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  • 1.
    Agarwal, Anubha
    et al.
    Washington Univ St Louis, Sch Med, St Louis, MO 63110 USA..
    Tromp, Jasper
    Natl Univ Singapore, Saw Swee Hock Sch Publ Hlth, Singapore, Singapore.;Natl Univ Hlth Syst, Singapore, Singapore..
    Almahmeed, Wael
    Cleveland Clin, Heart & Vasc Inst, Abu Dhabi, U Arab Emirates..
    Angermann, Christiane
    Univ Hosp Wuerzburg, Comprehens Heart Failure Ctr, Wurzburg, Germany..
    Chandramouli, Chanchal
    Natl Heart Ctr Singapore, Singapore, Singapore.;Duke NUS Med Sch, Singapore, Singapore..
    Cho, Hyunjai
    Seoul Natl Univ Hosp, Seoul, South Korea..
    Choi, Don-Ju
    Seoul Natl Univ Hosp, Seoul, South Korea..
    Damasceno, Albertino
    Eduardo Mondlane Univ, Maputo, Mozambique..
    Filippatos, Gerasimos
    Univ Cyprus, Sch Med, Nicosia, Cyprus.;Natl & Kapodistrian Univ Athens, Attikon Univ Hosp, Sch Med, Dept Cardiol, Athens, Greece..
    Fonarow, Gregg C.
    Ronald Reagan UCLA Med Ctr, Radiol, Los Angeles, CA USA..
    Harikrishnan, Sivadasanpillai
    Sree Chitra Tirunal Inst Med Sci & Technol, Trivandrum, Kerala, India..
    Lund, Lars
    Karolinska Univ Hosp, Stockholm, Sweden..
    Masoudi, Fred
    Univ Colorado, Sch Med, Anschutz Med Campus, Aurora, CO 80045 USA..
    Mensah, George A.
    NHLBI, NIH, Ctr Translat Res & Implementat Sci, Bethesda, MD USA..
    Pathan, Asad
    Tabba Heart Inst, Karachi, Pakistan..
    Perel, Pablo
    London Sch Hyg & Trop Med, London, England..
    Pinto, Fausto
    Univ Lisbon, Santa Maria Univ Hosp, Lisbon, Portugal..
    Ribeiro, Antonio Luiz
    Unversidade Fed Minas Gerais, Hosp Clin, Belo Horizonte, Brazil.;Unversidade Fed Minas Gerais, Sch Med, Belo Horizonte, Brazil..
    Rich, Stuart
    Northwestern Univ, Feinberg Sch Med, Chicago, IL USA..
    Sakata, Yasuhiko
    Tohoku Univ, Grad Sch Med, Sendai, Japan.;Natl Cerebral & Cardiovasc Ctr, Cardiovasc Surg, Suita, Japan..
    Sliwa, Karen
    Univ Cape Town, Cape Town, South Africa..
    Sundström, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Epidemiology.
    Wong, Renee
    NHLBI, NIH, Div Cardiovasc Sci, Heart Failure & Arrhythmias Branch, Bethesda, MD USA..
    Yancy, Clyde
    Northwestern Univ, Feinberg Sch Med, Chicago, IL USA..
    Yiu, Kelvin
    Univ Hong Kong, Inst Cardiovasc Sci & Med, Hong Kong, Peoples R China.;Univ Hong Kong, Shenzhen Hosp, Dept Med, Hong Kong, Peoples R China..
    Zhang, Jian
    Chinese Acad Med Sci & Peking Union Med Coll, Beijing, Peoples R China..
    Zhang, Yuhui
    Chinese Acad Med Sci & Peking Union Med Coll, Beijing, Peoples R China..
    Lam, Carolyn S. P.
    Natl Heart Ctr, Singapore, Singapore.;Duke NUS Med Sch, Singapore, Singapore.;Univ Med Ctr Groningen, Groningen, Netherlands..
    Roth, Gregory A.
    Univ Washington, Seattle, DC USA.;Populat Hlth Bldg Hans Rosling Ctr, Inst Hlth Metr & Evaluat, 3980 15th Ave NE, Seattle, WA 98195 USA..
    Toward a Universal Definition of Etiologies in Heart Failure: Categorizing Causes and Advancing Registry Science2024In: Circulation Heart Failure, ISSN 1941-3289, E-ISSN 1941-3297, Vol. 17, no 4, article id e011095Article, review/survey (Refereed)
    Abstract [en]

    Heart failure (HF) is a well-described final common pathway for a broad range of diseases however substantial confusion exists regarding how to describe, study, and track these underlying etiologic conditions. We describe (1) the overlap in HF etiologies, comorbidities, and case definitions as currently used in HF registries led or managed by members of the global HF roundtable; (2) strategies to improve the quality of evidence on etiologies and modifiable risk factors of HF in registries; and (3) opportunities to use clinical HF registries as a platform for public health surveillance, implementation research, and randomized registry trials to reduce the global burden of noncommunicable diseases. Investment and collaboration among countries to improve the quality of evidence in global HF registries could contribute to achieving global health targets to reduce noncommunicable diseases and overall improvements in population health.

  • 2.
    Ahlstedt, Carina
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Health Services Research.
    Eriksson Lindvall, Carin
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Business Studies.
    Holmström, Inger
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Health Services Research. School of Health, Care and Social Welfare, Mälardalen University, Västerås, Sweden.
    Muntlin, Åsa
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Health Services Research. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Epidemiology.
    Flourishing at work: Nurses' motivation through daily communication - An ethnographic approach2020In: Nursing and Health Sciences, ISSN 1441-0745, E-ISSN 1442-2018, Vol. 22, no 4, p. 1169-1176Article in journal (Refereed)
    Abstract [en]

    Shortage and turnover of registered nurses are worldwide challenges, and work motiva-tion is one factor in retaining staff in the healthcare sector. The aim of this study was toexplore registered nurses' motivation expressed in daily communication, using the basicneeds in self-determination theory as a framework. A secondary analysis of ethno-graphic data, collected through participant observations, informal interviews duringobservations, and individual interviews, was used. A total sample of all registered nursesemployed at a hospital unit in Sweden (n = 10) participated. The data were analyzed the-matically through the lens of the basic needs in self-determination theory: autonomy,competence, and relatedness. Self-regulation of learning, the possibilities to discuss work-related challenges with colleagues, and having registered nurses lead dialogues with phy-sicians were factors connected to autonomy. Having a registered nurse and physiciansolve problems together was a factor connected to competence.Asenseofbelongingand security in a permissive climate between registered nurses was co nnected to relat-edness. This paper has implications for increased awareness of the three basic motiva-tional needs, which could be used in the development of attractive workplaces

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  • 3.
    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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  • 4.
    Amritzer, Maria A.
    et al.
    Karolinska Univ Hosp Huddinge OOH, Emergency & Reparat Med Theme, Halsovgen 13, S-14157 Stockholm, Sweden.;Karolinska Inst, Dept Med, Stockholm, Sweden..
    Muntlin, Åsa
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Health Services Research. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Epidemiology. Uppsala Univ Hosp, Dept Emergency Care & Internal Med, Uppsala, Sweden..
    Berg, Lena M.
    Dalarna Univ, Sch Educ Hlth & Social Studies, Falun, Sweden..
    Göransson, Katarina E.
    Karolinska Inst, Dept Med, Stockholm, Sweden.;Karolinska Univ Hosp, Emergency & Reparat Med Theme, Stockholm, Sweden..
    Nursing staff ratio and skill mix in Swedish emergency departments: A national cross-sectional benchmark study2021In: Journal of Nursing Management, ISSN 0966-0429, E-ISSN 1365-2834, Vol. 29, no 8, p. 2594-2602Article in journal (Refereed)
    Abstract [en]

    Aim: The aim of this study is to describe ratio and skill mix for nursing staff in Swedish emergency departments over a specific 24-h period.

    Background: The link between number of patients per nursing staff and missed nursing care is well described within the in-hospital setting, showing association with negative outcomes such as increased mortality. Potential association within the emergency department setting is still unexplored.

    Method: This is a national descriptive cross-sectional benchmark study.

    Results: The majority (n = 54; 89%) of Swedish emergency departments participated. The patients-per-registered nurse ratio varied between the shifts, from 0.3 patients to 8.8 patients (mean 3.2). The variation of patients per licenced practical nurse varied, from 1.5 to 23.5 patients (mean 5.0). The average skill mix was constant at around 60% registered nurses and 40% licenced practical nurses.

    Conclusion: The varying ratios for patient per registered nurse and licenced practical nurse in Swedish emergency departments are noteworthy. Furthermore, the patient flow and nursing staff numbers did not match one another, resulting in higher nursing staff ratios during the evening shift.

    Implications for Nursing Management: Findings can be used to improve rosters in relation to crowding, to manage the challenging recruitment and retention situation for nursing staff and to improve patient safety.

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  • 5. Appelros, Peter
    et al.
    Åsberg, Signild
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Epidemiology.
    Sex differences in stroke.2020In: Handbook of Clinical Neurology, ISSN 0072-9752, E-ISSN 2212-4152, Vol. 175, p. 299-312, article id B978-0-444-64123-6.00021-7Article in journal (Other academic)
    Abstract [en]

    Sex disparities within the field of stroke, including subarachnoid hemorrhages (SAHs), have been in focus during the last 2 decades. It is clear that stroke incidence is higher in men, and also that men have their first stroke earlier than women. On the other hand, women have more severe strokes, mainly because cardioembolic strokes are more common in women. This leads to higher case fatality and worse functional outcome in women. It has often been pointed out that women more often have nontraditional stroke symptoms, and therefore may seek medical help later. After discharge from the hospital, female stroke survivors live alone in many cases and are dependent on external care. Therefore, these women frequently rate their quality of life (QoL) lower than men do. Female spouses more often provide help to their male stroke survivors than the reverse, and they accept a heavier burden. These caregivers are at high risk for depression, low QoL, and low psychologic wellbeing. SAH is a special form of stroke, often caused by a ruptured aneurysm. It is about 20% more common in women. The case fatality is high, but does not differ between the sexes.

  • 6.
    Avallin, Therese
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Nursing Research.
    Muntlin Athlin, Åsa
    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, Faculty of Medicine, Department of Public Health and Caring Sciences, Health Services Research. School of Nursing, University of Adelaide, Australia.
    Björck, Martin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Vascular Surgery.
    Jangland, Eva
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Nursing Research.
    Using communication to manage missed care: A case study applying the Fundamentals of Care framework2020In: Journal of Nursing Management, ISSN 0966-0429, E-ISSN 1365-2834, Vol. 28, no 8, p. 2091-2102Article in journal (Refereed)
    Abstract [en]

    AimTo explore, through the patient's perspective, how patient–provider communication is linked to missed nursing care vs. meeting patients’ fundamental care needs.BackgroundMissed nursing care causes severe consequences for patients. Person-centred fundamental care, in which communication is central, provides an approach to manage this challenge. However, the specific patient–provider communications linked to care outcomes are unknown.MethodsCase study using secondary analysis of observations and interviews. A purposeful sample of 20 patients with acute abdominal pain collected using ethnographic methodology at one emergency department and two surgical wards. The Fundamentals of Care framework guided the analysis.ResultsCommunications that included the patient as an equal member of the care team were observed to make a difference between adequate and missed nursing care. Four categories were identified: interpersonal respect, humanized context of care, available and accessible communication channels, and mutual holistic understanding of the care needs and care plan.ConclusionCommunication can be an essential tool to avoid missed nursing care and address the critical need for nursing managers to restore the fundamentals of care.Implications for Nursing ManagementNursing managers can use this new knowledge of communication to facilitate person-centred fundamental care and thereby avoid missed nursing care.

  • 7.
    Bahls, Martin
    et al.
    Univ Med Greifswald, Dept Internal Med B, Ferdinand Sauerbruch Str, D-17475 Greifswald, Germany.;German Ctr Cardiovasc Res DZHK, Partner Site Greifswald, Greifswald, Germany..
    Lorenz, Matthias W.
    Goethe Univ, Dept Neurol, Frankfurt, Germany..
    Doerr, Marcus
    Univ Med Greifswald, Dept Internal Med B, Ferdinand Sauerbruch Str, D-17475 Greifswald, Germany.;German Ctr Cardiovasc Res DZHK, Partner Site Greifswald, Greifswald, Germany..
    Gao, Lu
    Univ Cambridge, Inst Publ Hlth, MRC Biostat Unit, Univ Forvie Site, Cambridge, England..
    Kitagawa, Kazuo
    Tokyo Womens Med Univ, Dept Neurol, Tokyo, Japan..
    Tuomainen, Tomi-Pekka
    Univ Eastern Finland, Inst Publ Hlth & Clin Nutr, Kuopio Campus, Kuopio, Finland..
    Agewall, Stefan
    Univ Oslo, Inst Clin Sci, Oslo, Norway.;Oslo Univ Hosp Ulleval, Dept Cardiol, Oslo, Norway..
    Berenson, Gerald
    Tulane Univ, Sch Med, Dept Med Pediat Biochem Epidemiol, 1430 Tulane Ave, New Orleans, LA 70112 USA.;Tulane Univ, Sch Publ Hlth & Trop Med, Dept Med Pediat Biochem Epidemiol, New Orleans, LA USA..
    Catapano, Alberico L.
    IRCSS Multimed, Milan, Italy.;Univ Milan, Dept Pharmacol & Biomol Sci, Milan, Italy..
    Norata, Giuseppe D.
    Univ Milan, Dept Pharmacol & Biomol Sci, Milan, Italy.;Bassini Hosp, SISA Ctr Study Atherosclerosis, Cinisello Balsamo, Italy..
    Bots, Michiel L.
    Univ Utrecht, Univ Med Ctr Utrecht, Julius Ctr Hlth Sci & Primary Care, Utrecht, Netherlands..
    van Gilst, Wiek
    Univ Med Ctr Groningen, Dept Expt Cardiol, Groningen, Netherlands..
    Asselbergs, Folkert W.
    Univ Med Ctr Utrecht, Dept Cardiol, Utrecht, Netherlands.;UCL, Inst Cardiovasc Sci, London, England.;UCL, Hlth Data Res UK, London, England.;UCL, Inst Hlth Informat, London, England..
    Brouwers, Frank P.
    Univ Med Ctr Groningen, Dept Cardiol, Groningen, Netherlands..
    Uthoff, Heiko
    Univ Hosp Basel, Dept Angiol, Basel, Switzerland..
    Sander, Dirk
    Benedictus Hosp Tutzing, Dept Neurol, Tutzing, Germany..
    Poppert, Holger
    Tech Univ Munich, Dept Neurol, Munich, Germany..
    Olsen, Michael Hecht
    Univ Southern Denmark, Holbaek Hosp, Dept Internal Med, Odense, Denmark.;Univ Southern Denmark, Inst Reg Hlth Res, Odense, Denmark..
    Empana, Jean Philippe
    Univ Paris, INSERM U970, Paris Cardiovasc Res Ctr, Paris, France..
    Schminke, Ulf
    Univ Med Greifswald, Dept Neurol, Greifswald, Germany..
    Baldassarre, Damiano
    IRCCS, Ctr Cardiol Monzino, Milan, Italy.;Univ Milan, Dept Med Biotechnol & Translat Med, Milan, Italy..
    Veglia, Fabrizio
    IRCCS, Ctr Cardiol Monzino, Milan, Italy..
    Franco, Oscar H.
    Erasmus MC, Dept Epidemiol, Rotterdam, Netherlands.;Univ Bern, ISPM, Bern, Switzerland..
    Kavousi, Maryam
    Erasmus MC, Dept Epidemiol, Rotterdam, Netherlands..
    de Groot, Eric
    Imagelabonline & Cardiovasc, Erichem, Netherlands..
    Mathiesen, Ellisiv B.
    UiT Arctic Univ Norway, Dept Clin Med, Tromso, Norway.;Univ Hosp North Norway, Dept Neurol, Tromso, Norway..
    Grigore, Liliana
    Bassini Hosp, Ctr Sisa Studio Aterosclerosi, Cinisello Balsamo, Italy..
    Polak, Joseph F.
    Tufts Univ, Sch Med, Tufts Med Ctr, Boston, MA 02111 USA..
    Rundek, Tatjana
    Univ Miami, Miller Sch Med, Dept Neurol, Miami, FL 33136 USA..
    Stehouwer, Coen D. A.
    Maastricht Univ, Med Ctr, Dept Internal Med, Maastricht, Netherlands.;Maastricht Univ, Med Ctr, Cardiovasc Res Inst Maastricht CARIM, Maastricht, Netherlands..
    Skilton, Michael R.
    Univ Sydney, Boden Collaborat Obes Nutr Exercise & Eating Diso, Sydney, NSW, Australia..
    Hatzitolios, Apostolos, I
    Aristotle Univ Thessaloniki, Propedeut Dept Internal Med, AHEPA Hosp, Thessaloniki, Greece..
    Savopoulos, Christos
    Aristotle Univ Thessaloniki, Propedeut Dept Internal Med, AHEPA Hosp, Thessaloniki, Greece..
    Ntaios, George
    Univ Thessaly, Fac Med, Sch Hlth Sci, Dept Internal Med, Larisa, Greece..
    Plichart, Matthieu
    Bassini Hosp, Ctr Sisa Studio Aterosclerosi, Cinisello Balsamo, Italy.;Hop Broca, AP HP, Paris, France..
    McLachlan, Stela
    Univ Edinburgh, Usher Inst, Edinburgh, Midlothian, Scotland..
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Epidemiology.
    Willeit, Peter
    Med Univ Innsbruck, Dept Neurol, Innsbruck, Austria.;Univ Cambridge, Sch Clin Med, Dept Publ Hlth & Primary Care, Cambridge, England..
    Steinmetz, Helmuth
    Goethe Univ, Dept Neurol, Frankfurt, Germany..
    Desvarieux, Moise
    Columbia Univ, Mailman Sch Publ Hlth, Dept Epidemiol, New York, NY USA.;INSERM, UMR 1153, Ctr Rech Epidemiol & Stat Paris Sorbonne Cite CRE, METHODS Core, Paris, France..
    Ikram, M. Arfan
    Erasmus MC, Dept Epidemiol, Rotterdam, Netherlands.;Erasmus MC, Dept Neurol, Rotterdam, Netherlands.;Erasmus MC, Dept Radiol, Rotterdam, Netherlands..
    Johnsen, Stein Harald
    UiT Arctic Univ Norway, Dept Clin Med, Tromso, Norway.;Univ Hosp North Norway, Dept Neurol, Tromso, Norway..
    Schmidt, Caroline
    Sahlgrens Acad, Inst Med, Dept Mol & Clin Med, Gothenburg, Sweden..
    Willeit, Johann
    Med Univ Innsbruck, Dept Neurol, Innsbruck, Austria..
    Ducimetiere, Pierre
    Univ Paris Sud Xi, Le Kremlin Bicetre, France..
    Price, Jackie F.
    Univ Edinburgh, Usher Inst, Edinburgh, Midlothian, Scotland..
    Bergstrom, Goran
    Sahlgrens Acad, Inst Med, Dept Mol & Clin Med, Gothenburg, Sweden.;Sahlgrens Univ Hosp, Clin Physiol, Reg Vastra Gotaland, Gothenburg, Sweden..
    Kauhanen, Jussi
    Univ Eastern Finland, Inst Publ Hlth & Clin Nutr, Kuopio Campus, Kuopio, Finland..
    Kiechl, Stefan
    Med Univ Innsbruck, Dept Neurol, Innsbruck, Austria..
    Sitzer, Matthias
    Goethe Univ, Dept Neurol, Frankfurt, Germany.;Klinikum Herford, Dept Neurol, Herford, Germany..
    Bickel, Horst
    Tech Univ Munich, Dept Psychiat & Psychotherapy, Munich, Germany..
    Sacco, Ralph L.
    Univ Miami, Miller Sch Med, Dept Neurol, Miami, FL 33136 USA..
    Hofman, Albert
    Erasmus MC, Dept Epidemiol, Rotterdam, Netherlands.;Harvard TH Chan Sch Publ Hlth, Dept Epidemiol, Boston, MA USA..
    Voelzke, Henry
    German Ctr Cardiovasc Res DZHK, Partner Site Greifswald, Greifswald, Germany.;Univ Med Greifswald, Inst Community Med, SHIP Clin Epidemiol Res, Greifswald, Germany..
    Thompson, Simon G.
    Univ Cambridge, Sch Clin Med, Dept Publ Hlth & Primary Care, Cambridge, England..
    Progression of conventional cardiovascular risk factors and vascular disease risk in individuals: insights from the PROG-IMT consortium2020In: European Journal of Preventive Cardiology, ISSN 2047-4873, E-ISSN 2047-4881, Vol. 27, no 3, p. 234-243Article in journal (Refereed)
    Abstract [en]

    Aims Averaged measurements, but not the progression based on multiple assessments of carotid intima-media thickness, (cIMT) are predictive of cardiovascular disease (CVD) events in individuals. Whether this is true for conventional risk factors is unclear. Methods and results An individual participant meta-analysis was used to associate the annualised progression of systolic blood pressure, total cholesterol, low-density lipoprotein cholesterol and high-density lipoprotein cholesterol with future cardiovascular disease risk in 13 prospective cohort studies of the PROG-IMT collaboration (n = 34,072). Follow-up data included information on a combined cardiovascular disease endpoint of myocardial infarction, stroke, or vascular death. In secondary analyses, annualised progression was replaced with average. Log hazard ratios per standard deviation difference were pooled across studies by a random effects meta-analysis. In primary analysis, the annualised progression of total cholesterol was marginally related to a higher cardiovascular disease risk (hazard ratio (HR) 1.04, 95% confidence interval (CI) 1.00 to 1.07). The annualised progression of systolic blood pressure, low-density lipoprotein cholesterol and high-density lipoprotein cholesterol was not associated with future cardiovascular disease risk. In secondary analysis, average systolic blood pressure (HR 1.20 95% CI 1.11 to 1.29) and low-density lipoprotein cholesterol (HR 1.09, 95% CI 1.02 to 1.16) were related to a greater, while high-density lipoprotein cholesterol (HR 0.92, 95% CI 0.88 to 0.97) was related to a lower risk of future cardiovascular disease events. Conclusion Averaged measurements of systolic blood pressure, low-density lipoprotein cholesterol and high-density lipoprotein cholesterol displayed significant linear relationships with the risk of future cardiovascular disease events. However, there was no clear association between the annualised progression of these conventional risk factors in individuals with the risk of future clinical endpoints.

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  • 8.
    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.
    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.
    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.
    Lindberg, Eva
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Lung- allergy- and sleep research.
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Epidemiology.
    Elmståhl, Sölve
    Department of Clinical Sciences in Malmö, Division of Geriatric Medicine, Lund University, Sweden; CRC, Skåne University Hospital, Malmö, Sweden.
    Theorell-Haglöw, Jenny
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Lung- allergy- and sleep research. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology.
    Evening chronotype is associated with elevated biomarkers of cardiometabolic risk in the EpiHealth cohort: a cross-sectional study2022In: Sleep, ISSN 0161-8105, E-ISSN 1550-9109, Vol. 45, no 2, article id zsab226Article in journal (Refereed)
    Abstract [en]

    Study objectives: Individuals with evening chronotype have a higher risk of cardiovascular and metabolic disorders, although the underlying mechanisms are not well understood. In a population- based cohort, we aimed to investigate the association between chronotype and 242 circulating proteins from three panels of established or candidate biomarkers of cardiometabolic processes. 

    Methods: In 2,471 participants (49.7% men, mean age 61.2±8.4 SD years) from the EpiHealth cohort, circulating proteins were analyzed with a multiplex proximity extension technique. Participants self- reported their chronotype on a five-level scale from extreme morning to extreme evening chronotype. With the intermediate chronotype set as the reference, each protein was added as the dependent variable in a series of linear regression models adjusted for confounders. Next, the chronotype coefficients were jointly tested and the resulting p-values adjusted for multiple testing using false discovery rate (5%). For the associations identified, we then analyzed the marginal effect of each chronotype category. 

    Results: We identified 17 proteins associated with chronotype. Evening chronotype was positively associated with proteins previously linked to insulin resistance and cardiovascular risk, namely retinoic acid receptor protein 2, fatty acid-binding protein adipocyte, tissue-type plasminogen activator, and plasminogen activator inhibitor 1 (PAI-1). Additionally, PAI-1 was inversely associated with the extreme morning chronotype. 

    Conclusions: In this population-based study, proteins previously related with cardiometabolic risk were elevated in the evening chronotypes. These results may guide future research in the relation between chronotype and cardiometabolic disorders. 

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  • 9.
    Baldanzi, Gabriel
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology.
    Sayols-Baixeras, Sergi
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology.
    Ekblom-Bak, Elin
    Ekblom, Örjan
    Dekkers, Koen F.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology.
    Hammar, Ulf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology.
    Nguyen, Diem
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology.
    Ahmad, Shafqat
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology. Preventive Medicine Division, Harvard Medical School, Brigham and Women’s Hospital, Boston, MA, United States.
    Ericson, Ulrika
    Arvidsson, Daniel
    Börjesson, Mats
    Johansson, Peter J.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Occupational and Environmental Medicine. Occupational and Environmental Medicine, Uppsala University Hospital, Uppsala, Sweden.
    Smith, J. Gustav
    Bergström, Göran
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Epidemiology.
    Engström, Gunnar
    Ärnlöv, Johan
    Kennedy, Beatrice
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology.
    Orho-Melander, Marju
    Fall, Tove
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology.
    Accelerometer-based physical activity is associated with the gut microbiota in 8416 individuals in SCAPIS2024In: EBioMedicine, E-ISSN 2352-3964, Vol. 100, article id 104989Article in journal (Refereed)
    Abstract [en]

    Background

    Previous population-based studies investigating the relationship between physical activity and the gut microbiota have relied on self-reported activity, prone to reporting bias. Here, we investigated the associations of accelerometer-based sedentary (SED), moderate-intensity (MPA), and vigorous-intensity (VPA) physical activity with the gut microbiota using cross-sectional data from the Swedish CArdioPulmonary bioImage Study.

    Methods

    In 8416 participants aged 50–65, time in SED, MPA, and VPA were estimated with hip-worn accelerometer. Gut microbiota was profiled using shotgun metagenomics of faecal samples. We applied multivariable regression models, adjusting for sociodemographic, lifestyle, and technical covariates, and accounted for multiple testing.

    Findings

    Overall, associations between time in SED and microbiota species abundance were in opposite direction to those for MPA or VPA. For example, MPA was associated with lower, while SED with higher abundance of Escherichia coli. MPA and VPA were associated with higher abundance of the butyrate-producers Faecalibacterium prausnitzii and Roseburia spp. We observed discrepancies between specific VPA and MPA associations, such as a positive association between MPA and Prevotella copri, while no association was detected for VPA. Additionally, SED, MPA and VPA were associated with the functional potential of the microbiome. For instance, MPA was associated with higher capacity for acetate synthesis and SED with lower carbohydrate degradation capacity.

    Interpretation

    Our findings suggest that sedentary and physical activity are associated with a similar set of gut microbiota species but in opposite directions. Furthermore, the intensity of physical activity may have specific effects on certain gut microbiota species.

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  • 10.
    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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  • 11.
    Balliu, Brunilda
    et al.
    Stanford Univ, Dept Pathol, Sch Med, Stanford, CA USA.
    Durrant, Matthew
    Stanford Univ, Dept Genet, Sch Med, Stanford, CA USA.
    de Goede, Olivia
    Stanford Univ, Dept Genet, Sch Med, Stanford, CA USA.
    Abell, Nathan
    Stanford Univ, Dept Genet, Sch Med, Stanford, CA USA.
    Li, Xin
    Stanford Univ, Dept Pathol, Sch Med, Stanford, CA USA.
    Liu, Boxiang
    Stanford Univ, Dept Biol, Sch Med, Stanford, CA USA.
    Gloudemans, Michael J.
    Stanford Univ, Dept Genet, Sch Med, Stanford, CA USA.
    Cook, Naomi L.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology. Uppsala Univ, Dept Med Sci, Uppsala, Sweden.
    Smith, Kevin S.
    Stanford Univ, Dept Pathol, Sch Med, Stanford, CA USA.
    Knowles, David A.
    New York Genome Ctr, New York, NY USA.
    Pala, Mauro
    Univ Sassari, Dipartimento Sci Biomed, Sassari, Italy.
    Cucca, Francesco
    Univ Sassari, Dipartimento Sci Biomed, Sassari, Italy.
    Schlessinger, David
    NIA, Lab Genet, Bethesda, MD USA.
    Jaiswal, Siddhartha
    Stanford Univ, Dept Pathol, Sch Med, Stanford, CA USA.
    Sabatti, Chiara
    Stanford Univ, Dept Biomed Data Sci, Sch Med, Stanford, CA USA.
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Epidemiology.
    Ingelsson, Erik
    Stanford Univ, Sch Med, Div Cardiovasc Med, Dep Med, Stanford, CA USA; Stanford Univ, Stanford Cardiovasc Inst, Stanford, CA USA; Stanford Univ, Stanford Diabet Res Ctr, Stanford, CA USA.
    Montgomery, Stephen B.
    Stanford Univ, Dept Pathol, Sch Med, Stanford, CA USA; Stanford Univ, Dept Genet, Sch Med, Stanford, CA USA.
    Genetic regulation of gene expression and splicing during a 10-year period of human aging2019In: Genome Biology, ISSN 1465-6906, E-ISSN 1474-760X, Vol. 20, no 1, article id 230Article in journal (Refereed)
    Abstract [en]

    Background: Molecular and cellular changes are intrinsic to aging and age-related diseases. Prior cross-sectional studies have investigated the combined effects of age and genetics on gene expression and alternative splicing; however, there has been no long-term, longitudinal characterization of these molecular changes, especially in older age.

    Results: We perform RNA sequencing in whole blood from the same individuals at ages 70 and 80 to quantify how gene expression, alternative splicing, and their genetic regulation are altered during this 10-year period of advanced aging at a population and individual level. We observe that individuals are more similar to their own expression profiles later in life than profiles of other individuals their own age. We identify 1291 and 294 genes differentially expressed and alternatively spliced with age, as well as 529 genes with outlying individual trajectories. Further, we observe a strong correlation of genetic effects on expression and splicing between the two ages, with a small subset of tested genes showing a reduction in genetic associations with expression and splicing in older age.

    Conclusions: These findings demonstrate that, although the transcriptome and its genetic regulation is mostly stable late in life, a small subset of genes is dynamic and is characterized by a reduction in genetic regulation, most likely due to increasing environmental variance with age.

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  • 12.
    Bao, Xue
    et al.
    Tianjin Med Univ, Nutr Epidemiol Inst, Tianjin, Peoples R China;Tianjin Med Univ, Sch Publ Hlth, Tianjin, Peoples R China;Lund Univ, Dept Clin Sci, CRC, Jan Waldenstroms Gata 35,Hus 60 Plan 13, S-20502 Malmo, Sweden.
    Borne, Yan
    Lund Univ, Dept Clin Sci, CRC, Jan Waldenstroms Gata 35,Hus 60 Plan 13, S-20502 Malmo, Sweden.
    Muhammad, Iram Faqir
    Lund Univ, Dept Clin Sci, CRC, Jan Waldenstroms Gata 35,Hus 60 Plan 13, S-20502 Malmo, Sweden.
    Nilsson, Jan
    Lund Univ, Dept Clin Sci, CRC, Jan Waldenstroms Gata 35,Hus 60 Plan 13, S-20502 Malmo, Sweden.
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Epidemiology.
    Melander, Olle
    Lund Univ, Dept Clin Sci, CRC, Jan Waldenstroms Gata 35,Hus 60 Plan 13, S-20502 Malmo, Sweden.
    Niu, Kaijun
    Tianjin Med Univ, Nutr Epidemiol Inst, Tianjin, Peoples R China;Tianjin Med Univ, Sch Publ Hlth, Tianjin, Peoples R China.
    Orho-Melander, Marju
    Lund Univ, Dept Clin Sci, CRC, Jan Waldenstroms Gata 35,Hus 60 Plan 13, S-20502 Malmo, Sweden.
    Engström, Gunnar
    Lund Univ, Dept Clin Sci, CRC, Jan Waldenstroms Gata 35,Hus 60 Plan 13, S-20502 Malmo, Sweden.
    Growth differentiation factor 15 is positively associated with incidence of diabetes mellitus: the Malmö Diet and Cancer-Cardiovascular Cohort2019In: Diabetologia, ISSN 0012-186X, E-ISSN 1432-0428, Vol. 62, no 1, p. 78-86Article in journal (Refereed)
    Abstract [en]

    Aims/hypothesis: Growth differentiation factor 15 (GDF-15) is an anti-inflammatory cytokine of the transforming growth factor- superfamily. Circulating levels of GDF-15 are associated with hyperglycaemia among people with obesity or diabetes, but longitudinal evidence on the association between GDF-15 levels and diabetes risk is scarce. Our aim was to explore whether circulating levels of GDF-15 at baseline are positively associated with future diabetes incidence in a middle-aged urban population.

    Methods: Between 1991 and 1994, baseline fasting plasma GDF-15 levels were measured in 4360 individuals without diabetes (mean age 57.45.96years, 38.6% men) who were participants in the Malmo Diet and Cancer-Cardiovascular Cohort. After a follow-up of 19.05.16years (mean +/- SD), Cox proportional hazards regression analysis was used for the study of the relationship between baseline GDF-15 and incident diabetes, with adjustment for established confounders. A sensitivity analysis included further adjustment for levels of C-reactive protein (CRP).

    Results: During the follow-up period, 621 individuals developed diabetes. The multivariate-adjusted HR for diabetes incidence was 1.43 (95% CI 1.11, 1.83; p for trend = 0.007) for the fourth compared with the first quartile of GDF-15, and was 1.17 (95% CI 1.07, 1.28; p<0.001) per SD increase of GDF-15. If participants were grouped according to baseline fasting glucose, the association between GDF-15 and diabetes risk was only evident in the group without impaired fasting glucose (n=3973). The association tended to be less significant with increasing age: multivariate-adjusted HRs for diabetes per SD increase of GDF-15 were 1.24 (95% CI 1.08, 1.42), 1.19 (95% CI 1.00, 1.41) and 1.04 (95% CI 0.89, 1.23) for participants aged 55, 56-60 (>55 and 60) and >60years, respectively. With adjustment for levels of CRP, the HR per SD increase of GDF-15 (1.21, 95% CI 1.09, 1.35) was significant (p=0.015), but the HR for the fourth compared with the first quartile of GDF-15 was not significant (HR 1.30; 95% CI 1.01, 1.67; p for trend = 0.061).

    Conclusions/interpretation: GDF-15 may be useful for identification of people with a risk of incident diabetes, especially if those people are 60years old.

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  • 13.
    Bao, Xue
    et al.
    Nanjing Univ, Nanjing Drum Tower Hosp, Dept Cardiol, Affiliated Hosp,Med Sch, 321 Zhongshan Rd, Nanjing 210008, Peoples R China.;Lund Univ, Dept Clin Sci, Malmö, Sweden..
    Xu, Biao
    Nanjing Univ, Nanjing Drum Tower Hosp, Dept Cardiol, Affiliated Hosp,Med Sch, 321 Zhongshan Rd, Nanjing 210008, Peoples R China..
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Epidemiology.
    Engström, Gunnar
    Lund Univ, Dept Clin Sci, Malmö, Sweden..
    Carotid ultrasound and systematic coronary risk assessment 2 in the prediction of cardiovascular events2023In: European Journal of Preventive Cardiology, ISSN 2047-4873, E-ISSN 2047-4881, Vol. 30, no 10, p. 1007-1014Article in journal (Refereed)
    Abstract [en]

    Aims

    Subclinical carotid atherosclerosis adds predictive value to traditional risk factors for cardiovascular diseases (CVDs). Systematic Coronary Risk Assessment 2 (SCORE2), an algorithm composed of traditional risk factors, is a state-of-the-art to estimate the 10-year risk of first-onset CVDs. We aim to investigate whether and how subclinical carotid atherosclerosis affects the performance of SCORE2.

    Methods and results

    Carotid plaque presence and intima media thickness (IMT) were measured with ultrasound. The SCORE2 was calculated in 4588 non-diabetic participants aged 46–68 years. The incremental value for predicting CVD events of adding carotid plaque or IMT to SCORE2 was evaluated using C-statistics, continuous net reclassification improvement (NRI), and integrated discrimination improvement (IDI). The predicted 10-year CVD risk by SCORE2 and the observed event rate were compared between participants with and without carotid plaque. Adding plaque or IMT to SCORE2 significantly improved performance for predicting CVDs. The improvements in C-statistics, IDI, and NRI of adding plaque to SCORE2 for events occurring during the first 10 years were 2.20%, 0.70%, and 46.1%, respectively (all P < 0.0001). The SCORE2 over-predicted the 10-year CVD risk in those without carotid plaque (3.93% observed vs. 5.89% predicted, P < 0.0001) while under-predicted the risk in those with carotid plaque (9.69% observed vs. 8.12% predicted, P = 0.043).

    Conclusion

    Carotid ultrasound adds predictive performance to SCORE2 for assessment of CVD risk. Using SCORE2 without considering carotid atherosclerosis could under- or over-estimate the risk.

  • 14.
    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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  • 15.
    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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  • 16.
    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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  • 17.
    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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  • 18.
    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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  • 19.
    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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    fulltext
  • 20.
    Boden, Stina
    et al.
    Umea Univ, Dept Diagnost & Intervent Oncol, Umea, Sweden.;Umea Univ, Dept Clin Sci Pediat, Umea, Sweden..
    Zheng, Rui
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Epidemiology.
    Ribbenstedt, Anton
    Chalmers Univ Technol, Dept Life Sci, Gothenburg, Sweden..
    Landberg, Rikard
    Chalmers Univ Technol, Dept Life Sci, Gothenburg, Sweden..
    Harlid, Sophia
    Umea Univ, Dept Diagnost & Intervent Oncol, Umea, Sweden..
    Vidman, Linda
    Umea Univ, Dept Diagnost & Intervent Oncol, Umea, Sweden..
    Gunter, Marc J.
    Int Agcy Res Canc, Nutr & Metab Sect, F-69372 Lyon, France.;Imperial Coll London, Sch Publ Hlth, Dept Epidemiol & Biostat, Canc Epidemiol & Prevent Res Unit, London, England..
    Winkvist, Anna
    Univ Gothenburg, Inst Med, Sahlgrenska Acad, Dept Internal Med & Clin Nutr, Gothenburg, Sweden.;Umea Univ, Dept Publ Hlth & Clin Med, Sustainable Hlth, Umea, Sweden..
    Johansson, Ingegerd
    Umea Univ, Dept Odontol, Sect Cariol, Umea, Sweden..
    Van Guelpen, Bethany
    Umea Univ, Dept Diagnost & Intervent Oncol, Umea, Sweden.;Umea Univ, Wallenberg Ctr Mol Med, Umea, Sweden..
    Brunius, Carl
    Chalmers Univ Technol, Dept Life Sci, Gothenburg, Sweden..
    Dietary patterns, untargeted metabolite profiles and their association with colorectal cancer risk2024In: Scientific Reports, E-ISSN 2045-2322, Vol. 14, no 1, article id 2244Article in journal (Refereed)
    Abstract [en]

    We investigated data-driven and hypothesis-driven dietary patterns and their association to plasma metabolite profiles and subsequent colorectal cancer (CRC) risk in 680 CRC cases and individually matched controls. Dietary patterns were identified from combined exploratory/confirmatory factor analysis. We assessed association to LC-MS metabolic profiles by random forest regression and to CRC risk by multivariable conditional logistic regression. Principal component analysis was used on metabolite features selected to reflect dietary exposures. Component scores were associated to CRC risk and dietary exposures using partial Spearman correlation. We identified 12 data-driven dietary patterns, of which a breakfast food pattern showed an inverse association with CRC risk (OR per standard deviation increase 0.89, 95% CI 0.80-1.00, p = 0.04). This pattern was also inversely associated with risk of distal colon cancer (0.75, 0.61-0.96, p = 0.01) and was more pronounced in women (0.69, 0.49-0.96, p = 0.03). Associations between meat, fast-food, fruit soup/rice patterns and CRC risk were modified by tumor location in women. Alcohol as well as fruit and vegetables associated with metabolite profiles (Q2 0.22 and 0.26, respectively). One metabolite reflecting alcohol intake associated with increased CRC risk, whereas three metabolites reflecting fiber, wholegrain, and fruit and vegetables associated with decreased CRC risk.

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    FULLTEXT01
  • 21.
    Boman, Kurt
    et al.
    Umeå Univ, Dept Publ Hlth & Clin Med, Res Unit, Med, Umeå, Sweden..
    Lindmark, Krister
    Umeå Univ, Dept Publ Hlth, Umeå, Sweden.;Umeå Univ, Clin Med & Heart Ctr, Umeå, Sweden..
    Stålhammar, Jan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Family Medicine and Preventive Medicine.
    Olofsson, Mona
    Umeå Univ, Dept Publ Hlth & Clin Med, Res Unit, Med, Umeå, Sweden..
    Costa-Scharplatz, Madlaina
    Novartis Sweden AB, Med Affairs RWE, Stockholm, Sweden..
    Fonseca, Ana Filipa
    Novartis Pharma AG, Basel, Switzerland..
    Johansson, Stina
    IQVIA, Stockholm, Sweden..
    Heller, Vincent
    IQVIA, Solna, Sweden..
    Törnblom, Michael
    IQVIA Solut Sweden AB, Real World & Analyt Solut, Solna, Sweden..
    Wikström, Gerhard
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Epidemiology.
    Healthcare resource utilisation and costs associated with a heart failure diagnosis: a retrospective, population-based cohort study in Sweden2021In: BMJ Open, E-ISSN 2044-6055, Vol. 11, no 10, article id e053806Article in journal (Refereed)
    Abstract [en]

    Objectives To examine healthcare resource use (HRU) and costs among heart failure (HF) patients using population data from Sweden. Design Retrospective, non-interventional cohort study. Setting Two cohorts were identified from linked national health registers (cohort 1, 2005-2014) and electronic medical records (cohort 2, 2010-2012; primary/secondary care patients from Uppsala and Vasterbotten). Participants Patients (aged >= 18 years) with primary or secondary diagnoses of HF (>= 2 International Classification of Diseases and Related Health Problems, 10th revision classification) during the identification period of January 2005 to March 2015 were included. Outcome measures HRU across the HF phenotypes was assessed with logistic regression. Costs were estimated based on diagnosis-related group codes and general price lists. Results Total annual costs of secondary care of prevalent HF increased from SEK 6.23 (euro0.60) to 8.86 (euro0.85) billion between 2005 and 2014. Of 4648 incident patients, HF phenotype was known for 1715: reduced ejection fraction (HFrEF): 64.5%, preserved ejection fraction (HFpEF): 35.5%. Within 1 year of HF diagnosis, the proportion of patients hospitalised was only marginally higher for HFrEF versus HFpEF (all-cause (95% CI): 64.7% (60.8 to 68.4) vs 63.7% (60.8 to 66.5), HR 0.91, p=0.14; cardiovascular disease related (95% CI): 61.1% (57.1 to 64.8) vs 60.9% (58.0 to 63.7), HR 0.93, p=0.28). Frequency of hospitalisations and outpatient visits per patient declined after the first year. All-cause secondary care costs in the first year were SEK 122 758 (euro12 890)/patient/year, with HF-specific care accounting for 69% of the costs. Overall, 10% of the most expensive population (younger; predominantly male; more likely to have comorbidities) incurred similar to 40% of total secondary care costs. Conclusions HF-associated costs and HRU are high, especially during the first year of diagnosis. This is driven by high hospitalisations rates. Understanding the profile of resource-intensive patients being at younger age, male sex and high Charlson comorbidity index scores at the time of the HF diagnosis is most likely a sign of more severe disease.

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  • 22.
    Bonander, Carl
    et al.
    Univ Gothenburg, Sahlgrenska Acad, Sch Publ Hlth & Community Med, Inst Med, Gothenburg, Sweden..
    Nilsson, Anton
    Lund Univ, Epidemiol Populat Studies & Infrastruct EPI LUND, Lund, Sweden.;Lund Univ, Ctr Econ Demog, Lund, Sweden..
    Björk, Jonas
    Lund Univ, Epidemiol Populat Studies & Infrastruct EPI LUND, Lund, Sweden.;Skane Univ Hosp, Forum South, Clin Studies Sweden, Lund, Sweden..
    Blomberg, Anders
    Umeå Univ, Dept Publ Hlth & Clin Med, Sect Med, Umeå, Sweden..
    Engström, Gunnar
    Lund Univ, Dept Clin Sci, Malmö, Sweden..
    Jernberg, Tomas
    Danderyd Hosp, Karolinska Inst, Dept Clin Sci, 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..
    Östgren, Carl Johan
    Linköping Univ, Dept Hlth Med & Caring Sci, Linköping, Sweden..
    Bergström, Goran
    Univ Gothenburg, Sahlgrenska Acad, Inst Med, Dept Mol & Clin Med, Gothenburg, Sweden.;Sahlgrens Univ Hosp, Dept Clin Physiol, Reg Vastra Gotaland, Gothenburg, Sweden..
    Strömberg, Ulf
    Reg Halland, Dept Res & Dev, Halmstad, Sweden..
    The value of combining individual and small area sociodemographic data for assessing and handling selective participation in cohort studies: Evidence from the Swedish CardioPulmonary bioImage Study2022In: PLOS ONE, E-ISSN 1932-6203, Vol. 17, no 3, article id e0265088Article in journal (Refereed)
    Abstract [en]

    Objectives: To study the value of combining individual- and neighborhood-level sociodemographic data to predict study participation and assess the effects of baseline selection on the distribution of metabolic risk factors and lifestyle factors in the Swedish CardioPulmonary bioImage Study (SCAPIS).

    Methods: We linked sociodemographic register data to SCAPIS participants (n = 30,154, ages: 50-64 years) and a random sample of the study's target population (n = 59,909). We assessed the classification ability of participation models based on individual-level data, neighborhood-level data, and combinations of both. Standardized mean differences (SMD) were used to examine how reweighting the sample to match the population affected the averages of 32 cardiopulmonary risk factors at baseline. Absolute SMDs > 0.10 were considered meaningful.

    Results: Combining both individual-level and neighborhood-level data gave rise to a model with better classification ability (AUC: 71.3%) than models with only individual-level (AUC: 66.9%) or neighborhood-level data (AUC: 65.5%). We observed a greater change in the distribution of risk factors when we reweighted the participants using both individual and area data. The only meaningful change was related to the (self-reported) frequency of alcohol consumption, which appears to be higher in the SCAPIS sample than in the population. The remaining risk factors did not change meaningfully.

    Conclusions: Both individual- and neighborhood-level characteristics are informative in assessing study selection effects. Future analyses of cardiopulmonary outcomes in the SCAPIS cohort can benefit from our study, though the average impact of selection on risk factor distributions at baseline appears small.

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  • 23. Broadaway, K Alaine
    et al.
    Yin, Xianyong
    Williamson, Alice
    Parsons, Victoria A
    Wilson, Emma P
    Moxley, Anne H
    Vadlamudi, Swarooparani
    Varshney, Arushi
    Jackson, Anne U
    Ahuja, Vasudha
    Bornstein, Stefan R
    Corbin, Laura J
    Delgado, Graciela E
    Dwivedi, Om P
    Silva, Lilian Fernandes
    Frayling, Timothy M
    Grallert, Harald
    Gustafsson, Stefan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Epidemiology.
    Hakaste, Liisa
    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.
    Herder, Christian
    Herrmann, Sandra
    Højlund, Kurt
    Hughes, David A
    Kleber, Marcus E
    Lindgren, Cecilia M
    Liu, Ching-Ti
    Luan, Jian'an
    Malmberg, Anni
    Moissl, Angela P
    Morris, Andrew P
    Perakakis, Nikolaos
    Peters, Annette
    Petrie, John R
    Roden, Michael
    Schwarz, Peter E H
    Sharma, Sapna
    Silveira, Angela
    Strawbridge, Rona J
    Tuomi, Tiinamaija
    Wood, Andrew R
    Wu, Peitao
    Zethelius, Björn
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Baldassarre, Damiano
    Eriksson, Johan G
    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.
    Florez, Jose C
    Fritsche, Andreas
    Gigante, Bruna
    Hamsten, Anders
    Kajantie, Eero
    Laakso, Markku
    Lahti, Jari
    Lawlor, Deborah A
    Lind, Lars
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Disciplinary Domain of Medicine and Pharmacy, research centers etc., Centre for Research and Development, Gävleborg. 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. 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, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Epidemiology.
    März, Winfried
    Meigs, James B
    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, 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. Uppsala University, Science for Life Laboratory, SciLifeLab. 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, Faculty of Medicine, Department of Medical Sciences, Occupational and Environmental Medicine.
    Timpson, Nicholas J
    Wagner, Robert
    Walker, Mark
    Wareham, Nicholas J
    Watkins, Hugh
    Barroso, Inês
    O'Rahilly, Stephen
    Grarup, Niels
    Parker, Stephen Cj
    Boehnke, Michael
    Langenberg, Claudia
    Wheeler, Eleanor
    Mohlke, Karen L
    Loci for insulin processing and secretion provide insight into type 2 diabetes risk.2023In: American Journal of Human Genetics, ISSN 0002-9297, E-ISSN 1537-6605, Vol. 110, no 2, p. 284-299Article in journal (Refereed)
    Abstract [en]

    Insulin secretion is critical for glucose homeostasis, and increased levels of the precursor proinsulin relative to insulin indicate pancreatic islet beta-cell stress and insufficient insulin secretory capacity in the setting of insulin resistance. We conducted meta-analyses of genome-wide association results for fasting proinsulin from 16 European-ancestry studies in 45,861 individuals. We found 36 independent signals at 30 loci (p value < 5 × 10-8), which validated 12 previously reported loci for proinsulin and ten additional loci previously identified for another glycemic trait. Half of the alleles associated with higher proinsulin showed higher rather than lower effects on glucose levels, corresponding to different mechanisms. Proinsulin loci included genes that affect prohormone convertases, beta-cell dysfunction, vesicle trafficking, beta-cell transcriptional regulation, and lysosomes/autophagy processes. We colocalized 11 proinsulin signals with islet expression quantitative trait locus (eQTL) data, suggesting candidate genes, including ARSG, WIPI1, SLC7A14, and SIX3. The NKX6-3/ANK1 proinsulin signal colocalized with a T2D signal and an adipose ANK1 eQTL signal but not the islet NKX6-3 eQTL. Signals were enriched for islet enhancers, and we showed a plausible islet regulatory mechanism for the lead signal in the MADD locus. These results show how detailed genetic studies of an intermediate phenotype can elucidate mechanisms that may predispose one to disease.

  • 24.
    Cai, Gui-Hong
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Lung- allergy- and sleep research.
    Janson, Christer
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Lung- allergy- and sleep research.
    Theorell-Haglöw, Jenny
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Lung- allergy- and sleep research.
    Benedict, Christian
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Elmstahl, S.
    Lund Univ, Div Geriatr Med, Dept Hlth Sci, Lund, 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.
    Both weight at age 20 and weight gain have an impact on sleep disturbances later in life – results of the epihealth study2017In: Sleep Medicine, ISSN 1389-9457, E-ISSN 1878-5506, Vol. 40, no Supplement 1, p. E195-E195Article in journal (Other academic)
  • 25.
    Camacho-Munoz, Dolores
    et al.
    Univ Manchester, Manchester Acad Hlth Sci Ctr, Fac Biol Med & Hlth, Sch Hlth Sci,Lab Lipid & Lipid Biol,Div Pharm & O, Manchester, Lancs, England..
    Kiezel-Tsugunova, Magdalena
    Univ Manchester, Manchester Acad Hlth Sci Ctr, Fac Biol Med & Hlth, Sch Hlth Sci,Lab Lipid & Lipid Biol,Div Pharm & O, Manchester, Lancs, England..
    Kiss, Orsolya
    Univ Manchester, Manchester Acad Hlth Sci Ctr, Fac Biol Med & Hlth, Sch Hlth Sci,Lab Lipid & Lipid Biol,Div Pharm & O, Manchester, Lancs, England..
    Uddin, Mohib
    AstraZeneca Gothenburg, Biopharmaceut R&D, Mölndal, Sweden..
    Sunden, Mattias
    Univ Gothenburg, Dept Econ, Gothenburg, Sweden..
    Ryaboshapkina, Maria
    AstraZeneca Gothenburg, Biopharmaceut R&D, Mölndal, Sweden..
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Epidemiology.
    Oscarsson, Jan
    AstraZeneca Gothenburg, Biopharmaceut R&D, Mölndal, Sweden..
    Nicolaou, Anna
    Univ Manchester, Manchester Acad Hlth Sci Ctr, Fac Biol Med & Hlth, Sch Hlth Sci,Lab Lipid & Lipid Biol,Div Pharm & O, Manchester, Lancs, England.;Univ Manchester, Manchester Acad Hlth Sci Ctr, Fac Biol Med & Hlth, Lydia Becker Inst Immunol & Inflammat, Manchester, Lancs, England..
    Omega-3 carboxylic acids and fenofibrate differentially alter plasma lipid mediators in patients with non-alcoholic fatty liver disease2021In: The FASEB Journal, ISSN 0892-6638, E-ISSN 1530-6860, Vol. 35, no 11, article id e21976Article in journal (Refereed)
    Abstract [en]

    Fibrates and omega-3 polyunsaturated acids are used for the treatment of hypertriglyceridemia but have not demonstrated consistent effects on cardiovascular (CV) risk. In this study, we investigate how these two pharmacological agents influence plasma levels of bioactive lipid mediators, aiming to explore their efficacy beyond that of lipid-lowering agents. Plasma from overweight patients with non-alcoholic fatty liver disease (NAFLD) and hypertriglyceridemia, participating in a randomized placebo-controlled study investigating the effects of 12 weeks treatment with fenofibrate or omega-3 free carboxylic acids (OM-3CA) (200 mg or 4 g per day, respectively), were analyzed for eicosanoids and related PUFA species, N-acylethanolamines (NAE) and ceramides. OM-3CA reduced plasma concentrations of proinflammatory PGE(2), as well as PGE(1), PGD(1) and thromboxane B2 but increased prostacyclin, and eicosapentaenoic acid- and docosahexaenoic acid-derived lipids of lipoxygenase and cytochrome P450 monooxygenase (CYP) (e.g., 17-HDHA, 18-HEPE, 19,20-DiHDPA). Fenofibrate reduced plasma concentrations of vasoactive CYP-derived eicosanoids (DHETs). Although OM-3CA increased plasma levels of the NAE docosahexaenoyl ethanolamine and docosapentaenoyl ethanolamine, and fenofibrate increased palmitoleoyl ethanolamine, the effect of both treatments may have been masked by the placebo (olive oil). Fenofibrate was more efficacious than OM-3CA in significantly reducing plasma ceramides, pro-inflammatory lipids associated with CV disease risk. Neither treatment affected putative lipid species associated with NAFLD. Our results show that OM-3CA and fenofibrate differentially modulate the plasma mediator lipidome, with OM-3CA promoting the formation of lipid mediators with potential effects on chronic inflammation, while fenofibrate mainly reducing ceramides. These findings suggest that both treatments could ameliorate chronic inflammation with possible impact on disease outcomes, independent of triglyceride reduction.

  • 26.
    Canoy, Dexter
    et al.
    Univ Oxford, Nuffield Dept Womens & Reprod Hlth, Deep Med, Oxford, England.;Oxford Univ Hosp NHS Fdn Trust, NIHR Oxford Biomed Res Ctr, Oxford, England..
    Copland, Emma
    Univ Oxford, Nuffield Dept Womens & Reprod Hlth, Deep Med, Oxford, England..
    Nazarzadeh, Milad
    Univ Oxford, Nuffield Dept Womens & Reprod Hlth, Deep Med, Oxford, England..
    Ramakrishnan, Rema
    Univ Oxford, Nuffield Dept Populat Hlth, Natl Perinatal Epidemiol Unit, Oxford, England..
    Pinho-Gomes, Ana-Catarina
    Kings Coll London, Fac Life Sci & Med, Sch Populat Hlth & Environm Sci, London, England.;Univ Porto, Ctr Hlth Technol & Serv Res, Dept Community Med, Porto, Portugal..
    Salam, Abdul
    Univ New South Wales, George Inst Global Hlth, Sydney, NSW, Australia.;George Inst Global Hlth India, Hyderabad, India..
    Dwyer, Jamie P.
    Vanderbilt Univ, Med Ctr, Nashville, TN USA..
    Farzadfar, Farshad
    Univ Tehran Med Sci, Endocrinol & Metab Inst, Tehran, Iran..
    Sundström, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Epidemiology.
    Woodward, Mark
    Univ New South Wales, George Inst Global Hlth, Sydney, NSW, Australia.;Imperial Coll London, George Inst Global Hlth UK, London, England..
    Davis, Barry R.
    Univ Texas Houston, Dept Biostat, Sch Publ Hlth, Houston, TX USA..
    Rahimi, Kazem
    Univ Oxford, Nuffield Dept Womens & Reprod Hlth, Deep Med, Oxford, England.;Oxford Univ Hosp NHS Fdn Trust, NIHR Oxford Biomed Res Ctr, Oxford, England..
    Antihypertensive drug effects on long-term blood pressure: an individual-level data meta-analysis of randomised clinical trials2022In: Heart, ISSN 1355-6037, E-ISSN 1468-201X, Vol. 108, no 16, p. 1281-1289Article in journal (Refereed)
    Abstract [en]

    Objective: Evidence from randomised trials of pharmacological treatments on long-term blood pressure (BP) reduction is limited. We investigated the antihypertensive drug effects on BP over time and across different participant characteristics.

    Methods: We conducted an individual patient-level data meta-analysis of 52 large-scale randomised clinical trials in the Blood Pressure Lowering Treatment Trialists' Collaboration using mixed models to examine treatment effects on BP over 4 years of mean follow-up.

    Results: There were 363 684 participants (42% women), with baseline mean age=65 years and mean systolic/diastolic BP=152/87 mm Hg, and among whom 19% were current smokers, 49% had cardiovascular disease, 28% had diabetes and 69% were taking antihypertensive treatment at baseline. Drugs were effective in lowering BP showing maximal effect after 12 months and gradually attenuating towards later years. Based on measures taken >= 12 months postrandomisation, mean systolic/diastolic BP difference (95% CI) between more and less intense BP-lowering treatment was -11.1 (-11.3 to -10.8)/-5.6 (-5.7 to -5.4) mm Hg; between active treatment and placebo was -5.1 (-5.3 to -5.0)/-2.3 (-2.4 to -2.2) mm Hg; and between active and control arms for drug comparison trials was -1.4 (-1.5 to -1.3)/-0.6 (-0.7 to -0.6) mm Hg. BP reductions were observed across different baseline BP values and ages, and by sex, history of cardiovascular disease and diabetes and prior antihypertensive treatment use.

    Conclusion: These findings suggest that BP-lowering pharmacotherapy is effective in lowering BP, up to 4 years on average, in people with different characteristics. Appropriate treatment strategies are needed to sustain substantive long-term BP reductions.

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  • 27.
    Carland, Corinne
    et al.
    Univ Penn, Dept Med, Philadelphia, PA USA..
    Png, Grace
    Helmholtz Zent Munchen, Inst Translat Genom, German Res Ctr Environm Hlth, Neuherberg, Germany..
    Malarstig, Anders
    Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden.;Pfizer Worldwide Res Dev & Med, Stockholm, Sweden..
    Kho, Pik Fang
    Stanford Univ, Stanford Cardiovasc Inst, Dept Med, Div Cardiovasc Med,Sch Med, Palo Alto, CA 94305 USA..
    Gustafsson, Stefan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Epidemiology.
    Michaëlsson, Karl
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Medical epidemiology.
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Epidemiology.
    Tsafantakis, Emmanouil
    Anogia Med Ctr, Anogia, Greece..
    Karaleftheri, Maria
    Echinos Med Ctr, Echinos, Greece..
    Dedoussis, George
    Harokopio Univ Athens, Sch Hlth Sci & Educ, Dept Nutr & Dietet, Athens, Greece. Univ Geneva, Fac Med, Med Sch, Dept Genet Med & Dev, Geneva, Switzerland. Univ Edinburgh, Usher Inst, Ctr Global Hlth Res, Edinburgh, Scotland. Univ Edinburgh, Inst Genet & Mol Med, MRC Human Genet Unit, Edinburgh, Scotland. Karolinska Inst, Cardiovasc Med, Med, Stockholm, Sweden. Univ Cambridge, MRC Epidemiol Unit, Cambridge, England. Cornell Med Qatar Res, Bioinformat Core, Doha, Qatar. Tech Univ Munich TUM, TUM Sch Med, Munich, Germany..
    Ramisch, Anna
    Macdonald-Dunlop, Erin
    Klaric, Lucija K.
    Joshi, Peter
    Chen, Yan M.
    Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden..
    Bjoerck, Hanna
    Eriksson, Per
    Carrasco-Zanini, Julia
    Wheeler, Eleanor
    Suhre, Karsten
    Gilly, Arthur
    Helmholtz Zent Munchen, Inst Translat Genom, German Res Ctr Environm Hlth, Neuherberg, Germany..
    Zeggini, Eleftheria
    Helmholtz Zent Munchen, Inst Translat Genom, German Res Ctr Environm Hlth, Neuherberg, Germany.;Klinikum Rechts Der Isar, TUM Sch Med, Munich, Germany. Univ Newcastle, Biosci Inst, Fac Med Sci, Newcastle, England. Charite Univ Med Berlin, Berlin Inst Hlth, Computat Med, Berlin, Germany. Queen Mary Univ London, Precis Healthcare Univ Res Inst, London, England. Weill Cornell Med Qatar, Prote Core, Res, Doha, Qatar..
    Vinuela, Ana T.
    Dermitzakis, Emmanouil F.
    Wilson, James
    Langenberg, Claudia
    Thareja, Gaurav
    Halama, Anna
    Schmidt, Frank
    Zanetti, Daniela
    Stanford Univ, Stanford Cardiovasc Inst, Dept Med, Div Cardiovasc Med,Sch Med, Palo Alto, CA 94305 USA..
    Assimes, Themistocles
    Stanford Univ, Stanford Cardiovasc Inst, Dept Med, Div Cardiovasc Med,Sch Med, Palo Alto, CA 94305 USA..
    Consortium, S C A L L O P
    Proteomic analysis of 92 circulating proteins and their effects in cardiometabolic diseases2023In: Clinical Proteomics, ISSN 1542-6416, E-ISSN 1559-0275, Vol. 20, no 1, article id 31Article in journal (Refereed)
    Abstract [en]

    Background: Human plasma contains a wide variety of circulating proteins. These proteins can be important clinical biomarkers in disease and also possible drug targets. Large scale genomics studies of circulating proteins can identify genetic variants that lead to relative protein abundance.

    Methods: We conducted a meta-analysis on genome-wide association studies of autosomal chromosomes in 22,997 individuals of primarily European ancestry across 12 cohorts to identify protein quantitative trait loci (pQTL) for 92 cardiometabolic associated plasma proteins.

    Results: We identified 503 (337 cis and 166 trans) conditionally independent pQTLs, including several novel variants not reported in the literature. We conducted a sex-stratified analysis and found that 118 (23.5%) of pQTLs demonstrated heterogeneity between sexes. The direction of effect was preserved but there were differences in effect size and significance. Additionally, we annotate trans-pQTLs with nearest genes and report plausible biological relationships. Using Mendelian randomization, we identified causal associations for 18 proteins across 19 phenotypes, of which 10 have additional genetic colocalization evidence. We highlight proteins associated with a constellation of cardiometabolic traits including angiopoietin-related protein 7 (ANGPTL7) and Semaphorin 3F (SEMA3F).

    Conclusion: Through large-scale analysis of protein quantitative trait loci, we provide a comprehensive overview of common variants associated with plasma proteins. We highlight possible biological relationships which may serve as a basis for further investigation into possible causal roles in cardiometabolic diseases.

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  • 28.
    Carlsson, Axel C.
    et al.
    Karolinska Inst, Dept Neurobiol Care Sci & Soc NVS, Huddinge, Sweden.
    Nowak, Christoph
    Karolinska Inst, Dept Neurobiol Care Sci & Soc NVS, Huddinge, Sweden.
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Epidemiology.
    Östgren, Carl Johan
    Linköping Univ, Dept Med & Hlth Sci, Linköping, Sweden.
    Nyström, Fredrik H.
    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, Clinical Epidemiology.
    Carrero, Juan Jesus
    Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden.
    Risérus, Ulf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism.
    Ingelsson, Erik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology. Uppsala University, Science for Life Laboratory, SciLifeLab. Stanford Univ, Dept Med, Sch Med, Div Cardiovasc Med, Stanford, CA 94305 USA;Stanford Univ, Stanford Cardiovasc Inst, Stanford, CA 94305 USA;Stanford Univ, Stanford Diabet Res Ctr, Stanford, CA 94305 USA.
    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.
    Ärnlöv, Johan
    Karolinska Inst, Dept Neurobiol Care Sci & Soc NVS, Huddinge, Sweden;Dalarna Univ, Sch Hlth & Social Studies, Falun, Sweden.
    Growth differentiation factor 15 (GDF-15) is a potential biomarker of both diabetic kidney disease and future cardiovascular events in cohorts of individuals with type 2 diabetes: a proteomics approach2020In: Upsala Journal of Medical Sciences, ISSN 0300-9734, E-ISSN 2000-1967, Vol. 125, no 1, p. 37-43Article in journal (Refereed)
    Abstract [en]

    Background: Diabetic kidney disease (DKD) is a leading risk factor for end-stage renal disease and is one of the most important risk factors for cardiovascular disease in patients with diabetes. It is possible that novel markers portraying the pathophysiological underpinning processes may be useful. Aim: To investigate the associations between 80 circulating proteins, measured by a proximity extension assay, and prevalent DKD and major adverse cardiovascular events (MACE) in type 2 diabetes. Methods: We randomly divided individuals with type 2 diabetes from three cohorts into a two-thirds discovery and one-third replication set (total n = 813, of whom 231 had DKD defined by estimated glomerular filtration rate <60 mg/mL/1.73 m(2) and/or urinary albumin-creatinine ratio >= 3 g/mol). Proteins associated with DKD were also assessed as predictors for incident major adverse cardiovascular events (MACE) in persons with DKD at baseline. Results: Four proteins were positively associated with DKD in models adjusted for age, sex, cardiovascular risk factors, glucose control, and diabetes medication: kidney injury molecule-1 (KIM-1, odds ratio [OR] per standard deviation increment, 1.65, 95% confidence interval [CI] 1.27-2.14); growth differentiation factor 15 (GDF-15, OR 1.40, 95% CI 1.16-1.69); myoglobin (OR 1.57, 95% CI 1.30-1.91), and matrix metalloproteinase 10 (MMP-10, OR 1.43, 95% CI 1.17-1.74). In patients with DKD, GDF-15 was significantly associated with increased risk of MACE after adjustments for baseline age, sex, microalbuminuria, and kidney function and (59 MACE events during 7 years follow-up, hazard ratio per standard deviation increase 1.43 [95% CI 1.03-1.98]) but not after further adjustments for cardiovascular risk factors. Conclusion: Our proteomics approach confirms and extends previous associations of higher circulating levels of GDF-15 with both micro- and macrovascular disease in patients with type 2 diabetes. Our data encourage additional studies evaluating the clinical utility of our findings.

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  • 29.
    Carlsson, Lars
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Family Medicine and Preventive Medicine. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Disciplinary Domain of Medicine and Pharmacy, research centers etc., Center for Clinical Research Dalarna.
    Lytsy, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Epidemiology.
    Anderzén, Ingrid
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Social Medicine.
    Hallqvist, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Family Medicine and Preventive Medicine.
    Wallman, Thorne
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Family Medicine and Preventive Medicine. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Disciplinary Domain of Medicine and Pharmacy, research centers etc., Centre for Clinical Research Sörmland.
    Gustavsson, Catharina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Family Medicine and Preventive Medicine. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Disciplinary Domain of Medicine and Pharmacy, research centers etc., Center for Clinical Research Dalarna.
    Motivation for return to work and actual return to work among people on long-term sick leave due to pain syndrome or mental health conditions2019In: Disability and Rehabilitation, ISSN 0963-8288, E-ISSN 1464-5165, Vol. 41, no 25, p. 3061-3070Article in journal (Refereed)
    Abstract [en]

    Purpose: The purpose of this study was to investigate associations between motivation for return to work and actual return to work, or increased employability among people on long-term sick leave.

    Materials and methods: Data by responses to questionnaires was collected from 227 people on long-term sick leave (mean = 7.9 years) due to pain syndrome or mild to moderate mental health conditions who had participated in a vocational rehabilitation intervention. The participants’ motivation for return to work was measured at baseline. At 12-month follow-up, change in the type of reimbursement between baseline and at present was assessed and used to categorise outcomes as: “decreased work and employability”, “unchanged”, “increased employability”, and “increased work”. Associations between baseline motivation and return to work outcome were analysed using logistic and multinomial regression models.

    Results: Motivation for return to work at baseline was associated with return to work or increased employability at 12-month follow-up in the logistic regression model adjusting for potential confounders (OR 2.44, 95% CI 1.25–4.78).

    Conclusions: The results suggest that motivation for return to work at baseline was associated with actual chances of return to work or increased employability in people on long-term sick leave due to pain syndrome or mild to moderate mental health conditions.

    • Implication for rehabilitation
    • High motivation for return to work seems to increase the chances of actual return to work or increased employability in people on sick leave due to pain syndrome or mild to moderate mental health conditions.

    • The potential impact of motivation for return to work is suggested to be highlighted in vocational rehabilitation.

    • Rehabilitation professionals are recommended to recognise and take into consideration the patient’s stated motivation for return to work.

    • Rehabilitation professionals should be aware of that the patient’s motivation for return to work might have an impact on the outcome of vocational rehabilitation.

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  • 30.
    Cars, Thomas
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Epidemiology.
    Lindhagen, Lars
    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.
    A framework for monitoring of new drugs in Sweden2019In: Upsala Journal of Medical Sciences, ISSN 0300-9734, E-ISSN 2000-1967, Vol. 124, no 1, p. 46-50Article in journal (Refereed)
    Abstract [en]

    In order to monitor the net public health benefit of new drugs, especially in the light of recent stepwise approval approaches, there is a need to optimize real-time post-marketing evaluation of new drugs using data collected in routine care. Sweden, with its unique possibilities for observational research, can provide these data. We herein propose a framework for continuous monitoring of the effectiveness, safety, and cost-effectiveness of new drugs, using prospectively determined protocols designed in collaboration between all relevant stakeholders. We believe that this framework can be a useful tool for healthcare authorities and reimbursement agencies in the introduction of new drugs.

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  • 31.
    Chen, Ji
    et al.
    Univ Exeter, Med Sch, Exeter Ctr Excellence Diabet Res EXCEED, Genet Complex Traits, Exeter, Devon, England;Wellcome Sanger Inst, Dept Human Genet, Cambridge, England.
    Gustafsson, Stefan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Sennblad, Bengt
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology, Molecular Evolution. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Epidemiology.
    Barroso, Ines
    Univ Cambridge, Inst Metab Sci, MRC Epidemiol Unit, Cambridge, England;Univ Exeter, Med Sch, Exeter Ctr Excellence Diabet Res EXCEED, Genet Complex Traits, Exeter, Devon, England;Wellcome Sanger Inst, Dept Human Genet, Cambridge, England.
    The trans-ancestral genomic architecture of glycemic traits2021In: Nature Genetics, ISSN 1061-4036, E-ISSN 1546-1718, Vol. 53, no 6, p. 840-860Article in journal (Refereed)
    Abstract [en]

    Glycemic traits are used to diagnose and monitor type 2 diabetes and cardiometabolic health. To date, most genetic studies of glycemic traits have focused on individuals of European ancestry. Here we aggregated genome-wide association studies comprising up to 281,416 individuals without diabetes (30% non-European ancestry) for whom fasting glucose, 2-h glucose after an oral glucose challenge, glycated hemoglobin and fasting insulin data were available. Trans-ancestry and single-ancestry meta-analyses identified 242 loci (99 novel; P < 5 x 10(-8)), 80% of which had no significant evidence of between-ancestry heterogeneity. Analyses restricted to individuals of European ancestry with equivalent sample size would have led to 24 fewer new loci. Compared with single-ancestry analyses, equivalent-sized trans-ancestry fine-mapping reduced the number of estimated variants in 99% credible sets by a median of 37.5%. Genomic-feature, gene-expression and gene-set analyses revealed distinct biological signatures for each trait, highlighting different underlying biological pathways. Our results increase our understanding of diabetes pathophysiology by using trans-ancestry studies for improved power and resolution. A trans-ancestry meta-analysis of GWAS of glycemic traits in up to 281,416 individuals identifies 99 novel loci, of which one quarter was found due to the multi-ancestry approach, which also improves fine-mapping of credible variant sets.

  • 32.
    Chen, Qiao Sen
    et al.
    Karolinska Inst, Dept Med Solna, Div Cardiovasc Med, Solnavagen 30, S-17164 Stockholm, Sweden..
    Bergman, Otto
    Karolinska Inst, Dept Med Solna, Div Cardiovasc Med, Solnavagen 30, S-17164 Stockholm, Sweden..
    Ziegler, Louise
    Karolinska Inst, Danderyd Hosp, Div Med, Entrevagen 2, S-18288 Stockholm, Sweden.;Karolinska Inst, Danderyd Hosp, Dept Clin Sci, Entrevagen 2, S-18288 Stockholm, Sweden..
    Baldassarre, Damiano
    Univ Milan, Dept Med Biotechnol & Translat Med, Via Vanvitelli 32, I-20133 Milan, Italy.;IRCCS, Ctr Cardiol Monzino, Via Carlo Parea 4, I-20138 Milan, Italy..
    Veglia, Fabrizio
    Maria Cecilia Hosp, GVM Care & Res, Via Corriera 1, I-48033 Cotignola, RA, Italy..
    Tremoli, Elena
    Maria Cecilia Hosp, GVM Care & Res, Via Corriera 1, I-48033 Cotignola, RA, Italy..
    Strawbridge, Rona J.
    Karolinska Inst, Dept Med Solna, Div Cardiovasc Med, Solnavagen 30, S-17164 Stockholm, Sweden.;Univ Glasgow, Inst Hlth & Wellbeing, Clarice Pears Bldg,90 Byres Rd, Glasgow G12 8TB, Scotland.;Hlth Data Res, Clarice Pears Bldg,90 Byres Rd, Glasgow, Scotland..
    Gallo, Antonio
    Sorbonne Univ, Hop Pitie Salpetriere, AP HP, Lipidol & Cardiovasc Prevent Unit,Dept Nutr,INSERM, 47 Blvd Hop, F-75013 Paris, France..
    Pirro, Matteo
    Univ Perugia, Dept Med, Internal Med Angiol & Arteriosclerosis Dis, Piazzale Menghini 1, I-06129 Perugia, Italy..
    Smit, Andries J.
    Univ Med Ctr Groningen, Dept Med, Groningen & Isala Clin Zwolle, Dokter Spanjaardweg 29B, NL-8025 BT Groningen, Netherlands..
    Kurl, Sudhir
    Univ Eastern Finland, Inst Publ Hlth & Clin Nutr, Kuopio Campus,Yliopistonranta 1 C,Canth Bldg,B Win, FI-70211 Kuopio, Finland..
    Savonen, Kai
    Kuopio Res Inst Exercise Med, Haapaniementie 16, Kuopio 70100, Finland.;Kuopio Univ Hosp, Sci Serv Ctr, Dept Clin Physiol & Nucl Med, Yliopsistonranta 1F, FI-70211 Kuopio, Finland..
    Lind, Lars
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Disciplinary Domain of Medicine and Pharmacy, research centers etc., Centre for Research and Development, Gävleborg. 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. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Epidemiology. Uppsala Univ, Dept Med Sci, Uppsala Sci Pk,Dag Hammarskjoldsv 10B, S-75237 Uppsala, Sweden..
    Eriksson, Per
    Karolinska Inst, Dept Med Solna, Div Cardiovasc Med, Solnavagen 30, S-17164 Stockholm, Sweden..
    Gigante, Bruna
    Karolinska Inst, Dept Med Solna, Div Cardiovasc Med, Solnavagen 30, S-17164 Stockholm, Sweden.;Danderyd Hosp, Dept Cardiol, Entrevagen 2, S-18288 Stockholm, Sweden..
    A machine learning based approach to identify carotid subclinical atherosclerosis endotypes2023In: Cardiovascular Research, ISSN 0008-6363, E-ISSN 1755-3245, Vol. 119, no 16, p. 2594-2606Article in journal (Refereed)
    Abstract [en]

    Aims To define endotypes of carotid subclinical atherosclerosis. Methods and results We integrated demographic, clinical, and molecular data (n = 124) with ultrasonographic carotid measurements from study participants in the IMPROVE cohort (n = 3340). We applied a neural network algorithm and hierarchical clustering to identify carotid atherosclerosis endotypes. A measure of carotid subclinical atherosclerosis, the c-IMTmean-max, was used to extract atherosclerosis-related features and SHapley Additive exPlanations (SHAP) to reveal endotypes. The association of endotypes with carotid ultrasonographic measurements at baseline, after 30 months, and with the 3-year atherosclerotic cardiovascular disease (ASCVD) risk was estimated by linear (& beta;, SE) and Cox [hazard ratio (HR), 95% confidence interval (CI)] regression models. Crude estimates were adjusted by common cardiovascular risk factors, and baseline ultrasonographic measures. Improvement in ASCVD risk prediction was evaluated by C-statistic and by net reclassification improvement with reference to SCORE2, c-IMTmean-max, and presence of carotid plaques. An ensemble stacking model was used to predict endotypes in an independent validation cohort, the PIVUS (n = 1061). We identified four endotypes able to differentiate carotid atherosclerosis risk profiles from mild (endotype 1) to severe (endotype 4). SHAP identified endotype-shared variables (age, biological sex, and systolic blood pressure) and endotype-specific biomarkers. In the IMPROVE, as compared to endotype 1, endotype 4 associated with the thickest c-IMT at baseline (& beta;, SE) 0.36 (0.014), the highest number of plaques 1.65 (0.075), the fastest c-IMT progression 0.06 (0.013), and the highest ASCVD risk (HR, 95% CI) (1.95, 1.18-3.23). Baseline and progression measures of carotid subclinical atherosclerosis and ASCVD risk were associated with the predicted endotypes in the PIVUS. Endotypes consistently improved measures of ASCVD risk discrimination and reclassification in both study populations. Conclusions We report four replicable subclinical carotid atherosclerosis-endotypes associated with progression of atherosclerosis and ASCVD risk in two independent populations. Our approach based on endotypes can be applied for precision medicine in ASCVD prevention.

  • 33.
    Christou, Constantina
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Otolaryngology and Head and Neck Surgery.
    Ehrsson, Ylva Tiblom
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Otolaryngology and Head and Neck Surgery. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Caring Sciences.
    Lampa, Erik
    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, Occupational and Environmental Medicine. 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, Faculty of Medicine, Department of Surgical Sciences.
    Risérus, Ulf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism. 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, Faculty of Medicine, Department of Medical Sciences.
    Laurell, Göran
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Otolaryngology and Head and Neck Surgery.
    Circulating fatty acids in patients with head and neck cancer after treatment: an explorative study with a one-year perspective2021In: Acta Oto-Laryngologica, ISSN 0001-6489, E-ISSN 1651-2251, Vol. 141, no 9, p. 878-884Article in journal (Refereed)
    Abstract [en]

    Background: Unintended weight loss and nutritional problems are often seen in patients with head and neck cancer, but changes in lipid metabolism are poorly studied.

    Aim/Objectives: The present study aimed to explore the longitudinal changes in circulating fatty acid (FA) composition in patients with head and neck cancer.

    Materials and Methods: This study included 27 patients with head and neck cancer. Treatment consisted of single modality or combined modality treatments. The patients were assessed by repeated blood sampling and body weight assessments before treatment started and on three occasions after the start of treatment. FA profiling included gas chromatography analysis of unsaturated FAs and saturated FAs in serum.

    Results: The values of three fatty acids - FA 14:0, FA 18:3n3, and FA 20:3n6 - changed in a specific pattern over the course of the study and the change in FA 14:0 correlated with weight changes.

    Conclusions and significance: This study showed altered profiles of both saturated and unsaturated FAs. An improved understanding of the metabolic pathways in patients with head and neck cancer supports the development of better nutritional surveillance and nutritional treatments.

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  • 34.
    Chróinín, Danielle Ní
    et al.
    Natl Univ Ireland Univ Coll Dublin, Neurovasc Unit Appl Translat Res & Therapeut, Mater Univ Hosp, Dublin Acad Med Ctr, Dublin, Ireland.
    Asplund, Kjell
    Umeå Univ Hosp, Dept Med, Umeå, Sweden.
    Åsberg, Signild
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Epidemiology.
    Callaly, Elizabeth
    Natl Univ Ireland Univ Coll Dublin, Neurovasc Unit Appl Translat Res & Therapeut, Mater Univ Hosp, Dublin Acad Med Ctr, Dublin, Ireland.
    Cuadrado-Godia, Elisa
    Hosp del Mar IMIM, Dept Neurol, Barcelona, Spain.
    Diez-Tejedor, Exuperio
    Univ Autonoma Madrid, Dept Neurol, La Paz Univ Hosp, Madrid, Spain; Univ Autonoma Madrid, Stroke Ctr, La Paz Univ Hosp, Madrid, Spain.
    Di Napoli, Mario
    San Camillo deLellis Gen Hosp, Neurol Serv, Rieti, Italy; Ctr Cardiovasc Med & Cerebrovasc Dis Prevent, SMDN, Laquila, Italy .
    Engelter, Stefan T.
    Univ Basel Hosp, Dept Neurol, Basel, Switzerland.
    Furie, Karen L.
    Massachusetts Gen Hosp, J Philip Kistler Stroke Res Ctr, Ctr Human Genet Res, Boston, MA USA.
    Giannopoulos, Sotirios
    Univ Ioannina, Sch Med, Ioannina, Greece.
    Gotto, Antonio M., Jr.
    Weill Cornell Med Coll, New York, NY USA.
    Hannon, Niamh
    Natl Univ Ireland Univ Coll Dublin, Neurovasc Unit Appl Translat Res & Therapeut, Mater Univ Hosp, Dublin Acad Med Ctr, Dublin, Ireland.
    Jonsson, Fredrik
    Umeå Univ Hosp, Dept Med, Umeå, Sweden.
    Kapral, Moira K.
    Toronto Gen Hosp, Inst Clin Evaluat Sci, Toronto, ON, Canada.
    Martí-Fàbregas, Joan
    Hosp Santa Creu & Sant Pau, Barcelona, Spain.
    Martínez-Sánchez, Patricia
    Univ Autonoma Madrid, Dept Neurol, La Paz Univ Hosp, Madrid, Spain; Univ Autonoma Madrid, Stroke Ctr, La Paz Univ Hosp, Madrid, Spain.
    Milionis, Haralampos J.
    Univ Ioannina, Sch Med, Ioannina, Greece.
    Montaner, Joan
    Autonomous Univ Barcelona, Hosp Vall dHebron, Barcelona, Spain; Autonomous Univ Barcelona, Vall dHebron Res Inst VHIR, Barcelona, Spain.
    Muscari, Antonio
    Univ Bologna, S Orsola Malpighi Hosp, Bologna, Italy.
    Pikija, Slaven
    Gen Hosp Varazdin, Varazhdin, Croatia.
    Probstfield, Jeffrey
    Univ Washington, Dept Med, Seattle, WA USA; Univ Washington, Dept Epidemiol, Seattle, WA USA.
    Rost, Natalia S.
    Massachusetts Gen Hosp, J Philip Kistler Stroke Res Ctr, Ctr Human Genet Res, Boston, MA USA.
    Thrift, Amanda G.
    Monash Univ, Monash Med Ctr, Stroke & Ageing Res Ctr, Dept Med, Clayton, Vic, Australia; Natl Stroke Res Inst, Heidelberg, Vic, Australia.
    Vemmos, Konstantinos
    Univ Athens, Dept Therapeut, Alexandra Hosp, Athens, Greece.
    Kelly, Peter J.
    Natl Univ Ireland Univ Coll Dublin, Neurovasc Unit Appl Translat Res & Therapeut, Mater Univ Hosp, Dublin Acad Med Ctr, Dublin, Ireland.
    Statin Therapy and Outcome After Ischemic Stroke: Systematic Review and Meta-Analysis of Observational Studies and Randomized Trials2013In: Stroke, ISSN 0039-2499, E-ISSN 1524-4628, Vol. 44, no 2, p. 448-456Article, review/survey (Refereed)
    Abstract [en]

    Background and Purpose: Although experimental data suggest that statin therapy may improve neurological outcome after acute cerebral ischemia, the results from clinical studies are conflicting. We performed a systematic review and meta-analysis investigating the relationship between statin therapy and outcome after ischemic stroke.

    Methods: The primary analysis investigated statin therapy at stroke onset (prestroke statin use) and good functional outcome (modified Rankin score 0 to 2) and death. Secondary analyses included the following: (1) acute poststroke statin therapy (≤72 hours after stroke), and (2) thrombolysis-treated patients.

    Results: The primary analysis included 113 148 subjects (27 studies). Among observational studies, statin treatment at stroke onset was associated with good functional outcome at 90 days (pooled odds ratio [OR], 1.41; 95% confidence interval [CI], 1.29–1.56; P<0.001), but not 1 year (OR, 1.12; 95% CI, 0.9–1.4; P=0.31), and with reduced fatality at 90 days (pooled OR, 0.71; 95% CI, 0.62–0.82; P<0.001) and 1 year (OR, 0.80; 95% CI, 0.67–0.95; P=0.01). In the single randomized controlled trial reporting 90-day functional outcome, statin treatment was associated with good outcome (OR, 1.5; 95% CI, 1.0–2.24; P=0.05). No reduction in fatality was observed on meta-analysis of data from 3 randomized controlled trials (P=0.9). In studies restricted to of thrombolysis-treated patients, an association between statins and increased fatality at 90 days was observed (pooled OR, 1.25; 95% CI, 1.02–1.52; P=0.03, 3 studies, 4339 patients). However, this association was no longer present after adjusting for age and stroke severity in the largest study (adjusted OR, 1.14; 95% CI, 0.90–1.44; 4012 patients).

    Conclusion: In the largest meta-analysis to date, statin therapy at stroke onset was associated with improved outcome, a finding not observed in studies restricted to thrombolysis-treated patients. Randomized trials of statin therapy in acute ischemic stroke are needed.

  • 35. Clapham, Eric
    et al.
    Bodén, Robert
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Psychiatry.
    Linder, Marie
    Centrum för farmakoepidemiologi, Instititutionen för medicin Solna, Karolinska Universitetssjukhuset, Karolinska Institutet.
    Brandt, Lena
    Centrum för farmakoepidemiologi, Instititutionen för medicin Solna, Karolinska Universitetssjukhuset, Karolinska Institutet.
    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, 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. 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, Clinical Epidemiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Occupational and Environmental Medicine.
    Reutfors, Johan
    Centrum för farmakoepidemiologi, Instititutionen för medicin Solna, Karolinska Universitetssjukhuset, Karolinska Institutet.
    Perimyocarditis and heart failure after exposure to clozapine, olanzapine, and quetiapine: A population-based cohort studyManuscript (preprint) (Other academic)
  • 36.
    Clapham, Eric
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Psychiatry. Karolinska Univ Hosp, Karolinska Inst, Ctr Pharmacoepidemiol CPE, Dept Med Solna, Stockholm, Sweden..
    Reutfors, Johan
    Karolinska Univ Hosp, Karolinska Inst, Ctr Pharmacoepidemiol CPE, Dept Med Solna, Stockholm, Sweden..
    Linder, Marie
    Karolinska Univ Hosp, Karolinska Inst, Ctr Pharmacoepidemiol CPE, Dept Med Solna, Stockholm, Sweden..
    Brandt, Lena
    Karolinska Univ Hosp, Karolinska Inst, Ctr Pharmacoepidemiol CPE, Dept Med Solna, 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, Australia..
    Bodén, Robert
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Psychiatry.
    The association between exposure to clozapine, olanzapine, and quetiapine and the outcomes perimyocarditis and heart failure: A population-based cohort study2023In: Psychiatry Research, ISSN 0165-1781, E-ISSN 1872-7123, Vol. 326, article id 115336Article in journal (Refereed)
    Abstract [en]

    The risk of cardiac adverse events following clozapine use is debated and is unknown for the chemically related and widely used antipsychotics olanzapine and quetiapine. National Swedish registers were used to identify all patients 16-75 years old with antipsychotic dispensations between 2005 and 2018. The short-term outcome was a diagnosis of perimyocarditis (pericarditis and/or myocarditis) within two months of first dispensation, and the long-term outcome was heart failure (including cardiomyopathy) within three years. Cox regressions with time varying exposure were used to estimate hazard rates (HR) and their 95% confidence intervals (CI). A total of 201,045 individuals were included in the cohort. The risk of developing perimyocarditis during clozapine treatment tripled compared to no antipsychotic treatment (HR 3.4, CI 1.6-7.3), although the absolute rate remained comparably low. The long-term risk of heart failure during clozapine treatment was also elevated (HR 1.3, CI 1.1-1.7). Treatment with either or both olanzapine or quetiapine was not associated with an increased relative risk of perimyocarditis, or heart failure compared to no antipsychotic treatment. Clozapine use is therefore associated with a substantially elevated short-term risk of perimyocarditis and an increased risk of heart failure within three years.

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  • 37.
    Copland, Emma
    et al.
    Univ Oxford, Oxford Martin Sch, Deep Med, Oxford, England.;Univ Oxford, Nuffield Dept Womens & Reprod Hlth, Oxford OX1 2BQ, England.;Oxford Univ Hosp NHS Fdn Trust, Oxford Biomed Res Ctr, Natl Inst Hlth Res, Oxford, England..
    Canoy, Dexter
    Univ Oxford, Oxford Martin Sch, Deep Med, Oxford, England.;Univ Oxford, Nuffield Dept Womens & Reprod Hlth, Oxford OX1 2BQ, England.;Oxford Univ Hosp NHS Fdn Trust, Oxford Biomed Res Ctr, Natl Inst Hlth Res, Oxford, England..
    Nazarzadeh, Milad
    Univ Oxford, Oxford Martin Sch, Deep Med, Oxford, England.;Univ Oxford, Nuffield Dept Womens & Reprod Hlth, Oxford OX1 2BQ, England..
    Bidel, Zeinab
    Univ Oxford, Oxford Martin Sch, Deep Med, Oxford, England.;Univ Oxford, Nuffield Dept Womens & Reprod Hlth, Oxford OX1 2BQ, England.;Oxford Univ Hosp NHS Fdn Trust, Oxford Biomed Res Ctr, Natl Inst Hlth Res, Oxford, England..
    Ramakrishnan, Rema
    Univ Oxford, Oxford Martin Sch, Deep Med, Oxford, England.;Univ Oxford, Nuffield Dept Womens & Reprod Hlth, Oxford OX1 2BQ, England..
    Woodward, Mark
    Univ New South Wales, Inst Global Hlth, Sydney, NSW, Australia.;Imperial Coll London, George Inst Global Hlth, Dept Epidemiol & Biostat, London, Australia.;Johns Hopkins Univ, Dept Epidemiol, Baltimore, MD USA..
    Chalmers, John
    Univ New South Wales, Inst Global Hlth, Sydney, NSW, Australia..
    Teo, Koon K.
    McMaster Univ, Populat Hlth Res Inst, Hamilton Hlth Sci, Hamilton, ON, Canada..
    Pepine, Carl J.
    Univ Florida, Coll Med, Gainesville, FL USA..
    Davis, Barry R.
    Univ Texas Houston, Sch Publ Hlth, Houston, TX USA..
    Kjeldsen, Sverre
    Univ Oslo, Ullevaal Hosp, Dept Cardiol, Oslo, Norway..
    Sundström, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Epidemiology.
    Rahimi, Kazem
    Univ Oxford, Oxford Martin Sch, Deep Med, Oxford, England.;Univ Oxford, Nuffield Dept Womens & Reprod Hlth, Oxford OX1 2BQ, England.;Oxford Univ Hosp NHS Fdn Trust, Oxford Biomed Res Ctr, Natl Inst Hlth Res, Oxford, England..
    Antihypertensive treatment and risk of cancer: an individual participant data meta-analysis2021In: The Lancet Oncology, ISSN 1470-2045, E-ISSN 1474-5488, Vol. 22, no 4, p. 558-570Article in journal (Refereed)
    Abstract [en]

    Findings 33 trials met the inclusion criteria, and included 260 447 participants with 15 012 cancer events. Median follow-up of included participants was 4?2 years (IQR 3?0?5?0). In the individual participant data meta-analysis comparing each drug class with all other comparators, no associations were identified between any antihypertensive drug class and risk of any cancer (HR 0?99 [95% CI 0?95?1?04] for ACEIs; 0?96 [0?92?1?01] for ARBs; 0?98 [0?89?1?07] for 13 blockers; 1?01 [0?95?1?07] for thiazides), with the exception of calcium channel blockers (1?06 [1?01?1?11]). In the network meta-analysis comparing drug classes against placebo, we found no excess cancer risk with any drug class (HR 1?00 [95% CI 0?93?1?09] for ACEIs; 0?99 [0?92?1?06] for ARBs; 0?99 [0?89?1?11] for 13 blockers; 1?04 [0?96?1?13] for calcium channel blockers; 1?00 [0?90?1?10] for thiazides). Summary Background Some studies have suggested a link between antihypertensive medication and cancer, but the evidence is so far inconclusive. Thus, we aimed to investigate this association in a large individual patient data meta-analysis of randomised clinical trials. Methods We searched PubMed, MEDLINE, The Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov from Jan 1, 1966, to Sept 1, 2019, to identify potentially eligible randomised controlled trials. Eligible studies were randomised controlled trials comparing one blood pressure lowering drug class with a placebo, inactive control, or other blood pressure lowering drug. We also required that trials had at least 1000 participant years of follow-up in each treatment group. Trials without cancer event information were excluded. We requested individual participant data from the authors of eligible trials. We pooled individual participant-level data from eligible trials and assessed the effects of angiotensin-converting enzyme inhibitors (ACEIs), angiotensin II receptor blockers (ARBs), 13 blockers, calcium channel blockers, and thiazide diuretics on cancer risk in one-stage individual participant data and network meta-analyses. Cause-specific fixed-effects Cox regression models, stratified by trial, were used to calculate hazard ratios (HRs). The primary outcome was any cancer event, defined as the first occurrence of any cancer diagnosed after randomisation. This study is registered with PROSPERO (CRD42018099283). Findings 33 trials met the inclusion criteria, and included 260 447 participants with 15 012 cancer events. Median follow-up of included participants was 4 & middot;2 years (IQR 3 & middot;0 & ndash;5 & middot;0). In the individual participant data meta-analysis comparing each drug class with all other comparators, no associations were identified between any antihypertensive drug class and risk of any cancer (HR 0 & middot;99 [95% CI 0 & middot;95 & ndash;1 & middot;04] for ACEIs; 0 & middot;96 [0 & middot;92 & ndash;1 & middot;01] for ARBs; 0 & middot;98 [0 & middot;89 & ndash;1 & middot;07] for 13 blockers; 1 & middot;01 [0 & middot;95 & ndash;1 & middot;07] for thiazides), with the exception of calcium channel blockers (1 & middot;06 [1 & middot;01 & ndash;1 & middot;11]). In the network meta-analysis comparing drug classes against placebo, we found no excess cancer risk with any drug class (HR 1 & middot;00 [95% CI 0 & middot;93 & ndash;1 & middot;09] for ACEIs; 0 & middot;99 [0 & middot;92 & ndash;1 & middot;06] for ARBs; 0 & middot;99 [0 & middot;89 & ndash;1 & middot;11] for 13 blockers; 1 & middot;04 [0 & middot;96 & ndash;1 & middot;13] for calcium channel blockers; 1 & middot;00 [0 & middot;90 & ndash;1 & middot;10] for thiazides). Interpretation We found no consistent evidence that antihypertensive medication use had any effect on cancer risk. Although such findings are reassuring, evidence for some comparisons was insufficient to entirely rule out excess risk, in particular for calcium channel blockers.

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  • 38.
    Crilly, Julia
    et al.
    Gold Coast Hlth, Dept Emergency Med, 1 Hosp Blvd, Southport, Qld 4215, Australia.;Griffith Univ, Sch Nursing & Midwifery, Southport, Qld, Australia..
    Sweeny, Amy
    Gold Coast Hlth, Dept Emergency Med, 1 Hosp Blvd, Southport, Qld 4215, Australia.;Griffith Univ, Sch Nursing & Midwifery, Southport, Qld, Australia..
    Muntlin, Åsa
    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, Faculty of Medicine, Department of Public Health and Caring Sciences.
    Green, David
    Gold Coast Hlth, Dept Emergency Med, 1 Hosp Blvd, Southport, Qld 4215, Australia..
    Malyon, Lorelle
    Queensland Childrens Hosp, Emergency Dept, Childrens Hlth Queensland, Brisbane, Qld, Australia..
    Christofis, Luke
    Lyell McEwin Hosp, Emergency Dept, Elizabeth Vale, SA, Australia..
    Higgins, Malcolm
    Womens & Childrens Hosp, Paediat Emergency Dept, North Adelaide, SA, Australia..
    Kallberg, Ann-Sofie
    Dalarna Univ, Sch Hlth & Welf, Falun, Sweden.;Falun Cent Hosp, Dept Emergency Med, Falun, Sweden..
    Dellner, Sara
    Maternal Hlth Care Unit, Reg Stockholm, Stockholm, Sweden..
    Myrelid, Åsa
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Djarv, Therese
    Karolinska Univ Hosp, Emergency & Reparat Med Theme, Stockholm, Sweden.;Karolinska Inst, Dept Med, Stockholm, Sweden..
    Goransson, Katarina E.
    Dalarna Univ, Sch Hlth & Welf, Falun, Sweden.;Karolinska Inst, Dept Med, Stockholm, Sweden..
    Factors predictive of hospital admission for children via emergency departments in Australia and Sweden: an observational cross-sectional study2024In: BMC Health Services Research, E-ISSN 1472-6963, Vol. 24, no 1, article id 235Article in journal (Refereed)
    Abstract [en]

    Background: Identifying factors predictive of hospital admission can be useful to prospectively inform bed management and patient flow strategies and decrease emergency department (ED) crowding. It is largely unknown if admission rate or factors predictive of admission vary based on the population to which the ED served (i.e., children only, or both adults and children). This study aimed to describe the profile and identify factors predictive of hospital admission for children who presented to four EDs in Australia and one ED in Sweden.

    Methods: A multi-site observational cross-sectional study using routinely collected data pertaining to ED presentations made by children < 18 years of age between July 1, 2011 and October 31, 2012. Univariate and multivariate analysis were undertaken to determine factors predictive of hospital admission.

    Results: Of the 151,647 ED presentations made during the study period, 22% resulted in hospital admission. Admission rate varied by site; the children's EDs in Australia had higher admission rates (South Australia: 26%, Queensland: 23%) than the mixed (adult and children's) EDs (South Australia: 13%, Queensland: 17%, Sweden: 18%). Factors most predictive of hospital admission for children, after controlling for triage category, included hospital type (children's only) adjusted odds ratio (aOR):2.3 (95%CI: 2.2-2.4), arrival by ambulance aOR:2.8 (95%CI: 2.7-2.9), referral from primary health aOR:1.5 (95%CI: 1.4-1.6) and presentation with a respiratory or gastrointestinal condition (aOR:2.6, 95%CI: 2.5-2.8 and aOR:1.5, 95%CI: 1.4-1.6, respectively). Predictors were similar when each site was considered separately.

    Conclusions: Although the characteristics of children varied by site, factors predictive of hospital admission were mostly similar. The awareness of these factors predicting the need for hospital admission can support the development of clinical pathways.

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  • 39.
    Dekkers, Koen
    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. Inst Salud Carlos III, CIBER Cardiovasc Dis CIBERCV, Madrid, Spain..
    Baldanzi, Gabriel
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Nowak, Christoph
    Karolinska Inst, Dept Neurobiol Care Sci & Soc, Div Family Med & Primary Care, Huddinge, Sweden..
    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, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Varotsis, Georgios
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Brunkwall, Louise
    Lund Univ, Dept Clin Sci, Malmö, Sweden..
    Nielsen, Nynne
    Clin Microbi AS, Copenhagen, Denmark..
    Eklund, Aron C.
    Clin Microbi AS, Copenhagen, Denmark..
    Holm, Jacob Bak
    Clin Microbi AS, Copenhagen, Denmark..
    Nielsen, H. Bjorn
    Clin Microbi AS, Copenhagen, Denmark..
    Ottosson, Filip
    Lund Univ, Dept Clin Sci, Malmö, Sweden..
    Yi-Ting, Lin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    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.
    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. Univ New South Wales, George Inst Global Hlth, Sydney, NSW, Australia..
    Engstrom, Gunnar
    Lund Univ, Dept Clin Sci, Malmö, Sweden..
    Smith, J. Gustav
    Gothenburg Univ, Inst Med, Dept Mol & Clin Med, Wallenberg Lab, Gothenburg, Sweden.;Sahlgrens Univ Hosp, Dept Cardiol, Gothenburg, Sweden.;Lund Univ, Clin Sci, Dept Cardiol, Lund, Sweden.;Skane Univ Hosp, Lund, Sweden.;Lund Univ, Wallenberg Ctr Mol Med, Lund, Sweden.;Lund Univ, Diabet Ctr, Lund, Sweden..
    Arnlov, Johan
    Karolinska Inst, Dept Neurobiol Care Sci & Soc, Div Family Med & Primary Care, Huddinge, Sweden.;Dalarna Univ, Sch Hlth & Social Studies, Falun, Sweden..
    Orho-Melander, Marju
    Lund Univ, Dept Clin Sci, Malmö, 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.
    An online atlas of human plasma metabolite signatures of gut microbiome composition2022In: Nature Communications, E-ISSN 2041-1723, Vol. 13, no 1, article id 5370Article in journal (Refereed)
    Abstract [en]

    Human gut microbiota produce a variety of molecules, some of which enter the bloodstream and impact health. Conversely, dietary or pharmacological compounds may affect the microbiota before entering the circulation. Characterization of these interactions is an important step towards understanding the effects of the gut microbiota on health. In this cross-sectional study, we used deep metagenomic sequencing and ultra-high-performance liquid chromatography linked to mass spectrometry for a detailed characterization of the gut microbiota and plasma metabolome, respectively, of 8583 participants invited at age 50 to 64 from the population-based Swedish CArdioPulmonary bioImage Study. Here, we find that the gut microbiota explain up to 58% of the variance of individual plasma metabolites and we present 997 associations between alpha diversity and plasma metabolites and 546,819 associations between specific gut metagenomic species and plasma metabolites in an online atlas (https://gutsyatlas.serve.scilifelab.se/). We exemplify the potential of this resource by presenting novel associations between dietary factors and oral medication with the gut microbiome, and microbial species strongly associated with the uremic toxin p-cresol sulfate. This resource can be used as the basis for targeted studies of perturbation of specific metabolites and for identification of candidate plasma biomarkers of gut microbiota composition.

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  • 40.
    Diamanti, Klev
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology, Computational Biology and Bioinformatics.
    Visvanathar, Robin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences.
    Pereira, Maria J
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical diabetology and metabolism.
    Cavalli, Marco
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Medicinsk genetik och genomik. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Pan, Gang
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Medicinsk genetik och genomik.
    Kumar, Chanchal
    Translational Science & Experimental Medicine, Early Cardiovascular, Renal and Metabolism, R&D BioPharmaceuticals, AstraZeneca; Karolinska Institute/AstraZeneca Integrated CardioMetabolic Centre (KI/AZ ICMC), Department of Medicine.
    Stanko, Stanko
    Pharmaceutical Technology & Development, AstraZeneca AB; Department of Medicine, Sahlgrenska University Hospital, Gothenburg.
    Ingelsson, Martin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    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. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Lind, Lars
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular Medicine. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Research and Development, Gävleborg. 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 Public Health and Caring Sciences, Geriatrics. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Epidemiology.
    Risérus, Ulf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism. 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, Faculty of Medicine, Department of Medical Sciences.
    Eriksson, Jan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical diabetology and metabolism.
    Kullberg, Joel
    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, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Wadelius, Claes
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Medicinsk genetik och genomik.
    Ahlström, Håkan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Komorowski, Jan
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology, Computational Biology and Bioinformatics.
    Integration of whole-body PET/MRI with non-targeted metabolomics provides new insights into insulin sensitivity of various tissuesManuscript (preprint) (Other academic)
    Abstract [en]

    Background: Alteration of various metabolites has been linked to type 2 diabetes (T2D) and insulin resistance. However, identifying significant associations between metabolites and tissue-specific alterations is challenging and requires a multi-omics approach. In this study, we aimed at discovering associations of metabolites from subcutaneous adipose tissue (SAT) and plasma with the volume, the fat fraction (FF) and the insulin sensitivity (Ki) of specific tissues using [18F]FDG PET/MRI.

    Materials and Methods: In a cohort of 42 subjects with different levels of glucose tolerance (normal, prediabetes and T2D) matched for age and body-mass-index (BMI) we calculated associations between parameters of whole-body FDG PET/MRI during clamp and non-targeted metabolomics profiling for SAT and blood plasma. We also used a rule-based classifier to identify a large collection of prevalent patterns of co-dependent metabolites that characterize non-diabetes (ND) and T2D.

    Results: The plasma metabolomics profiling revealed that hepatic fat content was positively associated with tyrosine, and negatively associated with lysoPC(P-16:0). Ki in visceral adipose tissue (VAT) and SAT, was positively associated with several species of lysophospholipids while the opposite applied to branched-chain amino acids (BCAA) and their intermediates. The adipose tissue metabolomics revealed a positive association between non-esterified fatty acids and, VAT and liver Ki. On the contrary, bile acids and carnitines in adipose tissue were inversely associated with VAT Ki. Finally, we presented a transparent machine-learning model that predicted ND or T2D in “unseen” data with an accuracy of 78%.

    Conclusions: Novel associations of several metabolites from SAT and plasma with the FF, volume and insulin senstivity of various tissues throughout the body were discovered using PET/MRI and a new integrative multi-omics approach. A promising computational model that predicted ND and T2D with high certainty, suggested novel non-linear interdependencies of metabolites.

  • 41.
    Dumanski, Jan P.
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Medicinsk genetik och genomik. Uppsala University, Science for Life Laboratory, SciLifeLab. Faculty of Pharmacy, Medical University of Gdansk, Poland.
    Sundström, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Epidemiology.
    Forsberg, Lars A.
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Medicinsk genetik och genomik. Beijer Laboratory of Genome Research, Uppsala University.
    Loss of Chromosome Y in Leukocytes and Major Cardiovascular Events2017In: Circulation: Cardiovascular Genetics, ISSN 1942-325X, E-ISSN 1942-3268, Vol. 10, no 4Article in journal (Other academic)
  • 42.
    Dunder, Linda
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Occupational and Environmental Medicine.
    Lejonklou, Margareta Halin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Occupational and Environmental Medicine.
    Lind, P. Monica
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Occupational and Environmental Medicine.
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Epidemiology.
    Urinary bisphenol A and serum lipids: a meta-analysis of six NHANES examination cycles (2003-2014)2019In: Journal of Epidemiology and Community Health, ISSN 0143-005X, E-ISSN 1470-2738, Vol. 73, no 11, p. 1012-1019Article in journal (Refereed)
    Abstract [en]

    Background: Mounting evidence from both experimental and epidemiological studies suggest that exposure to the endocrine disruptor bisphenol A (BPA) has a role in metabolic disorders. The aim of the present study was to assess whether urinary BPA concentrations were associated with dyslipidaemia in children (<= 17 years old) and adults (>= 18 years old) by performing a meta-analysis of data from six cycles (2003-2014) in the National Health and Nutrition Examination Survey (NHANES).

    Methods: We conducted a meta-analysis of data from 4604 children and 10 989 adult participants who were part of a substudy of urinary BPA measurements from six NHANES cycles from 2003 to 2014. Linear regression models conducted in each cycle were used to perform a meta-analysis to investigate associations between urinary BPA and serum levels of low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), total cholesterol (TC), triglycerides (TG) and apolipoprotein B (ApoB).

    Results: The meta-analysis did not disclose any significant associations between urinary BPA concentrations and LDL-C, HDL-C, TC, TG and ApoB in children. In adults, the meta-analysis revealed negative regression coefficients for all five lipid variables. However, no associations were significant following Bonferroni correction for multiple tests.

    Conclusions: In the present meta-analysis of cross-sectional data from NHANES, no associations were found between urinary BPA and the five different lipid variables when investigated in both children and adults. However, considering the cross-sectional nature of the present study, results should be clarified in carefully designed longitudinal cohort studies with repeated BPA measurements.

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  • 43.
    Dunder, Linda
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Occupational and Environmental Medicine.
    Salihovic, Samira
    Örebro Univ, Sch Med Sci, Örebro, Sweden..
    Elmståhl, Sölve
    Lund Univ, Dept Clin Sci Malmö, Div Geriatr Med, Malmö, Sweden..
    Lind, P. Monica
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Occupational and Environmental Medicine.
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Epidemiology.
    Associations between per- and polyfluoroalkyl substances (PFAS) and diabetes in two population-based cohort studies from Sweden2023In: Journal of Exposure Science and Environmental Epidemiology, ISSN 1559-0631, E-ISSN 1559-064X, Vol. 33, p. 748-756Article in journal (Refereed)
    Abstract [en]

    Background: Per- and polyfluoroalkyl substances (PFAS) have been suggested to contribute to the development of metabolic diseases such as obesity, diabetes and non-alcoholic fatty liver disease (NAFLD). However, evidence from epidemiological studies remain divergent. The aim of the present study was to evaluate associations between PFAS exposure and prevalent diabetes in a cross-sectional analysis and fasting glucose in a longitudinal analysis.

    Methods: In 2373 subjects aged 45-75 years from the EpiHealth study, three PFAS; perfluorohexanesulfonic acid (PFHxS), perfluorooctanoic acid (PFOA) and perfluorooctane sulfonic acid (PFOS) were analyzed in plasma together with information on prevalent diabetes. Participants in the PIVUS study (n = 1016 at baseline, all aged 70 years) were followed over 10 years regarding changes in plasma levels of six PFAS; PFHxS, PFOA, PFOS, perfluorononanoic acid (PFNA), perfluorodecanoic acid (PFDA), and perfluoroundecanoic acid (PFUnDA), and changes in plasma levels of fasting glucose.

    Results: In the EpiHealth study, no overall associations could be observed between the levels of PFOA, PFOS or PFHxS and prevalent diabetes. However, there was a significant sex-interaction for PFOA (p = 0.02), and an inverse association could be seen between PFOA (on a SD-scale) and prevalent diabetes in women only (OR: 0.71, 95% CI: 0.52, 0.96, p-value: 0.02). This association showed a non-monotonic dose-response curve. In the PIVUS study, inverse relationships could be observed between the changes in levels (ln-transformed) of PFOA and PFUnDA vs the change in fasting glucose levels (ln-transformed) over 10 years (p = 0.04 and p = 0.02, respectively). As in EpiHealth, these inverse associations were significant only in women (PFOA: beta: -0.03, p = 0.02, PFUnDA: beta: -0.03, p = 0.03).

    Impact: Exposure to per- and polyfluoroalkyl substances (PFAS) has been linked to unfavorable human health, including metabolic disorders such as obesity, diabetes and non-alcoholic fatty liver disease. However, results from in vivo, in vitro and epidemiological studies are incoherent. The aim of the present study was therefore to investigate associations between PFAS and diabetes in a cross-sectional study and glucose levels in a longitudinal study. Results show inverse associations in women only. Results also display non-monotonic dose response curves (i.e., that only low levels of PFOA are related to higher probability of prevalent diabetes). This suggests that sex differences and complex molecular mechanisms may underlie the observed findings. A better understanding of the factors and molecular mechanisms contributing to such differences is recognized as an important direction for future research.

    Conclusions: PFOA was found to be inversely related to both prevalent diabetes and changes in plasma glucose levels among women only. Thus, our findings suggest there are sex differences in the inverse relationship of PFOA and type 2 diabetes and glucose levels.

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  • 44.
    Dunder, Linda
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Occupational and Environmental Medicine.
    Salihovic, Samira
    Univ Örebro, Sch Med Sci, Fac Med & Hlth, Örebro, Sweden..
    Varotsis, Georgios
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology.
    Lind, P. Monica
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Occupational and Environmental Medicine.
    Elmståhl, Sölve
    Lund Univ, Dept Clin Sci Malmö, Div Geriatr Med, Malmö, Sweden..
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Epidemiology.
    Plasma levels of per- and polyfluoroalkyl substances (PFAS) and cardiovascular disease - Results from two independent population-based cohorts and a meta-analysis2023In: Environment International, ISSN 0160-4120, E-ISSN 1873-6750, Vol. 181, article id 108250Article in journal (Refereed)
    Abstract [en]

    Background: Per- and polyfluoroalkyl substances (PFAS) are persistent chemicals that have been linked to increased cholesterol levels and thus may have a role in the development of cardiovascular disease (CVD).

    Objectives: To investigate associations between PFAS exposure and incident CVD (a combined CVD end-point consisting of myocardial infarction, ischemic stroke, or heart failure) in two independent population-based cohorts in Sweden. In addition, we performed a meta-analysis also including results from previous studies.

    Methods: In 2,278 subjects aged 45-75 years from the EpiHealth study, the risk of incident CVD in relation to relative plasma levels of perfluorohexanesulfonic acid (PFHxS), perfluorooctanoic acid (PFOA) and perfluorooctane sulfonic acid (PFOS) was investigated. Associations between plasma levels of six PFAS and incident CVD were also examined in the PIVUS-study (n = 1,016, all aged 70 years). In addition, a meta-analysis was performed including three previous prospective studies, together with the results from the present study.

    Results: There were no overall statistically significant associations between levels of the different PFAS and incident CVD, neither in EpiHealth nor in PIVUS. However, there was a significant sex interaction for PFOS in EpiHealth (p = 0.008), and an inverse association could be seen only in men (Men, HR: 0.68, 95 % CI: 0.52, 0.89) (Women, HR: 1.13, 95 % CI: 0.82, 1.55). A meta-analysis of five independent studies regarding PFOA and incident CVD showed a risk ratio (RR) of 0.80 (CI: 0.66, 0.94) when high levels were compared to low levels.

    Conclusions: This longitudinal study using data from two population-based cohort studies in Sweden did not indicate any increased risk of incident CVD for moderately elevated PFAS levels. A meta-analysis of five independent cohort studies rather indicated a modest inverse association between PFOA levels and incident CVD, further supporting that increasing PFAS levels are not linked to an increased risk of CVD.

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  • 45.
    Ekblom‐Bak, Elin
    et al.
    Department of Physical Activity and Health The Swedish School of Sport and Health Sciences Stockholm Sweden.
    Börjesson, Mats
    Center for Health and Performance Department of Molecular and Clinical Medicine Sahlgrenska Academy Gothenburg University Sweden;Dept MGA Sahlgrenska University Hospital Region Västra Götaland Gothenburg Sweden.
    Bergman, Frida
    Department of Public Health and Clinical Medicine Umeå University Umeå Sweden.
    Bergström, Göran
    Department of Molecular and Clinical Medicine Sahlgrenska Academy University of Gothenburg;Clinical Physiology Sahlgrenska University Hospital Gothenburg Sweden.
    Dahlin‐Almevall, Albin
    Department of Health, Learning and Technology Luleå University of Technology Luleå Sweden.
    Drake, Isabel
    Department of Clinical Sciences in Malmö Lund University, Malmö Sweden.
    Engström, Gunnar
    Department of Clinical Sciences in Malmö Lund University, Malmö Sweden.
    Engvall, Jan E.
    CMIV, Centre of Medical Image Science and Visualization Linköping University Linköping Sweden;Department of Clinical Physiology, and Department of Medical and Health Sciences Linköping University Linköping Sweden.
    Gummesson, Anders
    Department of Molecular and Clinical Medicine Sahlgrenska Academy University of Gothenburg;Clinical Genetics and Genomics Sahlgrenska University Hospital Gothenburg 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).
    Hjelmgren, Ola
    Department of Molecular and Clinical Medicine Sahlgrenska Academy University of Gothenburg;Clinical Physiology Sahlgrenska University Hospital Gothenburg Sweden.
    Jernberg, Tomas
    Department of Clinical Sciences Danderyd University Hospital Karolinska Institutet Stockholm Sweden.
    Johansson, Peter J.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Occupational and Environmental Medicine.
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Epidemiology.
    Mannila, Maria
    Heart and Vascular Theme Karolinska University Hospital Stockholm Sweden.
    Nyberg, André
    Department of Community Medicine and Rehabilitation Umeå University Umeå Sweden.
    Persson, Margaretha
    Department of Clinical Sciences in Malmö Lund University Malmö Sweden.
    Reitan, Christian
    Department of Clinical Sciences Danderyd University Hospital Karolinska Institutet Stockholm Sweden.
    Rosengren, Annika
    Department of Molecular and Clinical Medicine Sahlgrenska Academy University of Gothenburg;Clinical Physiology Sahlgrenska University Hospital Gothenburg Sweden.
    Rådholm, Karin
    Department of Health, Medicine and Caring Sciences Linköping University Linköping Sweden.
    Schmidt, Caroline
    Department of Molecular and Clinical Medicine Sahlgrenska Academy University of Gothenburg.
    Sköld, Magnus C.
    Department of Respiratory Medicine and Allergy Karolinska University Hospital Solna Stockholm Sweden;Respiratory Medicine Unit Department of Medicine Solna and Center for Molecular Medicine Karolinska Institutet Stockholm Sweden.
    Sonestedt, Emily
    Department of Clinical Sciences in Malmö Lund University Malmö Sweden.
    Sundström, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Occupational and Environmental Medicine. The George Institute for Global Health, University of New South Wales, Sydney, Australia.
    Swahn, Eva
    Department of Health, Medicine and Caring Sciences Linköping University Linköping Sweden;Department of Cardiology Linköping University Linköping Sweden.
    Öhlin, Jerry
    Department of Community Medicine and Rehabilitation Umeå University Umeå Sweden.
    Östgren, Carl Johan
    Department of Health, Medicine and Caring Sciences Linköping University Linköping Sweden.
    Ekblom, Örjan
    Department of Physical Activity and Health The Swedish School of Sport and Health Sciences Stockholm Sweden.
    Accelerometer derived physical activity patterns in 27.890 middle‐aged adults: The SCAPIS cohort study2022In: Scandinavian Journal of Medicine and Science in Sports, ISSN 0905-7188, E-ISSN 1600-0838, Vol. 32, no 5, p. 866-880Article in journal (Refereed)
    Abstract [en]

    The present study aims to describe accelerometer-assessed physical activity (PA) patterns and fulfillment of PA recommendations in a large sample of middle-aged men and women, and to study differences between subgroups of socio-demographic, socio-economic, and lifestyle-related variables. A total of 27 890 (92.5% of total participants, 52% women, aged 50–64 years) middle-aged men and women with at least four days of valid hip-worn accelerometer data (Actigraph GT3X+, wGT3X+ and wGT3X-BT) from the Swedish CArdioPulmonary bioImage Study, SCAPIS, were included. In total, 54.5% of daily wear time was spent sedentary, 39.1% in low, 5.4% in moderate, and only 0.1% in vigorous PA. Male sex, higher education, low financial strain, born in Sweden, and sedentary/light working situation were related to higher sedentary time, but also higher levels of vigorous PA. High BMI and having multiple chronic diseases associated strongly with higher sedentary time and less time in all three PA intensities. All-year physically active commuters had an overall more active PA pattern. The proportion fulfilling current PA recommendations varied substantially (1.4% to 92.2%) depending on data handling procedures and definition used. Twenty-eight percent was defined as having an “at-risk” behavior, which included both high sedentary time and low vigorous PA. In this large population-based sample, a majority of time was spent sedentary and only a fraction in vigorous PA, with clinically important variations between subgroups. This study provides important reference material and emphasizes the importance of a comprehensive assessment of all aspects of the individual PA pattern in future research and clinical practice.

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  • 46. Ekblom-Bak, Elin
    et al.
    Börjesson, Mats
    Ekblom, Örjan
    Angerås, Oskar
    Bergman, Frida
    Berntsson, Caroline
    Carlhäll, Carl-Johan
    Engström, Gunnar
    Engvall, Jan
    Fagman, Erika
    Flinck, Agneta
    Johansson, Peter
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Occupational and Environmental Medicine.
    Jujic, Amra
    Kero, Tanja
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology. Medical Image Centre, Uppsala University Hospital, Uppsala, Sweden.
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Epidemiology.
    Mannila, Maria
    Ostenfeld, Ellen
    Persson, Anders
    Persson, Jonas
    Persson, Margaretha
    Redfors, Björn
    Sandberg, Camilla
    Wennberg, Patrik
    Öhlin, Jerry
    Östgren, Carl Johan
    Jernberg, Tomas
    Accelerometer derived physical activity and subclinical coronary and carotid atherosclerosis: cross-sectional analyses in 22 703 middle-aged men and women in the SCAPIS study2023In: BMJ Open, E-ISSN 2044-6055, Vol. 13, no 11, article id e073380Article in journal (Refereed)
    Abstract [en]

    Objectives The aim included investigation of the associations between sedentary (SED), low-intensity physical activity (LIPA), moderate-to-vigorous intensity PA (MVPA) and the prevalence of subclinical atherosclerosis in both coronaries and carotids and the estimated difference in prevalence by theoretical reallocation of time in different PA behaviours.

    Design Cross-sectional.

    Setting Multisite study at university hospitals.

    Participants A total of 22 670 participants without cardiovascular disease (51% women, 57.4 years, SD 4.3) from the population-based Swedish CArdioPulmonary bioImage study were included. SED, LIPA and MVPA were assessed by hip-worn accelerometer.

    Primary and secondary outcomes Any and significant subclinical coronary atherosclerosis (CA), Coronary Artery Calcium Score (CACS) and carotid atherosclerosis (CarA) were derived from imaging data from coronary CT angiography and carotid ultrasound.

    Results High daily SED (>70% ≈10.5 hours/day) associated with a higher OR 1.44 (95% CI 1.09 to 1.91), for significant CA, and with lower OR 0.77 (95% CI 0.63 to 0.95), for significant CarA. High LIPA (>55% ≈8 hours/day) associated with lower OR for significant CA 0.70 (95% CI 0.51 to 0.96), and CACS, 0.71 (95% CI 0.51 to 0.97), but with higher OR for CarA 1.41 (95% CI 1.12 to 1.76). MVPA above reference level, >2% ≈20 min/day, associated with lower OR for significant CA (OR range 0.61–0.67), CACS (OR range 0.71–0.75) and CarA (OR range 0.72–0.79). Theoretical replacement of 30 min of SED into an equal amount of MVPA associated with lower OR for significant CA, especially in participants with high SED 0.84 (95% CI 0.76 to 0.96) or low MVPA 0.51 (0.36 to 0.73).

    Conclusions MVPA was associated with a lower risk for significant atherosclerosis in both coronaries and carotids, while the association varied in strength and direction for SED and LIPA, respectively. If causal, clinical implications include avoiding high levels of daily SED and low levels of MVPA to reduce the risk of developing significant subclinical atherosclerosis.

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  • 47.
    Ekermo, David
    et al.
    Linköping Univ, Dept Emergency Med, Dept Biomed & Clin Sci, Linköping, Sweden.
    Ronnas, Matilda
    Karolinska Univ Hosp, Dept Emergency Med, Stockholm, Sweden.
    Muntlin Athlin, Åsa
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Epidemiology. Uppsala Univ Hosp, Dept Emergency Care & Internal Med, Uppsala, Sweden.;Flinders Univ S Australia, Coll Nursing & Hlth Sci, Adelaide, SA, Australia.
    Fundamental nursing actions for frail older people in the emergency department: A national cross-sectional survey and a qualitative analysis of practice guidelines2023In: Journal of Advanced Nursing, ISSN 0309-2402, E-ISSN 1365-2648, Vol. 79, no 8, p. 3115-3126Article in journal (Refereed)
    Abstract [en]

    Aims To map how frailty among older people is assessed at Swedish emergency departments and to describe fundamental nursing care actions for these patients.

    Design Descriptive national survey and a qualitative analysis of text.

    Methods A majority (82%, n = 54) of the Swedish hospital-based emergency departments for adults were included, representing all six healthcare regions. An online survey was used to collect data, together with submitted local practice guidelines for older people at the emergency departments. Data were collected during February-October 2021. Descriptive and comparative statistics were performed together with a deductive content analysis framed by the Fundamentals of Care framework.

    Results Sixty-five per cent (35 of 54) of the emergency departments identified frailty, with less than half of them using an established assessment instrument. Twenty-eight (52%) of the emergency departments have practice guidelines containing fundamental nursing actions for the care of frail older people. The majority of nursing actions in the practice guidelines were related to patients' physical care needs (91%), followed by psychosocial care needs (9%). No actions could be identified as relational actions (0%) according to the Fundamentals of Care framework.

    Conclusion Many Swedish emergency departments identify frail older people, but they use a range of different assessment instruments. While practice guidelines directing fundamental nursing actions for frail older people are often in place, a holistic, person-centred view addressing the patient's physical, psychosocial and relational care needs is missing.

    Impact The population is growing older, and more people are needing more complex hospital care. Frail older people have an increased risk of negative outcomes. The use of a variety of assessment instruments for frailty may pose a challenge to equal care. To ensure a holistic, person-centred view of frail older people, the Fundamentals of Care framework can be used in developing and reviewing practice guidelines.

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  • 48.
    Ekström, Magnus
    et al.
    Lund Univ, Fac Med, Dept Clin Sci Lund Resp Med Allergol & Palliat Med, S-22184 Lund, Sweden..
    Sundh, Josefin
    Örebro Univ, Fac Med & Hlth, Dept Resp Med, Örebro, Sweden..
    Andersson, Anders
    Sahlgrens Univ Hosp, COPD Ctr, Dept Resp Med & Allergol, Gothenburg, Sweden.;Univ Gothenburg, Inst Med, Sahlgrenska Acad, COPD Ctr,Dept Internal Med & Clin Nutr, Gothenburg, Sweden..
    Angerås, Oskar
    Gothenburg Univ, Inst Med, Dept Mol & Clin Med, Gothenburg, Sweden.;Sahlgrens Univ Hosp, Dept Cardiol, Gothenburg, Sweden..
    Blomberg, Anders
    Umeå Univ, Dept Publ Hlth & Clin Med, Umeå, Sweden..
    Börjesson, Mats
    Sahlgrens Acad, Dept Mol & Clin Med, Gothenburg, Sweden.;Sahlgrens Univ Hosp, Ctr Lifestyle Intervent, Dept MGAO, Gothenburg, Sweden..
    Caidahl, Kenneth
    Karolinska Univ Hosp, Dept Clin Physiol, Stockholm, Sweden.;Karolinska Inst, Stockholm, Sweden.;Sahlgrens Univ Hosp, Dept Clin Physiol, Gothenburg, Sweden.;Sahlgrens Acad, Gothenburg, Sweden..
    Emilsson, Össur Ingi
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Lung- allergy- and sleep research.
    Engvall, Jan
    Linköping Univ, Ctr Med Image Sci & Visualizat, CMIV, Linköping, Sweden.;Linköping Univ, Dept Clin Physiol Linköping, Linköping, Sweden.;Linköping Univ, Dept Hlth Med & Caring Sci, Linköping, Sweden..
    Frykholm, Erik
    Umeå Univ, Dept Community Med & Rehabil, Physiotherapy, Umeå, Sweden..
    Grote, Ludger
    Gothenburg Univ, Inst Med, Sahlgrenska Acad, Ctr Sleep & Vigilance Disorders, Gothenburg, Sweden.;Sahlgrens Univ Hosp, Sleep Disorders Ctr, Dept Resp Med, Gothenburg, Sweden..
    Hedman, Kristofer
    Linköping Univ, Dept Clin Physiol Linköping, Linköping, Sweden.;Linköping Univ, Dept Hlth Med & Caring Sci, Linköping, Sweden..
    Jernberg, Tomas
    Danderyd Hosp, Karolinska Inst, Dept Clin Sci, Stockholm, Sweden..
    Lindberg, Eva
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Lung- allergy- and sleep research.
    Malinovschi, Andrei
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Physiology.
    Nyberg, Andre
    Umeå Univ, Dept Community Med & Rehabil, Physiotherapy, Umeå, Sweden..
    Rullman, Eric
    Karolinska Inst, Dept Lab Med, Sect Clin Physiol, Stockholm, Sweden.;Karolinska Univ Hosp, Dept Clin Physiol, Stockholm, Sweden..
    Sandberg, Jacob
    Lund Univ, Fac Med, Dept Clin Sci Lund Resp Med Allergol & Palliat Med, S-22184 Lund, Sweden..
    Sköld, Magnus
    Karolinska Inst, Dept Med Solna, Resp Med Unit, Stockholm, Sweden.;Karolinska Inst, Ctr Mol Med, Stockholm, Sweden.;Karolinska Univ Hosp, Dept Resp Med & Allergy, Stockholm, Sweden..
    Stenfors, Nikolai
    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, Clinical Epidemiology. Univ New South Wales, George Inst Global Hlth, Sydney, Australia..
    Tanash, Hanan
    Lund Univ, Skane Univ Hosp, Dept Resp Med, Malmö, Sweden..
    Zaigham, Suneela
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Physiology. Lund Univ, Dept Clin Sci Malmö, Malmö, Sweden..
    Carlhäll, Carl-Johan
    Linköping Univ, Dept Clin Physiol Linköping, Linköping, Sweden.;Linköping Univ, Ctr Med Image Sci & Visualizat, Linköping, Sweden..
    Exertional breathlessness related to medical conditions in middle-aged people: the population-based SCAPIS study of more than 25,000 men and women2024In: Respiratory Research, ISSN 1465-9921, E-ISSN 1465-993X, Vol. 25, article id 127Article in journal (Refereed)
    Abstract [en]

    Background: Breathlessness is common in the population and can be related to a range of medical conditions. We aimed to evaluate the burden of breathlessness related to different medical conditions in a middle-aged population.

    Methods: Cross-sectional analysis of the population-based Swedish CArdioPulmonary bioImage Study of adults aged 50-64 years. Breathlessness (modified Medical Research Council [mMRC] ≥ 2) was evaluated in relation to self-reported symptoms, stress, depression; physician-diagnosed conditions; measured body mass index (BMI), spirometry, venous haemoglobin concentration, coronary artery calcification and stenosis [computer tomography (CT) angiography], and pulmonary emphysema (high-resolution CT). For each condition, the prevalence and breathlessness population attributable fraction (PAF) were calculated, overall and by sex, smoking history, and presence/absence of self-reported cardiorespiratory disease.

    Results: We included 25,948 people aged 57.5 ± [SD] 4.4; 51% women; 37% former and 12% current smokers; 43% overweight (BMI 25.0-29.9), 21% obese (BMI ≥ 30); 25% with respiratory disease, 14% depression, 9% cardiac disease, and 3% anemia. Breathlessness was present in 3.7%. Medical conditions most strongly related to the breathlessness prevalence were (PAF 95%CI): overweight and obesity (59.6-66.0%), stress (31.6-76.8%), respiratory disease (20.1-37.1%), depression (17.1-26.6%), cardiac disease (6.3-12.7%), anemia (0.8-3.3%), and peripheral arterial disease (0.3-0.8%). Stress was the main factor in women and current smokers.

    Conclusion: Breathlessness mainly relates to overweight/obesity and stress and to a lesser extent to comorbidities like respiratory, depressive, and cardiac disorders among middle-aged people in a high-income setting-supporting the importance of lifestyle interventions to reduce the burden of breathlessness in the population.

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  • 49.
    Enarsson, Malin
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Disciplinary Domain of Medicine and Pharmacy, research centers etc., Center for Clinical Research Dalarna.
    Feldreich, Tobias
    Dalarna Univ, Sch Hlth & Social Studies, S-79188 Falun, Sweden..
    Byberg, Liisa
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Medical epidemiology.
    Nowak, Christoph
    Karolinska Inst, Div Family Med & Primary Care, Dept Neurobiol Care Sci & Soc NVS, Alfred Nobels Alle 23, S-14183 Huddinge, Sweden..
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Epidemiology.
    Ärnlöv, Johan
    Dalarna Univ, Sch Hlth & Social Studies, S-79188 Falun, Sweden.;Karolinska Inst, Div Family Med & Primary Care, Dept Neurobiol Care Sci & Soc NVS, Alfred Nobels Alle 23, S-14183 Huddinge, Sweden..
    Association between Cardiorespiratory Fitness and Circulating Proteins in 50-Year-Old Swedish Men and Women: a Cross-Sectional Study2021In: SPORTS MEDICINE-OPEN, ISSN 2199-1170, Vol. 7, article id 52Article in journal (Refereed)
    Abstract [en]

    Background and Aims: A strong cardiorespiratory fitness is suggested to have beneficial effects on cardiovascular risk; the exact mechanisms underlying the cardioprotective effects of fitness remain uncertain. Our aim was to investigate associations between cardiorespiratory fitness and multiple plasma proteins, in order to obtain insights about physiological pathways associated with the effects of exercise on cardiovascular health.

    Methods: In the Prospective investigation of Obesity, Energy and Metabolism (POEM) study (n=444 adults aged 50 years, 50% women), cardiorespiratory fitness was measured by a maximal exercise test on bicycle ergometer with gas exchange (VO(2)peak) normalized for body lean mass (dual-energy X-ray absorptiometry (DXA)). We measured 82 cardiovascular proteins associated with cardiovascular pathology and inflammation in plasma samples with a proximity extension assay.

    Results: In sex-adjusted linear regression, VO(2)peak was associated with 18 proteins after Bonferroni correction for multiple testing (p<0.0006). Following additional adjustment for fat mass (DXA), fasting glucose (mmol/L), low-density lipoprotein (LDL, mmol/L), smoking status, waist/hip ratio, blood pressure (mmHg), education level, and lpnr (lab sequence number), higher VO(2)peak was significantly associated with lower levels of 6 proteins: fatty-acid binding protein-4 (FABP4), interleukin-6 (IL-6), leptin, cystatin-B (CSTB), interleukin-1 receptor antagonist (IL-1RA), and growth differentiation factor 15 (GDF-15), and higher levels of 3 proteins: galanin, kallikrein-6 (KLK6), and heparin-binding EGF-like growth factor (HB-EGF), at nominal p-values (p<0.05).

    Conclusions: We identified multiple novel associations between cardiorespiratory fitness and plasma proteins involved in several atherosclerotic processes and key cellular mechanisms such as inflammation, energy homeostasis, and protease activity, which shed new light on how exercise asserts its beneficial effects on cardiovascular health. Our findings encourage additional studies in order to understand the underlying causal mechanisms for these associations.

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  • 50.
    Engdahl, Johan
    et al.
    Karolinska Inst, Danderyd Hosp, Dept Clin Sci, Stockholm, Sweden..
    Straat, Kajsa
    Karolinska Inst, Danderyd Hosp, Dept Clin Sci, Stockholm, Sweden..
    Isaksson, Eva
    Karolinska Inst, Danderyd Hosp, Dept Clin Sci, Stockholm, Sweden..
    Rooth, Elisabeth
    Karolinska Inst, Danderyd Hosp, Dept Clin Sci, Stockholm, Sweden..
    Svennberg, Emma
    Karolinska Univ Hosp, Dept Med, Karolinska Inst, Stockholm, Sweden..
    Norrving, Bo
    Lund Univ, Neurol Sect, Dept Clin Sci, Lund, Sweden..
    Euler, Mia von
    Örebro Univ, Sch Med, Dept Neurol, Örebro, Sweden..
    Hellqvist, Kjersti
    Alingsas lasarett, Dept Med, Alingsas, Sweden..
    Gu, Weigang
    Karolinska Inst, South Hosp, Dept Clin Sci, Stockholm, Sweden..
    Ström, Jakob O.
    Örebro Univ, Sch Med, Dept Neurol, Örebro, Sweden..
    Själander, Sara
    Umeå Univ, Dept Publ Hlth & Clin Med, Umeå, Sweden..
    Eriksson, Marie
    Umeå Univ, Dept Stat, USBE, Umeå, Sweden..
    Åsberg, Signild
    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, Faculty of Medicine, Department of Medical Sciences, Neurology.
    Wester, Per
    Karolinska Inst, Danderyd Hosp, Dept Clin Sci, Stockholm, Sweden.;Umeå Univ, Dept Publ Hlth & Clin Med, Umeå, Sweden..
    Multicentre, national, investigator-initiated, randomised, parallel-group, register-based superiority trial to compare extended ECG monitoring versus standard ECG monitoring in elderly patients with ischaemic stroke or transient ischaemic attack and the effect on stroke, death and intracerebral bleeding: the AF SPICE protocol2023In: BMJ Open, E-ISSN 2044-6055, Vol. 13, no 11, article id e073470Article in journal (Refereed)
    Abstract [en]

    Introduction: Atrial fibrillation (AF) is a major risk factor for ischaemic stroke and transient ischaemic attack (TIA), and AF detection can be challenged by asymptomatic and paroxysmal presentation. Long-term ECG monitoring after ischaemic stroke or TIA is recommended by all major societies in cardiology and cerebrovascular medicine as a secondary prophylactic measure. However, data on stroke reduction are lacking, and the recommendations show significant diversity.

    Methods and analysis: AF SPICE is a multicentre, national, investigator-initiated, randomised, parallel-group, register-based trial comparing extended ECG monitoring versus standard ECG monitoring in patients admitted with ischaemic stroke or TIA, with a composite endpoint of stroke, all-cause-mortality and intracerebral bleeding. Patients aged ≥ 70 years without previous AF will be randomised 1:1 to control (standard ECG monitoring) or intervention (extended ECG monitoring). In the control arm, patients will undergo 48±24 hours (ie, a range of 24-72hours) of continuous ECG monitoring according to national recommendations. In the intervention arm, patients will undergo 14+14 days of continuous ECG monitoring 3months apart using an ECG patch device, which will provide an easy-accessed, well-tolerated 14-day continuous ECG recording. All ECG patch recordings will be read in a core facility. In cases of AF detection, oral anticoagulation will be recommended if not contraindicated. A pilot phase has been concluded in 2022, which will transcend into the main trial during 2023-2026, including approximately 30 stroke units. The sample size was calculated to be 3262 patients. The primary outcome will be collected from register data during a 36-month follow-up.

    Ethics and dissemination: Ethical approval has been provided by the Swedish Ethical Review Authority, reference 2021-02770. The trial will be conducted according to the ethical principles of the Declaration of Helsinki and national regulatory standards. Positive results from the study have the potential for rapid dissemination in clinical practice. Trial registration number NCT05134454.

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