Meta-Analysis

. 2019 Feb 14;40(7):621-631.

doi: 10.1093/eurheartj/ehy653.

Equalization of four cardiovascular risk algorithms after systematic recalibration: individual-participant meta-analysis of 86 prospective studies

Lisa Pennells¹, Stephen Kaptoge¹, Angela Wood¹, Mike Sweeting¹, Xiaohui Zhao², Ian White³, Stephen Burgess^{1

4}, Peter Willeit^{1

5}, Thomas Bolton¹, Karel G M Moons⁶, Yvonne T van der Schouw⁷, Randi Selmer⁸, Kay-Tee Khaw¹, Vilmundur Gudnason^{9

10}, Gerd Assmann¹¹, Philippe Amouyel¹², Veikko Salomaa¹³, Mika Kivimaki¹⁴, Børge G Nordestgaard¹⁵, Michael J Blaha¹⁶, Lewis H Kuller¹⁷, Hermann Brenner^{18

19}, Richard F Gillum²⁰, Christa Meisinger²¹, Ian Ford²², Matthew W Knuiman²³, Annika Rosengren^{24

25}, Debbie A Lawlor²⁶, Henry Völzke²⁷, Cyrus Cooper²⁸, Alejandro Marín Ibañez²⁹, Edoardo Casiglia³⁰, Jussi Kauhanen³¹, Jackie A Cooper³², Beatriz Rodriguez³³, Johan Sundström³⁴, Elizabeth Barrett-Connor³⁵, Rachel Dankner^{36

37}, Paul J Nietert³⁸, Karina W Davidson³⁹, Robert B Wallace⁴⁰, Dan G Blazer⁴¹, Cecilia Björkelund⁴², Chiara Donfrancesco⁴³, Harlan M Krumholz⁴⁴, Aulikki Nissinen¹³, Barry R Davis⁴⁵, Sean Coady⁴⁶, Peter H Whincup⁴⁷, Torben Jørgensen^{48

49

50}, Pierre Ducimetiere⁵¹, Maurizio Trevisan⁵², Gunnar Engström⁵³, Carlos J Crespo⁵⁴, Tom W Meade⁵⁵, Marjolein Visser⁵⁶, Daan Kromhout⁵⁷, Stefan Kiechl⁵, Makoto Daimon⁵⁸, Jackie F Price⁵⁹, Agustin Gómez de la Cámara⁶⁰, J Wouter Jukema⁶¹, Benoît Lamarche⁶², Altan Onat⁶³, Leon A Simons⁶⁴, Maryam Kavousi⁶⁵, Yoav Ben-Shlomo⁶⁶, John Gallacher⁶⁷, Jacqueline M Dekker⁶⁸, Hisatomi Arima⁶⁹, Nawar Shara⁷⁰, Robert W Tipping⁷¹, Ronan Roussel⁷², Eric J Brunner⁷³, Wolfgang Koenig^{74

75}, Masaru Sakurai⁷⁶, Jelena Pavlovic⁶⁵, Ron T Gansevoort⁷⁷, Dorothea Nagel⁷⁸, Uri Goldbourt³⁷, Elizabeth L M Barr⁷⁹, Luigi Palmieri⁴³, Inger Njølstad⁸⁰, Shinichi Sato⁸¹, W M Monique Verschuren⁸², Cherian V Varghese⁸³, Ian Graham⁸⁴, Oyere Onuma⁸³, Philip Greenland⁸⁵, Mark Woodward^{86

87}, Majid Ezzati⁸⁸, Bruce M Psaty⁸⁹, Naveed Sattar⁹⁰, Rod Jackson⁹¹, Paul M Ridker⁹², Nancy R Cook⁹², Ralph B D'Agostino⁹³, Simon G Thompson¹, John Danesh¹, Emanuele Di Angelantonio¹; Emerging Risk Factors Collaboration

Collaborators, Affiliations

Collaborators

Emerging Risk Factors Collaboration:
Robert W Tipping, Lara M Simpson, Sara L Pressel, David J Couper, Vijay Nambi, Kunihiro Matsushita, Aaron R Folsom, Jonathan E Shaw, Dianna J Magliano, Paul Z Zimmet, Matthew W Knuiman, Peter H Whincup, S Goya Wannamethee, Johann Willeit, Peter Santer, Georg Egger, Juan Pablo Casas, Antoinette Amuzu, Yoav Ben-Shlomo, John Gallacher, Valérie Tikhonoff, Edoardo Casiglia, Susan E Sutherland, Paul J Nietert, Mary Cushman, Bruce M Psaty, Anne Johanne Søgaard, Lise Lund Håheim, Inger Ariansen, Anne Tybjærg-Hansen, Gorm B Jensen, Peter Schnohr, Simona Giampaoli, Diego Vanuzzo, Salvatore Panico, Luigi Palmieri, Beverley Balkau, Fabrice Bonnet, Michel Marre, Agustin Gómez de la Cámara, Miguel Angel Rubio Herrera, Yechiel Friedlander, John McCallum, Stela McLachlan, Jack Guralnik, Caroline L Phillips, Kay-Tee Khaw, Nick Wareham, Ben Schöttker, Kai-Uwe Saum, Bernd Holleczek, Aulikki Nissinen, Hanna Tolonen, Simona Giampaoli, Chiara Donfrancesco, Erkki Vartiainen, Pekka Jousilahti, Kennet Harald, Ralph B D’Agostino, Joseph M Massaro, Michael Pencina, Ramachandran Vasan, Takamasa Kayama, Takeo Kato, Toshihide Oizumi, Jørgen Jespersen, Lars Møller, Else Marie Bladbjerg, A Chetrit, Annika Rosengren, Lars Wilhelmsen, Cecilia Björkelund, Lauren Lissner, Dorothea Nagel, Elaine Dennison, Yutaka Kiyohara, Toshiharu Ninomiya, Yasufumi Doi, Beatriz Rodriguez, Giel Nijpels, Coen D A Stehouwer, Shinichi Sato, Yamagishi Kazumasa, Hiroyasu Iso, Uri Goldbourt, Veikko Salomaa, Erkki Vartiainen, Sudhir Kurl, Tomi-Pekka Tuomainen, Jukka T Salonen, Marjolein Visser, Dorly J H Deeg, Tom W Meade, Peter M Nilsson, Bo Hedblad, Olle Melander, Ian H De Boer, Andrew Paul DeFilippis, W M Monique Verschuren, Naveed Sattar, Graham Watt, Christa Meisinger, Wolfgang Koenig, Annika Rosengren, Lewis H Kuller, Aage Tverdal, Richard F Gillum, Jackie A Cooper, Susan Kirkland, Daichi Shimbo, Jonathan Shaffer, Shinichi Sato, Yamagishi Kazumasa, Hiroyasu Iso, Pierre Ducimetiere, Stephan J L Bakker, Pim van der Harst, Hans L Hillege, Carlos J Crespo, Philippe Amouyel, Jean Dallongeville, Gerd Assmann, Helmut Schulte, Stella Trompet, Roelof A J Smit, David J Stott, Yvonne T van der Schouw, Jean-Pierre Després, Bernard Cantin, Gilles R Dagenais, Gail Laughlin, Deborah Wingard, Maurizio Trevisan, Thor Aspelund, Gudny Eiriksdottir, Elias Freyr Gudmundsson, Arfan Ikram, Frank J A van Rooij, Oscar H Franco, Oscar L Rueda-Ochoa, Taulant Muka, Marija Glisic, Hugh Tunstall-Pedoe, Henry Völzke, Barbara V Howard, Ying Zhang, Stacey Jolly, John Gallacher, George Davey-Smith, Günay Can, Hüsniye Yüksel, Hideaki Nakagawa, Yuko Morikawa, Katsuyuki Miura, Inger Njølstad, Martin Ingelsson, Vilmantas Giedraitis, Paul M Ridker, J Michael Gaziano, Mika Kivimaki, Martin Shipley, Eric J Brunner, Volker Arndt, Hermann Brenner, Nancy Cook, Paul M Ridker, Ian Ford, Naveed Sattar, Alejandro Marín Ibañez, Johanna M Geleijnse

Affiliations

¹ Department of Public Health and Primary Care, University of Cambridge, 2 Worts' Causeway, Cambridge, UK.
² Department of Physiology, Development and Neuroscience, University of Cambridge, Downing Street, Cambridge, UK.
³ MRC Clinical Trials Unit, University College London, 90 High Holborn, London, UK.
⁴ MRC Biostatistics Unit, Cambridge Institute of Public Health, University of Cambridge, Forvie Site, Robinson Way, Cambridge, UK.
⁵ Department of Neurology and Neurosurgery, Medical University of Innsbruck, Anichstraße 35, Innsbruck, Austria.
⁶ Epidemiology: Methodology, Julius Center Research Program Methodology, University Medical Center Utrecht, Heidelberglaan 100, Utrecht, the Netherlands.
⁷ Department of Epidemiology, Julius Center Research Program Cardiovascular Epidemiology, University Medical Center Utrecht, Heidelberglaan 100, Utrecht, the Netherlands.
⁸ Division of Epidemiology, Norwegian Institute of Public Health, Postboks 222 Skøyen, Oslo, Norway.
⁹ Icelandic Heart Association, Hjartavernd Holtasmá¡ri 1, Kópavogur, Iceland.
¹⁰ Faculty of Medicine, University of Iceland, Vatnsmýrarvegur 16, Reykjavik, Iceland.
¹¹ Assmann-Foundation for Prevention, Gronowskistraße 33, Münster, Germany.
¹² Institut Pasteur de Lille, 1 rue du Professeur Calmette, Lille, France.
¹³ National Institute for Health and Welfare, Mannerheimintie 166, Helsinki, Finland.
¹⁴ Department of Epidemiology and Public Health, University College London, 1-19 Torrington Place, London, UK.
¹⁵ Department of Clinical Medicine, Copenhagen University Hospital, Blegdamsvej 3, Copenhagen, Denmark.
¹⁶ Ciccarone Center for the Prevention of Heart Disease, Johns Hopkins Hospital, 1800 Orleans St, Baltimore, MD, USA.
¹⁷ Department of Epidemiology, University of Pittsburgh, 200 Lothrop Street, Pittsburgh, PA, USA.
¹⁸ Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Neuenheimer Feld 581, Heidelberg, Germany.
¹⁹ University of Heidelberg, Grabengasse 1, Heidelberg, Germany.
²⁰ Department of Medicine, Howard University College of Medicine, 2041 Georgia Avenue, Washington, DC, USA.
²¹ German Research Center for Environmental Health, Ingolstädter Landstraße 1, Neuherberg, Germany.
²² Institute of Health & Wellbeing, University of Glasgow, Boyd Orr Building, University Avenue, Glasgow, UK.
²³ Faculty of Health and Medical Sciences, School of Population and Global Health, University of Western Australia, 35 Stirling Highway, Perth, Western Australia, Australia.
²⁴ Sahlgrenska Academy, University of Gothenburg, Medicinaregatan 3, Gothenburg, Sweden.
²⁵ Wallenberg Laboratory, Sahlgrenska University Hospital, Blå stråket 5, Gothenburg, Sweden.
²⁶ Department of Social Medicine, University of Bristol, Bristol, UK.
²⁷ Institute of Community Medicine, University of Greifswald, Ellernholzstraße 1/2, Greifswald, Germany.
²⁸ MRC Lifecourse Epidemiology Unit, University of Southampton, Tremona Rd, Southampton, UK.
²⁹ San Jose Norte Health Centre, 16 Lugar De Santuario Cabañas, Zaragoza, Spain.
³⁰ Department of Medicine, University of Padova, 2 Via Giustiniani, Padova, Italy.
³¹ Institute of Public Health and Clinical Nutrition, University of Eastern Finland, 1 Yliopistonranta, Kuopio, Finland.
³² Centre for Cardiovascular Genetics, University College London, 5 University Street, London, UK.
³³ Department of Geriatric Medicine, University of Hawaii, 1960 East-West Road, Honolulu, HI, USA.
³⁴ Department of Medical Sciences, Uppsala University, Ing 40, 5 tr, Uppsala, Sweden.
³⁵ University of California San Diego, 9500 Gilman Drive, La Jolla, CA, USA.
³⁶ Unit for Cardiovascular Epidemiology, The Gertner Institute for Epidemiology and Health Policy Research, Sheba Medical Center, Tel Hashomer, Israel.
³⁷ Department of Epidemiology and Preventive Medicine, Sackler Faculty of Medicine, School of Public Health, Tel Aviv University, Ramat Aviv, Tel Aviv, Israel.
³⁸ Department of Public Health Sciences, Medical University of South Carolina, 135 Cannon Street, Charleston, SC, USA.
³⁹ Department of Medicine, Columbia University Irving Medical Center, 622 West 168th Street, New York, NY, USA.
⁴⁰ College of Public Health, University of Iowa, 145 N. Riverside Drive, Iowa City, IA, USA.
⁴¹ Department of Surgery, Duke University Medical Center, 2301 Erwin Rd, Durham, NC, USA.
⁴² Department of Public Health and Community Medicine, University of Gothenburg, Medicinaregatan 16, Gothenburg, Sweden.
⁴³ Department of Cardiovascular, Dysmetabolic and Aging-Associated Diseases, Istituto Superiore di Sanità (ISS), 299 Viale Regina Elena, Rome, Italy.
⁴⁴ Yale School of Medicine, 1 Church Street, New Haven, CT, USA.
⁴⁵ Department of Biostatistics, The University of Texas School of Public Health, 1200 Pressler Street, Houston, TX, USA.
⁴⁶ Division of Cardiovascular Sciences, National Heart, Lung, and Blood Institute, 31 Center Drive, Bethesda, MD, USA.
⁴⁷ Population Health Research Institute, St George's, University of London, Cranmer Terrace, London, UK.
⁴⁸ Research Centre for Prevention and Health, 5 Øster Farimagsgade, Copenhagen, Denmark.
⁴⁹ Department of Public Health, University of Copenhagen, 5 Øster Farimagsgade, Copenhagen, Denmark.
⁵⁰ Aalborg University, Fredrik Bajers Vej 5, Aalborg, Denmark.
⁵¹ Faculté de Médecine, Université Paris Descartes, 12 Rue de l'Ecole de Médecine, Paris, France.
⁵² CUNY School of Medicine, City College of New York, 160 Convent Ave, New York, NY, USA.
⁵³ Department of Clinical Sciences, Lund University, Jan Waldenströms gata 35, Malmö, Sweden.
⁵⁴ School of Community Health, Portland State University, 506 SW Mill St, Portland, OR, USA.
⁵⁵ Department of Non-Communicable Disease Epidemiology, London School of Hygiene and Tropical Medicine, Keppel Street, London, UK.
⁵⁶ Department of Health Sciences, Vrije Universiteit Amsterdam, VU University Medical Center, De Boelelaan 1085, Amsterdam, the Netherlands.
⁵⁷ Department of Epidemiology, University Medical Centre Groningen, University of Grogingen, Hanzeplein 1, Groningen, the Netherlands.
⁵⁸ Faculty of Medicine, Yamagata University, 1-4-12 Kojirakawa-machi, Yamagata, Japan.
⁵⁹ Usher Institute of Population Health Sciences and Informatics, University of Edinburgh, Old Medical School, Teviot Place, Edinburgh, UK.
⁶⁰ Department of Clinical Research, Hospital 12 de Octubre, Av. Cordoba, Madrid, Spain.
⁶¹ Department of Cardiology, Leiden University Medical Center, Albinusdreef 2, Leiden, the Netherlands.
⁶² Pavillon Ferdinand-Vandry, Université Laval, 2440 Hochelaga, Quebec, Canada.
⁶³ Department of Cardiology, Cerrahpaşa Faculty of Medicine, Istanbul University, Beyazıt, Fatih, Istanbul, Turkey.
⁶⁴ Faculty of Medicine, UNSW, Sydney, Australia.
⁶⁵ Department of Epidemiology, Erasmus MC, University Medical Center Rotterdam, Doctor Molewaterplein 40, Rotterdam, the Netherlands.
⁶⁶ Bristol Neuroscience, Bristol University, Queens Road, Bristol, UK.
⁶⁷ Department of Psychiatry, University of Oxford, Warneford Hospital, Warneford Lane, Oxford, UK.
⁶⁸ The Institute for Health and Care Research, VU University Medical Center, De Boelelaan 1085, Amsterdam, the Netherlands.
⁶⁹ Kyushu University, 744 Motooka Nishi-ku, Fukuoka, Japan.
⁷⁰ Department of Biostatistics and Bioinformatics, MedStar Health Research Institute, 6525 Belcrest Road, Hyattsville, MD, USA.
⁷¹ Clinical Biostatistics, Merck, 2000 Galloping Hill Road, Kenilworth, NJ, USA.
⁷² Centre de Recherche des Cordeliers, INSERM, 15 rue de l'Ecole de Médecine, Paris, France.
⁷³ Institute of Epidemiology & Health, University College London, 1-19 Torrington Place, London, UK.
⁷⁴ Deutsches Herzzentrum München, Technische Universität München, 21 Arcisstraße, Munich, Germany.
⁷⁵ DZHK (German Centre for Cardiovascular Research), Partner Site Munich Heart Alliance, Biedersteiner Str. 29, Munich, Germany.
⁷⁶ Department of Social and Environmental Medicine, Kanazawa Medical University, 1-1 Daigaku, Uchinada, Ishikawa, Japan.
⁷⁷ Department of Internal Medicine, University Medical Centre Groningen, University of Grogingen, Hanzeplein 1, Groningen, the Netherlands.
⁷⁸ Klinikum der Universität München, Ludwig-Maximilians-Universität, 15 Marchioninistraße, Munich, Germany.
⁷⁹ Clinical Diabetes and Epidemiology, Baker Heart and Diabetes Institute, 75 Commercial Rd, Melbourne, Australia.
⁸⁰ Department of Public Health, University of Tromsø, Hansine Hansens veg 18, Tromsø, Norway.
⁸¹ Chiba Prefectural Institute of Public Health, 666-2 Nito-no-machi Chuo-ku, Chiba, Japan.
⁸² Department for Determinants of Chronic Diseases, National Institute for Public Health and the Environment (RIVM), Antonie van Leeuwenhoeklaan 9, Bilthoven, The Netherlands.
⁸³ Noncommunicable Diseases, Disability, Violence and Injury Prevention Department, World Health Organization, 20 Avenue Appia, Geneva 27, Switzerland.
⁸⁴ School of Medicine, Trinity College Dublin, The University of Dublin, College Green, Dublin 2, Ireland.
⁸⁵ Department of Preventive Medicine, Feinberg School of Medicine, Northwestern University, 420 East Superior Street, Chicago, IL, USA.
⁸⁶ The George Institute for Global Health, University of Oxford, 75 George Street, Oxford, UK.
⁸⁷ The George Institute for Global Health, University of New South Wales, 1 King Street Newtown, Sydney, Australia.
⁸⁸ Faculty of Medicine, School of Public Health, Norfolk Place, St Mary's Campus, Imperial College London, London, UK.
⁸⁹ Cardiovascular Health Research Unit, University of Washington, 1730 Minor Avenue, Seattle, WA, USA.
⁹⁰ Institute of Cardiovascular & Medical Sciences, University of Glasgow, 126 University Place, Glasgow, UK.
⁹¹ Faculty of Medical and Health Sciences, University of Auckland, 261 Morrin Road, Auckland, New Zealand.
⁹² Brigham and Women's Hospital, Harvard Medical School, 900 Commonwealth Avenue, Boston, MA, USA.
⁹³ Mathematics and Statistics Department, Boston University, 111 Cummington Mall, Boston, MA, USA.

PMID: 30476079
PMCID: PMC6374687
DOI: 10.1093/eurheartj/ehy653

Meta-Analysis

Equalization of four cardiovascular risk algorithms after systematic recalibration: individual-participant meta-analysis of 86 prospective studies

Lisa Pennells et al. Eur Heart J. 2019.

. 2019 Feb 14;40(7):621-631.

doi: 10.1093/eurheartj/ehy653.

Authors

Collaborators

Emerging Risk Factors Collaboration:
Robert W Tipping, Lara M Simpson, Sara L Pressel, David J Couper, Vijay Nambi, Kunihiro Matsushita, Aaron R Folsom, Jonathan E Shaw, Dianna J Magliano, Paul Z Zimmet, Matthew W Knuiman, Peter H Whincup, S Goya Wannamethee, Johann Willeit, Peter Santer, Georg Egger, Juan Pablo Casas, Antoinette Amuzu, Yoav Ben-Shlomo, John Gallacher, Valérie Tikhonoff, Edoardo Casiglia, Susan E Sutherland, Paul J Nietert, Mary Cushman, Bruce M Psaty, Anne Johanne Søgaard, Lise Lund Håheim, Inger Ariansen, Anne Tybjærg-Hansen, Gorm B Jensen, Peter Schnohr, Simona Giampaoli, Diego Vanuzzo, Salvatore Panico, Luigi Palmieri, Beverley Balkau, Fabrice Bonnet, Michel Marre, Agustin Gómez de la Cámara, Miguel Angel Rubio Herrera, Yechiel Friedlander, John McCallum, Stela McLachlan, Jack Guralnik, Caroline L Phillips, Kay-Tee Khaw, Nick Wareham, Ben Schöttker, Kai-Uwe Saum, Bernd Holleczek, Aulikki Nissinen, Hanna Tolonen, Simona Giampaoli, Chiara Donfrancesco, Erkki Vartiainen, Pekka Jousilahti, Kennet Harald, Ralph B D’Agostino, Joseph M Massaro, Michael Pencina, Ramachandran Vasan, Takamasa Kayama, Takeo Kato, Toshihide Oizumi, Jørgen Jespersen, Lars Møller, Else Marie Bladbjerg, A Chetrit, Annika Rosengren, Lars Wilhelmsen, Cecilia Björkelund, Lauren Lissner, Dorothea Nagel, Elaine Dennison, Yutaka Kiyohara, Toshiharu Ninomiya, Yasufumi Doi, Beatriz Rodriguez, Giel Nijpels, Coen D A Stehouwer, Shinichi Sato, Yamagishi Kazumasa, Hiroyasu Iso, Uri Goldbourt, Veikko Salomaa, Erkki Vartiainen, Sudhir Kurl, Tomi-Pekka Tuomainen, Jukka T Salonen, Marjolein Visser, Dorly J H Deeg, Tom W Meade, Peter M Nilsson, Bo Hedblad, Olle Melander, Ian H De Boer, Andrew Paul DeFilippis, W M Monique Verschuren, Naveed Sattar, Graham Watt, Christa Meisinger, Wolfgang Koenig, Annika Rosengren, Lewis H Kuller, Aage Tverdal, Richard F Gillum, Jackie A Cooper, Susan Kirkland, Daichi Shimbo, Jonathan Shaffer, Shinichi Sato, Yamagishi Kazumasa, Hiroyasu Iso, Pierre Ducimetiere, Stephan J L Bakker, Pim van der Harst, Hans L Hillege, Carlos J Crespo, Philippe Amouyel, Jean Dallongeville, Gerd Assmann, Helmut Schulte, Stella Trompet, Roelof A J Smit, David J Stott, Yvonne T van der Schouw, Jean-Pierre Després, Bernard Cantin, Gilles R Dagenais, Gail Laughlin, Deborah Wingard, Maurizio Trevisan, Thor Aspelund, Gudny Eiriksdottir, Elias Freyr Gudmundsson, Arfan Ikram, Frank J A van Rooij, Oscar H Franco, Oscar L Rueda-Ochoa, Taulant Muka, Marija Glisic, Hugh Tunstall-Pedoe, Henry Völzke, Barbara V Howard, Ying Zhang, Stacey Jolly, John Gallacher, George Davey-Smith, Günay Can, Hüsniye Yüksel, Hideaki Nakagawa, Yuko Morikawa, Katsuyuki Miura, Inger Njølstad, Martin Ingelsson, Vilmantas Giedraitis, Paul M Ridker, J Michael Gaziano, Mika Kivimaki, Martin Shipley, Eric J Brunner, Volker Arndt, Hermann Brenner, Nancy Cook, Paul M Ridker, Ian Ford, Naveed Sattar, Alejandro Marín Ibañez, Johanna M Geleijnse

Affiliations

¹ Department of Public Health and Primary Care, University of Cambridge, 2 Worts' Causeway, Cambridge, UK.
² Department of Physiology, Development and Neuroscience, University of Cambridge, Downing Street, Cambridge, UK.
³ MRC Clinical Trials Unit, University College London, 90 High Holborn, London, UK.
⁴ MRC Biostatistics Unit, Cambridge Institute of Public Health, University of Cambridge, Forvie Site, Robinson Way, Cambridge, UK.
⁵ Department of Neurology and Neurosurgery, Medical University of Innsbruck, Anichstraße 35, Innsbruck, Austria.
⁶ Epidemiology: Methodology, Julius Center Research Program Methodology, University Medical Center Utrecht, Heidelberglaan 100, Utrecht, the Netherlands.
⁷ Department of Epidemiology, Julius Center Research Program Cardiovascular Epidemiology, University Medical Center Utrecht, Heidelberglaan 100, Utrecht, the Netherlands.
⁸ Division of Epidemiology, Norwegian Institute of Public Health, Postboks 222 Skøyen, Oslo, Norway.
⁹ Icelandic Heart Association, Hjartavernd Holtasmá¡ri 1, Kópavogur, Iceland.
¹⁰ Faculty of Medicine, University of Iceland, Vatnsmýrarvegur 16, Reykjavik, Iceland.
¹¹ Assmann-Foundation for Prevention, Gronowskistraße 33, Münster, Germany.
¹² Institut Pasteur de Lille, 1 rue du Professeur Calmette, Lille, France.
¹³ National Institute for Health and Welfare, Mannerheimintie 166, Helsinki, Finland.
¹⁴ Department of Epidemiology and Public Health, University College London, 1-19 Torrington Place, London, UK.
¹⁵ Department of Clinical Medicine, Copenhagen University Hospital, Blegdamsvej 3, Copenhagen, Denmark.
¹⁶ Ciccarone Center for the Prevention of Heart Disease, Johns Hopkins Hospital, 1800 Orleans St, Baltimore, MD, USA.
¹⁷ Department of Epidemiology, University of Pittsburgh, 200 Lothrop Street, Pittsburgh, PA, USA.
¹⁸ Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Neuenheimer Feld 581, Heidelberg, Germany.
¹⁹ University of Heidelberg, Grabengasse 1, Heidelberg, Germany.
²⁰ Department of Medicine, Howard University College of Medicine, 2041 Georgia Avenue, Washington, DC, USA.
²¹ German Research Center for Environmental Health, Ingolstädter Landstraße 1, Neuherberg, Germany.
²² Institute of Health & Wellbeing, University of Glasgow, Boyd Orr Building, University Avenue, Glasgow, UK.
²³ Faculty of Health and Medical Sciences, School of Population and Global Health, University of Western Australia, 35 Stirling Highway, Perth, Western Australia, Australia.
²⁴ Sahlgrenska Academy, University of Gothenburg, Medicinaregatan 3, Gothenburg, Sweden.
²⁵ Wallenberg Laboratory, Sahlgrenska University Hospital, Blå stråket 5, Gothenburg, Sweden.
²⁶ Department of Social Medicine, University of Bristol, Bristol, UK.
²⁷ Institute of Community Medicine, University of Greifswald, Ellernholzstraße 1/2, Greifswald, Germany.
²⁸ MRC Lifecourse Epidemiology Unit, University of Southampton, Tremona Rd, Southampton, UK.
²⁹ San Jose Norte Health Centre, 16 Lugar De Santuario Cabañas, Zaragoza, Spain.
³⁰ Department of Medicine, University of Padova, 2 Via Giustiniani, Padova, Italy.
³¹ Institute of Public Health and Clinical Nutrition, University of Eastern Finland, 1 Yliopistonranta, Kuopio, Finland.
³² Centre for Cardiovascular Genetics, University College London, 5 University Street, London, UK.
³³ Department of Geriatric Medicine, University of Hawaii, 1960 East-West Road, Honolulu, HI, USA.
³⁴ Department of Medical Sciences, Uppsala University, Ing 40, 5 tr, Uppsala, Sweden.
³⁵ University of California San Diego, 9500 Gilman Drive, La Jolla, CA, USA.
³⁶ Unit for Cardiovascular Epidemiology, The Gertner Institute for Epidemiology and Health Policy Research, Sheba Medical Center, Tel Hashomer, Israel.
³⁷ Department of Epidemiology and Preventive Medicine, Sackler Faculty of Medicine, School of Public Health, Tel Aviv University, Ramat Aviv, Tel Aviv, Israel.
³⁸ Department of Public Health Sciences, Medical University of South Carolina, 135 Cannon Street, Charleston, SC, USA.
³⁹ Department of Medicine, Columbia University Irving Medical Center, 622 West 168th Street, New York, NY, USA.
⁴⁰ College of Public Health, University of Iowa, 145 N. Riverside Drive, Iowa City, IA, USA.
⁴¹ Department of Surgery, Duke University Medical Center, 2301 Erwin Rd, Durham, NC, USA.
⁴² Department of Public Health and Community Medicine, University of Gothenburg, Medicinaregatan 16, Gothenburg, Sweden.
⁴³ Department of Cardiovascular, Dysmetabolic and Aging-Associated Diseases, Istituto Superiore di Sanità (ISS), 299 Viale Regina Elena, Rome, Italy.
⁴⁴ Yale School of Medicine, 1 Church Street, New Haven, CT, USA.
⁴⁵ Department of Biostatistics, The University of Texas School of Public Health, 1200 Pressler Street, Houston, TX, USA.
⁴⁶ Division of Cardiovascular Sciences, National Heart, Lung, and Blood Institute, 31 Center Drive, Bethesda, MD, USA.
⁴⁷ Population Health Research Institute, St George's, University of London, Cranmer Terrace, London, UK.
⁴⁸ Research Centre for Prevention and Health, 5 Øster Farimagsgade, Copenhagen, Denmark.
⁴⁹ Department of Public Health, University of Copenhagen, 5 Øster Farimagsgade, Copenhagen, Denmark.
⁵⁰ Aalborg University, Fredrik Bajers Vej 5, Aalborg, Denmark.
⁵¹ Faculté de Médecine, Université Paris Descartes, 12 Rue de l'Ecole de Médecine, Paris, France.
⁵² CUNY School of Medicine, City College of New York, 160 Convent Ave, New York, NY, USA.
⁵³ Department of Clinical Sciences, Lund University, Jan Waldenströms gata 35, Malmö, Sweden.
⁵⁴ School of Community Health, Portland State University, 506 SW Mill St, Portland, OR, USA.
⁵⁵ Department of Non-Communicable Disease Epidemiology, London School of Hygiene and Tropical Medicine, Keppel Street, London, UK.
⁵⁶ Department of Health Sciences, Vrije Universiteit Amsterdam, VU University Medical Center, De Boelelaan 1085, Amsterdam, the Netherlands.
⁵⁷ Department of Epidemiology, University Medical Centre Groningen, University of Grogingen, Hanzeplein 1, Groningen, the Netherlands.
⁵⁸ Faculty of Medicine, Yamagata University, 1-4-12 Kojirakawa-machi, Yamagata, Japan.
⁵⁹ Usher Institute of Population Health Sciences and Informatics, University of Edinburgh, Old Medical School, Teviot Place, Edinburgh, UK.
⁶⁰ Department of Clinical Research, Hospital 12 de Octubre, Av. Cordoba, Madrid, Spain.
⁶¹ Department of Cardiology, Leiden University Medical Center, Albinusdreef 2, Leiden, the Netherlands.
⁶² Pavillon Ferdinand-Vandry, Université Laval, 2440 Hochelaga, Quebec, Canada.
⁶³ Department of Cardiology, Cerrahpaşa Faculty of Medicine, Istanbul University, Beyazıt, Fatih, Istanbul, Turkey.
⁶⁴ Faculty of Medicine, UNSW, Sydney, Australia.
⁶⁵ Department of Epidemiology, Erasmus MC, University Medical Center Rotterdam, Doctor Molewaterplein 40, Rotterdam, the Netherlands.
⁶⁶ Bristol Neuroscience, Bristol University, Queens Road, Bristol, UK.
⁶⁷ Department of Psychiatry, University of Oxford, Warneford Hospital, Warneford Lane, Oxford, UK.
⁶⁸ The Institute for Health and Care Research, VU University Medical Center, De Boelelaan 1085, Amsterdam, the Netherlands.
⁶⁹ Kyushu University, 744 Motooka Nishi-ku, Fukuoka, Japan.
⁷⁰ Department of Biostatistics and Bioinformatics, MedStar Health Research Institute, 6525 Belcrest Road, Hyattsville, MD, USA.
⁷¹ Clinical Biostatistics, Merck, 2000 Galloping Hill Road, Kenilworth, NJ, USA.
⁷² Centre de Recherche des Cordeliers, INSERM, 15 rue de l'Ecole de Médecine, Paris, France.
⁷³ Institute of Epidemiology & Health, University College London, 1-19 Torrington Place, London, UK.
⁷⁴ Deutsches Herzzentrum München, Technische Universität München, 21 Arcisstraße, Munich, Germany.
⁷⁵ DZHK (German Centre for Cardiovascular Research), Partner Site Munich Heart Alliance, Biedersteiner Str. 29, Munich, Germany.
⁷⁶ Department of Social and Environmental Medicine, Kanazawa Medical University, 1-1 Daigaku, Uchinada, Ishikawa, Japan.
⁷⁷ Department of Internal Medicine, University Medical Centre Groningen, University of Grogingen, Hanzeplein 1, Groningen, the Netherlands.
⁷⁸ Klinikum der Universität München, Ludwig-Maximilians-Universität, 15 Marchioninistraße, Munich, Germany.
⁷⁹ Clinical Diabetes and Epidemiology, Baker Heart and Diabetes Institute, 75 Commercial Rd, Melbourne, Australia.
⁸⁰ Department of Public Health, University of Tromsø, Hansine Hansens veg 18, Tromsø, Norway.
⁸¹ Chiba Prefectural Institute of Public Health, 666-2 Nito-no-machi Chuo-ku, Chiba, Japan.
⁸² Department for Determinants of Chronic Diseases, National Institute for Public Health and the Environment (RIVM), Antonie van Leeuwenhoeklaan 9, Bilthoven, The Netherlands.
⁸³ Noncommunicable Diseases, Disability, Violence and Injury Prevention Department, World Health Organization, 20 Avenue Appia, Geneva 27, Switzerland.
⁸⁴ School of Medicine, Trinity College Dublin, The University of Dublin, College Green, Dublin 2, Ireland.
⁸⁵ Department of Preventive Medicine, Feinberg School of Medicine, Northwestern University, 420 East Superior Street, Chicago, IL, USA.
⁸⁶ The George Institute for Global Health, University of Oxford, 75 George Street, Oxford, UK.
⁸⁷ The George Institute for Global Health, University of New South Wales, 1 King Street Newtown, Sydney, Australia.
⁸⁸ Faculty of Medicine, School of Public Health, Norfolk Place, St Mary's Campus, Imperial College London, London, UK.
⁸⁹ Cardiovascular Health Research Unit, University of Washington, 1730 Minor Avenue, Seattle, WA, USA.
⁹⁰ Institute of Cardiovascular & Medical Sciences, University of Glasgow, 126 University Place, Glasgow, UK.
⁹¹ Faculty of Medical and Health Sciences, University of Auckland, 261 Morrin Road, Auckland, New Zealand.
⁹² Brigham and Women's Hospital, Harvard Medical School, 900 Commonwealth Avenue, Boston, MA, USA.
⁹³ Mathematics and Statistics Department, Boston University, 111 Cummington Mall, Boston, MA, USA.

PMID: 30476079
PMCID: PMC6374687
DOI: 10.1093/eurheartj/ehy653

Abstract

Aims: There is debate about the optimum algorithm for cardiovascular disease (CVD) risk estimation. We conducted head-to-head comparisons of four algorithms recommended by primary prevention guidelines, before and after 'recalibration', a method that adapts risk algorithms to take account of differences in the risk characteristics of the populations being studied.

Methods and results: Using individual-participant data on 360 737 participants without CVD at baseline in 86 prospective studies from 22 countries, we compared the Framingham risk score (FRS), Systematic COronary Risk Evaluation (SCORE), pooled cohort equations (PCE), and Reynolds risk score (RRS). We calculated measures of risk discrimination and calibration, and modelled clinical implications of initiating statin therapy in people judged to be at 'high' 10 year CVD risk. Original risk algorithms were recalibrated using the risk factor profile and CVD incidence of target populations. The four algorithms had similar risk discrimination. Before recalibration, FRS, SCORE, and PCE over-predicted CVD risk on average by 10%, 52%, and 41%, respectively, whereas RRS under-predicted by 10%. Original versions of algorithms classified 29-39% of individuals aged ≥40 years as high risk. By contrast, recalibration reduced this proportion to 22-24% for every algorithm. We estimated that to prevent one CVD event, it would be necessary to initiate statin therapy in 44-51 such individuals using original algorithms, in contrast to 37-39 individuals with recalibrated algorithms.

Conclusion: Before recalibration, the clinical performance of four widely used CVD risk algorithms varied substantially. By contrast, simple recalibration nearly equalized their performance and improved modelled targeting of preventive action to clinical need.

Keywords: Calibration; Cardiovascular disease; Discrimination; Risk algorithms; Risk prediction.

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Figures

**Figure 1**
Discrimination abilities of original versions of three risk prediction algorithms compared with the Framingham risk score using alternative CVD definitions. Number of events observed according to CVD definitions used by the Pooled Cohort Equations, the Systematic COronary Risk Evaluation and the Reynolds Risk Score respectively were 14 564, 7433 and 17 642. Equivalent event numbers in the subset of participants with complete data for estimation of the Reynolds Risk Score were 6670, 2966 and 7953 respectively. FRS, Framingham risk score; PCE, pooled cohort equations; RRS, Reynolds risk score; SCORE, Systematic COronary Risk Evaluation. *P < 0.05; **P < 0.001.

**Figure 2**
Observed and predicted 10-year cardiovascular risk using original version of prediction algorithms. Points presented in each plot are for each 5-year age group between 40–44 to 75–79 years. Observed risk was calculated according to the CVD definition specific to each algorithm. Assessment of the Framingham Risk Score, the Systematic COronary Risk Evaluation and the Pooled Cohort Equations was based on 223 663 participants from 47 cohorts with at least 10 years of follow-up. Assessment of the Reynolds Risk Score was based on 91 008 participants from 27 cohorts with at least 10 years of follow-up. FRS, Framingham risk score; PCE, pooled cohort equations; RRS, Reynolds risk score; SCORE, Systematic COronary Risk Evaluation.

**Figure 3**
Estimated public health impact with screening using original and recalibrated cardiovascular disease risk prediction algorithms over a range of risk thresholds in a standard US population of 100 000 people aged over 40 years. Cardiovascular disease includes fatal coronary heart disease, fatal, and non-fatal myocardial infarction and any stroke. FRS, Framingham risk score; PCE, pooled cohort equations; RRS, Reynolds risk score; SCORE, Systematic COronary Risk Evaluation.

**Figure 4**
Pairwise overlap in those classified at high risk when applying CVD risk prediction algorithms to a US standard population of 100 000 individuals. Risk thresholds to define high risk were set at 7.5% for Framingham risk score, pooled cohort equations and Reynolds risk score and 5% for Systematic COronary Risk Evaluation before recalibration. After to recalibration to our common CVD endpoint a risk threshold of 7.5% was used for all algorithms. n represents the number of individuals classified at high risk with either algorithm. FRS, Framingham risk score; PCE, pooled cohort equations; RRS, Reynolds risk score; SCORE, Systematic COronary Risk Evaluation.

**Take home figure**
Recalibration equalizes the potential public health impact of different guideline recommended cardiovascular disease risk algorithms and should be regularly applied to improve targeting of intervention. Cardiovascular disease includes fatal coronary heart disease, fatal, and non-fatal myocardial infarction and any stroke. FRS, Framingham risk score; PCE, pooled cohort equations; RRS, Reynolds risk score; SCORE, Systematic COronary Risk Evaluation.

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Comment in

Is 're-calibration' of standard cardiovascular disease (CVD) risk algorithms the panacea to improved CVD risk prediction and prevention?
Laukkanen JA, Kunutsor SK. Laukkanen JA, et al. Eur Heart J. 2019 Feb 14;40(7):632-634. doi: 10.1093/eurheartj/ehy726. Eur Heart J. 2019. PMID: 30476017 No abstract available.

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Equalization of four cardiovascular risk algorithms after systematic recalibration: individual-participant meta-analysis of 86 prospective studies

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Equalization of four cardiovascular risk algorithms after systematic recalibration: individual-participant meta-analysis of 86 prospective studies

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