 3.4 to 9.3), adjusted OR (aOR) 8.7 min (95% CI 1.8 to 15.6)) and MPR group (cOR 9.7 min (95% CI 4.0 to 15.4), aOR 17.4 min (95% CI 9.6 to 25.2)), and association with early neurological improvement (cOR 1.21 (95% CI 1.03 to 1.42), aOR 1.40 (95% CI 1.18 to 1.67)) and favorable functional outcome (aOR 1.22 (95% CI 1.01 to 1.47)).Conclusions Our findings suggest that aspiration based thrombectomy was associated with a shorter procedure time and better clinical outcomes than treatment with a stent retriever. No difference was found in FPR rate.
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| 69. |
- Ken-Dror, Gie, et al.
(author)
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Gene-Gene Interaction Between Factor-XI and ABO Genes in Cerebral Venous Thrombosis The BEAST Study
- 2024
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In: NEUROLOGY. - 0028-3878 .- 1526-632X. ; 102:11
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Journal article (peer-reviewed)abstract
- Background and ObjectivesGene-gene interactions likely contribute to the etiology of multifactorial diseases such as cerebral venous thrombosis (CVT) and could be one of the main sources of known missing heritability. We explored Factor XI (F11) and ABO gene interactions among patients with CVT. MethodsPatients with CVT of European ancestry from the large Bio-Repository to Establish the Aetiology of Sinovenous Thrombosis (BEAST) international collaboration were recruited. Codominant modelling was used to determine interactions between genome-wide identified F11 and ABO genes with CVT status. ResultsWe studied 882 patients with CVT and 1,205 ethnically matched control participants (age: 42 +/- 15 vs 43 +/- 12 years, p = 0.08: sex: 71% male vs 68% female, p = 0.09, respectively). Individuals heterozygous (AT) for the risk allele (T) at both loci (rs56810541/F11 and rs8176645/ABO) had a 3.9 (95% CI 2.74-5.71, p = 2.75e-13) increase in risk of CVT. Individuals homozygous (TT) for the risk allele at both loci had a 13.9 (95% CI 7.64-26.17, p = 2.0e-15) increase in risk of CVT. The presence of a non-O blood group (A, B, AB) combined with TT/rs56810541/F11 increased CVT risk by OR = 6.8 (95% CI 4.54-10.33, p = 2.00e15), compared with blood group-O combined with AA. DiscussionInteractions between factor XI and ABO genes increase risk of CVT by 4- to 14-fold.
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| 70. |
- Ken-Dror, G., et al.
(author)
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Genome-Wide Association Study Identifies First Locus Associated with Susceptibility to Cerebral Venous Thrombosis
- 2021
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In: Annals of Neurology. - : Wiley. - 0364-5134 .- 1531-8249. ; 90:5, s. 777-788
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Journal article (peer-reviewed)abstract
- Objective Cerebral venous thrombosis (CVT) is an uncommon form of stroke affecting mostly young individuals. Although genetic factors are thought to play a role in this cerebrovascular condition, its genetic etiology is not well understood. Methods A genome-wide association study was performed to identify genetic variants influencing susceptibility to CVT. A 2-stage genome-wide study was undertaken in 882 Europeans diagnosed with CVT and 1,205 ethnicity-matched control subjects divided into discovery and independent replication datasets. Results In the overall case-control cohort, we identified highly significant associations with 37 single nucleotide polymorphisms (SNPs) within the 9q34.2 region. The strongest association was with rs8176645 (combined p = 9.15 x 10(-24); odds ratio [OR] = 2.01, 95% confidence interval [CI] = 1.76-2.31). The discovery set findings were validated across an independent European cohort. Genetic risk score for this 9q34.2 region increases CVT risk by a pooled estimate OR = 2.65 (95% CI = 2.21-3.20, p = 2.00 x 10(-16)). SNPs within this region were in strong linkage disequilibrium (LD) with coding regions of the ABO gene. The ABO blood group was determined using allele combination of SNPs rs8176746 and rs8176645. Blood groups A, B, or AB, were at 2.85 times (95% CI = 2.32-3.52, p = 2.00 x 10(-16)) increased risk of CVT compared with individuals with blood group O. Interpretation We present the first chromosomal region to robustly associate with a genetic susceptibility to CVT. This region more than doubles the likelihood of CVT, a risk greater than any previously identified thrombophilia genetic risk marker. That the identified variant is in strong LD with the coding region of the ABO gene with differences in blood group prevalence provides important new insights into the pathophysiology of CVT. ANN NEUROL 2021
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