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  • 151. Bang, Casper N.
    et al.
    Gerdts, Eva
    Aurigemma, Gerard P.
    Boman, Kurt
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Dahlof, Bjoern
    Roman, Mary J.
    Kober, Lars
    Wachtell, Kristian
    Devereux, Richard B.
    Systolic left ventricular function according to left ventricular concentricity and dilatation in hypertensive patients: the Losartan Intervention For Endpoint reduction in hypertension study2013In: Journal of Hypertension, ISSN 0263-6352, E-ISSN 1473-5598, Vol. 31, no 10, p. 2060-2068Article in journal (Refereed)
    Abstract [en]

    Background:Left ventricular hypertrophy [LVH, high left ventricular mass (LVM)] is traditionally classified as concentric or eccentric based on left ventricular relative wall thickness. We evaluated left ventricular systolic function in a new four-group LVH classification based on left ventricular dilatation [high left ventricular end-diastolic volume (EDV) index and concentricity (LVM/EDV(2/3))] in hypertensive patients.Methods and results:Nine hundred thirty-nine participants in the Losartan Intervention For Endpoint reduction in hypertension (LIFE) echocardiography substudy had measurable LVM at enrolment. Patients with LVH (LVM/body surface area 116g/m(2) in men and 96g/m(2) in women) were divided into four groups; eccentric nondilated' (normal LVM/EDV and EDV), eccentric dilated' (increased EDV, normal LVM/EDV), concentric nondilated' (increased LVM/EDV with normal EDV), and concentric dilated' (increased LVM/EDV and EDV) and compared to patients with normal LVM. At baseline, 12% had eccentric nondilated, 20% eccentric dilated, 29% concentric nondilated, and 14% concentric dilated LVH, with normal LVM in 25%. Compared with the concentric nondilated LVH group, those with concentric dilated LVH had significantly lower pulse pressure/stroke index and ejection fraction; higher LVM index, stroke volume, cardiac output, left ventricular midwall shortening, left atrial volume and isovolumic relaxation time; and more had segmental wall motion abnormalities (all P<0.05). Similar differences existed between patients with eccentric dilated and those with eccentric nondilated LVH (all P<0.05). Compared with patients with normal LVM, the eccentric nondilated had higher LV stroke volume, pulse pressure/stroke index, Cornell voltage product and SBP, and lower heart rate and fewer were African-American (all P<0.05).Conclusion:The new four-group classification of LVH identifies dilated subgroups with reduced left ventricular function among patients currently classified with eccentric or concentric LVH.

  • 152. Bang, Casper N.
    et al.
    Gerdts, Eva
    Aurigemma, Gerard P.
    Boman, Kurt
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    de Simone, Giovanni
    Dahlof, Bjorn
    Kober, Lars
    Wachtell, Kristian
    Devereux, Richard B.
    Four-Group Classification of Left Ventricular Hypertrophy Based on Ventricular Concentricity and Dilatation Identifies a Low-Risk Subset of Eccentric Hypertrophy in Hypertensive Patients2014In: Circulation Cardiovascular Imaging, ISSN 1941-9651, E-ISSN 1942-0080, Vol. 7, no 3, p. 422-429Article in journal (Refereed)
    Abstract [en]

    Background-Left ventricular hypertrophy (LVH; high LV mass [LVM]) is traditionally classified as concentric or eccentric based on LV relative wall thickness. We evaluated the prediction of subsequent adverse events in a new 4-group LVH classification based on LV dilatation (high LV end-diastolic volume [EDV] index) and concentricity (mass/end-diastolic volume [M/EDV](2/3)) in hypertensive patients. Methods and Results-In the Losartan Intervention for Endpoint Reduction (LIFE) echocardiography substudy, 939 hypertensive patients with measurable LVM at baseline were randomized to a mean of 4.8 years of losartan- or atenolol-based treatment. Patients with LVH (LVM/body surface area >= 116 and >= 96 g/m(2) in men and woman, respectively) were divided into 4 groups-concentric nondilated (increased M/EDV, normal EDV), eccentric dilated (increased EDV, normal M/EDV), concentric dilated (increased M/EDV and EDV), and eccentric nondilated (normal M/EDV and EDV)-and compared with patients with normal LVM. Time-varying LVH classes were tested for association with all-cause and cardiovascular mortality and a composite end point of myocardial infarction, stroke, heart failure, and cardiovascular death in multivariable Cox analyses. At baseline, the LVs were categorized as eccentric nondilated in 12%, eccentric dilated in 20%, concentric nondilated in 29%, concentric dilated in 14%, and normal LVM in 25%. Treatment changed the prevalence of 4 LVH groups to 23%, 4%, 5%, and 7%; 62% had normal LVM after 4 years. In time-varying Cox analyses, compared with normal LVM, those with eccentric dilated and both concentric nondilated and dilated LVH had increased risks of all-cause or cardiovascular mortality or the composite end point, whereas the eccentric nondilated group did not. Conclusions-Hypertensive patients with relatively mild LVH without either increased LV volume or concentricity have similar risk of all-cause mortality or cardiovascular events because hypertensive patients with normal LVM seem to be a low-risk group.

  • 153. Bang, Casper N.
    et al.
    Greve, Anders M.
    Boman, Kurt
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Egstrup, Kenneth
    Gohlke-Baerwolf, Christa
    Kober, Lars
    Nienaber, Christoph A.
    Ray, Simon
    Rossebo, Anne B.
    Wachtell, Kristian
    Effect of lipid lowering on new-onset atrial fibrillation in patients with asymptomatic aortic stenosis: The Simvastatin and Ezetimibe in Aortic Stenosis (SEAS) study2012In: American Heart Journal, ISSN 0002-8703, E-ISSN 1097-6744, Vol. 163, no 4, p. 690-696Article in journal (Refereed)
    Abstract [en]

    Background Lipid-lowering drugs, particularly statins, have anti-inflammatory and antioxidant properties that may prevent atrial fibrillation (AF). This effect has not been investigated on new-onset AF in asymptomatic patients with aortic stenosis (AS). Methods Asymptomatic patients with mild-to-moderate AS (n = 1,421) were randomized (1: 1) to double-blind simvastatin 40 mg and ezetimibe 10 mg combination or placebo and followed up for a mean of 4.3 years. The primary end point was the time to new-onset AF adjudicated by 12-lead electrocardiogram at a core laboratory reading center. Secondary outcomes were the correlates of new-onset AF with nonfatal nonhemorrhagic stroke and a combined end point of AS-related events. Results During the course of the study, new-onset AF was detected in 85 (6%) patients (14.2/1,000 person-years of follow-up). At baseline, patients who developed AF were, compared with those remaining in sinus rhythm, older and had a higher left ventricular mass index a smaller aortic valve area index. Treatment with simvastatin and ezetimibe was not associated with less new-onset AF (odds ratio 0.89 [95% CI 0.57-1.97], P = .717). In contrast, age (hazard ratio [HR] 1.07 [95% CI 1.05-1.10], P < .001) and left ventricular mass index (HR 1.01 [95% CI 1.01-1.02], P < .001) were independent predictors of new-onset AF. The occurrence of new-onset AF was independently associated with 2-fold higher risk of AS-related outcomes (HR 1.65 [95% CI 1.02-2.66], P = .04) and 4-fold higher risk of nonfatal nonhemorrhagic stroke (HR 4.04 [95% CI 1.18-13.82], P = .03). Conclusions Simvastatin and ezetimibe were not associated with less new-onset AF. Older age and greater left ventricular mass index were independent predictors of AF development. New-onset AF was associated with a worsening of prognosis. (Am Heart J 2012;163:690-6.)

  • 154. Bang, Casper N.
    et al.
    Greve, Anders M.
    Kober, Lars
    Rossebo, Anne B.
    Ray, Simon
    Boman, Kurt
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Nienaber, Christoph A.
    Devereux, Richard B.
    Wachtell, Kristian
    Renin-angiotensin system inhibition is not associated with increased sudden cardiac death, cardiovascular mortality or all-cause mortality in patients with aortic stenosis2014In: International Journal of Cardiology, ISSN 0167-5273, E-ISSN 1874-1754, Vol. 175, no 3, p. 492-498Article in journal (Refereed)
    Abstract [en]

    Background: Renin-angiotensin system inhibition (RASI) is frequently avoided in aortic stenosis (AS) patients because of fear of hypotension. We evaluated if RASI with angiotensin-converting enzyme inhibitor (ACEI) or angiotensin receptor blocker (ARB) increased mortality in patients with mild to moderate AS. Methods: All patients (n = 1873) from the Simvastatin and Ezetimibe in Aortic Stenosis study: asymptomatic patients with AS and preserved left ventricular (LV) ejection fraction were included. Risks of sudden cardiac death (SCD), cardiovascular death and all-cause mortality according to RASI treatment were analyzed by multivariable time-varying Cox models and propensity score matched analyses. Results: 769 (41%) patients received RASI. During a median follow-up of 4.3 +/- 0.9 years, 678 patients were categorized as having severe AS, 545 underwent aortic valve replacement, 40 SCDs, 103 cardiovascular and 205 all-cause deaths occurred. RASI was not associated with SCD (HR: 1.19 [95% CI: 0.50-2.83], p = 0.694), cardiovascular (HR: 1.05 [95% CI: 0.62-1.77], p = 0.854) or all-cause mortality (HR: 0.81 [95% CI: 0.55-1.20], p = 0.281). This was confirmed in propensity matched analysis (all p > 0.05). In separate analyses, RASI was associated with larger reduction in systolic blood pressure (p = 0.001) and less progression of LV mass (p = 0.040). Conclusions: RASI was not associated with SCD, cardiovascular or all-cause mortality in asymptomatic AS patients. However, RASI was associated with a potentially beneficial decrease in blood pressure and reduced LV mass progression. (C) 2014 Elsevier Ireland Ltd. All rights reserved.

  • 155. Bang, Casper N
    et al.
    Greve, Anders M
    La Cour, Morten
    Boman, Kurt
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Gohlke-Bärwolf, Christa
    Ray, Simon
    Pedersen, Terje
    Rossebø, Anne
    Okin, Peter M
    Devereux, Richard B
    Wachtell, Kristian
    Effect of Randomized Lipid Lowering With Simvastatin and Ezetimibe on Cataract Development (from the Simvastatin and Ezetimibe in Aortic Stenosis Study)2015In: American Journal of Cardiology, ISSN 0002-9149, E-ISSN 1879-1913, Vol. 116, no 12, p. 1840-1844Article in journal (Refereed)
    Abstract [en]

    Recent American College of Cardiology/American Heart Association guidelines on statin initiation on the basis of total atherosclerotic cardiovascular disease risk argue that the preventive effect of statins on cardiovascular events outweigh the side effects, although this is controversial. Studies indicate a possible effect of statin therapy on reducing risk of lens opacities. However, the results are conflicting. The Simvastatin and Ezetimibe in Aortic Stenosis study (NCT00092677) enrolled 1,873 patients with asymptomatic aortic stenosis and no history of diabetes, coronary heart disease, or other serious co-morbidities were randomized (1:1) to double-blind 40 mg simvastatin plus 10 mg ezetimibe versus placebo. The primary end point in this substudy was incident cataract. Univariate and multivariate Cox models were used to analyze: (1) if the active treatment reduced the risk of the primary end point and (2) if time-varying low-density lipoproteins (LDL) cholesterol lowering (annually assessed) was associated with less incident cataract per se. During an average follow-up of 4.3 years, 65 patients (3.5%) developed cataract. Mean age at baseline was 68 years and 39% were women. In Cox multivariate analysis adjusted for age, gender, prednisolone treatment, smoking, baseline LDL cholesterol and high sensitivity C-reactive protein; simvastatin plus ezetimibe versus placebo was associated with 44% lower risk of cataract development (hazard ratio 0.56, 95% confidence interval 0.33 to 0.96, p = 0.034). In a parallel analysis substituting time-varying LDL-cholesterol with randomized treatment, lower intreatment LDL-cholesterol was in itself associated with lower risk of incident cataract (hazard ratio 0.78 per 1 mmol/ml lower total cholesterol, 95% confidence interval 0.64 to 0.93, p = 0.008). In conclusion, randomized treatment with simvastatin plus ezetimibe was associated with a 44% lower risk of incident cataract development. This effect should perhaps be considered in the risk-benefit ratio of statin treatment.

  • 156. Bang, Casper N.
    et al.
    Greve, Anders M.
    Rossebø, Anne B.
    Ray, Simon
    Egstrup, Kenneth
    Boman, Kurt
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Nienaber, Christoph
    Okin, Peter M.
    Devereux, Richard B.
    Wachtell, Kristian
    Antihypertensive treatment with β-blockade in patients with asymptomatic aortic stenosis and association with cardiovascular events2017In: Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease, ISSN 2047-9980, E-ISSN 2047-9980, Vol. 6, no 12, article id e006709Article in journal (Refereed)
    Abstract [en]

    Background: Patients with aortic stenosis (AS) often have concomitant hypertension. Antihypertensive treatment with a beta-blocker (Bbl) is frequently avoided because of fear of depression of left ventricular function. However, it remains unclear whether antihypertensive treatment with a Bbl is associated with increased risk of cardiovascular events in patients with asymptomatic mild to moderate AS.

    Methods and results: We did a post hoc analysis of 1873 asymptomatic patients with mild to moderate AS and preserved left ventricular ejection fraction in the SEAS (Simvastatin and Ezetimibe in Aortic Stenosis) study. Propensity-matched Cox regression and competing risk analyses were used to assess risk ratios for all-cause mortality, sudden cardiac death, and cardiovascular death. A total of 932 (50%) patients received Bbl at baseline. During a median follow-up of 4.3 +/- 0.9 years, 545 underwent aortic valve replacement, and 205 died; of those, 101 were cardiovascular deaths, including 40 sudden cardiovascular deaths. In adjusted analyses, Bbl use was associated with lower risk of all-cause mortality (hazard ratio 0.5, 95% confidence interval 0.3-0.7, P<0.001), cardiovascular death (hazard ratio 0.4, 95% confidence interval 0.2-0.7, P<0.001), and sudden cardiac death (hazard ratio 0.2, 95% confidence interval 0.1-0.6, P=0.004). This was confirmed in competing risk analyses (all P<0.004). No interaction was detected with AS severity (all P>0.1).

    Conclusions: In post hoc analyses Bbl therapy did not increase the risk of all-cause mortality, sudden cardiac death, or cardiovascular death in patients with asymptomatic mild to moderate AS. A prospective study may be warranted to determine if Bbl therapy is in fact beneficial.

  • 157.
    Barath, Stefan
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Mills, Nicholas L
    Lundbäck, Magnus
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Törnqvist, Håkan
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Lucking, Andrew J
    Langrish, Jeremy P
    Söderberg, Stefan
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Boman, Christoffer
    Umeå University, Faculty of Science and Technology, Department of Applied Physics and Electronics, Energy Technology and Thermal Process Chemistry.
    Westerholm, Roger
    Löndahl, Jakob
    Donaldson, Ken
    Mudway, Ian S
    Sandström, Thomas
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Newby, David E
    Blomberg, Anders
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Impaired vascular function after exposure to diesel exhaust generated at urban transient running conditions2010In: Particle and fibre toxicology, ISSN 1743-8977, Vol. 7, no 1, p. 19-Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Traffic emissions including diesel engine exhaust are associated with increased respiratory and cardiovascular morbidity and mortality. Controlled human exposure studies have demonstrated impaired vascular function after inhalation of exhaust generated by a diesel engine under idling conditions.

    OBJECTIVES: To assess the vascular and fibrinolytic effects of exposure to diesel exhaust generated during urban-cycle running conditions that mimic ambient 'real-world' exposures.

    METHODS: In a randomised double-blind crossover study, eighteen healthy male volunteers were exposed to diesel exhaust (approximately 250 mug/m3) or filtered air for one hour during intermittent exercise. Diesel exhaust was generated during the urban part of the standardized European Transient Cycle. Six hours post-exposure, vascular vasomotor and fibrinolytic function was assessed during venous occlusion plethysmography with intra-arterial agonist infusions.

    MEASUREMENTS AND MAIN RESULTS: Forearm blood flow increased in a dose-dependent manner with both endothelial-dependent (acetylcholine and bradykinin) and endothelial-independent (sodium nitroprusside and verapamil) vasodilators. Diesel exhaust exposure attenuated the vasodilatation to acetylcholine (P < 0.001), bradykinin (P < 0.05), sodium nitroprusside (P < 0.05) and verapamil (P < 0.001). In addition, the net release of tissue plasminogen activator during bradykinin infusion was impaired following diesel exhaust exposure (P < 0.05).

    CONCLUSION: Exposure to diesel exhaust generated under transient running conditions, as a relevant model of urban air pollution, impairs vasomotor function and endogenous fibrinolysis in a similar way as exposure to diesel exhaust generated at idling. This indicates that adverse vascular effects of diesel exhaust inhalation occur over different running conditions with varying exhaust composition and concentrations as well as physicochemical particle properties. Importantly, exposure to diesel exhaust under ETC conditions was also associated with a novel finding of impaired of calcium channel-dependent vasomotor function. This implies that certain cardiovascular endpoints seem to be related to general diesel exhaust properties, whereas the novel calcium flux-related effect may be associated with exhaust properties more specific for the ETC condition, for example a higher content of diesel soot particles along with their adsorbed organic compounds.

  • 158. Batalli, A.
    et al.
    Ibrahimi, P.
    Bytyci, I.
    Ahmeti, A.
    Haliti, E.
    Elezi, S.
    Henein, Mark
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Bajraktari, G. Gani
    Different predictors of exercise capacity in HFpEF compared to HFrEF2017In: European Journal of Heart Failure, ISSN 1388-9842, E-ISSN 1879-0844, Vol. 19, no 1, p. 314-314, article id P1244Article in journal (Refereed)
    Abstract [en]

    Background and Aim: Quality of life is as important as survival in heart failure (HF) patients. Controversies exist with regards to echocardiographic predictors of exercise capacity in HF, particularly in patients with preserved ejection fraction (HFpEF). The aim of this study was to prospectively examine echocardiographic parameters that correlate and predict functional exercise capacity assessed by 6 min walk test (6-MWT) in patients with HFpEF.

    Methods: In 111 HF patients (mean age 63± 10 years, 47% female), an echo-Doppler study and a 6-MWT were performed in the same day. Patients were divided into two groups based on the 6-MWT distance (Group I: ≤ 300 m and Group II: >300 m).

    Results: Group I were older (p=0.008), had higher prevalence of diabetes (p=0.027), higher baseline heart rate (p=0.004), larger left atrium - LA (p=0.001), longer LV filling time - FT (p=0.019), shorter isovolumic relaxation time (p=0.037), shorter pulmonary acceleration time - PAAT (p=0.006), lower left atrial lateral wall myocardial velocity (a’) (p=0.018) and lower septal systolic myocardial velocity (s’) (p=0.023), compared with Group II. Patients with HF and reduced EF (HFrEF) had lower hemoglobin (p=0.007), higher baseline heart rate (p=0.005), higher NT-ProBNP (p=0.001), larger LA (p=0.004), lower septal s’, e’, a’ waves, and septal MAPSE, shorter PAAT (p < 0.001 for all), lower lateral MAPSE, higher E/A & E/e’, and shorter LVFT (p=0.001 for all), lower lateral e’ (p=0.009), s’ (p=0.006), RV e’ and LA emptying fraction (p=0.012 for both), compared with HFpEF patients. In multivariate analysis, only LA diameter [2.676 (1.242-5.766), p=0.012], and diabetes [0.274 (0.084 - 0.898), p=0.033] independently predicted poor 6-MWT performance in the group as a whole. In HFrEF, age [1.073 (1.012 - 1.137), p=0.018] and LA diameter [3.685 (1.348 - 10.071), p=0.011], but in HFpEF, lateral s’ [0.295 (0.099 - 0.882), p=0.029], and hemoglobin level [0.497 (0.248-0.998), p=0.049] independently predicted poor 6-MWT performance.

    Conclusion: In HF patients predictors of exercise capacity differ according to severity of overall LV systolic function, with left atrial enlargement in HFrEF and longitudinal systolic shortening in HFpEF as the the main predictors.

  • 159.
    Behndig, Annelie F.
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Linder, Robert
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Lindberg, Anne
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Pourazar, Jamshid
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Blomberg, Anders
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Inflammatory Markers In Different COPD Subgroups Compared To Smokers And Healthy Controls2015In: American Journal of Respiratory and Critical Care Medicine, ISSN 1073-449X, E-ISSN 1535-4970, Vol. 191, article id A2884Article in journal (Other academic)
  • 160.
    Behndig, Annelie F.
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Shanmuganathan, Karthika
    Whitmarsh, Laura
    Stenfors, Nikolai
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine. Östersund Research Unit, Umeå University. .
    Brown, Joanna L.
    Frew, Anthony J.
    Kelly, Frank J.
    Mudway, Ian S.
    Sandström, Thomas
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Wilson, Susan J.
    Effects of controlled diesel exhaust exposure on apoptosis and proliferation markers in bronchial epithelium: an in vivo bronchoscopy study on asthmatics, rhinitics and healthy subjects2015In: BMC Pulmonary Medicine, ISSN 1471-2466, E-ISSN 1471-2466, Vol. 15, article id 99Article in journal (Refereed)
    Abstract [en]

    Background: Epidemiological evidence demonstrates that exposure to traffic-derived pollution worsens respiratory symptoms in asthmatics, but controlled human exposure studies have failed to provide a mechanism for this effect. Here we investigated whether diesel exhaust (DE) would induce apoptosis or proliferation in the bronchial epithelium in vivo and thus contribute to respiratory symptoms.

    Methods: Moderate (n = 16) and mild (n = 16) asthmatics, atopic non-asthmatic controls (rhinitics) (n = 13) and healthy controls (n = 21) were exposed to filtered air or DE (100 μg/m 3 ) for 2 h, on two separate occasions. Bronchial biopsies were taken 18 h post-exposure and immunohistochemically analysed for pro-apoptotic and anti-apoptotic proteins (Bad, Bak, p85 PARP, Fas, Bcl-2) and a marker of proliferation (Ki67). Positive staining was assessed within the epithelium using computerized image analysis.

    Results: No evidence of epithelial apoptosis or proliferation was observed in healthy, allergic or asthmatic airways following DE challenge.

    Conclusion: In the present study, we investigated whether DE exposure would affect markers of proliferation and apoptosis in the bronchial epithelium of asthmatics, rhinitics and healthy controls, providing a mechanistic basis for the reported increased airway sensitivity in asthmatics to air pollutants. In this first in vivo exposure investigation, we found no evidence of diesel exhaust-induced effects on these processes in the subject groups investigated.

  • 161.
    Benckert, Martin
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Lilja, Mikael
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Family Medicine.
    Söderberg, Stefan
    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.
    Improved metabolic health among the obesein six population surveys 1986 to 2009: the Northern Sweden MONICA study2015In: BMC Obesity, ISSN 2052-9538, Vol. 2, no 7Article in journal (Refereed)
    Abstract [en]

    Background

    The incidence of CVD is decreasing in spite of increasing BMI in the population. We examined trends in metabolic health among overweight and obese individuals and the influence of lifestyle and socioeconomic status. Six cross sectional population surveys in the Northern Sweden MONICA Study between 1986 and 2009. 8 874 subjects 25 to 64 years participated (74% participation rate). Metabolic health was defined as a total cholesterol level below 5.0 mmol/l, blood pressure below 140/90 mmHg and not having diabetes. In 2009 the age span 25 to 74 years was studied.

    Results

    The prevalence of metabolic health among obese subjects increased by 7.9 % per year (95% confidence interval 5.4; 10.5), reaching 21.0% in 2009. The corresponding figures for overweight subjects were 5.9% per year (4.6; 7.3), reaching 18% in 2009, whereas for the normal-weight subjects, the increase was 6.2% per year (5.3; 7.2), reaching 39% in 2009. The prevalence of metabolic health among subjects with abdominal obesity increased by 5.8% (4.6; 7.0) per year, reaching 17.3% in 2009. Among those with no abdominal obesity the increase was 6.2% (5.2; 7.1), reaching 38% in 2009 (p = <0.001 for all groups). Only among non-obese men and obese women did the increase continue between 2004 and 2009. In the other groups a slight decline or levelling off was noted.

    In 2009 women had a 27% higher prevalence of metabolic health than men. The prevalence of metabolic health among the obese was 19.8% which declined to 15.8% if subjects treated for hypertension or hypercholesterolemia were classified as not healthy. Overweight and obese subjects were less often metabolically healthy (odds ratio 0.54 and 0.59 respectively) compared with normal-weight subjects, independent of sex and age as were subjects with abdominal obesity (odds ratio 0.52). Adjustments for smoking, physical activity and education level did not influence any estimates.

    Conclusions

    This report shows a large increase in prevalence of metabolic health from 1986 to 2009 for all anthropometric categories. Metabolic health remains considerably less prevalent among overweight and obese subjects than among those with normal weight.

  • 162.
    Bengrid, Tarek
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine.
    Zhao, Y.
    Ultrasound Department, Beijing Anzhen Hospital, Beijing, China.
    Henein, Michael
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Disturbed right ventricular function response to dobutamine stress in Syndrome X patients: a potential effect of coronary calcification2014In: Atherosclerosis, ISSN 0021-9150, E-ISSN 1879-1484, Vol. 235, no 2, p. E229-E229Article in journal (Other academic)
  • 163. Bennet, L.
    et al.
    Groop, L.
    Lindblad, U.
    Agardh, C-D
    Franks, Paul W.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine. Department of Clinical Sciences, Lund University, Malmö, Sweden and Genetic & Molecular Epidemiology Unit, Lund University, Malmö, Sweden and Department of Nutrition, Harvard School of Public Health, Boston Massachusetts, USA.
    Ethnicity is an independent risk indicator when estimating diabetes risk with FINDRISC scores: A cross sectional study comparing immigrants from the Middle East and native Swedes2014In: Primary Care Diabetes, ISSN 1751-9918, E-ISSN 1878-0210, Vol. 8, no 3, p. 231-238Article in journal (Refereed)
    Abstract [en]

    Aims: This study sought to compare type 2 diabetes (T2D) risk indicators in Iraqi immigrants with those in ethnic Swedes living in southern Sweden. Methods: Population-based, cross-sectional cohort study of men and women, aged 30-75 years, born in Iraq or Sweden conducted in 2010-2012 in Malmo, Sweden. A 75 g oral glucose tolerance test was performed and sociodemographic and lifestyle data were collected. T2D risk was assessed by the Finnish Diabetes Risk Score (FINDRISC). Results: In Iraqi versus Swedish participants, T2D was twice as prevalent (11.6 vs. 5.8%, p < 0.001). A large proportion of the excess T2D risk was attributable to larger waist circumference and first-degree family history of diabetes. However, Iraqi ethnicity was a risk factor for T2D independently of other FINDRISC factors (odds ratio (OR) 2.5, 95% CI 1.6-3.9). The FINDRISC algorithm predicted that more Iraqis than Swedes (16.2 vs. 12.3%, p < 0.001) will develop T2D within the next decade. The total annual costs for excess T2D risk in Iraqis are estimated to exceed 2.3 million euros in 2005, not accounting for worse quality of life. Conclusions: Our study suggests that Middle Eastern ethnicity should be considered an independent risk indicator for diabetes. Accordingly, the implementation of culturally tailored prevention programs may be warranted. (C) 2014 Primary Care Diabetes Europe. Published by Elsevier Ltd. All rights reserved.

  • 164. Bennet, L.
    et al.
    Lindblad, U.
    Franks, Paul W.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    A family history of diabetes determines poorer glycaemic control and younger age of diabetes onset in immigrants from the Middle East compared with native Swedes2015In: Diabetes & Metabolism, ISSN 1262-3636, E-ISSN 1878-1780, Vol. 41, no 1, p. 45-54Article in journal (Refereed)
    Abstract [en]

    Aims. - Immigrant populations from the Middle East develop diabetes earlier than indigenous European populations; however, the underlying etiology is poorly understood. This study looked at the risk factors associated with early diabetes onset and, in non-diabetics, glycaemic control in immigrants from Iraq compared with native Swedes.

    Methods. - This cross-sectional population-based study comprised 1398 Iraqi immigrants and 757 Swedes (ages 30-75 years) residing in the same area of Malmo, Sweden. Outcomes were age at diabetes onset and glycaemic control (HbA(1c)) as assessed by Cox proportional hazards and linear regression, respectively.

    Results. - In Iraqis vs Swedes, clustering in the family history (in two or more relatives) was more prevalent (23.2% vs 3.6%, P<0.001) and diabetes onset occurred earlier (47.6 years vs 53.4 years, P=0.001). Having an Iraqi background independently raised the hazard ratio (HR) for diabetes onset. Diabetes risk due to family history was augmented by obesity, with the highest HRs observed in obese participants with clustering in the family history (HR: 5.1, 95% CI: 3.2-8.2) after adjusting for country of birth and gender. In participants without previously diagnosed diabetes (Iraqis: n=1270; Swedes: n=728), HbA(1c), levels were slightly higher in Iraqis than in Swedes (4.5% vs 4.4%, P=0.038). This difference was explained primarily by clustering in the family history rather than age, obesity, lifestyle or socioeconomic status.

    Conclusion. - The study shows that the greater predisposition to diabetes in Middle Eastern immigrants may be explained by a more extensive family history of the disorder; clinical interventions tailored to Middle Eastern immigrants with such a family history are thus warranted.

  • 165. Bennet, Louise
    et al.
    Groop, Leif
    Franks, Paul W.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine. Department of Nutrition, Harvard School of Public Health, Boston, MA, USA; Department of Clinical Sciences, Lund University, Skåne University Hospital, Malmö, Sweden; Genetic and Molecular Epidemiology Unit, Lund University Diabetes Centre, Malmö, Sweden.
    Country of birth modifies the association of fatty liver index with insulin action in Middle Eastern immigrants to Sweden2015In: Diabetes Research and Clinical Practice, ISSN 0168-8227, E-ISSN 1872-8227, Vol. 110, no 1, p. 66-74Article in journal (Refereed)
    Abstract [en]

    Aims: Non-alcohol fatty liver disease (NAFLD) is a strong risk factor for insulin resistance and type 2 diabetes. The prevalence of NAFLD varies across populations of different ethnic backgrounds but the prevalence in Middle Eastern populations, which are at high risk of type 2 diabetes, is largely unknown. Using fatty liver index (FLI) as a proxy for NAFLD the aim was to calculate the odds of NAFLD (FLI >= 70) given country of origin and further to investigate the associations between ISI and FLI. Methods: In 2010-2012 we conducted a population-based study of individuals aged 30-75 years born in Iraq or Sweden, in whom anthropometrics, fasting blood samples and oral glucose tolerance tests were performed and sociodemography and lifestyle behaviors characterized. Results: A higher proportion of Iraqis (N = 1085) than Swedes (N = 605) had a high probability of NAFLD (FLI >= 70, 32.5 vs. 22.6%, p < 0.001, age-and sex-adjusted data) and ISI was more severely impaired (70.7 vs. 95.9%, p < 0.001). Independently of traditional risk factors for NAFLD, being born in Iraqi increased the risk of FLI >= 70 (OR 1.59: 95% CI 1.15, 2.20). Furthermore, country of birth presented a stronger association between ISI and FLI >= 70 in Iraqis than in Swedes (P-interaction = 0.019). Conclusions: Our data indicate that immigrants from Iraq are at higher risk of NAFLD. The finding that country of birth modifies the relationship of FLI with ISI, suggests that liver fat may be a stronger determinant of impaired insulin action and increased risk of type 2 diabetes in Iraqis than in Swedes.

  • 166. Bennet, Louise
    et al.
    Groop, Leif
    Franks, Paul W
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Ethnic differences in the contribution of insulin action and secretion to type 2 diabetes in immigrants from the Middle East compared to native Swedes2014In: Diabetes Research and Clinical Practice, ISSN 0168-8227, E-ISSN 1872-8227, Vol. 105, no 1, p. 79-87Article in journal (Refereed)
    Abstract [en]

    Aims: We investigated insulin action (insulin sensitivity index, ISI) and insulin secretion (oral disposition indices, DIo) and studied metabolic, demographic and lifestyle-related risk factors for type 2 diabetes and insulin action, in the largest non-European immigrant group to Sweden, immigrants from Iraq and native Swedes.

    Methods: Population-based, cross-sectional study conducted 2010-2012 including residents 30-75 years of age born in Iraq or Sweden, in whom oral glucose tolerance tests were performed and sociodemography and lifestyle behaviors were characterized.

    Results: In Iraqis compared to Swedes, ISI was more impaired (76.9 vs. 102.3, p < .001) whereas corrected insulin response CIR was higher (226.6 vs. 188.6, p = .016). However, insulin secretion was inadequate given the substantial insulin resistance, as indicated by lower DIo indices in Iraqis than in Swedes (DIo 12,712.9 vs. 14,659.2, p < .001). The crude ethnic difference in ISI was not offset by traditional risk factors like waist circumference, body mass index or family history of diabetes. In Iraqis, ISI conveyed somewhat higher odds of type 2 diabetes than in Swedes (odds ratio OR 0.98, 95% CI 0.97-0.99) vs. OR 0.95, 0.92-0.99), as indicated by an interaction between country of birth and ISI (P-interaction = .044).

    Conclusion: This study reports ethnic differences in the contribution of insulin action to type 2 diabetes. Our data suggests that the impaired insulin action observed in immigrants from the Middle East to Sweden is not fully explained by established risk factors.

    (C) 2014 The Authors. Published by Elsevier Ireland Ltd. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/3.0/).

  • 167.
    Bergenheim, A Tommy
    et al.
    Umeå University, Faculty of Medicine, Pharmacology and Clinical Neuroscience, Neurosurgery.
    Roslin, Michael
    Umeå University, Faculty of Medicine, Pharmacology and Clinical Neuroscience, Neurosurgery.
    Ungerstedt, Urban
    Waldenström, Anders
    Umeå University, Faculty of Medicine, Public Health and Clinical Medicine, Medicine.
    Henriksson, Roger
    Umeå University, Faculty of Medicine, Radiation Sciences, Oncology.
    Ronquist, Gunnar
    Metabolic manipulation of glioblastoma in vivo by retrograde microdialysis of L-2, 4 diaminobutyric acid (DAB).2006In: J Neurooncol, ISSN 0167-594X, Vol. 80, no 3, p. 285-293Article in journal (Refereed)
  • 168.
    Bergfors, M
    et al.
    Umeå University, Faculty of Science and Technology, Studies in Biology and Environmental Sciences. Umeå University, Faculty of Medicine, Public Health and Clinical Medicine, Medicine.
    Barnekow-Bergkvist, M
    Kalezic, N
    Umeå University, Faculty of Medicine, Surgical and Perioperative Sciences, Sports Medicine.
    Lyskov, E
    Eriksson, Jan
    Umeå University, Faculty of Medicine, Public Health and Clinical Medicine, Medicine.
    Short-term effects of repetitive arm work and dynamic exercise on glucose metabolism and insulin sensitivity.2005In: Acta Physiologica Scandinavica, ISSN 0001-6772, E-ISSN 1365-201X, Vol. 183, no 4, p. 345-356Article in journal (Refereed)
  • 169.
    Berglin, Ewa
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Reumatology.
    Rantapää-Dahlqvist, Solbritt M.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Reumatology. Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Comparison of the 1987 ACR and 2010 ACR/EULAR Classification Criteria for Rheumatoid Arthritis in Clinical Practice2011In: Arthritis and Rheumatism, ISSN 0004-3591, E-ISSN 1529-0131, Vol. 63, no 10, p. S117-S117Article in journal (Refereed)
  • 170.
    Bergman, Frida
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine. Umeå University, Faculty of Medicine, Department of Community Medicine and Rehabilitation, Physiotherapy.
    Active workstations: a NEAT way to prevent and treat overweight and obesity?2018Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Background: Modern society is triggering sedentary behaviours in different domains. Different strategies can be used to reduce the time spent sitting and increase physical activity in the office environment, which is one domain where sedentary time is often high. One such strategy could be to install treadmill workstations. With these, the office workers can walk on a treadmill while performing their usual work tasks at the computer. However, the long-term effects of these workstations are not known. 

    Aim: The overall aim of this thesis was to investigate the long-term effects on sedentary behaviour, physical activity and associated health factors of installing treadmill workstations in offices compared to regular office work.

    Method: In this randomized controlled trial, 80 sedentary, middle-aged, healthy office workers with overweight or obesity were individually randomized into either an intervention or a control group. Those in the intervention group had a treadmill workstation installed at their sit-stand desk, to use for at least one hour per day for 13 months. They further received boosting e-mails at four time-points during the study. Participants in the control group continued to work as normal at their sit-stand office desk. All participants also received a health consultation at the beginning of the study, where they got to discuss physical activity and diet recommendations. Measurements reported include physical activity and sedentary behaviour, anthropometric measurements, body composition, metabolic outcomes, stress, depression and anxiety, cognitive function, structural brain images and interview data. Linear mixed models were used for the main statistical analyses of the quantitative data. An exploratory approach was also undertaken, using orthogonal partial least squares regression on the baseline data. Finally, interview data from participants in the intervention group were analysed using a modified Grounded Theory approach.

    Results: The intervention group increased their daily walking time and their number of steps at all follow-ups compared to the control group. Concomitantly, a decrease in moderate-to-vigorous intensity physical activity (MVPA) was observed within both groups, mainly during weekends. No intervention effects were observed on any of the body, cognitive or brain volume measurements. Our exploratory analyses revealed a significant association between smaller hippocampal volume and percentage sitting time among participants over 51 years of age. From the interview data, we discovered a core category, “The Capacity to Benefit”. The categories were described as the ideal types the Convinced, the Competitive, the Responsible and the Vacillating, based on the principal characteristics of the participants representing their different motivational status and strategies to reach the goal of benefitting from the intervention.  

    Conclusion: It is possible to increase daily physical activity in office environments by introducing treadmill workstations. Future interventions should adapt strategies for the individuals based on their motivational level, but should also workwith the social and physical environment and with factors within the organization to gain the best effects of these interventions.

  • 171.
    Bergman, Frida
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Boraxbekk, Carl-Johan
    Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI). Umeå University, Faculty of Social Sciences, Centre for Demographic and Ageing Research (CEDAR).
    Wennberg, Patrik
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Family Medicine.
    Sörlin, Ann
    Umeå University, Faculty of Medicine, Department of Community Medicine and Rehabilitation, Physiotherapy.
    Olsson, Tommy
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Increasing physical activity in officeworkers – the Inphact Treadmill study: a study protocol for a 13-month randomized controlled trial of treadmill workstations2015In: BMC Public Health, ISSN 1471-2458, E-ISSN 1471-2458, Vol. 15, article id 632Article in journal (Refereed)
    Abstract [en]

    Background: Sedentary behaviour is an independent risk factor for mortality and morbidity, especially for type 2 diabetes. Since office work is related to long periods that are largely sedentary, it is of major importance to find ways for office workers to engage in light intensity physical activity (LPA). The Inphact Treadmill study aims to investigate the effects of installing treadmill workstations in offices compared to conventional workstations.

    Methods/Design: A two-arm, 13-month, randomized controlled trial (RCT) will be conducted. Healthy overweight and obese office workers (n = 80) with mainly sedentary tasks will be recruited from office workplaces in Umeå, Sweden. The intervention group will receive a health consultation and a treadmill desk, which they will use for at least one hour per day for 13 months. The control group will receive the same health consultation, but continue to work at their regular workstations. Physical activity and sedentary time during workdays and non-workdays as well as during working and non-working hours on workdays will be measured objectively using accelerometers (Actigraph and activPAL) at baseline and after 2, 6, 10, and 13 months of follow-up. Food intake will be recorded and metabolic and anthropometric variables, body composition, stress, pain, depression, anxiety, cognitive function, and functional magnetic resonance imaging will be measured at 3–5 time points during the study period. Interviews with participants from the intervention group will be performed at the end of the study.

    Discussion: This will be the first long-term RCT on the effects of treadmill workstations on objectively measured physical activity and sedentary time as well as other body functions and structures/morphology during working and non-working hours among office workers. This will provide further insight on the effects of active workstations on our health and could fill in some of the knowledge gaps regarding how we can reduce sedentary time in office environments.

  • 172.
    Bergman, Frida
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Mattson-Frost, Tove
    Jonasson, Lars
    Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI). Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Chorell, Elin
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Sörlin, Ann
    Umeå University, Faculty of Medicine, Department of Community Medicine and Rehabilitation, Physiotherapy.
    Wennberg, Patrik
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Family Medicine.
    Öhberg, Fredrik
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Ryberg, Mats
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Levine, James
    Olsson, Tommy
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Boraxbekk, Carl-Johan
    Umeå University, Faculty of Social Sciences, Centre for Demographic and Ageing Research (CEDAR).
    Installing treadmill workstations in offices does little for cognitive performance and brain structure, despite a baseline association between sitting time and hippocampus volumeManuscript (preprint) (Other academic)
  • 173.
    Bergman, Frida
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Wahlström, Viktoria
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Section of Sustainable Health.
    Stomby, Andreas
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Otten, Julia
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Lanthén, Ellen
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Section of Medicine.
    Renklint, Rebecka
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Section of Medicine.
    Waling, Maria
    Umeå University, Faculty of Social Sciences, Department of Food and Nutrition.
    Sörlin, Ann
    Umeå University, Faculty of Medicine, Department of Community Medicine and Rehabilitation, Physiotherapy.
    Boraxbekk, Carl-Johan
    Umeå University, Faculty of Social Sciences, Centre for Demographic and Ageing Research (CEDAR). Danish Research Center for Magnetic Resonance, Centre for Functional and Diagnostic Imaging and Research, Copenhagen University Hospital, Hvidovre, Denmark.
    Wennberg, Patrik
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Family Medicine.
    Öhberg, Fredrik
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Levine, James A.
    Department of Endocrinology, The Mayo Clinic, Rochester, MN, USA; Fondation IPSEN, Paris, France.
    Olsson, Tommy
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Treadmill workstations in office workers who are overweight or obese: a randomised controlled trial2018In: The Lancet Public Health, ISSN 2468-2667, Vol. 3, no 11, article id e523-e535Article in journal (Refereed)
    Abstract [en]

    Background: Treadmill workstations that enable office workers to walk on a treadmill while working at their computers might increase physical activity in offices, but long-term effects are unknown. We therefore investigated whether treadmill workstations in offices increased daily walking time.

    Methods: We did a randomised controlled trial of healthy office workers who were either overweight or obese. We recruited participants from 13 different companies, which comprised 17 offices, in Umeå, Sweden. We included people who were aged 40-67 years, had sedentary work tasks, and had a body-mass index (BMI) between 25 kg/m2 and 40 kg/m2. After the baseline measurement, we stratified participants by their BMI (25-30 kg/m2 and >30 to 40 kg/m2); subsequently, an external statistician randomly assigned these participants (1:1) to either the intervention group (who received treadmill workstations for optional use) or the control group (who continued to work at their sit-stand desks as usual). Participants in the intervention group received reminders in boosting emails sent out to them at four occasions during the study period. Researchers were masked to group assignment until after analysis of the primary outcome. After the baseline measurement, participants were not masked to group belongings. The primary outcome was total daily walking time at weekdays and weekends, measured at baseline, 2 months, 6 months, 10 months, and 13 months with the accelerometer activPAL (PAL Technologies, Glasgow, UK), which was worn on the thigh of participants for 24 h a day for 7 consecutive days. We used an intention-to-treat approach for our analyses. This trial is registered with ClinicalTrials.gov, number NCT01997970, and is closed to new participants.

    Findings: Between Nov 1, 2013, and June 30, 2014, a total of 80 participants were recruited and enrolled (n=40 in both the intervention and control groups). Daily walking time during total time awake at weekdays increased between baseline and 13 months by 18 min (95% CI 9 to 26) in the intervention group and 1 min (-7 to 9) in the control group (difference 22 min [95% CI 7 to 37], pinteraction=0·00045); for weekend walking, the change from baseline to 13 months was 5 min (-8 to 18) in the intervention group and 8 min (-5 to 21) in the control group (difference -1 min [-19 to 17]; pinteraction=0·00045). Neither measure met our predetermined primary outcome of 30 min difference in total walking time between the intervention and control group, so the primary outcome of the trial was not met. One adverse event was reported in a participant who accidently stepped on their Achilles tendon.

    Interpretation: In a sedentary work environment, treadmill workstations result in a statistically significant but smaller-than-expected increase in daily walking time. Future studies need to investigate how increasing physical activity at work might have potentially compensatory effects on non-work activity.

  • 174. Bergquist, Annika
    et al.
    Montgomery, Scott M
    Bahmanyar, Shahram
    Olsson, Rolf
    Danielsson, Åke
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Lindgren, Stefan
    Prytz, Hanne
    Hultcrantz, Rolf
    Lööf, Lars
    Sandberg-Gertzén, Hanna
    Almer, Sven
    Askling, Johan
    Ehlin, Anna
    Ekbom, Anders
    Increased risk of primary sclerosing cholangitis and ulcerative colitis in first-degree relatives of patients with primary sclerosing cholangitis2008In: Clinical Gastroenterology and Hepatology, ISSN 1542-3565, E-ISSN 1542-7714, Vol. 6, no 8, p. 939-943Article in journal (Refereed)
    Abstract [en]

    BACKGROUND & AIMS: The importance of genetic factors for the development of primary sclerosing cholangitis (PSC) is incompletely understood. This study assessed the risk of PSC and inflammatory bowel disease (IBD) among first-degree relatives of patients with PSC, compared with the first-degree relatives of a cohort without PSC.

    METHODS: Subjects from the national Swedish cohort of PSC patients (n = 678) were matched for date of birth, sex, and region to up to 10 subjects without a diagnosis of PSC (n = 6347). Linkage through general population registers identified first-degree relatives of subjects in both the PSC and comparison cohorts (n = 34,092). Diagnoses among first-degree relatives were identified by using the Inpatient Register.

    RESULTS: The risk of cholangitis was statistically significantly increased in offspring, siblings, and parents of the PSC patient cohort, compared with relatives of the comparison cohort, with the hazard ratios and 95% confidence intervals, 11.5 (1.6-84.4), 11.1 (3.3-37.8), and 2.3 (0.9-6.1), respectively. The hazard ratios for ulcerative colitis (UC) among first-degree relatives of all PSC patients was 3.3 (2.3-4.9) and for Crohn's disease 1.4 (0.8-2.5). The risk of UC for relatives of PSC patients without IBD was also increased, 7.4 (2.9-18.9).

    CONCLUSIONS: First-degree relatives of patients with PSC run an increased risk of PSC, indicating the importance of genetic factors in the etiology of PSC. First-degree relatives of PSC patients without IBD are also at an increased risk of UC, which might indicate shared genetic susceptibility factors for PSC and UC.

  • 175.
    Bergstedt Oscarsson, Kristina
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Infectious Diseases.
    Brorstad, Alette
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Infectious Diseases.
    Baudin, Maria
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Virology.
    Lindberg, Anne
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Forssén, Annika
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Family Medicine.
    Evander, Magnus
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Virology.
    Eriksson, Marie
    Umeå University, Faculty of Social Sciences, Umeå School of Business and Economics (USBE), Statistics.
    Ahlm, Clas
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Infectious Diseases.
    Human Puumala hantavirus infection in northern Sweden: increased seroprevalence and association to risk and health factors2016In: BMC Infectious Diseases, ISSN 1471-2334, E-ISSN 1471-2334, Vol. 16, article id 566Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: The rodent borne Puumala hantavirus (PUUV) causes haemorrhagic fever with renal syndrome in central and northern Europe. The number of cases has increased and northern Sweden has experienced large outbreaks in 1998 and 2006-2007 which raised questions regarding the level of immunity in the human population.

    METHODS: A randomly selected population aged between 25 and 74 years from northern Sweden were invited during 2009 to participate in a WHO project for monitoring of trends and determinants in cardiovascular disease. Health and risk factors were evaluated and sera from 1,600 participants were available for analysis for specific PUUV IgG antibodies using a recombinant PUUV nucleocapsid protein ELISA.

    RESULTS: The overall seroprevalence in the investigated population was 13.4 %, which is a 50 % increase compared to a similar study only two decades previously. The prevalence of PUUV IgG increased with age, and among 65-75 years it was 22 %. More men (15.3 %) than women (11.4 %) were seropositive (p < 0.05). The identified risk factors were smoking (OR = 1.67), living in rural areas (OR = 1.92), and owning farmland or forest (OR = 2.44). No associations were found between previous PUUV exposure and chronic lung disease, diabetes, hypertension, renal dysfunction, stroke or myocardial infarction.

    CONCLUSIONS: PUUV is a common infection in northern Sweden and there is a high life time risk to acquire PUUV infection in endemic areas. Certain risk factors as living in rural areas and smoking were identified. Groups with increased risk should be targeted for future vaccination when available, and should also be informed about appropriate protection from rodent secreta.

  • 176. Bergström, Erik
    et al.
    Boman, Kurt
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Dahlqvist, Rune
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Pharmacology.
    Birgander, Lisbeth Slunga
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Occupational and Environmental Medicine.
    [Do better next time]2009In: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 106, no 8, p. 527-Article in journal (Other academic)
  • 177. Bergström, Erik
    et al.
    Boman, Kurt
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Dahlqvist, Rune
    Birgander, Slunga Lisbeth
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Occupational and Environmental Medicine.
    [Criticism against a prioritization project in Vasterbotten. Serious prioritization work requires knowledge and open ethical principles]2009In: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 106, no 3, p. 126-127Article in journal (Other academic)
  • 178. Bergström, Joakim
    et al.
    Gustavsson, Åsa
    Hellman, Ulf
    Sletten, Knut
    Murphy, Charles L
    Weiss, Deborah T
    Solomon, Alan
    Olofsson, Bert-Ove
    Umeå University, Faculty of Medicine, Public Health and Clinical Medicine, Medicine.
    Westermark, Per
    Amyloid deposits in transthyretin-derived amyloidosis: cleaved transthyretin is associated with distinct amyloid morphology.2005In: J Pathol, ISSN 0022-3417, Vol. 206, no 2, p. 224-32Article in journal (Refereed)
  • 179.
    Bergström, Lisa
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Irewall, Anna-Lotta
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Söderström, Lars
    Ögren, Joachim
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Laurell, Katarina
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Mooe, Thomas
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    One-year incidence, time trends, and predictors of recurrent ischemic stroke in Sweden from 1998-2010: An observational studyManuscript (preprint) (Other academic)
  • 180.
    Berhan, Yonas
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Eliasson, Mats
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Möllsten, Anna
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Waernbaum, Ingeborg
    Umeå University, Faculty of Social Sciences, Umeå School of Business and Economics (USBE), Statistics.
    Dahlquist, Gisela
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Impact of Parental Socioeconomic Status on Excess Mortality in a Population-Based Cohort of Subjects With Childhood-Onset Type 1 Diabetes2015In: Diabetes Care, ISSN 0149-5992, E-ISSN 1935-5548, Vol. 38, no 5, p. 827-832Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: The aim of this study was to analyze the possible impact of parental and individual socioeconomic status (SES) on all-cause mortality in a population-based cohort of patients with childhood-onset type 1 diabetes.

    RESEARCH DESIGN AND METHODS: Subjects recorded in the Swedish Childhood Diabetes Registry (SCDR) from 1 January 1978 to 31 December 2008 were included (n =14,647). The SCDR was linked to the Swedish Cause of Death Registry (CDR) and the Longitudinal Integration Database for Health Insurance and Labour Market Studies (LISA).

    RESULTS: At a mean follow-up of 23.9 years (maximum 46.5 years), 238 deaths occurred in a total of 349,762 person-years at risk. In crude analyses, low maternal education predicted mortality for male patients only (P = 0.046), whereas parental income support predicted mortality in both sexes (P < 0.001 for both). In Cox models stratified by age-at-death group and adjusted for age at onset and sex, parental income support predicted mortality among young adults (≥18 years of age) but not for children. Including the adult patient’s own SES in a Cox model showed that individual income support to the patient predicted mortality occurring at ≥24 years of age when adjusting for age at onset, sex, and parental SES.

    CONCLUSIONS: Exposure to low SES, mirrored by the need for income support, increases mortality risk in patients with childhood-onset type 1 diabetes who died after the age of 18 years.

  • 181.
    Berhan, Yonas
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Eliasson, Mats
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Möllsten, Anna
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Waernbaum, Ingeborg
    Umeå University, Faculty of Social Sciences, Umeå School of Business and Economics (USBE), Statistics.
    Dahlquist, Gisela
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Impact of parental socioeconomic status on excess mortality in subjects with childhood onset type-1 diabetesManuscript (preprint) (Other academic)
    Abstract [en]

    Aims/Hypothesis: The aim of this study was to analyze the possible impact of parental and individual socioeconomic status (SES) on all cause mortality in a population based cohort of childhood onset T1D.

    Methods: Subjects recorded in the Swedish Childhood Diabetes Registry (SCDR) January 1 1978 to December 31 2008 were included (n=14 409). The SCDR was linked to the Swedish Cause of Death Register (CDR) and the Longitudinal Integration Database for Health Insurance and Labour Market Studies (LISA). SES measures (education and income support) wtypeere retrieved from the LISA for the years 1990-2010. Mortality data were retrieved from the CDR as of December 31, 2010.

    Results: At a mean follow-up of 24.4 years (maximum 47.5), 238 deaths occurred in a total of 357 048 person-years at risk. In crude analyses, low maternal education predicted mortality for male cases only (p=0.046), while parental income support predicted mortality in both sexes (p<0.001 for both). In Cox models stratified by age at death groups and adjusted for age at onset and sex, parental income support predicted mortality among young adults ( ≥18 years of age) but not for children. Including the adult patient´s own SES in a Cox model showed that individual income support to the patient predicted mortality occurring at ≥ 24 years of age when adjusting for age at onset, sex and parental SES.

    Conclusions/Interpretation: Low parental SES, mirrored by the need of income support, increases mortality risk in childhood onset type-1 diabetics who died after the age of 18 years.

  • 182. Berk, JL
    et al.
    Dyck, PJ
    Obici, L
    Zeldenrust, SR
    Sekijima, Y
    Yamashita, T
    Ando, Y
    Ikeda, S-I
    Gorevic, P
    Merlini, G
    Kelly, JW
    Skinner, M
    Bisbee, AB
    Suhr, Ole B
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    The diflunisal trial: update on study drug tolerance and disease progression2011In: Amyloid : the international journal of experimental and clinical investigation : the official journal of the International Society of Amyloidosis, ISSN 1744-2818, Vol. 18, no Suppl. 1, p. 191-192Article in journal (Refereed)
    Abstract [en]

    Abstract: Familial amyloidotic polyneuropathy (FAP) is a lethal genetic disorder that affects the peripheral and autonomic nervous systems, heart, gastro-intestinal (GI) tract, and soft tissues. Disease progression is increasingly reported following liver transplantation, the only proven treatment for FAP. Small molecule thyroxine mimetics stabilize transthyretin, inhibiting FAP amyloid fibril formation under stringent in vitro conditions. We report on the progress of an international, randomized placebo-controlled study designed to determine the effect of diflunisal, a thyroxine mimetic, on neurologic disease progression in patients with active FAP. Our experience to date indicates diflunisal is well tolerated by this study cohort and that neurologic disease advances more rapidly in FAP than it does in diabetes mellitus.

    Background: Transthyretin-related familial amyloidotic polyneuropathy (FAP) is a lethal autosomal dominant genetic disorder that predominantly affects the peripheral nervous system. FAP amyloid fibrils result from the misfolding of transthyretin, a transport protein predominantly produced by the liver. Although liver transplantation effectively treats patients with certain FAP mutations and limited disease, reports increasingly document progressive amyloid deposition following transplantation [1,2]. Alternative treatments are needed. In vitro investigations and a phase I clinical trial have demonstrated that thyroxine and small molecule mimetics, e.g. diflunisal, inhibit tetrameric transthyretin dissociation and suppress amyloid fibril formation [3,4].

    Methods: To examine the effect of diflunisal on disease progression in FAP, we designed a randomized, placebo controlled, double blind, multicenter international study employing the validated diabetic (DM) polyneuropathy metric, Neurologic Impairment Score + 7 attributes (NIS+7®), as the primary endpoint. A two-point change in NIS+7 correlates with clinically detectable progression of peripheral neuropathy among diabetics [5]. Entry criteria include proven FAP genotype, biopsy-proven amyloid deposits, and peripheral or autonomic neuropathy. Patients with alternate causes of neuropathy, other NSAID use, severe heart or kidney dysfunction, or previous liver transplantion are excluded. Study evaluations occur at entry, 6, 12, and 24 months. Adverse are collected by monthly telephone interviews, diary entries, and study site visit interactions. Relatedness of adverse events to study drug is assigned according to documentation in the investigational brochure, the protocol, the informed consent form; or at the investigator's discretion.

    Results: To date, 90 subjects have enrolled – 62 men and 28 women with median age 63 years (range 27–76 years). Adverse events tabulated by affected organ systems predominantly involved gastrointestinal events, more often attributed to disease complications than study drug side effects (Table 1). Although rare events, congestive heart failure in two subjects and GI bleeding in another prompted study drug discontinuation. Two disease-related deaths have occurred, both off study drug. Aggregate data from all study subjects (placebo and active drug arms) followed for at least 12 months identified a 3.2 point increase in median NIS+7 summated scores. In contrast, Dyck et al. [6] reported an annual 0.85 point increase in NIS+7 median scores in a large cohort of diabetics with polyneuropathy. Taken together, NIS+7 detected neurologic disease progression in this FAP cohort after 12 months observation. Additionally, NIS+7 measured disease advanced 3.5 times faster in our aggregate FAP study population than previously reported in DM.

    Conclusions: Diflunisal is well tolerated in FAP patients participating in the study. NIS+7, a composite scoring system, appears to be an effective study instrument for ATTR neuropathy, detecting significant change over 12 months observation. Neurologic disease progresses more rapidly in FAP than DM cohorts. The exact rate of disease progression in untreated FAP subjects detected by NIS+7 awaits unblinding of the data. These data will provide basis for future study design in FAP patients.

  • 183. Berk, John L
    et al.
    Suhr, Ole B
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Sekijima, Yoshiki
    Yamashita, Taro
    Heneghan, Michael
    Zeldenrust, Steven R
    Ando, Yukio
    Ikeda, Shu-ichi
    Gorevic, Peter
    Merlini, Giampaolo
    Kelly, Jeffrey W
    Skinner, Martha
    Bisbee, Alice B
    Dyck, Peter J
    Obici, Laura
    The diflunisal trial: study accrual and drug tolerance2012In: Amyloid: Journal of Protein Folding Disorders, ISSN 1350-6129, E-ISSN 1744-2818, Vol. 19, no S1, p. 37-38Article in journal (Refereed)
    Abstract [en]

    Familial amyloidotic polyneuropathy (FAP) is a protein folding disorder that induces neuropathy and cardiomyopathy, leading to death within 7-15 years after onset of clinical disease. In vitro, small ligands binding the thyroid hormone docking site stabilize tetrameric transthyretin, inhibiting amyloid fibril formation. We undertook a randomized, placebo-controlled clinical trial to determine whether diflunisal, a well-known non-steroidal anti-inflammatory drug (NSAID) alters neurologic disease progression in FAP. We enrolled 130 subjects with wide age and FAP mutation representation. To date, few recognized complications of NSAIDs have occurred in the study cohort. Data collection will be completed by November 2012.

  • 184. Berndt, Sonja I.
    et al.
    Gustafsson, Stefan
    Maegi, Reedik
    Ganna, Andrea
    Wheeler, Eleanor
    Feitosa, Mary F.
    Justice, Anne E.
    Monda, Keri L.
    Croteau-Chonka, Damien C.
    Day, Felix R.
    Esko, Tonu
    Fall, Tove
    Ferreira, Teresa
    Gentilini, Davide
    Jackson, Anne U.
    Luan, Jian'an
    Randall, Joshua C.
    Vedantam, Sailaja
    Willer, Cristen J.
    Winkler, Thomas W.
    Wood, Andrew R.
    Workalemahu, Tsegaselassie
    Hu, Yi-Juan
    Lee, Sang Hong
    Liang, Liming
    Lin, Dan-Yu
    Min, Josine L.
    Neale, Benjamin M.
    Thorleifsson, Gudmar
    Yang, Jian
    Albrecht, Eva
    Amin, Najaf
    Bragg-Gresham, Jennifer L.
    Cadby, Gemma
    den Heijer, Martin
    Eklund, Niina
    Fischer, Krista
    Goel, Anuj
    Hottenga, Jouke-Jan
    Huffman, Jennifer E.
    Jarick, Ivonne
    Johansson, Asa
    Johnson, Toby
    Kanoni, Stavroula
    Kleber, Marcus E.
    Koenig, Inke R.
    Kristiansson, Kati
    Kutalik, Zoltn
    Lamina, Claudia
    Lecoeur, Cecile
    Li, Guo
    Mangino, Massimo
    McArdle, Wendy L.
    Medina-Gomez, Carolina
    Mueller-Nurasyid, Martina
    Ngwa, Julius S.
    Nolte, Ilja M.
    Paternoster, Lavinia
    Pechlivanis, Sonali
    Perola, Markus
    Peters, Marjolein J.
    Preuss, Michael
    Rose, Lynda M.
    Shi, Jianxin
    Shungin, Dmitry
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Smith, Albert Vernon
    Strawbridge, Rona J.
    Surakka, Ida
    Teumer, Alexander
    Trip, Mieke D.
    Tyrer, Jonathan
    Van Vliet-Ostaptchouk, Jana V.
    Vandenput, Liesbeth
    Waite, Lindsay L.
    Zhao, Jing Hua
    Absher, Devin
    Asselbergs, Folkert W.
    Atalay, Mustafa
    Attwood, Antony P.
    Balmforth, Anthony J.
    Basart, Hanneke
    Beilby, John
    Bonnycastle, Lori L.
    Brambilla, Paolo
    Bruinenberg, Marcel
    Campbell, Harry
    Chasman, Daniel I.
    Chines, Peter S.
    Collins, Francis S.
    Connell, John M.
    Cookson, William O.
    de Faire, Ulf
    de Vegt, Femmie
    Dei, Mariano
    Dimitriou, Maria
    Edkins, Sarah
    Estrada, Karol
    Evans, David M.
    Farrall, Martin
    Ferrario, Marco M.
    Ferrieres, Jean
    Franke, Lude
    Frau, Francesca
    Gejman, Pablo V.
    Grallert, Harald
    Groenberg, Henrik
    Gudnason, Vilmundur
    Hall, Alistair S.
    Hall, Per
    Hartikainen, Anna-Liisa
    Hayward, Caroline
    Heard-Costa, Nancy L.
    Heath, Andrew C.
    Hebebrand, Johannes
    Homuth, Georg
    Hu, Frank B.
    Hunt, Sarah E.
    Hyppoenen, Elina
    Iribarren, Carlos
    Jacobs, Kevin B.
    Jansson, John-Olov
    Jula, Antti
    Kahonen, Mika
    Kathiresan, Sekar
    Kee, Frank
    Khaw, Kay-Tee
    Kivimaki, Mika
    Koenig, Wolfgang
    Kraja, Aldi T.
    Kumari, Meena
    Kuulasmaa, Kari
    Kuusisto, Johanna
    Laitinen, Jaana H.
    Lakka, Timo A.
    Langenberg, Claudia
    Launer, Lenore J.
    Lind, Lars
    Lindstrom, Jaana
    Liu, Jianjun
    Liuzzi, Antonio
    Lokki, Marja-Liisa
    Lorentzon, Mattias
    Madden, Pamela A.
    Magnusson, Patrik K.
    Manunta, Paolo
    Marek, Diana
    Maerz, Winfried
    Leach, Irene Mateo
    McKnight, Barbara
    Medland, Sarah E.
    Mihailov, Evelin
    Milani, Lili
    Montgomery, Grant W.
    Mooser, Vincent
    Muehleisen, Thomas W.
    Munroe, Patricia B.
    Musk, Arthur W.
    Narisu, Narisu
    Navis, Gerjan
    Nicholson, George
    Nohr, Ellen A.
    Ong, Ken K.
    Oostra, Ben A.
    Palmer, Colin N. A.
    Palotie, Aarno
    Peden, John F.
    Pedersen, Nancy
    Peters, Annette
    Polasek, Ozren
    Pouta, Anneli
    Pramstaller, Peter P.
    Prokopenko, Inga
    Puetter, Carolin
    Radhakrishnan, Aparna
    Raitakari, Olli
    Rendon, Augusto
    Rivadeneira, Fernando
    Rudan, Igor
    Saaristo, Timo E.
    Sambrook, Jennifer G.
    Sanders, Alan R.
    Sanna, Serena
    Saramies, Jouko
    Schipf, Sabine
    Schreiber, Stefan
    Schunkert, Heribert
    Shin, So-Youn
    Signorini, Stefano
    Sinisalo, Juha
    Skrobek, Boris
    Soranzo, Nicole
    Stancakova, Alena
    Stark, Klaus
    Stephens, Jonathan C.
    Stirrups, Kathleen
    Stolk, Ronald P.
    Stumvoll, Michael
    Swift, Amy J.
    Theodoraki, Eirini V.
    Thorand, Barbara
    Tregouet, David-Alexandre
    Tremoli, Elena
    Van der Klauw, Melanie M.
    van Meurs, Joyce B. J.
    Vermeulen, Sita H.
    Viikari, Jorma
    Virtamo, Jarmo
    Vitart, Veronique
    Waeber, Gerard
    Wang, Zhaoming
    Widen, Elisabeth
    Wild, Sarah H.
    Willemsen, Gonneke
    Winkelmann, Bernhard R.
    Witteman, Jacqueline C. M.
    Wolffenbuttel, Bruce H. R.
    Wong, Andrew
    Wright, Alan F.
    Zillikens, M. Carola
    Amouyel, Philippe
    Boehm, Bernhard O.
    Boerwinkle, Eric
    Boomsma, Dorret I.
    Caulfield, Mark J.
    Chanock, Stephen J.
    Cupples, L. Adrienne
    Cusi, Daniele
    Dedoussis, George V.
    Erdmann, Jeanette
    Eriksson, Johan G.
    Franks, Paul W.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Froguel, Philippe
    Gieger, Christian
    Gyllensten, Ulf
    Hamsten, Anders
    Harris, Tamara B.
    Hengstenberg, Christian
    Hicks, Andrew A.
    Hingorani, Aroon
    Hinney, Anke
    Hofman, Albert
    Hovingh, Kees G.
    Hveem, Kristian
    Illig, Thomas
    Jarvelin, Marjo-Riitta
    Joeckel, Karl-Heinz
    Keinanen-Kiukaanniemi, Sirkka M.
    Kiemeney, Lambertus A.
    Kuh, Diana
    Laakso, Markku
    Lehtimaki, Terho
    Levinson, Douglas F.
    Martin, Nicholas G.
    Metspalu, Andres
    Morris, Andrew D.
    Nieminen, Markku S.
    Njolstad, Inger
    Ohlsson, Claes
    Oldehinkel, Albertine J.
    Ouwehand, Willem H.
    Palmer, Lyle J.
    Penninx, Brenda
    Power, Chris
    Province, Michael A.
    Psaty, Bruce M.
    Qi, Lu
    Rauramaa, Rainer
    Ridker, Paul M.
    Ripatti, Samuli
    Salomaa, Veikko
    Samani, Nilesh J.
    Snieder, Harold
    Sorensen, Thorkild I. A.
    Spector, Timothy D.
    Stefansson, Kari
    Tonjes, Anke
    Tuomilehto, Jaakko
    Uitterlinden, Andre G.
    Uusitupa, Matti
    van der Harst, Pim
    Vollenweider, Peter
    Wallaschofski, Henri
    Wareham, Nicholas J.
    Watkins, Hugh
    Wichmann, H-Erich
    Wilson, James F.
    Abecasis, Goncalo R.
    Assimes, Themistocles L.
    Barroso, Ines
    Boehnke, Michael
    Borecki, Ingrid B.
    Deloukas, Panos
    Fox, Caroline S.
    Frayling, Timothy
    Groop, Leif C.
    Haritunian, Talin
    Heid, Iris M.
    Hunter, David
    Kaplan, Robert C.
    Karpe, Fredrik
    Moffatt, Miriam F.
    Mohlke, Karen L.
    O'Connell, Jeffrey R.
    Pawitan, Yudi
    Schadt, Eric E.
    Schlessinger, David
    Steinthorsdottir, Valgerdur
    Strachan, David P.
    Thorsteinsdottir, Unnur
    van Duijn, Cornelia M.
    Visscher, Peter M.
    Di Blasio, Anna Maria
    Hirschhorn, Joel N.
    Lindgren, Cecilia M.
    Morris, Andrew P.
    Meyre, David
    Scherag, Andr
    McCarthy, Mark I.
    Speliotes, Elizabeth K.
    North, Kari E.
    Loos, Ruth J. F.
    Ingelsson, Erik
    Genome-wide meta-analysis identifies 11 new loci for anthropometric traits and provides insights into genetic architecture2013In: Nature Genetics, ISSN 1061-4036, E-ISSN 1546-1718, Vol. 45, no 5, p. 501-U69Article in journal (Refereed)
    Abstract [en]

    Approaches exploiting trait distribution extremes may be used to identify loci associated with common traits, but it is unknown whether these loci are generalizable to the broader population. In a genome-wide search for loci associated with the upper versus the lower 5th percentiles of body mass index, height and waist-to-hip ratio, as well as clinical classes of obesity, including up to 263,407 individuals of European ancestry, we identified 4 new loci (IGFBP4, H6PD, RSRC1 and PPP2R2A) influencing height detected in the distribution tails and 7 new loci (HNF4G, RPTOR, GNAT2, MRPS33P4, ADCY9, HS6ST3 and ZZZ3) for clinical classes of obesity. Further, we find a large overlap in genetic structure and the distribution of variants between traits based on extremes and the general population and little etiological heterogeneity between obesity subgroups.

  • 185. Berne, C
    et al.
    Eriksson, Jan
    Umeå University, Faculty of Medicine, Public Health and Clinical Medicine, Medicine.
    A randomized study of orlistat in combination with a weight management programme in obese patients with Type 2 diabetes treated with metformin.2005In: Diabet Med, ISSN 0742-3071, Vol. 22, no 5, p. 612-8Article in journal (Refereed)
  • 186. Berne, C
    et al.
    Yki-Järvinen, H
    Taskinen, M-R
    Fritz, T
    Ekstrand, A
    Eliasson, B
    Eriksson, Jan
    Umeå University, Faculty of Medicine, Public Health and Clinical Medicine, Medicine.
    Rekommendationer för vård och behandling vid typ 2 diabetes.2004In: Recallmedicin Publication Helsinki, 2004, p. 1-32Chapter in book (Other (popular science, discussion, etc.))
  • 187.
    Bernspång, Birgitta
    et al.
    Umeå University, Faculty of Medicine, Department of Community Medicine and Rehabilitation, Occupational Therapy.
    Asplund, Kjell
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Eriksson, Sture
    Umeå University, Faculty of Medicine, Department of Community Medicine and Rehabilitation, Geriatric Medicine.
    Fugl-Meyer, Axel R.
    Umeå University, Faculty of Medicine, Department of Community Medicine and Rehabilitation, Rehabilitation Medicine.
    Motor and perceptual impairments in acute stroke patients: effects on self-care ability1987In: Stroke, ISSN 0039-2499, E-ISSN 1524-4628, Vol. 18, no 6, p. 1081-1086Article in journal (Refereed)
    Abstract [en]

    The relative importance of motor, perceptual, and some cognitive functions for self-care ability was analyzed in a representative sample of 109 subjects within 2 weeks of acute stroke. Forty-nine patients (45%) were dependent or partly dependent in self-care. Profound motor dysfunction was present in 39%, low-order perceptual deficits in 10%, high-order perceptual deficits in 60%, and disorientation in time and space in 13% of the patients. There was a significant covariation between motor function and self-care ability and between low-order perception and orientation function. Low-order and high-order perception covaried only weakly. Discriminant analyses showed that the actual level of self-care proficiency could be correctly predicted in 70% of the cases by the 4 indexes of motor function, low-order perception, high-order perception, and orientation. The dominating predictor was motor function, and the next highest was high-order perception. When a program for early training is designed with the aim to alleviate long-term self-care disability after stroke, correct assessment of motor and perceptual functions in the individual stroke patient is essential.

  • 188. Beyder, Arthur
    et al.
    Mazzone, Amelia
    Strege, Peter R.
    Tester, David J.
    Saito, Yuri A.
    Bernard, Cheryl E.
    Enders, Felicity T.
    Ek, Weronica E.
    Schmidt, Peter T.
    Dlugosz, Aldona
    Lindberg, Greger
    Karling, Pontus
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Ohlsson, Bodil
    Gazouli, Maria
    Nardone, Gerardo
    Cuomo, Rosario
    Usai-Satta, Paolo
    Galeazzi, Francesca
    Neri, Matteo
    Portincasa, Piero
    Bellini, Massimo
    Barbara, Giovanni
    Camilleri, Michael
    Locke, G. Richard, III
    Talley, Nicholas J.
    D'Amato, Mauro
    Ackerman, Michael J.
    Farrugia, Gianrico
    Loss-of-Function of the Voltage-Gated Sodium Channel Na(V)1.5 (Channelopathies) in Patients With Irritable Bowel Syndrome2014In: Gastroenterology, ISSN 0016-5085, E-ISSN 1528-0012, Vol. 146, no 7, p. 1659-1668Article in journal (Refereed)
    Abstract [en]

    BACKGROUND & AIMS: SCN5A encodes the a-subunit of the voltage-gated sodium channel Na(V)1.5. Many patients with cardiac arrhythmias caused by mutations in SCN5A also have symptoms of irritable bowel syndrome (IBS). We investigated whether patients with IBS have SCN5A variants that affect the function of Na(V)1.5. METHODS: We performed genotype analysis of SCN5A in 584 persons with IBS and 1380 without IBS (controls). Mutant forms of SCN5A were expressed in human embryonic kidney-293 cells, and functions were assessed by voltage clamp analysis. A genome-wide association study was analyzed for an association signal for the SCN5A gene, and replicated in 1745 patients in 4 independent cohorts of IBS patients and controls. RESULTS: Missense mutations were found in SCN5A in 13 of 584 patients (2.2%, probands). Diarrhea-predominant IBS was the most prevalent form of IBS in the overall study population (25%). However, a greater percentage of individuals with SCN5A mutations had constipation-predominant IBS (31%) than diarrhea-predominant IBS (10%; P < .05). Electrophysiologic analysis showed that 10 of 13 detected mutations disrupted Na(V)1.5 function (9 loss-of-function and 1 gain-of-function function). The p. A997T-Na(V)1.5 had the greatest effect in reducing Na(V)1.5 function. Incubation of cells that expressed this variant with mexiletine restored their sodium current and administration of mexiletine to 1 carrier of this mutation (who had constipation-predominant IBS) normalized their bowel habits. In the genome-wide association study and 4 replicated studies, the SCN5A locus was strongly associated with IBS. CONCLUSIONS: About 2% of patients with IBS carry mutations in SCN5A. Most of these are loss-of-function mutations that disrupt Na(V)1.5 channel function. These findings provide a new pathogenic mechanism for IBS and possible treatment options.

  • 189. Biber, Björn
    et al.
    Waldenström, Anders
    Umeå University, Faculty of Medicine, Public Health and Clinical Medicine, Medicine.
    [New data on hypothermia. Now we have to keep cool!]2004In: Läkartidningen, ISSN 0023-7205, Vol. 101, no 6, p. 438-9Article in journal (Other academic)
  • 190.
    Binsell-Gerdin, Emil
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Hemorrhagic stroke the first 30-days after an acute myocardial infarction: incidence, time trends and predictors of risk2012Independent thesis Advanced level (professional degree), 20 credits / 30 HE creditsStudent thesis
  • 191.
    Binsell-Gerdin, Emil
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Graipe, Anna
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine. Department of Internal Medicine, Section of Cardiology, Östersund Hospital, Sweden and Department of Public Health and Clinical Medicine, Östersund, Umeå University, Sweden.
    Ögren, Joachim
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine. Department of Internal Medicine, Section of Cerebrovascular Diseases, Östersund Hospital, Sweden and Department of Public Health and Clinical Medicine, Östersund, Umeå University, Sweden.
    Jernberg, Tomas
    Department of Medicine, Section of Cardiology, Huddinge, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.
    Mooe, Thomas
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine. Östersund Research Unit, Umeå University.
    Hemorrhagic stroke the first 30 days after an acute myocardial infarction: incidence, time trends and predictors of risk2014In: International Journal of Cardiology, ISSN 0167-5273, E-ISSN 1874-1754, Vol. 176, no 1, p. 133-138Article in journal (Refereed)
    Abstract [en]

    Background/objectives: Hemorrhagic stroke is a rare but serious complication after an acute myocardial infarction (AMI). The aims of our study were to establish the incidence, time trends and predictors of risk for hemorrhagic stroke within 30 days after an AMI in 1998-2008. Methods: We collected data from the Register of Information and Knowledge about Swedish Heart Intensive Care Admissions (RIKS-HIA). All patients with a myocardial infarction 1998-2008 were included, n = 173,233. The data was merged with the National Patient Register in order to identify patients suffering a hemorrhagic stroke. To identify predictors of risk we used Cox models. Results: Overall the incidence decreased from 0.2% (n = 94) in 1998-2000 to 0.1% (n = 41) in 2007-2008. In patients with ST-elevation myocardial infarction the corresponding incidences were 0.4% (n = 76) in 1998-2000 and 0.2% (n = 21) in 2007-2008, and after fibrin specific thrombolytic treatment 0.6% and 1.1%, respectively, with a peak of 1.4% during 2003-2004. In total 375 patients (0.22%) suffered a hemorrhagic stroke within 30 days of the AMI. The preferred method of reperfusion changed from thrombolysis to percutaneous coronary intervention (PCI). Older age (hazard ratio (HR) >65- <= 75 vs <= 65 years 1.84, 95% confidence interval (CI) 1.38-2.45), thrombolysis (HR 6.84, 95% CI 5.51-8.48), history of hemorrhagic stroke (HR 12.52, CI 8.36-18.78) and prior hypertension (HR 1.52, CI 1.23-1.86) independently predicted hemorrhagic stroke within 30 days. Conclusions: The rate of hemorrhagic stroke within 30 days of an AMI has decreased by 50% between 1998 and 2008. The main reason is the shift in reperfusion method from thrombolysis to PCI. 

  • 192. Birgegård, Gunnar
    et al.
    Björkholm, Magnus
    Kutti, Jack
    Larfars, Gerd
    Löfvenberg, Eva
    Markevärn, Berit
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Merup, Mats
    Palmblad, Jan
    Mauritzson, Nils
    Westin, Jan
    Samuelsson, Jan
    Adverse effects and benefits of two years of anagrelide treatment for thrombocythemia in chronic myeloproliferative disorders.2004In: Haematologica, ISSN 1592-8721, Vol. 89, no 5, p. 520-7Article in journal (Refereed)
  • 193.
    Birzniece, Vita
    Umeå University, Faculty of Medicine, Clinical Sciences, Obstetrics and Gynaecology. Umeå University, Faculty of Medicine, Public Health and Clinical Medicine, Medicine.
    Neuroactive steroids and rat CNS2004Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Several studies suggest profound effects on mood and cognition by neuroactive steroids. Estrogen alone or in combination with antidepressant drugs affecting the serotonin system has been used to treat mood disorders. On the other hand, progesterone is related to negative effects on mood and memory. A major part of the progesterone effects on the brain can be mediated by its metabolite allopregnanolone, which is also de novo synthesized in the brain, and affects the GABAA receptors. It would be of great importance to find a substance that antagonize allopregnanolone adverse effects.

    To investigate how long term supplementation of estradiol and progesterone, resembling postmenopausal hormone replacement therapy, affects serotonin receptors in different brain areas important for mood and memory functions, we used ovariectomized female rats. After 2 weeks of supplementation with 17β-estradiol alone or in combination with progesterone, or placebo pellets, estradiol alone decreases but estradiol supplemented together with progesterone increases 5HT1A mRNA expression in the hippocampus. Estradiol decreases the 5HT2C receptor gene expression, while estradiol in combination with progesterone increases the 5HT2A mRNA expression in the ventral hippocampus. Thus, estradiol alone has opposite effects compared to the estradiol/progesterone combination. To detect if acute tolerance develops to allopregnanolone, an EEG method was used where male rats by continuous allopregnanolone infusion were kept on anesthesia level of the silent second (SS). After different time intervals (first SS, 30 min or 90 min of anesthesia) several GABAA receptor subunit mRNAs were measured for detecting if changed expression of any GABAA receptor subunits is involved in development of acute tolerance. There is development of acute tolerance to allopregnanolone and brain regions of importance are hippocampus, thalamus and hypothalamus. The GABAA receptor alpha4 subunit in thalamus and alpha2 subunit in the dorsal hippocampus are related to development of acute tolerance. For assessing allopregnanolone behavioral effects, we studied how this neurosteroid affects spatial learning in the Morris water maze task Allopregnanolone inhibits spatial learning short after the injection and shows a specific behavioral pattern with swimming close to the pool wall. The steroid UC1011 can inhibit the increase in chloride ion uptake induced by allopregnanolone. UC1011 decreases allopregnanoloneinduced impairment of spatial learning in the water maze, as well as the specific behavioral swim pattern.

    In conclusion, the present work demonstrates that neuroactive steroids affect the 5HT and GABA systems in a brain region specific way. GABAA receptor subunit changes in hippocampus and thalamus are related to acute allopregnanolone tolerance. Allopregnanolone induces cognitive deficits, like spatial learning impairment and UC1011 can inhibit allopregnanolone-induced effects in vitro and in vivo.

    Key words: Estradiol, progesterone, HRT, allopregnanolone, UC1011, serotonin receptor, GABAA receptor, mRNA, Morris water maze, silent second, tolerance.

  • 194.
    Birzniece, Vita
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Obstetrics and Gynaecology.
    Bäckström, Torbjörn
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Obstetrics and Gynaecology.
    Johansson, Inga-Maj
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Obstetrics and Gynaecology.
    Lindblad, Charlotte
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Obstetrics and Gynaecology.
    Lundgren, Per
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Obstetrics and Gynaecology.
    Löfgren, Magnus
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Obstetrics and Gynaecology.
    Olsson, Tommy
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Ragagnin, Gianna
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Obstetrics and Gynaecology.
    Taube, Magdalena
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Obstetrics and Gynaecology.
    Turkmen, Sahruh
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Obstetrics and Gynaecology.
    Wahlström, Göran
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Pharmacology.
    Wang, Ming-De
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Obstetrics and Gynaecology.
    Wihlbäck, Anna-Carin
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Obstetrics and Gynaecology.
    Zhu, Di
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Obstetrics and Gynaecology.
    Neuroactive steroid effects on cognitive functions with a focus on the serotonin and GABA systems.2006In: Brain Research Reviews, ISSN 0165-0173, E-ISSN 1872-6321, Vol. 51, no 2, p. 212-239Article in journal (Refereed)
  • 195.
    Bjellerup, Jakob
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Timing of medical prevention in patients with symptomatic carotid stenosis2012Independent thesis Advanced level (professional degree), 20 credits / 30 HE creditsStudent thesis
  • 196. Bjorck, Lena
    et al.
    Rosengren, Annika
    Winkvist, Anna
    Capewell, Simon
    Adiels, Martin
    Bandosz, Piotr
    Critchley, Julia
    Boman, Kurt
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Guzman-Castillo, Maria
    O'Flaherty, Martin
    Johansson, Ingegerd
    Umeå University, Faculty of Medicine, Department of Odontology.
    Changes in Dietary Fat Intake and Projections for Coronary Heart Disease Mortality in Sweden: A Simulation Study2016In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 11, no 8, article id e0160474Article in journal (Refereed)
    Abstract [en]

    Objective In Sweden, previous favourable trends in blood cholesterol levels have recently levelled off or even increased in some age groups since 2003, potentially reflecting changing fashions and attitudes towards dietary saturated fatty acids (SFA). We aimed to examine the potential effect of different SFA intake on future coronary heart disease (CHD) mortality in 2025. Methods We compared the effect on future CHD mortality of two different scenarios for fat intake a) daily SFA intake decreasing to 10 energy percent (E%), and b) daily SFA intake rising to 20 E %. We assumed that there would be moderate improvements in smoking (5%), salt intake (1g/day) and physical inactivity (5% decrease) to continue recent, positive trends. Results In the baseline scenario which assumed that recent mortality declines continue, approximately 5,975 CHD deaths might occur in year 2025. Anticipated improvements in smoking, dietary salt intake and physical activity, would result in some 380 (-6.4%) fewer deaths (235 in men and 145 in women). In combination with a mean SFA daily intake of 10 E%, a total of 810 (-14%) fewer deaths would occur in 2025 (535 in men and 275 in women). If the overall consumption of SFA rose to 20 E%, the expected mortality decline would be wiped out and approximately 20 (0.3%) additional deaths might occur. Conclusion CHD mortality may increase as a result of unfavourable trends in diets rich in saturated fats resulting in increases in blood cholesterol levels. These could cancel out the favourable trends in salt intake, smoking and physical activity.

  • 197.
    Björ, Bodil
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Occupational and Environmental Medicine.
    Burström, Lage
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Occupational and Environmental Medicine.
    Karlsson, Marcus
    Nilsson, Tohr
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Occupational and Environmental Medicine.
    Näslund, Ulf
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Wiklund, Urban
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Acute effects on heart rate variability when exposed to hand transmitted vibration and noise.2007In: International Archives of Occupational and Environmental Health, ISSN 0340-0131, E-ISSN 1432-1246, Vol. 81, no 2, p. 193-199Article in journal (Refereed)
    Abstract [en]

    OBJECTIVES: This study investigates possible acute effects on heart rate variability (HRV) when people are exposed to hand transmitted vibration and noise individually and simultaneously. METHODS: Ten male and 10 female subjects were recruited by advertisement. Subjects completed a questionnaire concerning their work environment, general health, medication, hearing, and physical activity level. The test started with the subject resting for 15 min while sitting down. After resting, they were exposed to one of four exposure conditions: (1) only vibration; (2) only noise; (3) both noise and vibration; or (4) a control condition of exposure to the static load only. All four exposures lasted 15 min and the resting time between the exposures was 30 min. A continuous electrocardiogram (ECG) signal was recorded and the following HRV parameters were calculated: total spectral power (P(TOT)); the spectral power of the very low frequency component (P(VLF)); the low frequency component (P(LF)); the high frequency component (P(HF)); and the ratio LF/HF. RESULTS: Exposure to only vibration resulted in a lower P(TOT) compared to static load, whereas exposure to only noise resulted in a higher P(TOT). The mean values of P(TOT), P(VLF), P(LF), and P(HF) were lowest during exposure to vibration and simultaneous exposure to vibration and noise. CONCLUSIONS: Exposure to vibration and/or noise acutely affects HRV compared to standing without these exposures. Being exposed to vibration only and being exposed to noise only seem to generate opposite effects. Compared to no exposure, P(TOT) was reduced during vibration exposure and increased during noise exposure.

  • 198.
    Björck, Fredrik
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Ek, Agnes
    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.
    Själander, Anders
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Warfarin persistence among atrial fibrillation patients – why is treatment ended?2016In: Cardiovascular Therapeutics, ISSN 1755-5914, Vol. 34, no 6, p. 468-474Article in journal (Refereed)
    Abstract [en]

    Background and Aim

    Warfarin treatment discontinuation is significant among patients with atrial fibrillation (AF). Studies mainly focused on whether the proportion of warfarin persistence and discontinuationare clinically appropriate are absent. This study evaluates warfarin persistence with focus on predictors for, and reasons to, warfarin discontinuation in AF patients.

    Methods

    From the national quality register AuriculA, all AF patients in Sundsvall, Sweden, on warfarin treatment on January first, 2010 were included. These 478 patients were followed until discontinuation or study-stop December 31, 2013. By going through each patient’s medical record risk factors for thromboembolism, bleeding and causes of discontinuation were obtained.

    Results

    Proportion of warfarin persistence was 0.91 (95% confidence interval (CI) 0.89 to 0.93) after one year and 0.73 (95% CI 0.69 to 0.77) after four years. Previous intracranial bleeding, excessive alcohol use, anemia and pulmonary or peripheral emboli were each associated with over two times higher risk of discontinuation (hazard ratio (HR) 5.66, CI 2.23-14.36, HR 2.54, CI 1.48-4.37, HR 2.40, CI 1.38-4.17, and HR 2.13, CI 1.02-4.46). Among patients discontinuing, 50.5% were due to questionable causes, such as sinus rhythm (33.9%), patients demand (10.1%) and falls (8.2%). The majority (43.1%) of treatment discontinuers were changed to aspirin, while 40.4% of them were left without medical stroke prophylaxis.

    Conclusions

    Although persistence to warfarin among AF patients proves higher than previously reported, there is room for improvement since half of the discontinuers have questionable reasons for treatment stop and the majority of them receive no other efficient stroke prophylaxis.

  • 199.
    Björck, Fredrik
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Renlund, Henrik
    Lip, Gregory Y. H.
    Wester, Per
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Svensson, Peter J.
    Själander, Anders
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Outcomes in a Warfarin-Treated Population With Atrial Fibrillation2016In: JAMA cardiology, ISSN 2380-6583, E-ISSN 2380-6591, Vol. 1, no 2, p. 172-180Article in journal (Refereed)
    Abstract [en]

    IMPORTANCE: Vitamin K antagonist (eg, warfarin) use is nowadays challenged by the non-vitamin K antagonist oral anticoagulants (NOACs) for stroke prevention in atrial fibrillation (AF). NOAC studies were based on comparisons with warfarin arms with times in therapeutic range (TTRs) of 55.2% to 64.9%, making the results less credible in health care systems with higher TTRs.

    OBJECTIVES: To evaluate the efficacy and safety of well-managed warfarin therapy in patients with nonvalvular AF, the risk of complications, especially intracranial bleeding, in patients with concomitant use of aspirin, and the impact of international normalized ratio (INR) control.

    DESIGN, SETTING, AND PARTICIPANTS: A retrospective, multicenter cohort study based on Swedish registries, especially AuriculA, a quality register for AF and oral anticoagulation, was conducted. The register contains nationwide data, including that from specialized anticoagulation clinics and primary health care centers. A total of 40 449 patients starting warfarin therapy owing to nonvalvular AF during the study period were monitored until treatment cessation, death, or the end of the study. The study was conducted from January 1, 2006, to December 31, 2011, and data were analyzed between February 1 and November 15, 2015. Associating complications with risk factors and individual INR control, we evaluated the efficacy and safety of warfarin treatment in patients with concomitant aspirin therapy and those with no additional antiplatelet medications.

    EXPOSURES: Use of warfarin with and without concomitant therapy with aspirin.

    MAIN OUTCOMES AND MEASURES: Annual incidence of complications in association with individual TTR (iTTR), INR variability, and aspirin use and identification of factors indicating the probability of intracranial bleeding.

    RESULTS: Of the 40 449 patients included in the study, 16 201 (40.0%) were women; mean (SD) age of the cohort was 72.5 (10.1) years, and the mean CHA2DS2-VASc (cardiac failure or dysfunction, hypertension, age ≥75 years [doubled], diabetes mellitus, stroke [doubled]-vascular disease, age 65-74 years, and sex category [female]) score was 3.3 at baseline. The annual incidence, reported as percentage (95% CI) of all-cause mortality was 2.19% (2.07-2.31) and, for intracranial bleeding, 0.44% (0.39-0.49). Patients receiving concomitant aspirin had annual rates of any major bleeding of 3.07% (2.70-3.44) and thromboembolism of 4.90% (4.43-5.37), and those with renal failure were at higher risk of intracranial bleeding (hazard ratio, 2.25; 95% CI, 1.32-3.82). Annual rates of any major bleeding and any thromboembolism in iTTR less than 70% were 3.81% (3.51-4.11) and 4.41% (4.09-4.73), respectively, and, in high INR variability, were 3.04% (2.85-3.24) and 3.48% (3.27-3.69), respectively. For patients with iTTR 70% or greater, the level of INR variability did not alter event rates.

    CONCLUSIONS AND RELEVANCE: Well-managed warfarin therapy is associated with a low risk of complications and is still a valid alternative for prophylaxis of AF-associated stroke. Therapy should be closely monitored for patients with renal failure, concomitant aspirin use, and poor INR control.

  • 200.
    Björck, Fredrik
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Renlund, Henrik
    Svensson, Peter J
    Själander, Anders
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Warfarin persistence among stroke patients with atrial fibrillation2015In: Thrombosis Research, ISSN 0049-3848, E-ISSN 1879-2472, Vol. 136, no 4, p. 744-748Article in journal (Refereed)
    Abstract [en]

    INTRODUCTION: Warfarin treatment discontinuation is significant among patients with atrial fibrillation (AF). For AF patients with stroke a warfarin persistence rate of 0.45 after 2years has previously been reported. No consistent predictors for discontinuation have been established.

    AIMS: Evaluation of warfarin persistence and variables associated with discontinuation, in a large Swedish cohort with unselected stroke/TIA patients with AF treated with warfarin.

    MATERIALS AND METHODS: 4 583 patients with stroke/TIA and AF in the Swedish National Patient Register (NPR), from 1. Jan 2006 to 31. Dec 2011, were matched with the Swedish national quality register AuriculA. They were followed until treatment cessation, death or end of study. Baseline characteristics and CHA2DS2VASc score were retrieved from NPR. Treatment-time was retrieved from AuriculA.

    RESULTS: Overall proportion of warfarin persistence was 0.78 (95% confidence interval (CI) 0.76 to 0.80) after one year, 0.69 (95% CI 0.67 to 0.71) after 2years and 0.47 (95% CI 0.43 to 0.51) after 5years. Variables clearly associated with higher discontinuation were dementia (hazard ratio (HR) 2.22, CI 1.51-3.27) and alcohol abuse (HR 1.66, CI 1.19-2.33). Chronic obstructive pulmonary disease (COPD), cancer and chronic heart failure (CHF) were each associated with over 20% increased risk of treatment discontinuation. Higher CHA2DS2VASc score and start-age lead to lower persistence (p<0.001).

    CONCLUSIONS: Persistence to warfarin in unselected stroke/TIA patients with AF is in Sweden greater than previously reported. Lower persistence is found among patients with high treatment start-age, incidence of dementia, alcohol abuse, cancer, CHF, COPD and/or high CHA2DS2VASc score.

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