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  • 1. Afshin, A
    et al.
    Forouzanfar, M. H
    Reitsma, M. B
    Sur, P
    Estep, K
    Lee, A
    Marczak, L
    Mokdad, A. H
    Ärnlöv, Johan
    Dalarna University, School of Education, Health and Social Studies, Medical Science. Uppsala universitet.
    Murray, C. J. L
    Health effects of overweight and obesity in 195 countries over 25 years2017In: New England Journal of Medicine, ISSN 0028-4793, E-ISSN 1533-4406, Vol. 377, no 1, 13-27 p.Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Although the rising pandemic of obesity has received major attention in many countries, the effects of this attention on trends and the disease burden of obesity remain uncertain.

    METHODS: We analyzed data from 68.5 million persons to assess the trends in the prevalence of overweight and obesity among children and adults between 1980 and 2015. Using the Global Burden of Disease study data and methods, we also quantified the burden of disease related to high body-mass index (BMI), according to age, sex, cause, and BMI in 195 countries between 1990 and 2015.

    RESULTS: In 2015, a total of 107.7 million children and 603.7 million adults were obese. Since 1980, the prevalence of obesity has doubled in more than 70 countries and has continuously increased in most other countries. Although the prevalence of obesity among children has been lower than that among adults, the rate of increase in childhood obesity in many countries has been greater than the rate of increase in adult obesity. High BMI accounted for 4.0 million deaths globally, nearly 40% of which occurred in persons who were not obese. More than two thirds of deaths related to high BMI were due to cardiovascular disease. The disease burden related to high BMI has increased since 1990; however, the rate of this increase has been attenuated owing to decreases in underlying rates of death from cardiovascular disease.

    CONCLUSIONS: The rapid increase in the prevalence and disease burden of elevated BMI highlights the need for continued focus on surveillance of BMI and identification, implementation, and evaluation of evidence-based interventions to address this problem.

  • 2. Ahlm, Kristin
    et al.
    Lindqvist, Per
    Dalarna University, School of Education, Health and Social Studies, Medical Science. Karolinska institutet.
    Saveman, Britt-Inger
    Björnstig, Ulf
    Suicidal drowning deaths in northern Sweden 1992-2009: The role of mental disorder and intoxication2015In: Journal of Forensic and Legal Medicine, ISSN 1752-928X, E-ISSN 1878-7487, Vol. 34, 168-172 p.Article in journal (Refereed)
    Abstract [en]

    Suicides by drowning have received limited attention by researchers. A recent finding that almost one-third of all drowning deaths in Sweden were classified as suicide instigated this study. We identified 129 cases of suicide by drowning in Northern Sweden and analyzed the circumstances and the psychiatric history prior to the suicide. Information was obtained from autopsy, police and medical records, as well as from the National Inpatient Register. One-third of the suicide victims had previously attempted suicide and half of the victims had been hospitalized due to mental health problems. One-third of these had left the hospital less than one week before the suicide. Alcohol and psychoactive drugs were present in 16% and 62% of the cases, respectively. A history of mental disorder and previous suicide attempt (s), especially by drowning, is an ominous combination necessitating efficient clinical identification, treatment and follow-up if a complete suicide is to be prevented.

  • 3.
    Andersen, Kasper
    et al.
    Uppsala University, Uppsala, Sweden.
    Lind, Lars
    Uppsala University, Uppsala, Sweden.
    Ingelsson, Erik
    Uppsala University, Uppsala, Sweden.
    Ärnlöv, Johan
    Dalarna University, School of Education, Health and Social Studies, Medical Science. Uppsala University, Uppsala, Sweden.
    Byberg, Liisa
    Uppsala University, Uppsala, Sweden.
    Michaëlsson, Karl
    Uppsala University, Uppsala, Sweden.
    Sundström, Johan
    Uppsala University, Uppsala, Sweden.
    Skeletal muscle morphology and risk of cardiovascular disease in elderly men2015In: European Journal of Preventive Cardiology, ISSN 2047-4873, E-ISSN 2047-4881, Vol. 22, no 2, 231-239 p.Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: While it is well known that physical inactivity is a major risk factor for cardiovascular disease, there is still a search for the mechanisms by which exercise exerts its positive effect. Skeletal muscle fibre type can be affected to some extent by exercise, and different fibre types possess different anti-inflammatory and glucometabolic properties that may influence cardiovascular disease risk.

    DESIGN: Population-based cohort study.

    METHODS: We investigated relations of skeletal muscle morphology to risk of cardiovascular events in a sample of 466 71-year-old men without cardiovascular disease, of which 295 were physically active (strenuous physical activity at least 3 h/week).

    RESULTS: During a median of 13.1 years of follow up, 173 major cardiovascular events occurred. Among physically active men, 10% higher proportion of type-I (slow-twitch oxidative) fibres was associated with a hazard ratio (HR) of 0.84 (95% confidence interval 0.74-0.95) for cardiovascular events, and 10% higher proportion of type-IIx (fast-twitch glycolytic) fibres was associated with a HR of 1.24 (1.06-1.45), adjusting for age. Similar results were observed in several sets of multivariable-adjusted models. No association of muscle fibre type with risk of cardiovascular events was observed among physically inactive men.

    CONCLUSIONS: Higher skeletal muscle proportion of type-I fibres was associated with lower risk of cardiovascular events and a higher proportion of type-IIx fibres was associated with higher risk of cardiovascular events. These relations were only observed in physically active men. Skeletal muscle fibre composition may be a mediator of the protective effects of exercise against cardiovascular disease.

  • 4. Arefalk, Gabriel
    et al.
    Hergens, Maria-Pia
    Ingelsson, Erik
    Ärnlöv, Johan
    Dalarna University, School of Education, Health and Social Studies, Medical Science.
    Michaëlsson, Karl
    Lind, Lars
    Ye, Weimin
    Nyrén, Olof
    Lambe, Mats
    Sundström, Johan
    Smokeless tobacco (snus) and risk of heart failure: results from two Swedish cohorts2012In: European Journal of Cardiovascular Prevention & Rehabilitation, ISSN 1741-8267, E-ISSN 1741-8275, Vol. 19, no 5, 1120-1127 p.Article in journal (Refereed)
    Abstract [en]

    Background: Oral moist snuff (snus) is discussed as a safer alternative to smoking, and its use is increasing. Based on its documented effect on blood pressure, we hypothesized that use of snus increases the risk of heart failure.

    Design: Two independent Swedish prospective cohorts; the Uppsala Longitudinal Study of Adult Men (ULSAM), a community-based sample of 1076 elderly men, and the Construction Workers Cohort (CWC), a sample of 118,425 never-smoking male construction workers. Methods: Cox proportional hazards models were used to investigate possible associations of snus use with risk of a first hospitalization for heart failure.

    Results: In ULSAM, 95 men were hospitalized for heart failure, during a median follow up of 8.9 years. In a model adjusted for established risk factors including past and present smoking exposure, current snus use was associated with a higher risk of heart failure [hazard ratio (HR) 2.08, 95% confidence interval (CI) 1.03-4.22] relative to non-use. Snus use was particularly associated with risk of non-ischaemic heart failure (HR 2.55, 95% CI 1.12-5.82). In CWC, 545 men were hospitalized for heart failure, during a median follow up of 18 years. In multivariable-adjusted models, current snus use was moderately associated with a higher risk of heart failure (HR 1.28, 95% CI 1.00-1.64) and non-ischaemic heart failure (HR 1.28, 95% CI 0.97-1.68) relative to never tobacco use.

    Conclusion: Data from two independent cohorts suggest that use of snus may be associated with a higher risk of heart failure.

  • 5. Arefalk, Gabriel
    et al.
    Hergens, Maria-Pia
    Ingelsson, Erik
    Ärnlöv, Johan
    Dalarna University, School of Education, Health and Social Studies, Medical Science.
    Michaëlsson, Karl
    Lind, Lars
    Ye, Weimin
    Nyrén, Olof
    Lambe, Mats
    Sundström, Johan
    Smokeless tobacco (snus) and risk of heart failure: results from two Swedish cohorts2010In: Journal of Hypertension, ISSN 0263-6352, E-ISSN 1473-5598, Vol. 28, no suppl.A, E48-E49 p.Article in journal (Refereed)
  • 6. Arking, Dan E
    et al.
    Pulit, Sara L
    Crotti, Lia
    van der Harst, Pim
    Munroe, Patricia B
    Koopmann, Tamara T
    Sotoodehnia, Nona
    Rossin, Elizabeth J
    Ärnlöv, Johan
    Dalarna University, School of Education, Health and Social Studies, Medical Science. Uppsala universitet.
    Newton-Cheh, Christopher
    Genetic association study of QT interval highlights role for calcium signaling pathways in myocardial repolarization2014In: Nature Genetics, ISSN 1061-4036, E-ISSN 1546-1718, Vol. 46, no 8, 826-836 p.Article in journal (Refereed)
    Abstract [en]

    The QT interval, an electrocardiographic measure reflecting myocardial repolarization, is a heritable trait. QT prolongation is a risk factor for ventricular arrhythmias and sudden cardiac death (SCD) and could indicate the presence of the potentially lethal mendelian long-QT syndrome (LQTS). Using a genome-wide association and replication study in up to 100,000 individuals, we identified 35 common variant loci associated with QT interval that collectively explain similar to 8-10% of QT-interval variation and highlight the importance of calcium regulation in myocardial repolarization. Rare variant analysis of 6 new QT interval-associated loci in 298 unrelated probands with LQTS identified coding variants not found in controls but of uncertain causality and therefore requiring validation. Several newly identified loci encode proteins that physically interact with other recognized repolarization proteins. Our integration of common variant association, expression and orthogonal protein-protein interaction screens provides new insights into cardiac electrophysiology and identifies new candidate genes for ventricular arrhythmias, LQTS and SCD.

  • 7.
    Balaile, Gunnel
    Dalarna University, School of Health and Social Studies, Medical Science.
    The Meaning of Health and Sexuality as experienced by Tanzanian Men and Women living with HIV/AIDS2007Licentiate thesis, monograph (Other academic)
    Abstract [en]

    Background: Sub-Saharan Africa has for more than two decades been hit by Human immunodeficiency virus/ Acquired immune-deficiency Syndrome, HIV/AIDS pandemic with a few signs of decline. In Tanzania, the prevalence of HIV is estimated to 7 percent and about 1.8 million Tanzanians are living with HIV. Women are the hardest hit and most vulnerable are young women 15-24 years old, who are three times more likely to be infected than young men in the same age group and the prevalence is higher in urban than in rural areas. Aim: The overall aim of this thesis was to explore the meaning of health and sexuality among men and women living with HIV/AIDS. Methods: Two studies were conducted in Tanzania, Dar es Salaam during January and February in year 2004 (I, II). Twenty participants were recruited (10 men and 10 women) by the help from health staff and sampled purposely in order to get an equal variety of age, education, religion, sex, and marital status. The interviews took place at one district hospital, and at two different clinics run by Non Governmental Organizations (NGO) one located in a business area in central town, the other NGO clinic outside town in an industrial area. The interviews were transcribed and translated into English. A phenomenological – hermeneutic approach and in-depth interviews were used to collect data. The text was ana¬lysed following Ricoeur’s interpretation theory for text. Findings: The thesis presents aspects of men’s and women’s experiences of living with HIV/AIDS. Adjustment to living with the virus was different between men and women. Men often conceived a growing suspicion that they might be in¬fected by HIV, while women had to be asked by relatives or had to wait for others to be tested. The overwhelming fear of being tested was related to the fear of being stigmatized. Under¬standing the meaning of health and sexuality when living with HIV/AIDS, was for the men living life with a preserved sense of integrity and self-esteem, this meant not to be seen as victims. To the women, however, the reality was it meant being cast into poverty and created devastation of intimate relations. Men had learnt to perform safe sex and had chosen to live with one partner/wife giving them an opportunity to develop new aspects of their intimate life. Conversely, the women felt miserable and had not accepted their diagnosis in the same way. They lacked resources to maintain health and the ability to support their children. The women who lived in a single household had abandoned sex life, their worries and deep concerns were for their children who brought meaning and joy in their lives. Conclusion: For both men and women the meaning of health and sexuality had changed after knowing their sero-status. The men had accepted to live with an altered health and treated symptoms early. The were able to handle feelings, they felt optimistic and strived to live a normal life as possible health had for the women lost meaning in that sense it was not possible to maintain. The men viewed their sex life still important, and tried to be able live a normal life. The women had accepted a life there sexuality had no place. To prevent further HIV infection meant to be educated and fully understand how to prevent the spread of HIV, to act in a responsible way, to be faithful, and/or to accept abstinence. This new way of living meant to be a caring man or woman. The use of condoms had not been completely accepted as the knowledge on how to use the condoms properly was not entirely accomplished. Support from counselors and peers were proved invaluable adjust to a life of living with HIV/AIDS.

  • 8.
    Balaile, Gunnel
    et al.
    Dalarna University, School of Education, Health and Social Studies, Medical Science.
    Laisser, Rose
    Ransjö-Arvidson, Anna-Berit
    Höjer, Bengt
    Poverty and devastation of intimate relations: Tanzanian women's experience of living with HIV/AIDS2007In: Journal of the Association of Nurses in AIDS Care, ISSN 1055-3290, E-ISSN 1552-6917, Vol. 18, no 5, 6-16 p.Article in journal (Refereed)
    Abstract [en]

    In Tanzania, women of reproductive age constitute the largest group infected by HIV. This study aimed to explore the lived experiences related to health and sexuality of Tanzanian women who had known their positive serostatus for I year. In-depth interviews with 10 women were analyzed using a phenomeno-logical-hermeneutic approach and showed frustration and despair at not having resources to maintain daily life. The women needed regular medical treatment for themselves and for their HIV-positive children. Their sexual desires had declined or vanished, and they had come to view sexuality as a source of transmittable disease. For some women, casual sex was an option to solve urgent financial needs. Happiness was something for their children, not for them. Access to social support from the women's community would help prevent further HIV transmission and enhance survival so the children could grow up with at least one devoted parent.

  • 9. Bandak, Ghassan
    et al.
    Sang, Yingying
    Gasparini, Alessandro
    Chang, Alex R
    Ballew, Shoshana H
    Evans, Marie
    Ärnlöv, Johan
    Dalarna University, School of Education, Health and Social Studies, Medical Science. Uppsala universitet.
    Lund, Lars H
    Inker, Lesley A
    Grams, Morgan E
    Hyperkalemia after initiating renin-angiotensin system blockade: The Stockholm creatinine measurements (SCREAM) project2017In: Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease, ISSN 2047-9980, E-ISSN 2047-9980, Vol. 6, no 7, e005428Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Concerns about hyperkalemia limit the use of angiotensin-converting enzyme inhibitors (ACE-I) and angiotensin receptor blockers (ARBs), but guidelines conflict regarding potassium-monitoring protocols. We quantified hyperkalemia monitoring and risks after ACE-I/ARB initiation and developed and validated a hyperkalemia susceptibility score.

    METHODS AND RESULTS: We evaluated 69 426 new users of ACE-I/ARB therapy in the Stockholm Creatinine Measurements (SCREAM) project with medication initiation from January 1, 2007 to December 31, 2010, and follow-up for 1 year thereafter. Three fourths (76%) of SCREAM patients had potassium checked within the first year. Potassium >5 and >5.5 mmol/L occurred in 5.6% and 1.7%, respectively. As a comparison, we propensity-matched new ACE-I/ARB users to 20 186 new β-blocker users in SCREAM: 64% had potassium checked. The occurrence of elevated potassium levels was similar between new β-blocker and ACE-I/ARB users without kidney disease; only at estimated glomerular filtration rate <60 mL/min per 1.73 m(2) were risks higher among ACE-I/ARB users. We developed a hyperkalemia susceptibility score that incorporated estimated glomerular filtration rate, baseline potassium level, sex, diabetes mellitus, heart failure, and the concomitant use of potassium-sparing diuretics in new ACE-I/ARB users; this score accurately predicted 1-year hyperkalemia risk in the SCREAM cohort (area under the curve, 0.845, 95% CI: 0.840-0.869) and in a validation cohort from the US-based Geisinger Health System (N=19 524; area under the curve, 0.818, 95% CI: 0.794-0.841), with good calibration.

    CONCLUSIONS: Hyperkalemia within the first year of ACE-I/ARB therapy was relatively uncommon among people with estimated glomerular filtration rate >60 mL/min per 1.73 m(2), but rates were much higher with lower estimated glomerular filtration rate. Use of the hyperkalemia susceptibility score may help guide laboratory monitoring and prescribing strategies.

  • 10. Barber, Ryan M
    et al.
    Fullman, Nancy
    Sorensen, Reed J
    Bollyky, Thomas
    McKee, Martin
    Nolte, Ellen
    Abajobir, Amanuel Alemu
    Abete, Kalkidan Hassen
    Ärnlöv, Johan
    Dalarna University, School of Education, Health and Social Studies, Medical Science. Karolinska institutet.
    Murray, Christopher J L
    Healthcare Access and Quality Index based on mortality from causes amenable to personal health care in 195 countries and territories, 1990–2015: a novel analysis from the Global Burden of Disease Study 20152017In: The Lancet, ISSN 0140-6736, E-ISSN 1474-547X, Vol. 390, no 10091, 231-266 p.Article in journal (Refereed)
  • 11. Basu, S
    et al.
    Zethelius, B
    Helmersson, J
    Berne, C
    Larsson, A
    Ärnlöv, Johan
    Dalarna University, School of Education, Health and Social Studies, Medical Science.
    Cytokine-mediated inflammation is independently associated with insulin sensitivity measured by the euglycemic insulin clamp in a community-based cohort of elderly men2011In: International Journal of Clinical and Experimental Medicine, ISSN 1940-5901, Vol. 4, no 2, 164-168 p.Article in journal (Refereed)
    Abstract [en]

    Both clinical and experimental studies suggest a close relation between an inflammatory state and insulin resistance. We investigated the association between cytokine-mediated inflammation (high sensitivity C reactive protein [hsCRP] and interleukin [IL] 6) and insulin sensitivity (insulin-mediated glucose disposal rate, assessed by the euglycemic insulin clamp) in a community-based cohort, with subgroup analyses of normal weight individuals without diabetes mellitus and metabolic syndrome (NCEP). hsCRP and IL- 6 were inversely associated with insulin sensitivity (multivariable-adjusted regression coefficient for 1-SD increase of hsCRP -0.12 (-0.21-(-0.03), p=0.01) and of IL-6 - 0.11 (-0.21-(-0.02), p=0.01) in models adjusting for age and components of the metabolic syndrome (systolic and diastolic blood pressure, antihypertensive drugs, HDL-cholesterol, triglycerides, fasting plasma glucose, waist circumference). The multivariable-adjusted association between hsCRP, IL-6 and insulin sensitivity were of a similar magnitude in normal weight individuals without diabetes and without the metabolic syndrome. Our data show that cytokine -mediated subclinical inflammation is independently associated with decreased insulin sensitivity also in apparently metabolically healthy normal weight individuals, indicating that the interplay between inflammatory processes and insulin resistance is present already in the early stages of the development of glucometabolic disease. (IJCEM1012002).

  • 12.
    Bellardini, Helena
    et al.
    Dalarna University, School of Health and Social Studies, Sport and Health Science.
    Henriksson, Anders
    Dalarna University, School of Health and Social Studies, Sport and Health Science.
    Tonkonogi, Michail
    Dalarna University, School of Health and Social Studies, Medical Science.
    Bra och enkla fystester2013Book (Other academic)
  • 13.
    Bellardini, Helena
    et al.
    Dalarna University, School of Health and Social Studies, Medical Science.
    Henriksson, Anders
    Dalarna University, School of Health and Social Studies, Medical Science.
    Tonkonogi, Michail
    Dalarna University, School of Health and Social Studies, Medical Science.
    Tester och mätmetoder för idrott och hälsa2009Book (Other academic)
  • 14.
    Bellardini, Helena
    et al.
    Dalarna University, School of Health and Social Studies, Medical Science.
    Knutsson, Magnus
    Dalarna University, School of Health and Social Studies, Medical Science.
    Tonkonogi, Michail
    Dalarna University, School of Health and Social Studies, Medical Science.
    Inverkan av olika farthållningsstrategier på prestationsförmåga vid kortvarigt maximalt fysiskt arbete.2006In: Svensk Idrottsforskning: Organ för Centrum för Idrottsforskning, ISSN 1103-4629, no 2, 20-26 p.Article in journal (Other academic)
  • 15.
    Bellardini, Helena
    et al.
    Dalarna University, School of Health and Social Studies, Sport and Health Science.
    Tonkonogi, Michail
    Dalarna University, School of Health and Social Studies, Medical Science.
    Senior Power - Styrketräning för äldre2013 (ed. 1)Book (Other academic)
  • 16.
    Bengtsson, Anette
    et al.
    Dalarna University, School of Health and Social Studies, Medical Science.
    Lyckström, Marie
    Dalarna University, School of Health and Social Studies, Medical Science.
    Anhörigvårdarnas upplevelser i hemmet vid livets slutskede, med hjälp av palliativa teamet2008Independent thesis Basic level (degree of Bachelor)Student thesis
    Abstract [sv]

    Idag ökar den palliativa omvårdnaden i hemmet. För att den sjuke ofta har en önskan om att få dö hemma. Det ställer krav på anhörigvårdarna som är dem som kommer att bli dem primära vårdarna. Syftet med studien var att undersöka anhörigvårdarnas upplevelser av att vårda hemma, i livets slutskede, med hjälp av det palliativa teamet. Studien genomfördes som en systematisk litteraturstudie. Genom litteraturstudien fick man fram de positiva och negativa upplevelserna från anhörigvårdarna som vårdat den sjuke i hemmet. Studien visade att anhörigvårdarna skulle välja att vårda den sjuke i hemmet igen med hjälp av det palliativa teamet. Detta trots att flera negativa upplevelser kom fram. Anhörigvårdarna ville vara mer delaktiga i omvårdnadsarbetet och detta gjorde att anhörigvårdarna upplevde en större tillfredställelse av själv, genom att kunna ge något tillbaka till den sjuke. Anhörigvårdarna önskade mer stöd från vårdpersonalen eftersom de ansåg sig ha bristande kompetens om medicinteknik, kroppens hälsa, sjukdomen, dess symptom, behandling, och prognos etc.

  • 17.
    Bergqvist, Yngve
    et al.
    Dalarna University, School of Education, Health and Social Studies, Medical Science.
    Bergquist, Jonas
    In memory of Niklas Lindegardh2012In: Bioanalysis, ISSN 1757-6180, E-ISSN 1757-6199, Vol. 4, no 6, 751-751 p.Article in journal (Refereed)
  • 18. Bergström, Aileen L
    et al.
    Guidetti, Susanne
    Tistad, Malin
    Dalarna University, School of Education, Health and Social Studies, Medical Science.
    Tham, Kerstin
    von Koch, Lena
    Eriksson, Gunilla
    Perceived occupational gaps one year after stroke: An explorative study2011In: Journal of Rehabilitation Medicine, ISSN 1651-2081, Vol. 44, no 1, 36-42 p.Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: To explore and describe factors associated with occupational gaps and to identify factors at 3 months that predict occupational gaps one year post-stroke. A gap, a restriction in participation, is considered to be present when there is a discrepancy between what the individual wants to do and what they actually do in everyday life. DESIGN: Prospective longitudinal study. SUBJECTS: Two hundred persons with stroke. METHODS: Data from the Occupational Gaps Questionnaire, one year post-stroke, was used as the dependent variable in 3- and 12-month regression analyses. Domains of the Stroke Impact Scale, global life satisfaction, demographic and medical factors were used as independent variables. RESULTS: At 3 months, activities of daily living abilities, social participation and not being born in Sweden predicted occupational gaps at 12 months. Stroke severity and not being born in Sweden and 3 factors at 12 months: social participation, self-rated recovery, and global life satisfaction were associated with occupational gaps. CONCLUSION: Activities of daily living ability at 3 months predicted occupational gaps after stroke. Thus, it is possible to identify early on, and provide interventions for, those that risk participation restrictions. Not being born in the country might be an indicator of a risk for participation restrictions.

  • 19.
    Blessborn, Daniel
    et al.
    Dalarna University, School of Technology and Business Studies, Chemical Engineering.
    Römsing, Susanne
    Dalarna University, School of Education, Health and Social Studies, Chemistry.
    Bergqvist, Yngve
    Dalarna University, School of Education, Health and Social Studies, Medical Science.
    Lindegardh, Niklas
    Assay for screening for six antimalarial drugs and one metabolite using dried blood spot sampling, sequential extraction and ion-trap detection2010In: Bioanalysis, ISSN 1757-6180, E-ISSN 1757-6199, Vol. 2, no 11, 1839-1847 p.Article in journal (Refereed)
    Abstract [en]

    Background: More parasites are becoming resistant to antimalarial drugs, and in many areas a change in first-line drug treatment is necessary. The aim of the developed assay is to help determine drug use in these areas and also to be a complement to interviewing patients, which will increase reliability of surveys.

    Results: This assay detects quinine, mefloquine, sulfadoxine, pyrimethamine, lumefantrine, chloroquine and its metabolite desethylchloroquine in a 100-mu l dried blood spot. Most of the drugs also have long half-lives that make them detectable at least 7 days after administration. The drugs are extracted from the dried blood spot with sequential extraction (due to the big differences in physicochemical properties), solid-phase extraction is used as sample clean-up and separation is performed with gradient-LC with MS ion-trap detection.

    Conclusion: Detection limits (S/N > 5:1) at 50 ng/ml or better were achieved for all drugs except lumefantrine (200 ng/ml), and thus can be used to determine patient compliance. A major advantage of using the ion-trap MS it that it will be possible to go back into the data and look for other drugs as needed.

  • 20. Blomberg, Jonas
    et al.
    Blomberg, Fredrik
    Sjösten, Anna
    Sheikholvaezin, Ali
    Bolin-Wiener, Agnes
    Elfaitouri, Amal
    Hessel, Sanna
    Gottfries, Carl-Gerhard
    Zachrisson, Olof
    Ohrmalm, Christina
    Jobs, Magnus
    Dalarna University, School of Education, Health and Social Studies, Medical Science.
    Pipkorn, Ruediger
    No evidence for xenotropic murine leukemia-related virus infection in Sweden using internally controlled multiepitope suspension array serology2012In: Clinical and Laboratory Immunology, ISSN 1556-6811, E-ISSN 1556-679X, Vol. 19, no 9, 1399-1410 p.Article in journal (Refereed)
    Abstract [en]

    Many syndromes have a large number of differential diagnoses, a situation which calls for multiplex diagnostic systems. Myalgic encephalomyelitis (ME), also named chronic fatigue syndrome (CFS), is a common disease of unknown etiology. A mouse retrovirus, xenotropic murine leukemia-related virus (XMRV), was found in ME/CFS patients and blood donors, but this was not corroborated. However, the paucity of serological investigations on XMRV in humans prompted us to develop a serological assay which cover many aspects of XMRV antigenicity. It is a novel suspension array method, using a multiplex IgG assay with nine recombinant proteins from the env and gag genes of XMRV and 38 peptides based on known epitopes of vertebrate gamma-retroviruses. IgG antibodies were sought in 520 blood donors and 85 ME/CFS patients and in positive-and negative-control sera from animals. We found no differences in seroreactivity between blood donors and ME/CFS patients for any of the antigens. This did not support an association between ME/CFS and XMRV infection. The multiplex serological system had several advantages: (i) biotinylated protein G allowed us to run both human and animal sera, which is essential because of a lack of XMRV-positive humans; (ii) a novel quality control was a pan-peptide positive-control rabbit serum; and (iii) synthetic XMRV Gag peptides with degenerate positions covering most of the variation of murine leukemia-like viruses did not give higher background than nondegenerate analogs. The principle may be used for creation of variant tolerant peptide serologies. Thus, our system allows rational large-scale serological assays with built-in quality control.

  • 21.
    Brorsson, Sofia
    et al.
    Dalarna University, School of Education, Health and Social Studies, Sport and Health Science.
    Carlsson, Tomas
    Dalarna University, School of Education, Health and Social Studies, Medical Science.
    Carlsson, Magnus
    Dalarna University, School of Education, Health and Social Studies, Medical Science.
    A new electronic grip force measurement device for hand evaluation2013In: Abstracts of the Annual European Congress of Rheumatology EULAR. June 12-15, 2013. Madrid, Spain, 2013Conference paper (Refereed)
    Abstract [en]

    Background: Hand grip force is a good indicator of general muscle strength and can also be used to predict multiple outcomes such as changes in activities of daily living (ADL), disability, mortality and general upper extremity strength. Hand grip force is often measured as the amount of static grip force a subject can produce when measured with a hydraulic dynamometer such as the Jamar or with an electronic device such as the Grippit. The Grippit device measures an average grip force, a peak grip force and force over a set time period. Grippit has shown good reliability for healthy subjects. Grippit, which was developed over 20 years ago in Gothenburg, Sweden is no longer manufactured. Therefore, the need for anewly developed and modernized measurement instrument for use in evaluating hand rehabilitation has arisen.

    Objectives: The aim of this study was to evaluate the test-retest reliability of the newly developed instrument GRIP-it and to describe and validate the relationship between grip force measurements from GRIP-it and the original Grippit device.

    Methods: Healthy controls (n=43) were included in the study. Two devices were used to evaluate grip force (Newton, N), (i) GRIP-it a newly developed device and (ii) Grippit. Both instruments were used to measure mean and maximal force over 10 seconds.

    Results: GRIP-it displayed a mean measurement error of -1.7 ± 0.5% and the corresponding error for Grippit was -1.6 ± 1.9%. All subjects completed the grip force tests and the results for three attempts for each hand. The test-retest reliability was excellent for both pieces of equipment, with ICCs ranging from 0.963 to 0.947 (CI 95% between 0.103 and 0.041) for GRIP-it and from 0.979 to 0.968 (CI 95% between 0.087 and 0.042) for Grippit.

    Relationships between Grippit and GRIP-it

    There was a significant difference between the measured values derived from Grippit and GRIP-it for both the dominant hand (P < 0.001) and the non-dominant hand (P < 0.01). Grippit gives in general a higher grip force measurement than GRIP-it which is also indicated by the slope (β1) of the regression lines that deviates from 1. However, there were no substantial differences in the grip force when comparing the measurements for the dominant hand with the non-dominant hand for either Grippit (P = 0.071) or GRIP-it (P = 0.404). Based on these non-significant differences between hands and the fact that the model estimates for the intercept (β0) and the slope (β1) are contained within the confidence intervals of the model estimates for the opposite hand, a combined model was derived. The linear regression analysis, with grip force measurements for both hands included, gives: GRIP-it = 49.0 + 0.779 · Grippit. This explains 89.6% of the variance in grip force analyzed by GRIP-it (P < 0.001) see Figure 2. To enable an estimation of grip force measured by Grippit based on GRIP-it values a regression analysis with Grippit as dependent variable gives: Grippit = -18.1 + 1.15 · GRIP-it, which explains 89.6% of the variance in grip force analyzed by Grippit (P < 0.001).

    Conclusions: This study showed that GRIP-it has excellent test-retest reliability. Measurements of grip force with GRIP-it are strongly related to those from the original Grippit. The newly developed GRIP-it shows great potential for use in the assessment of hand function and the evaluation of hand rehabilitation.

  • 22. Brück, Katharina
    et al.
    Jager, Kitty J
    Dounousi, Evangelia
    Kainz, Alexander
    Nitsch, Dorothea
    Ärnlöv, Johan
    Dalarna University, School of Education, Health and Social Studies, Medical Science. Uppsala university.
    Rothenbacher, Dietrich
    Browne, Gemma
    Capuano, Vincenzo
    Ferraro, Pietro Manuel
    Methodology used in studies reporting chronic kidney disease prevalence: a systematic literature review2015In: Nephrology, Dialysis and Transplantation, ISSN 0931-0509, E-ISSN 1460-2385, Vol. 30, no Supp. 4, iv6-iv16 p.Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Many publications report the prevalence of chronic kidney disease (CKD) in the general population. Comparisons across studies are hampered as CKD prevalence estimations are influenced by study population characteristics and laboratory methods.

    METHODS: For this systematic review, two researchers independently searched PubMed, MEDLINE and EMBASE to identify all original research articles that were published between 1 January 2003 and 1 November 2014 reporting the prevalence of CKD in the European adult general population. Data on study methodology and reporting of CKD prevalence results were independently extracted by two researchers.

    RESULTS: We identified 82 eligible publications and included 48 publications of individual studies for the data extraction. There was considerable variation in population sample selection. The majority of studies did not report the sampling frame used, and the response ranged from 10 to 87%. With regard to the assessment of kidney function, 67% used a Jaffe assay, whereas 13% used the enzymatic assay for creatinine determination. Isotope dilution mass spectrometry calibration was used in 29%. The CKD-EPI (52%) and MDRD (75%) equations were most often used to estimate glomerular filtration rate (GFR). CKD was defined as estimated GFR (eGFR) <60 mL/min/1.73 m(2) in 92% of studies. Urinary markers of CKD were assessed in 60% of the studies. CKD prevalence was reported by sex and age strata in 54 and 50% of the studies, respectively. In publications with a primary objective of reporting CKD prevalence, 39% reported a 95% confidence interval.

    CONCLUSIONS: The findings from this systematic review showed considerable variation in methods for sampling the general population and assessment of kidney function across studies reporting CKD prevalence. These results are utilized to provide recommendations to help optimize both the design and the reporting of future CKD prevalence studies, which will enhance comparability of study results.

  • 23. Brück, Katharina
    et al.
    Stel, Vianda S
    Gambaro, Giovanni
    Hallan, Stein
    Völzke, Henry
    Ärnlöv, Johan
    Dalarna University, School of Education, Health and Social Studies, Medical Science. Uppsala universitet.
    Kastarinen, Mika
    Guessous, Idris
    Vinhas, José
    Stengel, Bénédicte
    CKD prevalence varies across the European general population2016In: Journal of the American Society of Nephrology, ISSN 1046-6673, E-ISSN 1533-3450, Vol. 27, no 7, 2135-2147 p.Article in journal (Refereed)
    Abstract [en]

    CKD prevalence estimation is central to CKD management and prevention planning at the population level. This study estimated CKD prevalence in the European adult general population and investigated international variation in CKD prevalence by age, sex, and presence of diabetes, hypertension, and obesity. We collected data from 19 general-population studies from 13 European countries. CKD stages 1-5 was defined as eGFR<60 ml/min per 1.73 m(2), as calculated by the CKD-Epidemiology Collaboration equation, or albuminuria >30 mg/g, and CKD stages 3-5 was defined as eGFR<60 ml/min per 1.73 m(2). CKD prevalence was age- and sex-standardized to the population of the 27 Member States of the European Union (EU27). We found considerable differences in both CKD stages 1-5 and CKD stages 3-5 prevalence across European study populations. The adjusted CKD stages 1-5 prevalence varied between 3.31% (95% confidence interval [95% CI], 3.30% to 3.33%) in Norway and 17.3% (95% CI, 16.5% to 18.1%) in northeast Germany. The adjusted CKD stages 3-5 prevalence varied between 1.0% (95% CI, 0.7% to 1.3%) in central Italy and 5.9% (95% CI, 5.2% to 6.6%) in northeast Germany. The variation in CKD prevalence stratified by diabetes, hypertension, and obesity status followed the same pattern as the overall prevalence. In conclusion, this large-scale attempt to carefully characterize CKD prevalence in Europe identified substantial variation in CKD prevalence that appears to be due to factors other than the prevalence of diabetes, hypertension, and obesity.

  • 24. Burgaz, A.
    et al.
    Byberg, L.
    Rautiainen, S.
    Orsini, N.
    Hakansson, N.
    Ärnlöv, Johan
    Dalarna University, School of Education, Health and Social Studies, Medical Science.
    Sundstrom, J.
    Lind, L.
    Melhus, H.
    Michaelsson, K.
    Wolk, A.
    Confirmed hypertension and plasma 25(OH)D concentrations amongst elderly men2011In: Journal of Internal Medicine, ISSN 0954-6820, E-ISSN 1365-2796, Vol. 269, no 2, 211-218 p.Article in journal (Refereed)
    Abstract [en]

    Objectives. The results of experimental studies suggest that vitamin D deficiency activates the renin-angiotensin system and predisposes to hypertension. Results of previous epidemiological studies investigating the association between 25-hydroxyvitamin D [25(OH)D] status and hypertension have not been consistent, perhaps because of their sole reliance on office blood pressure (BP) measurements leading to some misclassification of hypertension status. No previous studies have examined the association between 25(OH)D status and confirmed hypertension assessed with both office and 24-h BP measurements.

    Design. In this cross-sectional study, we investigated 833 Caucasian men, aged 71 +/- 0.6 years, to determine the association between plasma 25(OH)D concentrations, measured with high-pressure liquid chromatography mass spectrometry, and the prevalence of hypertension. We used both supine office and 24-h BP measurements for classifying participants as normotensive or confirmed hypertensive; participants with inconsistent classifications were excluded.

    Results. In a multivariable adjusted logistic regression model, men with 25(OH)D concentrations < 37.5 nmol L-1 had a 3-fold higher prevalence of confirmed hypertension compared to those with >= 37.5 nmol L-1 25(OH)D (odds ratio = 3.3, 95% CI: 1.0-11.0).

    Conclusions. Our results show that low plasma 25(OH)D concentration is associated with a higher prevalence of confirmed hypertension.

  • 25. Böger, Carsten A
    et al.
    Chen, Ming-Huei
    Tin, Adrienne
    Olden, Matthias
    Köttgen, Anna
    de Boer, Ian H
    Fuchsberger, Christian
    O'Seaghdha, Conall M
    Ärnlöv, Johan
    Dalarna University, School of Education, Health and Social Studies, Medical Science. Uppsala universitet.
    Kao, W. H. L
    CUBN is a gene locus for albuminuria2011In: Journal of the American Society of Nephrology, ISSN 1046-6673, E-ISSN 1533-3450, Vol. 22, no 3, 555-70 p.Article in journal (Refereed)
    Abstract [en]

    Identification of genetic risk factors for albuminuria may alter strategies for early prevention of CKD progression, particularly among patients with diabetes. Little is known about the influence of common genetic variants on albuminuria in both general and diabetic populations. We performed a meta-analysis of data from 63,153 individuals of European ancestry with genotype information from genome-wide association studies (CKDGen Consortium) and from a large candidate gene study (CARe Consortium) to identify susceptibility loci for the quantitative trait urinary albumin-to-creatinine ratio (UACR) and the clinical diagnosis microalbuminuria. We identified an association between a missense variant (I2984V) in the CUBN gene, which encodes cubilin, and both UACR (P = 1.1 × 10−11) and microalbuminuria (P = 0.001). We observed similar associations among 6981 African Americans in the CARe Consortium. The associations between this variant and both UACR and microalbuminuria were significant in individuals of European ancestry regardless of diabetes status. Finally, this variant associated with a 41% increased risk for the development of persistent microalbuminuria during 20 years of follow-up among 1304 participants with type 1 diabetes in the prospective DCCT/EDIC Study. In summary, we identified a missense CUBN variant that associates with levels of albuminuria in both the general population and in individuals with diabetes

  • 26. Carlsson, A. C.
    et al.
    Riserus, U.
    Engstrom, G.
    Ärnlöv, Johan
    Dalarna University, School of Education, Health and Social Studies, Medical Science.
    Melander, O.
    Leander, K.
    Gigante, B.
    Hellenius, M-L
    de Faire, U.
    Novel and established anthropometric measures and the prediction of incident cardiovascular disease: a cohort study2013In: International Journal of Obesity, ISSN 0307-0565, E-ISSN 1476-5497, Vol. 37, no 12, 1579-1585 p.Article in journal (Refereed)
    Abstract [en]

    OBJECTIVES: The aim of this study was to compare novel and established anthropometrical measures in their ability to predict cardiovascular disease (CVD), and to determine whether they improve risk prediction beyond classical risk factors in a cohort study of 60-year-old men and women. We also stratified the results according to gender to identify possible differences between men and women. Furthermore, we aimed to replicate our findings in a large independent cohort (The Malmo Diet and Cancer study-cardiovascular cohort).

    METHODS: This was a population-based study of 1751 men and 1990 women, aged 60 years and without CVD at baseline, with 375 incident cases of CVD during 11 years of follow-up. Weight, height, waist circumference (WC), hip circumference and sagittal abdominal diameter (SAD) were measured at baseline. Body mass index (BMI), waist-hip ratio (WHR), waist-hip-height ratio (WHHR), WC-to-height ratio (WCHR) and SAD-to-height ratio (SADHR) were calculated.

    RESULTS: All anthropometric measures predicted CVD in unadjusted Cox regression models per s.d. increment (hazard ratios, 95% confidence interval), while significant associations after adjustments for established risk CVD factors were noted for WHHR 1.20 (1.08-1.33), WHR 1.14 (1.02-1.28), SAD 1.13 (1.02-1.25) and SADHR 1.17 (1.06-1.28). WHHR had higher increases in C-statistics, and model improvements (likelihood ratio tests (P<0.001)). In the replication study (MDC-CC, n = 5180), WHHR was the only measure that improved Cox regression models in men (P = 0.01).

    CONCLUSION: WHHR, a new measure reflecting body fat distribution, showed the highest risk estimates after adjustments for established CVD risk factors. These findings were verified in men but not women in an independent cohort.

  • 27.
    Carlsson, A C
    et al.
    Division of Cardiovascular Epidemiology, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden ; Centre for Family Medicine, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Huddinge, Sweden.
    Riserus, Ulf
    Clinical Nutrition and Metabolism, Department of Public Health and Caring Sciences, Uppsala University, Uppsala, Sweden.
    Ärnlöv, Johan
    Dalarna University, School of Education, Health and Social Studies, Medical Science. Department of Public Health and Caring Sciences/Section of Geriatrics Uppsala University, Uppsala, Sweden.
    Borné, Y
    Department of Clinical Sciences, Lund University, Malmö, Sweden.
    Leander, K
    Division of Cardiovascular Epidemiology, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.
    Gigante, B
    Division of Cardiovascular Epidemiology, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden ; Clinical Nutrition and Metabolism, Department of Public Health and Caring Sciences, Uppsala University, Uppsala, Sweden.
    Hellénius, M-L
    Cardiology Unit, Department of Medicine, Karolinska Institutet, Stockholm, Sweden.
    Bottai, M
    Division of Biostatistics, Institute of Environmental Medicine, Karolinska Institute, Sweden.
    de Faire, U
    Division of Cardiovascular Epidemiology, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden ; Department of Cardiology, Karolinska University Hospital, Stockholm, Sweden.
    Prediction of cardiovascular disease by abdominal obesity measures is dependent on body weight and sex: results from two community based cohort studies2014In: NMCD. Nutrition Metabolism and Cardiovascular Diseases, ISSN 0939-4753, E-ISSN 1590-3729, Vol. 24, no 8, 891-899 p.Article in journal (Refereed)
    Abstract [en]

    AIM: To study waist-hip ratio (WHR), waist circumference (WC), sagittal abdominal diameter (SAD), and waist-hip-height ratio (WHHR) as predictors of CVD, in men and women stratified by BMI (cut-off ≥25).

    METHODS AND RESULTS: A cohort of n = 3741 (53% women) 60-year old individuals without CVD was followed for 11-years (375 CVD cases). To replicate the results, we also assessed another large independent cohort; The Malmö Diet and Cancer study - cardiovascular cohort (MDCC, (n = 5180, 60% women, 602 CVD cases during 16-years). After adjustment for established risk factors in normal-weight women, the hazard ratio (HR) per one standard deviation (SD) were; WHR; 1.91 (95% confidence interval (CI) 1.35-2.70), WC; 1.81 (95% CI 1.02-3.20), SAD; 1.25 (95% CI 0.74-2.11), and WHHR; 1.97 (95% CI 1.40-2.78). In men the association with WHR, WHHR and WC were not significant, whereas SAD was the only measure that significantly predicted CVD in men (HR 1.19 (95% CI 1.04-1.35). After adjustments for established risk factors in overweight/obese women, none of the measures were significantly associated with CVD risk. In men, however, all measures were significant predictors; WHR; 1.24 (955 CI 1.04-1.47), WC 1.19 (95% CI 1.00-1.42), SAD 1.21 (95% CI 1.00-1.46), and WHHR; 1.23 (95% CI 1.05-1.44). Only the findings in men with BMI ≥ 25 were verified in MDCC.

    CONCLUSION: In normal weight individuals, WHHR and WHR were the best predictors in women, whereas SAD was the only independent predictor in men. Among overweight/obese individuals all measures failed to predict CVD in women, whereas WHHR was the strongest predictor after adjustments for CVD risk factors in men.

  • 28. Carlsson, A. C.
    et al.
    Ärnlöv, Johan
    Dalarna University, School of Education, Health and Social Studies, Medical Science. Uppsala universitet.
    Sundström, J.
    Michaëlsson, K.
    Byberg, L.
    Lind, L.
    Physical activity, obesity and risk of cardiovascular disease in middle-aged men during a median of 30 years of follow-up2016In: European Journal of Preventive Cardiology, ISSN 2047-4873, E-ISSN 2047-4881, Vol. 23, no 4, 359-365 p.Article in journal (Refereed)
    Abstract [en]

    Background: We aimed to investigate associations between combinations of body mass index (BMI)-categories, levels of physical activity and long-term risk of cardiovascular disease.

    Method and results: At age 50 years, cardiovascular risk factors were assessed in 2196 participating men of the ULSAM-study. This investigation was repeated at age 60, 70, 77 and 82 years. Being physically active (PA) was defined as three hours of recreational or hard physical training per week. The men were categorized according to BMI/PA-status, as PA/normal weight (n = 593 at baseline), non-PA/normal weight (BMI &lt; 25 kg/m2, n = 580), PA/overweight (n = 418), non-PA/overweight (BMI 25-30 kg/m2, n = 462), PA/obese (n = 62), non-PA/obese (BMI &gt;30 kg/m2, n = 81). We used updated data on BMI and physical activity obtained at all examinations. During follow-up (median 30 years) 850 individuals suffered a cardiovascular disease (myocardial infarction, stroke or heart failure). Using updated data on BMI/PA categories, an increased risk for cardiovascular disease was seen with increasing BMI, but a high physical activity was associated with a lower risk of cardiovascular disease within each BMI category: non-PA/normal weight (hazard ratio (HR) 1.31, 95% confidence interval (CI) 1.04-1.66), PA/overweight (HR 1.52, 95% CI 1.20-1.94), non-PA/overweight (HR 1.65, 95% CI 1.31-2.07) PA/obese (HR 2.05, 95% CI 1.44-2.92) and non-PA/obese (HR 2.39, 95% CI 1.74-3.29), using PA/normal weight men as referent.

    Conclusions: Although physical activity was beneficial at all levels of BMI regarding the risk of future cardiovascular disease, there was still a substantial increased risk associated with being overweight or obese during 30 years of follow-up. 

  • 29. Carlsson, A C
    et al.
    Östgren, C J
    Länne, T
    Larsson, A
    Nystrom, F H
    Ärnlöv, Johan
    Dalarna University, School of Education, Health and Social Studies, Medical Science. Uppsala universitet.
    The association between endostatin and kidney disease and mortality in patients with type 2 diabetes2016In: Diabetes & Metabolism, ISSN 1262-3636, E-ISSN 1878-1780, Vol. 42, no 5, 351-357 p.Article in journal (Refereed)
    Abstract [en]

    AIM: Circulating endostatin, a biologically active derivate of collagen XVIII, is considered to be a marker of kidney disease and a risk factor for its related mortality. However, less is known of the role of endostatin in diabetes and the development of diabetic nephropathy. For this reason, our study investigated the associations between circulating endostatin and the prevalence and progression of kidney disease, and its mortality risk in patients with type 2 diabetes (T2D).

    METHODS: This was a cohort study of 607 patients with T2D (mean age: 61 years, 44% women). Estimated glomerular filtration rate (eGFR), calculated using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) creatinine equation, was used to assess the patients' kidney function decline and mortality.

    RESULTS: Of the total study cohort, 20 patients declined by ≥20% in eGFR over 4 years, and 44 died during the follow-up (mean duration: 6.7 years). At baseline, participants with diabetic nephropathy (defined as eGFR<60mL/min/1.73m(2)) and/or microalbuminuria [defined as a urinary albumin-to-creatinine ratio (ACR)>3g/mol] had higher median levels of endostatin than those without nephropathy (62.7μg/L vs 57.4μg/L, respectively; P=0.031). In longitudinal analyses adjusted for age, gender, baseline eGFR and ACR, higher endostatin levels were associated with a higher risk of decline (≥20% in eGFR, OR per 1 SD increase: 1.73, 95% CI: 1.13-2.65) and a higher risk of mortality (HR per 1 SD increase: 1.57, 95% CI: 1.19-2.07).

    CONCLUSION: In patients with T2D, circulating endostatin levels can predict the progression of kidney disease and mortality independently of established kidney disease markers. The clinical usefulness of endostatin as a risk marker in such patients merits further studies.

  • 30.
    Carlsson, Axel C
    et al.
    Centre for Family Medicine, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Huddinge, Sweden ; Department of Medical Sciences, Molecular Epidemiology and Science for Life Laboratory, Uppsala University, Uppsala, Sweden.
    Calamia, Michael
    Landstinget Dalarna, Falun, Sweden.
    Risérus, Ulf
    Department of Public Health and Caring Sciences/Section of Clinical Nutrition and Metabolism, Uppsala University, Uppsala, Sweden.
    Larsson, Anders
    Department of Medical Sciences, Uppsala University Hospital, Uppsala, Sweden.
    Helmersson-Karlqvist, Johanna
    Department of Medical Sciences, Uppsala University Hospital, Uppsala, Sweden.
    Lind, Lars
    Department of Medical Sciences, Uppsala University Hospital, Uppsala, Sweden.
    Ärnlöv, Johan
    Dalarna University, School of Education, Health and Social Studies, Medical Science. Department of Medical Sciences, Molecular Epidemiology and Science for Life Laboratory, Uppsala University, Uppsala, Sweden.
    Kidney injury molecule (KIM)-1 is associated with insulin resistance: results from two community-based studies of elderly individuals2014In: Diabetes Research and Clinical Practice, ISSN 0168-8227, E-ISSN 1872-8227, Vol. 103, no 3, 516-21 p.Article in journal (Refereed)
    Abstract [en]

    BACKGROUND AND OBJECTIVES: Insulin resistance has been shown to be closely associated with glomerular filtration rate and urinary albumin/creatinine ratio, even prior to the development of diabetes. Urinary kidney injury molecule 1 (KIM-1) is a novel, highly specific marker of kidney tubular damage. The role of insulin resistance in the development of kidney tubular damage is not previously reported. Thus, we aimed to investigate the associations between insulin sensitivity (assessed by HOMA) and urinary KIM-1.

    DESIGN, SETTING, PARTICIPANTS AND MEASUREMENTS: Two community-based cohorts of elderly individuals were investigated: Prospective Investigation of the vasculature in Uppsala seniors (PIVUS, n=701; mean age 75 years, 52% women); and Uppsala Longitudinal Study of adult men (ULSAM, n=533; mean age 78 years).

    RESULTS: Lower insulin sensitivity was associated with higher urinary KIM-1 in both cohorts after adjustments for age, BMI, blood pressure, antihypertensive treatment, glomerular filtration rate, and urinary albumin-creatinine ratio (PIVUS: regression coefficient for 1-SD higher HOMA-IR 0.11, 95% CI 0.03-0.20, p=0.009, and ULSAM: 0.13, 95% CI 0.04-0.22, p=0.007). Results were similar in individuals without diabetes, with normal kidney function and normo-albuminuria.

    CONCLUSIONS: Our findings in elderly individuals support the notion that the interplay between an impaired glucose metabolism and renal tubular damage is evident even prior to the development of diabetes and overt kidney disease.

  • 31. Carlsson, Axel C.
    et al.
    Carrero, Juan-Jesus
    Stenvinkel, Peter
    Bottai, Matteo
    Barany, Peter
    Larsson, Anders
    Ärnlöv, Johan
    Dalarna University, School of Education, Health and Social Studies, Medical Science.
    Endostatin, cathepsin S, and cathepsin L, and their association with inflammatory markers and mortality in patients undergoing hemodialysis2015In: Blood Purification, ISSN 0253-5068, E-ISSN 1421-9735, Vol. 39, no 4, 259-265 p.Article in journal (Refereed)
    Abstract [en]

    Background/Aims: Although both endostatin and cathepsins S have been associated with higher mortality, data in patients with end-stage renal disease (ESRD) are scarce.

    Methods: A longitudinal cohort study of 207 prevalent patients undergoing hemodialysis.

    Results: Cathepsins S and L were associated with soluble receptors for tumor necrosis factor (sTNFR1 and sTNFR2, rho between 0.28 and 0.43, p < 0.001 for all). Weaker or absent associations between endostatin, cathepsins S and L were seen with other inflammatory biomarkers, that is, CRP, interleukin 6, pentraxin 3, and TNF. In Cox and Laplace regression models adjusted for age, sex, dialysis vintage, and diabetes: standard deviation increments of endostatin was associated with a lower mortality (hazard ratio 0.75, 95% confidence interval (CI) 0.57-0.98), and with 6.8 months longer median survival.

    Conclusions: The high levels of endostatin, cathepsins S and L, and their associations with sTNFR1 and sTNFR2 warrant further studies exploring mortality, and the angiogenic and inflammatory pathways in ESRD. (C) 2015 S. Karger AG, Basel

  • 32. Carlsson, Axel C.
    et al.
    Carrero, Juan-Jesus
    Stenvinkel, Peter
    Bottai, Matteo
    Barany, Peter
    Larsson, Anders
    Ärnlöv, Johan
    Dalarna University, School of Education, Health and Social Studies, Medical Science. Uppsala universitet.
    High levels of soluble tumor necrosis factor receptors 1 and 2 and their association with mortality in patients undergoing hemodialysis2015In: CardioRenal Medicine, ISSN 1664-3828, Vol. 5, no 2, 89-95 p.Article in journal (Refereed)
    Abstract [en]

    Objective: Circulating soluble tumor necrosis factor receptors 1 and 2 (sTNFR1 and 5TNFR2) are associated with chronic kidney disease (CKD) progression in patients with CKD or diabetes, and with higher mortality. However, data in patients with end-stage renal disease are scarce. Therefore, we analyzed serum levels of sTNFR1 and sTNFR2 and investigated their association with inflammatory markers and mortality in dialysis patients. Research Design and Methods: This was a longitudinal cohort study of 207 prevalent patients (median age 66 years, 56% men) undergoing hemodialysis in Stockholm, Sweden. Demographics, clinical characteristics, including comorbidities and laboratory data, were obtained at baseline, together with prospective follow-up for mortality.

    Results: The median sTNFR1 and sTNFR2 levels were 17,680 ng/l [95% confidence interval (CI) 17,023-18,337] and 24,450 ng/l (95% CI 23,721-25,179), respectively. During a follow-up of 31 months (interquartile range, 21-38), 77 patients died. There was no association between the levels of sTNFRs and mortality in Cox regression models, and no consistent trend towards higher or lower mortality was seen in Laplace regression models. sTNFR1 and sTNFR2 levels were highly associated with other inflammatory markers including interleukin-6, pentraxin 3 and TNF-alpha. Conclusions:Prevalent hemodialysis patients have several-fold higher levels of sTNFRs compared to previous studies in CKD stage 4 patients. As no consistent association between TNFR and mortality was observed, clinical implications of measuring these receptors to predict outcome end-stage renal disease patients provide limited results.

  • 33. Carlsson, Axel C
    et al.
    Ingelsson, Erik
    Sundström, Johan
    Carrero, Juan Jesus
    Gustafsson, Stefan
    Feldreich, Tobias
    Stenemo, Markus
    Larsson, Anders
    Lind, Lars
    Ärnlöv, Johan
    Dalarna University, School of Education, Health and Social Studies, Medical Science. Uppsala universitet.
    Use of proteomics to investigate kidney function decline over 5 years2017In: American Society of Nephrology. Clinical Journal, ISSN 1555-9041, E-ISSN 1555-905X, Vol. 12, no 8, 1226-1235 p.Article in journal (Refereed)
    Abstract [en]

    BACKGROUND AND OBJECTIVES: Using a discovery/replication approach, we investigated associations between a multiplex panel of 80 circulating proteins associated with cardiovascular pathology or inflammation, and eGFR decline per year and CKD incidence.

    DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We used two cohorts, the Prospective Investigation of the Vasculature in Uppsala Seniors Study (PIVUS; n=687, mean age of 70 years, 51% women) and the Uppsala Longitudinal Study of Adult Men (ULSAM; n=360 men, mean age of 78 years), with 5-year follow-up data on eGFR. There were 231 and 206 incident cases of CKD during follow-up in the PIVUS and ULSAM studies, respectively. Proteomic profiling of 80 proteins was assessed by a multiplex assay (proximity extension assay). The assay uses two antibodies for each protein and a PCR step to achieve a high-specific binding and the possibility to measure multiple proteins in parallel, but gives no absolute concentrations.

    RESULTS: In the discovery cohort from the PIVUS Study, 28 plasma proteins were significantly associated with eGFR decline per year, taking into account the multiple testing. Twenty of these proteins were significantly associated with eGFR decline per year in the replication cohort from the ULSAM Study after adjustment for age, sex, cardiovascular risk factors, medications, and urinary albumin-to-creatinine ratio (in order of significance: TNF-related apoptosis-inducing ligand receptor 2*, CD40L receptor, TNF receptor 1*, placenta growth factor*, thrombomodulin*, urokinase plasminogen activator surface receptor*, growth/differentiation factor 15*, macrophage colony-stimulating factor 1, fatty acid-binding protein*, cathepsin D, resistin, kallikrein 11*, C-C motif chemokine 3, proteinase-activated receptor 1*, cathepsin L, chitinase 3-like protein 1, TNF receptor 2*, fibroblast growth factor 23*, monocyte chemotactic protein 1, and kallikrein 6). Moreover, 11 of the proteins predicted CKD incidence (marked with * above). No protein consistently predicted eGFR decline per year independently of baseline eGFR in both cohorts.

    CONCLUSIONS: Several circulating proteins involved in phosphate homeostasis, inflammation, apoptosis, extracellular matrix remodeling, angiogenesis, and endothelial dysfunction were associated with worsening kidney function. Multiplex proteomics appears to be a promising way of discovering novel aspects of kidney disease pathology.

  • 34. Carlsson, Axel C
    et al.
    Juhlin, C Christofer
    Larsson, Tobias E
    Larsson, Anders
    Ingelsson, Erik
    Sundström, Johan
    Lind, Lars
    Ärnlöv, Johan
    Dalarna University, School of Education, Health and Social Studies, Medical Science. Uppsala universitet.
    Soluble tumor necrosis factor receptor 1 (sTNFR1) is associated with increased total mortality due to cancer and cardiovascular causes: findings from two community based cohorts of elderly2014In: Atherosclerosis, ISSN 0021-9150, E-ISSN 1879-1484, Vol. 237, no 1, 236-242 p.Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Experimental evidence support soluble receptors for tumor necrosis factor alpha as important mediators of the underlying pathology leading to cardiovascular disease and cancer. However, prospective data concerning the relation between circulating soluble tumor necrosis factor receptor-1 (sTNFR1) and mortality in humans are lacking. We aimed to explore and validate the association between sTNFR1 and mortality, and to explore the influence of other established risk factors for mortality, including other inflammatory markers.

    METHODS: The association between serum sTNFR1and the risk for mortality was investigated in two community-based cohorts of elderly: the Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS; women 50%, n = 1005, mean age 70 years, median follow-up 7.9 years) and the Uppsala Longitudinal Study of Adult Men (ULSAM, n = 775, mean age 77 years, median follow-up 8.1 years).

    RESULTS: In total, 101 participants in PIVUS and 274 in ULSAM died during follow-up. In multivariable Cox regression models adjusted for inflammation, lifestyle and established cardiovascular risk factors, one standard deviation (SD) higher sTNFR1 was associated with a hazard ratio (HR) for mortality of 1.37, 95% confidence interval (CI) 1.17-1.60, in PIVUS and HR 1.22, 95% CI 1.10-1.37 in ULSAM. Moreover, circulatingsTNFR1 was associated with cardiovascular mortality (HR per SD of sTNFR1, 1.24, 95% CI 1.07-1.44) and cancer mortality (HR per SD of sTNFR1, 1.32, 95% CI 1.11-1.57) in the ULSAM cohort. High levels of sTNFR1 identified individuals with increased risk of mortality among those with high as well as low levels of systemic inflammation.

    CONCLUSIONS: An association between circulating sTNFR1 and an increased risk for mortality was found and validated in two independent community-based cohorts. The future clinical role of sTNFR1 to identify high risk patients for adverse outcomes and mortality has yet to be determined.

  • 35.
    Carlsson, Axel C
    et al.
    Centre for Family Medicine, Department of Neurobiology, Care Sciences, and Society, Karolinska Institute, Huddinge, Sweden; Department of Medical Sciences, Molecular Epidemiology and Science for Life Laboratory, Uppsala University, Uppsala, Sweden.
    Larsson, Anders
    Department of Medical Sciences, Uppsala University Hospital, Uppsala, Sweden.
    Helmersson-Karlqvist, Johanna
    Department of Medical Sciences, Uppsala University Hospital, Uppsala, Sweden.
    Lind, Lars
    Department of Medical Sciences, Uppsala University Hospital, Uppsala, Sweden.
    Ingelsson, Erik
    Department of Medical Sciences, Molecular Epidemiology and Science for Life Laboratory, Uppsala University, Uppsala, Sweden.
    Larsson, Tobias E
    Department of Clinical Science, Intervention and Technology, Karolinska Institutet, Stockholm, Sweden.
    Bottai, Matteo
    Division of Biostatistics, Institute of Environmental Medicine, Karolinska Institute, Stockholm, Sweden.
    Sundström, Johan
    Department of Medical Sciences, Molecular Epidemiology and Science for Life Laboratory, Uppsala University, Uppsala, Sweden.
    Ärnlöv, Johan
    Dalarna University, School of Education, Health and Social Studies, Medical Science. Department of Medical Sciences, Molecular Epidemiology and Science for Life Laboratory, Uppsala University, Uppsala, Sweden.
    Urinary kidney injury molecule-1 and the risk of cardiovascular mortality in elderly men2014In: American Society of Nephrology. Clinical Journal, ISSN 1555-9041, Vol. 9, no 8, 1393-1401 p.Article in journal (Refereed)
    Abstract [en]

    BACKGROUND AND OBJECTIVES: Kidney injury molecule-1 (KIM-1) has been suggested as a clinically relevant highly specific biomarker of acute kidney tubular damage. However, community-based data on the association between urinary levels of KIM-1 and the risk for cardiovascular mortality are lacking. This study aimed to investigate the association between urinary KIM-1 and cardiovascular mortality.DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: This was a prospective study, using the community-based Uppsala Longitudinal Study of Adult Men (N=590; mean age 77 years; baseline period, 1997-2001; median follow-up 8.1 years; end of follow-up, 2008).RESULTS: During follow-up, 89 participants died of cardiovascular causes (incidence rate, 2.07 per 100 person-years at risk). Models were adjusted for cardiovascular risk factors (age, systolic BP, diabetes, smoking, body mass index, total cholesterol, HDL cholesterol, antihypertensive treatment, lipid-lowering treatment, aspirin treatment, and history of cardiovascular disease) and for markers of kidney dysfunction and damage (cystatin C-based eGFR and urinary albumin/creatinine ratio). Higher urinary KIM-1/creatinine (from 24-hour urine collections) was associated with a higher risk for cardiovascular mortality (hazard ratio per SD increase, 1.27; 95% confidence interval [95% CI], 1.05 to 1.54; P=0.01). Participants with a combination of high KIM-1/creatinine (upper quintile, ≥175 ng/mmol), low eGFR (≤60 ml/min per 1.73 m(2)), and microalbuminuria/macroalbuminuria (albumin/creatinine ratio≥3 g/mol) had a >8-fold increased risk compared with participants with low KIM-1/creatinine (<175 ng/mmol), normal eGFR (>60 ml/min per 1.73 m(2)), and normoalbuminuria (albumin/creatinine ratio<3 g/mol) (hazard ratio, 8.56; 95% CI, 4.17 to 17.56; P<0.001).CONCLUSIONS: These findings suggest that higher urinary KIM-1 may predispose to a higher risk of cardiovascular mortality independently of established cardiovascular risk factors, eGFR, and albuminuria. Additional studies are needed to further assess the utility of measuring KIM-1 in the clinical setting.

  • 36. Carlsson, Axel C
    et al.
    Larsson, Anders
    Helmersson-Karlqvist, Johanna
    Lind, Lars
    Ingelsson, Erik
    Larsson, Tobias E
    Sundström, Johan
    Ärnlöv, Johan
    Dalarna University, School of Education, Health and Social Studies, Medical Science.
    Urinary kidney injury molecule 1 and incidence of heart failure in elderly men2013In: European Journal of Heart Failure, ISSN 1388-9842, E-ISSN 1879-0844, Vol. 15, no 4, 447-446 p.Article in journal (Refereed)
    Abstract [en]

    AIMS: There is growing recognition of the clinical importance of cardiorenal syndrome-the bidirectional interplay between kidney and cardiac dysfunction. Yet, the role of kidney tubular damage in the development of heart failure is less studied. The objective of this study was to investigate whether urinary kidney injury molecule (KIM)-1, a specific marker of tubular damage, predisposes to an increased heart failure risk.

    METHODS AND RESULTS: This was a community-based cohort study [Uppsala Longitudinal study of Adult Men (ULSAM)] of 565, 77-year-old men free from heart failure at baseline. Heart failure hospitalizations were used as outcome. During follow-up (median 8.0 years), 73 participants were hospitalized for heart failure. In models adjusted for cardiovascular risk factors (age, systolic blood pressure, diabetes, smoking, body mass index, LDL/HDL ratio, antihypertensive treatment, lipid-lowering treatment, aspirin treatment, LV hypertrophy, and prevalent cardiovascular disease) and markers of kidney dysfunction and damage [cystatin C-based glomerular filtration rate (GFR) and urinary albumin/creatinine ratio], a higher urinary KIM-1/creatinine ratio was associated with higher risk for heart failure (hazard ratio upper vs. lower tertile, 1.81; 95% confidence interval 1.01-3.29; P < 0.05). Participants with a combination of low GFR (<60 mL/min/1.72 m(2)) and high KIM-1/creatinine (>128 ng/mmol) had a 3-fold increase in heart failure risk compared with participants with normal GFR and KIM-1 (P < 0.001).

    CONCLUSION: Our findings suggest that kidney tubular damage predisposes to an increased risk for heart failure in the community. Further studies are needed to clarify the causal role of KIM-1 in the development of heart failure, and to evaluate the clinical utility of urinary KIM-1 measurements.

  • 37.
    Carlsson, Axel C
    et al.
    Centre for Family Medicine, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Huddinge, Sweden ; Department of Medical Sciences, Molecular Epidemiology and Science for Life Laboratory, Uppsala University, Uppsala, Sweden.
    Larsson, Tobias E
    Department of Clinical Science, Intervention and Technology, Karolinska Institutet, Stockholm, Sweden.
    Helmersson-Karlqvist, Johanna
    Department of Medical Sciences, Uppsala University Hospital, Uppsala, Sweden.
    Larsson, Anders
    Department of Medical Sciences, Uppsala University Hospital, Uppsala, Sweden.
    Lind, Lars
    Department of Medical Sciences, Uppsala University Hospital, Uppsala, Sweden.
    Ärnlöv, Johan
    Dalarna University, School of Education, Health and Social Studies, Medical Science. Department of Medical Sciences, Molecular Epidemiology and Science for Life Laboratory, Uppsala University, Uppsala, Sweden.
    Soluble TNF receptors and kidney dysfunction in the elderly2014In: Journal of the American Society of Nephrology, ISSN 1046-6673, Vol. 25, no 6, 1313-1320 p.Article in journal (Refereed)
    Abstract [en]

    The importance of TNF-α and its soluble receptors (sTNFR1 and sTNFR2) in the development of kidney disease is being unraveled. Yet, community-based data regarding the role of sTNFRs are lacking. We assessed serum sTNFRs and aspects of kidney damage cross-sectionally in two independent community-based cohorts of elderly participants: Prospective Investigation of the Vasculature in Uppsala Seniors (n=815; mean age, 75 years; 51% women) and Uppsala Longitudinal Study of Adult Men (n=778; mean age, 78 years). Serum sTNFR1 correlated substantially with different aspects of kidney pathology in the Uppsala Longitudinal Study of Adult Men cohort (R=-0.52 for estimated GFR, R=0.22 for urinary albumin-to-creatinine ratio, and R=0.17 for urinary kidney injury molecule-1; P<0.001 for all), with similar correlations in the Prospective Investigation of the Vasculature in Uppsala Seniors cohort. These associations remained significant after adjustment for age, sex, inflammatory markers, and cardiovascular risk factors and were also evident in participants without diabetes. Serum sTNFR2 was associated with all three markers in the Prospective Investigation of the Vasculature in Uppsala Seniors cohort (P<0.001 for all). Our findings from two independent community-based cohorts confirm and extend results of previous studies supporting circulating sTNFRs as relevant biomarkers for kidney damage and dysfunction in elderly individuals, even in the absence of diabetes.

  • 38. Carlsson, Axel C
    et al.
    Li, Xinjun
    Holzmann, Martin J
    Ärnlöv, Johan
    Dalarna University, School of Education, Health and Social Studies, Medical Science. Karolinska Institute.
    Wändell, Per
    Gasevic, Danijela
    Sundquist, Jan
    Sundquist, Kristina
    Neighborhood socioeconomic status at the age of 40 years and ischemic stroke before the age of 50 years: A nationwide cohort study from Sweden.2017In: International Journal of Stroke, ISSN 1747-4930, E-ISSN 1747-4949, Vol. 12, no 8, 815-826 p.Article in journal (Refereed)
    Abstract [en]

    Objective: We aimed to study the association between neighborhood socioeconomic status at the age of 40 years and risk of ischemic stroke before the age of 50 years.

    Methods: All individuals in Sweden were included if their 40th birthday occurred between 1998 and 2010. National registers were used to categorize neighborhood socioeconomic status into high, middle, and low and to retrieve information on incident ischemic strokes. Hazard ratios and their 95% confidence intervals were estimated.

    Results: A total of 1,153,451 adults (women 48.9%) were followed for a mean of 5.5 years (SD 3.5 years), during which 1777 (0.30%) strokes among men and 1374 (0.24%) strokes among women were recorded. After adjustment for sex, marital status, education level, immigrant status, region of residence, and neighborhood services, there was a lower risk of stroke in residents from high-socioeconomic status neighborhoods (hazard ratio 0.87, 95% confidence interval 0.78-0.96), and an increased risk of stroke in adults from low-socioeconomic status neighborhoods (hazard ratio 1.16, 95% confidence interval 1.06-1.27), compared to their counterparts living in middle-socioeconomic status neighborhoods. After further adjustment for hospital diagnoses of hypertension, diabetes, heart failure, and atrial fibrillation prior to the age of 40, the higher risk in neighborhoods with low socioeconomic status was attenuated, but remained significant (hazard ratio 1.12, 95% confidence interval 1.02-1.23).

    Conclusions: In a nationwide study of individuals between 40 and 50 years, we found that the risk of ischemic stroke differed depending on neighborhood socioeconomic status, which calls for increased efforts to prevent cardiovascular diseases in low socioeconomic status neighborhoods.

  • 39.
    Carlsson, Axel C.
    et al.
    Karolinska Institutet.
    Nordquist, Lina
    Uppsala Universitet.
    Larsson, Tobias E.
    Karolinska Institutet.
    Carrero, Juan-Jesus
    Karolinska Institutet.
    Larsson, Anders
    Uppsala Universitet.
    Lind, Lars
    Uppsala university hospital.
    Ärnlöv, Johan
    Dalarna University, School of Education, Health and Social Studies, Medical Science. Uppsala universitet.
    Soluble tumor necrosis factor receptor 1 is associated with glomerular filtration rate progression and incidence of chronic kidney disease in two community-based cohorts of elderly individuals2015In: CardioRenal Medicine, ISSN 1664-3828, Vol. 5, no 4, 278-288 p.Article in journal (Refereed)
    Abstract [en]

    Objective: We aimed to explore and validate the longitudinal associations between soluble tumor necrosis factor receptor 1 (sTNFR1), glomerular filtration rate (GFR) progression, and chronic kidney disease (CKD) incidence in two independent community-based cohorts of elderly individuals with prespecified subgroup analyses in individuals without prevalent diabetes.

    Research design and methods: Two community-based cohorts of elderly individuals were used with 5-year follow-up data on estimated GFR: the Uppsala Longitudinal Study of Adult Men (ULSAM; n = 437 men; mean age: 78 years) and the Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS; n = 703; mean age: 70 years; 51% women). GFR categories were defined as >= 60, 30-60, and <30 ml/min/1.73 m(2).

    Results: In longitudinal multivariable logistic regression models adjusted for inflammatory markers and established cardiovascular risk factors, higher serum sTNFR1 was significantly associated with an increased risk to progress to a lower GFR category in both ULSAM and PIVUS [odds ratio (OR) per standard deviation (SD) increase 1.28 (95% CI 1.03-1.60) and OR 1.56 (95% CI 1.30-1.87), respectively]. Also, in subgroup analyses in individuals with a GFR >= 60 ml/min/1.73 m(2) at baseline, higher sTNFRs were associated with incident CKD after 5 years in both cohorts [ULSAM: OR per SD increase 1.49 (95% CI 1.16-1.9) and PIVUS: OR 1.84 (95% CI 1.50-2.26)]. Associations were similar in individuals without diabetes.

    Conclusions: Higher circulating sTNFR1 independently predicts the progression to a worse GFR category and CKD incidence in elderly individuals even in the absence of diabetes. Further studies are warranted to investigate the underlying mechanisms, and to evaluate the clinical relevance of our findings. 

  • 40. Carlsson, Axel C.
    et al.
    Riserus, Ulf
    Ärnlöv, Johan
    Dalarna University, School of Education, Health and Social Studies, Medical Science.
    Hypertriglyceridemic waist phenotype is associated with decreased insulin sensitivity and incident diabetes in elderly men2014In: Obesity, ISSN 1930-7381, E-ISSN 1930-739X, Vol. 22, no 2, 526-529 p.Article in journal (Refereed)
    Abstract [en]

    Objective: To investigate the association between hypertriglyceridemic waist (HTGW) and insulin sensitivity (assessed by euglycemic clamp method), and the development of diabetes in a longitudinal community-based cohort of elderly men without diabetes at baseline.

    Design and Methods: The present cross-sectional study comprised 1,026, 70-year-old men without diabetes. The gold standard euglycaemic-hyperinsulinaemic clamp technique was used. Six-year follow-up on diabetes status were available in n = 667. The HTGW phenotype was defined as having waist circumference >= 90 cm, and triglycerides >= 2 mmol L-1. The men were stratified into those having normal WC and TG (n = 299), one HTGW component (n = 606), and HTGW (n = 121).

    Results: The association between insulin sensitivity and one HTGW component as well as HTGW was highly significant (P < 0.001) in the whole sample, as well as in individuals with high/low BMI (stratified at >= 25). In longitudinal analyses, participants with HTGW was associated with a more than fourfold increased risk for diabetes (Odds ratio 4.64, 95% CI 1.61-13.4, P = 0.004) compared to those with normal WC and TG.

    Conclusion: The present study both confirm and extend previous research suggesting that the HTGW-phenotype portrays an increased glucometabolic risk, also in lean individuals.

  • 41. Carlsson, Axel C
    et al.
    Ruge, Toralph
    Sundström, Johan
    Ingelsson, Erik
    Larsson, Anders
    Lind, Lars
    Ärnlöv, Johan
    Dalarna University, School of Education, Health and Social Studies, Medical Science.
    Association between circulating endostatin, hypertension duration, and hypertensive target-organ damage2013In: Hypertension, ISSN 0194-911X, E-ISSN 1524-4563, Vol. 62, no 6, 1146-1151 p.Article in journal (Refereed)
    Abstract [en]

    Our aim is to study associations between circulating endostatin, hypertension duration, and hypertensive target-organ damage. Long-term hypertension induces cardiovascular and renal remodeling. Circulating endostatin, a biologically active derivate of collagen XVIII, has been suggested to be a relevant marker for extracellular matrix turnover and remodeling in various diseases. However, the role of endostatin in hypertension and hypertensive target-organ damage is unclear. Serum endostatin was measured in 2 independent community-based cohorts: the Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS; women 51%; n=812; mean age, 75 years) and the Uppsala Longitudinal Study of Adult Men (ULSAM; n=785; mean age, 77.6 years). Retrospective data on blood pressure measurements and antihypertensive medication (PIVUS >5 years, ULSAM >27 years), and cross-sectional data on echocardiographic left ventricular mass, endothelial function (endothelium-dependent vasodilation assessed by the invasive forearm model), and urinary albumin/creatinine ratio were available. In PIVUS, participants with ≥5 years of history of hypertension portrayed 0.42 SD (95% confidence interval, 0.23-0.61; P<0.001) higher serum endostatin, compared with that of normotensives. This association was replicated in ULSAM, in which participants with 27 years hypertension duration had the highest endostatin (0.57 SD higher; 95% confidence interval, 0.35-0.80; P<0.001). In addition, higher endostatin was associated with higher left ventricular mass, worsened endothelial function, and higher urinary albumin/creatinine ratio (P<0.03 for all) in participants with prevalent hypertension. Circulating endostatin is associated with the duration of hypertension, and vascular, myocardial, and renal indices of hypertensive target-organ damage. Further studies are warranted to assess the prognostic role of endostatin in individuals with hypertension.

  • 42. Carlsson, Axel C
    et al.
    Sundström, Johan
    Carrero, Juan Jesus
    Gustafsson, Stefan
    Stenemo, Markus
    Larsson, Anders
    Lind, Lars
    Ärnlöv, Johan
    Dalarna University, School of Education, Health and Social Studies, Medical Science. Uppsala University.
    Use of a proximity extension assay proteomics chip to discover new biomarkers associated with albuminuria.2017In: European Journal of Preventive Cardiology, ISSN 2047-4873, E-ISSN 2047-4881, Vol. 24, no 4, 340-348 p.Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: The underlying mechanisms for the development of albuminuria and the increased cardiovascular risk in patients with elevated albuminuria levels are incompletely understood. We therefore investigated the associations between 80 cardiovascular proteins and the urinary albumin to creatinine ratio (ACR).

    METHODS: We used a discovery/replication approach in two independent community-based cohorts of elderly patients: the Uppsala Longitudinal Study of Adult Men (n = 662; mean age 78 years) and the Prospective Investigation of the Vasculature in Uppsala Seniors (n = 757; mean age 75 years; 51% women). A proteomic chip with a panel of 80 plasma proteins associated with different aspects of cardiovascular disease was analysed. In the discovery cohort, we used a false discovery rate of 5% to take into account the multiple statistical testing. Nominal p values were used in the replication.

    RESULTS: Higher levels of T-cell immunoglobulin mucin-1, placenta growth factor, growth/differentiation factor-15, urokinase plasminogen activator surface receptor and kallikrein-11 were robustly associated with a higher ACR in both cohorts in multivariable linear regression models adjusted for sex, established cardiovascular risk factors, antihypertensive treatment, prevalent cardiovascular disease and glomerular filtration rate (p < 0.02 for all). All associations were also significant in separate analyses of patients without diabetes.

    CONCLUSIONS: We discovered and replicated associations between ACR and five cardiovascular proteins involved in tubular injury, atherosclerosis, endothelial function, heart failure, inflammation, glomerulosclerosis and podocyte injury. Our findings put forward multiplex proteomics as a promising approach to explore novel aspects of the complex detrimental interplay between kidney function and the cardiovascular system.

  • 43. Carlsson, Axel C
    et al.
    Wändell, Per
    Riserus, Ulf
    Ärnlöv, Johan
    Dalarna University, School of Education, Health and Social Studies, Medical Science. Uppsala universitet.
    Borné, Yan
    Engström, Gunnar
    Leander, Karin
    Gigante, Bruna
    Hellénius, Mai-Lis
    de Faire, Ulf
    Differences in anthropometric measures in immigrants and Swedish-born individuals: results from two community-based cohort studies2014In: Preventive Medicine, ISSN 0091-7435, E-ISSN 1096-0260, Vol. 69, 151-156 p.Article in journal (Refereed)
    Abstract [en]

    AIM: To study differences in body mass index (BMI), waist-hip ratio (WHR), waist circumference (WC), sagittal abdominal diameter (SAD), waist-hip-height ratio (WHHR) and percent body fat in immigrants and Swedish-born men and women in two large population-based samples.

    METHODS: A cross-sectional analysis of 60-year-old individuals, n=4 232. To replicate the results, we also assessed another large independent cohort cross-sectionally, the Malmö Diet and Cancer Study (MDC, n=26 777). The data from both cohorts were collected in the 1990s in Sweden.

    RESULTS: Significant differences between Finnish-born, Middle Eastern and women from the rest of the world were seen for all anthropometric measures, using Swedish-born women as referent. However, WHHR was the only anthropometric measure that identified all these three groups of immigrant women as different from Swedish-born women with high statistical certainty (p<0.001). Apart from WHHR that identified differences in anthropometry in all immigrant groups of men using Swedish-born men as referent, few significant differences were seen in anthropometry among groups of immigrant men. These finding were observed in both cohorts, and remained after adjustments for smoking, physical activity and educational level.

    CONCLUSION: The present study confirms previous findings of more obesity among immigrants and is the first to report that WHHR measurements may detect anthropometric differences between different ethnic groups better than other anthropometrical measures.

  • 44. Carlsson, Axel C
    et al.
    Östgren, Carl Johan
    Nystrom, Fredrik H
    Länne, Toste
    Jennersjö, Pär
    Larsson, Anders
    Ärnlöv, Johan
    Dalarna University, School of Education, Health and Social Studies, Medical Science. Uppsala universitet.
    Association of soluble tumor necrosis factor receptors 1 and 2 with nephropathy, cardiovascular events, and total mortality in type 2 diabetes2016In: Cardiovascular Diabetology, ISSN 1475-2840, E-ISSN 1475-2840, Vol. 15, 40Article in journal (Refereed)
    Abstract [en]

    AIMS/HYPOTHESIS: Soluble tumor necrosis factor receptors 1 and 2 (sTNFR1 and sTNFR2) contribute to experimental diabetic kidney disease, a condition with substantially increased cardiovascular risk when present in patients. Therefore, we aimed to explore the levels of sTNFRs, and their association with prevalent kidney disease, incident cardiovascular disease, and risk of mortality independently of baseline kidney function and microalbuminuria in a cohort of patients with type 2 diabetes. In pre-defined secondary analyses we also investigated whether the sTNFRs predict adverse outcome in the absence of diabetic kidney disease.

    METHODS: The CARDIPP study, a cohort study of 607 diabetes patients [mean age 61 years, 44 % women, 45 cardiovascular events (fatal/non-fatal myocardial infarction or stroke) and 44 deaths during follow-up (mean 7.6 years)] was used.

    RESULTS: Higher sTNFR1 and sTNFR2 were associated with higher odds of prevalent kidney disease [odd ratio (OR) per standard deviation (SD) increase 1.60, 95 % confidence interval (CI) 1.32-1.93, p < 0.001 and OR 1.54, 95 % CI 1.21-1.97, p = 0.001, respectively]. In Cox regression models adjusting for age, sex, glomerular filtration rate and urinary albumin/creatinine ratio, higher sTNFR1 and sTNFR2 predicted incident cardiovascular events [hazard ratio (HR) per SD increase, 1.66, 95 % CI 1.29-2.174, p < 0.001 and HR 1.47, 95 % CI 1.13-1.91, p = 0.004, respectively]. Results were similar in separate models with adjustments for inflammatory markers, HbA1c, or established cardiovascular risk factors, or when participants with diabetic kidney disease at baseline were excluded (p < 0.01 for all). Both sTNFRs were associated with mortality.

    CONCLUSIONS/INTERPRETATIONS: Higher circulating sTNFR1 and sTNFR2 are associated with diabetic kidney disease, and predicts incident cardiovascular disease and mortality independently of microalbuminuria and kidney function, even in those without kidney disease. Our findings support the clinical utility of sTNFRs as prognostic markers in type 2 diabetes.

  • 45.
    Carlsson, Magnus
    et al.
    Dalarna University, School of Education, Health and Social Studies, Medical Science.
    Carlsson, Tomas
    Dalarna University, School of Education, Health and Social Studies, Medical Science.
    Hammarström, Daniel
    Dalarna University, School of Education, Health and Social Studies, Sport and Health Science.
    Granath, Johan
    Westergren, Jens
    Dalarna University, School of Education, Health and Social Studies, Sport and Health Science.
    Malm, Christer
    Tonkonogi, Michail
    Dalarna University, School of Education, Health and Social Studies, Sport and Health Science.
    Validation of off-season physiological tests with ski ranking in elite male junior cross-country skiing2012In: Medicine & Science in Sports & Exercise, ISSN 0195-9131, E-ISSN 1530-0315, Vol. 44, no s2, 516-516 p.Article in journal (Other academic)
  • 46.
    Carlsson, Magnus
    et al.
    Dalarna University, School of Education, Health and Social Studies, Medical Science.
    Carlsson, Tomas
    Dalarna University, School of Education, Health and Social Studies, Medical Science.
    Hammarström, Daniel
    Dalarna University, School of Education, Health and Social Studies, Sport and Health Science.
    Malm, Christer
    Tonkonogi, Michail
    Dalarna University, School of Education, Health and Social Studies, Sport and Health Science.
    Time trials predict the competitive performance capacity of junior cross-country skiers2014In: International Journal of Sports Physiology and Performance, ISSN 1555-0265, Vol. 9, no 1, 12-18 p.Article in journal (Refereed)
    Abstract [en]

    Purpose: This study investigated whether there is a correlation between time-trial performance and competitive performance capacity of male and female junior cross-country skiers and sought to explain sex-specific competitive performance capacity through multiple-regression modeling.

    Methods: The International Ski Federation's (FIS) junior ranking points for distance (FISdist) and sprint (FISsprint) competitions were used as performance parameters. A total of 38 elite junior (age 18.5 +/- 1.0 y) cross-country skiers (24 men and 14 women) completed 3 time-trial tests: a 3-km level-running time trial (TTRun), a 2-km moderate uphill (1.2 slope) roller-skiing time trial using the double-poling technique (TTDP), and a 2-km uphill (2.8 slope) roller-skiing time trial using the diagonal-stride technique (TTDiag). The correlations were investigated using Pearson correlation analysis, and regression models were created using multiple-linear-regression analysis. Results: For men, FISsprint and FISdist were correlated with the times for TTRun, TTDP, and TTDiag (all P < .001). For women, FISsprint was correlated with the times for TTRun (P < .05), TTDP (P < .01), and TTDiag (P < .01), whereas FISdist was correlated only with the times for TTDP (P < .01) and TTDiag (P < .05). The models developed for FISdist and FISsprint explained 73.9-82.3% of the variance in the performance capacity of male junior cross-country skiers. No statistically valid regression model was found for the women.

    Conclusions: Running and roller-skiing time trials are useful tests for accurately predicting the performance capacity of junior cross-country skiers.

  • 47.
    Carlsson, Magnus
    et al.
    Dalarna University, School of Education, Health and Social Studies, Sport and Health Science. Umeå universitet; Dala Sports Academy.
    Carlsson, Tomas
    Dalarna University, School of Education, Health and Social Studies, Sport and Health Science. Umeå universitet; Dala Sports Academy.
    Wedholm, Lars
    Dalarna University, School of Education, Health and Social Studies, Sport and Health Science. Dala Sports Academy.
    Nilsson, Mattias
    Regional Sports Federation of Dalarna.
    Malm, Christer
    Idrottsmedicin, Umeå Universitet.
    Tonkonogi, Michail
    Dalarna University, School of Education, Health and Social Studies, Medical Science.
    Physiological demands of competitive sprint and distance performance in elite female cross-country skiing2016In: Journal of Strength and Conditioning Research, ISSN 1064-8011, E-ISSN 1533-4287, Vol. 30, no 8, 2138-2144 p.Article in journal (Refereed)
    Abstract [en]

    The purpose was to investigate the relationship between elite females' competitive performance capability in sprint and distance cross-country skiing and the variables of gross efficiency (GE), work rate at the onset of blood-lactate accumulation (OBLA4mmol), maximal oxygen uptake (VO2max), maximal speed (Vmax), and peak upper-body oxygen uptake (VO2peak). Ten elite female cross-country skiers (age 24.5 ± 2.8 years) completed treadmill roller-skiing tests to determine GE, OBLA4mmol, and VO2max using the diagonal-stride technique as well as Vmax and VO2peak using the double-poling technique. International Ski Federations ranking points for sprint (FISsprint) and distance (FISdist) races were used as competitive performance data. There were correlations between the FISsprint and the VO2max expressed absolutely (P = 0.0040), Vmax (P = 0.012), and VO2peak expressed absolutely (P < 0.001) and as a simple ratio-standard (P = 0.049). The FISdist were correlated with OBLA4mmol (P = 0.048), VO2max expressed absolutely (L·min) (P = 0.015) and as a simple ratio-standard (P = 0.046), and VO2peak expressed absolutely (P = 0.036) and as a simple ratio-standard (mL·min·kg) (P = 0.040). The results demonstrate that the physiological abilities reflected by VO2max and VO2peak are indicators of competitive sprint and distance performance in elite female cross-country skiing. In addition, the ability to generate a high Vmax indicates the performance in sprint races whereas the skier's OBLA4mmol reflects the performance capability in distance races. Based on the results, when evaluating the performance capacity of elite female cross-country skiers, it is recommended to use physiological variables that reflect competitive performance.

  • 48.
    Carlsson, Tomas
    et al.
    Dalarna University, School of Education, Health and Social Studies, Sport and Health Science.
    Tonkonogi, Michail
    Dalarna University, School of Education, Health and Social Studies, Medical Science.
    Carlsson, Magnus
    Dalarna University, School of Education, Health and Social Studies, Sport and Health Science.
    Aerobic power and lean mass are indicators of competitive sprint performance among elite female cross-country skiers2016In: Open Access Journal of Sports Medicine, ISSN 1179-1543, E-ISSN 1179-1543, Vol. 7, 153-160 p.Article in journal (Refereed)
    Abstract [en]

    The purpose of this study was to establish the optimal allometric models to predict International Ski Federation’s ski-ranking points for sprint competitions (FISsprint) among elite female cross-country skiers based on maximal oxygen uptake (V̇O2max) and lean mass (LM). Ten elite female cross-country skiers (age: 24.5±2.8 years [mean ± SD]) completed a treadmill roller-skiing test to determine V̇O2max (ie, aerobic power) using the diagonal stride technique, whereas LM (ie, a surrogate indicator of anaerobic capacity) was determined by dual-emission X-ray anthropometry. The subjects’ FISsprint were used as competitive performance measures. Power function modeling was used to predict the skiers’ FISsprint based on V̇O2max, LM, and body mass. The subjects’ test and performance data were as follows: V̇O2max, 4.0±0.3 L min-1; LM, 48.9±4.4 kg; body mass, 64.0±5.2 kg; and FISsprint, 116.4±59.6 points. The following power function models were established for the prediction of FISsprint: 3.91×105 ∙ VO -6.002maxand 6.95×1010 ∙ LM-5.25; these models explained 66% (P=0.0043) and 52% (P=0.019), respectively, of the variance in the FISsprint. Body mass failed to contribute to both models; hence, the models are based on V̇O2max and LM expressed absolutely. The results demonstrate that the physiological variables that reflect aerobic power and anaerobic capacity are important indicators of competitive sprint performance among elite female skiers. To accurately indicate performance capability among elite female skiers, the presented power function models should be used. Skiers whose V̇O2max differs by 1% will differ in their FISsprint by 5.8%, whereas the corresponding 1% difference in LM is related to an FISsprint difference of 5.1%, where both differences are in favor of the skier with higher V̇O2max or LM. It is recommended that coaches use the absolute expression of these variables to monitor skiers’ performance-related training adaptations linked to changes in aerobic power and anaerobic capacity.

  • 49. Carrero, Juan Jesús
    et al.
    Grams, Morgan E
    Sang, Yingying
    Ärnlöv, Johan
    Dalarna University, School of Education, Health and Social Studies, Medical Science. Uppsala universitet.
    Gasparini, Alessandro
    Matsushita, Kunihiro
    Qureshi, Abdul R
    Evans, Marie
    Barany, Peter
    Coresh, Josef
    Albuminuria changes are associated with subsequent risk of end-stage renal disease and mortality2017In: Kidney International, ISSN 0085-2538, E-ISSN 1523-1755, Vol. 91, no 1, 244-251 p.Article in journal (Refereed)
    Abstract [en]

    Current guidelines for chronic kidney disease (CKD) recommend using albuminuria as well as estimated glomerular filtration rate (eGFR) to stage CKD. However, CKD progression is solely defined by change in eGFR with little regard to the risk implications of change in albuminuria. This is an observational study from the Stockholm CREAtinine Measurements (SCREAM) project, a health care utilization cohort from Stockholm, Sweden, with laboratory measures from 2006-2011 and follow-up through December 2012. Included were 31,732 individuals with two or more ambulatory urine albumin to creatinine ratio (ACR) tests. We assessed the association between change in ACR during a baseline period of 1, 2, or 3 years and end-stage renal disease (ESRD) or death. Using a 2-year baseline period, there were 378 ESRD events and 1712 deaths during a median of 3 years of follow-up. Compared to stable ACR, a 4-fold increase in ACR was associated with a 3.08-times (95% confidence interval 2.59 to 3.67) higher risk of ESRD while a 4-fold decrease in ACR was associated with a 0.34-times (0.26 to 0.45) lower risk of ESRD. Similar associations were found in people with and without diabetes mellitus, with and without hypertension, and also when adjusted for the change in eGFR during the same period. The association between change in ACR and mortality was weaker: ACR increase was associated with mortality, but the relationship was largely flat for ACR decline. Results were consistent for 1-, 2-, and 3-year ACR changes. Thus, changes in albuminuria are strongly and consistently associated with the risk of ESRD and death.

  • 50. Cederholm, Tommy
    et al.
    Kirn, Dylan R.
    Koochek, Afsaneh
    Reid, Kieran F.
    von Berens, Åsa
    Travison, Thomas G.
    Folta, Sara
    Sacheck, Jennifer
    Åberg, Anna Cristina
    Dalarna University, School of Education, Health and Social Studies, Medical Science. Uppsala University.
    Fielding, Roger A.
    Effect of nutritional supplementation and structured physical activity on physical function in mobility-limited older adults: results from the VIVE2 study2015Conference paper (Refereed)
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