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Epidemiology of Comorbidities in Early Rheumatoid Arthritis with Emphasis on Cardiovascular Disease

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Epidemiology of Comorbidities in Early Rheumatoid Arthritis with Emphasis on Cardiovascular Disease Recent Publications in this Series ANNE KEROLA Epidemiology of Comorbidities in Early Rheumatoid Arthritis with Emphasis on Cardiovascular Disease 2/2015 Jenni Vanhanen Neuronal Histamine and H3 Receptor in Alcohol-Related Behaviors - Focus on the Interaction with the Dopaminergic System 3/2015 Maria Voutilainen Molecular Regulation of Embryonic Mammary Gland Development 4/2015 Milica Maksimovic DISSERTATIONES SCHOLAE DOCTORALIS AD SANITATEM INVESTIGANDAM Behavioural and Pharmacological Characterization of a Mouse Model for Psychotic Disorders UNIVERSITATIS HELSINKIENSIS 20/2015 – Focus on Glutamatergic Transmission 5/2015 Mohammad-Ali Shahbazi Effect of Surface Chemistry on the Immune Responses and Cellular Interactions of Porous Silicon Nanoparticles 6/2015 Jinhyeon Yun Importance of Maternal Behaviour and Circulating Oxytocin for Successful Lactation in Sows - ANNE KEROLA Effects of Prepartum Housing Environment 7/2015 Tuomas Herva Animal Welfare and Economics in Beef Production 8/2015 Anna-Maria Kuivalainen Epidemiology of Comorbidities Pain and Associated Procedural Anxiety in Adults Undergoing Bone Marrow Aspiration and in Early Rheumatoid Arthritis Biopsy – Therapeutic Effi cacy and Feasibility of Various Analgesics 9/2015 Suvi Itkonen with Emphasis on Cardiovascular Disease Dietary Phosphorus – Bioavailability and Associations with Vascular Calcifi cation in a Middle- Aged Finnish Population 10/2015 Ilkka Liikanen Combining Oncolytic Immunotherapy with Conventional Cancer Treatments 11/2015 Katja Merkkiniemi Predictive Biomarkers in Diffuse Gliomas and Non-Small Cell Lung Cancer 12/2015 Chang-Fang Wang Chemical Surface Modifi cation of Porous Silicon Nanoparticles for Cancer Therapy 13/2015 Nina Nordman Microchip Technology in Mass Spectrometry-Based Bioanalysis: Advances in the Analysis of Peptides, Proteins, and Pharmaceuticals 14/2015 Heli Mönttinen The Structural Conservation and Phylogeny of Right-Hand-Shaped Polymerases and Structurally Related Proteins 15/2015 Pirkka-Pekka Laurila Molecular Link between Lipid Metabolism and Energy Homeostasis 16/2015 Matti Kankainen Computational Genomics of Lactobacilli 17/2015 Ilona Kareinen Mast Cells and HDL – Studies on Cholesterol Effl ux and Reverse Cholesterol Transport 18/2015 Janina Kaislasuo INTERNAL MEDICINE Intrauterine Contraception – Use in Nulligravid Women and Safety Aspects DEPARTMENT OF MEDICINE 19/2015 Kati Ahlqvist FACULTY OF MEDICINE The Effects of Mitochondrial DNA Mutagenesis on Somatic Stem Cells DOCTORAL PROGRAMME IN CLINICAL RESEARCH and Ageing UNIVERSITY OF HELSINKI 20/2015 Helsinki 2015 ISSN 2342-3161 ISBN 978-951-51-0899-9 cover.indd 1 2.4.2015 7:27:38 Internal Medicine Department of Medicine Faculty of Medicine Doctoral Programme in Clinical Research University of Helsinki Helsinki, Finland EPIDEMIOLOGY OF COMORBIDITIES IN EARLY RHEUMATOID ARTHRITIS WITH EMPHASIS ON CARDIOVASCULAR DISEASE Anne Kerola ACADEMIC DISSERTATION To be presented, with the permission of the Faculty of Medicine of the University of Helsinki, for public examination in Lecture Hall 1, Haartman Institute, Haartmaninkatu 3, Helsinki, on May 6th 2015, at 12 noon. Helsinki 2015 Supervisors Professor Tuomo Nieminen, MD, PhD Department of Medicine, Faculty of Medicine, University of Helsinki, Helsinki Department of Medicine, South Karelia Central Hospital, Lappeenranta, Finland Professor Markku Kauppi, MD, PhD Department of Internal Medicine, Päijät-Häme Central Hospital, Lahti School of Medicine, University of Tampere, Tampere, Finland Docent Tuomas Kerola, MD, PhD Department of Internal Medicine, Päijät-Häme Central Hospital, Lahti School of Medicine, University of Tampere, Tampere, Finland Reviewers Docent Tuomas Kiviniemi, MD, PhD Heart Center, Turku University Hospital and University of Turku, Finland Docent Pekka Kurki, MD, PhD Finnish Medicines Agency (FIMEA), Helsinki, Finland Opponent Professor Tore Kvien, MD, PhD Department of Rheumatology, Diakonhjemmet Hospital, Oslo University of Oslo, Norway Published in the series Dissertationes Scholae Doctoralis Ad Sanitatem Investigandam Universitatis Helsinkiensis © Anne Kerola Cover image © Heidi Hietanen Layout © PSWFolders Oy ISBN (paperback): 978-951-51-0899-9 ISSN (print): 2342-3161 ISBN (PDF): 978-951-51-0900-2 ISSN (online): 2342-317X Hansaprint Oy Helsinki, 2015 Finland To my family Contents Abstract Tiivistelmä List of original publications Abbreviations Introduction .............................................................................................................................................1 Review of the literature ..........................................................................................................................2 1 Rheumatoid arthritis ......................................................................................................................2 1.1 Overview ....................................................................................................................................2 1.2 Etiology ......................................................................................................................................2 1.3 Pathophysiology ........................................................................................................................3 1.3.1 Autoimmunity ..............................................................................................................3 1.3.2 Infl ammation and joint destruction ..........................................................................3 1.4 Epidemiology ............................................................................................................................4 1.5 What is early RA? .....................................................................................................................4 1.6 RA pharmacotherapy ...............................................................................................................5 1.7 Work disability ..........................................................................................................................6 1.8 Mortality ....................................................................................................................................6 2 Comorbidities in early RA .............................................................................................................7 2.1 Overview ....................................................................................................................................7 2.2 Cardiovascular disease .............................................................................................................7 2.2.1 Etiology and pathogenesis ..........................................................................................7 2.2.2 Cardiovascular risk in early RA .................................................................................9 2.2.2.1 Traditional cardiovascular risk factors .......................................................9 2.2.2.2 Non-traditional cardiovascular risk factors .............................................14 2.2.2.3 Preatherosclerotic processes.......................................................................15 2.2.2.4 Subclinical atherosclerosis ..........................................................................15 2.2.2.5 Subclinical myocardial damage .................................................................18 2.2.2.6 Symptomatic cardiovascular disease .........................................................20 2.2.2.7 Coronary heart disease and stroke ............................................................20 2.2.2.8 Congestive heart failure ..............................................................................24 2.2.2.9 Cardiac arrhythmias ....................................................................................24 2.2.2.10 Cardiovascular mortality ............................................................................24 2.2.3 RA medications and risk for CV morbidity and mortality ..................................27 2.2.4 Assessment and treatment of CV comorbidities in RA ........................................29 2.3 Autoimmune thyroiditis and hypothyroidism ...................................................................30 2.4 Psychiatric disorders ..............................................................................................................31 2.5 Comorbidities and work disability .......................................................................................31 Aims of the study ..................................................................................................................................33 Materials and methods .........................................................................................................................34 3 Background .....................................................................................................................................34 3.1 Register of special reimbursements for medicine expenses ..............................................34 3.1.1 Rheumatoid arthritis .................................................................................................35 3.1.2 Cardiovascular disease and its risk factors .............................................................35 3.1.3 Hypothyroidism .........................................................................................................36 3.2 Pension registers .....................................................................................................................36
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