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BMJ Open Is Committed to Open Peer Review. As Part of This Commitment We Make the Peer Review History of Every Article We Publish Publicly Available BMJ Open: first published as 10.1136/bmjopen-2018-023447 on 7 March 2019. Downloaded from BMJ Open is committed to open peer review. As part of this commitment we make the peer review history of every article we publish publicly available. When an article is published we post the peer reviewers’ comments and the authors’ responses online. We also post the versions of the paper that were used during peer review. These are the versions that the peer review comments apply to. The versions of the paper that follow are the versions that were submitted during the peer review process. They are not the versions of record or the final published versions. They should not be cited or distributed as the published version of this manuscript. BMJ Open is an open access journal and the full, final, typeset and author-corrected version of record of the manuscript is available on our site with no access controls, subscription charges or pay-per-view fees (http://bmjopen.bmj.com). If you have any questions on BMJ Open’s open peer review process please email [email protected] http://bmjopen.bmj.com/ on September 29, 2021 by guest. Protected copyright. BMJ Open BMJ Open: first published as 10.1136/bmjopen-2018-023447 on 7 March 2019. Downloaded from Dog ownership and Cardiovascular Risk Factors: a nationwide prospective register-based cohort study Journal: BMJ Open ManuscriptFor ID peerbmjopen-2018-023447 review only Article Type: Research Date Submitted by the Author: 09-Apr-2018 Complete List of Authors: Mubanga, Mwenya; Uppsala University, Department of Medical Sciences, Molecular Epidemiology and Science for Life Laboratory Byberg, Liisa; Uppsala Universitet, Department of Surgical Sciences, Orthopedics, Uppsala University Egenvall, Agneta; Swedish University of Agricultural Science, Department of Clinical Sciences, Division of Ruminant Medicine and Veterinary Epidemiology Sundström, Johan; Uppsala University Magnusson, Patrik; Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Ingelsson, Erik; Uppsala University, Department of Medical Sciences, Molecular Epidemiology and Science for Life Laboratory; Stanford University Department of Medicine, Division of Cardiovascular Medicine, Stanford University School of Medicine, http://bmjopen.bmj.com/ Fall, Tove; Uppsala University, Department of Medical Sciences, Molecular Epidemiology and Science for Life Laboratory Cardiac Epidemiology < CARDIOLOGY, EPIDEMIOLOGY, Hypertension < Keywords: CARDIOLOGY, General diabetes < DIABETES & ENDOCRINOLOGY on September 29, 2021 by guest. Protected copyright. For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml Page 1 of 45 BMJ Open 1 BMJ Open: first published as 10.1136/bmjopen-2018-023447 on 7 March 2019. Downloaded from 1 2 3 Dog ownership and Cardiovascular Risk Factors: a nationwide prospective 4 5 register-based cohort study 6 7 Mwenya Mubanga, MBChB, MPH1; Liisa Byberg, PhD2; Agneta Egenvall, VMD, PhD3; 8 9 Johan Sundström MD, PhD4, Patrik K Magnusson, PhD5; Erik Ingelsson, MD, PhD1,6,7; Tove 10 11 1* 12 Fall, VMD, PhD 13 14 15 1. Department of Medical Sciences, Molecular Epidemiology and Science for Life 16 For peer review only 17 Laboratory, Uppsala University, Uppsala, Sweden. 18 19 2. Department of Surgical Sciences, Orthopedics, Uppsala University, Uppsala, Sweden. 20 21 3. Department of Clinical Sciences, Division of Ruminant Medicine and Veterinary 22 23 Epidemiology, Swedish University of Agricultural Sciences, Uppsala, Sweden. 24 25 4. Department of Medical Sciences, Cardiovascular Epidemiology, Uppsala University, 26 27 28 Uppsala. Sweden. 29 30 5. Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, 31 32 Stockholm, Sweden. http://bmjopen.bmj.com/ 33 34 6. Department of Medicine, Division of Cardiovascular Medicine, Stanford University 35 36 School of Medicine, Stanford, CA, USA. 37 38 7. Stanford Cardiovascular Institute, Stanford University, Stanford, CA 94305, USA. 39 40 on September 29, 2021 by guest. Protected copyright. 41 42 43 44 *Corresponding author: Tove Fall, VMD, PhD, [email protected] 45 46 47 Word count: 3090 words (max 4000) 48 49 50 51 52 53 54 55 56 57 58 59 60 For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml BMJ Open Page 2 of 45 2 BMJ Open: first published as 10.1136/bmjopen-2018-023447 on 7 March 2019. Downloaded from 1 2 3 Abstract (297 words; max 300) 4 5 Objective: To study the association between dog ownership and cardiovascular risk factors. 6 7 Design: A nationwide register–based prospective cohort study with a cross-sectional study in 8 9 a subset of the population. Participants were followed up from October 1st, 2006 to December 10 31st, 2012. 11 12 13 Setting: A cohort of 2,026,865 participants was identified from the Register of the Total 14 Population and linked to other national registers for information on dog ownership, hospital 15 16 admissions, socio-economicFor peer status and countryreview of birth. Participants only were followed up to 17 medication for a cardiovascular risk factor, emigration, death or at the end of the study on 18 19 December 31st, 2012. Cross-sectional associations were further assessed in 10,110 individuals 20 21 from TwinGene. 22 st 23 Participants: All Swedish residents aged 45-80 years on October 1 , 2006. 24 25 Main outcome measures: Initiation of treatment for hypertension, dyslipidemia and diabetes 26 mellitus. 27 28 29 Results 30 31 The results indicated slightly higher likelihood of initiating anti-hypertensive (HR, 1.02; 95% 32 CI, 1.01-1.03) and lipid-lowering treatment (HR, 1.02; 95% CI, 1.01-1.04) in dog owners than http://bmjopen.bmj.com/ 33 34 in non-owners, particularly amongst those aged 45 to 60 and in those owning mixed breed or 35 36 companion/toy breed dogs. No association of dog ownership with initiation of treatment for 37 diabetes was found in the overall analysis (HR, 0.98; 95% CI, 0.95-1.01). Sensitivity analyses 38 39 in the TwinGene cohort indicated confounding from factors not available in the national 40 cohort, such as employment status and non-CVD chronic disease status. on September 29, 2021 by guest. Protected copyright. 41 42 43 Conclusions 44 45 In this large cohort study, dog ownership was not associated with any large reduction in 46 initiation of medication for classical cardiovascular risk factors, implying that the previously 47 48 reported lower risk of cardiovascular mortality among dog owners in this cohort is not 49 explained by reduced hypertension and dyslipidemia. 50 51 52 53 54 55 56 57 58 59 60 For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml Page 3 of 45 BMJ Open 3 BMJ Open: first published as 10.1136/bmjopen-2018-023447 on 7 March 2019. Downloaded from 1 2 3 Strengths and limitations of this study 4 5 • This is the largest study to date to examine the impact of dog ownership on 6 cardiovascular risk factors 7 • The nationwide register-based cohort study with a cross-sectional investigation in a 8 9 twin registry with a vast array of lifestyle and clinical variables strengthens the results 10 • The main outcome measures were extracted from nationwide registers thus decreasing 11 the risk of recall and selection bias. 12 Misclassification of dog ownership, particularly in the twin register, may have led to 13 • 14 some loss of power. 15 • Some important confounding factors were not available in the national data 16 For peer review only 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 http://bmjopen.bmj.com/ 33 34 35 36 37 38 39 40 on September 29, 2021 by guest. Protected copyright. 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml BMJ Open Page 4 of 45 4 BMJ Open: first published as 10.1136/bmjopen-2018-023447 on 7 March 2019. Downloaded from 1 2 3 Introduction 4 5 There is a growing interest in pet ownership as a possible intervention to enhance 6 1 2 7 cardiovascular health and well-being. We recently observed that being registered as a dog 8 owner was associated with a lower risk of cardiovascular and all-cause mortality in the 9 10 general Swedish population (n=3,432,153).3 Any causal association of dog ownership with 11 12 lower cardiovascular mortality could potentially be mediated through increased physical 13 activity or through the psychological benefits of companionship, which could in turn reduce 14 15 other important cardiovascular risk factors such as blood pressure, adiposity, dyslipidemia, 16 and insulin resistance.For An alternativepeer explanation review could be confounding only by socioeconomic, 17 18 cultural, demographic or psycho-social factors. A large number of cross-sectional and 19 20 longitudinal studies across different countries support the association of dog ownership with 21 physical activity;1 however, reports regarding the association of dog ownership with other 22 23 cardiovascular risk factors are less consistent.4-11 These inconsistences may be due to low 24 25 statistical power in small studies, use of restricted or homogenous populations, inability to 26 control for differences across breed of dogs, or simply an absence of effect. As dogs are 27 12-14 28 reported to be more common in rural areas compared to urban areas, as well as in 29 households with children,15 16 it is also important to account for these differences. 30 31 32 The aim of this study was to assess the association of dog ownership with three major clinical http://bmjopen.bmj.com/ 33 risk factors for cardiovascular disease, specifically initiation of treatment of hypertension, 34 35 dyslipidemia and diabetes mellitus. We investigated this using data from national registers on 36 37 dog ownership and drug prescriptions.
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