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  • 101.
    Grenholm, Anton
    et al.
    Högskolan Dalarna, Akademin Utbildning, hälsa och samhälle, Medicinsk vetenskap.
    Grenholm, Simon
    Helhetssyn2015Inngår i: Att slakta en guldkalv: Visioner för ett hållbart samhälle / [ed] Avner E, Granath G, Hasselgren B, Herlin B, Lundqvist E, Stockholm: Carlsson Bokförlag, 2015, 1, s. 15-26Kapittel i bok, del av antologi (Annet (populærvitenskap, debatt, mm))
  • 102. Griswald, Max G
    et al.
    Fullman, Nancy
    Hawley, Caitlin
    Arian, Nicholas
    Zimsen, Stephanie R. M
    Tymeson, Hayley D
    Venkateswaran, Vidhya
    Tapp, Austin Douglas
    Ärnlöv, Johan
    Högskolan Dalarna, Akademin Utbildning, hälsa och samhälle, Medicinsk vetenskap. Karolinska institutet.
    Gakidou, Emmanuela
    Alcohol use and burden for 195 countries and territories, 1990-2016: a systematic analysis for the Global Burden of Disease Study 20162018Inngår i: The Lancet, ISSN 0140-6736, E-ISSN 1474-547X, Vol. 392, nr 10152, s. 1015-1035Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background: Alcohol use is a leading risk factor for death and disability, but its overall association with health remains complex given the possible protective effects of moderate alcohol consumption on some conditions. With our comprehensive approach to health accounting within the Global Burden of Diseases, Injuries, and Risk Factors Study 2016, we generated improved estimates of alcohol use and alcohol-attributable deaths and disability-adjusted life-years (DALYs) for 195 locations from 1990 to 2016, for both sexes and for 5-year age groups between the ages of 15 years and 95 years and older. 

    Methods: Using 694 data sources of individual and population-level alcohol consumption, along with 592 prospective and retrospective studies on the risk of alcohol use, we produced estimates of the prevalence of current drinking, abstention, the distribution of alcohol consumption among current drinkers in standard drinks daily (defined as 10 g of pure ethyl alcohol), and alcohol-attributable deaths and DALYs. We made several methodological improvements compared with previous estimates: first, we adjusted alcohol sales estimates to take into account tourist and unrecorded consumption; second, we did a new meta-analysis of relative risks for 23 health outcomes associated with alcohol use; and third, we developed a new method to quantify the level of alcohol consumption that minimises the overall risk to individual health. 

    Findings: Globally, alcohol use was the seventh leading risk factor for both deaths and DALYs in 2016, accounting for 2.2% (95% uncertainty interval [UI] 1.5-3.0) of age-standardised female deaths and 6.8% (5.8-8.0) of age-standardised male deaths. Among the population aged 15-49 years, alcohol use was the leading risk factor globally in 2016, with 3.8% (95% UI 3.2-4-3) of female deaths and 12.2% (10.8-13-6) of male deaths attributable to alcohol use. For the population aged 15-49 years, female attributable DALYs were 2.3% (95% UI 2.0-2.6) and male attributable DALYs were 8.9% (7.8-9.9). The three leading causes of attributable deaths in this age group were tuberculosis (1.4% [95% UI 1. 0-1. 7] of total deaths), road injuries (1.2% [0.7-1.9]), and self-harm (1.1% [0.6-1.5]). For populations aged 50 years and older, cancers accounted for a large proportion of total alcohol-attributable deaths in 2016, constituting 27.1% (95% UI 21.2-33.3) of total alcohol-attributable female deaths and 18.9% (15.3-22.6) of male deaths. The level of alcohol consumption that minimised harm across health outcomes was zero (95% UI 0.0-0.8) standard drinks per week. 

    Interpretation: Alcohol use is a leading risk factor for global disease burden and causes substantial health loss. We found that the risk of all-cause mortality, and of cancers specifically, rises with increasing levels of consumption, and the level of consumption that minimises health loss is zero. These results suggest that alcohol control policies might need to be revised worldwide, refocusing on efforts to lower overall population-level consumption.

  • 103. Grooten, W.
    et al.
    Müller, M.
    Forsman, M.
    Kjellberg, K.
    Toomingas, A.
    Äng, Björn
    Högskolan Dalarna, Akademin Utbildning, hälsa och samhälle, Medicinsk vetenskap. Högskolan Dalarna, Akademin Utbildning, hälsa och samhälle, Idrotts- och hälsovetenskap. Karolinska institutet.
    Svartengren, M.
    Health risk appraisals in Swedish occupational health services2016Inngår i: Work: A journal of Prevention, Assesment and rehabilitation, ISSN 1051-9815, E-ISSN 1875-9270, Vol. 55, nr 4, s. 849-859Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    BACKGROUND: Health risk appraisals (HRAs) in occupational health services (OHS) in Sweden are very commonly used for health promotion issues, but not much research has explored the extent and nature of individual feedback that is provided. 

    OBJECTIVES: This study aimed to describe and explore HRAs in OHS regarding the content of the feedback in relation to the individual status and overall employee satisfaction. 

    METHODS: Feedback (evaluation and advice) and employee satisfaction with HRA were studied in employees that participated in health risk appraisals with a specific feedback session (HRA-F) (n = 272) and employees that participated in a single session (HRA-S) (n = 104). Associations between feedback and individual status concerning life style were assessed with Cohen's kappa (k). 

    RESULTS: The employees received mainly information and advice for improvement on health and lifestyle issues (89-100%), while advice for improvement of working conditions was less common (15-59%). The feedback provided on life style was not based on individual status (k < 0.4), except for smoking and risky alcohol consumption (k > 0.55). A great majority of employees reported good overall satisfaction with their HRAs. 

    CONCLUSIONS: The evaluation and feedback given to employees after HRAs should be based more on HRA-results and advice could be focused more on work-related factors.

  • 104. Grooten, Wilhelmus Johannes Andreas
    et al.
    Hansson, Amanda
    Forsman, Mikael
    Kjellberg, Katarina
    Toomingas, Allan
    Müller, Mira
    Svartengren, Magnus
    Äng, Björn
    Högskolan Dalarna, Akademin Utbildning, hälsa och samhälle, Medicinsk vetenskap. Karolinska Institutet; Uppsala University.
    Non-participation in initial and repeated health risk appraisals: a drop-out analysis based on a health project2019Inngår i: BMC Health Services Research, ISSN 1472-6963, E-ISSN 1472-6963, Vol. 19, nr 1, artikkel-id 130Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    BACKGROUND: Health risk assessment (HRAs) are commonly used by occupational health services (OHS) to aid workplaces in keeping their employees healthy, but for unknown reasons, many employees choose not to participate in the HRAs. The aim of the study was to explore whether demographic, lifestyle and health-related factors in employees are associated with non-participation in initial and repeated HRAs.

    METHODS: In an OHS-based health project, 2022 municipal employees were asked to participate in three repeated HRAs. Multiple logistic regression analyses were used so as to determine associations between non-participating and demographic, lifestyle and health-related factors (e.g. biomarkers).

    RESULTS: Among the employees who were asked to participate in the health project, more than half did not participate in any HRA and among those who did, more than one third did not participate in repeated HRAs. Young age, male sex and being employed in the Technical department or Health and Social Care department in comparison with being employed in the department for Childcare and Education were factors significantly associated with non-participation in the initial HRA. These factors, together with being on sick leave and having unhealthy dietary habits, were factors associated with non-participation in repeated HRAs.

    CONCLUSIONS: Among the non-participators in initial HRAs and in repeated HRAs younger men and those already related to ill-health were overrepresented. This implicates that health care providers to a higher extent should focus on "those most needed" and that employers should be more engaged in results of repeated HRA's. Future studies should focus on modifiable variables that could make the HRAs more attractive and inclusive.

  • 105.
    Gunnesson, Linnea
    et al.
    Högskolan Dalarna, Akademin Utbildning, hälsa och samhälle, Medicinsk vetenskap.
    Zetterlund, Anna
    Högskolan Dalarna, Akademin Utbildning, hälsa och samhälle, Medicinsk vetenskap.
    Fysisk aktivitetsnivå, smärtintensitet och funktionsnedsättning hos personer med ländryggssmärta: - En enkätstudie2018Independent thesis Advanced level (degree of Master (One Year)), 10 poäng / 15 hpOppgave
    Abstract [sv]

    Bakgrund

    Ländryggssmärta är mycket vanligt förekommande i västvärlden. Det innebär stort

    lidande för individen och stora kostnader för samhället. Idag behandlas ryggsmärta

    med information om att vara aktiv och vid behov rådgivning om smärtstillande

    läkemedel. Mer kunskap behövs gällande fysisk träning som prevention och

    behandling av akut- och subakut ländryggssmärta.

    Syfte

    Syftet med studien var att, för patienter med akut- och subakut ländryggsmärta,

    beskriva den fysiska aktivitetsnivån samt eventuella skillnader i smärtintensitet

    och funktionsnedsättning mellan grupper med olika aktivitetsnivåer. Syftet var

    även att undersöka samband mellan aktivitetsnivå och smärtintensitet respektive

    aktivitetsnivå och funktionsnedsättning.

    Metod

    Studien var en enkätstudie med tvärsnittsdesign. Deltagarna var 15 patienter, 9

    kvinnor och 6 män, medelålder 49,2 år, som sökt vård för akuta eller subakuta

    ländryggsbesvär till 4 olika primärvårdsenheter. Fysisk aktivitetsnivå skattades via

    Socialstyrelsens indikatorfrågor för fysisk aktivitet, smärtan med numerisk

    skattningsskala 0-10 (NRS) och Roland Morris Disability Questionnaire (RMDQ)

    besvarades. Data sammanställdes med deskriptiv statistik, skillnader testades med

    Mann-Whitney U-test och samband analyserades med Spearmans

    korrelationskoefficient.

    Resultat

    Åtta av 15 deltagare uppnådde Världshälsoorganisationens (WHO)

    rekommendationer för fysisk aktivitet (> 150 minuter i veckan). De som ägnade

    sig åt fysisk träning minst 90 minuter per vecka hade medianvärde NRS 5,5 och

    RMDQ 8, för de som tränade mindre var motsvarande värden NRS 7,5 (p=0,153)

    och RMDQ 11,5 (p=0,175). Ett svagt negativt samband identifierades mellan NRS

    (r=-0,316,) och nivå av fysisk aktivitet medans sådant samband mellan RMDQ och

    fysisk aktivitetsnivå var negligerbart (r=-0,158).

    Slutsats

    Det var ingen statistiskt signifikant skillnad mellan grupperna som tränade minst

    90 minuter per vecka och de som tränade mindre gällande varken smärtintensitet

    eller funktionsnedsättning. Ett svagt negativt men ej statistiskt signifikant

    samband kan ses mellan fysisk aktivitetsnivå och smärtintensitet.

  • 106.
    Gustavsson, Catharina
    et al.
    Högskolan Dalarna, Akademin Utbildning, hälsa och samhälle, Medicinsk vetenskap. Center for Clinical Research Dalarna; Mälardalens högskola; Uppsala universitet.
    Nordqvist, Maria
    Bröms, Kristina
    Jerdén, Lars
    Kallings, Lena V
    Wallin, Lars
    Högskolan Dalarna, Akademin Utbildning, hälsa och samhälle, Omvårdnad. Karolinska institutet; Göteborgs universitet.
    What is required to facilitate implementation of Swedish physical activity on prescription? - interview study with primary healthcare staff and management2018Inngår i: BMC Health Services Research, ISSN 1472-6963, E-ISSN 1472-6963, Vol. 18, nr 1, artikkel-id 196Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    BACKGROUND: The method, Swedish Physical Activity on Prescription (SPAP), has been launched in Swedish healthcare to promote physical activity for prevention and treatment of lifestyle related health disorders. Despite scientific support for the method, and education campaigns, it is used to a limited extent by health professionals. The aim of the study was to describe the views of health professionals on perceived facilitators, barriers and requirements for successful implementation of SPAP in primary healthcare.

    METHODS: Eighteen semi-structured interviews with stakeholders in SPAP, i.e. ten people working in local or central management and eight primary healthcare professionals in two regional healthcare organisations, were analysed using qualitative content analysis.

    RESULTS: We identified an overarching theme regarding requirements for successful implementation of SPAP: Need for knowledge and organisational support, comprising four main categories: Need for increased knowledge and affirmative attitude among health professionals; Need for clear and supportive management; Need for central supporting structures; Need for local supporting structures. Knowledge of the SPAP method content and core components was limited. Confidence in the method varied among health professionals. There was a discrepancy between the central organisation policy documents declaring that disease preventive methods were prioritised and a mandatory assignment, while the health professionals asked for increased interest, support and resources from management, primarily time and supporting structures. There were somewhat conflicting views between primary healthcare professionals and managers concerning perceived barriers and requirements. In contrast to some of the management's beliefs, all primary healthcare professionals undisputedly acknowledged the importance of promoting physical activity, but they lacked time, written routines and in some cases competence for SPAP counselling.

    CONCLUSION: The study provides knowledge regarding requirements to facilitate the implementation of SPAP in healthcare. There was limited knowledge among health professionals regarding core components of SPAP and how to practise the method, which speaks for in-depth training in the SPAP method. The findings highlight the importance of forming policies and guidelines and establishing organisational supporting structures, and ensuring that these are well known and approved in all parts of the healthcare organisation.

  • 107.
    Gustavsson, Catharina
    et al.
    Högskolan Dalarna, Akademin Utbildning, hälsa och samhälle, Medicinsk vetenskap. Uppsala universitet.
    von Koch, Lena
    A 9-year follow-up of a self-management group intervention for persistent neck pain in primary health care: a randomized controlled trial2017Inngår i: Journal of Pain Research, ISSN 1178-7090, E-ISSN 1178-7090, Vol. 10, s. 53-64Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    BACKGROUND AND OBJECTIVE: In previous short-term and 2-year follow-ups, a pain and stress self-management group intervention (PASS) had better effect on pain-related disability, self-efficacy, catastrophizing, and perceived pain control than individually administered physiotherapy (IAPT) for patients with persistent tension-type neck pain. Studies that have evaluated long-term effects of self-management approaches toward persistent neck pain are sparse. The objective of this study was to compare pain-related disability, self-efficacy for activities of daily living (ADL), catastrophizing, pain, pain control, use of analgesics, and health care utilization in people with persistent tension-type neck pain 9 years after they received the PASS or IAPT.

    MATERIALS AND METHODS: Of 156 people (PASS, n = 77; IAPT, n = 79) originally included in a randomized controlled trial, 129 people (PASS, n = 63; IAPT, n = 66) were eligible and were approached for the 9-year follow-up. They were sent a self-assessment questionnaire, comprising the Neck Disability Index, the Self-Efficacy Scale, the Coping Strategies Questionnaire, and questions regarding pain, analgesics, and health care utilization. Mixed linear models for repeated measures analysis or generalized estimating equations were used to evaluate the differences between groups and within groups over time (baseline, previous follow-ups, and 9-year follow-up) and the interaction effect of "time by group".

    RESULTS: Ninety-four participants (73%) responded (PASS, n = 48; IAPT, n = 46). At 9 years, PASS participants reported less pain-related disability, pain at worst, and analgesics usage, and a trend toward better self-efficacy compared to IAPT participants. There was a difference between groups in terms of change over time for disability, self-efficacy for ADL, catastrophizing, perceived pain control, and health care visits in favor of PASS. Analyses of simple main effects at 9 years showed that the PASS group had less disability (p = 0.006) and a trend toward better self-efficacy (p = 0.059) than the IAPT group.

    CONCLUSION: The favorable effects on pain-related disability of PASS were sustained 9 years after the intervention.

  • 108. Hagström, E
    et al.
    Hellman, P
    Larsson, T
    Ingelsson, E
    Berglund, L
    Sundström, J
    Melhus, H
    Held, C
    Lind, L
    Michaelsson, K
    Ärnlöv, Johan
    Högskolan Dalarna, Akademin Utbildning, hälsa och samhälle, Medicinsk vetenskap.
    Plasma parathyroid hormone and the risk of cardiovascular mortality in the community2009Inngår i: Circulation, ISSN 0009-7322, E-ISSN 1524-4539, Vol. 119, nr 21, s. 2765-2771Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background: Diseases with elevated levels of parathyroid hormone (PTH) such as primary and secondary hyperparathyroidism are associated with increased incidence of cardiovascular disease and death. However, data on the prospective association between circulating PTH levels and cardiovascular mortality in the community are lacking.

    Methods and Results: The Uppsala Longitudinal Study of Adult Men (ULSAM), a community-based cohort of elderly men (mean age, 71 years; n=958), was used to investigate the association between plasma PTH and cardiovascular mortality. During follow-up (median, 9.7 years), 117 participants died of cardiovascular causes. In Cox proportional-hazards models adjusted for established cardiovascular risk factors (age, systolic blood pressure, diabetes, smoking, body mass index, total cholesterol, high-density lipoprotein cholesterol, antihypertensive treatment, lipid-lowering treatment, and history of cardiovascular disease), higher plasma PTH was associated with higher risk for cardiovascular mortality (hazard ratio for 1-SD increase in PTH, 1.38; 95% confidence interval, 1.18 to 1.60;P<0.001). This association remained essentially unaltered in participants without previous cardiovascular disease and in participants with normal PTH (<6.8 pmol/L) with no other signs of a disturbed mineral metabolism (normal serum calcium, 2.2 to 2.6 mmol/L; normal glomerular filtration rate, >50 mL · min−1 · 1.73 m−2 and without vitamin D deficiency, plasma 25-OH vitamin D >37.5 nmol/L). Interestingly, elevated plasma PTH (>5.27 pmol/L) accounted for 20% (95% confidence interval, 10 to 26) of the population-attributable risk proportion for cardiovascular mortality.

    Conclusions: Plasma PTH levels predict cardiovascular mortality in the community, even in individuals with PTH within the normal range. Further studies are warranted to evaluate the clinical implications of measuring PTH in cardiovascular risk prediction and to elucidate whether PTH is a modifiable risk factor.

  • 109. Hagström, E
    et al.
    Ingelsson, E
    Sundström, J
    Hellman, P
    Larsson, TE
    Berglund, L
    Melhus, H
    Held, C
    Michaelsson, K
    Lind, L
    Ärnlöv, Johan
    Högskolan Dalarna, Akademin Utbildning, hälsa och samhälle, Medicinsk vetenskap.
    Plasma parathyroid hormone and risk of congestive heart failure in the community2010Inngår i: European Journal of Heart Failure, ISSN 1388-9842, E-ISSN 1879-0844, Vol. 12, nr 11, s. 1186-1192Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Aims. In experimental studies parathyroid hormone (PTH) has been associated with underlying causes of heart failure (HF) such as atherosclerosis, left ventricular hypertrophy, and myocardial fibrosis. Individuals with increased levels of PTH, such as primary or secondary hyperparathyroidism patients, have increased risk of ischaemic heart disease and HF. Moreover, increasing PTH is associated with worse prognosis in patients with overt HF. However, the association between PTH and the development HF in the community has not been reported.

    Methods and Results. In a prospective, community-based study of 864 elderly men without HF or valvular disease at baseline (mean age 71 years, the ULSAM study) the association between plasma (P)-PTH and HF hospitalization was investigated adjusted for established HF risk factors (myocardial infarction, hypertension, diabetes, electrocardiographic left ventricular hypertrophy, smoking, and hypercholesterolaemia) and variables reflecting mineral metabolism (S-calcium, S-phosphate, P-vitamin D, S-albumin, dietary calcium and vitamin D intake, physical activity, glomerular filtration rate, and blood draw season). During follow-up (median 8 years), 75 individuals were hospitalized due to HF. In multivariable Cox-regression analyses, higher P-PTH was associated with increased HF hospitalization (hazard ratio for 1-SD increase of PTH, 1.41, 95% CI 1.12–1.77, P = 0.003). Parathyroid hormone also predicted hospitalization in participants without apparent ischaemic HF and in participants with normal P-PTH.

    Conclusion In a large community-based sample of elderly men, PTH predicted HF hospitalizations, also after accounting for established risk factors and mineral metabolism variables. Our data suggest a role for PTH in the development of HF even in the absence of overt hyperparathyroidism.

  • 110. Hagström, E
    et al.
    Ingelsson, E
    Sundström, J
    Hellman, P
    Larsson, TE
    Berglund, L
    Melhus, H
    Held, C
    Michaelsson, K
    Lind, L
    Ärnlöv, Johan
    Högskolan Dalarna, Akademin Utbildning, hälsa och samhälle, Medicinsk vetenskap.
    Plasma parathyroid hormone and risk of congestive heart failure: population based study2009Inngår i: AHA Scientific Session, Orlando, Florida, USA, 2009Konferansepaper (Fagfellevurdert)
  • 111. Hagström, Emil
    et al.
    Kilander, Lena
    Nylander, Ruta
    Larsson, Elna-Marie
    Michaëlsson, Karl
    Melhus, Håkan
    Ahlström, Håkan
    Johansson, Lars
    Lind, Lars
    Ärnlöv, Johan
    Högskolan Dalarna, Akademin Utbildning, hälsa och samhälle, Medicinsk vetenskap. Uppsala universitet.
    Plasma parathyroid hormone is associated with vascular dementia and cerebral hyperintensities in two community-based cohorts2014Inngår i: Journal of Clinical Endocrinology and Metabolism, ISSN 0021-972X, E-ISSN 1945-7197, Vol. 99, nr 11, s. 4181-4189Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Context: In diseases with increased PTH such as hyperparathyroidism and chronic renal failure, dementia is common. Little is known of PTH and dementia in the community.

    Objective: We sought to investigate relations between PTH, clinical dementia and cerebral micro-vascular disease. Setting and Design: The Uppsala Longitudinal Study Of Adult Men (ULSAM) was prospective, baseline, 1991-1995; followup, 15.8 years. The Prospective Investigation Of The Vasculature In Uppsala Seniors (PIVUS) was cross-sectional, baseline, 2001. Both settings were community based.

    Participants and Main Outcome Measure: In the ULSAM study of 998 men (age 71) the association between PTH and dementia was investigated. In the PIVUS study of 406 men and women (age 70) the relation between PTH and magnetic resonance imaging signs of cerebral small vascular disease was investigated.

    Results: During followup, 56 individuals were diagnosed with vascular, 91 with Alzheimer's, and 59 with other dementias. In Cox-regression analyses, higher PTH was associated with vascular dementia (hazard ratio per 1 SD increase of PTH, 1.41; P < .01), but not with other dementias. The top tertile of PTH accounted for 18.5% of the population-attributable risk for vascular dementia, exceeding all other risk factors. In linear regression analysis in PIVUS, PTH was associated with increasing white matter hyperintensities (WMHI), reflecting increasing burden of cerebral small vessel disease (1 SD PTH increase, 0.31 higher category of WMHI; P = .016). All models were adjusted for vascular risk factors and mineral metabolism.

    Conclusions: In two community-based samples, PTH predicted clinically diagnosed and neuroimaging indices of vascular dementia and cerebral small vessel disease. Our data suggest a role for PTH in the development of vascular dementia.

  • 112.
    Hagström, Emil
    et al.
    Uppsala Clinical Research Center ; Medical Sciences Uppsala University, Uppsala, Sweden.
    Michaëlsson, Karl
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi.
    Melhus, Håkan
    Institutionen för medicinska vetenskaper, Klinisk farmakogenomik och osteoporos, Uppsala University, Uppsala, Sweden.
    Hansen, Thomas
    Departments of Radiology, Uppsala University, Uppsala, Sweden.
    Ahlström, Håkan
    Departments of Radiology, Uppsala University, Uppsala, Sweden.
    Johansson, Lars
    Departments of Radiology, Uppsala University, Uppsala, Sweden.
    Ingelsson, Erik
    Uppsala Clinical Research Center ; Medical Sciences Uppsala University, Uppsala, Sweden.
    Sundström, Johan
    Uppsala Clinical Research Center ; Medical Sciences Uppsala University, Uppsala, Sweden.
    Lind, Lars
    Medical Sciences Uppsala University, Uppsala, Sweden.
    Ärnlöv, Johan
    Högskolan Dalarna, Akademin Utbildning, hälsa och samhälle, Medicinsk vetenskap. Medical Sciences Uppsala University, Uppsala, Sweden.
    Plasma-parathyroid hormone is associated with subclinical and clinical atherosclerotic disease in 2 community-based cohorts2014Inngår i: Arteriosclerosis, Thrombosis and Vascular Biology, ISSN 1079-5642, E-ISSN 1524-4636, Vol. 34, nr 7, s. 1567-1579Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    OBJECTIVE: Cardiovascular risk factors have different impact on different arterial territories. Diseases with elevated circulating parathyroid hormone (PTH) such as primary hyperparathyroidism and chronic renal failure have been shown to be associated with an increased risk of cardiovascular disease, predominantly heart or cerebrovascular diseases. However, data on the associations between circulating PTH and peripheral atherosclerosis are limited.

    APPROACH AND RESULTS: Two prospective, community-based studies were used. In 306 men and women, who were 70 years old, from the Prospective investigation of the vasculature in Uppsala seniors (PIVUS) study, cross-sectional relations between PTH and atherosclerotic burden assessed by whole-body magnetic resonance angiography were investigated. In 998 men, who were 71 years old, from the Uppsala longitudinal study of adult men (ULSAM) study, the association between PTH concentration and risk of subsequent nonfatal atherosclerotic disease (excluding coronary or cerebrovascular disease) was investigated. Adjusting for established vascular risk factors, PTH was associated with burden of atherosclerosis (increase in total atherosclerotic score per SD PTH increase: 0.04, 0.003-0.08; P=0.03) in the PIVUS study. During follow-up in the ULSAM study (median 16.7 years), 89 men were diagnosed with nonfatal atherosclerotic disease. In Cox-regression analyses adjusting for established vascular risk factors and mineral metabolism, higher PTH was associated with an increased risk of nonfatal atherosclerotic disease (hazard ratio for 1 SD increase of PTH: 1.55, 1.33-1.88; P<0.0001). Results were similar when including fatal atherosclerotic disease in the outcome.

    CONCLUSIONS: In 2 independent community-based cohorts, PTH was associated to the degree of atherosclerosis and risk of clinically overt atherosclerotic disease, respectively. Our data confirm and extend previous studies supporting a role for PTH in the development of atherosclerotic disease.

  • 113.
    Hallmarker, Ulf
    et al.
    Uppsala universitet; Mora Hospital.
    Asberg, Signild
    Uppsala universitet.
    Michaelsson, Karl
    Uppsala universitet.
    Ärnlöv, Johan
    Högskolan Dalarna, Akademin Utbildning, hälsa och samhälle, Medicinsk vetenskap. Uppsala universitet.
    Hellberg, Dan
    Uppsala Univ, Dept Womens & Childrens Hlth, Uppsala, Sweden..
    Lindback, Johan
    Uppsala universitet.
    Wester, Per
    Umea universitet.
    James, Stefan
    Uppsala universitet.
    Risk of recurrent stroke and death after first stroke in long-distance ski race participants2015Inngår i: Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease, ISSN 2047-9980, E-ISSN 2047-9980, Vol. 4, nr 10, artikkel-id e002469Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background: Physical activity is of benefit for primary prevention of cardiovascular diseases, but it appears to increase the risk for atrial fibrillation. We aimed to study a cohort of patients following a first stroke in individuals with previous high physical activity, compare them to the general population with respect to recurrent stroke and death, and relate these to atrial fibrillation.

    Methods and results: From the participants of the Vasaloppet, the world's largest ski-race, and matched individuals from the general population (n=708 604), we identified 5964 patients hospitalized with a first-time stroke between 1994 and 2010. Individuals with severe diseases were excluded. One half percent of skiers and 1% of nonskiers were hospitalized due to stroke. The incidence rate was 8.3 per 100 person-years among skiers and 11.1 among nonskiers. The hazard ratio (HR) for recurrent stroke or death between the 2 groups was 0.76 (95% CI 0.67 to 0.86). The result was consistent in subgroups. The HR for death was 0.66 (95% CI 0.56 to 0.78) and for recurrent stroke 0.82 (95% CI 0.70 to 0.96). After adjustment for smoking and socioeconomic factors, the HR for death was consistent at 0.70 (95% CI 0.56 to 0.87) while the HR for recurrent stroke was not statistically significant. Outcomes for skiers with atrial fibrillation tended to show a lower risk than for nonskiers.

    Conclusions: This large cohort study supports the hypothesis that patients with a stroke and with prior regular physical activity have a lower risk of death, while their risk for recurrent stroke is similar to that of nonskiers. The skiers had a higher incidence of atrial fibrillation, but still no increased risk of recurring stroke.

  • 114. Hallmarker, Ulf
    et al.
    James, Stefan
    Michaelsson, Karl
    Ärnlöv, Johan
    Högskolan Dalarna, Akademin Utbildning, hälsa och samhälle, Medicinsk vetenskap.
    Sandin, Fredrik
    Holmberg, Lars
    Cancer incidence in participants in a long-distance ski race (Vasaloppet, Sweden) compared to the background population2015Inngår i: European Journal of Cancer, ISSN 0959-8049, E-ISSN 1879-0852, Vol. 51, nr 4, s. 558-568Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background: We studied the association between taking part in a long distance ski race and cancer incidence to address the hypothesis that a lifestyle involving a high degree of physical activity (PA) lowers cancer incidence with a pattern that is different by cancer site. Methods: Cancer incidence was estimated in a large cohort of skiers (n = 185,412) participating in the Vasaloppet long distance ski race in Sweden 1989-2010 and non-participants in the ski race, randomly selected from the Swedish general population (n = 184,617). Data include race finishing times as a measurement of physical fitness. Hazard ratios (HRs) and net probability of cancer over twenty years of follow-up were estimated for all invasive cancer, and separately for prostate, breast, colo-rectal and lung cancer, and groups of cancers with presumed relation to lifestyle. Findings: Participating in Vasaloppet was associated with a relative risk reduction for all invasive cancer of 6% (95% confidence interval 2-9%) and a relative risk reduction of 32% (95% confidence interval 28-37%) of cancer sites where there is epidemiological evidence that smoking, bodyweight, regular PA and consumption of fruit and vegetables are aetiological factors. For skin cancer the risk was increased, as for prostate cancer. Skiers with shorter finishing times had lower incidence of cancer. Interpretation: This study indicates that it is unrealistic to reduce overall population cancer incidence drastically with life style. However, cancers that are epidemiologically associated with life style factors were significantly reduced by what presumably is a blend of nonsmoking, normal body weight, sound dietary habits and PA. Our data thus provide additional support for present days' recommendations about life style prevention. Higher health awareness is associated with attendance to screening, which may explain our results for prostate cancer.

  • 115. Hansson, J
    et al.
    Vasan, RS
    Ärnlöv, Johan
    Högskolan Dalarna, Akademin Utbildning, hälsa och samhälle, Medicinsk vetenskap.
    Ingelsson, E
    Lind, l
    Larsson, A
    Michaelsson, K
    Sundström, J
    Biomarkers of extracellular matrix metabolism (MMP-9 and TIMP-1) and risk of stroke, myocardial infarction and cause-specific mortality: cohort study2011Inngår i: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 6, nr 1, artikkel-id e16185Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Objective: Turnover of the extracellular matrix in all solid organs is governed mainly by a balance between the degrading matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs). An altered extracellular matrix metabolism has been implicated in a variety of diseases. We investigated relations of serum levels of MMP-9 and TIMP-1 to mortality risk from an etiological perspective.

    Design: The prospective Uppsala Longitudinal Study of Adult Men (ULSAM) cohort, followed from 1991–1995 for up to 18.1 years. A random population-based sample of 1,082 71-year-old men, no loss to follow-up. Endpoints were all-cause (n = 628), cardiovascular (n = 230), non-cardiovascular (n = 398) and cancer mortality (n = 178), and fatal or non-fatal myocardial infarction (n = 138) or stroke (n = 163).

    Results: Serum MMP-9 and TIMP-1 levels were associated with risk of all-cause mortality (Cox proportional hazard ratio [HR] per standard deviation 1.10, 95% confidence interval [CI] 1.03–1.19; and 1.11, 1.02–1.20; respectively). TIMP-1 levels were mainly related to risks of cardiovascular mortality and stroke (HR per standard deviation 1.22, 95% CI 1.09–1.37; and 1.18, 1.04–1.35; respectively). All relations except those of TIMP-1 to stroke risk were attenuated by adjustment for cardiovascular disease risk factors. Relations in a subsample without cardiovascular disease or cancer were similar to those in the total sample.

    Conclusion: In this community-based cohort of elderly men, serum MMP-9 and TIMP-1 levels were related to mortality risk. An altered extracellular matrix metabolism may be involved in several detrimental pathways, and circulating MMP-9 or TIMP-1 levels may be relevant markers thereof.

  • 116. Helmersson, J
    et al.
    Ärnlöv, Johan
    Högskolan Dalarna, Akademin Hälsa och samhälle, Medicinsk vetenskap.
    Axelsson, T
    Basu, S
    A polymorphism in the cyclooxygenase 1 gene is associated with decreased inflammatory prostaglandin F2-a formation and lower risk of cardiovascular disease.2009Inngår i: Prostaglandins, Leukotrienes and Essential Fatty Acids, ISSN 0952-3278, E-ISSN 1532-2823, Vol. 80, nr 1, s. 51-56Artikkel i tidsskrift (Fagfellevurdert)
  • 117. Helmersson-Karlqvist, Johanna
    et al.
    Larsson, Anders
    Carlsson, Axel C.
    Venge, Per
    Sundstrom, Johan
    Ingelsson, Erik
    Lind, Lars
    Ärnlöv, Johan
    Högskolan Dalarna, Akademin Utbildning, hälsa och samhälle, Medicinsk vetenskap. Uppsala Univ, Dept Publ Hlth & Caring Sci, Uppsala, Sweden.
    Urinary neutrophil gelatinase-associated lipocalin (NGAL) is associated with mortality in a community-based cohort of older Swedish men2013Inngår i: Atherosclerosis, ISSN 0021-9150, E-ISSN 1879-1484, Vol. 227, nr 2, s. 408-413Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Objective: Neutrophil gelatinase-associated lipocalin (NGAL) indicates tubular kidney damage, neutrophil activation and possibly atherogenesis, however the prospective association between urinary NGAL (u-NGAL) and cardiovascular death in the community is not known.

    Methods: This study evaluates the association between urinary and serum NGAL and mortality in a Swedish population of 597 men aged 78 years. During the study (median follow-up 8.1 years) 261 men died, 90 of cardiovascular causes.

    Results: U-NGAL was associated with increased all-cause and cardiovascular mortality (HR 2.0 for quartile 4 vs. quartile 1, 95% CI 1.0-4.0, P < 0.05) in Cox regression models independently of cardiovascular risk factors, CRP and cystatin C estimated glomerular filtration rate (eGFR(CysC)) but not urinary Albumin (u-Alb). A combination of low eGFR(CysC) (<= 60 mL/min), high u-Alb (>= 3 mg/mmol Cr) and high u-NGAL (>= 1.19 mu g/mmol Cr) was associated with a 9-fold increased cardiovascular mortality (P < 0.001) and a 3-fold increased all-cause mortality (P < 0.001). Serum NGAL was associated with increased all-cause mortality risk independent of other cardiovascular risk factors (HR 1.4 for quartile 4 vs. 1, 95% CI 1.0-1.9, P < 0.05) but not after adjustment with CRP, eGFR(CysC) or u-Alb.

    Conclusion: This community study is the first to show that the tubular kidney biomarker u-NGAL associated with increased cardiovascular and all-cause mortality independent of cardiovascular risk factors and glomerular filtration. Additional research is needed to evaluate the utility of NGAL in clinical practice. (C) 2013 Elsevier Ireland Ltd. All rights reserved.

  • 118. Helmersson-Karlqvist, Johanna
    et al.
    Riserus, Ulf
    Sundström, Johan
    Larsson, Anders
    Jobs, Elisabeth
    Högskolan Dalarna, Akademin Hälsa och samhälle, Medicinsk vetenskap.
    Basu, Samar
    Ingelsson, Erik
    Ärnlöv, Johan
    Högskolan Dalarna, Akademin Hälsa och samhälle, Medicinsk vetenskap.
    Cytokine mediated inflammation is involved in the early stages of kidney damage and dysfunction2011Inngår i: XIII Svenska Kardiovaskulära vårmötet, Örebro, 2011Konferansepaper (Annet vitenskapelig)
    Abstract [en]

    Background: Patients with severe chronic kidney disease (CKD) are characterized by increased inflammatory activity and higher oxidative stress, conditions that have been suggested to mediate the substantially increased risk for cardiovascular disease (CVD) in these patients. However, also individuals with mild signs of kidney damage and dysfunction have been shown to have an increased risk for CVD. Yet, data on the association between mild signs of kidney damage and dysfunction and markers of inflammation and oxidative stress in the community is scarce. Research Design and Methods: Accordingly, we investigated the cross-sectional associations between cystatin C based glomerular filtration rate (GFR), urinary albumin creatinine ratio (ACR), and markers of cytokine mediated inflammation (interleukin 6 [IL-6], high sensitivity C reactive protein [hsCRP], serum amyloid A [SAA]), cyclooxygenas-mediated inflammation (urinary prostaglandin F2-alpha [PGF2alpha]) and oxidative stress (urinary F2-isprostanes) in a sub-sample of a community based cohort (Uppsala Longitudinal Study of Adult Men, ULSAM, n=648, mean age 77 year) with normal eGFR (>60 ml/min/1.73m2 ) and normal ACR (<30 µmol/L) Results: In multivariable linear regression models adjusting for age, BMI, smoking, systolic and diastolic blood pressure, total cholesterol, LDL-cholesterol, HDL-cholesterol, and triglycerides and treatment with statin, ACE-inhibit-, ASA-, anti inflammation- , cortisone medication, eGFR was inversely associated with lower hsCRP (p<0.008), lower IL-6 (p<0.01), and ACR was positive associated with higher hsCRP (p=0.01), higher IL-6 (p=<0.004) and higher SAA (p=0.001). No significant association was seen between PGF2alpha, F2-isoprostanes and eGFR and ACR. Conclusion: Our community based data suggest that cytokine mediated inflammation is involved in the early stages of kidney damage and dysfunction, while cyclooxygenas-mediated inflammation and oxidative stress is not. Further studies are needed in order to evaluate to what extent cytokine mediated inflammation mediates the increased CVD risk seen in individuals with mild signs of kidney damage and dysfunction.

  • 119. Helmersson-Karlqvist, Johanna
    et al.
    Riserus, Ulf
    Sundström, Johan
    Larsson, Anders
    Jobs, Elisabeth
    Högskolan Dalarna, Akademin Hälsa och samhälle, Medicinsk vetenskap.
    Basu, Samar
    Ingelsson, Erik
    Ärnlöv, Johan
    Högskolan Dalarna, Akademin Hälsa och samhälle, Medicinsk vetenskap.
    Cytokine mediated inflammation is involved in the early stages of kidney damage and dysfunction – Possible link to cardiovascular disease2011Inngår i: European Society of Cardiology, Paris, 2011Konferansepaper (Annet vitenskapelig)
    Abstract [en]

    Purpose: Patients with severe chronic kidney disease (CKD) are characterized by increased inflammatory activity and higher oxidative stress, conditions that have been suggested to mediate the substantially increased risk for cardiovascular disease (CVD) in these patients. However, also individuals with mild signs of kidney damage and dysfunction have been shown to have an increased risk for CVD. Yet, data on the association between mild signs of kidney damage and dysfunction and markers of inflammation and oxidative stress in the community is scarce. Methods: Accordingly, we investigated the cross-sectional associations between cystatin C based glomerular filtration rate (GFR), urinary albumin creatinine ratio (ACR), and markers of cytokine mediated inflammation (interleukin 6 [IL-6], high sensitivity C reactive protein [hsCRP], serum amyloid A [SAA]), cyclooxygenas-mediated inflammation (urinary prostaglandin F2-alpha [PGF2alpha]) and oxidative stress (urinary F2-isprostanes) in a sub-sample of a community based cohort (Uppsala Longitudinal Study of Adult Men, ULSAM, n=648, mean age 77 year) with normal eGFR (>60 ml/min/1.73m2 ) and normal ACR (<30 µmol/L) Results: In multivariable linear regression models adjusting for age, BMI, smoking, systolic and diastolic blood pressure, total cholesterol, LDL-cholesterol, HDL-cholesterol, and triglycerides and treatment with statin, ACE-inhibit-, ASA-, anti inflammation- , cortisone medication, eGFR was inversely associated with lower hsCRP (p<0.008), lower IL-6 (p<0.01), and ACR was positive associated with higher hsCRP (p=0.01), higher IL-6 (p=<0.004) and higher SAA (p=0.001). No significant association was seen between PGF2alpha, F2-isoprostanes and eGFR and ACR. Conclusions: Our community based data suggest that cytokine mediated inflammation is involved in the early stages of kidney damage and dysfunction, while cyclooxygenas-mediated inflammation and oxidative stress is not. Further studies are needed in order to evaluate to what extent cytokine mediated inflammation mediates the increased CVD risk seen in individuals with mild signs of kidney damage and dysfunction.

  • 120.
    Helmersson-Karlqvist, Johanna
    et al.
    Department of Medical Sciences, Uppsala University, Uppsala, Sweden.
    Ärnlöv, Johan
    Högskolan Dalarna, Akademin Utbildning, hälsa och samhälle, Medicinsk vetenskap. Department of Medical Sciences, Uppsala University, Uppsala, Sweden ; Science for Life Laboratory, Uppsala University, Uppsala, Sweden.
    Carlsson, Axel C
    Department of Medical Sciences, Uppsala University, Uppsala, Sweden ; Science for Life Laboratory, Uppsala University, Uppsala, Sweden ; Centre for Family and Community Medicine, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Huddinge, Sweden.
    Härmä, Johan
    Department of Medical Sciences, Uppsala University, Uppsala, Sweden.
    Larsson, Anders
    Department of Medical Sciences, Uppsala University, Uppsala, Sweden.
    Increased urinary cystatin C indicated higher risk of cardiovascular death in a community cohort2014Inngår i: Atherosclerosis, ISSN 0021-9150, E-ISSN 1879-1484, Vol. 234, nr 1, s. 108-113Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    OBJECTIVES: Urinary cystatin C (u-CysC) is a new biomarker for acute tubular kidney dysfunction and may also indicate chronic tubular dysfunction. Chronic kidney disease is an important cardiovascular risk factor, however it is not known if u-CysC is a risk marker for cardiovascular death.

    METHODS: The association between u-CysC and cardiovascular mortality was investigated in a Swedish community-based cohort of 604 men aged 78 years. During follow-up (mean 6.7 years), 203 participants died, of which 90 due to cardiovascular causes.

    RESULTS: High u-CysC (>0.029 mg/mmol Cr) was associated with a more than 2-fold risk of cardiovascular death (multivariable hazard ratio for quintile 5 vs. 1: 2.5, 95% CI 1.2-5.2, P < 0.05) in Cox regression models independent of cardiovascular risk factors, glomerular filtration rate (eGFR) and urinary Albumin. Participants with low eGFR (≤60 mL/min), albuminuria (≥3 mg/mmol Cr) and high u-CysC (>0.029 mg/mmol Cr) combined had a significantly higher cardiovascular mortality risk compared to participants with one or two of these biomarkers normal (hazard ratio 15, 95% CI: 6.7-36, P < 0.001, compared to all three biomarkers normal).

    CONCLUSIONS: This study is the first to show that increased concentrations of the tubular kidney biomarker u-CysC indicated risk of cardiovascular death independently of other cardiovascular risk factors, glomerular filtration and albuminuria. Additional research is needed to further establish the usefulness of u-CysC in clinical practice.

  • 121. Helmersson-Karlqvist, Johanna
    et al.
    Ärnlöv, Johan
    Högskolan Dalarna, Akademin Utbildning, hälsa och samhälle, Medicinsk vetenskap. Uppsala universitet.
    Carlsson, Axel C
    Lind, Lars
    Larsson, Anders
    Urinary KIM-1, but not urinary cystatin C, should be corrected for urinary creatinine2016Inngår i: Clinical Biochemistry, ISSN 0009-9120, E-ISSN 1873-2933, Vol. 49, nr 15, s. 1164-1166Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    OBJECTIVES: The interest for tubular damage markers such as urinary cystatin C (U-CystC) and kidney injury molecule-1 (U-KIM-1) grows, especially for the diagnosis of acute kidney injury. The trend to measure proteins in spot urine samples instead of 24-h urine collections calls for adjustment of urine dilution with urinary creatinine (UCr). However, it is not known whether UCr adjustment provides a more true value of basal U-CystC and U-KIM-1 levels than absolute values.

    DESIGN & METHODS: This study examines the rationale for UCr correction for U-CystC and U-KIM-1 by exploring the linear relations between U-CystC and U-KIM-1 and UCr, respectively, and the biological day to day variation of absolute concentrations and UCr adjusted values of the two biomarkers.

    RESULTS: Both U-CystC and U-KIM-1 concentrations correlated positively with UCr (R=0.37, P<0.001 and R=0.62, P<0.001, respectively) in 378 participants in a community cohort, which indicated a rationale for adjustment with UCr. However, U-CystC/Cr ratio associated negatively with UCr (R=- 0.31, P<0.001), which could indicate a certain amount of 'over-adjustment'. Morning urine collected for 10 consecutive days from 13 healthy volunteers showed a biological day to day variation of 82% for U-CystC, 75% for U-cystC/Cr ratio, 70% for U-KIM-1 and 46% for U-KIM-1/Cr ratio.

    CONCLUSIONS: This study supports the use of U-KIM-1/Cr ratio in clinical population studies. Data supporting the use of U-CysC/U-Cr ratio were less convincing and the possible confounding of UCr has to be acknowledged in clinical settings.

  • 122. Helmersson-Karlqvist, Johanna
    et al.
    Ärnlöv, Johan
    Högskolan Dalarna, Akademin Utbildning, hälsa och samhälle, Medicinsk vetenskap. Uppsala university.
    Larsson, Anders
    Cystatin C-based glomerular filtration rate associates more closely with mortality than creatinine-based or combined glomerular filtration rate equations in unselected patients2016Inngår i: European Journal of Preventive Cardiology, ISSN 2047-4873, E-ISSN 2047-4881, Vol. 23, nr 15, s. 1649-1657Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    BACKGROUND: Decreased glomerular filtration rate (GFR) is an important cardiovascular risk factor, but estimated GFR (eGFR) may differ depending on whether it is based on creatinine or cystatin C. A combined creatinine/cystatin C equation has recently been shown to best estimate GFR; however, the benefits of using the combined equation for risk prediction in routine clinical care have been less studied. This study compares mortality risk prediction by eGFR using the combined creatinine/cystatin C equation (CKD-EPI), a sole creatinine equation (CKD-EPI) and a sole cystatin C equation (CAPA), respectively, using assays that are traceable to international calibrators.

    METHODS AND RESULTS: All patients analysed for both creatinine and cystatin C from the same blood sample tube (n = 13,054) during 2005-2007 in Uppsala University Hospital Laboratory were divided into eGFR risk categories>60, 30-60 and <30 mL/min/1.73 m(2) by each eGFR equation. During follow-up (median 4.6 years), 4398 participants died, of which 1396 deaths were due to cardiovascular causes. Reduced eGFR was significantly associated with death as assessed by all eGFR equations. The net reclassification improvement (NRI) for the combination equation compared with the sole creatinine equation was 0.10 (p < 0.001) for all-cause mortality and 0.08 (p < 0.001) for cardiovascular mortality, indicating improved reclassification. In contrast, NRI for the combination equation, compared with the sole cystatin C equation, was -0.06 (p < 0.001) for all-cause mortality and -0.02 (p = 0.032) for cardiovascular mortality, indicating a worsened reclassification.

    CONCLUSIONS: In routine clinical care, cystatin C-based eGFR was more closely associated with mortality compared with both creatinine-based eGFR and creatinine/cystatin C-based eGFR.

  • 123. Helmersson-Karlqvist, Johanna
    et al.
    Ärnlöv, Johan
    Högskolan Dalarna, Akademin Utbildning, hälsa och samhälle, Medicinsk vetenskap.
    Larsson, Anders
    Day-to-day variation of urinary NGAL and rational for creatinine correction2013Inngår i: Clinical Biochemistry, ISSN 0009-9120, E-ISSN 1873-2933, Vol. 46, nr 1-2, s. 70-72Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    OBJECTIVES: The number of clinical studies evaluating the new tubular biomarker urinary neutrophil gelatinase-associated lipocalin (U-NGAL) in urine are increasing. There is no consensus whether absolute U-NGAL concentrations or urinary NGAL/creatinine (U-NGAL/Cr) ratios should be used when chronic tubular dysfunction is studied. The aim was to study the biological variation of U-NGAL in healthy subjects and the rational for urinary creatinine (U-Cr) correction in two different study samples.

    DESIGN AND METHODS: To study biological variation of U-NGAL and U-NGAL/Cr ratio and the association between U-NGAL and U-Cr in healthy subjects 13 young males and females (median age 29years) collected morning urine in 10 consecutive days. Additionally, a random subsample of 400 males from a population-based cohort (aged 78years) collecting 24-hour urine during 1day was studied.

    RESULTS: The calculated biological variation for absolute U-NGAL was 27% and for U-NGAL/Cr ratio, 101%. Absolute U-NGAL increased linearly with U-Cr concentration (the theoretical basis for creatinine adjustment) in the older males (R=0.19, P<0.001) and with borderline significance in the young adults (R=0.16, P=0.08). The U-NGAL/Cr ratio was, however, negatively associated with creatinine in the older males (R=-0.14, P<0.01) and in the young adults (R=-0.16, P=0.07) indicating a slight "overadjustment."

    CONCLUSIONS: The study provides some support for the use of U-NGAL/Cr ratio but the rather large biological variation and risk of possible overadjustment need to be considered. Both absolute U-NGAL and U-NGAL/Cr ratios should be reported for the estimation of chronic tubular dysfunction.

  • 124.
    Helmersson-Karlqvist, Johanna
    et al.
    Department of Medical Sciences/Clinical Chemistry, Uppsala University, Uppsala SE-751 85, Sweden.
    Ärnlöv, Johan
    Högskolan Dalarna, Akademin Utbildning, hälsa och samhälle, Medicinsk vetenskap. Department of Public Health and Caring Sciences/Geriatrics, Uppsala University, Uppsala, Sweden.
    Larsson, Anders
    Department of Medical Sciences/Clinical Chemistry, Uppsala University, Uppsala SE-751 85, Sweden.
    Basu, Samar
    Department of Public Health and Caring Sciences/Oxidative Stress and Inflammation, Uppsala University, Uppsala, Sweden, Centre of Excellence-Inflammation, Uppsala University Hospital, Uppsala, Sweden, Laboratory of Biochemistry, Molecular Biology, and Nutrition, University d'Auvergne, Clermont-Ferrand, France.
    Prostaglandin F2α formation is associated with mortality in a Swedish community-based cohort of older males2015Inngår i: European Heart Journal, ISSN 0195-668X, E-ISSN 1522-9645, Vol. 36, nr 4, s. 238-243Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    AIMS: An increasing number of clinical studies highlight the importance of the inflammatory mediator prostaglandin F2α (PGF2α). Prostaglandin F2α activity has been suggested to play pivotal roles in the development of cardiovascular diseases and cancer. However, whether systemic PGF2α concentrations may signal mortality is unknown. The aim was to evaluate in vivo PGF2α formation, by measuring urinary 15-keto-dihydro-PGF2α, and mortality risk in a community setting.

    METHODS AND RESULTS: Urinary 15-keto-dihydro-PGF2α was measured in a Swedish population of 670 men (aged 77-78 years) and the participants were followed up for a median of 9.7 years (383 died, among them 156 of cardiovascular causes and 102 of cancer). In Cox regression models, urinary 15-keto-dihydro-PGF2α was significantly associated with cardiovascular mortality [multivariate hazard ratio (HR) for 1 SD increase of urinary 15-keto-dihydro-PGF2α: 1.18; 95% CI:1.04-1.34; P = 0.01) independent of established cardiovascular risk factors including C-reactive protein. Urinary 15-keto-dihydro-PGF2α was also independently associated with total mortality (multivariate HR for 1 SD increase of urinary 15-keto-dihydro-PGF2α: 1.11; 95% CI: 1.01-1.21; P = 0.03). The combination of 15-keto-dihydro-PGF2α concentrations above the median and high serum high-sensitive C-reactive protein (>3 mg/L) was independently associated with a two-fold increased risk of cancer and total mortality (P = 0.02 and P < 0.001, respectively).

    CONCLUSION: This is the first study to show that the inflammatory mediator PGF2α was independently associated with mortality and specifically cardiovascular mortality 10 years later. The results are in line with the emerging evidence of the importance of the inflammatory mediator PGF2α in fatal cardiovascular disease.

  • 125. Herlitz, Johan
    et al.
    Svensson, Leif
    Strömsöe, Anneli
    Högskolan Dalarna, Akademin Utbildning, hälsa och samhälle, Medicinsk vetenskap.
    Several factors affect the prognosis2015Inngår i: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 112Artikkel i tidsskrift (Annet vitenskapelig)
  • 126. Hessulf, F.
    et al.
    Karlsson, T.
    Lundgren, P.
    Aune, S.
    Strömsöe, Anneli
    Högskolan Dalarna, Akademin Utbildning, hälsa och samhälle, Medicinsk vetenskap.
    Södersved Källestedt, M. -L
    Djärv, T.
    Herlitz, J.
    Engdahl, J.
    Factors of importance to 30-day survival after in-hospital cardiac arrest in Sweden - A population-based register study of more than 18,000 cases2018Inngår i: International Journal of Cardiology, ISSN 0167-5273, E-ISSN 1874-1754, Vol. 255, s. 237-242Artikkel i tidsskrift (Fagfellevurdert)
  • 127. Hildenwall, Helena
    et al.
    Lindkvist, Jenny
    Tumwine, James
    Bergqvist, Yngve
    Högskolan Dalarna, Akademin Utbildning, hälsa och samhälle, Medicinsk vetenskap.
    Pariyo, George
    Tomson, Göran
    Peterson, Stefan
    Low validity of caretakers’ reports on antimalarial and antibiotic use in children with severe pneumonia at hospital in Uganda2009Inngår i: Transactions of the Royal Society of Tropical Medicine and Hygiene, ISSN 0035-9203, E-ISSN 1878-3503, Vol. 103, nr 1, s. 95-101Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Febrile children in low-income countries receive care from multiple sources, and caretakers’ ability to report drug intake is crucial for appropriate prescription of drugs when reaching health facilities. This study describes and validates caretakers’ reported use of sulfamethoxazole, chloroquine and sulfadoxine in their children. We performed a cross-sectional study in 139 children diagnosed with severe pneumonia at hospital in Kampala, Uganda. Caretakers were interviewed regarding treatments given prior to arrival at the hospital. Reported drug intake was compared to drug levels in blood sampled on filter paper, analyzed by HPLC methods. Caretakers under-reported intake of the studied drugs. Positive and negative predictive values were 67 and 64% for sulfamethoxazole, 69 and 52% for chloroquine and 85 and 62% for sulfadoxine. Many caretakers were unaware of what drug had been given to the child, and more so if treated outside the home (risk ratio 2.6, 95% CI 1.2–5.6). We conclude that caretakers’ reports of drug intake have limited validity. Health workers need to improve counseling of caretakers during drug dispensing, especially for antibiotics. The roles and names of different drugs should be emphasized during counseling, and existing information systems such as immunization cards should be considered for record-keeping of treatment given.

  • 128.
    Hildingsson, Victoria
    et al.
    Högskolan Dalarna, Akademin Utbildning, hälsa och samhälle, Medicinsk vetenskap.
    Clarström, Anders
    Högskolan Dalarna, Akademin Utbildning, hälsa och samhälle, Medicinsk vetenskap.
    Kartläggning av fysioterapeutiska interventioner i multimodal smärtrehabilitering inom primärvården.: En enkätstudie.2018Independent thesis Advanced level (degree of Master (One Year)), 10 poäng / 15 hpOppgave
    Abstract [sv]

    Bakgrund:

    Långvarig smärta är ett stort folkhälsoproblem som innebär stora kostnader för

    samhället och självklart också stort lidande för individen. Multimodal smärtrehabilitering

    (MMR) innebär att olika yrkeskategorier arbetar gemensamt kring dessa patienter.

    Forskningen visar måttligt till starkt vetenskapligt stöd för MMR vid komplex

    smärtproblematik. Det finns kunskapsluckor kring vilken typ av fysioterapeutiska

    interventioner som används vid multimodal smärtrehabilitering.

    Syfte:

    Syftet med studien var att kartlägga fysioterapeuternas arbete inom ramen för

    multimodal smärtrehabilitering i primärvården.

    Metod:

    Enkätstudie av tvärsnittstyp med kvantitativ ansats baserad på en egenkonstruerad

    webbenkät. Populationen utgjordes av fysioterapeuter anslutna till Nationella Registret över

    Smärtrehabilitering (NRS) primärvård och resultatet bygger på de 23 fysioterapeuter som

    valde att svara på webbenkäten.

    Resultat:

    Resultaten baseras på svar från 71 % av de NRS-anslutna klinikerna.

    Sammanfattning av resultaten visade framför allt att råd/undervisning samt olika former av

    fysisk träning utgjorde grunden i fysioterapeutens arbete inom MMR-team i primärvården.

    Det framkommer att så gott som alla patienter träffade fysioterapeut under

    behandlingsperioden. Det var en klar övervikt mot gruppbehandling eller en kombination av

    grupp och individuell behandling gällande de fysioterapeutiska interventionerna.

    Behandlingsperioderna var för det mesta fyra till elva veckor där patienten träffade

    fysioterapeut oftast varje vecka eller flera gånger/vecka. I primärvårdens MMR-team var

    fysioterapeut, arbetsterapeut, KBT terapeut, läkare och rehabkoordinator de vanligast

    förekommande yrkeskategorierna i teamen.

    Slutsats:

    Fysioterapeuten har en central roll i primärvårdens MMR-team och använder sig

    primärt av evidensbaserade, aktiva interventioner.

  • 129. Holzmann, Martin J
    et al.
    Carlsson, Axel C
    Hammar, Niklas
    Ivert, Torbjörn
    Walldius, Göran
    Jungner, Ingmar
    Wändell, Per
    Ärnlöv, Johan
    Högskolan Dalarna, Akademin Utbildning, hälsa och samhälle, Medicinsk vetenskap. Uppsala university.
    Chronic kidney disease and 10-year risk of cardiovascular death2016Inngår i: European Journal of Preventive Cardiology, ISSN 2047-4873, E-ISSN 2047-4881, Vol. 23, nr 11, s. 1187-1194Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    BACKGROUND: In recent clinical guidelines, individuals with chronic kidney disease are considered to have a similar 10-year absolute risk of cardiovascular death as individuals with diabetes or established cardiovascular disease. There is limited evidence to support this claim.

    METHODS: We investigated the 10-year risk for cardiovascular death in individuals with moderate or severe chronic kidney disease (glomerular filtration rate of 30-60 or <30 mL/min/1.73 m(2), respectively) in a cohort of primary care health check-ups in Stockholm, Sweden (n = 295,191, 46% women, 4290 cardiovascular deaths during 10 years follow-up). We also assessed the risk associated with diabetes or cardiovascular disease. The inclusion criteria, exposure, study outcome and follow-up period adhered strictly to the definitions of the European Society of Cardiology guidelines.

    RESULTS: The absolute 10-year risk of cardiovascular death was 3.9% and 14.0% in individuals with moderate and severe chronic kidney disease, respectively, but was substantially lower in women and in younger individuals. The risk in individuals with prevalent diabetes and cardiovascular disease was approximately two and three times higher compared to the risk estimate for moderate chronic kidney disease (hazard ratio (HR) 4.1, 95% confidence interval (CI) 3.8-4.5 and HR 6.2, 95% CI 5.7-6.7 vs. HR 2.3 95% CI 2.0-2.6, respectively) while the risk for individuals with severe chronic kidney disease appeared more congruent to that of diabetes and cardiovascular disease (HR 5.5, 95% CI 3.3-8.9).

    CONCLUSIONS: Although moderate chronic kidney disease is an independent predictor for an increased 10-year risk of cardiovascular death, only those with severe chronic kidney disease had similar risk to those with diabetes or cardiovascular disease.

  • 130. Huang, Biying
    et al.
    Svensson, Per
    Ärnlöv, Johan
    Högskolan Dalarna, Akademin Utbildning, hälsa och samhälle, Medicinsk vetenskap. Uppsala university.
    Sundström, Johan
    Lind, Lars
    Ingelsson, Erik
    Effects of cigarette smoking on cardiovascular-related protein profiles in two community-based cohort studies2016Inngår i: Atherosclerosis, ISSN 0021-9150, E-ISSN 1879-1484, Vol. 254, s. 52-58Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    BACKGROUND AND AIMS: Cardiovascular diseases account for the largest fraction of smoking-induced deaths. Studies of smoking in relation to cardiovascular-related protein markers can provide novel insights into the biological effects of smoking. We investigated the associations between cigarette smoking and 80 protein markers known to be related to cardiovascular diseases in two community-based cohorts, the Prospective Study of the Vasculature in Uppsala Seniors (PIVUS, n = 969, 50% women, all aged 70 years) and the Uppsala Longitudinal Study of Adult Men (ULSAM, n = 717, all men aged 77 years).

    METHODS: Smoking status was self-reported and defined as current smoker, former smoker or never-smoker. Levels of the 80 proteins were measured using the proximity extension assay, a novel PCR-based proteomics technique.

    RESULTS: We found 30 proteins to be significantly associated with current cigarette smoking in PIVUS (FDR<5%); and ten were replicated in ULSAM (p < 0.05). Matrix metalloproteinase-12 (MMP-12), growth/differentiation factor 15 (GDF-15), urokinase plasminogen activator surface receptor (uPAR), TNF-related apoptosis-inducing ligand receptor 2 (TRAIL-R2), lectin-like oxidized LDL receptor 1 (LOX-1), hepatocyte growth factor (HGF), matrix metalloproteinase-10 (MMP-10) and matrix metalloproteinase-1 (MMP-1) were positively associated, while endothelial cell-specific molecule 1 (ESM-1) and interleukin-27 subunit alpha (IL27-A) showed inverse associations. All of them remained significant in a subset of individuals without manifest cardiovascular disease.

    CONCLUSIONS: The findings of the present study suggest that cigarette smoking may interfere with several essential parts of the atherosclerosis process, as evidenced by associations with protein markers representing endothelial dysfunction, inflammation, neointimal formation, foam cell formation and plaque instability.

  • 131.
    Huang, X
    et al.
    Divisions of Renal Medicine and Baxter Novum, Department of Clinical Science, Intervention, and Technology, Karolinska Institutet, Stockholm, Sweden.
    Sjögren, P
    Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism, Uppsala University, Uppsala, Sweden.
    Ärnlöv, Johan
    Högskolan Dalarna, Akademin Utbildning, hälsa och samhälle, Medicinsk vetenskap. Department of Public Health and Caring Sciences, Section of Geriatrics, Uppsala University, Uppsala, Sweden.
    Cederholm, T
    Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism, Uppsala University, Uppsala, Sweden.
    Lind, L
    Department of Medical Sciences, Acute and Internal Medicine, Uppsala University, Uppsala, Sweden.
    Stenvinkel, P
    Divisions of Renal Medicine and Baxter Novum, Department of Clinical Science, Intervention, and Technology, Karolinska Institutet, Stockholm, Sweden.
    Lindholm, B
    Divisions of Renal Medicine and Baxter Novum, Department of Clinical Science, Intervention, and Technology, Karolinska Institutet, Stockholm, Sweden.
    Risérus, U
    Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism, Uppsala University, Uppsala, Sweden.
    Carrero, J J
    Divisions of Renal Medicine and Baxter Novum, Department of Clinical Science, Intervention, and Technology, Karolinska Institutet, Stockholm, Sweden, Center for Molecular Medicine, Karolinska Institutet, Stockholm, Sweden .
    Serum fatty acid patterns, insulin sensitivity and the metabolic syndrome in individuals with chronic kidney disease2014Inngår i: Journal of Internal Medicine, ISSN 0954-6820, E-ISSN 1365-2796, Vol. 275, nr 1, s. 71-83Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    OBJECTIVES: The causes of the multiple metabolic disorders of individuals with chronic kidney disease (CKD) are not fully known. We investigated the relationships between dietary fat quality, the metabolic syndrome (MetS), insulin sensitivity and inflammation in individuals with CKD.

    SUBJECTS: Two population-based surveys were conducted in elderly Swedish individuals (aged 70 years) with serum cystatin C-estimated glomerular filtration rate <60 mL min(-1) /1.73 m(2) : the Uppsala Longitudinal Study of Adult Men (ULSAM) and the Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS) surveys. The present population comprised 274 men and 187 subjects (63% women) from the ULSAM and PIVUS cohorts, respectively.

    DESIGN: Factor analyses of serum fatty acids were used to evaluate dietary fat quality. Insulin sensitivity was measured by homeostasis model assessment of insulin resistance (IR) and, in ULSAM, also by euglycaemic clamp.

    RESULTS: Factor analyses generated two fatty acid patterns of (i) low linoleic acid (LA)/high saturated fatty acid (SFA) or (ii) high n-3 polyunsaturated fatty acid (n-3 PUFA) levels. In both surveys, the low LA/high SFA pattern increased the odds of having MetS [adjusted odds ratio 0.60 [95% confidence interval (CI) 0.44-0.81] and 0.45 (95% CI 0.30-0.67) per SD decrease in factor score in the ULSAM and PIVUS surveys, respectively] and was directly associated with both IR and C-reactive protein. The n-3 PUFA pattern was not consistently associated with these risk factors.

    CONCLUSIONS: A serum fatty acid pattern reflecting low LA and high SFA was strongly associated with MetS, IR and inflammation in two independent surveys of elderly individuals with CKD. At present, there are no specific dietary guidelines for individuals with CKD; however, these findings indirectly support current recommendations to replace SFAs with PUFAs from vegetable oils.

  • 132. Huang, Xiaoyan
    et al.
    Jiménez-Moleón, José Juan
    Lindholm, Bengt
    Cederholm, Tommy
    Ärnlöv, Johan
    Högskolan Dalarna, Akademin Utbildning, hälsa och samhälle, Medicinsk vetenskap.
    Risérus, Ulf
    Sjögren, Per
    Carrero, Juan Jesús
    Mediterranean diet, kidney function, and mortality in men with CKD2013Inngår i: Clinical journal of the American Society of Nephrology : CJASN, ISSN 1555-905X, Vol. 8, nr 9, s. 1548-1555Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    BACKGROUND AND OBJECTIVES: Adherence to a Mediterranean diet may link to a better preserved kidney function in the community as well as a favorable cardiometabolic profile and reduced mortality risk in individuals with manifest CKD.

    DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Dietary habits were determined by 7-day dietary records in a population-based cohort of 1110 Swedish men (age 70 years) from 1991 to 1995, 506 of whom were considered to have CKD because of a GFR<60 ml/min per 1.73 m(2). A Mediterranean Diet Score was calculated, and participants were categorized as having low, medium, or high adherence. Adequate dietary reporters were identified with Goldberg cutoffs (n=597). Deaths were registered during a median follow-up of 9.9 years.

    RESULTS: Compared with low adherents, medium and high adherents were 23% and 42% less likely to have CKD, respectively (adjusted odds ratio [95% confidence interval]=0.77 [0.57 to 1.05] and 0.58 [0.38 to 0.87], respectively, P for trend=0.04). Among those individuals with CKD, phosphate intake and net endogenous acid production were progressively lower across increasing adherence groups. No differences were observed regarding other cardiometabolic risk factors across adherence groups. As many as 168 (33%) CKD individuals died during follow-up. Compared with low adherents, proportional hazards regression associated medium and high adherents to a 25% and 23% lower mortality risk, respectively (adjusted hazard ratio [95% confidence interval]=0.75 [0.52 to 1.06] and 0.77 [0.44 to 1.36], respectively, P for trend=0.10). Sensitivity analyses showed significant and stronger associations when only adequate dietary reporters were considered.

    CONCLUSIONS: Adherence to a Mediterranean dietary pattern is associated with lower likelihood of CKD in elderly men. A greater adherence to this diet independently predicted survival in those patients with manifest CKD. Clinical trials are warranted to test the hypothesis that following such a diet could improve outcomes (independent of other healthy lifestyles) in CKD patients.

  • 133. Huang, Xiaoyan
    et al.
    Sjögren, Per
    Cederholm, Tommy
    Ärnlöv, Johan
    Högskolan Dalarna, Akademin Utbildning, hälsa och samhälle, Medicinsk vetenskap.
    Lindholm, Bengt
    Risérus, Ulf
    Carrero, Juan Jesús
    Serum and adipose tissue fatty acid composition as biomarkers of habitual dietary fat intake in elderly men with chronic kidney disease2014Inngår i: Nephrology, Dialysis and Transplantation, ISSN 0931-0509, E-ISSN 1460-2385, Vol. 29, nr 1, s. 128-136Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background Fatty acid (FA) composition in serum cholesterol esters (CE) and adipose tissue (AT) reflect the long-term FA intake in the general population. Because both dietary intake and FA biomarkers associate with renal function, our aim was to identify which CE and AT FAs are useful biomarkers of habitual FA intake in individuals with chronic kidney disease (CKD).

    Methods Cross-sectional analysis was performed in 506 men (aged 70 years) with a glomerular filtration rate (GFR) of <60 mL/min per 1.73 m(2) from the Uppsala Longitudinal Study of Adult Men cohort. Dietary habits were evaluated with a 7-day dietary record. FA compositions in CE and AT were analyzed by gas-liquid chromatography in two random subsamples of 248 and 318 individuals, respectively.

    Results Both CE and AT linoleic acid and docosahexaenoic acid (DHA) were strongly associated with their corresponding intake, after adjustments for non-dietary factors. The proportions of eicosapentaenoic acid (EPA) and palmitic acid in CE and AT moderately correlated with dietary intake, whereas correlations of other FAs were weaker or absent. Proportions of EPA and DHA in CE and AT were positively associated with the total energy-adjusted fish intake. Results were confirmed in adequate reporters as identified by the Goldberg cutoff method. These relationships held constant, regardless of a GFR above or below 45 mL/min per 1.73 m(2) or the prevalence of microalbuminuria.

    Conclusions Proportions of EPA, DHA, palmitic and linoleic acid in serum CE and AT are good indicators of their dietary intake in men with CKD. They can be considered valid biomarkers for epidemiological studies and assessment of compliance.

  • 134.
    Hultén, Petra
    Högskolan Dalarna, Akademin Utbildning, hälsa och samhälle, Medicinsk vetenskap.
    Upplevelser av behandlingskonceptet Lee Silverman Voice Treatment BIG bland personer med Parkinsons sjukdom: -­ En kvalitativ intervjustudie2018Independent thesis Advanced level (degree of Master (One Year)), 10 poäng / 15 hpOppgave
    Abstract [sv]

    Bakgrund: Dagens forskning fokuseras främst på de mätbara effekterna av fysioterapeutiska interventioner vid Parkinsons sjukdom och i mindre utsträckning på personernas upplevelser av behandling. Forskning som beskriver personers upplevelser av Lee Silverman Voice Treatment BIG (LSVT BIG) saknas.

    Syfte: Att undersöka och beskriva hur personer med diagnostiserad Parkinsons sjukdom upplever instruktörsledd individuell behandling utifrån behandlingskonceptet LSVT BIG.

    Metod: Kvalitativ ansats innefattande tre fokusgrupper om sammanlagt 19 personer med Parkinsons sjukdom som startat behandlingskonceptet LSVT BIG. Intervjufrågorna fokuserades på personernas upplevelser av behandlingsinterventionen. Intervjuerna transkriberades innan de analyserades genom kvalitativ innehållsanalys.

    Resultat: I analysen framkom två överordnade teman;; Förutsättningar för behandlingseffekter som innefattar kategorierna En stor satsning, Betydelsen av instruktörens roll, Eget ansvar och Stöd från omgivningen. Det andra temat var Behandlingseffekter av LSVT BIG vilket innefattar kategorierna Fysiska, Psykiska och Sociala effekter samt Beteendeförändring.

    Slutsats: För goda resultat av LSVT BIG krävs en stor satsning av individen, av dennes anhöriga och av vården. Den stora satsningen kräver anpassningar av behandlingsinterventionen utifrån förutsättningar hos förutnämnda parter. Instruktörens roll, stöd från närstående, självdisciplin och en känsla av att kunna påverka sin situation definierades i resultaten som motiverande faktorer som ger förutsättningar för goda behandlingseffekter. Behandlingseffekterna upplevdes som mångfacetterade och återspeglade alla delar av den biopsykosociala modellen. Tydligast framkom förbättringar av forskningspersonernas fysiska funktioner vilka upplevdes överförbara till aktiviteter i det dagliga livet.

  • 135. Hållmarker, U
    et al.
    Lindbäck, J
    Michaëlsson, K
    Ärnlöv, Johan
    Högskolan Dalarna, Akademin Utbildning, hälsa och samhälle, Medicinsk vetenskap. Karolinska institutet.
    Åsberg, S
    Wester, P
    Hellberg, D
    Lagerqvist, B
    James, S
    Survival and incidence of cardiovascular diseases in participants in a long-distance ski race (Vasaloppet, Sweden) compared to the background population2018Inngår i: European Heart Journal - Quality of Care and Clinical Outcomes, ISSN 2058-5225, E-ISSN 2058-1742, Vol. 4, nr 2, s. 91-97Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Aims

    We studied the relationship between taking part in a long-distance ski race and incidence of cardiovascular diseases (CVDs) to address the hypothesis that lifestyle lowers the incidence.

    Methods and results

    A cohort of 399 630 subjects in Sweden, half were skiers in the world’s largest ski race, and half were non-skiers. Non-skiers were frequency matched for sex, age, and year of race. Individuals with severe diseases were excluded. The endpoints were death, myocardial infarction, or stroke. The subjects were followed up for a maximum of 21.8 years and median of 9.8 years. We identified 9399 death, myocardial infarction, or stroke events among non-skiers and 4784 among the Vasaloppet skiers. The adjusted hazard ratios (HRs) comparing skiers and non-skiers were 0.52 [95% confidence interval (CI) 0.49–0.54] for all-cause mortality, 0.56 (95% CI 0.52–0.60) for myocardial infarction and 0.63 (95% CI 0.58–0.67) for stroke and for all three outcomes 0.56 (95% CI 0.54–0.58). The results were consistent across subgroups: age, sex, family status, education, and race year. For skiers, a doubling of race time was associated with a higher age-adjusted risk of 19%, and male skiers had a doubled risk than female skiers, with a HR 2.06 (95% CI 1.89–2.41). The outcome analyses revealed no differences in risk of atrial fibrillation between skiers and non-skiers.

    Conclusion

    This large cohort study provides additional support for the hypothesis that individuals with high level of physical activity representing a healthy lifestyle, as evident by their participation in a long-distance ski race, have a lower risk of CVD or death.

  • 136. Hållmarker, Ulf
    et al.
    Michaëlsson, Karl
    Ärnlöv, Johan
    Högskolan Dalarna, Akademin Utbildning, hälsa och samhälle, Medicinsk vetenskap. Uppsala universitet.
    Hellberg, Dan
    Lagerqvist, Bo
    Lindbäck, Johan
    James, Stefan
    Risk of recurrent ischaemic events after myocardial infarction in long-distance ski race participants2016Inngår i: European Journal of Preventive Cardiology, ISSN 2047-4873, E-ISSN 2047-4881, Vol. 23, nr 3, s. 282-290Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Aims: To study whether a high level of physical activity prior to myocardial infarction (MI) also protects against recurrent MI (re-MI) or death.

    Methods and Results: A longitudinal study of a primary cohort consisting of 204,038 skiers with a proved substantially high level of physical activity in the world's largest long-distance ski race, Vasaloppet, and 499,543 non-skiers selected from the Swedish population. Individuals with severe diseases at baseline were excluded. In the nationwide clinical register, Swedeheart, we identified 7092 individuals with a first MI incident between 1989 and 2010. Of these, 1039 (0.5%) were skiers and 6053 (1.2%) were non-skiers. One hundred and sixty-three (15.7%) skiers and 1352 (22.3%) non-skiers suffered a re-MI or died during follow-up (median 4.44 years), corresponding to an incidence rate of 38.9 (95% confidence interval (CI) 33.2-45.4)/1000 person-years and 55.6 (95% CI 52.7-58.7)/1000 person-years, respectively. Severity of MI in both groups was the same. For skiers compared to non-skiers the unadjusted hazard ratio (HR) for re-MI was 0.66 (95% CI 0.52-0.82). For death or re-MI, HR was 0.70 (95% CI 0.59-0.82) with consistent results in subgroups based on race year, age, gender, education level, marital status. After adjustment for also smoking, diabetes, hypertension and cardiovascular medication, HR was 0.80 (95% CI 0.67-0.97).

    Conclusions: This large cohort study supports the hypothesis that patients with MI and with prior physical activity and healthy lifestyle, as evidenced by their participation in a long-distance ski race, have a lower risk of subsequent re-MI or death. 

  • 137. Hållmarker, Ulf
    et al.
    Michaëlsson, Karl
    Ärnlöv, Johan
    Högskolan Dalarna, Akademin Utbildning, hälsa och samhälle, Medicinsk vetenskap.
    James, Stefan
    Cardiac arrest in a long-distance ski race (Vasaloppet) in Sweden2012Inngår i: Journal of the American College of Cardiology, ISSN 0735-1097, E-ISSN 1558-3597, Vol. 60, nr 15, s. 1431-1432Artikkel i tidsskrift (Fagfellevurdert)
  • 138. Iggman, D
    et al.
    Ärnlöv, Johan
    Högskolan Dalarna, Akademin Utbildning, hälsa och samhälle, Medicinsk vetenskap.
    Vessby, B
    Cederholm, T
    Sjögren, P
    Risérus, U
    Adipose tissue fatty acids and insulin sensitivity in elderly men2010Inngår i: Diabetologia, ISSN 0012-186X, E-ISSN 1432-0428, Vol. 53, nr 5, s. 850-857Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Aims/hypothesis: Dietary fatty acids may affect insulin sensitivity. Adipose tissue fatty acid composition partly reflects long-term dietary intake, but data from large studies regarding relationships with insulin sensitivity are lacking. We aimed to determine the association between adipose tissue fatty acids and insulin sensitivity in elderly Swedish men. Methods In a cross-sectional analysis of the community-based Uppsala Longitudinal Study of Adult Men (n?=?795, mean age 71 years), adipose tissue biopsies were obtained and fatty acid composition was determined by gas–liquid chromatography. Insulin sensitivity was measured directly by a euglycaemic clamp. Results Palmitic acid (16:0), the major saturated fatty acid (SFA) in the diet and in adipose tissue, was negatively correlated with insulin sensitivity (r?=?-0.14), as were 16:1 n-7 (r?=?-0.15), 20:3 n-6 (r?=?-0.31), 20:4 n-6 (r?=?-0.38), 22:4 n-6 (r?=?-0.37) and 22:5 n-3 (r?=?-0.24; p?<?0.001 for all). Some minor SFAs were positively correlated; 12:0 (r?=?0.46), 14:0 (r?=?0.32), 17:0 (r?=?0.21) and 18:0 (r?=?0.41; p?<?0.001 for all), as were essential polyunsaturated fatty acids (PUFAs) 18:2 n-6 (r?=?0.10, p?<?0.01) and 18:3 n-3 (r?=? 0.16, p?<?0.001). Docosahexaenoic acid (22:6 n-3) was negatively correlated (r?=?-0.11, p?<?0.01), whereas eicosapentaenoic acid (20:5 n-3) was not (r?=?-0.02, NS). Most associations diminished or disappeared in lean individuals, indicating an effect of obesity. Conclusions/interpretation Adipose tissue enriched with palmitic acid and depleted of essential PUFAs is associated with insulin resistance. The positive association between minor SFAs and insulin sensitivity merits further investigation.

  • 139. Iggman, David
    et al.
    Rosqvist, Fredrik
    Larsson, Anders
    Ärnlöv, Johan
    Högskolan Dalarna, Akademin Utbildning, hälsa och samhälle, Medicinsk vetenskap. Uppsala universitet.
    Beckman, Lena
    Rudling, Mats
    Risérus, Ulf
    Role of dietary fats in modulating cardiometabolic risk during moderate weight gain: a randomized double-blind overfeeding trial (LIPOGAIN study)2014Inngår i: Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease, ISSN 2047-9980, E-ISSN 2047-9980, Vol. 3, nr 5, artikkel-id e001095Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    BACKGROUND: Whether the type of dietary fat could alter cardiometabolic responses to a hypercaloric diet is unknown. In addition, subclinical cardiometabolic consequences of moderate weight gain require further study.

    METHODS AND RESULTS: In a 7-week, double-blind, parallel-group, randomized controlled trial, 39 healthy, lean individuals (mean age of 27±4) consumed muffins (51% of energy [%E] from fat and 44%E refined carbohydrates) providing 750 kcal/day added to their habitual diets. All muffins had identical contents, except for type of fat; sunflower oil rich in polyunsaturated fatty acids (PUFA diet) or palm oil rich in saturated fatty acids (SFA diet). Despite comparable weight gain in the 2 groups, total: high-density lipoprotein (HDL) cholesterol, low-density lipoprotein:HDL cholesterol, and apolipoprotein B:AI ratios decreased during the PUFA versus the SFA diet (-0.37±0.59 versus +0.07±0.29, -0.31±0.49 versus +0.05±0.28, and -0.07±0.11 versus +0.01±0.07, P=0.003, P=0.007, and P=0.01 for between-group differences), whereas no significant differences were observed for other cardiometabolic risk markers. In the whole group (ie, independently of fat type), body weight increased (+2.2%, P<0.001) together with increased plasma proinsulin (+21%, P=0.007), insulin (+17%, P=0.003), proprotein convertase subtilisin/kexin type 9, (+9%, P=0.008) fibroblast growth factor-21 (+31%, P=0.04), endothelial markers vascular cell adhesion molecule-1, intercellular adhesion molecule-1, and E-selectin (+9, +5, and +10%, respectively, P<0.01 for all), whereas nonesterified fatty acids decreased (-28%, P=0.001).

    CONCLUSIONS: Excess energy from PUFA versus SFA reduces atherogenic lipoproteins. Modest weight gain in young individuals induces hyperproinsulinemia and increases biomarkers of endothelial dysfunction, effects that may be partly outweighed by the lipid-lowering effects of PUFA.

    CLINICAL TRIAL REGISTRATION URL: http://ClinicalTrials.gov. Unique identifier: NCT01427140.

  • 140. Iggman, David
    et al.
    Ärnlöv, Johan
    Högskolan Dalarna, Akademin Utbildning, hälsa och samhälle, Medicinsk vetenskap. Uppsala universitet.
    Cederholm, Tommy
    Risérus, Ulf
    Association of adipose tissue fatty acids with cardiovascular and all-cause mortality in elderly men2016Inngår i: JAMA cardiology, ISSN 2380-6583, E-ISSN 2380-6591, Vol. 1, nr 7, s. 745-753Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Importance: The major polyunsaturated fatty acids in adipose tissue objectively reflect long-term dietary intake, and may provide more reliable information than would self-reported intake. Whether adipose tissue fatty acids predict cardiovascular and all-cause mortality needs investigation.

    Objective: To investigate associations between adipose tissue fatty acids and cardiovascular and overall mortality in a cohort of elderly men.

    Design, Setting, and Participants: We hypothesized that polyunsaturated fatty acids reflecting dietary intake, are inversely associated with cardiovascular and all-cause mortality. In the Swedish cohort study Uppsala Longitudinal Cohort of Adult Men, buttock fatty acid composition was analyzed by gas-liquid chromatography in 1992 to 1993 and 2008. The study participants were followed during 11 311 person-years, between 1991 and 2011 (median follow-up, 14.8 years). In this community-based study that took place from 1970 to 1973, all men born in 1920 to 1924 in Uppsala, Sweden, were invited and 2322 (82%) were included (at age 50 years). At the reinvestigation at age 71 years, 1221 (73%) of the 1681 invited men participated. Adipose tissue biopsy specimens were taken in a subsample of 853 men. There was no loss to follow-up.

    Exposures: Adipose tissue proportions of 4 polyunsaturated fatty acids that were considered to mainly reflect dietary intake (linoleic acid, 18:2n-6; α-linolenic acid, 18:3n-3; eicosapentaenoic acid, 20:5n-3; and docosahexaenoic acid, 22:6n-3) comprised primary analyses, and all other available fatty acids were secondary analyses.

    Main Outcomes and Measures: Hazard ratios (HRs) for cardiovascular and all-cause mortality using Cox proportional hazards regression analyses, performed in 2015.

    Results: Among the 853 Swedish men, there were 605 deaths, of which 251 were cardiovascular deaths. After adjusting for risk factors, none of the 4 primary fatty acids were associated with cardiovascular mortality (HR, 0.92-1.05 for each standard deviation increase; P ≥ .27). Linoleic acid was inversely associated with all-cause mortality (HR, 0.90; 95% CI, 0.82-0.98; P = .02) and directly associated with intake (P < .001). In secondary analyses, palmitoleic acid, 16:1n-7 (HR, 1.11; 95% CI, 1.02-1.21; P = .02) was associated with higher all-cause mortality, whereas heptadecanoic acid, 17:0, tended to be associated with lower all-cause mortality (HR, 0.89; 95% CI, 0.79-1.00; P = .05). Arachidonic:linoleic acid ratio was associated with both cardiovascular (HR, 1.15; 95% CI, 1.05-1.31; P = .04) and all-cause (HR, 1.13; 95% CI, 1.04-1.23; P = .005) mortality.

    Conclusions and Relevance: Adipose tissue linoleic acid was inversely associated with all-cause mortality in elderly men, although not significantly with cardiovascular mortality.

  • 141. Ingelsson, E
    et al.
    Sundström, J
    Melhus, H
    Michaelsson, K
    Berne, C
    Vasan, RS
    Risérus, U
    Blomhoff, R
    Lind, L
    Ärnlöv, Johan
    Högskolan Dalarna, Akademin Utbildning, hälsa och samhälle, Medicinsk vetenskap. Department of Public Health and Caring Sciences, Uppsala University, Uppsala, Sweden.
    Circulating retinol-binding protein 4, cardiovascular risk factors and prevalent cardiovascular disease in elderly2009Inngår i: Atherosclerosis, ISSN 0021-9150, E-ISSN 1879-1484, Vol. 206, nr 1, s. 239-244Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Objective: Our aim was to examine relations of serum retinol-binding protein 4 (RBP4) to cardiovascular risk factors, and prevalent metabolic syndrome (MetS) and cardiovascular disease (CVD) in a large community-based sample of elderly.

    Methods: We evaluated cross-sectional relations of serum RBP4 to cardiovascular risk factors including anthropometrical measures, blood pressure, lipid measures, fasting glucose and insulin, body fat distribution including truncal fat by dual-energy x-ray absorptiometry (DXA), homeostasis model assessment insulin resistance (HOMA-IR) and prevalent MetS in one thousand eight 70-year old participants (50% women) of the Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS), and in five hundred seven 82-year old men from Uppsala Longitudinal Study of Adult Men (ULSAM). In ULSAM, we also examined associations with prevalent CVD.

    Results: RBP4 concentrations were positively correlated with serum triglycerides (r = 0.30; P < 0.0001 in both samples), whereas correlations with body mass index (BMI), waist circumference, sagittal abdominal diameter, total and truncal fat mass, total cholesterol, fasting glucose and HOMA-IR were weak. In multivariable-adjusted models, RBP-4 was associated with MetS (odds ratio (OR), 1.16 and 1.33; 95% confidence interval (CI), 0.99–1.37 and 1.05–1.67 per 1-standard deviation (SD) increase in PIVUS and ULSAM, respectively), and prior cerebrovascular disease (OR, 1.37; 95% CI, 1.00-1.88 per 1-SD increase in ULSAM), but not with prior myocardial infarction.

    Conclusion: In elderly, RBP4 concentrations were associated with MetS and its components in both sexes, and prior cerebrovascular disease in men. These findings are consistent with the hypothesis that circulating RBP4 could be a marker of metabolic complications and possibly also atherosclerosis and overt CVD.

  • 142. Ingelsson, E
    et al.
    Ärnlöv, Johan
    Högskolan Dalarna, Akademin Utbildning, hälsa och samhälle, Medicinsk vetenskap.
    Sundström, J
    Risérus, U
    Michaelsson, K
    Byberg, L
    Relative importance and conjoint effects of obesity and physical inactivity for development of insulin resistance.2009Inngår i: European Journal of Cardiovascular Prevention & Rehabilitation, ISSN 1741-8267, E-ISSN 1741-8275, Vol. 16, nr 1, s. 28-33Artikkel i tidsskrift (Fagfellevurdert)
  • 143. Ingelsson, E
    et al.
    Ärnlöv, Johan
    Högskolan Dalarna, Akademin Utbildning, hälsa och samhälle, Medicinsk vetenskap. Uppsala University, Department of Health and Social Sciences.
    Zethelius, B
    Vasan, RS
    Flyvbjerg, A
    Frystyk, J
    Berne, C
    Hänni, A
    Lind, L
    Sundström, J
    Associations of serum adiponectin with skeletal muscle morphology and insulin sensitivity2009Inngår i: Journal of Clinical Endocrinology and Metabolism, ISSN 0021-972X, E-ISSN 1945-7197, Vol. 94, nr 3, s. 953-957Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Context: Skeletal muscle morphology and function are strongly associated with insulin sensitivity.

    Objective: The objective of the study was to test the hypothesis that circulating adiponectin is associated with skeletal muscle morphology and that adiponectin mediates the relation of muscle morphology to insulin sensitivity.

    Design, Settings, and Participants: This was a cross-sectional investigation of 461 men aged 71 yr, participants of the community-based Uppsala Longitudinal Study of Adult Men study.

    Main Outcome Measures: Measures included serum adiponectin, insulin sensitivity measured with euglycemic insulin clamp technique, and capillary density and muscle fiber composition determined from vastus lateralis muscle biopsies.

    Results: In multivariable linear regression models (adjusting for age, physical activity, fasting glucose, and pharmacological treatment for diabetes), serum adiponectin levels rose with increasing capillary density (β, 0.30 per 50 capillaries per square millimeter increase; P = 0.041) and higher proportion of type I muscle fibers (β, 0.27 per 10% increase; P = 0.036) but declined with a higher proportion of type IIb fibers (β, −0.39 per 10% increase; P = 0.014). Using bootstrap methods to examine the potential role of adiponectin in associations between muscle morphology and insulin sensitivity and the associations of capillary density (β difference, 0.041; 95% confidence interval 0.001, 0.085) and proportion of type IIb muscle fibers (β difference, −0.053; 95% confidence interval −0.107, −0.002) with insulin sensitivity were significantly attenuated when adiponectin was included in the models.

    Conclusions: Circulating adiponectin concentrations were higher with increasing skeletal muscle capillary density and in individuals with higher proportion of slow oxidative muscle fibers. Furthermore, our results indicate that adiponectin could be a partial mediator of the relations between skeletal muscle morphology and insulin sensitivity.

    Circulating adiponectin concentrations are associated with skeletal muscle morphology and could be involved in the relations between muscle morphology and insulin sensitivity.

  • 144. Ivert, Torbjörn
    et al.
    Malmström, Håkan
    Hammar, Niklas
    Carlsson, Axel C
    Wändell, Per E
    Holzmann, Martin J
    Jungner, Ingmar
    Ärnlöv, Johan
    Högskolan Dalarna, Akademin Utbildning, hälsa och samhälle, Medicinsk vetenskap. Karolinska Institutet.
    Walldius, Göran
    Cardiovascular events in patients under age fifty with early findings of elevated lipid and glucose levels - The AMORIS study2018Inngår i: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 13, nr 8, artikkel-id e0201972Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    BACKGROUND: The long-term trajectories of lipid and glucose levels in subjects who experience a major cardiovascular (CV) event at a young age has not been well studied. Our objective was to investigate lipid, lipoprotein, apolipoprotein (apo), and glucose levels in individuals experiencing a CV event before 50 years of age.

    METHODS AND FINDINGS: A first CV event [non-fatal myocardial infarction (MI), coronary revascularisation, or CV related death] before age 50 was recorded in 2,939 (cumulative incidence 1.2% in males and 0.3% in females) of 361,353 individuals included in the prospective Swedish AMORIS (Apolipoprotein-related MOrtality RISk) study with health examinations 1985-1996 and follow-up through 2011. In a nested case-control analysis, cases with a CV event were matched to randomly selected controls. Population risk factor trajectories were calculated up to 20 years prior to an event. Total cholesterol (TC), triglyceride (TG), and glucose levels were higher in cases than in controls as early as 20 years prior to the event with differences increasing over time. Low density lipoprotein, apoB, and the apoB/apoA-1 ratio were higher and increased over time, while HDL and apoA-1 were lower in cases compared to controls. The odds ratio was 2.5 (95% confidence interval 1.6-3.7) for TC ≥5 mmol/L and TG ≥1.7 mmol/L in cases versus controls. The adjusted population-attributable fractions including lipids, glucose, diabetes, smoking, hypertension, and obesity indicated that about 50% of CV events before age 50 may be associated with elevated lipid and glucose levels.

    CONCLUSIONS: Elevated TC, TG, LDL, apoB, and glucose levels and high apoB/apo A-1 ratio documented two decades before a CV event in subjects younger than 50 years may account for about half of CV events before age 50, which calls for early recognition and possibly treatment of modifiable CV risk factors in young individuals.

  • 145. James, Matthew T
    et al.
    Grams, Morgan E
    Woodward, Mark
    Elley, C Raina
    Green, Jamie A
    Wheeler, David C
    de Jong, Paul
    Gansevoort, Ron T
    Levey, Andrew S
    Ärnlöv, Johan
    Högskolan Dalarna, Akademin Utbildning, hälsa och samhälle, Medicinsk vetenskap.
    A meta-analysis of the association of estimated GFR, albuminuria, diabetes mellitus, and hypertension with acute kidney injury2015Inngår i: American Journal of Kidney Diseases, ISSN 0272-6386, E-ISSN 1523-6838, Vol. 66, nr 4, s. 552-554Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    BACKGROUND: Diabetes mellitus and hypertension are risk factors for acute kidney injury (AKI). Whether estimated glomerular filtration rate (eGFR) and urine albumin-creatinine ratio (ACR) remain risk factors for AKI in the presence and absence of these conditions is uncertain.

    STUDY DESIGN: Meta-analysis of cohort studies.

    SETTING & POPULATION: 8 general-population (1,285,045 participants) and 5 chronic kidney disease (CKD; 79,519 participants) cohorts.

    SELECTION CRITERIA FOR STUDIES: Cohorts participating in the CKD Prognosis Consortium.

    PREDICTORS: Diabetes and hypertension status, eGFR by the 2009 CKD Epidemiology Collaboration creatinine equation, urine ACR, and interactions.

    OUTCOME: Hospitalization with AKI, using Cox proportional hazards models to estimate HRs of AKI and random-effects meta-analysis to pool results.

    RESULTS: During a mean follow-up of 4 years, there were 16,480 episodes of AKI in the general-population and 2,087 episodes in the CKD cohorts. Low eGFRs and high ACRs were associated with higher risks of AKI in individuals with or without diabetes and with or without hypertension. When compared to a common reference of eGFR of 80mL/min/1.73m(2) in nondiabetic patients, HRs for AKI were generally higher in diabetic patients at any level of eGFR. The same was true for diabetic patients at all levels of ACR compared with nondiabetic patients. The risk gradient for AKI with lower eGFRs was greater in those without diabetes than with diabetes, but similar with higher ACRs in those without versus with diabetes. Those with hypertension had a higher risk of AKI at eGFRs>60mL/min/1.73m(2) than those without hypertension. However, risk gradients for AKI with both lower eGFRs and higher ACRs were greater for those without than with hypertension.

    LIMITATIONS: AKI identified by diagnostic code.

    CONCLUSIONS: Lower eGFRs and higher ACRs are associated with higher risks of AKI among individuals with or without either diabetes or hypertension.

  • 146. James, Spencer L. G
    et al.
    Abate, Degu
    Abate, Kalkidan Hessen
    Abay, Solomon M
    Abbafati, Cristiana
    Abbasi, Nooshin
    Abbastabar, Hedayat
    Abd-Allah, Foad
    Ärnlöv, Johan
    Högskolan Dalarna, Akademin Utbildning, hälsa och samhälle, Medicinsk vetenskap. Karolinska institutet.
    Murray, Christopher J. L
    Global, regional, and national incidence, prevalence, and years lived with disability for 354 diseases and injuries for 195 countries and territories, 1990-2017: a systematic analysis for the Global Burden of Disease Study 20172018Inngår i: The Lancet, ISSN 0140-6736, E-ISSN 1474-547X, Vol. 392, nr 10159, s. 1789-1858Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background The Global Burden of Diseases, Injuries, and Risk Factors Study 2017 (GBD 2017) includes a comprehensive assessment of incidence, prevalence, and years lived with disability (YLDs) for 354 causes in 195 countries and territories from 1990 to 2017. Previous GBD studies have shown how the decline of mortality rates from 1990 to 2016 has led to an increase in life expectancy, an ageing global population, and an expansion of the non-fatal burden of disease and injury. These studies have also shown how a substantial portion of the world's population experiences non-fatal health loss with considerable heterogeneity among different causes, locations, ages, and sexes. Ongoing objectives of the GBD study include increasing the level of estimation detail, improving analytical strategies, and increasing the amount of high-quality data. 

    Methods We estimated incidence and prevalence for 354 diseases and injuries and 3484 sequelae. We used an updated and extensive body of literature studies, survey data, surveillance data, inpatient admission records, outpatient visit records, and health insurance claims, and additionally used results from cause of death models to inform estimates using a total of 68 781 data sources. Newly available clinical data from India, Iran, Japan, Jordan, Nepal, China, Brazil, Norway, and Italy were incorporated, as well as updated claims data from the USA and new claims data from Taiwan (province of China) and Singapore. We used DisMod-MR 2.1, a Bayesian meta-regression tool, as the main method of estimation, ensuring consistency between rates of incidence, prevalence, remission, and cause of death for each condition. YLDs were estimated as the product of a prevalence estimate and a disability weight for health states of each mutually exclusive sequela, adjusted for comorbidity. We updated the Socio-demographic Index (SDI), a summary development indicator of income per capita, years of schooling, and total fertility rate. Additionally, we calculated differences between male and female YLDs to identify divergent trends across sexes. GBD 2017 complies with the Guidelines for Accurate and Transparent Health Estimates Reporting. 

    Findings Globally, for females, the causes with the greatest age-standardised prevalence were oral disorders, headache disorders, and haemoglobinopathies and haemolytic anaemias in both 1990 and 2017. For males, the causes with the greatest age-standardised prevalence were oral disorders, headache disorders, and tuberculosis including latent tuberculosis infection in both 1990 and 2017. In terms of YLDs, low back pain, headache disorders, and dietary iron deficiency were the leading Level 3 causes of YLD counts in 1990, whereas low back pain, headache disorders, and depressive disorders were the leading causes in 2017 for both sexes combined. All-cause age-standardised YLD rates decreased by 39% (95% uncertainty interval [UI] 3.1-4. 6) from 1990 to 2017; however, the all-age YLD rate increased by 7.2% (6.0-8.4) while the total sum of global YLDs increased from 562 million (421-723) to 853 million (642-1100). The increases for males and females were similar, with increases in all-age YLD rates of 7.9% (6 6-9. 2) for males and 6.5% (5.4-7.7) for females. We found significant differences between males and females in terms of age-standardised prevalence estimates for multiple causes. The causes with the greatest relative differences between sexes in 2017 included substance use disorders (3018 cases [95% UI 2782-3252] per 100 000 in males vs 1400 [1279-1524] per 100 000 in females), transport injuries (3322 [3082-3583] vs 2336 [2154-2535]), and self-hatin and interpersonal violence (3265 [2943-3630] vs 5643 [5057-6302]). 

    Interpretation Global all-cause age-standardised YLD rates have improved only slightly over a period spanning nearly three decades. However, the magnitude of the non-fatal disease burden has expanded globally, with increasing numbers of people who have a wide spectrum of conditions. A subset of conditions has remained globally pervasive since 1990, whereas other conditions have displayed more dynamic trends, with different ages, sexes, and geographies across the globe experiencing varying burdens and trends of health loss. This study emphasises how global improvements in premature mortality for select conditions have led to older populations with complex and potentially expensive diseases, yet also highlights global achievements in certain domains of disease and injury.

  • 147.
    Jia, Ting
    et al.
    Divisions of Renal Medicine and Baxter Novum, Department of Clinical Science, Intervention, and Technology, Karolinska Institutet, Stockholm, Sweden.
    Huang, Xiaoyan
    Divisions of Renal Medicine and Baxter Novum, Department of Clinical Science, Intervention, and Technology, Karolinska Institutet, Stockholm, Sweden ; Division of Nephrology, Peking University Shenzhen Hospital, Peking University, Shenzhen, China..
    Qureshi, Abdul R
    Divisions of Renal Medicine and Baxter Novum, Department of Clinical Science, Intervention, and Technology, Karolinska Institutet, Stockholm, Sweden.
    Xu, Hong
    Divisions of Renal Medicine and Baxter Novum, Department of Clinical Science, Intervention, and Technology, Karolinska Institutet, Stockholm, Sweden ; Division of Renal Medicine, Peking Union Medical College Hospital, Beijing, China.
    Ärnlöv, Johan
    Högskolan Dalarna, Akademin Utbildning, hälsa och samhälle, Medicinsk vetenskap. Department of Public Health and Caring Sciences, Section of Geriatrics, Uppsala University, Uppsala, Sweden.
    Lindholm, Bengt
    Divisions of Renal Medicine and Baxter Novum, Department of Clinical Science, Intervention, and Technology, Karolinska Institutet, Stockholm, Sweden.
    Cederholm, Tommy
    Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism, Uppsala University, Uppsala, Sweden.
    Stenvinkel, Peter
    Divisions of Renal Medicine and Baxter Novum, Department of Clinical Science, Intervention, and Technology, Karolinska Institutet, Stockholm, Sweden.
    Risérus, Ulf
    Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism, Uppsala University, Uppsala, Sweden.
    Carrero, Juan J
    Divisions of Renal Medicine and Baxter Novum, Department of Clinical Science, Intervention, and Technology, Karolinska Institutet, Stockholm, Sweden ; Center for Molecular Medicine, Karolinska Institutet, Stockholm, Sweden.
    Validation of insulin sensitivity surrogate indices and prediction of clinical outcomes in individuals with and without impaired renal function2014Inngår i: Kidney International, ISSN 0085-2538, E-ISSN 1523-1755, Vol. 86, nr 2, s. 383-391Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    As chronic kidney disease (CKD) progresses with abnormalities in glucose and insulin metabolism, commonly used insulin sensitivity indices (ISIs) may not be applicable in individuals with CKD. Here we sought to validate surrogate ISIs against the glucose disposal rate by the gold-standard hyperinsulinemic euglycemic glucose clamp (HEGC) technique in 1074 elderly men of similar age (70 years) of whom 495 had and 579 did not have CKD (estimated glomerular filtration rate (eGFR) under 60 ml/min per 1.73 m(2) (median eGFR of 46 ml/min per 1.73 m(2))). All ISIs provided satisfactory (weighted κ over 0.6) estimates of the glucose disposal rate in patients with CKD. ISIs derived from oral glucose tolerance tests (OGTTs) agreed better with HEGC than those from fasting samples (higher predictive accuracy). Regardless of CKD strata, all ISIs allowed satisfactory clinical discrimination between the presence and absence of insulin resistance (glucose disposal rate under 4 mg/kg/min). We also assessed the ability of both HEGC and ISIs to predict all-cause and cardiovascular mortality during a 10-year follow-up. Neither HEGC nor ISIs independently predicted mortality. Adjustment for renal function did not materially change these associations. Thus, ISIs can be applied in individuals with moderately impaired renal function for diagnostic purposes. For research matters, OGTT-derived ISIs may be preferred. Our data do not support the hypothesis of kidney function mediating insulin sensitivity (IS)-associated outcomes nor a role for IS as a predictor of mortality.Kidney International advance online publication, 29 January 2014; doi:10.1038/ki.2014.1.

  • 148. Jia, Ting
    et al.
    Risérus, Ulf
    Xu, Hong
    Lindholm, Bengt
    Ärnlöv, Johan
    Högskolan Dalarna, Akademin Utbildning, hälsa och samhälle, Medicinsk vetenskap. Uppsala universitet.
    Sjögren, Per
    Cederholm, Tommy
    Larsson, Tobias E
    Ikizler, Talat A
    Carrero, Juan J
    Kidney function, β-cell function and glucose tolerance in older men2015Inngår i: Journal of Clinical Endocrinology and Metabolism, ISSN 0021-972X, E-ISSN 1945-7197, Vol. 100, nr 2, s. 587-593Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Context: Kidney dysfunction induces insulin resistance, but it is unknown if β cell function is affected.

    Objective: To investigate insulin release (β cell function) and glucose tolerance following a standardized oral glucose tolerance test (OGTT) across kidney function strata.

    Setting and Design: Community-based cohort study from the Uppsala Longitudinal Study of Adult Men (ULSAM).

    Participants and Main Outcome Measure: Included were 1015 non-diabetic Swedish men aged 70-71 years. All participants underwent OGTT and euglycaemic hyperinsulinaemic clamp (HEGC) tests, allowing determination of insulin sensitivity, β cell function and glucose tolerance. Kidney function was estimated by cystatin C-algorithms. Mixed models were used to identify determinants of insulin secretion after the hyperglycemic load.

    Results: As many as 466 (46%) of participants presented moderate-advanced kidney disease. Insulin sensitivity (by HEGC) decreased across decreasing kidney function quartiles. After the OGTT challenge, however, β cell function indices (area under the curve for insulin release, the estimated first phase insulin release and the insulinogenic index) were incrementally higher. Neither the oral disposition index nor ths 2-hour post-load glucose tolerance differed across kidney function strata. Mixed models showed that dynamic insulin release during the OGTT was inversely associated to kidney function despite correction for each individual's insulin sensitivity or its risk factors.

    Conclusions: In older men, β cell function after a hyperglycemic load appropriately compensated the loss in insulin sensitivity that accompanies kidney dysfunction. As a result, the net balance between insulin sensitivity and β cell function was preserved.

  • 149.
    Jobs, Elisabeth
    Högskolan Dalarna, Akademin Utbildning, hälsa och samhälle, Medicinsk vetenskap. Uppsala University.
    Cathepsin S as a biomarker of low-grade inflammation, insulin resistance, and cardiometabolic disease risk2014Doktoravhandling, med artikler (Annet vitenskapelig)
    Abstract [en]

    Cathepsin S is a protease important in major histocompatibility complex (MHC) class II antigen presentation and also in degrading the extracellular matrix. Studies, most of them experimental, have shown that cathepsin S is involved in different pathological conditions such as obesity, inflammation, atherosclerosis, diabetes, and cancer.

       The overall hypothesis of this report is that high levels of circulating cathepsin S, is a biomarker that reflects pathology induced by inflammation and obesity. The overall aim of this report was to investigate possible associations between circulating cathepsin S, inflammation, glucometabolic disturbance, and its associated diseases in the community. As cathepsin S appears to be a novel risk marker for several pathological conditions, we also wanted to examine the effect of dietary intervention on circulating cathepsin S concentrations.

       This thesis is based on data from three community-based cohorts, the Uppsala longitudinal study of adult men (ULSAM), the prospective investigation of the vasculature in Uppsala seniors (PIVUS), and a post-hoc study from the randomized controlled NORDIET trial.

       In the first study, we identified a cross-sectional positive association between serum cathepsin S and two markers of cytokine-mediated inflammation, CRP and IL-6. These associations were similar in non-obese individuals. In longitudinal analyses, higher cathepsin S at baseline was associated with higher CRP and IL-6 levels after six years of follow-up. In the second study, we identified a cross-sectional association between increased serum levels of cathepsin S and reduced insulin sensitivity. These associations were similar in non-obese individuals. No significant association was observed between cathepsin S and insulin secretion. In longitudinal analysis, higher cathepsin S levels were associated with an increased risk of developing diabetes during the six-year follow-up. In the third study, we found that higher serum levels of cathepsin S were associated with increased mortality risk. Moreover, in the ULSAM cohort, serum cathepsin S was independently associated with cause-specific mortality from cardiovascular disease and cancer. In the fourth study, we identified that adherence to an ad libitum healthy Nordic diet for 6 weeks slightly decreased the levels of plasma cathepsin S in normal or marginally overweight individuals, relative to the control group. Changes in circulating cathepsin S concentrations were correlated with changes in body weight, LDL-C, and total cholesterol.

       Conclusion: This thesis shows that circulating cathepsin S is a biomarker that independently reflects inflammation, insulin resistance, the risk of developing diabetes, and mortality risk. Furthermore, a Nordic diet moderately reduced cathepsin S levels in normal-weight and overweight men and women. This effect may be partially mediated by diet-induced weight loss and possibly by reduced LDL-C concentrations. 

  • 150.
    Jobs, Elisabeth
    et al.
    Högskolan Dalarna, Akademin Utbildning, hälsa och samhälle, Medicinsk vetenskap. Uppsala universitetet.
    Adamsson, Viola
    Larsson, Anders
    Jobs, Magnus
    Högskolan Dalarna, Akademin Utbildning, hälsa och samhälle, Medicinsk vetenskap.
    Nerpin, Elisabet
    Högskolan Dalarna, Akademin Utbildning, hälsa och samhälle, Medicinsk vetenskap.
    Ingelsson, Erik
    Ärnlöv, Johan
    Högskolan Dalarna, Akademin Utbildning, hälsa och samhälle, Medicinsk vetenskap. Uppsala universitet.
    Risérus, Ulf
    Influence of a prudent diet on circulating cathepsin S in humans2014Inngår i: Nutrition Journal, ISSN 1475-2891, E-ISSN 1475-2891, Vol. 13, nr 84Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    BACKGROUND: Increased circulating cathepsin S levels have been linked to increased risk of cardiometabolic diseases and cancer. However, whether cathepsin S is a modifiable risk factor is unclear. We aimed to investigate the effects of a prudent diet on plasma cathepsin S levels in healthy individuals.

    FINDINGS: Explorative analyses of a randomized study were performed in 88 normal to slightly overweight and hyperlipidemic men and women (aged 25 to 65) that were randomly assigned to ad libitum prudent diet, i.e. healthy Nordic diet (ND) or a control group (habitual Western diet) for 6 weeks. Whereas all foods in the ND were provided, the control group was advised to consume their habitual diet throughout the study. The ND was in line with dietary recommendations, e.g. low in saturated fats, sugars and salt, but high in plant-based foods rich in fibre and unsaturated fats.The ND significantly decreased cathepsin S levels (from 20.1 (+/-4.0 SD) to 19.7 μg/L (+/-4.3 SD)) compared with control group (from 18.2 (+/-2.9 SD) to 19.1 μg/L (+/-3.8 SD)). This difference remained after adjusting for sex and change in insulin sensitivity (P = 0.03), and near significant after adjusting for baseline cathepsin S levels (P = 0.06), but not for change in weight or LDL-C. Changes in cathepsin S levels were directly correlated with change in LDL-C.

    CONCLUSIONS: Compared with a habitual control diet, a provided ad libitum healthy Nordic diet decreased cathepsin S levels in healthy individuals, possibly mediated by weight loss or lowered LDL-C. These differences between groups in cathepsin S were however not robust and therefore need further investigation.

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