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  • 1. Abarca-Gómez, L.
    et al.
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Lytsy, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Social Medicine.
    Sundström, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Yngve, Agneta
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Food, Nutrition and Dietetics.
    Ezzati, M
    Worldwide trends in body-mass index, underweight, overweight, and obesity from 1975 to 2016: a pooled analysis of 2416 population-based measurement studies in 128·9 million children, adolescents, and adults.2017In: The Lancet, ISSN 0140-6736, E-ISSN 1474-547X, Vol. 390, no 10113, p. 2627-2642Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Underweight, overweight, and obesity in childhood and adolescence are associated with adverse health consequences throughout the life-course. Our aim was to estimate worldwide trends in mean body-mass index (BMI) and a comprehensive set of BMI categories that cover underweight to obesity in children and adolescents, and to compare trends with those of adults.

    METHODS: We pooled 2416 population-based studies with measurements of height and weight on 128·9 million participants aged 5 years and older, including 31·5 million aged 5-19 years. We used a Bayesian hierarchical model to estimate trends from 1975 to 2016 in 200 countries for mean BMI and for prevalence of BMI in the following categories for children and adolescents aged 5-19 years: more than 2 SD below the median of the WHO growth reference for children and adolescents (referred to as moderate and severe underweight hereafter), 2 SD to more than 1 SD below the median (mild underweight), 1 SD below the median to 1 SD above the median (healthy weight), more than 1 SD to 2 SD above the median (overweight but not obese), and more than 2 SD above the median (obesity).

    FINDINGS: Regional change in age-standardised mean BMI in girls from 1975 to 2016 ranged from virtually no change (-0·01 kg/m(2) per decade; 95% credible interval -0·42 to 0·39, posterior probability [PP] of the observed decrease being a true decrease=0·5098) in eastern Europe to an increase of 1·00 kg/m(2) per decade (0·69-1·35, PP>0·9999) in central Latin America and an increase of 0·95 kg/m(2) per decade (0·64-1·25, PP>0·9999) in Polynesia and Micronesia. The range for boys was from a non-significant increase of 0·09 kg/m(2) per decade (-0·33 to 0·49, PP=0·6926) in eastern Europe to an increase of 0·77 kg/m(2) per decade (0·50-1·06, PP>0·9999) in Polynesia and Micronesia. Trends in mean BMI have recently flattened in northwestern Europe and the high-income English-speaking and Asia-Pacific regions for both sexes, southwestern Europe for boys, and central and Andean Latin America for girls. By contrast, the rise in BMI has accelerated in east and south Asia for both sexes, and southeast Asia for boys. Global age-standardised prevalence of obesity increased from 0·7% (0·4-1·2) in 1975 to 5·6% (4·8-6·5) in 2016 in girls, and from 0·9% (0·5-1·3) in 1975 to 7·8% (6·7-9·1) in 2016 in boys; the prevalence of moderate and severe underweight decreased from 9·2% (6·0-12·9) in 1975 to 8·4% (6·8-10·1) in 2016 in girls and from 14·8% (10·4-19·5) in 1975 to 12·4% (10·3-14·5) in 2016 in boys. Prevalence of moderate and severe underweight was highest in India, at 22·7% (16·7-29·6) among girls and 30·7% (23·5-38·0) among boys. Prevalence of obesity was more than 30% in girls in Nauru, the Cook Islands, and Palau; and boys in the Cook Islands, Nauru, Palau, Niue, and American Samoa in 2016. Prevalence of obesity was about 20% or more in several countries in Polynesia and Micronesia, the Middle East and north Africa, the Caribbean, and the USA. In 2016, 75 (44-117) million girls and 117 (70-178) million boys worldwide were moderately or severely underweight. In the same year, 50 (24-89) million girls and 74 (39-125) million boys worldwide were obese.

    INTERPRETATION: The rising trends in children's and adolescents' BMI have plateaued in many high-income countries, albeit at high levels, but have accelerated in parts of Asia, with trends no longer correlated with those of adults.

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  • 2.
    Ahmad, Shafqat
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Hammar, Ulf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Kennedy, Beatrice
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Salihovic, Samira
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology. Uppsala University, Science for Life Laboratory, SciLifeLab. School of Medical Sciences, Örebro University, Örebro, Sweden.
    Ganna, Andrea
    Program in Medical and Population Genetics, Broad Institute of MIT and Harvard; Department of Medical Epidemiology and Biostatistics, Karolinska Institutet.
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Epidemiology.
    Sundström, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Epidemiology. The George Institute for Global Health, Sydney, Australia.
    Ärnlöv, Johan
    Division of and Primary Care, Department of Neurobiology, Care Sciences, and Society, Karolinska Institutet; School of Health and Social Studies, Dalarna University.
    Berne, Christian
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Risérus, Ulf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism.
    Magnusson, Patrik KE
    Department of Medical Epidemiology and Biostatistics, Karolinska Institutet.
    Larsson, Susanna C.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Medical epidemiology. Unit of Cardiovascular and Nutritional Epidemiology, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden..
    Fall, Tove
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology.
    Effect of General Adiposity and Central Body Fat Distribution on the Circulating Metabolome: A Multi-Cohort Nontargeted Metabolomics Observational and Mendelian Randomization Study2022In: Diabetes, ISSN 0012-1797, E-ISSN 1939-327X, Vol. 71, no 2, p. 329-339Article in journal (Refereed)
    Abstract [en]

    Obesity is associated with adverse health outcomes, but the metabolic effects have not yet been fully elucidated. We aimed to investigate the association between adiposity with circulating metabolites and to address causality with Mendelian randomization (MR). Metabolomics data was generated by non-targeted ultra-performance liquid-chromatography coupled to time-of-flight mass-spectrometry in plasma and serum from three population-based Swedish cohorts: ULSAM (N=1,135), PIVUS (N=970), and TwinGene (N=2,059). We assessed associations between general adiposity measured as body mass index (BMI) and central body fat distribution measured as waist-to-hip ratio adjusted for BMI (WHRadjBMI) with 210 annotated metabolites. We employed MR analysis to assess causal effects. Lastly, we attempted to replicate the MR findings in the KORA and TwinsUK cohorts (N=7,373), the CHARGE consortium (N=8,631), the Framingham Heart Study (N=2,076) and the DIRECT consortium (N=3,029). BMI was associated with 77 metabolites, while WHRadjBMI was associated with 11 and 3 metabolites in women and men, respectively. The MR analyses in the Swedish cohorts suggested a causal association (p-value <0.05) of increased general adiposity and reduced levels of arachidonic acid, dodecanedioic acid and lysophosphatidylcholine (P-16:0) as well as with increased creatine levels. The replication effort provided support for a causal association of adiposity on reduced levels of arachidonic acid (p-value 0.03). Adiposity is associated with variation of large parts of the circulating metabolome, however causality needs further investigation in well-powered cohorts.

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  • 3.
    Alassaad, Anna
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical pharmacogenomics and osteoporosis.
    Bertilsson, Maria
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Gillespie, Ulrika
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.
    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.
    Hammarlund-Udenaes, Margareta
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.
    Melhus, Håkan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical pharmacogenomics and osteoporosis.
    The effects of pharmacist intervention on emergency department visits in patients 80 years and older: subgroup analyses by number of prescribed drugs and appropriate prescribing2014In: PLOS ONE, E-ISSN 1932-6203, Vol. 9, no 11, p. e111797-Article in journal (Refereed)
    Abstract [en]

    Background: Clinical pharmacist interventions have been shown to have positive effect on occurrence of drug-related issues as well as on clinical outcomes. However, evidence about which patients benefiting most from the interventions is limited. We aimed to explore whether pharmacist intervention is equally effective in preventing emergency department (ED) visits in patients with few or many prescribed drugs and in those with different levels of inappropriate prescribing. Methods: Patient and outcome data from a randomized controlled trial exploring the clinical effects of a ward-based pharmacist intervention in patients, 80 years and older, were used. The patients were divided into subgroups according to the number of prescribed drugs (< 5 or >= 5 drugs) and the level of inappropriate prescribing [using the Screening Tool Of Older People's potentially inappropriate Prescriptions (STOPP) and the Screening Tool to Alert doctors to Right Treatment (START) with a score of >= 2 (STOPP) and >= 1 (START) as cutoff points]. The effect of the intervention on the number of times the different subgroups visited the ED was analyzed. Results: The pharmacist intervention was more effective with respect to the number of subsequent ED visits in patients taking < 5 drugs on admission than in those taking >= 5 drugs. The rate ratio (RR) for a subsequent ED visit was 0.22 [95% confidence interval (CI) 0.09-0.52] for,5 drugs and 0.70 (95% CI 0.47-1.04) for >= 5 drugs (p = 0.02 for the interaction). The effect of intervention did not differ between patients with high or low STOPP or START scores. Conclusion: In this exploratory study, the pharmacist intervention appeared to be more effective in preventing visits to the ED for patients who were taking fewer drugs before the intervention. Our analysis of STOPP and START scores indicated that the level of inappropriate prescribing on admission had no effect on the outcomes of intervention with respect to ED visits.

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  • 4.
    Alassaad, Anna
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical pharmacogenomics and osteoporosis.
    Melhus, Håkan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical pharmacogenomics and osteoporosis.
    Hammarlund-Udenaes, Margareta
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.
    Bertilsson, Maria
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Gillespie, Ulrika
    Uppsala University Hospital, Uppsala, Sweden.
    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.
    A tool for prediction of risk of rehospitalisation and mortality in the hospitalised elderly: secondary analysis of clinical trial data2015In: BMJ Open, E-ISSN 2044-6055, Vol. 5, no 2, article id e007259Article in journal (Refereed)
    Abstract [en]

    Objectives: To construct and internally validate a risk score, the '80+ score', for revisits to hospital and mortality for older patients, incorporating aspects of pharmacotherapy. Our secondary aim was to compare the discriminatory ability of the score with that of three validated tools for measuring inappropriate prescribing: Screening Tool of Older Person's Prescriptions (STOPP), Screening Tool to Alert doctors to Right Treatment (START) and Medication Appropriateness Index (MAI). Setting: Two acute internal medicine wards at Uppsala University hospital. Patient data were used from a randomised controlled trial investigating the effects of a comprehensive clinical pharmacist intervention. Participants: Data from 368 patients, aged 80 years and older, admitted to one of the study wards. Primary outcome measure: Time to rehospitalisation or death during the year after discharge from hospital. Candidate variables were selected among a large number of clinical and drug-specific variables. After a selection process, a score for risk estimation was constructed. The 80+ score was internally validated, and the discriminatory ability of the score and of STOPP, START and MAI was assessed using C-statistics. Results: Seven variables were selected. Impaired renal function, pulmonary disease, malignant disease, living in a nursing home, being prescribed an opioid or being prescribed a drug for peptic ulcer or gastroesophageal reflux disease were associated with an increased risk, while being prescribed an antidepressant drug (tricyclic antidepressants not included) was linked to a lower risk of the outcome. These variables made up the components of the 80+ score. The C-statistics were 0.71 (80+), 0.57 (STOPP), 0.54 (START) and 0.63 (MAI). Conclusions: We developed and internally validated a score for prediction of risk of rehospitalisation and mortality in hospitalised older people. The score discriminated risk better than available tools for inappropriate prescribing. Pending external validation, this score can aid in clinical identification of high-risk patients and targeting of interventions.

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  • 5. Andell, P.
    et al.
    Erlinge, D.
    Smith, J. G.
    James, Stefan
    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, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Lindahl, Bertil
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Koul, S.
    The effect of beta-blockers on mortality in COPD patients after myocardial infarction: A Swedish nation-wide observational study2014In: European Heart Journal, ISSN 0195-668X, E-ISSN 1522-9645, Vol. 35, p. 686-687Article in journal (Refereed)
  • 6. Andell, Pontus
    et al.
    Erlinge, David
    Smith, J. Gustav
    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.
    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.
    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.
    Koul, Sasha
    beta-Blocker Use and Mortality in COPD Patients After Myocardial Infarction: A Swedish Nationwide Observational Study2015In: Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease, ISSN 2047-9980, E-ISSN 2047-9980, Vol. 4, no 4, article id e001611Article in journal (Refereed)
    Abstract [en]

    Background-Patients with myocardial infarction (MI) and concomitant chronic obstructive pulmonary disease (COPD) constitute a high-risk group with increased mortality. beta-Blocker therapy has been shown to reduce mortality, prevent arrhythmias, and delay heart failure development after an MI in broad populations. However, the effect of beta-blockers in COPD patients is less well established and they may also be less treated due to fear of adverse reactions. We investigated beta-blocker prescription at discharge in patients with COPD after MI. ethods and Results-Patients hospitalized for MI between 2005 and 2010 were identified from the nationwide Swedish SWEDEHEART registry. Patients with COPD who were alive and discharged after an MI were selected as the study population. In this cohort, patients who were discharged with beta-blockers were compared to patients not discharged with beta-blockers. The primary end point was all-cause mortality. A total of 4858 patients were included, of which 4086 (84.1%) were discharged with a beta-blocker while 772 (15.9%) were not. After adjusting for potential confounders including baseline characteristics, comorbidities, and in-hospital characteristics, patients discharged with a beta-blocker had lower all-cause mortality (hazard ratio 0.87, 95% CI 0.78 to 0.98) during the total follow-up time (maximum 7.2 years). In the subgroup of patients with a history of heart failure, the corresponding hazard ratio was 0.77 (95% CI 0.63 to 0.95). Conclusions-Patients with COPD discharged with beta-blockers after an MI had a lower all-cause mortality compared to patients not prescribed beta-blockers. The results indicate that MI patients with COPD may benefit from beta-blockers.

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  • 7. Andell, Pontus
    et al.
    Koul, Sasha
    Martinsson, Andreas
    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.
    Jernberg, Tomas
    Smith, J Gustav
    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.
    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.
    Erlinge, David
    Impact of chronic obstructive pulmonary disease on morbidity and mortality after myocardial infarction2014In: Open heart, E-ISSN 2053-3624, Vol. 1, no 1, p. e000002-Article in journal (Refereed)
    Abstract [en]

    AIM:

    To gain a better understanding of the impact of chronic obstructive pulmonary disease (COPD) on long-term mortality in patients with myocardial infarction (MI) and identify areas where the clinical care for these patients may be improved.

    METHODS:

    Patients hospitalised for MI between 2005 and 2010 were identified from the nationwide Swedish SWEDEHEART registry. Patients with MI and a prior COPD hospital discharge diagnosis were compared to patients with MI without a prior COPD hospital discharge diagnosis for the primary endpoint of all-cause mortality at 1 year after MI. Secondary endpoints included rates of reinfarction, new-onset stroke, new-onset bleeding and new-onset heart failure at 1 year.

    RESULTS:

    A total of 81 191 MI patients were included, of which 4867 (6%) had a COPD hospital discharge diagnosis at baseline. Patients with COPD showed a significantly higher unadjusted 1-year mortality (24.6 vs 13.8%) as well as a higher rate of reinfarction, new-onset bleeding and new-onset heart failure post-MI. After adjustment for potential confounders, including comorbidities and treatment, the patients with COPD still showed a significantly higher 1-year mortality (HR 1.14, 95% CI 1.07 to 1.21) as well as a higher rate of new-onset heart failure (HR 1.35, 95% CI 1.24 to 1.47), whereas no significant association between COPD and myocardial reinfarction or new-onset bleeding remained.

    CONCLUSIONS:

    In this nationwide contemporary study, patients with COPD frequently had an atypical presentation, less often underwent revascularisation and less often received guideline-recommended secondary preventive medications of established benefit. Prior COPD was associated with a higher 1-year mortality and a higher risk of subsequent new-onset heart failure after MI. The association seems to be mainly explained by differences in background characteristics, comorbidities and treatment, although a minor part might be explained by COPD in itself. Improved in-hospital MI treatment and post-MI secondary prevention according to the guidelines may lower the mortality in this high-risk population.

  • 8.
    Andersen, Kasper
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Daniela, Mariosa
    Adami, Hans-Olov
    Held, Claes
    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.
    Ingelsson, Erik
    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, Molecular epidemiology.
    Lagerros, Ylva Trolle
    Nyren, Olof
    Ye, Weimin
    Bellocco, Rino
    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.
    Dose–Response Relationship of Total and Leisure Time Physical Activity to Risk of Heart Failure: a prospective cohort study2014In: Circulation Heart Failure, ISSN 1941-3289, E-ISSN 1941-3297, Vol. 7, no 5, p. 16p. 701-708Article in journal (Refereed)
    Abstract [en]

    Background—The nature of the association between levels of physical activity and risk of heart failure is little known. We investigated nonlinear associations of total and leisure time physical activity with risk of heart failure.

    Methods and Results—In 1997, 39 805 persons without heart failure completed a questionnaire of lifestyle factors and medical history. We used Cox regression models to investigate total (adjusting for education and previous myocardial infarction) and direct (multivariable-adjusted) effects of self-reported total and leisure time physical activity on risk of heart failure of any cause and heart failure of nonischemic origin. Heart failure diagnoses were obtained until December 31, 2010. Higher leisure time physical activity was associated with lower risk of heart failure of any cause; hazard ratio of the total effect of leisure time physical activity was for fifth versus first quintile 0.54; 95% confidence interval was 0.44 to 0.66. The direct effect was similar. High total daily physical activity level was associated with lower risk of heart failure, although the effect was less pronounced than for leisure time physical activity (total effect hazard ratio, 0.81; 95% confidence interval, 0.69–0.95; fifth versus first quintile). A similar direct effect observed.

    Conclusions—Leisure time physical activity was inversely related to risk of developing heart failure in a dose–response fashion. This was reflected in a similar but less pronounced association of total physical activity with risk of heart failure. Only part of the effects appeared to be mediated by traditional risk factors.

  • 9.
    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.

  • 10.
    Andersen, Kasper
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Held, Claes
    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.
    Neovius, Martin
    Tynelius, Per
    Rasmussen, Finn
    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.
    Exercise capacity and muscle strength and risk of vascular disease and arrhythmias: A cohort study of 1.26 million young menManuscript (preprint) (Other academic)
    Abstract [en]

    Background:

    While physical activity and exercise protects against cardiovascular disease, athletes have higher risk of atrial fibrillation and other arrhythmias. Graded independent and joint influences of exercise capacity and muscle strength on these diseases are unknown.

    Methods:

    All 1.26 million Swedish men who participated in mandatory military conscription between 1972 and 1995 (at a median age of 18.2 years) contributed. Multivariable-adjusted Cox proportional hazards models were used to evaluate the associations of maximal exercise capacity and muscle strength at conscription to subsequent risk of vascular disease and arrhythmias, as identified in national registries.

    Results:

    During a median follow-up of 26.3 years, about 26,000 hospitalizations for vascular disease events and 17,000 for arrhythmias occurred. Exercise capacity was inversely associated with risk of vascular disease (hazard ratio [HR] 0.64; 95% confidence interval [CI] 0.61-0.67]; for 5th vs. 1st quintile) and so was muscle strength (HR 0.79; 0.76-0.83; for 5th vs. 1st quintile ). Similar associations were seen across a range of major vascular disease events. Exercise capacity was associated with incidence of arrhythmias in a U-shaped fashion (HR 0.91; 0.86-0.96; for 3rd vs. 1st quintile, and 0.99; 0.94-1.04; for 5th vs. 1st quintile). Higher muscle strength was associated with lower risk of arrhythmias (HR 0.87; 0.83-0.91; for 5th vs. 1st quintile). 

    Conclusion:

    Exercise capacity and muscle strength in late adolescence are independently and jointly associated with long-term risk of vascular disease and arrhythmias. The lower risk of vascular events with higher exercise capacity was not outweighed by higher risk of arrhythmias.

  • 11.
    Andersen, Kasper
    et al.
    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.
    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. Department of Internal Medicine, Mora Hospital, Sweden.
    James, Stefan
    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.
    Long-Distance Skiing and Incidence of Hypertension: A Cohort Study of 206,889 Participants in a Long-Distance Cross-Country Skiing Event2020In: Circulation, ISSN 0009-7322, E-ISSN 1524-4539, Vol. 141, no 9, p. 743-750Article in journal (Refereed)
    Abstract [en]

    Background: Hypertension is the leading risk factor for death worldwide and high levels of physical activity is associated with lower incidence of hypertension. The associations of excessive levels of exercise and incidence of hypertension is less known. We aim to compare the incidence of hypertension among 206,889 participants in a long-distance cross-country skiing event and 505,542 persons randomly sampled from the general population (matched to the skiers on age sex and place of residence). Methods: Skiers best performance (in per cent of winning time) and number of completed races during the study period were associated to incidence of hypertension after participation in Vasaloppet. Hypertension was defined as prescription of blood pressure-lowering drugs as obtained from the national drug registry. Models were adjusted for sex, age, education and income (total effect). Results: During a median time-of-risk of 8.3 years skiers had lower incidence of hypertension compared to non-skiers (HR 0.59; 95% confidence interval [CI] 0.58-0.60). Among the skiers, better performance (in % of winning time) in Vasaloppet was strongly associated with lower incidence of hypertension (Fastest fifth: HR 0.41; 95% CI 0.39-0.42. Slowest fifth: 0.78 CI 0.75-0.81). The association was near linear and did not differ between sexes. Among the skiers, a weaker association of number of completed races during the study period with incidence of hypertension (1 race: HR 0.63; 95% CI 0.62-0.65.>5 races: HR 0.51; 95% CI 0.50-0.53). A sub-analysis of 10,804 participants including adjustment for lifestyle factors showed similar results. Conclusions: Participation in a long-distance skiing event was associated with 41% lower incidence of hypertension over the next 8 years, compared to non-participation; and the better the performance, the lower the incidence of hypertension. This adds to the list of beneficial effects of intensive training, as hypertension is the leading risk factor of premature death globally.

  • 12.
    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)
  • 13.
    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.

  • 14.
    Andersen, Kasper
    et al.
    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.
    Mariosa, D.
    Adami, H. O.
    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.
    Ingelsson, E.
    Lagerros, Y.
    Nyren, O.
    Weimin, Y.
    Bellocco, R.
    Sundström, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Total and leisure time physical activity and risk of heart failure: a prospective cohort study2012In: European Heart Journal, ISSN 0195-668X, E-ISSN 1522-9645, Vol. 33, no Suppl 1, p. 1052-1052Article in journal (Other academic)
  • 15.
    Andersen, Kasper
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Rasmussen, F.
    Karolinska Inst, Dept Publ Hlth Sci, Stockholm, Sweden..
    Neovius, M.
    Karolinska Inst, Dept Med, Clin Epidemiol Unit, Stockholm, Sweden..
    Tynelius, P.
    Karolinska Inst, Dept Publ Hlth Sci, Stockholm, Sweden..
    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.
    Anthropometric measures and risk of atrial fibrillation - a cohort study of 1.2 million young men2015In: European Heart Journal, ISSN 0195-668X, E-ISSN 1522-9645, Vol. 36, no Suppl. 1, p. 910-910Article in journal (Other academic)
  • 16.
    Andersen, Kasper
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Rasmussen, F.
    Lund Univ, Dept Hlth Sci, Lund, Sweden.
    Neovius, M.
    Karolinska Inst, Dept Med, Clin Epidemiol Unit, Stockholm, Sweden.
    Tynelius, P.
    Karolinska Inst, Dept Publ Hlth Sci, Stockholm, Sweden;Stockholm Cty Council, Ctr Epidemiol & Community Med, Stockholm, Sweden.
    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.
    Body size and risk of atrial fibrillation: a cohort study of 1.1 million young men2018In: Journal of Internal Medicine, ISSN 0954-6820, E-ISSN 1365-2796, Vol. 283, no 4, p. 346-355Article in journal (Refereed)
    Abstract [en]

    Background: Whilst tall stature has been related to lower risk of vascular disease, it has been proposed as a risk factor for atrial fibrillation. Little is known about other anthropometric measures and their joint effects on risk of atrial fibrillation.

    Objectives: We aim to investigate associations and potential joint effects of height, weight, body surface area (BSA) and body mass index (BMI) with risk of atrial fibrillation.

    Methods: In a cohort covering 1 153 151 18-year-old men participating in the Swedish military conscription (1972-1995), Cox regression was used to investigate associations of height, weight, BSA and BMI with risk of atrial fibrillation.

    Results: During a median of 26.3 years of follow-up, higher height was associated with higher risk of atrial fibrillation (hazard ratio [HR] 2.80; 95% CI 2.63-2.98; for 5th vs. 1st quintile) and so was larger BSA (HR 3.05; 95% CI 2.82-3.28; for 5th vs. 1st quintile). Higher weight and BMI were to a lesser extent associated with risk of atrial fibrillation (BMI: 1.42; 95% CI 1.33-1.52, for 5th vs. 1st quintile). We found a multiplicative joint effect of height and weight. Adjusting for muscle strength, exercise capacity and diseases related to atrial fibrillation attenuated these measures.

    Conclusions: Higher height and weight are strongly associated with higher risk of atrial fibrillation. These associations are multiplicative and independent of each other and are summarized in a strong association of body surface area with risk of atrial fibrillation. The mechanisms remain unknown but may involve increased atrial volume load with larger body size.

  • 17.
    Andersen, Kasper
    et al.
    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.
    Rasmussen, Finn
    Karolinska Inst, Dept Publ Hlth Sci, Child & Adolescent Publ Hlth Epidemiol Unit, Stockholm, Sweden..
    Held, Claes
    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.
    Neovius, Martin
    Karolinska Inst, Dept Med, Clin Epidemiol Unit, Stockholm, Sweden..
    Tynelius, Per
    Karolinska Inst, Dept Publ Hlth Sci, Child & Adolescent Publ Hlth Epidemiol Unit, Stockholm, Sweden..
    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.
    Exercise capacity and muscle strength and risk of vascular disease and arrhythmia in 1.1 million young Swedish men: cohort study2015In: BMJ-BRITISH MEDICAL JOURNAL, ISSN 1756-1833, Vol. 351, article id h4543Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE To investigate the associations of exercise capacity and muscle strength in late adolescence with risk of vascular disease and arrhythmia. DESIGN Cohort study. SETTING General population in Sweden. PARTICIPANTS 1.1 million men who participated in mandatory military conscription between 1 August 1972 and 31 December 1995, at a median age of 18.2 years. Participants were followed until 31 December 2010. MAIN OUTCOMES Associations between exercise capacity and muscle strength with risk of vascular disease and subgroups (ischaemic heart disease, heart failure, stroke, and cardiovascular death) and risk of arrhythmia and subgroups (atrial fibrillation or flutter, bradyarrhythmia, supraventricular tachycardia, and ventricular arrhythmia or sudden cardiac death). Maximum exercise capacity was estimated by the ergometer bicycle test, and muscle strength was measured as handgrip strength by a hand dynamometer. High exercise capacity or muscle strength was deemed as above the median level. RESULTS During a median follow-up of 26.3 years, 26 088 vascular disease events and 17 312 arrhythmia events were recorded. Exercise capacity was inversely associated with risk of vascular disease and its subgroups. Muscle strength was also inversely associated with vascular disease risk, driven by associations of higher muscle strength with lower risk of heart failure and cardiovascular death. Exercise capacity had a U shaped association with risk of arrhythmia, driven by a direct association with risk of atrial fibrillation and a U shaped association with bradyarrhythmia. Higher muscle strength was associated with lower risk of arrhythmia (specifically, lower risk of bradyarrhythmia and ventricular arrhythmia). The combination of high exercise capacity and high muscle strength was associated with a hazard ratio of 0.67 (95% confidence interval 0.65 to 0.70) for vascular events and 0.92 (0.88 to 0.97) for arrhythmia compared with the combination of low exercise capacity and low muscle strength. CONCLUSIONS Exercise capacity and muscle strength in late adolescence are independently and jointly associated with long term risk of vascular disease and arrhythmia. The health benefit of lower risk of vascular events with higher exercise capacity was not outweighed by higher risk of arrhythmia.

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  • 18.
    Andersson, Jessika
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Sundström, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Gustavsson, Thomas
    Hulthe, Johannes
    Elmgren, Anders
    Zilmer, Kersti
    Zilmer, Mihkel
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Echogenecity of the carotid intima-media complex is related to cardiovascular risk factors, dyslipidemia, oxidative stress and inflammation The Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS) study2008In: Atherosclerosis, ISSN 1879-1484Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Increased carotid artery intima-media thickness (IMT), measured by ultrasound, is related to an increased risk of cardiovascular disease. Since presence of echolucent plaques increases the risk further, we investigated if echogenecity of the carotid intima-media complex is related to markers of cardiovascular risk. Our aim was therefore to investigate if intima-media echogenecity is related to cardiovascular risk factors, or to markers of inflammation and oxidation in an exploratory investigation. METHODS: The PIVUS cohort study is an observational study of 1016 (509 women and 507 men) randomly chosen individuals aged 70 living in Uppsala, Sweden. Carotid artery ultrasound measurements were performed. IMT and the grey scale median (GSM) value were calculated in the intima-media complex (IM-GSM) in the far wall of the common carotid artery. Traditional risk factors were evaluated together with indices of oxidative stress and inflammation. RESULTS: In the multiple regression analysis, HDL-cholesterol, body mass index, conjugated diens, glutathione, e-selectin and TNF alfa were significantly related to IM-GSM. IMT was independently related to blood pressure, smoking and body mass index. CONCLUSION: The echolucency of the carotid intima-media was related to several cardiovascular risk factors not related to IMT, such as dyslipidemia, oxidative stress and inflammation. Since the echogenecity of the carotid intima-media complex was related to different risk factors compared to carotid IMT, it is worthwhile to further explore the usefulness of this new marker of the vascular wall.

  • 19.
    Andersson, Jessika
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Sundström, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Kurland, Lisa
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Gustavsson, Thomas
    Hulthe, Johannes
    Elmgren, Anders
    Zilmer, Kersti
    Zilmer, Mihkel
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    The carotid artery plaque size and echogenicity are related to different cardiovascular risk factors in the elderly: the Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS) study2009In: Lipids, ISSN 0024-4201, E-ISSN 1558-9307, Vol. 44, no 5, p. 397-403Article in journal (Refereed)
    Abstract [en]

    Carotid plaques can be characterised by ultrasound by size and echogenicity. Both size and echogenicity are predictors of cardiovascular events. The aim of this study was to examine whether traditional risk factors and markers of inflammation and oxidation were associated with plaque size and echogenicity. Computerised analysis of carotid plaque size and echogenicity (grey scale median, GSM) were performed by ultrasound in a population-based health survey in 1,016 subjects aged 70 years (PIVUS study). Information on cardiovascular risk factors was collected, together with markers of inflammation and oxidation. Increased Framingham risk score, systolic blood pressure, higher BMI and decreased HDL, lower glutathione levels were related to echolucent plaques. Previous or present smoking was common with significantly more pack-years related to the echorich plaques. Plaque size was associated with increased Framingham risk score, systolic blood pressure, blood glucose levels, smoking, ApoB/A1 ratio, OxLDL, TNF alpha, HOMA insulin resistance, leucocyte count, decreased BCD-LDL and low levels of l-selectin. Low HDL, increased BMI and decreased glutathione levels were associated with the echolucency of carotid plaques, implying metabolic factors to play a role for plaque composition. Markers of inflammation were related to plaque size alone, implying inflammation to be predominantly associated with the amount of atherosclerosis. These results suggest that plaque size and echogenicity are influenced by different risk factors.

  • 20.
    Arefalk, Gabriel
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Galanti, Rosaria
    Lundberg, Michael
    Ye, Weimin
    Norberg, Margareta
    Lindmark, Krister
    Pedersen, Nancy
    Trolle Lagerros, Ylva
    Bellocco, Rino
    Lager, Anton
    Wennberg, Patrik
    Eriksson, Marie
    Östergren, Per-Olof
    Alfredsson, Lars
    Sundström, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics. 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. 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, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Magnusson, Cecilia
    Smokeless Tobacco (Snus) and Risk of Heart Failure of Ischemic and Non-Ischemic Origin: a Pooled Analysis of Eight Prospective Cohort StudiesManuscript (preprint) (Other academic)
    Abstract [en]

    Background

    Snus, a Swedish type of smokeless tobacco, has potent acute hemodynamic effects, which could provoke stress on the cardiovascular system, including the myocardium. Snus has, however, not been linked to risk of ischemic heart disease. Therefore, we hypothesized that snus use increases the risk for heart failure of non-ischemic origin.

    Methods

    We conducted a pooled analysis of eight Swedish prospective cohort studies involving individual participant data from 350,711 men. Shared frailty models with random effects at the cohort level, were used to estimate hazard ratios (HRs) with 95 % confidence intervals (CIs) of heart failure in relation to snus use. We investigated dose-response associations, and association with ischemic and non-ischemic heart failure in separate. For positive control purposes, we also investigated associations between smoking and risk of heart failure.

    Results

    During a median follow-up time of 16 years, 5,404 men were hospitalized for heart failure. In models adjusting for age, smoking, previous myocardial infarction and educational level, current snus use was associated with a higher risk of heart failure (HR 1.27, 95 % CI 1.07-1.50), relative to non-current snus use. A dose-response pattern was observed, with higher risk with more snus cans used per week. We observed an association of snus use with non-ischemic heart failure, HR 1.34 (95 % CI 1.11-1.63), but not with ischemic heart failure, HR 1.01 (95 % CI 0.72-1.42). Smoking was more strongly associated with heart failure, particularly of ischemic origin, than snus use.

    Conclusions

    Snus use was associated with a modestly increased risk for heart failure of non-ischemic origin in a dose-response manner. This finding has public health implications for the risk assessment of snus use, and potentially other modes of smokeless use of nicotine.

  • 21.
    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.

  • 22.
    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)
  • 23.
    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)
  • 24.
    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.

  • 25.
    Arefalk, Gabriel
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Svennblad, Bodil
    Uppsala University, Disciplinary Domain of Science and Technology, Mathematics and Computer Science, Department of Mathematics. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Andersen, Kasper
    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.
    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. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Physiology.
    Varenhorst, Christoph
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Sundström, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics. 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. 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, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Smokeless Tobacco (Snus) and Outcome of Myocardial Infarction: a SWEDEHEART StudyManuscript (preprint) (Other academic)
    Abstract [en]

    Background

    Based on effects of nicotine and snus (a smokeless tobacco) on hemodynamics, pro-arrhythmia and remodelling, in combination with indications of increased risk for fatal myocardial infarction (MI) in snus users; we hypothesised that the outcome of an MI may be worse in snus users.

    Methods

    Data was extracted from the SWEDEHEART registry for all patients who underwent coronary angiography in Sweden due to MI between December 2009 and December 2014. In snus users (n=4,950) relative to snus non-users (n=55,412), we compared risks of a large MI (defined as hs-cTnT of  > 10,000 ng/L, cTnT > 10 μg/L or cTnI > 10 μg/L) and death in the acute (in-hospital) setting, and death+HF (a combined endpoint of all-cause death or hospitalization for heart failure) and all-cause death at short- (<28 days) and long-term follow-up. Relations of snus use to outcomes were also analysed in pre-specified subgroups of never, previous and current smokers.

    Results

    A large MI was diagnosed in 10,975 patients. During long-term follow-up (median 1.9 years), 7,758 either died (n=6,044) or were hospitalized due to heart failure (n=1,714). In models adjusting for age, gender, smoking, previous MI and occupational classification (employed, unemployed/sick leave and retired), snus use was not associated with risk of large MI (odds ratio 1.01; 95% confidence interval (CI) 0.93-1.09) or death+HF (long-term Cox proportional hazard ratio (HR) 0.99; 95% CI 0.90-1.10). Nonetheless, among never-smokers snus use was associated with an increased risk for death+HF (long-term HR 1.26, 95% CI 1.03-1.55), driven by a higher mortality risk (long-term HR for death of any cause 1.29, 95% CI 1.02-1.64).

    Conclusions

    In this study, snus use was unrelated to acute, short-term or long-term adverse outcomes after an MI. Among never-smokers, snus use was associated with an increased risk of post-MI death.

  • 26. Arnlov, Johan
    et al.
    Carlsson, Axel C.
    Sundström, Johan
    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.
    Larsson, Anders
    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, Cardiovascular epidemiology.
    Larsson, Tobias E.
    Serum FGF23 and Risk of Cardiovascular Events in Relation to Mineral Metabolism and Cardiovascular Pathology2013In: American Society of Nephrology. Clinical Journal, ISSN 1555-9041, E-ISSN 1555-905X, Vol. 8, no 5, p. 781-786Article in journal (Refereed)
    Abstract [en]

    Background and objectives Circulating fibroblast growth factor-23 is associated with adverse cardiovascular outcomes in CKD and non-CKD individuals, but the underlying mechanism remains unclear. This study tested whether this association is independent of mineral metabolism and indices of subclinical cardiovascular pathology. Design, setting, participants, & measurements The prospective association between fibroblast growth factor-23 and major cardiovascular events (a composite of hospital-treated myocardial infarction, hospital-treated stroke, or all-cause mortality) was investigated in the community-based Prospective Investigation of the Vasculature in Uppsala Seniors (n=973; mean age=70 years, 50% women) using multivariate logistic regression. Subjects were recruited between January of 2001 and June of 2004. Results During follow-up (median=5.1 years), 112 participants suffered a major cardiovascular event. In logistic regression models adjusted for age, sex, and estimated GFR, higher fibroblast growth factor-23 was associated with increased risk for major cardiovascular events (odds ratio for tertiles 2 and 3 versus tertile 1=1.92, 95% confidence interval=1.19-3.09, P<0.01). After additional adjustments in the model, adding established cardiovascular risk factors, confounders of mineral metabolism (calcium, phosphate, parathyroid hormone, and 25 (OH)-vitamin D), and indices of subclinical pathology (flow-mediated vasodilation, endothelial-dependent and -independent vasodilation, arterial stiffness, and atherosclerosis and left ventricular mass) attenuated this relationship, but it remained significant (odds ratio for tertiles 2 and 3 versus tertile 1=1.69, 95% confidence interval=1.01-2.82, P<0.05). Conclusions Fibroblast growth factor-23 is an independent predictor of cardiovascular events in the community, even after accounting for mineral metabolism abnormalities and subclinical cardiovascular damage. Circulating fibroblast growth factor-23 may reflect novel and important aspects of cardiovascular risk yet to be unraveled.

  • 27.
    Arnlöv, Johan
    et al.
    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. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Ingelsson, Erik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Internal Medicine.
    Impact of BMI and the metabolic syndrome on the risk of diabetes in middle-aged men2011In: Diabetes Care, ISSN 0149-5992, E-ISSN 1935-5548, Vol. 34, no 1, p. 61-65Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE- The existence of an obese subgroup with a healthy metabolic profile and low diabetes risk has been proposed; yet long-term data are lacking. We aimed to investigate associations between combinations of BMI categories and metabolic syndrome and risk of type 2 diabetes in middle-aged men.

    RESEARCH DESIGN AND METHODS- At age 50, cardiovascular risk factors were assessed in 1,675 participants without diabetes in the community-based Uppsala Longitudinal Study of Adult Men (ULSAM) study. According to BMI/metabolic syndrome status, they were categorized as normal weight (BMI <25 kg/m(2)) without metabolic syndrome (National Cholesterol Education Program criteria, n = 853), normal weight with metabolic syndrome (n = 60), overweight (BMI 25-30 kg/m(2)) without metabolic syndrome (n = 557), overweight with metabolic syndrome (n = 117), obese (BMI >30 kg/m(2)) without metabolic syndrome (n = 28), and obese with metabolic syndrome (n = 60). We investigated the associations between BMI/metabolic syndrome categories at baseline and diabetes incidence.

    RESULTS- After 20 years, 160 participants had developed diabetes. In logistic regression models adjusting for age, smoking, and physical activity, increased risks for diabetes were observed in the normal weight with metabolic syndrome (odds ratio 3.28 [95% CI] 1.38-7.81; P = 0.007), overweight without metabolic syndrome (3.49[2.26-5.42]; P < 0.001), overweight with metabolic syndrome (7.77 [4.44-13.62]; P < 0.001), obese without metabolic syndrome (11.72 [4.88-28.16]; P < 0.001), and obese with metabolic syndrome (10.06 [5.19-19.51]; P < 0.001) categories compared with the normal weight without metabolic syndrome category.

    CONCLUSIONS- Overweight or obese men without metabolic syndrome were at increased risk for diabetes. Our data provide further evidence that overweight and obesity in the absence of the metabolic syndrome should not be considered a harmless condition.

  • 28.
    Arnlöv, Johan
    et al.
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Medical Sciences. Department of Public Health and Caring Sciences.
    Sundström, Johan
    Department of Public Health and Caring Sciences.
    Lind, Lars
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Medical Sciences.
    Andrén, Bertil
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Medical Sciences.
    Andersson, Maria
    Department of Public Health and Caring Sciences.
    Reneland, Richard
    Department of Public Health and Caring Sciences.
    Berglund, Lars
    Kashuba, Vladimir
    Protopopov, Alexei
    Zabarovsky, Eugene
    Lithell, Hans
    Department of Public Health and Caring Sciences.
    hUNC-93B1, a novel gene mainly expressed in the heart, is related to left ventricular diastolic function, heart failure morbidity and mortality in elderly men.2005In: Eur J Heart Fail, ISSN 1388-9842, Vol. 7, no 6, p. 958-65Article in journal (Refereed)
  • 29.
    Baldanzi, Gabriel
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Sayols-Baixeras, Sergi
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology. Uppsala University, Science for Life Laboratory, SciLifeLab. CIBER Cardiovascular Diseases (CIBERCV), Instituto de Salud Carlos III, Madrid, Spain.
    Theorell-Haglöw, Jenny
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology. Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Lung- allergy- and sleep research.
    Dekkers, Koen F.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Hammar, Ulf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Nguyen, Diem
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology.
    Lin, Yi-Ting
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology. Uppsala University, Science for Life Laboratory, SciLifeLab. Division of Family Medicine and Primary Care, Department of Neurobiology, Care Science and Society, Karolinska Institute, Huddinge, Sweden; Department of Family Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Taiwan.
    Ahmad, Shafqat
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology. Uppsala University, Science for Life Laboratory, SciLifeLab. Preventive Medicine Division, Harvard Medical School, Brigham and Women’s Hospital, Boston, MA.
    Bak Holm, Jacob
    Nielsen, Henrik Bjørn
    Brunkwall, Louise
    Benedict, Christian
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.
    Cedernaes, Jonathan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Transplantation and regenerative medicine. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Koskiniemi, Sanna
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology, Microbiology and Immunology.
    Phillipson, Mia
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology, Integrative Physiology.
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Epidemiology.
    Sundström, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Epidemiology. The George Institute for Global Health, University of New South Wales, Sydney, NSW, Australia.
    Bergström, Göran
    Engström, Gunnar
    Smith, J. Gustav
    Orho-Melander, Marju
    Ärnlöv, Johan
    Kennedy, Beatrice
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Lindberg, Eva
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Lung- allergy- and sleep research.
    Fall, Tove
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology.
    OSA Is Associated With the Human Gut Microbiota Composition and Functional Potential in the Population-Based Swedish CardioPulmonary bioImage Study2023In: Chest, ISSN 0012-3692, E-ISSN 1931-3543, Vol. 164, no 2, p. 503-516Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Obstructive sleep apnea (OSA) is a common sleep-breathing disorder linked to increased risk of cardiovascular disease. Intermittent hypoxia and intermittent airway obstruction, hallmarks of OSA, have been shown in animal models to induce substantial changes to the gut microbiota composition and subsequent transplantation of fecal matter to other animals induced changes in blood pressure and glucose metabolism.

    RESEARCH QUESTION: Does obstructive sleep apnea in adults associate with the composition and metabolic potential of the human gut microbiota?

    STUDY DESIGN AND METHODS: We used respiratory polygraphy data from up to 3,570 individuals aged 50-64 from the population-based Swedish CardioPulmonary bioImage Study combined with deep shotgun metagenomics of fecal samples to identify cross-sectional associations between three OSA parameters covering apneas and hypopneas, cumulative sleep time in hypoxia and number of oxygen desaturation events with gut microbiota composition. Data collection about potential confounders was based on questionnaires, on-site anthropometric measurements, plasma metabolomics, and linkage with the Swedish Prescribed Drug Register.

    RESULTS: We found that all three OSA parameters were associated with lower diversity of species in the gut. Further, the OSA-related hypoxia parameters were in multivariable-adjusted analysis associated with the relative abundance of 128 gut bacterial species, including higher abundance of Blautia obeum and Collinsela aerofaciens. The latter species was also independently associated with increased systolic blood pressure. Further, the cumulative time in hypoxia during sleep was associated with the abundance of genes involved in nine gut microbiota metabolic pathways, including propionate production from lactate. Lastly, we observed two heterogeneous sets of plasma metabolites with opposite association with species positively and negatively associated with hypoxia parameters, respectively.

    INTERPRETATION: OSA-related hypoxia, but not the number of apneas/hypopneas, is associated with specific gut microbiota species and functions. Our findings lay the foundation for future research on the gut microbiota-mediated health effects of OSA.

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  • 30.
    Baron, Tomasz
    et al.
    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.
    Hambraeus, Kristina
    Falun Cent Hosp, Dept Cardiol, Falun, Sweden..
    Sundstrom, 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.
    Erlinge, David
    Lund Univ, Skane Univ Hosp, Dept Cardiol, Lund, Sweden..
    Jernberg, Tomas
    Karolinska Inst, Karolinska Univ Hosp, Dept Cardiol, Dept Med, Stockholm, Sweden..
    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.
    Impact on Long-Term Mortality of Presence of Obstructive Coronary Artery Disease and Classification of Myocardial Infarction2016In: American Journal of Medicine, ISSN 0002-9343, E-ISSN 1555-7162, Vol. 129, no 4, p. 398-406Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: In contrast to the associated-with-thromboembolic-event type 1 myocardial infarction, type 2 myocardial infarction is caused by acute imbalance between oxygen supply and demand of myocardium. Type 2 myocardial infarction may be present in patients with or without obstructive coronary artery disease, but knowledge about patient characteristics, treatments, and outcome in relation to coronary artery status is lacking. We aimed to compare background characteristics, triggering mechanisms, treatment, and long-term prognosis in a large real-life cohort of patients with type 1 and type 2 myocardial infarction with and without obstructive coronary artery disease.

    METHODS: All 41,817 consecutive patients with type 1 and type 2 myocardial infarction registered in the Swedish myocardial infarction registry (SWEDEHEART) who underwent coronary angiography between January 1, 2011 and December 31, 2013, with the last follow-up on December 31, 2014, were studied.

    RESULTS: In 92.8% of 40,501 patients classified as type 1 and in 52.5% of patients classified as type 2 myocardial infarction, presence of an obstructive coronary artery disease could be shown. Within the patients with obstructive coronary artery disease, those with type 2 myocardial infarction were older, and had more comorbidities and smaller necrosis as compared with type 1 myocardial infarction. In contrast, there was almost no difference in risk profile and extent of myocardial infarction between type 1 and type 2 myocardial infarction patients with nonobstructive coronary artery stenosis. The crude long-term mortality was higher in type 2 as compared with type 1 myocardial infarction with obstructive coronary artery disease (hazard ratio [HR] 1.72; 95% confidence interval [CI], 1.45-2.03), but was lower after adjustment (HR 0.76; 95% CI, 0.61-0.94). In myocardial infarction patients with nonobstructive coronary artery stenosis, the mortality risk was similar regardless of the clinical myocardial infarction type (crude HR 1.14; 95% CI, 0.84-1.55; adjusted HR 0.82; 95% CI, 0.52-1.29).

    CONCLUSIONS: The substantial differences in risk factors, treatment, and outcome in patients with type 1 and type 2 myocardial infarction with obstructive coronary artery disease supports the relevance of the division between type 1 and type 2 in this population. On the contrary, in patients with nonobstructive coronary artery stenosis, irrespective of the clinical type, a similar risk profile, extent of necrosis, and longterm prognosis were observed, indicating that distinction between type 1 and type 2 myocardial infarction in these patients seems to be inappropriate.

  • 31.
    Baron, Tomasz
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Hambraeus, Kristina
    Falun Cent Hosp, Dept Cardiol, Falun, Sweden..
    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.
    Erlinge, David
    Lund Univ, Dept Cardiol, Skane Univ Hosp, Lund, Sweden..
    Jernberg, Tomas
    Karolinska Univ Hosp, Dept Cardiol, Karolinska Inst, Dept Med Huddinge, Stockholm, Sweden..
    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.
    Reply to: Prognosis in Patients with Different Types of Myocardial Infarction and Presence of Obstructive Coronary Artery Disease Reply2017In: American Journal of Medicine, ISSN 0002-9343, E-ISSN 1555-7162, Vol. 130, no 9, p. E417-E418Article in journal (Other academic)
  • 32.
    Baron, Tomasz
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Hambraeus, Kristina
    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.
    Erlinge, David
    Jernberg, Tomas
    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.
    Type 2 myocardial infarction in clinical practice2015In: Heart, ISSN 1355-6037, E-ISSN 1468-201X, Vol. 101, no 2, p. 101-106Article in journal (Refereed)
    Abstract [en]

    Objective We aimed to assess differences in incidence, clinical features, current treatment strategies and outcome in patients with type 2 vs. type 1 acute myocardial infarction (AMI). Methods and results All 20 138 hospitalisations in Sweden with a diagnosis of AMI registered during 2011 in the Swedish Web-system for Enhancement and Development of Evidence-based care in Heart disease Evaluated According to Recommended Therapies were classified into types 1-5 in accordance with the universal definition of myocardial infarction (MI) from 2007. Type 1 AMI was present in 88.5% of the cases while 7.1% were classified as type 2 AMI. Higher age, female sex, comorbidities, impaired renal function, anaemia and smaller extent of myocardial necrosis characterised patients with type 2 AMI. While normal coronary arteries were more frequently seen (42.4% vs. 7.4%), an invasive treatment was less common, and antiplatelet medications were less prescribed in patients with type 2 AMI compared with type 1 AMI. The group with type 2 AMI had significantly higher crude 1-year mortality compared with the group with type 1 AMI (24.7% vs. 13.5%, p< 0.001). However, after adjustment, the HR for 1-year mortality in patients with type 2 AMI was 1.03 (95% CI 0.86 to 1.23). Conclusions In this real-life study, 7.1% of myocardial infarctions were classified as type 2 AMI. These patients were older, predominantly women and had more comorbidities. Invasive treatment strategies and cardioprotective medications were less used. Patients with type 2 AMI had higher crude mortality compared with type 1 patients with MI. However, after adjustment, the 1-year mortality was similar.

  • 33.
    Beijer, Kristina
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Organismal Biology, Environmental toxicology.
    Lampa, Erik
    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, 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.
    Nilsson, Peter M.
    SUS Malmo, Dept Clin Sci, Malmo, Sweden..
    Elmstahl, Solve
    Lund Univ, Div Geriatr Med, Dept Hlth Sci, Malmo Univ Hosp, Malmo, Sweden..
    Pedersen, Nancy L.
    Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden..
    Lind, Lars
    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.
    Interaction between physical activity and television time on blood pressure level: cross-sectional data from 45000 individuals2018In: Journal of Hypertension, ISSN 0263-6352, E-ISSN 1473-5598, Vol. 36, no 5, p. 1041-1050Article in journal (Refereed)
    Abstract [en]

    Objectives:The aim was to investigate if there is an interaction between sitting time and leisure time physical activity on blood pressure and if there are age differences and sex differences in this respect.

    Methods:Linear regression analysis on cross-sectional data was performed in more than 45000 men and women from two Swedish cohort studies, EpiHealth (45-75 years) and LifeGene (18-45 years). Self-reported leisure time physical activity was given in five levels from low (level 1) to vigorous physical activity (level 5) and television time was used as a proxy measure of sitting time.

    Results:High physical activity was associated with lower DBP (P=0.001), but not SBP. Active middle-aged men had lower DBP (-1.1mmHg; 95% CI -1.7 to -0.4) compared with inactive participants. Prolonged television time was associated with higher SBP (P<0.001) and DBP (P=0.011) in both sexes and in most age groups. Watching 3h instead of 1h television per day was associated with higher SBP in middle-aged women (SBP: 1.1mmHg; 95% CI 0.7-1.4) and men (SBP: 1.2mmHg; 95% CI 0.8-1.6). Only in young men, a high physical activity (level 4 instead of level 1) could compensate for a prolonged television time (3h per day) in terms of DBP.

    Conclusion:Prolonged television time was associated with higher SBP and DBP in both sexes and at most ages, whereas an increased physical activity was mainly associated with a lower DBP. Only in young men, a high physical activity could compensate for prolonged television time regarding DBP.

  • 34.
    Beijer, Kristina
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Epidemiology.
    Lampa, Erik
    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, 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, Clinical Epidemiology.
    Nilsson, Peter M.
    SUS Malmö, Dept Clin Sci, Malmö, Sweden.
    Elmståhl, Sölve
    Lund Univ, Malmö Univ Hosp, Dept Hlth Sci, Div Geriatr Med, Malmö, Sweden.
    Pedersen, Nancy L.
    Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden.
    Lind, Lars
    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, Clinical Epidemiology.
    Physical activity may compensate for prolonged TV time regarding pulse rate-a cross-sectional study2018In: Upsala Journal of Medical Sciences, ISSN 0300-9734, E-ISSN 2000-1967, Vol. 123, no 4, p. 247-254Article in journal (Refereed)
    Abstract [en]

    Background: Regular exercise reduces pulse rate, but it is less clear how prolonged sitting time affects pulse rate. Our hypothesis was that high physical activity could compensate for prolonged sitting time regarding the pulse rate.

    Methods: Regression analysis was performed on cross-sectional data including 47,457 men and women based on two Swedish cohort studies, EpiHealth (18–45 years) and LifeGene (45–75 years). Self-reported leisure time physical activity was given in five levels, from low (level 1) to vigorous (level 5), and television time was used as a proxy of sitting time.

    Results: A higher physical activity (level 4 compared to level 1) was associated with a lower pulse rate in middle-aged females (-2.7 beats per minute [bpm]; 95% CI -3.3 to -2.2) and males (-4.0 bpm; 95% CI -4.7 to -3.4). The relationship between physical activity and pulse rate was strongest in the young. A prolonged television time (3 h compared to 1 h per day) was associated with a slightly higher pulse rate in middle-aged females (+0.6 bpm; 95% CI +0.3 to +0.8) and males (+0.9 bpm; 95% CI +0.7 to +1.2). Among participants with a prolonged television time (3 h), those with a high physical activity (level 4) had a lower pulse rate compared to those with a low physical activity (level 1).

    Conclusions: A prolonged television time was associated with a high pulse rate, while high physical activity was associated with a low pulse rate. The results suggest that a high physical activity could compensate for a prolonged television time regarding pulse rate.

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  • 35.
    Beijer, Kristina
    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.
    Nowak, Christoph
    Karolinska Inst, Div Family Med & Primary Care, Dept Neurobiol Care Sci & Soc, Stockholm, Sweden.
    Sundström, Johan
    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.
    Ärnlöv, Johan
    Karolinska Inst, Div Family Med & Primary Care, Dept Neurobiol Care Sci & Soc, Stockholm, Sweden;Dalarna Univ, Sch Hlth & Social Sci, Falun, Sweden.
    Fall, Tove
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology.
    Lind, Lars
    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.
    In search of causal pathways in diabetes: a study using proteomics and genotyping data from a cross-sectional study2019In: Diabetologia, ISSN 0012-186X, E-ISSN 1432-0428, Vol. 62, no 11, p. 1998-2006Article in journal (Refereed)
    Abstract [en]

    Aims/hypothesis: The pathogenesis of type 2 diabetes is not fully understood. We investigated whether circulating levels of preselected proteins were associated with the outcome 'diabetes' and whether these associations were causal.

    Methods: In 2467 individuals of the population-based, cross-sectional EpiHealth study (45-75 years, 50% women), 249 plasma proteins were analysed by the proximity extension assay technique. DNA was genotyped using the Illumina HumanCoreExome-12 v1.0 BeadChip. Diabetes was defined as taking glucose-lowering treatment or having a fasting plasma glucose of >= 7.0 mmol/l. The associations between proteins and diabetes were assessed using logistic regression. To investigate causal relationships between proteins and diabetes, a bidirectional two-sample Mendelian randomisation was performed based on large, genome-wide association studies belonging to the DIAGRAM and MAGIC consortia, and a genome-wide association study in the EpiHealth study.

    Results: Twenty-six proteins were positively associated with diabetes, including cathepsin D, retinal dehydrogenase 1, alpha-l-iduronidase, hydroxyacid oxidase 1 and galectin-4 (top five findings). Three proteins, lipoprotein lipase, IGF-binding protein 2 and paraoxonase 3 (PON-3), were inversely associated with diabetes. Fourteen of the proteins are novel discoveries. The Mendelian randomisation study did not disclose any significant causal effects between the proteins and diabetes in either direction that were consistent with the relationships found between the protein levels and diabetes.

    Conclusions/interpretation: The 29 proteins associated with diabetes are involved in several physiological pathways, but given the power of the study no causal link was identified for those proteins tested in Mendelian randomisation. Therefore, the identified proteins are likely to be biomarkers for type 2 diabetes, rather than representing causal pathways.

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  • 36.
    Beijer, Kristina
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences. Uppsala Univ, Med Sci, Uppsala, Sweden.
    Sundström, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Arnlöv, J.
    Karolinska Inst, Stockholm, Sweden.
    Fall, Tove
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology.
    Ingelsson, E.
    Stanford Univ, Palo Alto, CA 94304 USA.
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    A targeted proteomic profile of prevalent diabetes in a population-based sample2018In: Diabetologia, ISSN 0012-186X, E-ISSN 1432-0428, Vol. 61, p. S252-S252Article in journal (Other academic)
  • 37.
    Bell, Katy J. L.
    et al.
    Univ Sydney, Sydney Sch Publ Hlth, Sydney, NSW, Australia.
    Azizi, Lamiae
    Univ Sydney, Sch Math & Stat, Sydney, NSW, Australia.
    Nilsson, Peter M.
    Lund Univ, Dept Clin Sci, Univ Hosp, Malmö, Sweden.
    Hayen, Andrew
    UTS, Australian Ctr Publ & Populat Hlth Res, Sydney, NSW, Australia.
    Irwig, Les
    Univ Sydney, Sydney Sch Publ Hlth, Sydney, NSW, Australia.
    Östgren, Carl J.
    Linköping Univ, Dept Med & Hlth Sci, Linköping, Sweden.
    Sundström, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Prognostic impact of systolic blood pressure variability in people with diabetes2018In: PLOS ONE, E-ISSN 1932-6203, Vol. 13, no 4, article id e0194084Article in journal (Refereed)
    Abstract [en]

    Objective: Blood pressure variability (BPV) has been associated with risk of cardiovascular events in observational studies, independently of mean BP levels. In states with higher autonomic imbalance, such as in diabetes, the importance of BP variability may theoretically be even greater. We aimed to investigate the incremental value of BPV for prediction of cardiovascular and all-cause mortality in patients with type 2 diabetes.

    Methods: We identified 9,855 patients without pre-existing cardiovascular disease who did not change BP-lowering treatment during the observation period from a Swedish primary health care cohort of patients with type 2 diabetes. BPV was summarized as the standard deviation (SD), coefficient of variation (CV), or variation independent of mean (VIM). Patients were followed for a median of 4 years and associations with cardiovascular and all-cause mortality were investigated using Cox proportional hazards models.

    Results: BPV was not associated with cardiovascular specific or all-cause mortality in the total sample. In patients who were not on BP-lowering drugs during the observation period (n = 2,949), variability measures were associated with all-cause mortality: hazard ratios were 1.05, 1.04 and 1.05 for 50% increases in SD, CV and VIM, respectively, adjusted for Framingham risk score risk factors, including mean BP. However, the addition of the variability measures in this subgroup only led to very minimal improvement in discrimination, indicating they may have limited clinical usefulness (change in C-statistic ranged from 0.000–0.003 in all models).

    Conclusions: Although BPV was independently associated with all-cause mortality in diabetes patients in primary care who did not have pre-existing cardiovascular disease or BP-lowering drugs, it may be of minimal clinical usefulness above and beyond that of other routinely measured predictors, including mean BP.

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  • 38. Bell, Katy J. L.
    et al.
    Beller, Elaine
    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.
    McGeechan, Kevin
    Hayen, Andrew
    Irwig, Les
    Neal, Bruce
    Glasziou, Paul
    Ambulatory blood pressure adds little to Framingham Risk Score for the primary prevention of cardiovascular disease in older men: secondary analysis of observational study data2014In: BMJ Open, E-ISSN 2044-6055, Vol. 4, no 9, p. e006044-Article in journal (Refereed)
    Abstract [en]

    Objective: To determine the incremental value of ambulatory blood pressure (BP) in predicting cardiovascular risk when the Framingham Risk Score (FRS) is known. Methods: We included 780 men without cardiovascular disease from the Uppsala Longitudinal Study of Adult Men, all aged approximately 70 years at baseline. We first screened ambulatory systolic BP (ASBP) parameters for their incremental value by adding them to a model with 10-year FRS. For the best ASBP parameter we estimated HRs and changes in discrimination, calibration and reclassification. We also estimated the difference in the number of men started on treatment and in the number of men protected against a cardiovascular event. Results: Mean daytime ASBP had the highest incremental value; adding other parameters did not yield further improvements. While ASBP was an independent risk factor for cardiovascular disease, addition to FRS led to only small increases to the overall model fit, discrimination (a 1% increase in the area under the receiver operating characteristic (ROC) curve), calibration and reclassification. We estimated that for every 10 000 men screened with ASBP, 141 fewer would start a new BP-lowering treatment (95% CI 62 to 220 less treated), but this would result in 7 fewer cardiovascular events prevented over the subsequent 10 years (95% CI 21 fewer events prevented to 7 more events prevented). Conclusions: In addition to a standard cardiovascular risk assessment it is not clear that ambulatory BP measurement provides further incremental value. The clinical role of ambulatory BP requires ongoing careful consideration.

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  • 39. Bellavia, Andrea
    et al.
    Wallentin, Lars
    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.
    Orsini, Nicola
    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.
    Cannon, Christopher P
    Himmelmann, Anders
    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.
    Renlund, Henrik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Lytsy, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Social Medicine.
    Time-based measures of treatment effect: reassessment of ticagrelor and clopidogrel from the PLATO trial2017In: Open heart, E-ISSN 2053-3624, Vol. 4, no 2, article id e000557Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: Treatment effects to binary endpoints using time-to-event data in randomised controlled trials are typically summarised by reporting HRs derived with Cox proportional hazard models. Alternative and complementary methods include summarising the between-treatment differences on the metric time scale, quantifying the effect as delay of the event (DoE). The aim of this study was to reassess data from the PLATO study expressing the effects as the time by which the main outcomes are delayed or hastened due to treatment.

    METHODS: PLATO was a randomised controlled double-blind multicentre study (n=18,624), conducted between 2006 and 2008, which demonstrated superiority of the antiplatelet treatment ticagrelor over clopidogrel in reducing risk of several cardiovascular events. In the present study, four of the main PLATO outcomes were reassessed by calculating the time by which an event may be delayed due to the treatment.

    RESULTS: The effects of ticagrelor, as compared with clopidogrel, consisted of a substantial delay of the evaluated outcomes, ranging from 83 to 98 days over 400-day follow-up. The Delay of Events Curves showed that the effects progressively increased over time, and the significant findings were concordant with those presented in the original PLATO study.

    CONCLUSIONS: This study confirmed evidence of a beneficial effect of ticagrelor over clopidogrel, and provided the magnitude of such effects in terms of delayed event time. Investigating time-to-event data with a percentile approach allows presenting treatment effects from randomised controlled studies as absolute measures of the time by which an event may be delayed due to the treatment.

    TRIAL REGISTRATION NUMBER: PLATO (www.clinicaltrials.gov; NCT00391872); Results.

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  • 40.
    Berglund, Erik
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences.
    Westerling, Ragnar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Social Medicine.
    Sundstrom, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Lytsy, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences.
    Treatment effect expressed as the novel Delay of Event measure is associated with high willingness to initiate preventive treatment - A randomized survey experiment comparing effect measures2016In: Patient Education and Counseling, ISSN 0738-3991, E-ISSN 1873-5134, Vol. 99, no 12, p. 2005-2011Article in journal (Refereed)
    Abstract [en]

    Objectives: This study aimed to investigate patients' willingness to initiate a preventive treatment and compared two established effect measures to the newly developed Delay of Events (DoE) measure that expresses treatment effect as a gain in event-free time. Methods: In this cross-sectional, randomized survey experiment in the general Swedish population, 1079 respondents (response rate 60.9%) were asked to consider a preventive cardiovascular treatment. Respondents were randomly allocated to one of three effect descriptions: DoE, relative risk reduction (RRR), or absolute risk reduction (ARR). Univariate and multivariate analyses were performed investigating willingness to initiate treatment, views on treatment benefit, motivation and importance to adhere and willingness to pay for treatment. Results: Eighty-one percent were willing to take the medication when the effect was described as DoE, 83.0% when it was described as RRR and 62.8% when it was described as ARR. DoE and RRR was further associated with positive views on treatment benefit, motivation, importance to adhere and WTP. Conclusions: Presenting treatment effect as DoE or RRR was associated with a high willingness to initiate treatment. Practice implications: An approach based on the novel time-based measure DoE may be of value in clinical communication and shared decision making.

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  • 41.
    Berglund, Erik
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Social Medicine.
    Westerling, Ragnar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Social Medicine.
    Sundström, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Epidemiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Lytsy, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Social Medicine.
    Length of time periods in treatment effect descriptions and willingness to initiate preventive therapy: a randomised survey experiment2018In: BMC Medical Informatics and Decision Making, E-ISSN 1472-6947, Vol. 18, article id 106Article in journal (Refereed)
    Abstract [en]

    Background Common measures used to describe preventive treatment effects today are proportional, i.e. they compare the proportions of events in relative or absolute terms, however they are not easily interpreted from the patient's perspective and different magnitudes do not seem to clearly discriminate between levels of effect presented to people. Methods In this randomised cross-sectional survey experiment, performed in a Swedish population-based sample (n=1041, response rate 58.6%), the respondents, aged between 40 and 75years were given information on a hypothetical preventive cardiovascular treatment. Respondents were randomised into groups in which the treatment was described as having the effect of delaying a heart attack for different periods of time (Delay of Event,DoE): 1month, 6months or 18months. Respondents were thereafter asked about their willingness to initiate such therapy, as well as questions about how they valued the proposed therapy. ResultsLonger DoE:s were associated with comparatively greater willingness to initiate treatment. The proportions accepting treatment were 81, 71 and 46% when postponement was 18months, 6months and 1month respectively. In adjusted binary logistic regression models the odds ratio for being willing to take therapy was 4.45 (95% CI 2.72-7.30) for a DoE of 6months, and 6.08 (95% CI 3.61-10.23) for a DoE of 18months compared with a DoE of 1month. Greater belief in the necessity of medical treatment increased the odds of being willing to initiate therapy. ConclusionsLay people's willingness to initiate preventive therapy was sensitive to the magnitude of the effect presented as DoE. The results indicate that DoE is a comprehensible effect measure, of potential value in shared clinical decision-making.

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  • 42.
    Bergqvist, Rita
    et al.
    Karolinska Inst, Dept Global Publ Hlth, Stockholm, Sweden..
    Ahlqvist, Viktor H.
    Karolinska Inst, Dept Global Publ Hlth, Stockholm, Sweden..
    Lundberg, Michael
    Karolinska Inst, Dept Global Publ Hlth, Stockholm, Sweden.;Reg Stockholm, Ctr Epidemiol & Community Med, Stockholm, Sweden..
    Hergens, Maria-Pia
    Karolinska Inst, Dept Global Publ Hlth, Stockholm, Sweden.;Reg Stockholm, Dept Communicable Dis Control & Prevent, Stockholm, Sweden..
    Sundström, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Epidemiology. Univ New South Wales, George Inst Global Hlth, Sydney, NSW, Australia..
    Bell, Max
    Karolinska Univ Hosp, Dept Perioperat Med & Intens Care, Stockholm, Sweden.;Karolinska Inst, Dept Physiol & Pharmacol, Stockholm, Sweden..
    Magnusson, Cecilia
    Karolinska Inst, Dept Global Publ Hlth, Stockholm, Sweden.;Reg Stockholm, Ctr Epidemiol & Community Med, Stockholm, Sweden..
    HMG-CoA reductase inhibitors and COVID-19 mortality in Stockholm, Sweden: A registry-based cohort study2021In: PLoS Medicine, ISSN 1549-1277, E-ISSN 1549-1676, Vol. 18, no 10, article id e1003820Article in journal (Refereed)
    Abstract [en]

    Background: The relationship between statin treatment and Coronavirus Disease 2019 (COVID-19) mortality has been discussed due to the pleiotropic effects of statins on coagulation and immune mechanisms. However, available observational studies are hampered by study design flaws, resulting in substantial heterogeneity and ambiguities. Here, we aim to determine the relationship between statin treatment and COVID-19 mortality.

    Methods and findings: This cohort study included all Stockholm residents aged 45 or older (N = 963,876), followed up from 1 March 2020 until 11 November 2020. The exposure was statin treatment initiated before the COVID-19-pandemic, defined as recorded statin dispensation in the Swedish Prescribed Drug Register between 1 March 2019 and 29 February 2020. COVID-19-specific mortality was ascertained from the Swedish Cause of Death Registry. Hazard ratios (HRs) were calculated using multivariable Cox regression models. We further performed a target trial emulation restricted to initiators of statins.In the cohort (51.6% female), 169,642 individuals (17.6%) were statin users. Statin users were older (71.0 versus 58.0 years), more likely to be male (53.3% versus 46.7%), more often diagnosed with comorbidities (for example, ischemic heart disease 23.3% versus 1.6%), more frequently on anticoagulant and antihypertensive treatments, less likely to have a university-level education (34.5% versus 45.4%), and more likely to have a low disposable income (20.6% versus 25.2%), but less likely to reside in crowded housing (6.1% versus 10.3%).A total of 2,545 individuals died from COVID-19 during follow-up, including 765 (0.5%) of the statin users and 1,780 (0.2%) of the nonusers. Statin treatment was associated with a lowered COVID-19 mortality (adjusted HR, 0.88; 95% CI, 0.79 to 0.97, P = 0.01), and this association did not vary appreciably across age groups, sexes, or COVID-19 risk groups. The confounder adjusted HR for statin treatment initiators was 0.78 (95% CI, 0.59 to 1.05, P = 0.10) in the emulated target trial. Limitations of this study include the observational design, reliance on dispensation data, and the inability to study specific drug regimens.

    Conclusions: Statin treatment had a modest negative association with COVID-19 mortality. While this finding needs confirmation from randomized clinical trials, it supports the continued use of statin treatment for medical prevention according to current recommendations also during the COVID-19 pandemic.

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  • 43.
    Bergstrom, Goran
    et al.
    Sahlgrens Acad, Dept Mol & Clin Med, Gothenburg, Sweden.;Reg Vastra Gotaland, Dept Clin Physiol, Gothenburg, Sweden..
    Persson, Margaretha
    Lund Univ, Dept Clin Sci, Malmö, Sweden.;Skane Univ Hosp, Dept Internal Med, Malmö, Sweden..
    Adiels, Martin
    Univ Gothenburg, Inst Med, Sch Publ Hlth & Community Med, Gothenburg, Sweden..
    Bjornson, Elias
    Sahlgrens Acad, Dept Mol & Clin Med, Gothenburg, Sweden..
    Bonander, Carl
    Univ Gothenburg, Inst Med, Sch Publ Hlth & Community Med, Gothenburg, Sweden..
    Ahlström, Håkan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Alfredsson, Joakim
    Linköping Univ, Dept Cardiol Hlth Med & Caring Sci, Linköping, Sweden..
    Angeras, Oskar
    Sahlgrens Acad, Dept Mol & Clin Med, Gothenburg, Sweden.;Reg Vastra Gotaland, Dept Cardiol, Gothenburg, Sweden..
    Berglund, Goran
    Lund Univ, Dept Clin Sci, Malmö, Sweden..
    Blomberg, Anders
    Umeå Univ, Dept Publ Hlth & Clin Med Med, Umeå, Sweden.;Umeå Univ, Heart Ctr, Umeå, Sweden..
    Brandberg, John
    Sahlgrens Acad, Dept Radiol, Inst Clin Sci, Gothenburg, Sweden.;Reg Vastra Gotaland, Dept Radiol, Gothenburg, Sweden..
    Borjesson, Mats
    Sahlgrens Acad, Inst Med, Gothenburg, Sweden.;Univ Gothenburg, Ctr Hlth & Performance, Gothenburg, Sweden.;Sahlgrens Univ Hosp, Reg Vastra Gotaland, Gothenburg, Sweden..
    Cederlund, Kerstin
    Karolinska Inst, Dept Clin Sci Intervent & Technol, Stockholm, Sweden..
    de Faire, Ulf
    Karolinska Inst, Inst Environm Med, Unit Cardiovasc & Nutr Epidemiol, Stockholm, Sweden..
    Duvernoy, Olov
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology. Olov.Duvernoy@radiol.uu.se.
    Ekblom, Orjan
    Swedish Sch Sport & Hlth Sci GIH, Dept Phys Act & Hlth, Stockholm, Sweden..
    Engstrom, Gunnar
    Lund Univ, Dept Clin Sci, Malmö, Sweden..
    Engvall, Jan E.
    Linköping Univ, Dept Cardiol Hlth Med & Caring Sci, Linköping, Sweden.;Linköping Univ, Dept Clin Physiol, Linköping, Sweden.;Linköping Univ, CMIV, Ctr Med Image Sci & Visualizat, Linköping, Sweden..
    Fagman, Erika
    Sahlgrens Acad, Dept Radiol, Inst Clin Sci, Gothenburg, Sweden.;Reg Vastra Gotaland, Dept Radiol, Gothenburg, Sweden..
    Eriksson, Mats
    Karolinska Univ Hosp Huddinge, Dept Endocrinol Metab & Diabet, Stockholm, Sweden.;Karolinska Univ Hosp Huddinge, Clin Res Ctr, Stockholm, Sweden..
    Erlinge, David
    Lund Univ, Cardiol, Dept Clin Sci Lund, Lund, Sweden.;Skane Univ Hosp, Lund, Sweden..
    Fagerberg, Bjorn
    Sahlgrens Acad, Dept Mol & Clin Med, Gothenburg, Sweden.;Sahlgrens Univ Hosp, Reg Vastra Gotaland, Gothenburg, Sweden..
    Flinck, Agneta
    Sahlgrens Acad, Dept Radiol, Inst Clin Sci, Gothenburg, Sweden.;Reg Vastra Gotaland, Dept Radiol, Gothenburg, Sweden..
    Goncalves, Isabel
    Lund Univ, Dept Clin Sci Malmö, Lund, Sweden..
    Hagström, Emil
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Disciplinary Domain of Medicine and Pharmacy, research centers etc., Uppsala Clinical Research Center (UCR). Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Hjelmgren, Ola
    Sahlgrens Acad, Dept Mol & Clin Med, Gothenburg, Sweden.;Reg Vastra Gotaland, Dept Clin Physiol, Gothenburg, Sweden..
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Epidemiology.
    Lindberg, Eva
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Lung- allergy- and sleep research.
    Lindqvist, Per
    Umeå Univ, Dept Surg & Perioperat Sci, Umeå, Sweden..
    Ljungberg, Johan
    Umeå Univ, Dept Publ Hlth & Clin Med Med, Umeå, Sweden.;Umeå Univ, Heart Ctr, Umeå, Sweden..
    Magnusson, Martin
    Lund Univ, Dept Clin Sci, Malmö, Sweden.;Skane Univ Hosp, Dept Cardiol, Malmö, Sweden.;Lund Univ, Wallenberg Ctr Mol Med, Lund, Sweden.;North West Univ, Hypertens Africa Res Team HART, Potchefstroom, South Africa..
    Mannila, Maria
    Karolinska Univ Hosp, Dept Cardiol & Clin Genet, Heart & Vasc Theme, Stockholm, Sweden..
    Markstad, Hanna
    Lund Univ, Clin Sci Malmö, Clin Res Ctr, Expt Cardiovasc Res, Malmö, Sweden.;Lund Univ, Ctr Med Imaging & Physiol, Lund, Sweden..
    Mohammad, Moman A.
    Lund Univ, Cardiol, Dept Clin Sci Lund, Lund, Sweden.;Skane Univ Hosp, Lund, Sweden..
    Nystrom, Fredrik H.
    Linköping Univ, Dept Cardiol Hlth Med & Caring Sci, Linköping, Sweden..
    Ostenfeld, Ellen
    Skane Univ Hosp, Lund, Sweden.;Lund Univ, Dept Clin Sci Lund, Clin Physiol, Lund, Sweden..
    Persson, Anders
    Linköping Univ, Dept Cardiol Hlth Med & Caring Sci, Linköping, Sweden.;Linköping Univ, Dept Radiol, Linköping, Sweden.;Linköping Univ, CMIV, Ctr Med Image Sci & Visualizat, Linköping, Sweden..
    Rosengren, Annika
    Sahlgrens Acad, Dept Mol & Clin Med, Gothenburg, Sweden.;Sahlgrens Univ Hosp, Reg Vastra Gotaland, Gothenburg, Sweden..
    Sandstrom, Anette
    Umeå Univ, Dept Publ Hlth & Clin Med Med, Umeå, Sweden.;Umeå Univ, Heart Ctr, Umeå, Sweden..
    Sjalander, Anders
    Umeå Univ, Dept Publ Hlth & Clin Med Med, Umeå, Sweden.;Umeå Univ, Heart Ctr, Umeå, Sweden..
    Skold, Magnus C.
    Karolinska Inst, Dept Med Solna, Resp Med Unit, Stockholm, Sweden.;Karolinska Inst, Ctr Mol Med, Stockholm, Sweden.;Karolinska Univ Hosp Solna, Dept Resp Med & Allergy, Stockholm, Sweden..
    Sundström, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Epidemiology. Univ New South Wales, George Inst Global Hlth, Sydney, NSW, Australia..
    Swahn, Eva
    Linköping Univ, Dept Cardiol Hlth Med & Caring Sci, Linköping, Sweden..
    Soderberg, Stefan
    Umeå Univ, Dept Publ Hlth & Clin Med Med, Umeå, Sweden.;Umeå Univ, Heart Ctr, Umeå, Sweden..
    Toren, Kjell
    Univ Gothenburg, Sch Publ Hlth & Community Med, Occupat & Environm Med, Gothenburg, Sweden.;Sahlgrens Univ Hosp, Reg Vastra Gotaland, Gothenburg, Sweden..
    Ostgren, Carl Johan
    Linköping Univ, Dept Cardiol Hlth Med & Caring Sci, Linköping, Sweden.;Linköping Univ, CMIV, Ctr Med Image Sci & Visualizat, Linköping, Sweden..
    Jernberg, Tomas
    Danderyd Hosp, Karolinska Inst, Dept Clin Sci, Stockholm, Sweden..
    Prevalence of Subclinical Coronary Artery Atherosclerosis in the General Population2021In: Circulation, ISSN 0009-7322, E-ISSN 1524-4539, Vol. 144, no 12, p. 916-929Article in journal (Refereed)
    Abstract [en]

    Background: Early detection of coronary atherosclerosis using coronary computed tomography angiography (CCTA), in addition to coronary artery calcification (CAC) scoring, may help inform prevention strategies. We used CCTA to determine the prevalence, severity, and characteristics of coronary atherosclerosis and its association with CAC scores in a general population. Methods: We recruited 30 154 randomly invited individuals age 50 to 64 years to SCAPIS (the Swedish Cardiopulmonary Bioimage Study). The study includes individuals without known coronary heart disease (ie, no previous myocardial infarctions or cardiac procedures) and with high-quality results from CCTA and CAC imaging performed using dedicated dual-source CT scanners. Noncontrast images were scored for CAC. CCTA images were visually read and scored for coronary atherosclerosis per segment (defined as no atherosclerosis, 1% to 49% stenosis, or >= 50% stenosis). External validity of prevalence estimates was evaluated using inverse probability for participation weighting and Swedish register data. Results: In total, 25 182 individuals without known coronary heart disease were included (50.6% women). Any CCTA-detected atherosclerosis was found in 42.1%; any significant stenosis (>= 50%) in 5.2%; left main, proximal left anterior descending artery, or 3-vessel disease in 1.9%; and any noncalcified plaques in 8.3% of this population. Onset of atherosclerosis was delayed on average by 10 years in women. Atherosclerosis was more prevalent in older individuals and predominantly found in the proximal left anterior descending artery. Prevalence of CCTA-detected atherosclerosis increased with increasing CAC scores. Among those with a CAC score >400, all had atherosclerosis and 45.7% had significant stenosis. In those with 0 CAC, 5.5% had atherosclerosis and 0.4% had significant stenosis. In participants with 0 CAC and intermediate 10-year risk of atherosclerotic cardiovascular disease according to the pooled cohort equation, 9.2% had CCTA-verified atherosclerosis. Prevalence estimates had excellent external validity and changed marginally when adjusted to the age-matched Swedish background population. Conclusions: Using CCTA in a large, random sample of the general population without established disease, we showed that silent coronary atherosclerosis is common in this population. High CAC scores convey a significant probability of substantial stenosis, and 0 CAC does not exclude atherosclerosis, particularly in those at higher baseline risk.

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  • 44.
    Bergstrom, Goran
    et al.
    Univ Gothenburg, Inst Med, Sahlgrenska Acad, Dept Mol & Clin Med, Gothenburg, Sweden.;Sahlgrens Univ Hosp, Clin Physiol, Gothenburg, Sweden..
    Rosengren, Annika
    Univ Gothenburg, Inst Med, Sahlgrenska Acad, Dept Mol & Clin Med, Gothenburg, Sweden.;Sahlgrenska Univ Hosp Ostra Hosp, Dept Med Geriatr & Emergency Med, Gothenburg, Sweden..
    Brolin, Elin Bacsovics
    Karolinska Inst, Dept Clin Sci Intervent & Technol, Stockholm, Sweden.;Capio St Goran Hosp, Dept Radiol, Stockholm, Sweden..
    Brandberg, John
    Univ Gothenburg, Inst Clin Sci, Sahlgrenska Acad, Dept Radiol, Gothenburg, Sweden.;Sahlgrens Univ Hosp, Dept Radiol, Gothenburg, Sweden..
    Cederlund, Kerstin
    Karolinska Inst, Dept Clin Sci Intervent & Technol, Stockholm, Sweden..
    Engstrom, Gunnar
    Lund Univ, Dept Clin Sci Malmö, Malmö, Sweden..
    Engvall, Jan E.
    Linköping Univ, Ctr Med Image Sci & Visualizat, CMIV, Linköping, Sweden.;Linköping Univ, Dept Clin Physiol, Linköping, Sweden.;Linköping Univ, Dept Hlth Med & Caring Sci, Linköping, Sweden..
    Eriksson, Maria J.
    Karolinska Inst, Dept Mol Med & Surg, Stockholm, Sweden.;Karolinska Univ Hosp, Dept Clin Physiol, Stockholm, Sweden..
    Goncalves, Isabel
    Skane Univ Hosp, Dept Cardiol, Malmö, Sweden.;Lund Univ, Dept Clin Sci Malmö, Cardiovasc Res Translat Studies, Malmö, Sweden..
    Hagström, Emil
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Disciplinary Domain of Medicine and Pharmacy, research centers etc., Uppsala Clinical Research Center (UCR).
    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, Disciplinary Domain of Medicine and Pharmacy, research centers etc., Uppsala Clinical Research Center (UCR).
    Jernberg, Tomas
    Danderyd Hosp, Karolinska Inst, Dept Clin Sci, Stockholm, Sweden..
    Lilja, Mikael
    Umeå Univ, Östersund Hosp, Dept Publ Hlth & Clin Med, Unit Res Educ & Dev, Umeå, Sweden..
    Magnusson, Martin
    Lund Univ, Dept Clin Sci Malmö, Malmö, Sweden.;Skane Univ Hosp, Dept Cardiol, Malmö, Sweden.;Lund Univ, Wallenberg Ctr Mol Med, Lund, Sweden.;North West Univ, Hypertens Africa Res Team HART, Potchefstroom, South Africa..
    Persson, Anders
    Linköping Univ, Ctr Med Image Sci & Visualizat, CMIV, Linköping, Sweden.;Linköping Univ, Dept Hlth Med & Caring Sci, Linköping, Sweden.;Linköping Univ, Dept Radiol, Linköping, Sweden.;Karolinska Inst, Huddinge Univ Hosp, Dept Clin Sci, Stockholm, Sweden..
    Persson, Margaretha
    Lund Univ, Dept Clin Sci Malmö, Malmö, Sweden.;Skane Univ Hosp, Dept Internal Med, Malmö, Sweden..
    Sandstrom, Anette
    Umeå Univ, Heart Ctr, Umeå, Sweden.;Umeå Univ, Dept Publ Hlth & Clin Med, Umeå, Sweden..
    Schmidt, Caroline
    Univ Gothenburg, Inst Med, Sahlgrenska Acad, Dept Mol & Clin Med, Gothenburg, Sweden..
    Larsson, Linn Skoglund
    Umeå Univ, Dept Publ Hlth & Clin Med, Umeå, Sweden..
    Sundström, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences. Univ New South Wales, George Inst Global Hlth, Sydney, Australia..
    Swahn, Eva
    Linköping Univ, Dept Hlth Med & Caring Sci, Linköping, Sweden.;Linköping Univ, Dept Cardiol, Linköping, Sweden..
    Soderberg, Stefan
    Umeå Univ, Dept Publ Hlth & Clin Med, Umeå, Sweden..
    Toren, Kjell
    Univ Gothenburg, Sahlgrenska Acad, Sch Publ Hlth & Community Med, Inst Med,Sect Occupat & Environm Med, Gothenburg, Sweden.;Sahlgrens Univ Hosp, Dept Occupat & Environm Med, Gothenburg, Sweden..
    Ostgren, Carl Johan
    Linköping Univ, Ctr Med Image Sci & Visualizat, CMIV, Linköping, Sweden.;Linköping Univ, Dept Hlth Med & Caring Sci, Linköping, Sweden..
    Lampa, Erik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Occupational and Environmental Medicine. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Disciplinary Domain of Medicine and Pharmacy, research centers etc., Uppsala Clinical Research Center (UCR). Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Epidemiology.
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Body weight at age 20 and in midlife is more important than weight gain for coronary atherosclerosis: Results from SCAPIS2023In: Atherosclerosis, ISSN 0021-9150, E-ISSN 1879-1484, Vol. 373, p. 46-54Article in journal (Refereed)
    Abstract [en]

    Background and aims: Elevated body weight in adolescence is associated with early cardiovascular disease, but whether this association is traceable to weight in early adulthood, weight in midlife or to weight gain is not known. The aim of this study is to assess the risk of midlife coronary atherosclerosis being associated with body weight at age 20, body weight in midlife and body weight change.

    Methods: We used data from 25,181 participants with no previous myocardial infarction or cardiac procedure in the Swedish CArdioPulmonary bioImage Study (SCAPIS, mean age 57 years, 51% women). Data on coronary atherosclerosis, self-reported body weight at age 20 and measured midlife weight were recorded together with potential confounders and mediators. Coronary atherosclerosis was assessed using coronary computed tomog-raphy angiography (CCTA) and expressed as segment involvement score (SIS).

    Results: The probability of having coronary atherosclerosis was markedly higher with increasing weight at age 20 and with mid-life weight (p < 0.001 for both sexes). However, weight increase from age 20 until mid-life was only modestly associated with coronary atherosclerosis. The association between weight gain and coronary atherosclerosis was mainly seen in men. However, no significant sex difference could be detected when adjusting for the 10-year delay in disease development in women.

    Conclusions: Similar in men and women, weight at age 20 and weight in midlife are strongly related to coronary atherosclerosis while weight increase from age 20 until midlife is only modestly related to coronary atherosclerosis.

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  • 45. Bergström, G
    et al.
    Berglund, G
    Blomberg, A
    Brandberg, J
    Engström, G
    Engvall, J
    Eriksson, M
    de Faire, U
    Flinck, A
    Hansson, Mats G
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Centre for Research Ethics and Bioethics.
    Hedblad, B
    Hjelmgren, O
    Janson, Christer
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Jernberg, T
    Johnsson, Å
    Johansson, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Löfdahl, C-G
    Melander, O
    Östgren, C J
    Persson, A
    Persson, M
    Sandström, A
    Schmidt, C
    Söderberg, S
    Sundström, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Toren, K
    Waldenström, A
    Wedel, H
    Vikgren, J
    Fagerberg, B
    Rosengren, A
    The Swedish CArdioPulmonary BioImage Study: objectives and design2015In: Journal of Internal Medicine, ISSN 0954-6820, E-ISSN 1365-2796, Vol. 278, no 6, p. 645-659Article in journal (Refereed)
    Abstract [en]

    Cardiopulmonary diseases are major causes of death worldwide, but currently recommended strategies for diagnosis and prevention may be outdated because of recent changes in risk factor patterns. The Swedish CArdioPulmonarybioImage Study (SCAPIS) combines the use of new imaging technologies, advances in large-scale 'omics' and epidemiological analyses to extensively characterize a Swedish cohort of 30 000 men and women aged between 50 and 64 years. The information obtained will be used to improve risk prediction of cardiopulmonary diseases and optimize the ability to study disease mechanisms. A comprehensive pilot study in 1111 individuals, which was completed in 2012, demonstrated the feasibility and financial and ethical consequences of SCAPIS. Recruitment to the national, multicentre study has recently started.

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  • 46.
    Bixby, Honor
    et al.
    Imperial College London, London, UK.
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Epidemiology.
    Lytsy, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Social Medicine.
    Sundström, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Epidemiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Yngve, Agneta
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Food, Nutrition and Dietetics.
    Ezzati, Majid
    Imperial College London, London, UK.
    Rising rural body-mass index is the main driver of the global obesity epidemic in adults2019In: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 569, no 7755, p. 260-264Article in journal (Other academic)
    Abstract [en]

    Body-mass index (BMI) has increased steadily in most countries in parallel with a rise in the proportion of the population who live in cities1,2. This has led to a widely reported view that urbanization is one of the most important drivers of the global rise in obesity3,4,5,6. Here we use 2,009 population-based studies, with measurements of height and weight in more than 112 million adults, to report national, regional and global trends in mean BMI segregated by place of residence (a rural or urban area) from 1985 to 2017. We show that, contrary to the dominant paradigm, more than 55% of the global rise in mean BMI from 1985 to 2017-and more than 80% in some low- and middle-income regions-was due to increases in BMI in rural areas. This large contribution stems from the fact that, with the exception of women in sub-Saharan Africa, BMI is increasing at the same rate or faster in rural areas than in cities in low- and middle-income regions. These trends have in turn resulted in a closing-and in some countries reversal-of the gap in BMI between urban and rural areas in low- and middle-income countries, especially for women. In high-income and industrialized countries, we noted a persistently higher rural BMI, especially for women. There is an urgent need for an integrated approach to rural nutrition that enhances financial and physical access to healthy foods, to avoid replacing the rural undernutrition disadvantage in poor countries with a more general malnutrition disadvantage that entails excessive consumption of low-quality calories.

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  • 47. Bodegard, J.
    et al.
    Sundström, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences.
    Svennblad, Bodil
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Östgren, C. J.
    Nilsson, P. M.
    Johansson, Gunnar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Family Medicine and Preventive Medicine.
    Changes in body mass index following newly diagnosed type 2 diabetes and risk of cardiovascular mortality: A cohort study of 8486 primary-care patients2013In: Diabetes & Metabolism, ISSN 1262-3636, E-ISSN 1878-1780, Vol. 39, no 4, p. 306-313Article in journal (Refereed)
    Abstract [en]

    Aims

    Elevated body mass index (BMI) is associated with an increased risk of type 2 diabetes and cardiovascular disease (CVD). This study explored the association between BMI changes in the first 18 months of newly diagnosed type 2 diabetes and the risk of long-term CVD mortality.

    Methods

    A total of 8486 patients with newly diagnosed type 2 diabetes and no previous history of CVD or cancer were identified from 84 primary-care centres in Sweden. During the first year after diagnosis, patients were grouped according to BMI change: 'Increase', or >= +1 BMI unit; 'unchanged', or between +1 and-1 BMI unit; and 'decrease', or <=-1 BMI unit. Associations between BMI change and CVD mortality, defined as death from stroke, myocardial infarction or sudden death, were estimated using adjusted Cox proportional hazards models (NCT 01121315).

    Results

    Baseline mean age was 60.0 years and mean BMI was 30.2 kg/m(2). Patients were followed for up to 9 years (median: 4.6 years). During the first 18 months, 53.4% had no change in their BMI, while 32.2% decreased and 14.4% increased. Compared with patients with unchanged BMI, those with an increased BMI had higher risks of CVD mortality (hazard ratio: 1.63, 95% CI: 1.11-2.39) and all-cause mortality (1.33, 1.01-1.76). BMI decreases had no association with these risks compared with unchanged BMI: 1.06 (0.76-1.48) and 1.06 (0.85-1.33), respectively.

    Conclusion

    Increased BMI within the first 18 months of type 2 diabetes diagnosis was associated with an increased long-term risk of CVD mortality. However, BMI decrease did not lower the long-term risk of mortality.

  • 48.
    Boden, Robert
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Psychiatry, University Hospital.
    Molin, E.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Psychiatry, University Hospital.
    Jernberg, T.
    Kieler, H.
    Lindahl, Bertil
    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, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Higher mortality after myocardial infarction in patients with severe mental illness: a nationwide cohort study2015In: Journal of Internal Medicine, ISSN 0954-6820, E-ISSN 1365-2796, Vol. 277, no 6, p. 727-736Article in journal (Refereed)
    Abstract [en]

    ObjectivesThe aim of this study was to explore the impact of severe mental illness (SMI) on myocardial infarction survival and determine the influence of risk factor burden, myocardial infarction severity and different treatments. Design, setting and participantsThis population-based cohort study, conducted in Sweden during the period 1997-2010, included all patients with a first diagnosis of myocardial infarction in the Swedish nationwide myocardial infarction register SWEDEHEART (n=209592). Exposure was defined as a diagnosis of SMI (i.e. bipolar disorder or schizophrenia) in the national patient register prior to infarction. Bias-minimized logistic regression models were identified using directed acyclic graphs and included covariates age, gender, smoking, diabetes, previous cardiovascular disease, myocardial infarction characteristics and treatment. Main outcome measuresThe outcomes were 30-day and 1-year mortality, obtained through linkage with national population registers. ResultsPatients with bipolar disorder (n=442) and schizophrenia (n=541) were younger (mean age 68 and 63years, respectively) than those without SMI (n=208609; mean age 71years). The overall 30-day and 1-year mortality rates were 10% and 18%, respectively. Compared with patients without SMI, patients with SMI had higher 30-day [odds ratio (OR) 1.99, 95% confidence interval (CI) 1.55-2.56] and 1-year mortality (OR 2.11, 95% CI 1.74-2.56) in the fully adjusted model. The highest mortality was observed amongst patients with schizophrenia (30-day mortality: OR 2.58, 95% CI 1.88-3.54; 1-year mortality: OR 2.55, 95% CI 1.98-3.29). ConclusionSMI is associated with a markedly higher mortality after myocardial infarction, also after accounting for contributing factors. It is imperative to identify the reasons for this higher mortality.

  • 49. Boden, Robert
    et al.
    Molina, E.
    Jernberg, T.
    Kieler, H.
    Lindahl, Bertil
    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, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Myocardial infarction survival in patients with bipolar disorder or schizophrenia spectrum disorders- a nationwide cohort study2014In: Bipolar Disorders, ISSN 1398-5647, E-ISSN 1399-5618, Vol. 16, p. 62-63Article in journal (Other academic)
  • 50.
    Bodén, Robert
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Psychiatry, University Hospital.
    Lindström, Leif
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Psychiatry, University Hospital.
    Rautaharju, Pentti
    Wake Forest Univ, Dept Epidemiol & Prevent, Div Publ Hlth Sci, Winston Salem, NC 27109 USA.
    Sundström, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Internal Medicine.
    Electrocardiographic signs of autonomic imbalance in medicated patients with first-episode schizophrenia spectrum disorders: relations to first treatment discontinuation and five-year remission status2012In: European psychiatry, ISSN 0924-9338, E-ISSN 1778-3585, Vol. 27, no 3, p. 213-218Article in journal (Refereed)
    Abstract [en]

    PURPOSE:

    To explore measures in electrocardiograms (ECG) influenced by autonomic balance in early schizophrenia spectrum disorders and to examine their relation to subsequent first antipsychotic pharmacotherapy discontinuation and five-year remission status.

    SUBJECTS AND METHODS:

    Twelve-lead ECGs were recorded at baseline in 58 patients with first-episode schizophrenia spectrum disorders and in 47 healthy controls of similar age. Selected ECG variables included heart rate and measures of repolarization. Pharmacotherapy data were extracted from medical records. At a five-year follow-up the patients were interviewed and assessed with the Positive and Negative Syndrome Scale.

    RESULTS:

    Patients had higher heart rate and a different ST-T pattern than the controls. High T-wave amplitudes in the leads aVF and V5 and ST-elevations in V5 were associated both with higher risk of an earlier discontinuation of first antipsychotic pharmacotherapy and with non-remission five years later.

    DISCUSSION AND CONCLUSION:

    In this longitudinal cohort study, simple ECG measures influenced by autonomic balance in the early phase of schizophrenia spectrum disorders contained prognostic information. As this is the first report of this association and is based on a relatively small sample, the results should be interpreted with caution.

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