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Wiklund, Per-Gunnar
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Publications (10 of 32) Show all publications
Johansson, K., Jansson, J.-H., Johansson, L., Wiklund, P.-G., Nilsson, T. K. & Lind, M. (2018). D-Dimer is associated with first-ever intracerebral hemorrhage: a nested case-control study. Stroke, 49(9), 2034-2039
Open this publication in new window or tab >>D-Dimer is associated with first-ever intracerebral hemorrhage: a nested case-control study
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2018 (English)In: Stroke, ISSN 0039-2499, E-ISSN 1524-4628, Vol. 49, no 9, p. 2034-2039Article in journal (Refereed) Published
Abstract [en]

Background and Purpose - Hypertension is the most important risk factor for intracerebral hemorrhage (ICH), but further characterization is needed for groups at high risk of ICH. One way to predict the risk of developing a disease is with plasma biomarkers. This study aimed to investigate the association between the biomarker, D-dimer, and ICH risk.

Methods - This population-based, nested case-control study was conducted using data from 2 population-based surveys; the Vasterbotten Intervention Programme and MONICA Northern Sweden (Monitoring Trends and Determinants in Cardiovascular Disease). All participants underwent a health examination and blood sampling at baseline before the event. Cases (n=141) were diagnosed with a first-ever ICH between 1985 and March 2007. One or 2 controls (n=255) were matched to each case.

Results - The median age was 60 years; 39% of participants were women; and the median time from blood sampling to ICH was 5.2 years. When D-dimer was evaluated as a continuous variable, it was significantly associated with ICH. After multivariable adjustment (for hypertension, body mass index, cholesterol levels, diabetes mellitus, and smoking), the odds ratio was 1.36 per SD of D-dimcr (95% CI, 1.05-1.77). When participants were stratified in 3 groups according to time from blood sampling at health examination to ICH, we found that the association between D-dimer levels and ICH was most pronounced in individuals with the shortest time from blood sampling to ICH event (<3.5 years; odds ratio, 1.78; 95% CI, 1.05-3.05).

Conclusions - High plasma concentrations of D-dimer were associated with increased risk of a future ICH, after adjusting for cardiovascular risk factors. This association was predominantly driven by the cases with the shortest time from blood sampling to ICH event.

Place, publisher, year, edition, pages
Lippincott Williams & Wilkins, 2018
Keywords
biomarkers, case-control studies, cerebral hemorrhage, fibrin fragment, fibrinolysis
National Category
Neurology
Identifiers
urn:nbn:se:umu:diva-153829 (URN)10.1161/STROKEAHA.118.021751 (DOI)000442858100014 ()30354971 (PubMedID)
Funder
Västerbotten County CouncilNorrbotten County Council
Available from: 2018-12-11 Created: 2018-12-11 Last updated: 2019-08-20Bibliographically approved
Johansson, K., Jansson, J.-H., Johansson, L., Wiklund, P.-G., Nilsson, T. K. & Lind, M. (2018). D-dimer is associated with first-ever intracerebral hemorrhage. A prospective ease-control study. Cerebrovascular Diseases, 45, 213-213
Open this publication in new window or tab >>D-dimer is associated with first-ever intracerebral hemorrhage. A prospective ease-control study
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2018 (English)In: Cerebrovascular Diseases, ISSN 1015-9770, E-ISSN 1421-9786, Vol. 45, p. 213-213Article in journal, Meeting abstract (Other academic) Published
Place, publisher, year, edition, pages
S. Karger, 2018
National Category
Cardiac and Cardiovascular Systems
Identifiers
urn:nbn:se:umu:diva-151802 (URN)000440013700104 ()
Note

Supplement: 1

Meeting Abstract: P165

Available from: 2018-09-14 Created: 2018-09-14 Last updated: 2019-08-20Bibliographically approved
Pennlert, J., Overholser, R., Asplund, K., Carlberg, B., Van Rompaye, B., Wiklund, P.-G. & Eriksson, M. (2017). Optimal Timing of Anticoagulant Treatment After Intracerebral Hemorrhage in Patients With Atrial Fibrillation. Stroke, 48(2), 314-320
Open this publication in new window or tab >>Optimal Timing of Anticoagulant Treatment After Intracerebral Hemorrhage in Patients With Atrial Fibrillation
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2017 (English)In: Stroke, ISSN 0039-2499, E-ISSN 1524-4628, Vol. 48, no 2, p. 314-320Article in journal (Refereed) Published
Abstract [en]

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.

Place, publisher, year, edition, pages
American Heart Association, 2017
Keywords
anticoagulants, atrial fibrillation, cerebral hemorrhage, ischemia, stroke
National Category
Neurology
Identifiers
urn:nbn:se:umu:diva-129335 (URN)10.1161/STROKEAHA.116.014643 (DOI)000394510300024 ()27999135 (PubMedID)
Note

Presented in part at the 2nd European Stroke Organisation Conference (ESOC 2016), Barcelona, Spain, May 10–12, 2016

Available from: 2016-12-22 Created: 2016-12-22 Last updated: 2018-06-09Bibliographically approved
Wennberg, M., Jansson, J.-H., Norberg, M., Skerfving, S., Strömberg, U., Wiklund, P.-G. & Bergdahl, I. A. (2016). Fish consumption and risk of stroke: a second prospective case-control study from northern Sweden. Nutrition Journal, 15(1), Article ID 98.
Open this publication in new window or tab >>Fish consumption and risk of stroke: a second prospective case-control study from northern Sweden
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2016 (English)In: Nutrition Journal, ISSN 1475-2891, E-ISSN 1475-2891, Vol. 15, no 1, article id 98Article in journal (Refereed) Published
Abstract [en]

BACKGROUND: Fish consumption has been concluded to be associated with decreased risk of stroke in several reviews. However, among men, but not women, an increased risk of stroke was previously found at high fish consumption (>3 meals/week) in northern Sweden. This study investigates if previous results on elevated stroke risk with high fish consumption in men in northern Sweden can be confirmed in a larger study with new cases in the same population.

METHODS: A prospective nested case-control study was performed within the population-based Northern Sweden Health and Disease Study cohort. Information on fish consumption, other lifestyle and medical data was collected at baseline. Incident stroke cases (1987-2007, n = 735) were identified and 2698 controls matched for gender, age, year of baseline and geographical region.

RESULTS: There were no associations between total fish or fatty fish consumption and stroke risk; thus the previous finding of increased risk of stroke with high fish consumption in men could not be repeated. High intake of lean fish (>twice/week compared to < once/month) was associated with increased stroke risk in men [OR 1.80 (95% CI 1.00, 3.21), but not in women [OR 0.50 (95% CI 0.24, 1.10)]. The association was driven by men living alone.

CONCLUSIONS: The previous association between high total fish consumption and risk of stroke in men could not be repeated. The increased risk found in men with high intake of lean fish may be due to chance or confounding specific for this group.

Keywords
Fish consumption, Ischaemic stroke, Hemorraghic stroke, Lifestyle, Confounding
National Category
Public Health, Global Health, Social Medicine and Epidemiology
Identifiers
urn:nbn:se:umu:diva-127937 (URN)10.1186/s12937-016-0216-3 (DOI)000389007100002 ()27852254 (PubMedID)
Available from: 2016-11-21 Created: 2016-11-21 Last updated: 2018-06-09Bibliographically approved
Dehghan, A., Bis, J. C., White, C. C., Smith, A. V., Morrison, A. C., Cupples, L. A., . . . O'Donnell, C. J. (2016). Genome-Wide Association Study for Incident Myocardial Infarction and Coronary Heart Disease in Prospective Cohort Studies: The CHARGE Consortium. PLoS ONE, 11(3), Article ID e0144997.
Open this publication in new window or tab >>Genome-Wide Association Study for Incident Myocardial Infarction and Coronary Heart Disease in Prospective Cohort Studies: The CHARGE Consortium
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2016 (English)In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 11, no 3, article id e0144997Article in journal (Refereed) Published
Abstract [en]

Background Data are limited on genome-wide association studies (GWAS) for incident coronary heart disease (CHD). Moreover, it is not known whether genetic variants identified to date also associate with risk of CHD in a prospective setting. Methods We performed a two-stage GWAS analysis of incident myocardial infarction (MI) and CHD in a total of 64,297 individuals (including 3898 MI cases, 5465 CHD cases). SNPs that passed an arbitrary threshold of 5x10(-6) in Stage I were taken to Stage II for further discovery. Furthermore, in an analysis of prognosis, we studied whether known SNPs from former GWAS were associated with total mortality in individuals who experienced MI during follow-up. Results In Stage I 15 loci passed the threshold of 5x10(-6); 8 loci for MI and 8 loci for CHD, for which one locus overlapped and none were reported in previous GWAS meta-analyses. We took 60 SNPs representing these 15 loci to Stage II of discovery. Four SNPs near QKI showed nominally significant association with MI (p-value<8.8x10(-3)) and three exceeded the genome-wide significance threshold when Stage I and Stage II results were combined (top SNP rs6941513: p = 6.2x10(-9)). Despite excellent power, the 9p21 locus SNP (rs1333049) was only modestly associated with MI (HR = 1.09, p-value = 0.02) and marginally with CHD (HR = 1.06, p-value = 0.08). Among an inception cohort of those who experienced MI during follow-up, the risk allele of rs1333049 was associated with a decreased risk of subsequent mortality (HR = 0.90, p-value = 3.2x10(-3)). Conclusions QKI represents a novel locus that may serve as a predictor of incident CHD in prospective studies. The association of the 9p21 locus both with increased risk of first myocardial infarction and longer survival after MI highlights the importance of study design in investigating genetic determinants of complex disorders.

National Category
General Practice
Identifiers
urn:nbn:se:umu:diva-119067 (URN)10.1371/journal.pone.0144997 (DOI)000371990100004 ()
Available from: 2016-04-20 Created: 2016-04-11 Last updated: 2018-06-07Bibliographically approved
Pennlert, J., Asplund, K., Carlberg, B., Wiklund, P.-G., Wisten, A., Åsberg, S. & Eriksson, M. (2015). Antithrombotic Treatment Following Intracerebral Hemorrhage in Patients With and Without Atrial Fibrillation. Stroke, 46(8), 2094-2099
Open this publication in new window or tab >>Antithrombotic Treatment Following Intracerebral Hemorrhage in Patients With and Without Atrial Fibrillation
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2015 (English)In: Stroke, ISSN 0039-2499, E-ISSN 1524-4628, Vol. 46, no 8, p. 2094-2099Article in journal (Refereed) Published
Abstract [en]

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 CHA2DS2-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 CHA2DS2-VASc and HAS-BLED (hypertension, abnormal renal/liver function, stroke, bleeding history or predisposition, labile international normalized ratio, elderly, drugs/alcohol) scores (rs=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 CHA2DS2-VASc in ICH survivors with concurrent AF are used to guide the anticoagulant treatment decision in Swedish clinical practice.

National Category
Clinical Medicine
Identifiers
urn:nbn:se:umu:diva-106687 (URN)10.1161/STROKEAHA.115.009087 (DOI)000359972200026 ()26159794 (PubMedID)
Available from: 2015-08-03 Created: 2015-08-03 Last updated: 2018-06-07Bibliographically approved
Pennlert, J., Asplund, K., Carlberg, B., Wiklund, P. G., Wisten, A., Asberg, S. & Eriksson, M. (2015). Antithrombotic treatment following intracerebral hemorrhage in patients with and without atrial fibrillation. A nationwide study based on Riksstroke. International Journal of Stroke, 10, 294-295
Open this publication in new window or tab >>Antithrombotic treatment following intracerebral hemorrhage in patients with and without atrial fibrillation. A nationwide study based on Riksstroke
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2015 (English)In: International Journal of Stroke, ISSN 1747-4930, E-ISSN 1747-4949, Vol. 10, p. 294-295Article in journal, Meeting abstract (Other academic) Published
National Category
Cardiac and Cardiovascular Systems
Identifiers
urn:nbn:se:umu:diva-108168 (URN)000359304002050 ()
Note

Supplement: 2 Special Issue: SI Meeting Abstract: ESOC-1343

Available from: 2015-09-09 Created: 2015-09-04 Last updated: 2018-06-07Bibliographically approved
Pennlert, J., Eriksson, M., Carlberg, B. & Wiklund, P.-G. (2014). Long-Term Risk and Predictors of Recurrent Stroke Beyond the Acute Phase. Stroke, 45(6), 1839-1841
Open this publication in new window or tab >>Long-Term Risk and Predictors of Recurrent Stroke Beyond the Acute Phase
2014 (English)In: Stroke, ISSN 0039-2499, E-ISSN 1524-4628, Vol. 45, no 6, p. 1839-1841Article in journal (Refereed) Published
Abstract [en]

Background and Purpose-Previous studies have shown heterogeneous results on predictors and rates of stroke recurrence. This study set out to investigate the long-term risk and predictors of recurrent stroke in Northern Sweden 1995 to 2008.

Methods-In the population-based Monitoring Trends and Determinants of Cardiovascular Disease (MONICA) stroke incidence registry, stroke survivors of either ischemic stroke or intracerebral hemorrhage were followed for recurrent stroke or death. Cox regression was used to identify predictors of stroke recurrence.

Results-The study comprised 6700 patients and 26 597 person-years. During follow-up, 928 (13.9%) patients had a recurrent stroke. Comparison between the first time period (1995-1998) and the last (2004-2008) showed declined risk of stroke recurrence (hazard ratio, 0.64 [95% confidence interval, 0.52-0.78]). Previous myocardial infarction was less prevalent in the most recent cohort (P<0.001). Predictors of stroke recurrence were age (hazard ratio, 1.03 [95% confidence interval, 1.02-1.04]) and diabetes mellitus (hazard ratio, 1.34 [95% confidence interval, 1.15-1.57]). After an index intracerebral hemorrhage (n=815), a major part of recurrent events were ischemic (63%), and compared with the ischemic stroke group (n=5885), a tendency toward lower risk of recurrence was observed.

Conclusions-Despite declining recurrence rates in this relatively young stroke population, almost one third are either dead or have experienced a second stroke in 5 years.

Keywords
epidemiology, stroke
National Category
Cardiac and Cardiovascular Systems
Identifiers
urn:nbn:se:umu:diva-91150 (URN)10.1161/STROKEAHA.114.005060 (DOI)000337090700049 ()
Available from: 2014-07-16 Created: 2014-07-15 Last updated: 2018-06-07Bibliographically approved
Williams, F. M. K., Carter, A. M., Hysi, P. G., Surdulescu, G., Hodgkiss, D., Soranzo, N., . . . Spector, T. D. (2013). Ischemic stroke is associated with the ABO locus: the EuroCLOT study. Annals of Neurology, 73(1), 16-31
Open this publication in new window or tab >>Ischemic stroke is associated with the ABO locus: the EuroCLOT study
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2013 (English)In: Annals of Neurology, ISSN 0364-5134, E-ISSN 1531-8249, Vol. 73, no 1, p. 16-31Article in journal (Refereed) Published
Abstract [en]

Objective: End-stage coagulation and the structure/function of fibrin are implicated in the pathogenesis of ischemic stroke. We explored whether genetic variants associated with end-stage coagulation in healthy volunteers account for the genetic predisposition to ischemic stroke and examined their influence on stroke subtype. Methods: Common genetic variants identified through genome-wide association studies of coagulation factors and fibrin structure/function in healthy twins (n = 2,100, Stage 1) were examined in ischemic stroke (n = 4,200 cases) using 2 independent samples of European ancestry (Stage 2). A third clinical collection having stroke subtyping (total 8,900 cases, 55,000 controls) was used for replication (Stage 3). Results: Stage 1 identified 524 single nucleotide polymorphisms (SNPs) from 23 linkage disequilibrium blocks having significant association (p < 5 x 10(-8)) with 1 or more coagulation/fibrin phenotypes. The most striking associations included SNP rs5985 with factor XIII activity (p = 2.6 x 10(-186)), rs10665 with FVII (p = 2.4 x 10(-47)), and rs505922 in the ABO gene with both von Willebrand factor (p = 4.7 x 10(-57)) and factor VIII (p = 1.2 x 10(-36)). In Stage 2, the 23 independent SNPs were examined in stroke cases/noncases using MOnica Risk, Genetics, Archiving and Monograph (MORGAM) and Wellcome Trust Case Control Consortium 2 collections. SNP rs505922 was nominally associated with ischemic stroke (odds ratio = 0.94, 95% confidence interval = 0.88-0.99, p = 0.023). Independent replication in Meta-Stroke confirmed the rs505922 association with stroke, beta (standard error, SE) = 0.066 (0.02), p = 0.001, a finding specific to large-vessel and cardioembolic stroke (p = 0.001 and p = < 0.001, respectively) but not seen with small-vessel stroke (p = 0.811). Interpretation: ABO gene variants are associated with large-vessel and cardioembolic stroke but not small-vessel disease. This work sheds light on the different pathogenic mechanisms underpinning stroke subtype.

Place, publisher, year, edition, pages
Wiley-Blackwell, 2013
National Category
Neurology
Identifiers
urn:nbn:se:umu:diva-67055 (URN)10.1002/ana.23838 (DOI)000314660800007 ()
Note

Errata Annals of Neurology, 2014: 75 (1), 166-167. doi:10.1002/ana.24105

Available from: 2013-03-24 Created: 2013-03-12 Last updated: 2018-06-08Bibliographically approved
Hughes, M. F., Saarela, O., Stritzke, J., Kee, F., Silander, K., Klopp, N., . . . Schunkert, H. (2012). Genetic Markers Enhance Coronary Risk Prediction in Men: The MORGAM Prospective Cohorts. PLoS ONE, 7(7), e40922
Open this publication in new window or tab >>Genetic Markers Enhance Coronary Risk Prediction in Men: The MORGAM Prospective Cohorts
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2012 (English)In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 7, no 7, p. e40922-Article in journal (Refereed) Published
Abstract [en]

Background: More accurate coronary heart disease (CHD) prediction, specifically in middle-aged men, is needed to reduce the burden of disease more effectively. We hypothesised that a multilocus genetic risk score could refine CHD prediction beyond classic risk scores and obtain more precise risk estimates using a prospective cohort design. Methods: Using data from nine prospective European cohorts, including 26,221 men, we selected in a case-cohort setting 4,818 healthy men at baseline, and used Cox proportional hazards models to examine associations between CHD and risk scores based on genetic variants representing 13 genomic regions. Over follow-up (range: 5-18 years), 1,736 incident CHD events occurred. Genetic risk scores were validated in men with at least 10 years of follow-up (632 cases, 1361 non-cases). Genetic risk score 1 (GRS1) combined 11 SNPs and two haplotypes, with effect estimates from previous genome-wide association studies. GRS2 combined 11 SNPs plus 4 SNPs from the haplotypes with coefficients estimated from these prospective cohorts using 10-fold cross-validation. Scores were added to a model adjusted for classic risk factors comprising the Framingham risk score and 10-year risks were derived. Results: Both scores improved net reclassification (NRI) over the Framingham score (7.5%, p = 0.017 for GRS1, 6.5%, p = 0.044 for GRS2) but GRS2 also improved discrimination (c-index improvement 1.11%, p = 0.048). Subgroup analysis on men aged 50-59 (436 cases, 603 non-cases) improved net reclassification for GRS1 (13.8%) and GRS2 (12.5%). Net reclassification improvement remained significant for both scores when family history of CHD was added to the baseline model for this male subgroup improving prediction of early onset CHD events. Conclusions: Genetic risk scores add precision to risk estimates for CHD and improve prediction beyond classic risk factors, particularly for middle aged men.

Place, publisher, year, edition, pages
SAN FRANCISCO, USA: PUBLIC LIBRARY SCIENCE, 2012
National Category
Cardiac and Cardiovascular Systems
Identifiers
urn:nbn:se:umu:diva-61227 (URN)10.1371/journal.pone.0040922 (DOI)000306806600029 ()
Available from: 2012-11-08 Created: 2012-11-07 Last updated: 2018-06-08Bibliographically approved
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