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  • 1. Almqvist, Catarina
    et al.
    Adami, Hans-Olov
    Franks, Paul W.
    Groop, Leif
    Ingelsson, Erik
    Kere, Juha
    Lissner, Lauren
    Litton, Jan-Eric
    Maeurer, Markus
    Michaëlsson, Karl
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Palmgren, Juni
    Pershagen, Göran
    Ploner, Alexander
    Sullivan, Patrick F.
    Tybring, Gunnel
    Pedersen, Nancy L.
    LifeGene - A large prospective population-based study of global relevance2011In: European Journal of Epidemiology, ISSN 0393-2990, E-ISSN 1573-7284, Vol. 26, no 1, p. 67-77Article in journal (Refereed)
    Abstract [en]

    Studying gene-environment interactions requires that the amount and quality of the lifestyle data is comparable to what is available for the corresponding genomic data. Sweden has several crucial prerequisites for comprehensive longitudinal biomedical research, such as the personal identity number, the universally available national health care system, continuously updated population and health registries and a scientifically motivated population. LifeGene builds on these strengths to bridge the gap between basic research and clinical applications with particular attention to populations, through a unique design in a research-friendly setting. LifeGene is designed both as a prospective cohort study and an infrastructure with repeated contacts of study participants approximately every 5 years. Index persons aged 18-45 years old will be recruited and invited to include their household members (partner and any children). A comprehensive questionnaire addressing cutting-edge research questions will be administered through the web with short follow-ups annually. Biosamples and physical measurements will also be collected at baseline, and re-administered every 5 years thereafter. Event-based sampling will be a key feature of LifeGene. The household-based design will give the opportunity to involve young couples prior to and during pregnancy, allowing for the first study of children born into cohort with complete pre-and perinatal data from both the mother and father. Questions and sampling schemes will be tailored to the participants' age and life events. The target of LifeGene is to enrol 500,000 Swedes and follow them longitudinally for at least 20 years.

  • 2.
    Andersen, Kasper
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Farahmand, Bahman
    Ahlbom, Anders
    Held, Claes
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Ljunghall, Sverker
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrinology and mineral metabolism.
    Michaëlsson, Karl
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Sundström, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Risk of arrhythmias in 52 755 long-distance cross-country skiers: a cohort study2013In: European Heart Journal, ISSN 0195-668X, E-ISSN 1522-9645, Vol. 34, no 47, p. 3624-3631Article in journal (Refereed)
    Abstract [en]

    AIMS:

    We aimed to investigate the association of number of completed races and finishing time with risk of arrhythmias among participants of Vasaloppet, a 90 km cross-country skiing event.

    METHODS AND RESULTS:

    All the participants without cardiovascular disease who completed Vasaloppet during 1989-98 were followed through national registries until December 2005. Primary outcome was hospitalization for any arrhythmia and secondary outcomes were atrial fibrillation/flutter (AF), bradyarrhythmias, other supraventricular tachycardias (SVT), and ventricular tachycardia/ventricular fibrillation/cardiac arrest (VT/VF/CA). Among 52 755 participants, 919 experienced arrhythmia during follow-up. Adjusting for age, education, and occupational status, those who completed the highest number of races during the period had higher risk of any arrhythmias [hazard ratio (HR)1.30; 95% CI 1.08-1.58; for ≥5 vs. 1 completed race], AF (HR 1.29; 95% CI 1.04-1.61), and bradyarrhythmias (HR 2.10; 95% CI 1.28-3.47). Those who had the fastest relative finishing time also had higher risk of any arrhythmias (HR 1.30; 95% CI 1.04-1.62; for 100-160% vs. >240% of winning time), AF (1.20; 95% CI 0.93-1.55), and bradyarrhythmias (HR 1.85; 95% CI 0.97-3.54). SVT or VT/VF/CA was not associated with finishing time or number of completed races.

    CONCLUSIONS:

    Among male participants of a 90 km cross-country skiing event, a faster finishing time and a high number of completed races were associated with higher risk of arrhythmias. This was mainly driven by a higher incidence of AF and bradyarrhythmias. No association with SVT or VT/VF/CA was found.

  • 3.
    Andersen, Kasper
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Ingelsson, Erik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences.
    Ärnlöv, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences.
    Byberg, Liisa
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences.
    Michaëlsson, Karl
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences.
    Sundström, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Muscle Morphology And Risk Of Cardiovascular Disease2010In: Journal of Hypertension, ISSN 0263-6352, E-ISSN 1473-5598, Vol. 28, p. E353-E353Article in journal (Other academic)
  • 4.
    Andersen, Kasper
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Ingelsson, Erik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology.
    Ärnlöv, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Byberg, Liisa
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Michaëlsson, Karl
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Sundström, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Skeletal muscle morphology and risk of cardiovascular disease in elderly men2015In: European Journal of Preventive Cardiology, ISSN 2047-4873, E-ISSN 2047-4881, Vol. 22, no 2, p. 231-239Article in journal (Refereed)
    Abstract [en]

    BACKGROUND:

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

    DESIGN:

    Population-based cohort study.

    METHODS:

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

    RESULTS:

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

    CONCLUSIONS:

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

  • 5.
    Arefalk, Gabriel
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Hambraeus, Kristina
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Michaëlsson, Karl
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Lindahl, Bertil
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Sundström, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Discontinuation of Smokeless Tobacco and Mortality Risk After Myocardial Infarction2014In: Circulation, ISSN 0009-7322, E-ISSN 1524-4539, Vol. 130, no 4, p. 325-323Article in journal (Refereed)
    Abstract [en]

    Background-Given the indications of increased risk for fatal myocardial infarction (MI) in people who use snus, a moist smokeless tobacco product, we hypothesized that discontinuation of snus use after an MI would reduce mortality risk. Methods and Results-All patients who were admitted to coronary care units for an MI in Sweden between 2005 and 2009 and were <75 years of age underwent a structured examination 2 months after discharge (the baseline of the present study). We investigated the risk of mortality in post-MI snus quitters (n=675) relative to post-MI continuing snus users (n=1799) using Cox proportional hazards analyses. During follow-up (mean 2.1 years), 83 participants died. The mortality rate was 9.7 (95% confidence interval, 5.7-16.3) per 1000 person-years at risk in post-MI snus quitters and 18.7 (14.8-23.6) per 1000 person-years at risk in post-MI continuing snus users. After adjustment for age and sex, post-MI snus quitters had half the mortality risk of post-MI continuing snus users (hazard ratio, 0.51; 95% confidence interval, 0.29-0.91). In a multivariable-adjusted model, the hazard ratio was 0.57 (95% confidence interval, 0.32-1.02). The corresponding estimate for people who quit smoking after MI versus post-MI continuing smokers was 0.54 (95% confidence interval, 0.42-0.69). Conclusions-In this study, discontinuation of snus use after an MI was associated with a nearly halved mortality risk, similar to the benefit associated with smoking cessation. These observations suggest that the use of snus after MI should be discouraged.

  • 6.
    Arefalk, Gabriel
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Hambraeus, Kristina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Center for Clinical Research Dalarna.
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Michaëlsson, Karl
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Lindahl, Bertil
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Sundström, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Response to Letter Regarding Article, "Discontinuation of Smokeless Tobacco and Mortality Risk After Myocardial Infarction"2015In: Circulation, ISSN 0009-7322, E-ISSN 1524-4539, Vol. 131, no 17, p. E423-E423Article in journal (Refereed)
  • 7.
    Arefalk, Gabriel
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Hergens, M. P.
    Ingelsson, Erik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences.
    Ärnlöv, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences.
    Michaëlsson, Karl
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Ye, W.
    Nyrén, O.
    Lambe, M.
    Sundström, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Smokeless Tobacco (Snus) And Risk Of Heart Failure In Two Swedish Cohorts2010In: Journal of Hypertension, ISSN 0263-6352, E-ISSN 1473-5598, Vol. 28, p. E48-E49Article in journal (Other academic)
  • 8.
    Arefalk, Gabriel
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Hergens, Maria-Pia
    Ingelsson, Erik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Ärnlöv, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Michaëlsson, Karl
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Ye, Weimin
    Nyrén, Olof
    Lambe, Mats
    Sundström, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Smokeless Tobacco (Snus) and Risk of Heart Failure: Results from Two Swedish Cohorts2012In: European Journal of Cardiovascular Prevention & Rehabilitation, ISSN 1741-8267, E-ISSN 1741-8275, Vol. 19, no 5, p. 1120-1127Article in journal (Refereed)
    Abstract [en]

    Background:

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

    Design:

    Two independent Swedish prospective cohorts; the Uppsala Longitudinal Study of Adult Men (ULSAM), a community-based sample of 1076 elderly men, and the Construction Workers Cohort (CWC), a sample of 118,425 never-smoking male construction workers.

    Methods:

    Cox proportional hazards models were used to investigate possible associations of snus use with risk of a first hospitalization for heart failure.

    Results:

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

    Conclusion:

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

  • 9. Arnold, Melina
    et al.
    Freisling, Heinz
    Stolzenberg-Solomon, Rachael
    Kee, Frank
    O'Doherty, Mark George
    Ordóñez-Mena, José Manuel
    Wilsgaard, Tom
    May, Anne Maria
    Bueno-de-Mesquita, Hendrik Bas
    Tjønneland, Anne
    Orfanos, Philippos
    Trichopoulou, Antonia
    Boffetta, Paolo
    Bray, Freddie
    Jenab, Mazda
    Soerjomataram, Isabelle
    Michaëlsson, Karl
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences.
    Overweight duration in older adults and cancer risk: a study of cohorts in Europe and the United States.2016In: European Journal of Epidemiology, ISSN 0393-2990, E-ISSN 1573-7284, Vol. 31, no 9, p. 893-904Article in journal (Refereed)
    Abstract [en]

    Recent studies have shown that cancer risk related to overweight and obesity is mediated by time and might be better approximated by using life years lived with excess weight. In this study we aimed to assess the impact of overweight duration and intensity in older adults on the risk of developing different forms of cancer. Study participants from seven European and one US cohort study with two or more weight assessments during follow-up were included (n = 329,576). Trajectories of body mass index (BMI) across ages were estimated using a quadratic growth model; overweight duration (BMI ≥ 25) and cumulative weighted overweight years were calculated. In multivariate Cox models and random effects analyses, a longer duration of overweight was significantly associated with the incidence of obesity-related cancer [overall hazard ratio (HR) per 10-year increment: 1.36; 95 % CI 1.12-1.60], but also increased the risk of postmenopausal breast and colorectal cancer. Additionally accounting for the degree of overweight further increased the risk of obesity-related cancer. Risks associated with a longer overweight duration were higher in men than in women and were attenuated by smoking. For postmenopausal breast cancer, increased risks were confined to women who never used hormone therapy. Overall, 8.4 % of all obesity-related cancers could be attributed to overweight at any age. These findings provide further insights into the role of overweight duration in the etiology of cancer and indicate that weight control is relevant at all ages. This knowledge is vital for the development of effective and targeted cancer prevention strategies.

  • 10. Baron, John A.
    et al.
    Farahmand, Bahman Y.
    Weiderpass, Elisabete
    Michaëlsson, Karl
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences.
    Alberts, Akke
    Persson, Ingemar
    Ljunghall, Sverker
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Cigarette smoking, alcohol consumption, and risk of hip fracture in women2001In: Archives of Internal Medicine, ISSN 0003-9926, E-ISSN 1538-3679, Vol. 161, no 7, p. 983-8Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Previous studies regarding the impact of cigarette smoking on the risk of hip fracture in postmenopausal women have been inconsistent, suggesting different effects in different groups. The effect of alcohol intake on fracture risk is puzzling: moderate alcohol intake appears to increase bone density, and its association with hip fracture is not clear. METHODS: To assess the associations of cigarette smoking and alcohol consumption with hip fracture risk among postmenopausal women, we conducted an analysis of a population-based case-control study from Sweden. Cases were postmenopausal women, aged 50 to 81 years, who sustained a hip fracture after minor trauma between October 1, 1993, and February 28, 1995; controls were randomly selected from a population-based register during the same period. A mailed questionnaire requesting information on lifestyle habits and medical history was used 3 months after the hip fracture for cases and simultaneously for controls. Age-adjusted odds ratios (ORs) and 95% confidence intervals (CIs) were computed by means of logistic regression. RESULTS: Of those eligible, 1328 cases (82.5%) and 3312 controls (81.6%) responded. Compared with never smokers, current smokers had an increased risk of hip fracture (age-adjusted OR, 1.66; 95% CI, 1.41-1.95). Duration of smoking-particularly postmenopausal smoking-was more important than the amount smoked. Former smokers had a small increase in risk (age-adjusted OR, 1.15; 95% CI, 0.97-1.37) that decreased with the duration of cessation. The age-adjusted OR for women consuming alcohol was 0.80 (95% CI, 0.69-0.93). CONCLUSIONS: Cigarette smoking is a risk factor for hip fracture among postmenopausal women; risk decreases after cessation. Alcohol consumption has a weak inverse association with risk.

  • 11. Benetou, V
    et al.
    Orfanos, P
    Feskanich, D
    Michaëlsson, Karl
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Pettersson-Kymmer, U
    Ahmed, L A
    Peasey, A
    Wolk, A
    Brenner, H
    Bobak, M
    Wilsgaard, T
    Schöttker, B
    Saum, K-U
    Bellavia, A
    Grodstein, F
    Klinaki, E
    Valanou, E
    Papatesta, E-M
    Boffetta, P
    Trichopoulou, A
    Education, marital status, and risk of hip fractures in older men and women: the CHANCES project2015In: Osteoporosis International, ISSN 0937-941X, E-ISSN 1433-2965, Vol. 26, no 6, p. 1733-1746Article in journal (Refereed)
    Abstract [en]

    The role of socioeconomic status in hip fracture incidence is unclear. In a diverse population of elderly, higher education was found to be associated with lower, whereas living alone, compared to being married/cohabiting, with higher hip fracture risk. Educational level and marital status may contribute to hip fracture risk.

    INTRODUCTION: The evidence on the association between socioeconomic status and hip fracture incidence is limited and inconsistent. We investigated the potential association of education and marital status with hip fracture incidence in older individuals from Europe and USA.

    METHODS: A total of 155,940 participants (79 % women) aged 60 years and older from seven cohorts were followed up accumulating 6456 incident hip fractures. Information on education and marital status was harmonized across cohorts. Hip fractures were ascertained through telephone interviews/questionnaires or through record linkage with registries. Associations were assessed through Cox proportional hazard regression adjusting for several factors. Summary estimates were derived using random effects models.

    RESULTS: Individuals with higher education, compared to those with low education, had lower hip fracture risk [hazard ratio (HR) = 0.84, 95 % confidence interval (CI) 0.72-0.95]. Respective HRs were 0.97 (95 % CI 0.82-1.13) for men and 0.75 (95 % CI 0.65-0.85) for women. Overall, individuals living alone, especially those aged 60-69 years, compared to those being married/cohabiting, tended to have a higher hip fracture risk (HR = 1.12, 95 % CI 1.02-1.22). There was no suggestion for heterogeneity across cohorts (P heterogeneity > 0.05).

    CONCLUSIONS: The combined data from >150,000 individuals 60 years and older suggest that higher education may contribute to lower hip fracture risk. Furthermore, this risk may be higher among individuals living alone, especially among the age group 60-69 years, when compared to those being married/cohabiting.

  • 12.
    Benetou, V.
    et al.
    Univ Athens, WHO Collaborating Ctr Nutr & Hlth, Unit Nutr Epidemiol & Nutr Publ Hlth, Dept Hyg Epidemiol & Med Stat,Sch Med, 75 Mikras Asias St, Athens 11527, Greece.
    Orfanos, P.
    Hellen Hlth Fdn, Athens, Greece;Univ Athens, WHO Collaborating Ctr Nutr & Hlth, Unit Nutr Epidemiol & Nutr Publ Hlth, Dept Hyg Epidemiol & Med Stat,Sch Med, 75 Mikras Asias St, Athens 11527, Greece.
    Feskanich, D.
    Harvard Med Sch, Boston, MA USA;Brigham & Womens Hosp, Dept Med, Channing Div Network Med, 75 Francis St, Boston, MA 02115 USA.
    Michaëlsson, Karl
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Pettersson-Kymmer, U.
    Umea Univ, Dept Pharmacol & Clin Neurosci, Umea, Sweden;Umea Univ, Dept Publ Hlth & Clin Med, Umea, Sweden.
    Byberg, Liisa
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Eriksson, S.
    Umea Univ, Dept Community Med, Umea, Sweden.
    Grodstein, F.
    Harvard Med Sch, Boston, MA USA;Brigham & Womens Hosp, Dept Med, Channing Div Network Med, 75 Francis St, Boston, MA 02115 USA.
    Wolk, Alicja
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics. Karolinska Inst, Inst Environm Med, Div Nutr Epidemiol, Stockholm, Sweden.
    Jankovic, N.
    Wageningen Univ, Div Human Nutr, Wageningen, Netherlands;Univ Duisburg Essen, Inst Med Informat Biometry & Epidemiol, Ctr Clin Epidemiol, Fac Med, Essen, Germany.
    de Groot, L. C. P. G. M.
    Wageningen Univ, Div Human Nutr, Wageningen, Netherlands.
    Boffetta, P.
    Icahn Sch Med Mt Sinai, Inst Translat Epidemiol, New York, NY 10029 USA;Icahn Sch Med Mt Sinai, Tisch Canc Inst, New York, NY 10029 USA.
    Trichopoulou, A.
    Hellen Hlth Fdn, Athens, Greece.
    Mediterranean diet and hip fracture incidence among older adults: the CHANCES project2018In: Osteoporosis International, ISSN 0937-941X, E-ISSN 1433-2965, Vol. 29, no 7, p. 1591-1599Article in journal (Refereed)
    Abstract [en]

    The association between adherence to Mediterranean diet (MD) and hip fracture incidence is not yet established. In a diverse population of elderly, increased adherence to MD was associated with lower hip fracture incidence. Except preventing major chronic diseases, adhering to MD might have additional benefits in lowering hip fracture risk. Hip fractures constitute a major public health problem among older adults. Latest evidence links adherence to Mediterranean diet (MD) with reduced hip fracture risk, but still more research is needed to elucidate this relationship. The potential association of adherence to MD with hip fracture incidence was explored among older adults. A total of 140,775 adults (116,176 women, 24,599 men) 60 years and older, from five cohorts from Europe and the USA, were followed-up for 1,896,219 person-years experiencing 5454 hip fractures. Diet was assessed at baseline by validated, cohort-specific, food-frequency questionnaires, and hip fractures were ascertained through patient registers or telephone interviews/questionnaires. Adherence to MD was evaluated by a scoring system on a 10-point scale modified to be applied also to non-Mediterranean populations. In order to evaluate the association between MD and hip fracture incidence, cohort-specific hazard ratios (HR), adjusted for potential confounders, were estimated using Cox proportional-hazards regression and pooled estimates were subsequently derived implementing random-effects meta-analysis. A two-point increase in the score was associated with a significant 4% decrease in hip fracture risk (pooled adjusted HR 0.96; 95% confidence interval (95% CI) 0.92-0.99, p(heterogeneity) = 0.446). In categorical analyses, hip fracture risk was lower among men and women with moderate (HR 0.93; 95% CI 0.87-0.99) and high (HR 0.94; 95% CI 0.87-1.01) adherence to the score compared with those with low adherence. In this large sample of older adults from Europe and the USA, increased adherence to MD was associated with lower hip fracture incidence.

  • 13.
    Benetou, Vassiliki
    et al.
    Univ Athens, Sch Med, Dept Hyg Epidemiol & Med Stat, 75 Mikras Asias Str, Athens 11527, Greece.; Hellen Hlth Fdn, Athens, Greece.
    Orfanos, Philippos
    Univ Athens, Sch Med, Dept Hyg Epidemiol & Med Stat, 75 Mikras Asias Str, Athens 11527, Greece.; Hellen Hlth Fdn, Athens, Greece.
    Feskanich, Diane
    Brigham & Womens Hosp, Dept Med, Channing Div Network Med, 75 Francis St, Boston, MA 02115 USA.; Harvard Med Sch, Boston, MA USA.
    Michaëlsson, Karl
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Pettersson-Kymmer, Ulrika
    Umea Univ, Dept Pharmacol & Clin Neurosci, Umea, Sweden.; Umea Univ, Dept Publ Hlth & Clin Med, Umea, Sweden.
    Eriksson, Sture
    Umea Univ, Dept Community Med, Umea, Sweden.
    Grodstein, Francine
    Brigham & Womens Hosp, Dept Med, Channing Div Network Med, 75 Francis St, Boston, MA 02115 USA.; Harvard Med Sch, Boston, MA USA.
    Wolk, Alicja
    Karolinska Inst, Inst Environm Med, Div Nutr Epidemiol, Stockholm, Sweden.
    Bellavia, Andrea
    Karolinska Inst, Inst Environm Med, Div Nutr Epidemiol, Stockholm, Sweden.
    Ahmed, Luai A
    UiT, Fac Hlth Sci, Dept Hlth & Care Sci, Tromso, Norway.; United Arab Emirates Univ, Coll Med & Hlth Sci, Inst Publ Hlth, Al Ain, U Arab Emirates.
    Boffeta, Paolo
    Icahn Sch Med Mt Sinai, Inst Translat Epidemiol, New York, NY 10029 USA.; Icahn Sch Med Mt Sinai, Tisch Canc Inst, New York, NY 10029 USA.
    Trichopoulou, Antonia
    Univ Athens, Sch Med, Dept Hyg Epidemiol & Med Stat, 75 Mikras Asias Str, Athens 11527, Greece.; Hellen Hlth Fdn, Athens, Greece .
    Fruit and Vegetable Intake and Hip Fracture Incidence in Older Men and Women: The CHANCES Project2016In: Journal of Bone and Mineral Research, ISSN 0884-0431, E-ISSN 1523-4681, Vol. 31, no 9, p. 1743-1752Article in journal (Refereed)
    Abstract [en]

    The role of fruit and vegetable intake in relation to fracture prevention during adulthood and beyond is not adequately understood. We investigated the potential association between fruit and vegetable intake and hip fracture incidence in a large sample of older adults from Europe and the United States. A total of 142,018 individuals (116,509 women) aged ≥60 years, from five cohorts, were followed up prospectively for 1,911,482 person-years, accumulating 5552 hip fractures. Fruit and vegetable intake was assessed by validated, cohort-specific, food-frequency questionnaires (FFQ). Ηip fractures were ascertained through national patient registers or telephone interviews/questionnaires. Adjusted hazard ratios (HRs) derived by Cox proportional hazards regression were estimated for each cohort and subsequently pooled using random effects meta-analysis. Intake of ≤1 serving/day of fruit and vegetables combined was associated with 39% higher hip fracture risk (pooled adjusted HR, 1.39; 95% confidence interval [CI], 1.20 to 1.58) in comparison with moderate intake (>3 and ≤5 servings/day) (pfor heterogeneity  = 0.505), whereas higher intakes (>5 servings/day) were not associated with lower risk in comparison with the same reference. Associations were more evident among women. We concluded that a daily intake of 1 or <1 servings of fruits and vegetables was associated with increased hip fracture risk in relation to moderate daily intakes. Older adults with such low fruit and vegetable consumption may benefit from raising their intakes to moderate amounts in order to reduce their hip fracture risk.

  • 14. Bergkvist, Charlotte
    et al.
    Åkesson, Agneta
    Glynn, Anders
    Michaëlsson, Karl
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Rantakokko, Panu
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences.
    Kiviranta, Hannu
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences.
    Wolk, Alicja
    Berglund, Marika
    Validation of questionnaire-based long-term dietary exposure to polychlorinated biphenyls using biomarkers2012In: Molecular Nutrition & Food Research, ISSN 1613-4125, E-ISSN 1613-4133, Vol. 56, no 11, p. 1748-1754Article in journal (Refereed)
    Abstract [en]

    Scope The health consequences of lifelong low-level exposure to polychlorinated biphenyls (PCBs) via food are largely unknown, mainly due to the lack of large population-based prospective studies addressing this issue. We validated long-term food frequency questionnaire (FFQ)-based dietary PCB exposure against concentrations of six PCB congeners in serum. Methods and results Dietary PCB exposure was estimated in the Swedish Mammography Cohort by constructing a recipe-based database of CB-153, an indicator for total PCBs in food. The Spearman rank correlation (adjusted for within-person variability) was assessed between concurrent (20042006), past (1997), and long-term (mean of 1997 and 20042006) FFQ-based dietary PCB exposure, respectively, and the following serum PCB congeners, CB-118, CB-138, CB-153, CB-156, CB-170, and CB-180, in women (5685 years of age, n = 201). The correlation between FFQ-based dietary PCB exposure and serum CB-153 was 0.41 (p < 0.001) for the concurrent (median 1.6 ng/kg body weight) and 0.34 (p < 0.05) for the past (median 2.6 ng/kg body weight) exposure assessment. Long-term validity of FFQ-based PCB estimates and the six serum PCB congeners ranged from 0.30 to 0.58 (p < 0.05). Conclusion FFQ-based PCB exposure estimates show acceptable validity in relation to PCB concentrations in serum, justifying their use in large-scale epidemiological studies.

  • 15.
    Bergström, Monica Frick
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Byberg, Liisa
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Melhus, Håkan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Michaëlsson, Karl
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Gedeborg, Rolf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Extent and consequences of misclassified injury diagnoses in a national hospital discharge registry2011In: Injury Prevention, ISSN 1353-8047, E-ISSN 1475-5785, Vol. 17, no 2, p. 108-113Article in journal (Refereed)
    Abstract [en]

    Background Classification of injuries and estimation of injury severity on the basis of ICD-10 injury coding are powerful epidemiological tools. Little is known about the characteristics and consequences of primary coding errors and their consequences for such applications. Materials and methods From the Swedish national hospital discharge register, 15 899 incident injury cases primarily admitted to the two hospitals in Uppsala County between 2000 and 2004 were identified. Of these, 967 randomly selected patient records were reviewed. Errors in injury diagnosis were corrected, and the consequences of these changes were analysed. Results Out of 1370 injury codes, 10% were corrected, but 95% of the injury codes were correct to the third position. In 21% (95% CI 19% to 24%) of 967 hospital admissions, at least one ICD-10 code for injury was changed or added, but only 13% (127) had some change made to their injury mortality diagnosis matrix classification. Among the cases with coding errors, the mean ICD-based injury severity score changed slightly (difference 0.016; 95% CI 0.007 to 0.032). The area under the receiver operating characteristics curve was 0.892 for predicting hospital mortality and remained essentially unchanged after the correction of codes (95% CI for difference -0.022 to 0.013). Conclusion Errors in ICD-10-coded injuries in hospital discharge data were common, but the consequences for injury categorisation were moderate and the consequences for injury severity estimates were in most cases minor. The error rate for detailed levels of cause-of-injury codes was high and may be detrimental for identifying specific targets for prevention.

  • 16. Björnsdottir, Sigridur
    et al.
    Sääf, Maria
    Bensing, Sophie
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Kämpe, Olle
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Michaelsson, Karl
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Ludvigsson, Jonas F
    Risk of Hip Fracture in Addison's Disease: A Population-based Cohort Study2011In: Journal of Internal Medicine, ISSN 0954-6820, E-ISSN 1365-2796, Vol. 270, no 2, p. 187-195Article in journal (Refereed)
    Abstract [en]

    Objectives:  The results of studies of bone mineral density (BMD) in Addison's disease (AD) are inconsistent. There are no published data on hip fracture risk in patients with AD. In this study we compare hip fracture risk in adults with and without AD. Design:  A population-based cohort study. Methods:  Through the Swedish National Patient Register and the Total Population Register, we identified 3,219 patients without prior hip fracture who were diagnosed with AD at the age of ≥30 years during the period 1964-2006, and 31,557 age- and sex-matched controls. Time to hip fracture was measured. Results:  We observed 221 hip fractures (6.9%) in patients with AD and 846 (2.7%) in the controls. Patients with AD had a higher risk of hip fracture (hazard ratio (HR) = 1.8; 95% confidence interval (CI), 1.6-2.1; p < 0.001). This risk increase was independent of sex and age at or calendar period of diagnosis. Risk estimates did not change with adjustment for type 1 diabetes, autoimmune thyroid disease, rheumatoid arthritis or coeliac disease. Women diagnosed with AD ≤50 years old had the highest risk of hip fracture (HR = 2.7; 95% CI, 1.6-4.5). We found a positive association between hip fracture and undiagnosed AD (odds ratio (OR) = 2.4; 95% CI, 2.1- 3.0) with the highest risk estimates in the last year before AD diagnosis (OR = 2.8; 95% CI, 1.8-4.2). Conclusion:  Both clinically undiagnosed and diagnosed AD were associated with hip fractures, with the highest relative risk seen in women diagnosed with AD ≤50 years of age.

  • 17.
    Blomberg, Hans
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Svennblad, Bodil
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Michaelsson, Karl
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Byberg, Liisa
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Johansson, Jakob
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Gedeborg, Rolf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Impact of prehospital trauma life support (PHTLS) training of ambulance caregivers on the outcome of traffic injury victims – a nation-wide study.Manuscript (preprint) (Other academic)
    Abstract [en]

    Background: Prehospital trauma life support (PHTLS) is a widely implemented educational program for prehospital trauma care. Evidence for improved patient outcome is, however, limited. The primary aim of this nation-wide study was to investigate the association between regional implementation of PHTLS training and mortality after traffic injuries.

    Methods: We extracted from the Swedish National Patient Registry and the Cause of Death Registry information on victims of motor vehicle traffic injuries in Sweden from 2001 to 2004 (n=28 041). During this time period, PHTLS training was implemented at a varying pace in different regions. We used a Bayesian approach with Markov chain Monte Carlo to estimate odds ratios (OR) for prehospital and 30-day mortality. We entered region and hospital into hierarchical models and controlled for the calendar year for each injury. We analyzed the time to death and time to return to work using Cox’s proportional hazards frailty models.

    Results: A total of 1395 individuals died before being admitted to hospital. After multivariable adjustment, the OR for prehospital mortality with PHTLS-trained prehospital staff was 1.11 (95% credibility interval, 0.88 to 1.38). For 30-day mortality (365 deaths), the adjusted OR was 0.80 (95% credibility interval, 0.53 to 1.17). There was no association between PHTLS training and time to death (hazard ratio 0.99; 95% confidence interval, 0.85 to 1.14) or time to return to work (hazard ratio 0.98, 95% confidence interval, 0.92 to 1.05).

    Conclusion: The implementation of PHTLS training did not appear to reduce mortality or disability after motor vehicle traffic injuries. 

  • 18.
    Blomberg, Hans
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Svennblad, Bodil
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Michaëlsson, Karl
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Byberg, Liisa
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Johansson, Jakob
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Gedeborg, Rolf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Prehospital Trauma Life Support Training of Ambulance Caregivers and the Outcomes of Traffic-Injury Victims in Sweden2013In: Journal of the American College of Surgeons, ISSN 1072-7515, E-ISSN 1879-1190, Vol. 217, no 6, p. 1010-1019Article in journal (Refereed)
    Abstract [en]

    BACKGROUND:

    There is limited evidence that the widely implemented Prehospital Trauma Life Support (PHTLS) educational program improves patient outcomes. The primary aim of this national study in Sweden was to investigate the association between regional implementation of PHTLS training and mortality after traffic injuries.

    STUDY DESIGN:

    We extracted information from the Swedish National Patient Registry and the Cause of Death Registry on victims of motor-vehicle traffic injuries in Sweden from 2001 to 2004 (N = 28,041). During this time period, PHTLS training was implemented at a varying pace in different regions. To control for other influences on patient outcomes related to regional and hospital-level effects, such as variations in performance of trauma care systems, we used Bayesian hierarchical regression models to estimate odds ratios for prehospital mortality and 30-day mortality after hospital admission. We also controlled for the calendar year for each injury to account for period effects. We analyzed the time to death after hospital admission and time to return to work using Cox's proportional hazards frailty models.

    RESULTS:

    After multivariable adjustment, the odds ratio for prehospital mortality with PHTLS-trained prehospital staff was 1.54 (95% credibility interval, 1.07-2.13). For 30-day mortality among those surviving to hospital admission, the odds ratio was 0.85 (95% credibility interval, 0.45-1.48). There was no association between PHTLS training and time to death (hazard ratio = 0.99; 95% CI, 0.85-1.14) or time to return to work (hazard ratio = 0.98; 95% CI, 0.92-1.05).

    CONCLUSIONS:

    In this observational study, the implementation of PHTLS training did not appear to be associated with reduced mortality or ability to return to work after motor-vehicle traffic injuries.

  • 19.
    Bornefalk, Eva
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Dahlen, Inger
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Michaëlsson, Karl
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences.
    Ljunggren, M.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Ljunghall, Sverker
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Age-dependent effect of oral glucocorticoids on markers of bone resorption in patients with acute asthma1998In: Calcified Tissue International, ISSN 0171-967X, E-ISSN 1432-0827, Vol. 63, no 1, p. 9-13Article in journal (Refereed)
    Abstract [en]

    It is generally accepted that bone formation is depressed during corticosteroid treatment, but the effects of glucocorticoids on bone resorption are less well characterized. We have investigated the effects of short-term treatment with high-dose oral glucocorticoids on biochemical markers of bone turnover in 20 consecutive patients with asthma who sought help for acute respiratory obstruction in our emergency department. Serum concentrations of the carboxy-terminal cross-linked telopeptide of type 1 collagen (1CTP), reflecting bone resorption, and the carboxy-terminal propeptide of type 1 procollagen (P1CP), reflecting bone formation, were measured by radioimmunoassay. Changes of the circulating levels of the bone resorption marker 1CTP after treatment were age dependent with a significant negative correlation (r = -0.54, P = 0.01). The dependency on age remained when correcting, in a multiple linear regression analysis, for 1CTP levels at admission, weight, sex, and daily maintenance dose of inhaled glucocorticoids. Circulating levels of P1CP were suppressed in the whole group 1 week after initiation of glucocorticoid therapy, from 123.3 +/- 10.2 ng/ml at admission to 88.1 +/- 6.3 ng/ml after 1 week (P < 0.01). The changes in P1CP levels were not related to age. Our data indicate that bone formation is suppressed by glucocorticoids in all age groups, whereas the effect of glucocorticoids on markers of bone resorption is dependent on age.

  • 20.
    Brahm, Helena
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Mallmin, Hans
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences.
    Michaëlsson, Karl
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences.
    Ström, Håkan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences.
    Ljunghall, Sverker
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Relationships between bone mass measurements and lifetime physical activity in a Swedish population1998In: Calcified Tissue International, ISSN 0171-967X, E-ISSN 1432-0827, Vol. 62, no 5, p. 400-412Article in journal (Refereed)
    Abstract [en]

    Lifetime occupational and leisure time activities were assessed by a questionnaire in order to evaluate their relationship to bone mass measurements and biochemical markers of bone metabolism in a population of 61 women and 61 men, randomly selected from a Swedish population register, to represent ages between 22 and 85 years. We also considered possible confounders by using questions about smoking habits, milk consumption, hormone replacement therapy (HRT), and menopausal age. Bone mineral density (BMD) and bone mineral content (bone mass, BMC) of the total body, lumbar spine, and proximal femur (neck, trochanter, Ward's triangle) were measured by dual energy X-ray absorptiometry (DXA), and BMD of the forearm with single energy X-ray absorptiometry (SXA). In addition, both DXA and SXA provided information on bone area. Quantitative ultrasound measurements (QUS) at the heel were performed to assess the speed of sound (SOS) and broadband ultrasound attenuation (BUA). Fasting blood samples were analyzed for biochemical markers of bone metabolism as well as parathyroid hormone (PTH) and total serum calcium. After adjustment for confounding factors, neither BMD nor QUS measurements were consistently related to lifetime leisure time or occupational activities; nor were there any consistent patterns relating biochemical markers of bone metabolism to bone mass measurements. However, physical activity seemed to influence bone mass, area, and width more than density. In men, high levels of leisure time activity were associated with raised values for lumbar spine area (6.2%) and width (3.3%) as well as for femoral neck area (5.5%) compared with their low activity counterpart. Men exposed to high levels of occupational activity demonstrated lower lumbar spine BMD (10.9%) and area (5.3%) than men with low activity levels. Within an unselected Swedish population, estimation of lifetime occupational and sport activities as well as bedrest, using a questionnaire, demonstrated no major effects on bone density. However, the association between high levels of lifetime activity and raised values for bone mass, area, and width indicate that geometrical changes in bone may provide better estimations of mechanically induced bone strength than bone density, at least in men.

  • 21. Burgaz, A.
    et al.
    Byberg, Liisa
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Rautiainen, S.
    Orsini, N.
    Håkansson, N.
    Ärnlöv, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Sundström, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Melhus, Håkan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Michaëlsson, Karl
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Wolk, A.
    Confirmed hypertension and plasma 25(OH)D concentrations amongst elderly men2011In: Journal of Internal Medicine, ISSN 0954-6820, E-ISSN 1365-2796, Vol. 269, no 2, p. 211-218Article in journal (Refereed)
    Abstract [en]

    Objectives.

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

    Design.

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

    Results.

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

    Conclusions.

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

  • 22. Burgaz, Ann
    et al.
    Åkesson, A.
    Michaëlsson, Karl
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Wolk, A.
    25-hydroxyvitamin D accumulation during summer in elderly women at latitude 60 degrees N2009In: Journal of Internal Medicine, ISSN 0954-6820, E-ISSN 1365-2796, Vol. 266, no 5, p. 476-483Article in journal (Refereed)
    Abstract [en]

    OBJECTIVES: During half of the year, cutaneous synthesis of 25-hydroxyvitamin D (25(OH)D) is not detectable at northern latitudes, leaving the population dependent on other sources for optimal vitamin D status. During April to September, 25(OH)D status may be improved by solar exposure. In this study, we measured seasonal differences in serum 25(OH)D concentrations and identified the major predictors of summer 25(OH)D concentrations. DESIGN: We assessed serum 25(OH)D concentrations during both winter and summer amongst 100 women, aged 61-83 years, randomly sampled from the Swedish Mammography Cohort. Participants completed two detailed questionnaires covering diet, use of dietary supplements and sun-related behaviour, the first in January through March and a second time in August through September. RESULTS: The mean seasonal increase in serum 25(OH)D concentrations was 38% from mean 72 +/- 23 nmol L(-1) during winter to 99 +/- 29 nmol L(-1) in summer. High summer 25(OH)D concentrations were associated with higher winter concentrations, preference of staying in sun instead of shade, having a nonsensitive skin type and normal body mass index. Based on multiple linear regression modelling, preferring sun, having nonsensitive skin type and normal weight as compared with preferring shade, having sensitive skin type and being obese, was associated with a 64 nmol L(-1) higher 25(OH)D concentrations during summer. CONCLUSIONS: Women with high winter 25(OH)D serum concentrations, with preference of staying in the sun instead of shade during summer, a skin type allowing for longer sun exposure and a normal weight had the highest summer 25(OH)D concentrations.

  • 23. Burgaz, Ann
    et al.
    Åkesson, Agneta
    Öster, Annette
    Michaëlsson, Karl
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences.
    Wolk, Alicja
    Associations of diet, supplement use, and ultraviolet B radiation exposure with vitamin D status in Swedish women during winter2007In: American Journal of Clinical Nutrition, ISSN 0002-9165, E-ISSN 1938-3207, Vol. 86, no 5, p. 1399-1404Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Vitamin D is produced endogenously after sun exposure but can also be obtained from natural food sources, food fortification, and dietary supplements. OBJECTIVE: We aimed to determine the vitamin D status of women (61-86 y old) living in central Sweden (latitude 60 degrees ) during winter and its relation with vitamin D intake and exposure to ultraviolet B radiation. DESIGN: In a cross-sectional study, we assessed the vitamin D status (serum 25-hydroxyvitamin D [25(OH)D]) of 116 women by using an enzyme immunoassay. The women completed questionnaires covering food habits, use of dietary supplements, and sun-related behavior. RESULTS: In a multiple linear regression model, the main determinants of serum 25(OH)D concentrations (x +/- SD: 69 +/- 23 mmol/L) were dietary vitamin D (6.0 +/- 1.8 mug/d), travel to a sunny location during winter within the previous 6 mo (26%), and the use of dietary supplements (16%). There was no association between serum 25(OH)D status during the winter and age, time spent outdoors, the use of sunscreen, or skin type. Serum 25(OH)D concentrations increased by 25.5 nmol/L with 2-3 servings (130 g/wk) fatty fish/wk, by 6.2 nmol/L with the daily intake of 300 g vitamin D-fortified reduced-fat dairy products, by 11.0 nmol/L with regular use of vitamin D supplements, and by 14.5 nmol/L with a sun vacation during winter. Among nonsupplement users without a wintertime sun vacation, 2-3 servings fatty fish/wk increased serum vitamin D concentrations by 45%. CONCLUSION: Fatty fish, vitamin D-fortified reduced-fat dairy products, regular supplement use, and taking a sun vacation are important predictors for serum concentrations of 25(OH)D during winter at a latitude of 60 degrees .

  • 24.
    Byberg, Liisa
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Bellavia, Andrea
    Karolinska Inst, Unit Nutr Epidemiol, Inst Environm Med, Solna, Sweden.
    Orsini, Nicola
    Karolinska Inst, Unit Nutr Epidemiol, Inst Environm Med, Solna, Sweden.
    Wolk, Alicja
    Karolinska Inst, Unit Nutr Epidemiol, Inst Environm Med, Solna, Sweden.
    Michaëlsson, Karl
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Fruit and vegetable intake and risk of hip fracture: A cohort study of Swedish men and women2015In: Journal of Bone and Mineral Research, ISSN 0884-0431, E-ISSN 1523-4681, Vol. 30, no 6, p. 976-984Article in journal (Refereed)
    Abstract [en]

    Dietary guidelines recommend a daily intake of five servings of fruit and vegetables. Whether such intakes are associated with a lower risk of hip fracture is at present unclear. The aim of the present study was to investigate the dose-response association between habitual fruit and vegetable intake and hip fracture in a cohort study based on 40,644 men from the Cohort of Swedish Men (COSM) and 34,947 women from the Swedish Mammography Cohort (SMC) (total n=75,591), free from cardiovascular disease and cancer, who answered lifestyle questionnaires in 1997 (age 45-83 years). Intake of fruit and vegetables (servings/day) was assessed by food frequency questionnaire and incident hip fractures were retrieved from the Swedish Patient Register (1998-2010). The mean follow-up time was 14.2 years. One third of the participants reported an intake of fruit and vegetables of >5 servings/day, one third >3 to ≤5 servings/day, 28% >1 to ≤3 servings/day, and 6% reported ≤1 serving/day. During 1,037,645 person-years we observed 3,644 hip fractures (2,266, 62%, in women). The doseresponse association was found to be strongly non-linear (P<0.001). Men and women with zero consumption had 88% higher rate of hip fracture compared with those consuming 5 servings/day; adjusted hazard ratio (HR), 1.88 (95% CI, 1.53-2.32). The rate was gradually lower with higher intakes; adjusted HR for 1 vs 5 servings/day, 1.35 (95% CI, 1.21-1.58). However, more than 5 servings/day did not confer additionally lower HRs (adjusted HR for 8 vs. 5 servings/day, 0.96 (95% CI, 0.90-1.03). Similar results were observed when men and women were analyzed separately. We conclude that there is a dose-response association between fruit and vegetable intake and hip fracture such that an intake below the recommended 5 servings/day confers higher rates of hip fracture. Intakes above this recommendation do not seem to further lower the risk.

  • 25.
    Byberg, Liisa
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Gedeborg, Rolf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Cars, Thomas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Sundström, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Internal Medicine.
    Berglund, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Kilander, Lena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Melhus, Håkan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical pharmacogenomics and osteoporosis.
    Michaëlsson, Karl
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Prediction of fracture risk in men: A cohort study2012In: Journal of Bone and Mineral Research, ISSN 0884-0431, E-ISSN 1523-4681, Vol. 27, no 4, p. 797-807Article in journal (Refereed)
    Abstract [en]

    FRAX is a tool that identifies individuals with high fracture risk who will benefit from pharmacological treatment of osteoporosis. However, a majority of fractures among elderly occur in people without osteoporosis and most occur after a fall. Our aim was to accurately identify men with a high future risk of fracture, independent of cause. In the population-based Uppsala Longitudinal Study of Adult Men (ULSAM) and using survival analysis we studied different models' prognostic values (R(2) ) for any fracture and hip fracture within 10 years from age 50 (n = 2322), 60 (n = 1852), 71 (n = 1221), and 82 (n = 526). During the total follow-up period from age 50, 897 fractures occurred in 585 individuals. Of these, 281 were hip fractures occurring in 189 individuals. The rates of any fracture were 5.7/1000 person-years at risk from age 50 and 25.9/1000 person-years at risk from age 82. Corresponding hip fractures rates were 2.9 and 11.7/1000 person-years at risk. The FRAX model included all variables in FRAX except bone mineral density. The full model combining FRAX variables, comorbidity, medications, and behavioral factors explained 25-45% of all fractures and 80-92% of hip fractures, depending on age. The corresponding prognostic values of the FRAX model were 7-17% for all fractures and 41-60% for hip fractures. Net reclassification improvement (NRI) comparing the full model with the FRAX model ranged between 40 and 53% for any fracture and between 40 and 87% for hip fracture. Within the highest quintile of predicted fracture risk with the full model, 1/3 of the men will have a fracture within 10 years after age 71 years and 2/3 after age 82 years. We conclude that the addition of comorbidity, medication and behavioral factors to the clinical components of FRAX can substantially improve the ability to identify men at high risk of fracture, especially hip fracture. 

  • 26.
    Byberg, Liisa
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Kilander, Lena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Warensjö Lemming, Eva
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Michaëlsson, Karl
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Vessby, Bengt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism.
    Cancer death is related to high palmitoleic acid in serum and to polymorphisms in the SCD-1 gene in healthy Swedish men2014In: American Journal of Clinical Nutrition, ISSN 0002-9165, E-ISSN 1938-3207, Vol. 99, no 3, p. 551-558Article in journal (Refereed)
    Abstract [en]

    BACKGROUND:

    A high proportion of monounsaturated fatty acids (MUFAs) or a high ratio of MUFAs to saturated fatty acids in plasma, reflecting a high activity of the lipogenic enzyme stearoyl-CoA desaturase-1 (SCD-1), has been shown to be related to cancer death and incidence in some studies.

    OBJECTIVES:

    The objective was to study whether the serum cholesteryl ester proportion of palmitoleic acid [16:1n-7 (16:1ω-3)] and the ratio of palmitoleic to palmitic acid (16:1n-7/16:0), as an estimation of the activity of SCD-1, are related to cancer death and to investigate whether polymorphisms in the SCD-1 gene are related to cancer mortality.

    DESIGN:

    A community-based cohort of 50-y-old men was followed for a maximum of >40 y. Survival analysis was used to relate fatty acid composition in serum, analyzed at baseline by gas-liquid chromatography (n = 1981), and single nucleotide polymorphisms in the SCD-1 gene (n = 986) to cancer death. A 7-d dietary record was completed at age 70 y (n = 880).

    RESULTS:

    The proportions of 16:1n-7 and the ratio of 16:1n-7 to 16:0 were associated with cancer mortality during follow-up in a comparison of the highest with the lowest quartile of 16:1n-7 (adjusted HR: 1.37; 95% CI: 1.04, 1.82). Inherited variance of the SCD-1 gene seemed to be related to cancer death, especially among men with a low proportion of PUFA in the diet in a comparison of the highest with the lowest weighted genetic risk score (HR: 2.14; 95% CI: 1.13, 4.04).

    CONCLUSION:

    The findings are compatible with the hypothesis that there is an association between endogenously synthesized MUFAs and cancer death.

  • 27.
    Byberg, Liisa
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Melhus, Håkan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Gedeborg, Rolf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Sundström, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Internal Medicine.
    Ahlbom, Anders
    Zethelius, Björn
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Berglund, Lars G.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Wolk, Alicja
    Michaëlsson, Karl
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Total mortality after changes in leisure time physical activity in 50 year old men: 35 year follow-up of population based cohort2009In: BMJ. British Medical Journal, E-ISSN 1756-1833, Vol. 338, p. b688-Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: To examine how change in level of physical activity after middle age influences mortality and to compare it with the effect of smoking cessation. DESIGN: Population based cohort study with follow-up over 35 years. SETTING: Municipality of Uppsala, Sweden. PARTICIPANTS: 2205 men aged 50 in 1970-3 who were re-examined at ages 60, 70, 77, and 82 years. MAIN OUTCOME MEASURE: Total (all cause) mortality. RESULTS: The absolute mortality rate was 27.1, 23.6, and 18.4 per 1000 person years in the groups with low, medium, and high physical activity, respectively. The relative rate reduction attributable to high physical activity was 32% for low and 22% for medium physical activity. Men who increased their physical activity level between the ages of 50 and 60 continued to have a higher mortality rate during the first five years of follow-up (adjusted hazard ratio 2.64, 95% confidence interval 1.32 to 5.27, compared with unchanged high physical activity). After 10 years of follow-up their increased physical activity was associated with reduced mortality to the level of men with unchanged high physical activity (1.10, 0.87 to 1.38). The reduction in mortality associated with increased physical activity (0.51, 0.26 to 0.97, compared with unchanged low physical activity) was similar to that associated with smoking cessation (0.64, 0.53 to 0.78, compared with continued smoking). CONCLUSIONS: Increased physical activity in middle age is eventually followed by a reduction in mortality to the same level as seen among men with constantly high physical activity. This reduction is comparable with that associated with smoking cessation.

  • 28.
    Byberg, Liisa
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Melhus, Håkan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Pharmacology.
    Gedeborg, Rolf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Sundström, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Ahlbom, Anders
    Zethelius, Björn
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Berglund, Lars G.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Wolk, Alicja
    Michaëlsson, Karl
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Total mortality after changes in leisure time physical activity in 50 year old men: 35 year follow-up of population based cohort (Reprinted from BMJ, vol 338, b688, 2009)2009In: British Journal of Sports Medicine, ISSN 0306-3674, E-ISSN 1473-0480, Vol. 43, no 7, p. 482-Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: To examine how change in level of physical activity after middle age influences mortality and to compare it with the effect of smoking cessation.

    DESIGN: Population based cohort study with follow-up over 35 years.

    SETTING: Municipality of Uppsala, Sweden.

    PARTICIPANTS: 2205 men aged 50 in 1970-3 who were reexamined at ages 60, 70, 77, and 82 years.

    MAIN OUTCOME MEASURE: Total (all cause) mortality.

    RESULTS: The absolute mortality rate was 27.1, 23.6, and 18.4 per 1000 person years in the groups with low, medium, and high physical activity, respectively. The relative rate reduction attributable to high physical activity was 32% for low and 22% for medium physical activity. Men who increased their physical activity level between the ages of 50 and 60 continued to have a higher mortality rate during the first five years of follow-up (adjusted hazard ratio 2.64, 95% confidence interval 1.32 to 5.27, compared with unchanged high physical activity). After 10 years of follow-up their increased physical activity was associated with reduced mortality to the level of men with unchanged high physical activity (1.10, 0.87 to 1.38). The reduction in mortality associated with increased physical activity (0.51, 0.26 to 0.97, compared with unchanged low physical activity) was similar to that associated with smoking cessation (0.64, 0.53 to 0.78, compared with continued smoking).

    CONCLUSIONS: Increased physical activity in middle age is eventually followed by a reduction in mortality to the same level as seen among men with constantly high physical activity. This reduction is comparable with that associated with smoking cessation

  • 29.
    Byberg, Liisa
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Michaëlsson, Karl
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Milk and other dairy foods and risk of hip fracture in men and women: Comments on Feskanich et al.2018In: Osteoporosis International, ISSN 0937-941X, E-ISSN 1433-2965, Vol. 29, no 5, p. 1221-1222Article in journal (Refereed)
  • 30.
    Byberg, Liisa
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Michaëlsson, Karl
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Goodman, Anna
    Zethelius, Björn
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Koupil, Ilona
    Birth Weight is not Associated With Risk of Fracture: Results from Two Swedish Cohort Studies2014In: Journal of Bone and Mineral Research, ISSN 0884-0431, E-ISSN 1523-4681, Vol. 29, no 10, p. 2152-2160Article in journal (Refereed)
    Abstract [en]

    Development and growth in utero has been suggested to influence bone health. However, the relationship with risk of fracture in old age is largely unknown. Using Cox proportional hazards regression, we studied the association between birth weight and fractures at ages 50-94 among 10,893 men and women (48% women) from the Uppsala Birth Cohort Study (UBCoS, born 1915-29) and 1334 men from the Uppsala Longitudinal Study of Adult Men (ULSAM, born 1920-24). Measured birth weight was collected from hospital or midwives' records and fractures from the Swedish National Patient Register. We observed 2796 fractures (717 of these were hip fractures) in UBCoS and 335 fractures (102 hip fractures) in ULSAM. In UBCoS, the hazard ratio (HR) per 1 kg increase in birth weight, adjusted for sex and socioeconomic status at birth, was 1.01 [95% confidence interval (CI), 0.94-1.09] for any fracture and 1.06 (95% CI, 0.91-1.23) for hip fracture. Estimates in ULSAM were similar. We did not observe a differential association of birth weight with fractures occurring before age 70 or after age 70 years. Neither birth weight standardized for gestational age nor gestational duration was associated with fracture rate. In linear regression, birth weight was not associated with bone mineral density among 303 men who were 82-years-old in ULSAM but showed positive associations with total body bone mineral content (β per kg increase in birth weight, adjusted for social class and age, 133; 95% CI, 30-227). This association was attenuated after further adjustment for body mass index and height (β, 41; 95% CI, -43-126). We conclude that birth weight is associated with bone mineral content but this association does not translate into an association with risk of fracture in men and women aged 50-94 years.

  • 31.
    Byberg, Liisa
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Michaëlsson, Karl
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Koupil, I
    Size at birth is not associated with risk of hip fracture: results from two population-based cohorts2013In: Bone Abstracts, ISSN 2052-1219, Vol. 1, p. OC1.3-Article in journal (Other academic)
    Abstract [en]

    Early life growth has been suggested to influence bone health. However, the relationship with risk of hip fracture in old age has not been thoroughly investigated. We therefore studied the association between birth weight and hip fracture incidence after age 50 among 10 893 men and women (48% women) from the Uppsala Birth Cohort Study (UBCoS, born 1915–1929) and 1334 men from the Uppsala Longitudinal Study of Adult Men (ULSAM, born 1920–1924). Birth weight was collected from hospital or midwives’ records and hip fractures were obtained from the Swedish Hospital Discharge Register.

    We observed 717 hip fractures in UBCoS (458 in women, 259 in men, end of follow-up: 31 December 2008) and 102 hip fractures in ULSAM (end of follow-up: 31 December 2009). There were no indications of non-linear associations. Results are presented as hazard ratios (HR) and 95% CI per 1 kg increase in birth weight.

    The crude HR for 1 kg increase in birth weight on hip fracture rate in UBCoS was 0.99 (95% CI: 0.85–1.14). After controlling for gender and socioeconomic status at birth, the HR was 1.06 (95% CI: 0.91–1.23). Additional adjustment for adult height and comorbidity in a subgroup of UBCoS men (n=1241, 50 hip fractures) gave a HR of 0.97 (95% CI: 0.52–1.80). Parity and gestational age did not largely influence the estimates. Neither birth weight standardized for gestational age nor gestational duration was associated with hip fracture rate.

    The unadjusted HR in ULSAM was 1.06 (95% CI: 0.73–1.53). After adjustment for adult body mass index, height, social class, comorbidity, and smoking status, the HR was 1.03 (95% CI: 0.70–1.51).

    Based on the results from two population-based cohorts with accurate assessment of both birth weight and hip fractures, we conclude that there is no association between birth weight and risk of hip fracture.

  • 32.
    Canova, Cristina
    et al.
    Univ Padua, Dept Cardiol Thorac & Vasc Sci, Padua, Italy.
    Pitter, Gisella
    Univ Padua, Dept Cardiol Thorac & Vasc Sci, Padua, Italy.
    Zanier, Loris
    Hlth Directorate, Epidemiol Serv, Udine, Italy.
    Simonato, Lorenzo
    Univ Padua, Dept Cardiol Thorac & Vasc Sci, Padua, Italy.
    Michaëlsson, Karl
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Ludvigsson, Jonas E.
    Columbia Univ, Coll Phys & Surg, Dept Med, New York, NY USA;Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden;Orebro Univ, Orebro Univ Hosp, Dept Pediat, Orebro, Sweden;Univ Nottingham, Sch Med, Div Epidemiol & Publ Hlth, Nottingham, England.
    Risk of Fractures in Youths with Celiac Disease-A Population-Based Study2018In: Journal of Pediatric Surgery Case Reports, ISSN 0022-3476, E-ISSN 2213-5766, Vol. 198, p. 117-120Article in journal (Refereed)
    Abstract [en]

    Objective To assess the risk of any fracture requiring hospital care in a cohort of individuals with celiac disease diagnosed in childhood/adolescence compared with reference individuals matched by age and sex. Study design Our study cohort consisted of 213 635 people born and residing in Friuli-Venezia Giulia Region, Italy, in 1989-2011. We selected, through pathology reports, hospital discharge records, or co-payment exemptions, 1233 individuals with celiac disease (aged 0-17 years at diagnosis) and compared them with 6167 reference individuals matched by sex and year of birth. Fractures were identified through hospital discharge records. We calculated hazard ratios (HRs) for any fracture after celiac disease diagnosis (or index date for reference individuals) with Cox regression and ORs for any fracture before celiac disease diagnosis with conditional logistic regression. Results During the follow-up period (maximum 23 years), 22 individuals with celiac disease (9394 person-years) and 128 reference individuals (47 308 person-years) experienced a fracture. giving an overall HR of 0.87 (95% CI 0.55-1.37). The risk was not modified by sex, age at diagnosis, or calendar period of diagnosis. We obtained similar HRs when excluding fractures occurring after the age of 18 years and adjusting for maternal education or vitamin D supplementation. The odds of previous fracture also did not differ between subjects with celiac disease and reference individuals (22 and 96 cases, respectively: OR 1.15: 95% CI 0.72-1.84). Conclusions We did not find any evidence of an increased risk of fractures during childhood and youth among patients with celiac disease.

  • 33.
    Carlsson, Axel C
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Ärnlöv, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Sundström, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Michaëlsson, Karl
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Byberg, Liisa
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Physical activity, obesity and risk of cardiovascular disease in middle-aged men during a median of 30 years of follow-up2016In: European Journal of Preventive Cardiology, ISSN 2047-4873, E-ISSN 2047-4881, Vol. 23, no 4, p. 359-365Article in journal (Refereed)
    Abstract [en]

    BACKGROUND:

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

    METHOD AND RESULTS:

    At age 50 years, cardiovascular risk factors were assessed in 2196 participating men of the ULSAM-study. This investigation was repeated at age 60, 70, 77 and 82 years. Being physically active (PA) was defined as three hours of recreational or hard physical training per week. The men were categorized according to BMI/PA-status, as PA/normal weight (n = 593 at baseline), non-PA/normal weight (BMI < 25 kg/m(2), n = 580), PA/overweight (n = 418), non-PA/overweight (BMI 25-30 kg/m(2), n = 462), PA/obese (n = 62), non-PA/obese (BMI >30 kg/m(2), n = 81). We used updated data on BMI and physical activity obtained at all examinations. During follow-up (median 30 years) 850 individuals suffered a cardiovascular disease (myocardial infarction, stroke or heart failure). Using updated data on BMI/PA categories, an increased risk for cardiovascular disease was seen with increasing BMI, but a high physical activity was associated with a lower risk of cardiovascular disease within each BMI category: non-PA/normal weight (hazard ratio (HR) 1.31, 95% confidence interval (CI) 1.04-1.66), PA/overweight (HR 1.52, 95% CI 1.20-1.94), non-PA/overweight (HR 1.65, 95% CI 1.31-2.07) PA/obese (HR 2.05, 95% CI 1.44-2.92) and non-PA/obese (HR 2.39, 95% CI 1.74-3.29), using PA/normal weight men as referent.

    CONCLUSIONS:

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

  • 34. Carlsson, Sofia
    et al.
    Andersson, Tomas
    de Faire, Ulf
    Lichtenstein, Paul
    Michaelsson, Karl
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Ahlbom, Anders
    Using Twin Controls to Study the Effects of BMI on Mortality2011In: Epidemiology, ISSN 1044-3983, E-ISSN 1531-5487, Vol. 22, no 1, p. 107-108Article in journal (Refereed)
  • 35. Carlsson, Sofia
    et al.
    Andersson, Tomas
    de Faire, Ulf
    Lichtenstein, Paul
    Michaëlsson, Karl
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm , UCR-Uppsala Clinical Research center.
    Ahlbom, Anders
    Body mass index and mortality: is the association explained by genetic factors?2011In: Epidemiology, ISSN 1044-3983, E-ISSN 1531-5487, Vol. 22, no 1, p. 98-103Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Numerous studies have shown that higher body mass index (BMI) is associated with higher mortality. We investigated the extent to which this association might be explained by genetic factors. METHODS: We used data from the Swedish Twin Registry on twins born 1886-1958 who answered a questionnaire in 1969/1970 or 1972 (n = 44,258). Information on mortality from all-causes (n = 14,217), cardiovascular disease (CVD; n = 9009), and coronary heart disease (CHD; n = 3564) was obtained by linkage to the national Causes of Death Registry for the years 1972-2004. The association between BMI and mortality was studied without control for genetic factors in cohort analyses and with control for genetic factors in co-twin control analyses. RESULTS: In cohort analyses, there was a clear dose-response relationship between BMI and mortality. Hazard ratios per 1 unit increase in BMI in subjects with BMI ≥18.5 were 1.05 (95% confidence interval = 1.05-1.06) for all-cause mortality, 1.07 (1.07-1.09) for CVD mortality, and 1.09 (1.08-1.10) for CHD mortality. Similar results were seen in co-twin control analyses of dizygotic twins. However, within monozygotic twins, BMI was associated with death from CHD (OR = 1.06; 1.00-1.12), whereas the association with all-cause mortality (1.01, 0.98-1.04) and CVD mortality (1.02, 0.98-1.06) was weak. CONCLUSIONS: Our findings indicate that there is an association between high BMI and mortality from CHD that is not explained by genetic confounding. However, a large part of the association between BMI and other causes of death may be explained by genes rather than by a causal link between these factors.

  • 36. Carlsson, Sofia
    et al.
    Andersson, Tomas
    Lichtenstein, Paul
    Michaëlsson, Karl
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Ahlbom, Anders
    Genetic effects on physical activity: results from the Swedish Twin Registry2006In: Medicine & Science in Sports & Exercise, ISSN 0195-9131, E-ISSN 1530-0315, Vol. 38, no 8, p. 1396-1401Article in journal (Refereed)
    Abstract [en]

    PURPOSE: The aim of this study was to investigate the genetic effects on leisure-time physical activity using data from the Swedish Twin Registry. METHODS: We investigated 13,362 twin pairs (5334 monozygotic and 8028 dizygotic pairs) aged 14-46 yr. Information on leisure-time physical activity was obtained by questionnaire. Correlations and odds ratios of physical activity were calculated for males, females, and monozygotic and dizygotic twins, respectively. Structural equation modeling was used to estimate the contribution of genetic effects as well as common and nonshared environmental factors on leisure-time physical activity. RESULTS: About one third of the twins reported that they exercised regularly (26% in females and 39% in males). The correlations of physical activity were twice as high in monozygotic compared with dizygotic twins, suggesting the presence of genetic effects. The variation in physical activity due to heritage was 57% (95% confidence interval (CI) = 0.49-0.63) in males and 50% (95% CI = 0.49-0.55) in females. The common environmental influence on physical activity was very small compared with the influence from environmental factors unique to the individual. CONCLUSIONS: Our study establishes heredity as an important component behind individual differences in physical activity in adult men and women. This may be one reason behind difficulties in convincing people to adopt an active lifestyle. Still, this study shows that there is a substantial influence on physical activity from environmental factors unique to the individual.

  • 37. Carlsson, Sofia
    et al.
    Andersson, Tomas
    Lichtenstein, Paul
    Michaëlsson, Karl
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Ahlbom, Anders
    Physical activity and mortality: is the association explained by genetic selection?2007In: American Journal of Epidemiology, ISSN 0002-9262, E-ISSN 1476-6256, Vol. 166, no 3, p. 255-259Article in journal (Refereed)
    Abstract [en]

    Public health recommendations promote physical activity to improve health and longevity. Recent data suggest that the association between physical activity and mortality may be due to genetic selection. Using data on twins, the authors investigated whether genetic selection explains the association between physical activity and mortality. Data were based on a postal questionnaire answered by 13,109 Swedish twin pairs in 1972. The national Cause of Death Register was used for information about all-cause mortality (n=1,800) and cardiovascular disease mortality (n=638) during 1975-2004. The risk of death was reduced by 34% for men (relative risk=0.64, 95% confidence interval: 0.50, 0.83) and by 25% for women (relative risk=0.75, 95% confidence interval: 0.50, 1.14) reporting high physical activity levels. Within-pair comparisons of monozygotic twins showed that, compared with their less active co-twin, the more active twin had a 20% (odds ratio=0.80, 95% confidence interval: 0.65, 0.99) reduced risk of all-cause mortality and a 32% (odds ratio=0.68, 95% confidence interval: 0.49, 0.95) reduced risk of cardiovascular disease mortality. Results indicate that physical activity is associated with a reduced risk of mortality not due to genetic selection. This finding supports a causal link between physical activity and mortality.

  • 38. Carlsson, Sofia
    et al.
    Andersson, Tomas
    Michaëlsson, Karl
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Vågerö, Denny
    Ahlbom, Anders
    Late retirement is not associated with increased mortality, results based on all Swedish retirements 1991-20072012In: European Journal of Epidemiology, ISSN 0393-2990, E-ISSN 1573-7284, Vol. 27, no 6, p. 483-486Article in journal (Refereed)
  • 39.
    Collins, Gary S.
    et al.
    Univ Oxford, Ctr Stat Med, Wolfson Coll Annexe, Oxford OX2 6UD, England.
    Michaëlsson, Karl
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Fracture risk assessment: state of the art, methodologically unsound, or poorly reported?2012In: Current osteoporosis reports, ISSN 1544-2241, Vol. 10, no 3, p. 199-207Article in journal (Refereed)
    Abstract [en]

    Osteoporotic fractures, including hip fractures, are a global health concern associated with significant morbidity and mortality as well as a major economic burden. Identifying individuals who are at an increased risk of osteoporotic fracture is an important challenge to be resolved. Recently, multivariable prediction tools have been developed to assist clinicians in the management of their patients by calculating their 10-year risk of fracture (FRAX, QFracture, Garvan) using a combination of known risk factors. These prediction models have revolutionized the way clinicians assess the risk of fracture. Studies evaluating the performance of prediction models in this and other areas of medicine have, however, been characterized by poor design, methodological conduct, and reporting. We examine recently developed fracture prediction models and critically discuss issues in their design, validation, and transparency.

  • 40. Cornelis, M C
    et al.
    Byrne, E M
    Esko, T
    Nalls, M A
    Ganna, A
    Paynter, N
    Monda, K L
    Amin, N
    Fischer, K
    Renstrom, F
    Ngwa, J S
    Huikari, V
    Cavadino, A
    Nolte, I M
    Teumer, A
    Yu, K
    Marques-Vidal, P
    Rawal, R
    Manichaikul, A
    Wojczynski, M K
    Vink, J M
    Zhao, J H
    Burlutsky, G
    Lahti, J
    Mikkilä, V
    Lemaitre, R N
    Eriksson, J
    Musani, S K
    Tanaka, T
    Geller, F
    Luan, J
    Hui, J
    Mägi, R
    Dimitriou, M
    Garcia, M E
    Ho, W-K
    Wright, M J
    Rose, L M
    Magnusson, P K E
    Pedersen, N L
    Couper, D
    Oostra, B A
    Hofman, A
    Ikram, M A
    Tiemeier, H W
    Uitterlinden, A G
    van Rooij, F J A
    Barroso, I
    Johansson, I
    Xue, L
    Kaakinen, M
    Milani, L
    Power, C
    Snieder, H
    Stolk, R P
    Baumeister, S E
    Biffar, R
    Gu, F
    Bastardot, F
    Kutalik, Z
    Jacobs, D R
    Forouhi, N G
    Mihailov, E
    Lind, Lars
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Lindgren, C
    Michaëlsson, Karl
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Morris, A
    Jensen, M
    Khaw, K-T
    Luben, R N
    Wang, J J
    Männistö, S
    Perälä, M-M
    Kähönen, M
    Lehtimäki, T
    Viikari, J
    Mozaffarian, D
    Mukamal, K
    Psaty, B M
    Döring, A
    Heath, A C
    Montgomery, G W
    Dahmen, N
    Carithers, T
    Tucker, K L
    Ferrucci, L
    Boyd, H A
    Melbye, M
    Treur, J L
    Mellström, D
    Hottenga, J J
    Prokopenko, I
    Tönjes, A
    Deloukas, P
    Kanoni, S
    Lorentzon, M
    Houston, D K
    Liu, Y
    Danesh, J
    Rasheed, A
    Mason, M A
    Zonderman, A B
    Franke, L
    Kristal, B S
    Karjalainen, J
    Reed, D R
    Westra, H-J
    Evans, M K
    Saleheen, D
    Harris, T B
    Dedoussis, G
    Curhan, G
    Stumvoll, M
    Beilby, J
    Pasquale, L R
    Feenstra, B
    Bandinelli, S
    Ordovas, J M
    Chan, A T
    Peters, U
    Ohlsson, C
    Gieger, C
    Martin, N G
    Waldenberger, M
    Siscovick, D S
    Raitakari, O
    Eriksson, J G
    Mitchell, P
    Hunter, D J
    Kraft, P
    Rimm, E B
    Boomsma, D I
    Borecki, I B
    Loos, R J F
    Wareham, N J
    Vollenweider, P
    Caporaso, N
    Grabe, H J
    Neuhouser, M L
    Wolffenbuttel, B H R
    Hu, F B
    Hyppönen, E
    Järvelin, M-R
    Cupples, L A
    Franks, P W
    Ridker, P M
    van Duijn, C M
    Heiss, G
    Metspalu, A
    North, K E
    Ingelsson, Erik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Nettleton, J A
    van Dam, R M
    Chasman, D I
    Genome-wide meta-analysis identifies six novel loci associated with habitual coffee consumption2015In: Molecular Psychiatry, ISSN 1359-4184, E-ISSN 1476-5578, Vol. 20, no 5, p. 647-656Article in journal (Refereed)
    Abstract [en]

    Coffee, a major dietary source of caffeine, is among the most widely consumed beverages in the world and has received considerable attention regarding health risks and benefits. We conducted a genome-wide (GW) meta-analysis of predominately regular-type coffee consumption (cups per day) among up to 91 462 coffee consumers of European ancestry with top single-nucleotide polymorphisms (SNPs) followed-up in ~30 062 and 7964 coffee consumers of European and African-American ancestry, respectively. Studies from both stages were combined in a trans-ethnic meta-analysis. Confirmed loci were examined for putative functional and biological relevance. Eight loci, including six novel loci, met GW significance (log10Bayes factor (BF)>5.64) with per-allele effect sizes of 0.03-0.14 cups per day. Six are located in or near genes potentially involved in pharmacokinetics (ABCG2, AHR, POR and CYP1A2) and pharmacodynamics (BDNF and SLC6A4) of caffeine. Two map to GCKR and MLXIPL genes related to metabolic traits but lacking known roles in coffee consumption. Enhancer and promoter histone marks populate the regions of many confirmed loci and several potential regulatory SNPs are highly correlated with the lead SNP of each. SNP alleles near GCKR, MLXIPL, BDNF and CYP1A2 that were associated with higher coffee consumption have previously been associated with smoking initiation, higher adiposity and fasting insulin and glucose but lower blood pressure and favorable lipid, inflammatory and liver enzyme profiles (P<5 × 10(-8)).Our genetic findings among European and African-American adults reinforce the role of caffeine in mediating habitual coffee consumption and may point to molecular mechanisms underlying inter-individual variability in pharmacological and health effects of coffee.

  • 41. Cornelis, M C
    et al.
    Gustafsson, Stefan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Ärnlöv, J
    Elmståhl, S
    Söderberg, S
    Sundström, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Michaëlsson, Karl
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Ingelsson, Erik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology. Stanford Univ, Sch Med, Dept Med, Div Cardiovasc Med, Stanford, CA 94305 USA.
    Targeted proteomic analysis of habitual coffee consumption.2018In: Journal of Internal Medicine, ISSN 0954-6820, E-ISSN 1365-2796, Vol. 283, no 2, p. 200-211Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Coffee drinking has been implicated in mortality and a variety of diseases but potential mechanisms underlying these associations are unclear. Large-scale systems epidemiological approaches may offer novel insights to mechanisms underlying associations of coffee with health.

    OBJECTIVE: We performed an analysis of known and novel protein markers linked to cardiovascular disease and their association with habitual coffee intake in the Prospective Study of the Vasculature in Uppsala Seniors (PIVUS, n = 816) and followed up top proteins in the Uppsala Longitudinal Study of Adult Men (ULSAM, n = 635) and EpiHealth (n = 2418).

    METHODS: In PIVUS and ULSAM, coffee intake was measured by 7-day dietary records whilst a computer-based food frequency questionnaire was used in EpiHealth. Levels of up to 80 proteins were assessed in plasma by a proximity extension assay.

    RESULTS: Four protein-coffee associations adjusted for age, sex, smoking and BMI, met statistical significance in PIVUS (FDR < 5%, P < 2.31 × 10(-3) ): leptin (LEP), chitinase-3-like protein 1 (CHI3L), tumour necrosis factor (TNF) receptor 6 and TNF-related apoptosis-inducing ligand. The inverse association between coffee intake and LEP replicated in ULSAM (β, -0.042 SD per cup of coffee, P = 0.028) and EpiHealth (β, -0.025 SD per time of coffee, P = 0.004). The negative coffee-CHI3L association replicated in EpiHealth (β, -0.07, P = 1.15 × 10(-7) ), but not in ULSAM (β, -0.034, P = 0.16).

    CONCLUSIONS: The current study supports an inverse association between coffee intake and plasma LEP and CHI3L1 levels. The coffee-CHI3L1 association is novel and warrants further investigation given links between CHI3L1 and health conditions that are also potentially influenced by coffee.

  • 42.
    Ekman, Anna
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences.
    Mallmin, Hans
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences.
    Michaëlsson, Karl
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences.
    Ljunghall, Sverker
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    External hip protectors to prevent osteoporotic hip fractures1997In: The Lancet, ISSN 0140-6736, E-ISSN 1474-547X, Vol. 350, no 9077, p. 563-4Article in journal (Refereed)
  • 43.
    Ekman, Anna
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences.
    Michaëlsson, Karl
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences.
    Ljunghall, Sverker
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Mallmin, Hans
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences.
    Almost all institutionalized women are osteoporotic, when measured by heeland finger ultrasound2001In: Journal of Internal Medicine, ISSN 0954-6820, E-ISSN 1365-2796, Vol. 249, no 2, p. 173-80Article in journal (Refereed)
    Abstract [en]

    OBJECTIVES: Since there is a need for simple methods to identify individuals with osteoporosis, we investigated bone status (heel and finger) with ultrasound in an institutionalized elderly population and studied the association between these measures, risk factors for osteoporosis and prevalent osteoporotic fractures. DESIGN: Cross-sectional study. Subjects. Nursing home residents, 237 women and 84 men, mean age 84 years. RESULTS: Altogether 82% of those eligible could undergo heel ultrasound, 65% finger ultrasound and 41% measurements at both sites. Using a transcription of the WHO criterion of osteoporosis, 95% of the women who underwent heel ultrasound were classified as osteoporotic (mean T-score = -4.8) and 92% had Z-scores below zero (mean Z-score=-1.6), whereas 51% of the men were osteoporotic (mean T-score=-2.6) and 77% had Z-scores below zero (mean Z-score=-1.3). Based on finger ultrasound measurements, 99% of the women were classified as osteoporotic (mean T-score=-5.0) and 93% had Z-scores below zero (mean -1.6). The variations in ultrasound values were only moderately explained by age, current weight and walking ability. Amongst women, the association with a prevalent osteoporotic fracture decreased by 43% (95% CI=10-63%) for every SD increase in speed of sound (SOS) of the heel, but no such relationship was found for finger SOS. CONCLUSIONS: Our results from ultrasound measurements at two different anatomical sites indicate that virtually all institutionalized elderly women could be classified as osteoporotic, when measured by these techniques.

  • 44.
    Ekman, Anna
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences.
    Michaëlsson, Karl
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Petren-Mallmin, M.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology.
    Ljunghall, Sverker
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Mallmin, Hans
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences.
    DXA of the hip and heel ultrasound but not densitometry of the fingers can discriminate female hip fracture patients from controls: a comparison between four different methods2001In: Osteoporosis International, ISSN 0937-941X, E-ISSN 1433-2965, Vol. 12, no 3, p. 185-191Article in journal (Refereed)
    Abstract [en]

    Dual-energy X-ray absorptiometry (DXA) of the proximal femur and in more recent years quantitative ultrasound (QUS) of the heel are the most established methods for assessing hip fracture risk. Measurement of the fingers offers a new approach. We performed DXA of the proximal femur, QUS of the heel and fingers, and radiographic absorptiometry (RA) of the fingers in 87 non-institutionalized women, 65-85 years of age, with a first hip fracture and compared them with 195 randomly selected age-matched controls. Bone mineral density (BMD) of the femoral neck and heel Stiffness Index were significantly lower among cases than among controls (by 15% and 17%, respectively; p < 0.0001), whereas no significant differences were found for finger measurements. When applying the WHO criterion of osteoporosis, 62-98% of the patients were classified as osteoporotic, compared with 19-85% of the controls, depending on method and site. The risks of hip fracture, estimated as odds ratios for every 1 SD reduction in femoral neck BMD, heel Stiffness Index, finger QUS and finger RA, were: 3.6 (95% CI 2.4-5.5), 3.4 (95% CI 2.2-5.0), 1.0 (95% CI 0.7-1.3) and 1.2 (95% CI 0.8-1.6), respectively. Compared with women with normal BMD of the femoral neck, those classified as osteopenic had an odds ratio of hip fracture of 14 (95% CI 2-110), whereas those classified as osteoporotic had an odds ratio of 63 (95% CI 8-501). We conclude that hip DXA and heel QUS have similar capacities to discriminate the risk of a first hip fracture, whereas QUS and RA of the phalanges seem inferior techniques for differentiating female hip fracture patients from controls.

  • 45.
    Ekman, Anna
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.
    Michaëlsson, Karl
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Petrén-Mallmin, M.
    Ljunghall, Sverker
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Mallmin, Hans
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences.
    Dual X-ray absorptiometry of hip, heel ultrasound, and densitometry of fingers can discriminate male patients with hip fracture from control subjects: a comparison of four different methods2002In: Journal of clinical densitometry, ISSN 1094-6950, E-ISSN 1559-0747, Vol. 5, no 1, p. 79-85Article in journal (Refereed)
    Abstract [en]

    Few studies have examined different bone densitometry techniques to determine male hip fracture risk. We conducted a case-control study of 31 noninstitutionalized men, mean age 77 yr, with a first hip fracture and compared the results with 68 randomly selected age-matched control subjects. The methods used were dual X-ray absorptiometry (DXA) of the proximal femur, quantitative ultrasound (QUS) of the heel and fingers, and radiographic absorptiometry of the fingers. Case patients had significantly lower values (4-17%; p < 0.01) for all methods. The odds ratios for every SD reduction in bone values were 4.8 (95% confidence interval [CI]: 2.3-9.9) for DXA of the femoral neck, 2.2 (95% CI: 1.2-3.9) for QUS of the heel, 2.0 (95% CI: 1.2-3.3) for QUS of the phalanges, and 3.1 (95% CI: 1.5-6.6) for radiographic absorptiometry of the phalanges. The results indicate a strong capability of DXA of the femoral neck to distinguish between men with a first hip fracture and control subjects. Furthermore, ultrasound of the heel and fingers as well as radiographic absorptiometry proved capable of discriminating men with hip fractures from control subjects.

  • 46.
    Englund, Gunilla
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmacy.
    Hallberg, Pär
    Artursson, Per
    Michaëlsson, Karl
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences.
    Melhus, Håkan
    Association between the number of coadministered P-glycoprotein inhibitors and serum digoxin levels in patients on therapeutic drug monitoring2004In: BMC Medicine, p. 2-8Article in journal (Refereed)
  • 47.
    Englund, Gunilla
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmacy.
    Hallberg, Pär
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences. klin farm.
    Artursson, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmacy.
    Michaëlsson, Karl
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences.
    Melhus, Håkan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Association between the number of coadministered P-glycoprotein inhibitors and serum digoxin levels in patients on therapeutic drug monitoring2004In: BMC Medicine, ISSN 1741-7015, E-ISSN 1741-7015, Vol. 2, p. 8-Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: The ABC transporter P-glycoprotein (P-gp) is recognized as a site for drug-drug interactions and provides a mechanistic explanation for clinically relevant pharmacokinetic interactions with digoxin. The question of whether several P-gp inhibitors may have additive effects has not yet been addressed. METHODS: We evaluated the effects on serum concentrations of digoxin (S-digoxin) in 618 patients undergoing therapeutic drug monitoring. P-gp inhibitors were classified as Class I, with a known effect on digoxin kinetics, or Class II, showing inhibition in vitro but no documented effect on digoxin kinetics in humans. Mean S-digoxin values were compared between groups of patients with different numbers of coadministered P-gp inhibitors by a univariate and a multivariate model, including the potential covariates age, sex, digoxin dose and total number of prescribed drugs. RESULTS: A large proportion (47%) of the digoxin patients undergoing therapeutic drug monitoring had one or more P-gp inhibitor prescribed. In both univariate and multivariate analysis, S-digoxin increased in a stepwise fashion according to the number of coadministered P-gp inhibitors (all P values < 0.01 compared with no P-gp inhibitor). In multivariate analysis, S-digoxin levels were 1.26 +/- 0.04, 1.51 +/- 0.05, 1.59 +/- 0.08 and 2.00 +/- 0.25 nmol/L for zero, one, two and three P-gp inhibitors, respectively. The results were even more pronounced when we analyzed only Class I P-gp inhibitors (1.65 +/- 0.07 for one and 1.83 +/- 0.07 nmol/L for two). CONCLUSIONS: Polypharmacy may lead to multiple drug-drug interactions at the same site, in this case P-gp. The S-digoxin levels increased in a stepwise fashion with an increasing number of coadministered P-gp inhibitors in patients taking P-gp inhibitors and digoxin concomitantly. As coadministration of digoxin and P-gp inhibitors is common, it is important to increase awareness about P-gp interactions among prescribing clinicians.

  • 48. Engstrom, Annette
    et al.
    Michaëlsson, Karl
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Vahter, Marie
    Julin, Bettina
    Wolk, Alicja
    Akesson, Agneta
    Associations between dietary cadmium exposure and bone mineral density and risk of osteoporosis and fractures among women2012In: Bone, ISSN 8756-3282, E-ISSN 1873-2763, Vol. 50, no 6, p. 1372-1378Article in journal (Refereed)
    Abstract [en]

    Osteoporosis and its main health outcome, fragility fractures, are large and escalating public health problems. Cadmium, a widespread food contaminant, is a proposed risk factor; still the association between estimated dietary cadmium exposure and bone mineral density (BMD) has never been assessed. Within a sub-cohort of the Swedish Mammography Cohort, we assessed dietary cadmium exposure based on a food frequency questionnaire (1997) and urinary cadmium (2004-2008) in relation to total-body BMD and risk of osteoporosis and fractures (1997-2009) among 2676 women (aged 56-69 years). In multivariable-adjusted linear regression, dietary cadmium was inversely associated with BMD at the total body and lumbar spine. After further adjustment for dietary factors important for bone health and cadmium bioavailability-calcium, magnesium, iron and fiber, the associations became more pronounced. A 32% increased risk of osteoporosis (95% Cl: 2-71%) and 31% increased risk for any first incident fracture (95% Cl; 2-69%) were observed comparing high dietary cadmium exposure (>= 13 mu g/day, median) with lower exposures (<13 mu g/day). By combining high dietary with high urinary cadmium (>= 0.50 mu g/g creatinine), odds ratios among never-smokers were 2.65 (95% Cl: 1.43-4.91) for osteoporosis and 3.05 (95% Cl; 1.66-5.59) for fractures. In conclusion, even low-level cadmium exposure from food is associated with low BMD and an increased risk of osteoporosis and fractures. The partial masking of the associations by essential nutrients indicates important interplay between dietary factors and contaminants present in food. In separate analyses, dietary and urinary cadmium underestimated the association with bone effects.

  • 49. Engström, Annette
    et al.
    Michaëlsson, Karl
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm , UCR-Uppsala Clinical Research Center.
    Suwazono, Yasushi
    Wolk, Alicja
    Vahter, Marie
    Åkesson, Agneta
    Long-term cadmium exposure and the association with bone mineral density and fractures in a population-based study among women2011In: Journal of Bone and Mineral Research, ISSN 0884-0431, E-ISSN 1523-4681, Vol. 26, no 3, p. 486-495Article in journal (Refereed)
    Abstract [en]

    BACKGROUND:: All people are exposed to cadmium (Cd) via food, smokers are additionally exposed. High Cd exposure is associated with severe bone damage, but the public health impact in relation to osteoporosis and fractures at low environmental exposure remains to be clarified. METHODS:: Within the population-based Swedish Mammography Cohort, we assessed urinary Cd (U-Cd, mug/g creatinine, cr) as a marker of life-time exposure and bone mineral density (BMD) by DXA among 2,688 women. Register-based information on fractures was retrieved from 1997 to 2009. Associations were evaluated by multivariable regression analyses. RESULTS:: In linear regression U-Cd was inversely associated with BMD at the total body (p<0.001), femoral neck (p=0.025), total hip (p=0.004), lumbar spine (p=0.088), and volumetric femoral neck (p=0.013). In comparison to women with U-Cd <0.50 mug/g cr, those with U-Cd >/=0.75 mug/g cr had OR 2.45 (95% CI, 1.51-3.97) and 1.97 (95% CI, 1.24-3.14) for osteoporosis at the femoral neck and lumbar spine, respectively. Among never-smokers, the corresponding ORs were 3.45 (95% CI, 1.46-8.23) and 3.26 (95% CI, 1.44-7.38). For any first fracture (n=395) OR was 1.16 (95% CI, 0.89-1.50) comparing U-Cd >/=0.5 mug/g cr with lower levels. Among never-smokers, the ORs (95% CIs) were 2.03 (1.33-3.09) for any first fracture, 2.06 (1.28-3.32) for first osteoporotic fracture, 2.18 (1.20-3.94) for first distal forearm fracture and 1.89 (1.25-2.85) for multiple incident fractures. CONCLUSIONS:: U-Cd at low environmental exposure from food in a general population of women showed modest but significant association with both BMD and fractures especially in never smokers indicating a larger concern than previously known.

  • 50.
    Fang, Fang
    et al.
    Karolinska Inst, Dept Med Epidemiol & Biostat, Box 281, S-17177 Stockholm, Sweden.
    Hållmarker, Ulf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Mora Hosp, Dept Internal Med, Mora, Sweden.
    James, Stefan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Ingre, Caroline
    Karolinska Univ Hosp, Dept Neurol, Stockholm, Sweden.; Karolinska Inst, Dept Clin Neurosci, S-17177 Stockholm, Sweden.
    Michaëlsson, Karl
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Ahlbom, Anders
    Karolinska Inst, Inst Environm Med, S-17177 Stockholm, Sweden.
    Feychting, Maria
    Karolinska Inst, Inst Environm Med, S-17177 Stockholm, Sweden.
    Amyotrophic lateral sclerosis among cross-country skiers in Sweden.2016In: European Journal of Epidemiology, ISSN 0393-2990, E-ISSN 1573-7284, Vol. 31, no 3, p. 247-253Article in journal (Refereed)
    Abstract [en]

    A highly increased risk of amyotrophic lateral sclerosis (ALS) has been suggested among professional athletes. We aimed to examine whether long distance cross-country skiers have also a higher risk of ALS and whether the increased risk was modified by skiing performance. We followed 212,246 cross-country skiers in the Swedish Vasaloppet cohort and a random selection of 508,176 general Swedes not participating in the Vasaloppet during 1989-2010. The associations between cross-country skiing as well as skiing performance (i.e., type of race, finishing time and number of races) and the consequent risk of ALS were estimated through hazard ratios (HRs) derived from Cox model. During the study, 39 cases of ALS were ascertained among the skiers. The fastest skiers (100-150 % of winner time) had more than fourfold risk of ALS (HR 4.31, 95 % confidence interval [CI] 1.78-10.4), as compared to skiers that finished at >180 % of winner time. Skiers who participated >4 races during this period had also a higher risk (HR 3.13, 95 % CI 1.37-7.17) than those participated only one race. When compared to the non-skiers, the fastest skiers still had a higher risk (HR 2.08, 95 % CI 1.12-3.84), as skiers who had >4 races (HR 1.88, 95 % CI 1.05-3.35), but those finishing at >180 % of winner time had a lower risk (HR 0.46, 95 % CI 0.24-0.87). In conclusion, long distance cross-country skiing is associated with a higher risk of ALS, but only among the best skiers; recreational skiers appear to have a largely reduced risk.

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