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Johansson, M., Johansson, L., Wennberg, M. & Lind, M. (2019). Alcohol Consumption and Risk of First-Time Venous Thromboembolism in Men and Women. Thrombosis and Haemostasis, 119(6), 962-970
Open this publication in new window or tab >>Alcohol Consumption and Risk of First-Time Venous Thromboembolism in Men and Women
2019 (English)In: Thrombosis and Haemostasis, ISSN 0340-6245, Vol. 119, no 6, p. 962-970Article in journal (Refereed) Published
Abstract [en]

BACKGROUND: The relationship between alcohol intake and risk of venous thromboembolism (VTE) is unclear. Men and women differ in their drinking habits, which may affect a possible association.

OBJECTIVE: This article investigates the association between alcohol consumption, alcohol dependence and VTE in the total population as well as in men and women separately.

METHODS: We performed a prospective, population-based cohort study in northern Sweden. Study participants were 108,025 (51% women) persons aged 30 to 60 years who underwent a health examination between 1985 and 2014. We assessed alcohol consumption and defined alcohol dependence using a questionnaire. The outcome was a validated first-time VTE.

RESULTS: The mean follow-up time was 13.9 years, and 2,054 participants had a first-time VTE. The mean alcohol consumption was 3.5 standard drinks weekly in men and 1.5 in women. Alcohol dependence was found in 10% of men and 3% of women. There was an association between alcohol consumption (hazard ratio [HR], 1.02; 95% confidence interval [CI], 1.00-1.03 per standard drink weekly) as well as alcohol dependence (HR, 1.27; 95% CI, 1.06-1.52) and VTE after adjustments. In men, the risk of VTE increased over quartiles of weekly alcohol consumption (p for trend 0.02), with a HR of 1.22 (95% CI, 1.01-1.47) for the highest quartile. Alcohol dependence was associated with VTE in men (HR, 1.30; 95% CI, 1.07-1.59). In women, there were no significant associations.

CONCLUSION: High alcohol consumption and alcohol dependence were associated with increased risk of first-time VTE in men, but not in women.

Place, publisher, year, edition, pages
Georg Thieme Verlag KG, 2019
Keywords
venous thromboembolism, venous thrombosis, alcohol consumption, alcohol intake, alcohol drinking, alcohol dependence, risk marker, prospective studies, cohort studies
National Category
Other Clinical Medicine
Research subject
Medicine
Identifiers
urn:nbn:se:umu:diva-157495 (URN)10.1055/s-0039-1681100 (DOI)000474924300013 ()30900224 (PubMedID)2-s2.0-85066132287 (Scopus ID)
Projects
Venous thromboEmbolism In Northern Sweden
Funder
Swedish Research CouncilForte, Swedish Research Council for Health, Working Life and WelfareVästerbotten County Council
Available from: 2019-03-24 Created: 2019-03-24 Last updated: 2019-09-09Bibliographically approved
Johansson, M., Johansson, L., Wennberg, P. & Lind, M. (2019). Physical activity and risk of first-time venous thromboembolism. European Journal of Preventive Cardiology, 26(11), 1181-1187
Open this publication in new window or tab >>Physical activity and risk of first-time venous thromboembolism
2019 (English)In: European Journal of Preventive Cardiology, ISSN 2047-4873, E-ISSN 2047-4881, Vol. 26, no 11, p. 1181-1187Article in journal (Refereed) Published
Abstract [en]

Background: Physical activity may have a protective effect against venous thromboembolism (VTE). The aim of this study was to investigate the association between leisure time physical activity, occupational physical activity, and the risk of VTE in men and women separately.

Methods: The population-based, prospective Venous thromboEmbolism In Northern Sweden (VEINS) cohort study included 108,025 participants of health examinations between 1985 and 2014. Physical activity data were collected by questionnaire. Participants were followed from health examination to first-time VTE event, death, emigration or the end of the study. All VTE events were validated by reviewing medical records and radiology reports.

Results: During 1,496,669 person-years, 2054 participants experienced VTE. Women who performed leisure time physical activity at least once a week had a lower risk of first-time VTE (hazard ratio (HR) 0.83; 95% confidence interval (CI) 0.71–0.98 after adjustments) compared with women with less or no physical activity. Furthermore, women with high occupational physical activity also had a lower risk of VTE (HR 0.85; 95% CI 0.74–0.98). In men, there was no consistent association between either measure of physical activity and the risk of VTE.

Conclusion: We found an association between increased physical activity and a lower risk of first-time VTE in women.

Place, publisher, year, edition, pages
Sage Publications, 2019
Keywords
Venous thromboembolism, exercise, physical activity, venous thrombosis
National Category
Other Clinical Medicine
Research subject
Medicine
Identifiers
urn:nbn:se:umu:diva-156241 (URN)10.1177/2047487319829310 (DOI)000472573700010 ()30727768 (PubMedID)2-s2.0-85061651499 (Scopus ID)
Funder
Västerbotten County Council
Available from: 2019-03-01 Created: 2019-03-01 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 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
Johansson, M., Lind, M., Jansson, J.-H., Fhärm, E. & Johansson, L. (2018). Fasting plasma glucose, oral glucose tolerance test, and the risk of first-time venous thromboembolism. A report from the VEINS cohort study. Thrombosis Research, 165, 86-94
Open this publication in new window or tab >>Fasting plasma glucose, oral glucose tolerance test, and the risk of first-time venous thromboembolism. A report from the VEINS cohort study
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2018 (English)In: Thrombosis Research, ISSN 0049-3848, E-ISSN 1879-2472, Vol. 165, p. 86-94Article in journal (Refereed) Published
Abstract [en]

Introduction: It remains unclear whether high plasma glucose levels are associated with venous thromboembolism (VTE). This study investigated the association between fasting plasma glucose (FPG), oral glucose tolerance test (two-hour post-load plasma glucose (2HPG)), diabetes, and VTE. Materials and methods: The population-based, prospective Venous thromboEmbolism In Northern Sweden (VEINS) cohort study included 108,025 residents of Vasterbotten County in northern Sweden. The participants were aged 30 to 60 years and had no previous VTE events. They were included from 1985 onwards and were followed until a VTE event, death, emigration, or the study end on September 5, 2014. All underwent a health examination that measured weight, height, FPG, and 2HPG and included a questionnaire regarding smoking, education level, and history of diabetes. Potential VTE events were identified by an extensive diagnosis registry search and were validated by reviewing medical records and radiology reports. Results: An objectively verified first-time VTE event was experienced by 2054 participants during 1,496,669 person-years of follow-up. In univariable analysis, there were associations between FPG, 2HPG, diabetes, and the risk of VTE. These associations disappeared after adjustment for potential confounders (age, sex, body mass index, cancer at inclusion, education level, smoking, and hypertension). The adjusted hazard ratios were 1.01 (95% confidence interval 0.83-1.23) for diabetes, 1.01 for each standard deviation of FPG (95% confidence interval 0.97-1.05), and 0.96 for each standard deviation of 2HPG (95% confidence interval 0.91-1.00). Conclusions: There were no independent associations between FPG, 2HPG, diabetes, and future risk of VTE.

Place, publisher, year, edition, pages
Elsevier, 2018
Keywords
Venous thromboembolism, Venous thrombosis, Pulmonary embolism, Diabetes, Glucose, Glucose lerance test
National Category
Cardiac and Cardiovascular Systems
Identifiers
urn:nbn:se:umu:diva-148754 (URN)10.1016/j.thromres.2018.03.015 (DOI)000432891600015 ()29604434 (PubMedID)
Available from: 2018-06-19 Created: 2018-06-19 Last updated: 2019-08-20Bibliographically approved
Öhman, L., Johansson, M., Jansson, J.-H., Lind, M. & Johansson, L. (2018). Positive predictive value and misclassification of diagnosis of pulmonary embolism and deep vein thrombosis in Swedish patient registries. Clinical Epidemiology, 10, 1215-1221
Open this publication in new window or tab >>Positive predictive value and misclassification of diagnosis of pulmonary embolism and deep vein thrombosis in Swedish patient registries
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2018 (English)In: Clinical Epidemiology, ISSN 1179-1349, E-ISSN 1179-1349, Vol. 10, p. 1215-1221Article in journal (Refereed) Published
Abstract [en]

Purpose: To validate diagnoses of pulmonary embolism (PE) and deep vein thrombosis (DVT) in administrative registries. We also estimated the frequency of misclassified PE and DVT events.

Patients and methods: A registry search for ICD codes representing PE and DVT was performed between 1985 and 2014 in a large population-based cohort in northern Sweden. An additional search using an extended set of ICD codes was performed to identify misclassified events. Diagnoses were validated manually by reviewing medical records and radiology reports.

Results: Searching ICD codes in the National Patient Registry and Cause of Death Registry identified 2,450 participants with a first-time diagnosis of PE or DVT. The positive predictive value (PPV) for a diagnosis of PE or DVT was 80.7% and 59.2%, respectively. For the period of 2009 to 2014, the PPV was higher for PE (85.8%) but lower for DVT (54.1%). Misclassification occurred in 16.4% of DVT events and 1.1% of PE events.

Conclusion: Registry-based data on PE, especially in recent years, are of acceptable quality and can be considered for use in registry-based studies. For DVT, we found that data were of low quality in regards to both PPV and misclassification and should not be used without validation.

Place, publisher, year, edition, pages
Dove Medical Press, 2018
Keywords
pulmonary embolism, deep vein thrombosis, positive predictive value, International Classification of diseases, validation
National Category
Cardiac and Cardiovascular Systems
Identifiers
urn:nbn:se:umu:diva-152428 (URN)10.2147/CLEP.S177058 (DOI)000445048000002 ()30271217 (PubMedID)
Funder
Västerbotten County Council
Available from: 2018-10-04 Created: 2018-10-04 Last updated: 2019-08-20Bibliographically approved
Johansson, K., Jansson, J.-H., Johansson, L., Bylesjö, I., Nilsson, T. K., Eliasson, M., . . . Lind, M. (2017). Factor XII as a Risk Marker for Hemorrhagic Stroke: A Prospective Cohort Study. Cerebrovascular diseases extra, 7(1), 84-94
Open this publication in new window or tab >>Factor XII as a Risk Marker for Hemorrhagic Stroke: A Prospective Cohort Study
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2017 (English)In: Cerebrovascular diseases extra, ISSN 1664-5456, Vol. 7, no 1, p. 84-94Article in journal (Refereed) Published
Abstract [en]

BACKGROUND: Coagulation factor XII (FXII) is involved in pathological thrombus formation and is a suggested target of anticoagulants. It is unclear whether FXII levels are correlated with cardiovascular risk factors and whether they are associated with myocardial infarction or ischemic or hemorrhagic stroke. The aim of this study was to investigate the correlation between FXII and cardiovascular risk factors in the general population. We also aimed to study the associations between FXII levels and future myocardial infarction and ischemic and hemorrhagic stroke.

METHODS: This prospective cohort study measured FXII levels in 1,852 randomly selected participants in a health survey performed in northern Sweden in 1994. Participants were followed until myocardial infarction, stroke, death, or until December 31, 2011.

RESULTS: During the median follow-up of 17.9 years, 165 individuals were diagnosed with myocardial infarction, 108 with ischemic stroke, and 30 with hemorrhagic stroke. There were weak correlations between FXII and body mass index, cholesterol, and hypertension. There was no association between FXII and myocardial infarction or ischemic stroke, neither in univariable Cox regression analysis nor after adjustment for age, sex, smoking, body mass index, cholesterol, hypertension, and diabetes. In univariable Cox regression analysis, the hazard ratio for the association between FXII levels and hemorrhagic stroke was 1.42 per SD (95% confidence interval: 0.99-2.05). In the multivariable model, higher levels of FXII were associated with increased risk of hemorrhagic stroke (hazard ratio 1.51 per SD; 95% confidence interval: 1.03-2.21).

CONCLUSION: We found an independent association between FXII levels and the risk of hemorrhagic stroke, but not between FXII levels and ischemic stroke or myocardial infarction.

Place, publisher, year, edition, pages
S. Karger, 2017
Keywords
Coagulation, Biomarkers, Intracranial hemorrhage, Cohort study, Cardiovascular disease
National Category
Cardiac and Cardiovascular Systems
Identifiers
urn:nbn:se:umu:diva-136401 (URN)10.1159/000468994 (DOI)000405098500004 ()28433996 (PubMedID)
Available from: 2017-06-16 Created: 2017-06-16 Last updated: 2019-08-20Bibliographically approved
Lind, M., Jansson, J.-H., Nilsson, T. K. & Johansson, L. (2016). High homocysteine and low folate plasma concentrations are associated with cardiovascular events but not bleeding during warfarin treatment. Clinical Chemistry and Laboratory Medicine, 54(12), 1981-1986
Open this publication in new window or tab >>High homocysteine and low folate plasma concentrations are associated with cardiovascular events but not bleeding during warfarin treatment
2016 (English)In: Clinical Chemistry and Laboratory Medicine, ISSN 1434-6621, E-ISSN 1437-4331, Vol. 54, no 12, p. 1981-1986Article in journal (Refereed) Published
Abstract [en]

Background: Previous studies have shown that homocysteine and folate levels in plasma are associated with risk for cardiovascular events and mortality. The aim of this study was to investigate if plasma concentrations of total homocysteine and folate can predict major bleeding, cardiovascular events, and all-cause mortality in patients being treated with warfarin. Methods: In a longitudinal cohort study, 719 patients who were taking warfarin were followed for 3001 treatment years. The following were recorded and classified: major bleeding; cardiovascular events including stroke, arterial emboli, and myocardial infarction (MI); and mortality. Blood samples collected at baseline were analysed for plasma homocysteine and folate levels. Results: After adjustment for age, C-reactive protein, and creatinine, high homocysteine levels were associated with cardiovascular events [hazard ratio (HR) 1.23 per standard deviation (SD); 95% confidence interval (CI): 1.03-1.47], MI (HR 1.38 per SD; 95% CI: 1.03-1.85), and all-cause mortality (HR 1.41 per SD; 95% CI: 1.19-1.68). The highest tertile of folate compared to the lowest tertile was associated with decreased risk for both cardiovascular events (HR 0.64; 95% CI: 0.43-0.91) and MI (HR 0.45; 95% CI: 0.21-0.97). There was no association between major bleeding and homocysteine or folate levels. Conclusions: In patients receiving warfarin treatment, high homocysteine and low folate plasma concentrations are associated with increased risk for cardiovascular events but not major bleeding. For homocysteine levels, there is also an association with all-cause mortality.

Keywords
cardiovascular events, homocysteine, mortality, warfarin
National Category
Cardiac and Cardiovascular Systems
Identifiers
urn:nbn:se:umu:diva-129796 (URN)10.1515/cclm-2016-0092 (DOI)000387508700028 ()27289003 (PubMedID)
Available from: 2017-01-10 Created: 2017-01-09 Last updated: 2019-08-20Bibliographically approved
Lind, M., Johansson, L., Nilsson, T., Jansson, J.-H. & Hollestelle, M. J. (2015). von Willebrand activation factor as a marker of mortality, cardiovascular events, and bleeding complications in patients treated with oral anticoagulants. Thrombosis Research, 136(5), 878-882
Open this publication in new window or tab >>von Willebrand activation factor as a marker of mortality, cardiovascular events, and bleeding complications in patients treated with oral anticoagulants
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2015 (English)In: Thrombosis Research, ISSN 0049-3848, E-ISSN 1879-2472, Vol. 136, no 5, p. 878-882Article in journal (Refereed) Published
Abstract [en]

Background: Serious bleeding is a frequent and feared treatment complication in patients treated with oral anticoagulants (OACs). Levels of von Willebrand factor (VWF) antigen have been linked to the risk of bleeding complications, mortality, and cardiovascular events. Objectives: In this longitudinal cohort study of evaluating patients treated with OACs, we aimed to evaluate the relationship between VWF displaying a glycoprotein Ib binding conformation (VWF activation factor) and the risk of cardiovascular events, bleeding complications, or all-cause mortality. Materials and methods: Blood samples were collected at baseline in 356 patients on OACs. Patients were followed for an average of 48 months and bleeding complications leading to admission to hospital or death, cardiovascular events (myocardial infarction, ischemic stroke, and peripheral arterial emboli), and all-cause mortality were recorded and classified. Results: During the study period, 47 bleeding complications, 84 cardiovascular events, and 97 deaths occurred. In multivariate Cox regression analyses, VWF activation factor was significantly associated with all-cause mortality (HR 1.62; 95% CI: 1.25-2.08) and cardiovascular events (HR 1.28; 95% CI: 1.01-1.63). There was no association observed between VWF activation factor and bleeding complications. Conclusions: Patients with high levels of VWF activation factor had an increased risk of cardiovascular events and all cause mortality during OAC treatment. The selectivity for thrombotic complications adds to the potential value of VWF activation factor as a biomarker or pharmacological target. (C) 2015 Elsevier Ltd. All rights reserved.

Keywords
Anticoagulants, Hemorrhage, Biological marker, Mortality, VWF
National Category
Public Health, Global Health, Social Medicine and Epidemiology
Identifiers
urn:nbn:se:umu:diva-114033 (URN)10.1016/j.thromres.2015.08.016 (DOI)000366712000009 ()26364970 (PubMedID)
Available from: 2016-01-11 Created: 2016-01-11 Last updated: 2019-08-20Bibliographically approved
Lind, M., Boman, K., Johansson, L., Nilsson, T., Slunga-Järvholm, L. & Jansson, J.-H. (2014). D-dimer predicts major bleeding, cardiovascular events and all-cause mortality during warfarin treatment. Clinical Biochemistry, 47(7-8), 570-573
Open this publication in new window or tab >>D-dimer predicts major bleeding, cardiovascular events and all-cause mortality during warfarin treatment
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2014 (English)In: Clinical Biochemistry, ISSN 0009-9120, E-ISSN 1873-2933, Vol. 47, no 7-8, p. 570-573Article in journal (Refereed) Published
Abstract [en]

Objectives: Previous studies have shown that biomarkers in blood plasma can predict bleeding complications during anticoagulant treatment as well as thromboembolic events and may improve existing risk stratification schemes in patients on or considered for oral anticoagulant treatment. The aim of this study was to investigate if levels of D-dimer, tissue plasminogen activator (tPA) and its complex with plasminogen inhibitor type 1 (tPA/PAI-1 complex) can predict major bleedings, cardiovascular events and all-cause mortality in patients with warfarin treatment.

Design and methods: In a longitudinal cohort study, 719 patients on oral anticoagulant treatment were followed for a total of 3001 treatment years. Major bleeding, stroke, arterial emboli, myocardial infarction and death were recorded and classified. Blood samples collected at baseline were analyzed for D-dimer, tPA, and tPA/PAI-1 complex.

Results: In multivariate Cox regression analysis, high levels of D-dimer were associated with major bleeding (HR 1.27 per SD; 95% CI: 1.01-1.60), cardiovascular events (HR 1.23 per SD; 95% CI: 1.05-1.45) and all-cause mortality (HR 1.25 per SD; 95% CI: 1.06-1.47). Neither tPA nor the tPA/PAI-1 complex was associated with major bleeding, cardiovascular events or all-cause mortality.

Conclusion: We conclude that high levels of D-dimer predict major bleeding, cardiovascular events and all-cause mortality during warfarin treatment. (C) 2014 The Canadian Society of Clinical Chemists. 

Keywords
D-dimer, Bleeding, Warfarin, Mortality, PAI-1, Cardiovascular events
National Category
Cardiac and Cardiovascular Systems
Identifiers
urn:nbn:se:umu:diva-90777 (URN)10.1016/j.clinbiochem.2014.03.003 (DOI)000335905200012 ()24636802 (PubMedID)
Available from: 2014-10-10 Created: 2014-07-01 Last updated: 2019-08-20Bibliographically approved
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ORCID iD: ORCID iD iconorcid.org/0000-0003-4423-4135

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