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  • 1.
    Boman, Kurt
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Davidson, Thomas
    Gustavsson, Mats
    Olofsson, Mona
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Renström, Gun-Britt
    Johansson, Lars
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Telemedicine improves the monitoring process in anticoagulant treatment2012In: Journal of Telemedicine and Telecare, ISSN 1357-633X, E-ISSN 1758-1109, Vol. 18, no 6, p. 312-316Article in journal (Refereed)
    Abstract [en]

    We compared the INR (International Normalized Ratio) monitoring process using a telemedicine device with the conventional approach in which blood samples were sent to the hospital for analysis. We conducted a randomized controlled trial. We enrolled 40 patients on chronic warfarin therapy from two primary healthcare centres (PHCs). Half were monitored using the telemedicine device and half were monitored conventionally. Each patient received three INR measurements. The total processing time was measured from blood sampling until warfarin dosing was performed in the anticoagulant clinic. The median total processing time was significantly shorter with telemedicine than usual care (34 vs. 260 min, P < 0.001). This was mainly because sample transport was avoided using the point-of-care device and automatic data transmission. Telemedicine reduced the total processing time for INR monitoring and has the potential to improve the management of patients undergoing anticoagulant treatment at PHCs.

  • 2.
    Hernestål-Boman, Jenny
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Jansson, Jan-Håkan
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Eliasson, Mats
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Nilsson, Torbjörn K
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Clinical chemistry.
    Johansson, Lars
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine.
    Individual PAI-1 increase over nine years relates differently in men and women to changes in anthropometric, glycaemic, inflammatory and lipid markers.Manuscript (preprint) (Other academic)
    Abstract [en]

    Background: Levels of plasminogen activator inhibitor-1 (PAI-1) is known to correlate to factors related to the metabolic syndrome. We have previously shown that PAI-1 antigen increased by 75% in men and 95% in women over nine years.

    Objective: The aim of this study was to explore relationships between intra-individual changes in PAI-1 and changes in anthropometric measurements, blood pressure, glycaemic, lipid and inflammatory markers, separately for men and women.

    Method: In northern Sweden, 125 men and 116 women were examined first in 1990 and re-examined in 1999 during the morning hours. Changes over time (Δ) were calculated as the value at 1999 minus the value at 1990.

    Results: In men, ΔPAI-1 was significantly correlated to ΔBMI (r =0.33), ΔCRP (r =0.25), Δtriglycerides (r =0.39), Δfasting plasma glucose (r =0.41) and Δ2-hour plasma glucose (r =0.29). In women, ΔPAI-1 was significantly correlated to ΔBMI (r =0.36), Δwaist circumference (r =0.38), Δhip circumference (r =0.27), ΔCRP (r =0.27) and Δtotal cholesterol (r =0.19). The multivariate linear regression analysis showed that ΔPAI-1 was significantly related to Δfasting plasma glucose and ΔCRP in men (R2 for the complete model was 0.31). In women, ΔPAI-1 was significantly related to Δwaist circumference (R2 for the complete model was 0.17).

    Conclusion: We expected that changes in anthropometric, glycaemic, inflammatory and lipid markers would explain a large part of the observed PAI-1 increase. However, the multivariate analysis explained only 20% of the variation in ΔPAI-1 in women and 30% in men. Interestingly, the patterns of components correlating with the changes in PAI-1 differed between sexes.

  • 3.
    Hernestål-Boman, Jenny
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Jansson, Jan-Håkan
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Nilsson, Torbjörn
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Clinical chemistry.
    Eliasson, Mats
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Johansson, Lars
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine.
    Individual changes in fibrinolytic factors, von Willebrand factor, and C-reactive protein over a nine-year period.Manuscript (preprint) (Other academic)
    Abstract [en]

    Background: Intra-individual changes in haemostatic factor concentrations over time are unknown, in the general population.

    Objective: To describe intra-individual longitudinal changes in tissue plasminogen activator (tPA), plasminogen activator inhibitor-1 (PAI-1), tPA/PAI-1 complex, von Willebrand factor (VWF), and C-reactive protein (CRP) over nine years, in different age groups, stratified for sex.

    Methods: The MONICA survey in 1990 examined randomly selected men and women in four age groups (25–64 years) who were re-examined in 1999. A total of 309 individuals donated venous blood samples in Stabilyte tubes for both surveys during the morning hours, after an overnight fast. We analysed tPA activity and antigens of tPA, PAI-1, tPA/PAI-1 complex, VWF, and CRP.

    Results: Over nine years, in both men and women, we found significant intra-individual increases in the antigen levels of tPA, PAI-1, tPA/PAI-1 complex, VWF, and CRP (P < 0.001). PAI-1 antigen levels increased by 75% for men and 95% for women. Compared to men, women had a significantly higher CRP increase (0.92 vs. 0.22 mg/L; P = 0.044). The P for trend for mean Δ1999–1990 across age groups showed a significant linear trend for VWF (P = 0.001 for men; P < 0.001 for women), but not for the other studied variables.

    Conclusions: There were intra-individual longitudinal increases in the antigen levels of tPA, PAI-1, tPA/PAI-1 complex, VWF, and CRP over nine years in both men and women, with PAI-1 showing the highest relative increase. VWF increased significantly across age groups; however, fibrinolytic variables did not.

  • 4.
    Hernestål-Boman, Jenny
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Jansson, Jan-Håkan
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Nilsson, Torbjörn K
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Clinical chemistry.
    Eliasson, Mats
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Johansson, Lars
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Long-term stability of fibrinolytic factors stored at -80 degrees C.2010In: Thrombosis Research, ISSN 0049-3848, E-ISSN 1879-2472, Vol. 125, no 5, p. 451-456Article in journal (Refereed)
    Abstract [en]

    INTRODUCTION: Blood samples in epidemiological studies are often stored for several years and analysed at different occasions. The reagent kits are continually modified for better precision and accuracy. Our hypothesis was that epidemiological studies are affected by long-term storage and/or modifications of reagent kits.

    MATERIALS AND METHODS: Plasma samples stored at -80( degrees )C from two populations were used: A case-referent study with samples collected from 1985 to 2000 and analysed 2005 (n=1598) were used to study influence of long-term storage. A cross-sectional study analysed 1990 (n=1558) and re-analysed 2001 (n=78) and 2005 (n=828) was used to study influence of reagent kit modifications. Fibrinolytic analyses included immunoassays of tPA, PAI-1 and tPA-PAI-1 complex and chromogenic substrate assays of the activities of tPA and PAI-1.

    RESULTS: Long-term storage for a median time of 11.6years (range 5 to 20) showed an effect of time on tPA antigen R(2)=0.01, PAI-1 antigen R(2)=0.01 and tPA-PAI-1 complex R(2) = 0.02. Modifications in reagent kits affected the levels of fibrinolytic factors; for tPA antigen the slope coefficients were between 0.72 and 0.95 (R(2) 0.47 - 0.75), whereas tPA activity showed an agreement with slope coefficients 1.06 to 1.09 (R(2) 0.67 - 0.93).

    CONCLUSIONS: This study showed that long-term storage affects fibrinolytic variables to a negligible extent, but modifications in reagent kits introduced an element of bias. We conclude that analysis of samples on a single occasion is preferable to multiple occasions, as storage has negligible effect.

  • 5.
    Hernestål-Boman, Jenny
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Norberg, Margareta
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Epidemiology and Global Health.
    Jansson, Jan-Håkan
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Eliasson, Mats
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine. Department of Medicine, Sunderby Hospital, Luleå, Sweden.
    Eriksson, Jan W
    Department of Molecular and Clinical Medicine, Sahlgrenska University Hospital, Gothenburg and AstraZeneca R&D, Mölndal, Sweden.
    Lindahl, Bernt
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Occupational and Environmental Medicine.
    Johansson, Lars
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Signs of dysregulated fibrinolysis precede the development of type 2 diabetes mellitus in a population-based study2012In: Cardiovascular Diabetology, ISSN 1475-2840, E-ISSN 1475-2840, Vol. 11, p. 152-Article in journal (Refereed)
    Abstract [en]

    Background: Diabetic patients experience stimulated coagulation and dysfibrinolysis, which is associated with an increased risk of cardiovascular events. This imbalance may precede the manifest diagnosis. We investigated whether elevated antigen levels of tissue plasminogen activator (tPA), plasminogen activator inhibitor-1 (PAI-1), the tPA/PAI-1 complex, or von Willebrand Factor (VWF) precede type 2 diabetes mellitus (T2DM) diagnosis, and whether this elevation occurs before increased fasting plasma glucose (FPG) or 2-hour plasma glucose (2hPG) in individuals who later develop T2DM.

    Methods: We conducted a prospective incident case-referent study within the Vasterbotten Intervention Programme. Cardiovascular risk factor data as well as FPG and 2hPG and blood samples for future research were collected at a baseline health examination between 1989 and 2000, (n= 28 736). During follow-up in January 2001, 157 cases had developed T2DM. Referents without T2DM were matched for sex, age, and year of participation (n=277). Subgroup analysis was performed for cases with normal baseline glucose levels (FPG <6.1 mmol/L and 2hPG < 8.9 mmol/L) and cases with elevated levels (FPG 6.1-6.9 mmol/L and/or 2hPG 8.9-12.1 mmol/L).

    Results: After adjusting for BMI, family history of diabetes, physical activity, smoking, systolic blood pressure and levels of C-reactive protein and triglycerides, independent associations were found between incident T2DM and elevated levels of tPA (OR=1.54, 95% CI 1.06-2.23), PAI-1 (OR=1.61, 95% CI 1.14-2.28), and tPA/PAI-1 complex (OR=2.45, 95% CI 1.56-3.84). In participants with normal glucose levels, PAI-1 (OR=2.06, 95% CI 1.10 - 3.86) exhibited an independent relationship with incident T2DM after the adjustments.

    Conclusions: Elevated levels of fibrinolytic variables precede the manifestation of T2DM after adjusting for metabolic and cardiovascular risk factors and can be detected several years before changes in glucose tolerance.

  • 6.
    Johansson, Cecilia
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Hägg, Lovisa
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Johansson, Lars
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Jansson, Jan-Håkan
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Characterization of patients with atrial fibrillation not treated with oral anticoagulants2014In: Scandinavian Journal of Primary Health Care, ISSN 0281-3432, E-ISSN 1502-7724, Vol. 32, no 4, p. 226-231Article in journal (Refereed)
    Abstract [en]

    Objective: An underuse of oral anticoagulants (OAC) in patients with atrial fibrillation (AF) has been suggested, as only 50% of all patients with AF receive OAC treatment. Whether this is due to contraindications, lack of an indication to treat, or an expression of underuse is sparsely investigated. This study therefore aimed to characterize individuals without OAC treatment in a real-life population of patients with AF. Design: Retrospective cross-sectional study. The medical records were scrutinized in order to identify the type of AF, risk factors for embolism and bleeding, and other factors of importance for OAC treatment. Setting: The municipalities of Skellefteå and Norsjö, northern Sweden. Subjects: A total of 2274 living residents with at least one verified episode of AF on or before December 31, 2010. Main outcome measures: Prevalence of treatment with OAC and documented reasons to withhold OAC treatment. Results: Among all 2274 patients with AF, 1187 (52%) were not treated with OAC. Of the untreated patients, 19% had no indication or had declined or had experienced adverse effects other than bleeding on warfarin treatment. The most common reason to withhold OAC was presence of risk factors for bleeding, found in 38% of all untreated patients. Furthermore, a documented reason could be identified to withhold OAC in 75%. Conclusions: Among patients with AF without OAC treatment a reason could be identifi ed to withhold OAC in 75%. The underuse of OAC is estimated to be 25%.

  • 7.
    Johansson, Kristina
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Jansson, Jan-Håkan
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Johansson, Lars
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Bylesjö, Ingemar
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Family Medicine.
    Nilsson, Torbjörn K
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Clinical chemistry.
    Eliasson, Mats
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Söderberg, Stefan
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Lind, Marcus
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Section of Medicine.
    Factor XII as a Risk Marker for Hemorrhagic Stroke: A Prospective Cohort Study2017In: Cerebrovascular diseases extra, ISSN 1664-5456, Vol. 7, no 1, p. 84-94Article in journal (Refereed)
    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.

  • 8.
    Johansson, Kristina
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Section of Medicine.
    Jansson, Jan-Håkan
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Section of Medicine.
    Johansson, Lars
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Section of Medicine.
    Wiklund, Per-Gunnar
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Section of Medicine.
    Nilsson, Torbjörn K.
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Clinical chemistry.
    Lind, Marcus
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    D-Dimer is associated with first-ever intracerebral hemorrhage: a nested case-control study2018In: Stroke, ISSN 0039-2499, E-ISSN 1524-4628, Vol. 49, no 9, p. 2034-2039Article in journal (Refereed)
    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.

  • 9.
    Johansson, Lars
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Jansson, Jan-Håkan
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Stegmayr, Birgitta
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Nilsson, Torbjörn K
    Hallmans, Göran
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research.
    Boman, Kurt
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Hemostatic factors as risk markers for intracerebral hemorrhage: a prospective incident case-referent study.2004In: Stroke, ISSN 1524-4628, Vol. 35, no 4, p. 826-30Article in journal (Refereed)
  • 10.
    Johansson, Magdalena
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Johansson, Lars
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Lind, Marcus
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Incidence of venous thromboembolism in northern Sweden (VEINS): a population-based study2014In: Thrombosis Journal, ISSN 1477-9560, E-ISSN 1477-9560, Vol. 12, article id 6Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: The reported incidence of venous thromboembolism (VTE) varies considerably among studies. The primary aim of this study was to describe the incidence of VTE in relation to age and sex. The secondary aim was to describe the risk factor pattern at the time of diagnosis.

    METHODS: This retrospective, population-based cohort study included all adult residents in the County of Västerbotten in northern Sweden during the year 2006 (n = 204,836). All potential VTE events were manually validated and classified according to location. The presence of risk factors for VTE at the time of diagnosis was recorded.

    RESULTS: We identified 517 adult individuals with potential VTE. Among these, 343 individuals (158 men and 185 women) had a verified VTE event in 2006. The mean incidence was 167 individuals per 100,000 person years; 155 for men and 180 for women. The mean age at diagnosis was 67.6 years in men and 72.5 years in women. The incidence of VTE increased with age. The incidence was highest in women aged 85 years or more. Pulmonary embolism with or without concurrent deep vein thrombosis was diagnosed in 161 individuals (46.9%); lower extremity deep vein thrombosis without concurrent pulmonary embolism was diagnosed in 157 individuals (45.8%); and VTE in another location was diagnosed in 25 individuals (7.3%). The most common risk factors for VTE were recent hospitalization and concurrent malignancy.

    CONCLUSION: The incidence of VTE was 167 per 100,000 person years and increased with age. The incidence was highest among older women. Pulmonary embolism was the most common form of VTE; it affected 47% of individuals with VTE. Malignancy and hospitalization were the most prevalent risk factors for VTE.

  • 11.
    Johansson, Magdalena
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine.
    Johansson, Lars
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine.
    Wennberg, Maria
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research.
    Lind, Marcus
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine.
    Alcohol Consumption and Risk of First-Time Venous Thromboembolism in Men and Women2019In: Thrombosis and Haemostasis, ISSN 0340-6245, Vol. 119, no 6, p. 962-970Article in journal (Refereed)
    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.

  • 12.
    Johansson, Magdalena
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine. Skellefteå Research Unit.
    Johansson, Lars
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine. Skellefteå Research Unit.
    Wennberg, Patrik
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Family Medicine.
    Lind, Marcus
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine. Skellefteå Research Unit.
    Physical activity and risk of first-time venous thromboembolism2019In: European Journal of Preventive Cardiology, ISSN 2047-4873, E-ISSN 2047-4881, Vol. 26, no 11, p. 1181-1187Article in journal (Refereed)
    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.

  • 13.
    Lind, Marcus
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Boman, Kurt
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Johansson, Lars
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Nilsson, Torbjörn K
    Ohlin, Ann-Kristin
    Birgander, Lisbeth Slunga
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Occupational and Environmental Medicine.
    Jansson, Jan-Håkan
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Thrombomodulin as a marker for bleeding complications during warfarin treatment.2009In: Archives of Internal Medicine, ISSN 0003-9926, E-ISSN 1538-3679, Vol. 169, no 13, p. 1210-1215Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: The major adverse effect of warfarin treatment is hemorrhage. Several risk factors for bleeding complications are also risk factors for thromboembolic events, making the clinical decision to initiate or withhold anticoagulant treatment difficult. Specific markers that solely identify patients at high risk of bleeding would have great clinical impact. This study aimed to test if thrombomodulin (TM) concentrations were associated with bleeding complications, cardiovascular events, or mortality in long-term anticoagulant-treated patients. METHODS: In a longitudinal cohort study we followed up 719 patients receiving warfarin treatment for a mean duration of 4.2 years. All bleeding complications causing hospitalization were registered and classified. Soluble TM antigen (sTM) concentration in plasma was measured with an enzyme-linked immunosorbent assay method. RESULTS: During the follow-up time, 113 clinically relevant bleeding events and 73 major bleeding events occurred. Increased concentration of sTM was associated with both clinically relevant bleeding and major bleeding events after adjustment for age. In the multivariable models, hazard ratios for the highest tertiles compared with the lowest were 2.29 (95% confidence interval, 1.35-3.89) and 2.33 (95% confidence interval, 1.21-4.48), respectively. No association between sTM concentration and nonfatal ischemic cardiovascular events or all-cause mortality was found. CONCLUSIONS: Increased levels of sTM are associated with bleeding complications during warfarin treatment but not with cardiovascular events or all-cause mortality. Soluble TM antigen concentration has potential as a new specific marker to identify patients at high risk of bleeding during warfarin treatment.

  • 14.
    Lind, Marcus
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Boman, Kurt
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Johansson, Lars
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Nilsson, Torbjörn K
    Slunga-Järvholm, Lisbeth
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Occupational and Environmental Medicine.
    Jansson, Jan-Håkan
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Von Willebrand factor predicts major bleeding and mortality during oral anticoagulant treatment2012In: Journal of Internal Medicine, ISSN 0954-6820, E-ISSN 1365-2796, Vol. 271, no 3, p. 239-246Article in journal (Refereed)
    Abstract [en]

    Aims.  Oral anticoagulation (OAC), predominantly with warfarin, is an effective treatment to prevent thromboembolic events. Serious bleeding is a frequent and feared treatment complication. In this longitudinal cohort study of OAC-treated patients, we aimed to evaluate the relationship between von Willebrand factor (VWF) levels and risk of bleeding complications, cardiovascular mortality and all-cause mortality.

    Methods and results.  A total of 719 patients receiving warfarin treatment were observed for a mean duration of 4.2 years. All bleeding complications causing hospitalization were registered and classified into clinically relevant bleeding (CRB) and major bleeding. Ischaemic stroke, peripheral arterial embolism, myocardial infarction, and death were also recorded. We identified 113 cases of CRB and 73 of major bleeding. In total, 161 deaths occurred during follow-up with cardiovascular disease identified as the cause of death in 110 patients. Patients in the highest tertile of VWF had a significantly increased risk of bleeding complications: hazard ratio (HR) 2.53 (95% CI 1.41-4.56) for major bleeding and HR 2.19 (95% CI 1.38-3.48) for CRB. VWF, expressed either in tertiles or as a continuous variable, showed a significant association with cardiovascular mortality (HR 1.68, 95% CI 1.40-2.01) and all-cause mortality (HR 1.77, 95% CI 1.52-2.05). In multivariate Cox regression analysis, the findings remained significant after adjusting for age, high-sensitivity C-reactive protein and creatinine.

    Conclusions.  Patients with high levels of VWF had an increased risk of bleeding complications, cardiovascular mortality and all-cause mortality during OAC treatment. Our findings imply that the use of VWF as a risk marker for thromboembolic events is complicated by the association of VWF with bleeding complications.

  • 15.
    Lind, Marcus
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Jansson, Jan-Håkan
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Nilsson, Torbjörn K.
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Clinical chemistry.
    Järvholm, Lisbeth Slunga
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Occupational and Environmental Medicine.
    Johansson, Lars
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Cystatin C and creatinine as markers of bleeding complications, cardiovascular events and mortality during oral anticoagulant treatment2013In: Thrombosis Research, ISSN 0049-3848, E-ISSN 1879-2472, Vol. 132, no 2, p. E77-E82Article in journal (Refereed)
    Abstract [en]

    Introduction: Impaired kidney function has been linked to both ischemic events as well as bleeding complications in several clinical conditions. Our aim was to investigate if cystatin C, creatinine and calculated glomerular filtration rate (eGFR) were related to future risk of bleeding complications, cardiovascular events or all-cause mortality during oral anticoagulant treatment.

    Materials and methods: In a cohort study, 719 patients on long-term vitamin K antagonist (VKA) treatment were followed for a mean of 4.2 years. Blood sampling was taken at inclusion and patients were followed prospectively. Cystatin C and creatinine were analysed and eGFR was calculated. All medical records were reviewed. Major bleeding events, myocardial infarctions, strokes, arterial emboli, and deaths were recorded and classified.

    Results: After adjustment for age, no association between cystatin C, creatinine or eGFR and major bleeding was found. Cystatin C was independently associated with cardiovascular events (hazard ratio 1.50 (95% CI: 1.27-1.77)) and all-cause mortality (hazard ratio 1.62 (95% CI: 1.38-1.90)). Creatinine was only associated with all-cause mortality, while eGFR was not associated with any of the outcomes.

    Conclusions: Our findings underscore the superiority of cystatin C as a marker of cardiovascular risk compared to creatinine or eGFR. VKA-treated patients with increased cystatin C levels should be considered to be at an increased risk of cardiovascular events, and not bleeding complications.

  • 16.
    Norberg, Johannes
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine.
    Bäckström, Svante
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine.
    Jansson, Jan-Håkan
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Johansson, Lars
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Estimating the prevalence of atrial fibrillation in a general population using validated electronic health data2013In: Clinical Epidemiology, ISSN 1179-1349, E-ISSN 1179-1349, Vol. 5, no 1, p. 475-481Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: The purpose of this study was to determine the prevalence of atrial fibrillation (AF) in the general population and to validate an administrative diagnosis register, ie, the National Patient Register (NPR), and an electrocardiography (ECG) database in estimating disease prevalence.

    METHODS: The study was conducted in a well defined region in northern Sweden (population n=75,945) which consists of one hospital and eleven primary health care centers. Subjects with AF were identified by searching the combined inpatient and outpatient International Classification of Diseases (ICD)-based NPR (ICD-10 code I48) and an ECG database with computer-interpreted AF from January 1, 2004 to December 31, 2010. All identified cases with AF were validated.

    RESULTS: AF was confirmed in 2,274 patients. The overall prevalence was 3.0% (3.4% in men and 2.6% in women). AF prevalence rose steadily with age, and was 16.8% in patients aged 75 years and older and 21.9% in patients 85 years and older. Of all patients with validated AF, the NPR identified 93.2%. The ECG database identified an additional 6.8%, of which 81% were over 70 years of age. According to the NPR, the proportion of false positives and false negatives was 3.5% and 6.8%, respectively. The corresponding figure for the ECG database was 11.3% and 9.2%, respectively.

    CONCLUSION: Our study shows a high prevalence of AF, especially among the elderly. Searching the ECG database enhanced the detection of AF. The reliability of the NPR was high, with a relatively low proportion of false positives and negatives.

  • 17.
    Wennberg, Patrik
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Family Medicine.
    Eliasson, Mats
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Hallmans, Göran
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research.
    Johansson, Lars
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Boman, Kurt
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Jansson, Jan-Håkan
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine. Medicin.
    The risk of myocardial infarction and sudden cardiac death amongst snuff users with or without a previous history of smoking.2007In: Journal of Internal Medicine, ISSN 0954-6820, E-ISSN 1365-2796, Vol. 262, no 3, p. 360-7Article in journal (Refereed)
    Abstract [en]

    OBJECTIVES: To investigate the risk of a first myocardial infarction (MI) and sudden cardiac death (SCD) amongst male snuff users. DESIGN: We used a prospective incident case-referent study design nested in the population-based Västerbotten Intervention Program and the Northern Sweden MONICA study. SUBJECTS: Tobacco habits and cardiovascular risk factors were assessed at baseline screening and compared in 525 male MI cases (including 93 SCD cases) and 1798 matched referents. RESULTS: Myocardial infarction occurred on average 4 years and 2 months after the baseline screening. No increased risk for MI was found amongst snuff users without a previous history of smoking compared with nontobacco users after adjustments for body mass index, leisure time physical activity, educational level and cholesterol level (OR 0.82; 95% CI, 0.46-1.43). For snuff users with a previous history of smoking, the adjusted OR was 1.25 (95% CI, 0.80-1.96). Significantly increased risk for MI was found in current smokers with or without current snuff use. For SCD cases with survival time<24 h, the adjusted OR for snuff users without previous history of smoking was 1.18 (95% CI, 0.38-3.70) and for cases with survival time<1 h the OR was 0.38 (95% CI, 0.08-1.89). CONCLUSIONS: We found no increased risk for MI amongst snuff users without a previous history of smoking. Amongst snuff users with a previous history of smoking, the tendency towards an increased risk for MI may reflect the residual risk from former smoking. This study does not support the hypothesis that the risk for SCD is increased amongst snuff users.

  • 18.
    Wennberg, Patrik
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Family Medicine.
    Wensley, Frances
    Di Angelantonio, Emanuele
    Johansson, Lars A
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Boman, Kurt
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Rumley, Ann
    Lowe, Gordon
    Hallmans, Göran
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research.
    Danesh, John
    Jansson, Jan-Håkan
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Haemostatic and inflammatory markers are independently associated with myocardial infarction in men and women2012In: Thrombosis Research, ISSN 0049-3848, E-ISSN 1879-2472, Vol. 129, no 1, p. 68-73Article in journal (Refereed)
    Abstract [en]

    INTRODUCTION: Previous studies have shown that plasma levels of haemostatic and inflammatory markers are associated with risk of coronary heart disease (CHD). As haemostatic markers are also acute-phase reactants, it is not clear if their association with CHD is independent of inflammatory markers and established cardiovascular risk factors.

    MATERIALS AND METHODS: We used a prospective incident case-control study design nested in two cohorts from Sweden. Baseline measurements of a panel of cardiovascular risk factors and eight established markers of haemostasis or inflammation were assessed in 469 first-ever myocardial infarction (MI) cases and 895 matched controls.

    RESULTS: After adjustment for baseline values of established risk factors, von Willebrand factor appeared to have the strongest association with MI among the haemostatic markers assayed, with an odds ratio of 2.52 (95% CI, 1.72-3.67) for a comparison of individuals in extreme thirds of baseline levels. For a similar comparison, after adjustment for established risk factors and haemostatic markers, odds ratios for IL-6 and CRP were 1.67 (95% CI, 1.08-2.60) and 1.58 (95% CI, 1.03-2.41), respectively. The relative predictive ability of the individual markers over and above established risk factors was modest according to comparisons of Area under the Receiver Operating Characteristic (AUROC) curves. However, when all eight markers were combined in a single model, the AUROC curve was significantly increased to 0.820 (95% CI, 0.795-0.846) compared to 0.762 (95% CI, 0.732-0.791) for established risk factors only.

    CONCLUSIONS: These findings suggest that haemostasis and inflammation have at least partially separate roles in risk of myocardial infarction.

  • 19.
    Wennberg, Patrik
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Family Medicine.
    Wensley, Frances
    Di Angeloantonio, Emanuele
    Johansson, Lars
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Boman, Kurt
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Rumley, Ann
    Lowe, Gordon
    Hallmans, Göran
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research.
    Danesh, John
    Jansson, Jan-Håkan
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Haemostatic and inflammatory markers are independently associated with a first-ever myocardial infarction in men and women2012In: Thrombosis Research, ISSN 0049-3848, E-ISSN 1879-2472, Vol. 129, no 1, p. 68-73Article in journal (Refereed)
    Abstract [en]

    Introduction: Previous studies have shown that plasma levels of haemostatic and inflammatory markers are associated with risk of coronary heart disease (CHD). As haemostatic markers are also acute-phase reactants, it is not clear if their association with CHD is independent of inflammatory markers and established cardiovascular risk factors.

    Materials and Methods: We used a prospective incident case-control study design nested in two cohorts from Sweden. Baseline measurements of a panel of cardiovascular risk factors and eight established markers of haemostasis or inflammation were assessed in 469 first-ever myocardial infarction (MI) cases and 895 matched controls.

    Results: After adjustment for baseline values of established risk factors, von Willebrand factor appeared to have the strongest association with MI among the haemostatic markers assayed, with an odds ratio of 2.52 (95% CI, 1.72-3.67) for a comparison of individuals in extreme thirds of baseline levels. For a similar comparison, after adjustment for established risk factors and haemostatic markers, odds ratios for IL-6 and CRP were 1.67 (95% CI, 1.08-2.60) and 1.58 (95% CI, 1.03-2.41), respectively. The relative predictive ability of the individual markers over and above established risk factors was modest according to comparisons of Area under the Receiver Operating Characteristic (AUROC) curves. However, when all eight markers were combined in a single model, the AUROC curve was significantly increased to 0.820 (95% CI, 0.795-0.846) compared to 0.762 (95% CI, 0.732-0.791) for established risk factors only.

    Conclusions: These findings suggest that haemostasis and inflammation have at least partially separate roles in risk of myocardial infarction.

  • 20.
    Wennberg, Patrik
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Family Medicine.
    Wensley, Frances
    Johansson, Lars
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Boman, Kurt
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Di Angeloantonio, Emanuele
    Rumley, Ann
    Lowe, Gordon
    Hallmans, Göran
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research.
    Jansson, Jan-Håkan
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Reduced risk of myocardial infarction related to active commuting: inflammatory and haemostatic effects are potential major mediating mechanisms2010In: European Journal of Cardiovascular Prevention & Rehabilitation, ISSN 1741-8267, E-ISSN 1741-8275, Vol. 17, no 1, p. 56-62Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Regular physical activity is inversely associated with risk of coronary heart disease, but the precise mechanisms remain unclear. Active commuting is an environmental friendly way to achieve the recommended 30 min of daily physical activity. The aim of this study was to explore the relative contribution of markers from different potential mediating pathways on the association between active commuting and risk of myocardial infarction (MI) in a general population. DESIGN: Prospective incident nested case-control study. METHODS: Commuting habits, traditional risk factors and biomarkers were assessed at baseline and compared in 204 MI cases and 327 matched controls. RESULTS: Car commuting was significantly associated with MI risk, even after adjusting for potential confounders (odds ratio: 1.77, 95% confidence interval: 1.05-2.99). When potential mediators were included in the model, the risk was substantially attenuated. Among the traditional risk factors, apolipoprotein B/apolipoprotein A-1 ratio seemed to be the largest mediator (26.0%), followed by body mass index (18.7%). The inflammatory and haemostatic markers similarly dampened the effect, with tissue plasminogen activator/plasminogen activator inhibitor-1 complex and IL-6 explaining 33.6 and 27.6% of MI risk, respectively. Combined, the potential mediators investigated seemed to explain 40.1% of MI risk related to car commuting. CONCLUSION: Overall, the traditional, inflammatory and haemostatic markers seemed to explain a substantial proportion of the reduction in MI risk related to active commuting in this study population. The predominant effect of the inflammatory and haemostatic markers supports the hypothesis that regular physical activity may work through additional biological mechanisms to reduce coronary risk beyond traditional risk factors. However, these findings need to be confirmed in larger studies.

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