Lars Lind1, Johan Sundström1,2, Johan Ärnlöv3,4, Martin Ingelsson5, Albert Henry6,7,8, R Thomas Lumbers7,8,9,10, Erik Lampa11. 1. Department of Medical Sciences (L.L., J.S.), Uppsala University, Sweden. 2. The George Institute for Global Health, University of New South Wales, Sydney, Australia (J.S.). 3. Division of Family Medicine and Primary Care, Department of Neurobiology, Care Sciences & Society, Karolinska Institutet, Huddinge (J.A.). 4. School of Health and Social Sciences, Dalarna University, Falun, Sweden (J.A.). 5. Department of Public Health and Caring Sciences/Geriatrics (M.I.), Uppsala University, Sweden. 6. Institute of Cardiovascular Science (A.H.), University College London. 7. British Heart Foundation Research Accelerator (A.H., R.T.L.), University College London. 8. Institute of Health Informatics (A.H., R.T.L.), University College London. 9. Health Data Research UK London (R.T.L.), University College London. 10. Bart's Heart Centre, St. Bartholomew's Hospital, London, United Kingdom (R.T.L.). 11. Uppsala Clinical Research Centre (UCR) (E.L.), Uppsala University, Sweden.
Abstract
BACKGROUND: It is known that certain cardiovascular diseases (CVD) are associated, like atrial fibrillation and stroke. However, for other CVDs, the links and temporal trends are less studied. In this longitudinal study, we have investigated temporal epidemiological and genetic associations between different CVDs. METHODS: The ULSAM (Uppsala Longitudinal Study of Adult Men; 2322 men aged 50 years) has been followed for 40 years regarding 4 major CVDs (incident myocardial infarction, ischemic stroke, heart failure, and atrial fibrillation). For the genetic analyses, publicly available data were used. RESULTS: Using multistate modeling, significant relationships were seen between pairs of all of the 4 investigated CVDs. However, the risk of obtaining one additional CVD differed substantially both between different CVDs and between their temporal order. The relationship between heart failure and atrial fibrillation showed a high risk ratio (risk ratios, 24-26) regardless of the temporal order. A consistent association was seen also for myocardial infarction and atrial fibrillation but with a lower relative risk (risk ratios, 4-5). In contrast, the risk of receiving a diagnosis of heart failure following a myocardial infarction was almost twice as high as for the reverse temporal order (risk ratios, 16 versus 9). Genetic loci linked to traditional risk factors could partly explain the observed associations between the CVDs, but pathway analyses disclosed also other pathophysiological links. CONCLUSIONS: During 40 years, all of the 4 investigated CVDs were pairwise associated with each other regardless of the temporal order of occurrence, but the risk magnitude differed between different CVDs and their temporal order. Genetic analyses disclosed new pathophysiological links between CVDs.
BACKGROUND: It is known that certain cardiovascular diseases (CVD) are associated, like atrial fibrillation and stroke. However, for other CVDs, the links and temporal trends are less studied. In this longitudinal study, we have investigated temporal epidemiological and genetic associations between different CVDs. METHODS: The ULSAM (Uppsala Longitudinal Study of Adult Men; 2322 men aged 50 years) has been followed for 40 years regarding 4 major CVDs (incident myocardial infarction, ischemic stroke, heart failure, and atrial fibrillation). For the genetic analyses, publicly available data were used. RESULTS: Using multistate modeling, significant relationships were seen between pairs of all of the 4 investigated CVDs. However, the risk of obtaining one additional CVD differed substantially both between different CVDs and between their temporal order. The relationship between heart failure and atrial fibrillation showed a high risk ratio (risk ratios, 24-26) regardless of the temporal order. A consistent association was seen also for myocardial infarction and atrial fibrillation but with a lower relative risk (risk ratios, 4-5). In contrast, the risk of receiving a diagnosis of heart failure following a myocardial infarction was almost twice as high as for the reverse temporal order (risk ratios, 16 versus 9). Genetic loci linked to traditional risk factors could partly explain the observed associations between the CVDs, but pathway analyses disclosed also other pathophysiological links. CONCLUSIONS: During 40 years, all of the 4 investigated CVDs were pairwise associated with each other regardless of the temporal order of occurrence, but the risk magnitude differed between different CVDs and their temporal order. Genetic analyses disclosed new pathophysiological links between CVDs.
Authors: Panos Deloukas; Stavroula Kanoni; Christina Willenborg; Martin Farrall; Themistocles L Assimes; John R Thompson; Erik Ingelsson; Danish Saleheen; Jeanette Erdmann; Benjamin A Goldstein; Kathleen Stirrups; Inke R König; Jean-Baptiste Cazier; Asa Johansson; Alistair S Hall; Jong-Young Lee; Cristen J Willer; John C Chambers; Tõnu Esko; Lasse Folkersen; Anuj Goel; Elin Grundberg; Aki S Havulinna; Weang K Ho; Jemma C Hopewell; Niclas Eriksson; Marcus E Kleber; Kati Kristiansson; Per Lundmark; Leo-Pekka Lyytikäinen; Suzanne Rafelt; Dmitry Shungin; Rona J Strawbridge; Gudmar Thorleifsson; Emmi Tikkanen; Natalie Van Zuydam; Benjamin F Voight; Lindsay L Waite; Weihua Zhang; Andreas Ziegler; Devin Absher; David Altshuler; Anthony J Balmforth; Inês Barroso; Peter S Braund; Christof Burgdorf; Simone Claudi-Boehm; David Cox; Maria Dimitriou; Ron Do; Alex S F Doney; NourEddine El Mokhtari; Per Eriksson; Krista Fischer; Pierre Fontanillas; Anders Franco-Cereceda; Bruna Gigante; Leif Groop; Stefan Gustafsson; Jörg Hager; Göran Hallmans; Bok-Ghee Han; Sarah E Hunt; Hyun M Kang; Thomas Illig; Thorsten Kessler; Joshua W Knowles; Genovefa Kolovou; Johanna Kuusisto; Claudia Langenberg; Cordelia Langford; Karin Leander; Marja-Liisa Lokki; Anders Lundmark; Mark I McCarthy; Christa Meisinger; Olle Melander; Evelin Mihailov; Seraya Maouche; Andrew D Morris; Martina Müller-Nurasyid; Kjell Nikus; John F Peden; N William Rayner; Asif Rasheed; Silke Rosinger; Diana Rubin; Moritz P Rumpf; Arne Schäfer; Mohan Sivananthan; Ci Song; Alexandre F R Stewart; Sian-Tsung Tan; Gudmundur Thorgeirsson; C Ellen van der Schoot; Peter J Wagner; George A Wells; Philipp S Wild; Tsun-Po Yang; Philippe Amouyel; Dominique Arveiler; Hanneke Basart; Michael Boehnke; Eric Boerwinkle; Paolo Brambilla; Francois Cambien; Adrienne L Cupples; Ulf de Faire; Abbas Dehghan; Patrick Diemert; Stephen E Epstein; Alun Evans; Marco M Ferrario; Jean Ferrières; Dominique Gauguier; Alan S Go; Alison H Goodall; Villi Gudnason; Stanley L Hazen; Hilma Holm; Carlos Iribarren; Yangsoo Jang; Mika Kähönen; Frank Kee; Hyo-Soo Kim; Norman Klopp; Wolfgang Koenig; Wolfgang Kratzer; Kari Kuulasmaa; Markku Laakso; Reijo Laaksonen; Ji-Young Lee; Lars Lind; Willem H Ouwehand; Sarah Parish; Jeong E Park; Nancy L Pedersen; Annette Peters; Thomas Quertermous; Daniel J Rader; Veikko Salomaa; Eric Schadt; Svati H Shah; Juha Sinisalo; Klaus Stark; Kari Stefansson; David-Alexandre Trégouët; Jarmo Virtamo; Lars Wallentin; Nicholas Wareham; Martina E Zimmermann; Markku S Nieminen; Christian Hengstenberg; Manjinder S Sandhu; Tomi Pastinen; Ann-Christine Syvänen; G Kees Hovingh; George Dedoussis; Paul W Franks; Terho Lehtimäki; Andres Metspalu; Pierre A Zalloua; Agneta Siegbahn; Stefan Schreiber; Samuli Ripatti; Stefan S Blankenberg; Markus Perola; Robert Clarke; Bernhard O Boehm; Christopher O'Donnell; Muredach P Reilly; Winfried März; Rory Collins; Sekar Kathiresan; Anders Hamsten; Jaspal S Kooner; Unnur Thorsteinsdottir; John Danesh; Colin N A Palmer; Robert Roberts; Hugh Watkins; Heribert Schunkert; Nilesh J Samani Journal: Nat Genet Date: 2012-12-02 Impact factor: 38.330
Authors: Ali Seifi; Kevin Carr; Mitchell Maltenfort; Michael Moussouttas; Lee Birnbaum; Augusto Parra; Owoicho Adogwa; Rodney Bell; Fred Rincon Journal: PLoS One Date: 2014-08-28 Impact factor: 3.240
Authors: Robert A Scott; Laura J Scott; Reedik Mägi; Letizia Marullo; Kyle J Gaulton; Marika Kaakinen; Natalia Pervjakova; Tune H Pers; Andrew D Johnson; John D Eicher; Anne U Jackson; Teresa Ferreira; Yeji Lee; Clement Ma; Valgerdur Steinthorsdottir; Gudmar Thorleifsson; Lu Qi; Natalie R Van Zuydam; Anubha Mahajan; Han Chen; Peter Almgren; Ben F Voight; Harald Grallert; Martina Müller-Nurasyid; Janina S Ried; Nigel W Rayner; Neil Robertson; Lennart C Karssen; Elisabeth M van Leeuwen; Sara M Willems; Christian Fuchsberger; Phoenix Kwan; Tanya M Teslovich; Pritam Chanda; Man Li; Yingchang Lu; Christian Dina; Dorothee Thuillier; Loic Yengo; Longda Jiang; Thomas Sparso; Hans A Kestler; Himanshu Chheda; Lewin Eisele; Stefan Gustafsson; Mattias Frånberg; Rona J Strawbridge; Rafn Benediktsson; Astradur B Hreidarsson; Augustine Kong; Gunnar Sigurðsson; Nicola D Kerrison; Jian'an Luan; Liming Liang; Thomas Meitinger; Michael Roden; Barbara Thorand; Tõnu Esko; Evelin Mihailov; Caroline Fox; Ching-Ti Liu; Denis Rybin; Bo Isomaa; Valeriya Lyssenko; Tiinamaija Tuomi; David J Couper; James S Pankow; Niels Grarup; Christian T Have; Marit E Jørgensen; Torben Jørgensen; Allan Linneberg; Marilyn C Cornelis; Rob M van Dam; David J Hunter; Peter Kraft; Qi Sun; Sarah Edkins; Katharine R Owen; John R B Perry; Andrew R Wood; Eleftheria Zeggini; Juan Tajes-Fernandes; Goncalo R Abecasis; Lori L Bonnycastle; Peter S Chines; Heather M Stringham; Heikki A Koistinen; Leena Kinnunen; Bengt Sennblad; Thomas W Mühleisen; Markus M Nöthen; Sonali Pechlivanis; Damiano Baldassarre; Karl Gertow; Steve E Humphries; Elena Tremoli; Norman Klopp; Julia Meyer; Gerald Steinbach; Roman Wennauer; Johan G Eriksson; Satu Mӓnnistö; Leena Peltonen; Emmi Tikkanen; Guillaume Charpentier; Elodie Eury; Stéphane Lobbens; Bruna Gigante; Karin Leander; Olga McLeod; Erwin P Bottinger; Omri Gottesman; Douglas Ruderfer; Matthias Blüher; Peter Kovacs; Anke Tonjes; Nisa M Maruthur; Chiara Scapoli; Raimund Erbel; Karl-Heinz Jöckel; Susanne Moebus; Ulf de Faire; Anders Hamsten; Michael Stumvoll; Panagiotis Deloukas; Peter J Donnelly; Timothy M Frayling; Andrew T Hattersley; Samuli Ripatti; Veikko Salomaa; Nancy L Pedersen; Bernhard O Boehm; Richard N Bergman; Francis S Collins; Karen L Mohlke; Jaakko Tuomilehto; Torben Hansen; Oluf Pedersen; Inês Barroso; Lars Lannfelt; Erik Ingelsson; Lars Lind; Cecilia M Lindgren; Stephane Cauchi; Philippe Froguel; Ruth J F Loos; Beverley Balkau; Heiner Boeing; Paul W Franks; Aurelio Barricarte Gurrea; Domenico Palli; Yvonne T van der Schouw; David Altshuler; Leif C Groop; Claudia Langenberg; Nicholas J Wareham; Eric Sijbrands; Cornelia M van Duijn; Jose C Florez; James B Meigs; Eric Boerwinkle; Christian Gieger; Konstantin Strauch; Andres Metspalu; Andrew D Morris; Colin N A Palmer; Frank B Hu; Unnur Thorsteinsdottir; Kari Stefansson; Josée Dupuis; Andrew P Morris; Michael Boehnke; Mark I McCarthy; Inga Prokopenko Journal: Diabetes Date: 2017-05-31 Impact factor: 9.337
Authors: Lars Lind; Daniela Zanetti; Martin Ingelsson; Stefan Gustafsson; Johan Ärnlöv; Themistocles L Assimes Journal: J Am Heart Assoc Date: 2021-11-30 Impact factor: 5.501