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  • 1. Ahl, Matilda
    et al.
    Avdic, Una
    Strandberg, Maria Compagno
    Chugh, Deepti
    Andersson, Emelie
    Hållmarker, Ulf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Department of Internal Medicine, Mora Hospital, Mora, Sweden.
    James, Stefan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Deierborg, Tomas
    Ekdahl, Christine T
    Physical Activity Reduces Epilepsy Incidence: a Retrospective Cohort Study in Swedish Cross-Country Skiers and an Experimental Study in Seizure-Prone Synapsin II Knockout Mice2019In: Sports medicine - open, ISSN 2199-1170, Vol. 5, no 1, article id 52Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Epilepsy patients commonly exercise less than the general population. Animal studies indicate beneficial effects of physical activity in established epilepsy, while its effect on the development is currently less known.

    METHODS: Here, we investigated the incidence of epilepsy during 20 years in a cohort of participants from the long-distance Swedish cross-country ski race Vasaloppet (n = 197,685) and compared it to the incidence of non-participating-matched controls included in the Swedish population register (n = 197,684). Individuals diagnosed with diseases such as stroke and epilepsy before entering the race were excluded from both groups. Experimentally, we also determined how physical activity could affect the development of epilepsy in epilepsy-prone synapsin II knockout mice (SynIIKO), with and without free access to a running wheel.

    RESULTS: We identified up to 40-50% lower incidence of epilepsy in the Vasaloppet participants of all ages before retirement. A lower incidence of epilepsy in Vasaloppet participants was seen regardless of gender, education and occupation level compared to controls. The participants included both elite and recreational skiers, and in a previous survey, they have reported a higher exercise rate than the general Swedish population. Sub-analyses revealed a significantly lower incidence of epilepsy in participants with a faster compared to slower finishing time. Dividing participants according to specified epilepsy diagnoses revealed 40-50% decrease in focal and unspecified epilepsy, respectively, but no differences in generalized epilepsy. Voluntary exercise in seizure-prone SynIIKO mice for 1 month before predicted epilepsy development decreased seizure manifestation from > 70 to 40%. Brain tissue analyses following 1 month of exercise showed increased hippocampal neurogenesis (DCX-positive cells), while microglial (Iba1) and astrocytic activation (GFAP), neuronal Map2, brain-derived neurotrophic factor and its receptor tyrosine receptor kinase B intensity were unaltered. Continued exercise for additionally 2 months after predicted seizure onset in SynIIKO mice resulted in a 5-fold reduction in seizure manifestation (from 90 to 20%), while 2 months of exercise initiated at the time of predicted seizure development gave no seizure relief, suggesting exercise-induced anti-epileptogenic rather than anti-convulsive effect.

    CONCLUSION: The clinical study and the experimental findings in mice indicate that physical activity may prevent or delay the development of epilepsy.

  • 2.
    Farahmand, B
    et al.
    Karolinska institutet.
    Hållmarker, Ulf
    Mora sjukhus.
    Brobert, G. P.
    Ahlbom, A.
    Acute mortality during long-distance ski races (Vasaloppet)2007In: Scandinavian Journal of Medicine and Science in Sports, ISSN 0905-7188, E-ISSN 1600-0838, Vol. 17, no 4, p. 356-361Article in journal (Refereed)
  • 3.
    Hansson, Oskar
    et al.
    Lund Univ, Dept Clin Sci Malmo, Clin Memory Res Unit, Malmo, Sweden;Skane Univ Hosp, Memory Clin, Malmo, Sweden.
    Svensson, Martina
    Lund Univ, Dept Expt Med Sci, Expt Neuroinflammat Lab, S-22184 Lund, Sweden.
    Gustaysson, Anna-Marta
    Lund Univ, Dept Clin Sci Malmo, Clin Memory Res Unit, Malmo, Sweden;Skane Univ Hosp, Memory Clin, Malmo, Sweden.
    Andersson, Emelie
    Lund Univ, Dept Clin Sci Malmo, Clin Memory Res Unit, Malmo, Sweden.
    Yang, Yiyi
    Lund Univ, Dept Expt Med Sci, Expt Neuroinflammat Lab, S-22184 Lund, Sweden.
    Nagga, Katarina
    Lund Univ, Dept Clin Sci Malmo, Clin Memory Res Unit, Malmo, Sweden;Linkoping Univ, Dept Acute Internal Med & Geriatr, Linkoping, Sweden.
    Hållmarker, Ulf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    James, Stefan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Deierborg, Tomas
    Lund Univ, Dept Expt Med Sci, Expt Neuroinflammat Lab, S-22184 Lund, Sweden.
    Midlife physical activity is associated with lower incidence of vascular dementia but not Alzheimer's disease2019In: Alzheimer's Research & Therapy, E-ISSN 1758-9193, Vol. 11, article id 87Article in journal (Refereed)
    Abstract [en]

    Background: Physical activity might reduce the risk of developing dementia. However, it is still unclear whether the protective effect differs depending on the subtype of dementia. We aimed to investigate if midlife physical activity affects the development of vascular dementia (VaD) and Alzheimer's disease (AD) differently in two large study populations with different designs.

    Methods: Using a prospective observational design, we studied whether long-distance skiers of the Swedish Vasaloppet (n = 197,685) exhibited reduced incidence of VaD or AD compared to matched individuals from the general population (n = 197,684) during 21 years of follow-up (median 10, interquartile range (IQR) 5-15 years). Next, we studied the association between self-reported physical activity, stated twice 5 years apart, and incident VaD and AD in 20,639 participants in the Swedish population-based Malmo Diet and Cancer Study during 18 years of follow-up (median 15, IQR 14-17 years). Finally, we used a mouse model of AD and studied brain levels of amyloid-beta, synaptic proteins, and cognitive function following 6 months of voluntary wheel running.

    Results Vasaloppet skiers (median age 36.0 years [IQR 29.0-46.0], 38% women) had lower incidence of all-cause dementia (adjusted hazard ratio (HR) 0.63, 95% CI 0.52-0.75) and VaD (adjusted HR 0.49, 95% CI 0.33-0.73), but not AD, compared to non-skiers. Further, faster skiers exhibited a reduced incidence of VaD (adjusted HR 0.38, 95% CI 0.16-0.95), but not AD or all-cause dementia compared to slower skiers. In the Malmo Diet and Cancer Study (median age 57.5 years [IQR 51.0-63.8], 60% women), higher physical activity was associated with reduced incidence of VaD (adjusted HR 0.65, 95% CI 0.49-0.87), but not AD nor all-cause dementia. These findings were also independent of APOE-epsilon 4 genotype. In AD mice, voluntary running did not improve memory, amyloid-beta, or synaptic proteins.

    Conclusions: Our results indicate that physical activity in midlife is associated with lower incidence of VaD. Using three different study designs, we found no significant association between physical activity and subsequent development of AD.

  • 4.
    Hållmarker, Ulf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Medicinkliniken Mora lasarett, Landstinget Dalarna.
    Epidemiological Studies on Long Distance Cross-Country Skiers: Participants in the Vasaloppet 1955-20102015Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    The overall aim of this thesis was to study the influence of physical activity on health. Risks and benefits of physical activity is of particular interest since there is a global trend of less physical activity among youths and adults.

    In order to investigate this aim we used a database from a large cross country ski race, Vasaloppet, with participants with a wide age range, and with both elite athletes and ordinary people who exercise and promote their health. The most serious risk of strenuous exercise is sudden death and it is challenging to identify preventive effects of major endemic diseases.

    Using epidemiological methodology we studied 200 000 Vasaloppet skiers and compared them with the general population. Based on personal identification numbers we added data from Swedish national personal and health registers, clinical registers as the cancer register, Swedeheart, or Swedish stroke register, and socioeconomic information from Statistics Sweden. In the Vasaloppet database we collected data on age, gender, finish time and number of races during the period 1989 to 2010.

    We evaluated risk of death during the race in two papers (I,II). During 90 years of annual races, cardiac arrest occurred in 20 skiers, of which five survived. The death rate is in average two per 100 000 skiers.

    We also studied the association with cancer incidence (paper III). The overall reduction of cancer was modest among skiers compared with the general population, but for cancers related to lifestyle the risks were markedly lower.

    We investigated the risk for recurrent myocardial infarction and found a 30% reduction among skiers (paper IV). In paper V we showed that skiers with a first stroke have a lower incidence of all-cause death. The skiers had a higher frequency of atrial fibrillation but had less severe stroke and no increased risk of recurrent stroke. Thus our data suggest that a lifestyle with a high level of physical activity may work as a protection after a cardiovascular event.

    Summary: The short excess mortality in endurance physical activity is by far outweighed by the long term protective effect of exercise in cardiovascular diseases and cancer.

     

    List of papers
    1. Acute mortality during long-distance ski races (Vasaloppet)
    Open this publication in new window or tab >>Acute mortality during long-distance ski races (Vasaloppet)
    2007 (English)In: Scandinavian Journal of Medicine and Science in Sports, ISSN 0905-7188, E-ISSN 1600-0838, Vol. 17, no 4, p. 356-361Article in journal (Refereed) Published
    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:uu:diva-261003 (URN)10.1111/j.1600-0838.2006.00582.x (DOI)
    Available from: 2015-08-27 Created: 2015-08-27 Last updated: 2017-12-04Bibliographically approved
    2. Cardiac Arrest in a Long-Distance Ski Race (Vasaloppet) in Sweden
    Open this publication in new window or tab >>Cardiac Arrest in a Long-Distance Ski Race (Vasaloppet) in Sweden
    2012 (English)In: Journal of the American College of Cardiology, ISSN 0735-1097, E-ISSN 1558-3597, Vol. 60, no 15, p. 1431-1432Article in journal, Letter (Refereed) Published
    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:uu:diva-184589 (URN)10.1016/j.jacc.2012.05.046 (DOI)000309508700022 ()22981556 (PubMedID)
    Available from: 2012-11-12 Created: 2012-11-09 Last updated: 2017-12-07
    3. Cancer incidence in participants in a long-distance ski race (Vasaloppet, Sweden) compared to the background population.
    Open this publication in new window or tab >>Cancer incidence in participants in a long-distance ski race (Vasaloppet, Sweden) compared to the background population.
    Show others...
    2015 (English)In: European Journal of Cancer, ISSN 0959-8049, E-ISSN 1879-0852, Vol. 51, no 4, p. 558-568Article in journal (Refereed) Published
    Abstract [en]

    BACKGROUND: We studied the association between taking part in a long distance ski race and cancer incidence to address the hypothesis that a lifestyle involving a high degree of physical activity (PA) lowers cancer incidence with a pattern that is different by cancer site.

    METHODS: Cancer incidence was estimated in a large cohort of skiers (n=185,412) participating in the Vasaloppet long distance ski race in Sweden 1989-2010 and non-participants in the ski race, randomly selected from the Swedish general population (n=184,617). Data include race finishing times as a measurement of physical fitness. Hazard ratios (HRs) and net probability of cancer over twenty years of follow-up were estimated for all invasive cancer, and separately for prostate, breast, colo-rectal and lung cancer, and groups of cancers with presumed relation to lifestyle.

    FINDINGS: Participating in Vasaloppet was associated with a relative risk reduction for all invasive cancer of 6% (95% confidence interval 2-9%) and a relative risk reduction of 32% (95% confidence interval 28-37%) of cancer sites where there is epidemiological evidence that smoking, bodyweight, regular PA and consumption of fruit and vegetables are aetiological factors. For skin cancer the risk was increased, as for prostate cancer. Skiers with shorter finishing times had lower incidence of cancer.

    INTERPRETATION: This study indicates that it is unrealistic to reduce overall population cancer incidence drastically with life style. However, cancers that are epidemiologically associated with life style factors were significantly reduced by what presumably is a blend of non-smoking, normal body weight, sound dietary habits and PA. Our data thus provide additional support for present days' recommendations about life style prevention. Higher health awareness is associated with attendance to screening, which may explain our results for prostate cancer.

    FUNDING: University fund, independent funds from an insurance company and a private foundation.

    National Category
    Cancer and Oncology
    Identifiers
    urn:nbn:se:uu:diva-245060 (URN)10.1016/j.ejca.2014.12.009 (DOI)000350915600014 ()25670239 (PubMedID)
    Available from: 2015-02-24 Created: 2015-02-24 Last updated: 2017-12-04Bibliographically approved
    4. Risk of recurrent ischaemic events after myocardial infarction in long-distance ski race participants
    Open this publication in new window or tab >>Risk of recurrent ischaemic events after myocardial infarction in long-distance ski race participants
    Show others...
    2016 (English)In: European Journal of Preventive Cardiology, ISSN 2047-4873, E-ISSN 2047-4881, Vol. 23, no 3, p. 282-290Article in journal (Refereed) Published
    Abstract [en]

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

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

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

    Keywords
    Myocardial infarction Cross-country skiing Vasaloppet Physical activity Sports Medicine
    National Category
    Public Health, Global Health, Social Medicine and Epidemiology Cardiac and Cardiovascular Systems
    Research subject
    Epidemiology
    Identifiers
    urn:nbn:se:uu:diva-260137 (URN)10.1177/2047487315578664 (DOI)000369526800007 ()25827685 (PubMedID)
    Available from: 2015-08-17 Created: 2015-08-17 Last updated: 2017-12-04Bibliographically approved
    5. Risk of Recurrent Stroke and Death After First Stroke in Long‐Distance Ski Race Participants
    Open this publication in new window or tab >>Risk of Recurrent Stroke and Death After First Stroke in Long‐Distance Ski Race Participants
    Show others...
    2015 (English)In: Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease, ISSN 2047-9980, E-ISSN 2047-9980, Vol. 4, no 10, article id e002469Article in journal (Refereed) Published
    Abstract [en]

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

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

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

    Keywords
    atrial fibrillation; cerebrovascular disease; cross-country skiing; epidemiology; lifestyle; physical activity; prevention; recurrent stroke; sports medicine; Sweden; Vasaloppet
    National Category
    Public Health, Global Health, Social Medicine and Epidemiology
    Research subject
    Epidemiology
    Identifiers
    urn:nbn:se:uu:diva-260198 (URN)10.1161/JAHA.115.002469 (DOI)000364153000039 ()
    Available from: 2015-08-17 Created: 2015-08-17 Last updated: 2019-03-11Bibliographically approved
  • 5.
    Hållmarker, Ulf
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Mora Hosp, Dept Internal Med, S-79285 Mora, Sweden.
    Lindbäck, Johan
    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.
    Ärnlöv, Johan
    Dalarna Univ, Sch Hlth & Social Studies, S-79188 Falun, Sweden;Karolinska Inst, Dept Neurobiol Care Sci & Soc, Div Family Med & Primary Care, S-17177 Stockholm, Sweden.
    Åsberg, Signild
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Wester, Per
    Umea Univ, Dept Publ Hlth & Clin Sci, S-90185 Umea, Sweden;Danderyd Hosp, Karolinska Inst, Dept Clin Sci, S-18288 Stockholm, Sweden.
    Hellberg, Dan
    Ctr Clin Res, S-79182 Falun, Sweden.
    Lagerqvist, Bo
    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.
    James, Stefan K
    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.
    Survival and incidence of cardiovascular diseases in participants in a long-distance ski race (Vasaloppet, Sweden) compared to the background population2018In: European Heart Journal - Quality of Care and Clinical Outcomes, ISSN 2058-5225, E-ISSN 2058-1742, Vol. 4, no 2, p. 91-97Article in journal (Refereed)
    Abstract [en]

    We studied the relationship between taking part in a long-distance ski race and incidence of cardiovascular diseases (CVDs) to address the hypothesis that lifestyle lowers the incidence. A cohort of 399 630 subjects in Sweden, half were skiers in the world's largest ski race, and half were non-skiers. Non-skiers were frequency matched for sex, age, and year of race. Individuals with severe diseases were excluded. The endpoints were death, myocardial infarction, or stroke. The subjects were followed up for a maximum of 21.8 years and median of 9.8 years. We identified 9399 death, myocardial infarction, or stroke events among non-skiers and 4784 among the Vasaloppet skiers. The adjusted hazard ratios (HRs) comparing skiers and non-skiers were 0.52 [95% confidence interval (CI) 0.49-0.54] for all-cause mortality, 0.56 (95% CI 0.52-0.60) for myocardial infarction and 0.63 (95% CI 0.58-0.67) for stroke and for all three outcomes 0.56 (95% CI 0.54-0.58). The results were consistent across subgroups: age, sex, family status, education, and race year. For skiers, a doubling of race time was associated with a higher age-adjusted risk of 19%, and male skiers had a doubled risk than female skiers, with a HR 2.06 (95% CI 1.89-2.41). The outcome analyses revealed no differences in risk of atrial fibrillation between skiers and non-skiers. This large cohort study provides additional support for the hypothesis that individuals with high level of physical activity representing a healthy lifestyle, as evident by their participation in a long-distance ski race, have a lower risk of CVD or death.

  • 6.
    Hållmarker, Ulf
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Michaelsson, Karl
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Arnlov, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    James, Stefan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Cardiac Arrest in a Long-Distance Ski Race (Vasaloppet) in Sweden2012In: Journal of the American College of Cardiology, ISSN 0735-1097, E-ISSN 1558-3597, Vol. 60, no 15, p. 1431-1432Article in journal (Refereed)
  • 7.
    Hållmarker, Ulf
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Medicinkliniken Mora Landstinget Dalarna.
    Michaëlsson, Karl
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Ärnlöv, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology. Högskolan Dalarna, Falun.
    Hellberg, Dan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology. Centrum för klinisk forskning, Dalarna, Falun.
    Lagerqvist, Bo
    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.
    Lindbäck, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    James, Stefan K.
    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.
    Risk of recurrent ischaemic events after myocardial infarction in long-distance ski race participants2016In: European Journal of Preventive Cardiology, ISSN 2047-4873, E-ISSN 2047-4881, Vol. 23, no 3, p. 282-290Article in journal (Refereed)
    Abstract [en]

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

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

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

  • 8.
    Hållmarker, Ulf
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Michaëlsson, Karl
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Ärnlöv, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    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.
    Reply to" Airway Remodeling and Cardiac Arrest in Long-Distance Ski Races" Journal of the American College of Cardiology, Volume 61, Issue 3, 22 January 2013, Pages 388-3892013In: Journal of the American College of Cardiology, ISSN 0735-1097, E-ISSN 1558-3597, Vol. 61, no 3, p. 389-Article in journal (Other academic)
  • 9.
    Hållmarker, Ulf
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Åsberg, Signild
    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.
    Ärnlöv, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology. Högskolan Dalarna Falun.
    Hellberg, Dan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology. Centrum klinisk forskning Dalarna Falun.
    Lindbäck, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Wester, Per
    Medicin och folhälsa Umeå Universitet.
    James, Stefan K.
    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.
    Risk of Recurrent Stroke and Death After First Stroke in Long‐Distance Ski Race Participants2015In: Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease, ISSN 2047-9980, E-ISSN 2047-9980, Vol. 4, no 10, article id e002469Article in journal (Refereed)
    Abstract [en]

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

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

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

  • 10. Olsson, Tomas T
    et al.
    Svensson, Martina
    Hållmarker, Ulf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Department of Internal Medicine, Mora hospital, Mora, Sweden.
    James, Stefan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Deierborg, Tomas
    Delayed Clinical Manifestation of Parkinson's Disease Among Physically Active: Do Participants in a Long-Distance Ski Race Have a Motor Reserve?2020In: Journal of Parkinson's Disease, ISSN 1877-7171, E-ISSN 1877-718X, Vol. 10, no 1, p. 267-274Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Physical activity is associated with reduced risk of Parkinson's disease (PD). The explanations for this association are not completely elucidated. We use long-term PD-incidence data from long-distance skiers to study the relationship between exercise and PD.

    OBJECTIVE: We aimed to investigate if physical activity is associated with long-term lower risk of PD and if this association could be explained by physically active people being able to sustain more PD neuropathology before clinical symptoms, a motor reserve.

    METHODS: Using a prospective observational design, we studied whether long-distance skiers of the Swedish Vasaloppet (n = 197,685), exhibited reduced incidence of PD compared to matched individuals from the general population (n = 197,684) during 21 years of follow-up (median 10, interquartile range (IQR) 5-15 years).

    RESULTS: Vasaloppet skiers (median age 36.0 years [IQR 29.0-46.0], 38% women) had lower incidence of PD (HR: 0.71; 95 % CI 0.56-0.90) compared to non-skiers. When reducing risk for reverse causation by excluding PD cases within the first five years from race participation, there was still a trend for lower risk of PD (HR: 0.80; 95 % CI 0.62-1.03). Further, the PD prevalence converged between skiers and non-skiers after 15 years of follow-up, which is more consistent with a motor reserve in the physically active rather than neuroprotection.

    CONCLUSIONS: A physical active lifestyle is associated with reduced risk for PD. This association weakens with time and might be explained by a motor reserve among the physically active.

  • 11.
    Stattin, Karl
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Hållmarker, Ulf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Mora Lasarett, Dept Internal Med, Mora, Sweden.
    Ärnlöv, Johan
    Karolinska Inst, Div Family Med & Primary Care, Dept Neurobiol Care Sci & Soc, Stockholm, Sweden;Dalarna Univ, Sch Hlth & Social Studies, Falun, Dalarna, 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.
    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.
    Decreased Hip, Lower Leg, and Humeral Fractures but Increased Forearm Fractures in Highly Active Individuals2018In: Journal of Bone and Mineral Research, ISSN 0884-0431, E-ISSN 1523-4681, Vol. 33, no 10, p. 1842-1850Article in journal (Refereed)
    Abstract [en]

    It is not known how physical exercise affects the risk of different types of fractures, especially in highly active individuals. To investigate this association, we studied a cohort of 118,204 men and 71,757 women who from 1991 to 2009 participated in Vasaloppet, a long-distance cross-country skiing race in Sweden, and 505,194 nonparticipants frequency-matched on sex, age, and county of residence from the Swedish population. Participants ranged from recreational exercisers to world-class skiers. Race participation, distance of race run, number of races participated in, and finishing time were used as proxies for physical exercise. Incident fractures from 1991 to 2010 were obtained from national Swedish registers. Over a median follow-up of 8.9 years, 53,175 fractures of any type, 2929 hip, 3107 proximal humerus, 11,875 lower leg, 11,733 forearm, and 2391 vertebral fractures occurred. In a Cox proportional hazard regression analysis using time-updated exposure and covariate information, participation in the race was associated with an increased risk of any type of fracture (hazard ratio [HR], 1.02; 95% CI, 1.00 to 1.05); forearm fractures had an HR, 1.11 with a 95% CI, 1.06 to 1.15. There was a lower risk of hip (HR, 0.75; 95% CI, 0.67 to 0.83), proximal humerus (HR, 0.90; 95% CI, 0.82 to 0.98), and lower leg fractures (HR, 0.93; 95% CI, 0.89 to 0.97), whereas the HR of vertebral fracture was 0.97 with a 95% CI, 0.88 to 1.07. Among participants, the risk of fracture was similar irrespective of race distance and number of races run. Participants close to the median finishing time had a lower risk of fracture compared with faster and slower participants. In summary, high levels of physical exercise were associated with a slightly higher risk of fractures of any type, including forearm fractures, but a lower risk of hip, proximal humerus, and lower leg fractures. © 2018 American Society for Bone and Mineral Research.

  • 12.
    Stattin, Karl
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Höijer, Jonas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    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.
    Larsson, Susanna C.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Wolk, Alicja
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics. Unit of Cardiovascular and Nutritional Epidemiology, Institute for Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.
    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.
    The risk of different fracture types across a wide range of physical activity levels, from sedentary individuals to elite athletesManuscript (preprint) (Other academic)
    Abstract [en]

    Abstract

    Background Physical activity has been associated with a lower risk of fragility fractures, but the shape of the association is not known.

    Methods Individuals aged 49-68 years were drawn from the population-based Swedish Mammography Cohort (n=22,256) and Cohort of Swedish Men (n=28,749) as well as from a cohort of highly physically active participants in the Vasaloppet skiing race (n=12,984). A common measure of physical activity was created from lifestyle questionnaires and race data using generalized structural equation modeling. The median physical activity corresponded to 2-3 hours of weekly exercise or 20-40 minutes of daily walking/bicycling.  The rate of any, wrist, proximal humerus, spine and hip fractures were estimated using restricted cubic splines in Cox proportional hazard models.

    Results During a maximal follow-up of 13 years, 8,506 fractures at any site, 2,164 wrist, 779 proximal humerus, 346 spine and 908 hip fractures occurred. The rate of any fracture was lowest close to the median physical activity and higher in both low and high levels of physical activity, hazard ratio (HR) 1.05 (95% confidence interval (CI) 1.01-1.08) and 1.11 (95% CI 1.05-1.17) for physical activity 1 SD below and 1.5 SD above the average, respectively. The rate of wrist fracture was lowest among individuals with low levels of physical activity, HR 0.92 (95% CI 0.86-0.99) for physical activity 1 SD below the average, and increased until the median level of physical activity. Proximal humerus fracture was not associated with physical activity. Spine fracture had a U-shaped association with physical activity with wide confidence intervals. Low physical activity was associated with higher rate of hip fracture, HR 1.24 (95% CI 1.12-1.36) for physical activity 1 SD below the average.

    Discussion In this combination of cohorts including individuals with a wide range of physical activity, from sedentary individuals to elite athletes, the associations between physical activity and fractures were non-linear and differed according to fracture site. For wrist and hip fractures, there appears to be a threshold value above which further physical activity is not associated with further changes in the rate of fracture.

  • 13.
    Svedberg, Niclas
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Falun Cent Hosp, Dept Cardiol, S-79182 Falun, Sweden.
    Sundström, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Epidemiology.
    James, Stefan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Hållmarker, Ulf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Mora Hosp, Dept Med, Mora, Sweden.
    Hambraeus, Kristina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Falun Cent Hosp, Dept Cardiol, S-79182 Falun, Sweden.
    Andersen, Kasper
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Epidemiology.
    Long-Term Incidence of Atrial Fibrillation and Stroke Among Cross-Country Skiers Cohort Study of Endurance-Trained Male and Female Athletes2019In: Circulation, ISSN 0009-7322, E-ISSN 1524-4539, Vol. 140, no 11, p. 910-920Article in journal (Refereed)
    Abstract [en]

    Background: Studies have revealed a higher incidence of atrial fibrillation among well-trained athletes. We aim to investigate associations of endurance training with incidence of atrial fibrillation and stroke and to establish potential sex differences of such associations in a cohort of endurance trained athletes. Methods: All Swedish skiers (208 654) completing 1 or more races in the 30 to 90 km cross-country skiing event Vasaloppet (1989-2011) and a matched sample (n=527 448) of nonskiers were followed until first event of atrial fibrillation or stroke. Cox regression was used to investigate associations of number of completed races and finishing time with incidence of atrial fibrillation and stroke. Results: Female skiers in Vasaloppet had a lower incidence of atrial fibrillation than did female nonskiers (hazard ratio [HR], 0.55; 95% CI, 0.48-0.64), independent of finishing time and number of races. Male skiers had a similar incidence to that of nonskiers (HR, 0.98; 95% CI, 0.93-1.03). Skiers with the highest number of races or fastest finishing times had the highest incidence. Skiers of either sex had a lower incidence of stroke than did nonskiers (HR, 0.64; 95% CI, 0.60-0.67), independent of the number of races and finishing time. Skiers with atrial fibrillation had higher incidence of stroke than did skiers and nonskiers without atrial fibrillation (men: HR, 2.28; 95% CI, 1.93-2.70; women: HR, 3.51; 95% CI, 2.17-5.68; skiers with atrial fibrillation vs. skiers without atrial fibrillation). After diagnosis of atrial fibrillation, skiers with atrial fibrillation had a lower incidence of stroke (HR, 0.73; 95% CI, 0.50-0.91) and lower mortality compared with nonskiers with atrial fibrillation (HR, 0.57; 95% CI, 0.49-0.65). Conclusions: Female skiers in Vasaloppet had lower incidence of atrial fibrillation and stroke. Male skiers had similar incidence of atrial fibrillation and lower risk of stroke. Men with higher number of races and faster finishing times had the highest incidence of atrial fibrillation. After diagnosis of atrial fibrillation, skiers had lower incidence of stroke and death than did nonskiers with atrial fibrillation. This indicates that although on an individual level atrial fibrillation in well-trained individuals is associated with higher incidence of stroke, on population level, risk of stroke is low and that exercise should not be avoided.

  • 14.
    Svensson, Martina
    et al.
    Lund Univ, Dept Expt Med Sci, Expt Neuroinfiammat Lab, BMC B11, S-22184 Lund, Sweden.
    Brundin, Lena
    Van Andel Res Inst, Ctr Neurodegenerat Sci, Grand Rapids, MI USA.
    Erhardt, Sophie
    Karolinska Inst, Dept Physiol & Pharmacol, Stockholm, Sweden.
    Madaj, Zachary
    Van Andel Res Inst, Ctr Neurodegenerat Sci, Grand Rapids, MI USA.
    Hållmarker, Ulf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Mora Hosp, Dept Internal Med, Mora, Sweden.
    James, Stefan
    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.
    Deierborg, Tomas
    Lund Univ, Dept Expt Med Sci, Expt Neuroinfiammat Lab, BMC B11, S-22184 Lund, Sweden.
    Long distance ski racing is associated with lower long-term incidence of depression in a population based, large-scale study2019In: Psychiatry Research, ISSN 0165-1781, E-ISSN 1872-7123, Vol. 281, article id 112546Article in journal (Refereed)
    Abstract [en]

    Physical activity has been proposed to be beneficial for prevention of depression, although the importance of exercise intensity, sex-specific mechanisms, and duration of the effects need to be clarified. Using an observational study design, following 395,369 individuals up to 21 years we studied whether participation in an ultralong-distance cross-country ski race was associated with lower risk of developing depression. Skiers (participants in the race) and matched non-skiers from the general population (non-participants in the race) were studied after participation (same year for non-participation) in the race using the Swedish population and patient registries. The risk of depression in skiers (n = 197,685, median age 36 years, 38% women) was significantly lower, to nearly half of that in non-skiers (adjusted hazard ratio, HR 0.53) over the follow-up period. Further, a higher fitness level (measured as the finishing time to complete the race, a proxy for higher exercise dose) was associated with lower incidence of depression in men (adjusted HR 0.65), but not in women. Our results support the recommendations of engaging in physical activity as a preventive strategy decreasing the risk for depression in both men and women. Furthermore, the exercise could reduce risk for depression in a dose-dependent matter, in particular in males.

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