High-Sensitivity Troponin I in Atrial Fibrillation
Total Page：16
File Type：pdf, Size：1020Kb
High-Sensitivity Troponin I in Atrial Fibrillation Impact of rate and rhythm control and associations with biomarkers related to atrial fibrillation pathophysiology PhD Thesis Anja Wiedswang Horjen Department of Medical Research Bærum Hospital, Vestre Viken Hospital Trust Faculty of Medicine University of Oslo 2018 © Anja Wiedswang Horjen, 2018 Series of dissertations submitted to the Faculty of Medicine, University of Oslo ISBN 978-82-8377-297-5 All rights reserved. No part of this publication may be reproduced or transmitted, in any form or by any means, without permission. Cover: Hanne Baadsgaard Utigard. Print production: Reprosentralen, University of Oslo. CONTENTS Acknowledgements ............................................................................................................................................... 3 Papers Included in this Thesis ............................................................................................................................. 5 Abbreviations ......................................................................................................................................................... 6 1 Introduction .................................................................................................................................................. 7 1.1 Atrial Fibrillation ..................................................................................................................................... 7 1.2 Cardiac Troponins ................................................................................................................................ 15 1.3 Cardiac Troponins in Atrial Fibrillation.................................................................................................. 18 2 Aims of this Thesis .................................................................................................................................... 20 3 Methods ...................................................................................................................................................... 21 3.1 Study Populations ................................................................................................................................ 22 3.2 Ethical Approval and Funding .............................................................................................................. 28 3.3 Laboratory Analyses ............................................................................................................................ 28 3.4 Statistical Analyses .............................................................................................................................. 29 4 Summary of Results .................................................................................................................................. 31 4.1 Paper I ................................................................................................................................................. 31 4.2 Paper II ................................................................................................................................................ 31 4.3 Paper III ............................................................................................................................................... 32 4.4 Paper IV ............................................................................................................................................... 32 5 Methodological Considerations ................................................................................................................ 33 5.1 Study Designs ...................................................................................................................................... 33 5.2 Study Populations ................................................................................................................................ 34 5.3 Analyses of Biomarkers ....................................................................................................................... 35 5.4 Analyses and Presentation of Data ...................................................................................................... 36 5.5 Validity ................................................................................................................................................. 37 6 Discussion of Results ............................................................................................................................... 38 6.1 Levels of Hs-TnI in 75-year-olds .......................................................................................................... 38 6.2 Impact of Rate Control on Levels of Hs-TnI ......................................................................................... 39 6.3 Impact of Rhythm Control on Levels of Hs-TnI .................................................................................... 41 6.4 Prognostic Value of Hs-TnI in AF ......................................................................................................... 42 6.5 Correlations Between Hs-TnI and Biomarkers Related to AF Pathophysiology ................................... 43 7 Conclusions ............................................................................................................................................... 45 8 Clinical Implications .................................................................................................................................. 46 9 Future Research ......................................................................................................................................... 47 10 References .................................................................................................................................................. 48 Papers .................................................................................................................................................................. 55 1 2 ACKNOWLEDGEMENTS This PhD project was a collaboration between Department of Medical Research at Bærum Hospital and Clinic for Medical Diagnostics, both Vestre Viken Hospital Trust, and Centre for Clinical Heart Research at Oslo University Hospital Ullevål. Financial support was provided by Vestre Viken Hospital Trust. The work for my PhD thesis was carried out at the Department of Medical Research at Bærum Hospital under supervision of Professor Arnljot Tveit, Professor Ingebjørg Seljeflot, cardiologist and PhD Sara Reinvik Ulimoen, and dr.med. Jon Norseth. I would like to thank all the participants of the three research projects included in this PhD project for valuable contributions, and for making this thesis possible. First and foremost, I want to express my sincere gratitude to my primary supervisor, Arnljot Tveit. His ideas and dedication have been fundamental to this work. I appreciate his positive spirit, patience and always open door, and for conveying confidence in my commitment and capabilities. My warmest appreciation also goes to co-supervisor Sara Ulimoen, who has generously shared data with me. Her grounded, rational attitude, constant positivity and clinical perspective have inspired me, and been essential to this project. Co-supervisor Jon Norseth deserves credit for analysing high-sensitivity troponin I and T, and for his useful advices and encouragement. Ingebjørg Seljeflot has been my co-supervisor, for which I am very grateful. Her expertise in the field of biomarkers has formed the basis of this work, and it has been a privilege to be part of her group at the Center for Clinical Heart Research. I would also like to thank co-author Harald Arnesen for being my best in-house reviewer. His friendly and constructive feedback on all my manuscripts has certainly lifted the quality of this work. I am forever grateful to all my colleagues at the Department of Medical Research at Bærum Hospital. The magnificent research milieu with skilful, friendly and professional colleagues has made this journey memorable in so many ways. A special thanks to Mona Olufsen for participating in data collection, for her unparalleled overview of the art of research, and for creating such a harmonious working environment. My gratitude also goes to Steve Enger for his endeavours in data collection for this project, and for his sense of humour. I want to thank Sophia Onarheim for her warm enthusiasm and for introducing me to the lab, and Kristine Seland Folkenborg for always helping me out with technical support. My office-mates Sara Reinvik Ulimoen, Sigrun Losada Eskeland, Jana Kuhn, Elisabeth Andersson, Trygve Berge and Katrine Enge – thank you for your helpful advices and for sharing ups and downs with me! Last, but not least, I would like to thank my first supervisor, Mons Lie. During medical school, he introduced me to the world of cardiac research, and guided me through every step of my first research project from 2006-2011, culminating in my first scientific paper. His educational skills have been important to me. Finally, this thesis would not have been possible without the loyalty and love from my husband and superman, Atle. The unwavering support from my parents, Gro and Fredrik, has always been, and continues to be, exceptional. My children, Olav and Erik, contribute to the non-scientific aspects of life, make me leave the hospital in time, and remind me that being their mother is a far more important and challenging task than any thesis.