| 1. |
- Asplund, Kjell, et al.
(författare)
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Relative risks for stroke by age, sex, and population based on follow-up of 18 European populations in the MORGAM Project
- 2009
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Ingår i: Stroke. - 0039-2499 .- 1524-4628. ; 40:7, s. 2319-2326
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND AND PURPOSE: Within the framework of the MOnica Risk, Genetics, Archiving and Monograph (MORGAM) Project, the variations in impact of classical risk factors of stroke by population, sex, and age were analyzed. METHODS: Follow-up data were collected in 43 cohorts in 18 populations in 8 European countries surveyed for cardiovascular risk factors. In 93 695 persons aged 19 to 77 years and free of major cardiovascular disease at baseline, total observation years were 1 234 252 and the number of stroke events analyzed was 3142. Hazard ratios were calculated by Cox regression analyses. RESULTS: Each year of age increased the risk of stroke (fatal and nonfatal together) by 9% (95% CI, 9% to 10%) in men and by 10% (9% to 10%) in women. A 10-mm Hg increase in systolic blood pressure involved a similar increase in risk in men (28%; 24% to 32%) and women (25%; 20% to 29%). Smoking conferred a similar excess risk in women (104%; 78% to 133%) and in men (82%; 66% to 100%). The effect of increasing body mass index was very modest. Higher high-density lipoprotein cholesterol levels decreased the risk of stroke more in women (hazard ratio per mmol/L 0.58; 0.49 to 0.68) than in men (0.80; 0.69 to 0.92). The impact of the individual risk factors differed somewhat between countries/regions with high blood pressure being particularly important in central Europe (Poland and Lithuania). CONCLUSIONS: Age, sex, and region-specific estimates of relative risks for stroke conferred by classical risk factors in various regions of Europe are provided. From a public health perspective, an important lesson is that smoking confers a high risk for stroke across Europe.
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| 2. |
- Janunger, Tomas, et al.
(författare)
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A novel stroke locus identified in a northern Sweden pedigree : linkage to chromosome 9q31-33.
- 2009
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Ingår i: Neurology. - 0028-3878 .- 1526-632X. ; 73:21, s. 1767-1773
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: The population of northern Sweden is characterized by reduced genetic diversity and a high incidence of stroke. We sought to reduce genetic variation further, using genealogic analysis in a set of nuclear families affected by stroke, and we subsequently performed a genome-wide scan to identify novel stroke susceptibility loci. METHODS: Through genealogy, 7 nuclear families with a common ancestor, connected over 8 generations, were identified. A genome-wide scan using 449 microsatellite markers was performed with subsequent haplotype analyses. RESULTS: A maximum allele-sharing lod score of 4.81 on chromosome 9q31-q33 was detected. Haplotype analysis identified a common 2.2-megabase interval in the chromosomal region in 4 of the nuclear families, where an overrepresentation of intracerebral hemorrhage was observed. CONCLUSIONS: We have identified a novel susceptibility locus for stroke. Haplotype analysis suggests that a shared genetic factor is of particular importance for intracerebral hemorrhage.
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| 3. |
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| 4. |
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| 5. |
- Nilsson-Ardnor, Sofie, et al.
(författare)
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Linkage of ischemic stroke to the PDE4D region on 5q in a Swedish population.
- 2005
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Ingår i: Stroke. - 0039-2499 .- 1524-4628. ; 36:8, s. 1666-1671
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND AND PURPOSE: Recent Icelandic studies have demonstrated linkage for common forms of stroke to chromosome 5q12 and association between phosphodiesterase4D (PDE4D) and ischemic stroke. Using a candidate region approach, we wanted to test the validity of these findings in a different population from northern Sweden. METHODS: A total of 56 families with 117 affected individuals were included in the linkage study. Genotyping was performed with polymorphic microsatellite markers with an average distance of 4.5 cM on chromosome 5. In the association study, 275 cases of first-ever stroke were included together with 550 matched community controls. Polymorphisms were tested individually for association of PDE4D to stroke. RESULTS: Maximum allele-sharing lod score in favor of linkage was observed at marker locus D5S424 (lod score=2.06; P=0.0010). Conditional logistic regression calculations revealed no significant association of ischemic stroke to the defined at-risk allele in PDE4D (odds ratio, 1.1; 95% confidence interval, 0.84 to 1.45). A protective effect may though be implied for 2 of the polymorphisms analyzed in PDE4D. CONCLUSIONS: Using a candidate region approach in a set of stroke families from northern Sweden, we have replicated linkage of stroke susceptibility to the PDE4D gene region on chromosome 5q. Association studies in an independent nested case-control sample from the same geographically located population suggested that different alleles confer susceptibility/protection to stroke in the Icelandic and the northern Swedish populations.
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| 6. |
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| 7. |
- Pennlert, Johanna, et al.
(författare)
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Antithrombotic Treatment Following Intracerebral Hemorrhage in Patients With and Without Atrial Fibrillation
- 2015
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Ingår i: Stroke. - 0039-2499 .- 1524-4628. ; 46:8, s. 2094-2099
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Tidskriftsartikel (refereegranskat)abstract
- Background and Purpose-Patients who survive intracerebral hemorrhage (ICH) often have compelling indications for anticoagulant and antiplatelet medication. This nationwide observational study aimed to determine the extent and predictors of antithrombotic treatment after ICH in Sweden. Methods-Patients with a first-ever ICH in the Swedish Stroke Register (Riksstroke) 2005 to 2012 who survived hospital discharge were included. Riksstroke data were individually linked with other national registers to determine comorbid conditions and dispensed prescriptions of antithrombotic agents. Results-Among the 2777 patients with atrial fibrillation (AF), the proportion with a dispensed prescription of antithrombotic agents was 8.5% (anticoagulants) and 36.6% (antiplatelet agents) within 6 months and 11.1% (anticoagulants) and 43.6% (antiplatelet agents) within 1 year. Among the 11 268 patients without AF, the corresponding figures were 1.6% (anticoagulants) and 13.8% (antiplatelet agents) within 6 months and 2.0% (anticoagulants) and 17.5% (antiplatelet agents) within 1 year. In patients with AF, predictors of anticoagulant treatment were less severe ICH, younger age, previous anticoagulation, valvular disease, and previous ischemic stroke. High CHA(2)DS(2)-VASc (congestive heart failure, hypertension, age, diabetes mellitus, stroke [doubled], vascular disease, age, and sex category [female]) scores did not correlate with anticoagulant treatment. There was a positive correlation between high CHA(2)DS(2)-VASc and HAS-BLED (hypertension, abnormal renal/liver function, stroke, bleeding history or predisposition, labile international normalized ratio, elderly, drugs/alcohol) scores (r(s)=0.590, P<0.001). Conclusions-In majority of patients who receive antithrombotic agents, treatment is initiated within 6 months of ICH. Still, many patients with compelling indications for antithrombotic treatment are not prescribed antithrombotic agents. Factors other than high risk of embolic stroke by CHA(2)DS(2)-VASc in ICH survivors with concurrent AF are used to guide the anticoagulant treatment decision in Swedish clinical practice.
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| 8. |
- Pennlert, Johanna, et al.
(författare)
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Optimal Timing of Anticoagulant Treatment After Intracerebral Hemorrhage in Patients With Atrial Fibrillation
- 2017
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Ingår i: Stroke. - : American Heart Association. - 0039-2499 .- 1524-4628. ; 48:2, s. 314-320
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND AND PURPOSE: This study aims to provide observational data on the relationship between the timing of antithrombotic treatment and the competing risks of severe thrombotic and hemorrhagic events in a cohort of Swedish patients with atrial fibrillation and intracerebral hemorrhage (ICH).METHODS: Patients with atrial fibrillation and a first-ever ICH were identified in the Swedish Stroke Register, Riksstroke, 2005 to 2012. Riksstroke was linked with other national registers to find information on treatment, comorbidity, and outcome. The optimal timing of treatment in patients with low and high thromboembolic risk was described through cumulative incidence functions separately for thrombotic and hemorrhagic events and for the combined end point vascular death or nonfatal stroke.RESULTS: The study included 2619 ICH survivors with atrial fibrillation with 5759 person-years of follow-up. Anticoagulant treatment was associated with a reduced risk of vascular death and nonfatal stroke in high-risk patients with no significantly increased risk of severe hemorrhage. The benefit seemed to be greatest when treatment was started 7 to 8 weeks after ICH. For high-risk women, the total risk of vascular death or stroke recurrence within 3 years was 17.0% when anticoagulant treatment was initiated 8 weeks after ICH and 28.6% without any antithrombotic treatment (95% confidence interval for difference, 1.4%-21.8%). For high-risk men, the corresponding risks were 14.3% versus 23.6% (95% confidence interval for difference, 0.4%-18.2%).CONCLUSIONS: This nationwide observational study suggests that anticoagulant treatment may be initiated 7 to 8 weeks after ICH in patients with atrial fibrillation to optimize the benefit from treatment and minimize risk.
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| 9. |
- Wiklund, Per-Gunnar, 1963-
(författare)
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Genetic aspects of stroke : association and linkage studies in a northern Swedish population
- 2005
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Stroke is a common, multifactorial cardiovascular disease. A stroke event is the result of traditional risk factors (i.e. hypertension, diabetes, smoking), environmental exposures and genetic factors in a complex interplay. The genetic contribution is, as estimated by studies on the influence of family history on the risk of stroke, limited on the individual level, and overridden by, for example the excess risk associated with smoking. On the population level, and as a means to better understand the etiology of stroke, genetics can play a major role.Northern Sweden is well suited for studying the genetic aspects of stroke. The population shows signs of founder effects, and is relatively homogeneous. Large-scale cardiovascular health surveys, the MONICA Project and the Västerbotten Intervention Program, allow studies on risk factors in relation to stroke. Two prospective nested case-referent study samples, (113 cases and 226 controls; 275 cases and 549 controls), and a set of 56 families (117 affected) were collected for functional candidate gene association, and linkage, studies.The selected candidate genes included haemostatic factors and genes within the renin angiotensin system (RAS). Functional single nucleotide polymorphisms (SNPs) that influence the levels of PAI-1 (PAI-1 4G/5G), and tPA (tPA -7,351C>T), have been identified. The angiotensin converting enzyme insertion/deletion polymorphism (ACE I/D) has been shown to be associated with ischaemic stroke. The angiotensin II receptor type 1 A1166C polymorphism (AT1R A1166C), less extensively studied, has been suggested to be associated with stroke, and to interact with the ACE I/D.We found that the PAI-1 4G/4G genotype was associated with an increased risk of future ischaemic stroke (OR 1.79, 95%CI 1.01-3.19), and this was replicated in a second study sample. Furthermore, levels of serum triglycerides modulated the effect of the genotype. In the study on tPA, no association between the tPA -7,351C>T polymorphism and the risk of stroke was found in an analysis of the two study samples pooled. The two RAS polymorphisms were prospectively associated with ischaemic stroke independently of each other and other risk factors (OR 1.60, p=0.02 and OR 1.60, p=0.04, respectively).A candidate region linkage study, focusing on a previously reported stroke susceptibility locus on chromosome 5, was performed in a set of families. In addition, association between ischemic stroke and the positional candidate gene phosphodiesterase 4D (PDE4D) was tested. Linkage to 5q12 was replicated in this independent population, but not PDE4D association with stroke. This suggests that alternative genotypes in this stroke susceptibility locus contribute in different populations.In conclusion, the genetic component in the causation of stroke was investigated. The results of the functional candidate gene association studies showed (1) interaction between PAI-1 genotype and a putatively modifiable risk factor, triglycerides, (2) a prospective testing of the tPA SNP with no association detected, and (3) a novel, hypothesis-generating, finding in the case of AT1R polymorphism and the risk of ischaemic stroke. The replication of linkage to chromosome 5q12 in our northern Swedish population was interesting, and it will be further explored.
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| 10. |
- Wiklund, Per-Gunnar, et al.
(författare)
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Plasminogen activator inhibitor-1 4G/5G polymorphism and risk of stroke : replicated findings in two nested case-control studies based on independent cohorts.
- 2005
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Ingår i: Stroke. - 0039-2499 .- 1524-4628. ; 36:8, s. 1661-1665
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND AND PURPOSE: Impaired fibrinolytic function secondary to elevated plasminogen activator inhibitor-1 (PAI-1) levels has been implicated in ischemic stroke. PAI-1 levels are determined by genetic factors and environmental factors, triglyceride levels in particular. The aim of this study was to investigate the common functional 4/5 guanosine (4G/5G) polymorphism in the promoter region of the PAI-1 gene and the risk of stroke. METHODS: A nested case-control study design was applied, using baseline data for 2 independent cohorts obtained at population-based surveys in northern Sweden. In study A, there were 113, and in study B, there were 275 individuals without major concomitant disease at baseline who later experienced a first-ever stroke. Blood samples obtained at baseline were analyzed for potential risk factors, including the 4G/5G polymorphism of the PAI-1 gene. RESULTS: The 4G allele of the PAI-1 polymorphism was associated with an increased risk of future ischemic stroke in both studies (odds ratio [OR] of 4G homozygosity, 1.87; 95% CI, 1.12 to 3.15 in study A; OR of 4G homozygosity, 1.56; 95% CI, 1.12 to 2.16 in study B). Individuals with the combination of hypertriglyceridemia and 4G homozygosity were at the greatest risk of developing stroke. Multiple logistic regression analysis identified 4G homozygosity, systolic blood pressure, and diabetes as independent predictors of ischemic stroke. CONCLUSIONS: Identical findings in 2 independent studies strongly suggest a true and clinically important association between PAI-1 4G/5G genotype and risk of future ischemic stroke. The observed modification of the genotype effect by triglycerides may be interpreted as a gene-environment interaction.
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