Global Effect of Modifiable Risk Factors on Cardiovascular Disease and Mortality

doi:10.1056/NEJMoa2206916

Meta-Analysis

. 2023 Oct 5;389(14):1273-1285.

doi: 10.1056/NEJMoa2206916. Epub 2023 Aug 26.

Global Effect of Modifiable Risk Factors on Cardiovascular Disease and Mortality

Global Cardiovascular Risk Consortium; Christina Magnussen¹, Francisco M Ojeda¹, Darryl P Leong¹, Jesus Alegre-Diaz¹, Philippe Amouyel¹, Larissa Aviles-Santa¹, Dirk De Bacquer¹, Christie M Ballantyne¹, Antonio Bernabé-Ortiz¹, Martin Bobak¹, Hermann Brenner¹, Rodrigo M Carrillo-Larco¹, James de Lemos¹, Annette Dobson¹, Marcus Dörr¹, Chiara Donfrancesco¹, Wojciech Drygas¹, Robin P Dullaart¹, Gunnar Engström¹, Marco M Ferrario¹, Jean Ferrières¹, Giovanni de Gaetano¹, Uri Goldbourt¹, Clicerio Gonzalez¹, Guido Grassi¹, Allison M Hodge¹, Kristian Hveem¹, Licia Iacoviello¹, M Kamran Ikram¹, Vilma Irazola¹, Modou Jobe¹, Pekka Jousilahti¹, Pontiano Kaleebu¹, Maryam Kavousi¹, Frank Kee¹, Davood Khalili¹, Wolfgang Koenig¹, Anna Kontsevaya¹, Kari Kuulasmaa¹, Karl J Lackner¹, David M Leistner¹, Lars Lind¹, Allan Linneberg¹, Thiess Lorenz¹, Magnus Nakrem Lyngbakken¹, Reza Malekzadeh¹, Sofia Malyutina¹, Ellisiv B Mathiesen¹, Olle Melander¹, Andres Metspalu¹, J Jaime Miranda¹, Marie Moitry¹, Joseph Mugisha¹, Mahdi Nalini¹, Vijay Nambi¹, Toshiharu Ninomiya¹, Karen Oppermann¹, Eleonora d'Orsi¹, Andrzej Pająk¹, Luigi Palmieri¹, Demosthenes Panagiotakos¹, Arokiasamy Perianayagam¹, Annette Peters¹, Hossein Poustchi¹, Andrew M Prentice¹, Eva Prescott¹, Ulf Risérus¹, Veikko Salomaa¹, Susana Sans¹, Satoko Sakata¹, Ben Schöttker¹, Aletta E Schutte¹, Sadaf G Sepanlou¹, Sanjib Kumar Sharma¹, Jonathan E Shaw¹, Leon A Simons¹, Stefan Söderberg¹, Abdonas Tamosiunas¹, Barbara Thorand¹, Hugh Tunstall-Pedoe¹, Raphael Twerenbold¹, Diego Vanuzzo¹, Giovanni Veronesi¹, Julia Waibel¹, S Goya Wannamethee¹, Masafumi Watanabe¹, Philipp S Wild¹, Yao Yao¹, Yi Zeng¹, Andreas Ziegler¹, Stefan Blankenberg¹

Collaborators, Affiliations

Collaborators

Global Cardiovascular Risk Consortium:
Fereidoun Azizi, Alireza Ansari-Moghaddam, Stephan Bakker, Fabian J Brunner, Günay Can, Giancarlo Cesana, William Checkley, Jean Dallongeville, Abdoulie Faal, Mojtaba Farjam, Simona Giampaoli, Graham Giles, Alina Goßling, Tuija Jääskeläinen, Torben Jørgensen, Bijoy Joseph, Line Lund Kårhus, Jens Klotsche, Fariborz Mansour-Ghanaei, Mahmood Moosazadeh, Pablo Kuri-Morales, David A Leon, Sarah Lewington, Farid Najafi, Johannes T Neumann, Peter M Nilsson, Torbjørn Omland, Abbas Rezaianzadeh, Nader Saki, Isaac Sekitoleko, Mohammad Hossein Somi, Poli Mara Spritzer, Roberto Tapia-Conyer, Tetsu Watanabe, Jessica Weimann, Peter Whincup, Tanja Zeller

Affiliation

¹ The authors' affiliations are as follows: the Center for Population Health Innovation, University Heart and Vascular Center Hamburg (C.M., F.M.O., T.L., R.T., J.W., A.Z., S.B.), University Medical Center Hamburg-Eppendorf (C.M., F.M.O., T.L., R.T., J.W., A.Z., S.B.), the German Center for Cardiovascular Research (DZHK) Partner Site Hamburg-Kiel-Lübeck (C.M., T.L., R.T., J.W., S.B.), the Division of Clinical Epidemiology and Aging Research, German Cancer Research Center, and Network Aging Research, Heidelberg University, Heidelberg (H.B., B.S.), the Department of Internal Medicine B, University Medicine Greifswald, and DZHK Partner Site Greifswald, Greifswald (M.D.), DZHK Partner Site Munich Heart Alliance (W.K., A. Peters), the German Heart Center, Technical University of Munich (W.K.), and the Institute for Medical Information Processing, Biometry, and Epidemiology, Medical Faculty, Ludwig Maximilians Universität München (A. Peters, B.T.), Munich, the Institute of Epidemiology and Medical Biometry, University of Ulm, Ulm (W.K.), the Institute of Clinical Chemistry and Laboratory Medicine (K.J.L.), Preventive Cardiology and Preventive Medicine (P.S.W.), and Clinical Epidemiology and Systems Medicine, Center for Thrombosis and Hemostasis (P.S.W.), University Medical Center of the Johannes Gutenberg-University Mainz, DZHK Partner Site Rhine-Main (K.J.L., P.S.W.), and Institute for Molecular Biology (P.S.W.), Mainz, the University Heart and Vascular Center Frankfurt, DZHK Partner Site Rhine-Main, Frankfurt (D.M.L.), the Institute of Epidemiology, Helmholtz Zentrum München, German Research Center for Environmental Health (A. Peters, B.T.), and German Center for Diabetes Research (DZD) Partner Site Munich-Neuherberg (A. Peters, B.T.), Neuherberg - all in Germany; the Department of Medicine (Cardiology), McMaster University, Hamilton, Canada (D.P.L.); the Experimental Medicine Research Unit, School of Medicine, National Autonomous University of Mexico, Mexico City (J.A.-D.), and Centro de Estudios en Diabetes, Centro de Investigacion en Salud Poblacional, Instituto Nacional de Salud Publica, Cuernavaca (C.G.) - both in Mexico; Université de Lille, INSERM, Centre Hospitalier University de Lille, Institut Pasteur de Lille, UMR1167-RID-AGE-Risk Factors and Molecular Determinants of Aging-Related Diseases, Epidemiology and Public Health Department, Lille (P.A.), the Department of Cardiology, INSERM UMR1295, Toulouse Rangueil University Hospital, Toulouse (J.F.), and the Department of Public Health, Strasbourg University Hospital, University of Strasbourg, Strasbourg (M.M.) - all in France; the Division of Clinical and Health Services Research, National Institute on Minority Health and Health Disparities (L.A.-S.), and the Metabolic Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute (M.N.), National Institutes of Health, Bethesda, MD; the Department of Public Health and Primary Care, Ghent University, Ghent, Belgium (D.D.B.); the Department of Medicine, Baylor College of Medicine (C.M.B.), and Michael E. DeBakey Veterans Affairs Hospital and Baylor College of Medicine (V.N.), Houston, and the Division of Cardiology, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas (J.L.) - all in Texas; the CRONICAS Center of Excellence in Chronic Diseases, Universidad Peruana Cayetano Heredia, Lima, Peru (A.B.-O., J.J.M.); the Department of Epidemiology and Public Health (M.B.) and the Research Department of Primary Care and Population Health (S.G.W.), University College London, London, the Centre for Public Health, Queens University Belfast, Belfast (F.K.), and the Cardiovascular Epidemiology Unit, Institute of Cardiovascular Research, University of Dundee, Dundee (H.T.-P.) - all in the United Kingdom; the Emory Global Diabetes Research Center and Hubert Department of Global Health, Rollins School of Public Health, Emory University, Atlanta (R.M.C.-L.); the School of Public Health, University of Queensland, Brisbane (A.D.), the Division of Cancer Epidemiology, Cancer Council Victoria (A.M.H.), the Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, the University of Melbourne (A.M.H.), and Baker Heart and Diabetes Institute (J.E.S.), Melbourne, the Sydney School of Public Health, Faculty of Medicine and Health, University of Sydney (J.J.M.), and the George Institute for Global Health (A.E.S.), Sydney, and the School of Population Health (A.E.S.), University of New South Wales, Kensington (L.A.S.) - all in Australia; the Department of Cardiovascular and Endocrine-Metabolic Diseases and Aging, Istituto Superiore di Sanità, Rome (C.D., L.P.), the Research Center in Epidemiology and Preventive Medicine, Department of Medicine and Surgery, University of Insubria, Varese (M.M.F., L.I., G.V.), the Department of Epidemiology and Prevention, IRCCS Neuromed, Pozzilli (G. de Gaetano, L.I.), Clinica Medica, University of Milano-Bicocca, Milan (G. Grassi), and the MONICA (Monitoring Cardiovascular Diseases)-Friuli Study Group, Udine (D.V.) - all in Italy; the Department of Epidemiology, Cardiovascular Disease Prevention and Health Promotion, National Institute of Cardiology, and Lazarski University, Warsaw (W.D.), and the Department of Epidemiology and Population Studies, Institute of Public Health, Faculty of Health Sciences, Jagiellonian University Medical College, Krakow (A. Pajak) - all in Poland; the Department of Endocrinology, University Medical Center Groningen, University of Groningen, Groningen (R.P.D.), and the Departments of Neurology (M.K.I.) and Epidemiology (M.K.I., M.K.), Erasmus University Medical Center Rotterdam, Rotterdam - both in the Netherlands; the Department of Clinical Sciences Malmö, Lund University, Malmö (G.E., O.M.), the Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism, Uppsala University (U.R.), and the Department of Medical Sciences, Uppsala University, Uppsala (L.L.), and the Department of Public Health and Clinical Medicine, University of Umea, Umea (S. Söderberg) - all in Sweden; the Department of Epidemiology, Tel Aviv University School of Public Health, Tel Aviv, Israel (U.G.); HUNT (Trøndelag Health Study) Research Center, Department of Public Health and Nursing, Norwegian University of Science and Technology, Levanger (K.H.), the K.G. Jebsen Center for Genetic Epidemiology, Department of Public Health and Nursing, Trondheim(K.H.), the Department of Cardiology, Division of Medicine, Akershus University Hospital, Lørenskog (M.N.L.), the K.G. Jebsen Center for Cardiac Biomarkers, Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo (M.N.L.), and the Department of Clinical Medicine, University of Tromsø the Arctic University of Norway, Tromsø (E.B.M.) - all in Norway; the Department of Chronic Diseases, Institute for Clinical Effectiveness and Health Policy, Buenos Aires (V.I.); Medical Research Council Unit The Gambia at London School of Hygiene and Tropical Medicine, Banjul, Gambia (M.J., A.M.P.); the Department of Public Health and Welfare, Finnish Institute for Health and Welfare, Helsinki (P.J., K.K., V.S.); Medical Research Council-Uganda Virus Research Institute and London School of Hygiene and Tropical Medicine Uganda Research Unit, Entebbe, Uganda (P.K., J.M.); the Prevention of Metabolic Disorders Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences (D.K.), the Liver and Pancreaticobiliary Disease Research Center (R.M.), the Digestive Oncology Research Center (R.M., H.P.), and the Digestive Disease Research Center (R.M., M.N., H.P., S.G.S.), Digestive Disease Research Institute, Shariati Hospital, Tehran University of Medical Sciences - all in Tehran, Iran; the National Research Center for Therapy and Preventive Medicine, Ministry of Healthcare of the Russian Federation, Moscow (A.K.), and the Research Institute of Internal and Preventive Medicine-Branch of the Federal Research Center Institute of Cytology and Genetics, Siberian Branch of Russian Academy of Sciences, Novosibirsk (S.M.) - both in Russia; the Department of Clinical Medicine, Faculty of Health and Medical Sciences (A.L.), and the Department of Cardiology, Bispebjerg Hospital (E.P.), University of Copenhagen, and the Center for Clinical Research and Prevention, Bispebjerg and Frederiksberg Hospital (A.L.) - both in Copenhagen; the Estonian Genome Center, Institute of Genomics, University of Tartu, Tartu, Estonia (A.M.); the Department of Epidemiology and Public Health, Graduate School of Medical Sciences, Kyushu University, Fukuoka (T.N., S. Sakata), and the Global Center of Excellence Program Study Group, Yamagata University School of Medicine, Yamagata (M.W.) - both in Japan; the School of Medicine, University of Passo Fundo, Passo Fundo (K.O.), and the Department of Public Health, Postgraduate Program in Public Health, Federal University of Santa Catarina, Florianopolis (E.O.) - both in Brazil; the School of Health Sciences and Education, Harokopio University, Athens, Greece (D.P.); the National Council of Applied Economic Research, Delhi (A. Perianayagam), and the International Institute for Population Sciences, Mumbai (A. Perianayagam) - both in India; the Catalan Department of Health, Barcelona (S. Sans); the Hypertension in Africa Research Team, South African Medical Research Council Unit for Hypertension and Cardiovascular Disease, North-West University, Potchefstroom (A.E.S.), and the School of Mathematics, Statistics, and Computer Science, University of KwaZulu-Natal, Pietermaritzburg (A.Z.) - both in South Africa; the Department of Internal Medicine, B.P. Koirala Institute of Health Sciences, Dharan, Nepal (S.K.S.); the Laboratory of Population Studies, Institute of Cardiology, and the Department of Preventive Medicine, Faculty of Public Health, Lithuanian University of Health Sciences, Kaunas, Lithuania (A.T.); the China Center for Health Development Studies (Y.Y.) and Center for Healthy Aging and Development Studies, National School of Development (Y.Z.), Peking University, and the Key Laboratory of Epidemiology of Major Diseases, Peking University, Ministry of Education (Y.Y.) - both in Beijing; the Center for the Study of Aging and Human Development and Geriatrics Division, Medical School of Duke University, Durham, NC (Y.Z.); and Cardio-CARE, Davos (A.Z., S.B.), and the Swiss Institute of Bioinformatics, Lausanne (A.Z.) - both in Switzerland.

PMID: 37632466
PMCID: PMC10589462
DOI: 10.1056/NEJMoa2206916

Meta-Analysis

Global Effect of Modifiable Risk Factors on Cardiovascular Disease and Mortality

Global Cardiovascular Risk Consortium et al. N Engl J Med. 2023.

. 2023 Oct 5;389(14):1273-1285.

doi: 10.1056/NEJMoa2206916. Epub 2023 Aug 26.

Authors

Collaborators

Global Cardiovascular Risk Consortium:
Fereidoun Azizi, Alireza Ansari-Moghaddam, Stephan Bakker, Fabian J Brunner, Günay Can, Giancarlo Cesana, William Checkley, Jean Dallongeville, Abdoulie Faal, Mojtaba Farjam, Simona Giampaoli, Graham Giles, Alina Goßling, Tuija Jääskeläinen, Torben Jørgensen, Bijoy Joseph, Line Lund Kårhus, Jens Klotsche, Fariborz Mansour-Ghanaei, Mahmood Moosazadeh, Pablo Kuri-Morales, David A Leon, Sarah Lewington, Farid Najafi, Johannes T Neumann, Peter M Nilsson, Torbjørn Omland, Abbas Rezaianzadeh, Nader Saki, Isaac Sekitoleko, Mohammad Hossein Somi, Poli Mara Spritzer, Roberto Tapia-Conyer, Tetsu Watanabe, Jessica Weimann, Peter Whincup, Tanja Zeller

Affiliation

¹ The authors' affiliations are as follows: the Center for Population Health Innovation, University Heart and Vascular Center Hamburg (C.M., F.M.O., T.L., R.T., J.W., A.Z., S.B.), University Medical Center Hamburg-Eppendorf (C.M., F.M.O., T.L., R.T., J.W., A.Z., S.B.), the German Center for Cardiovascular Research (DZHK) Partner Site Hamburg-Kiel-Lübeck (C.M., T.L., R.T., J.W., S.B.), the Division of Clinical Epidemiology and Aging Research, German Cancer Research Center, and Network Aging Research, Heidelberg University, Heidelberg (H.B., B.S.), the Department of Internal Medicine B, University Medicine Greifswald, and DZHK Partner Site Greifswald, Greifswald (M.D.), DZHK Partner Site Munich Heart Alliance (W.K., A. Peters), the German Heart Center, Technical University of Munich (W.K.), and the Institute for Medical Information Processing, Biometry, and Epidemiology, Medical Faculty, Ludwig Maximilians Universität München (A. Peters, B.T.), Munich, the Institute of Epidemiology and Medical Biometry, University of Ulm, Ulm (W.K.), the Institute of Clinical Chemistry and Laboratory Medicine (K.J.L.), Preventive Cardiology and Preventive Medicine (P.S.W.), and Clinical Epidemiology and Systems Medicine, Center for Thrombosis and Hemostasis (P.S.W.), University Medical Center of the Johannes Gutenberg-University Mainz, DZHK Partner Site Rhine-Main (K.J.L., P.S.W.), and Institute for Molecular Biology (P.S.W.), Mainz, the University Heart and Vascular Center Frankfurt, DZHK Partner Site Rhine-Main, Frankfurt (D.M.L.), the Institute of Epidemiology, Helmholtz Zentrum München, German Research Center for Environmental Health (A. Peters, B.T.), and German Center for Diabetes Research (DZD) Partner Site Munich-Neuherberg (A. Peters, B.T.), Neuherberg - all in Germany; the Department of Medicine (Cardiology), McMaster University, Hamilton, Canada (D.P.L.); the Experimental Medicine Research Unit, School of Medicine, National Autonomous University of Mexico, Mexico City (J.A.-D.), and Centro de Estudios en Diabetes, Centro de Investigacion en Salud Poblacional, Instituto Nacional de Salud Publica, Cuernavaca (C.G.) - both in Mexico; Université de Lille, INSERM, Centre Hospitalier University de Lille, Institut Pasteur de Lille, UMR1167-RID-AGE-Risk Factors and Molecular Determinants of Aging-Related Diseases, Epidemiology and Public Health Department, Lille (P.A.), the Department of Cardiology, INSERM UMR1295, Toulouse Rangueil University Hospital, Toulouse (J.F.), and the Department of Public Health, Strasbourg University Hospital, University of Strasbourg, Strasbourg (M.M.) - all in France; the Division of Clinical and Health Services Research, National Institute on Minority Health and Health Disparities (L.A.-S.), and the Metabolic Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute (M.N.), National Institutes of Health, Bethesda, MD; the Department of Public Health and Primary Care, Ghent University, Ghent, Belgium (D.D.B.); the Department of Medicine, Baylor College of Medicine (C.M.B.), and Michael E. DeBakey Veterans Affairs Hospital and Baylor College of Medicine (V.N.), Houston, and the Division of Cardiology, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas (J.L.) - all in Texas; the CRONICAS Center of Excellence in Chronic Diseases, Universidad Peruana Cayetano Heredia, Lima, Peru (A.B.-O., J.J.M.); the Department of Epidemiology and Public Health (M.B.) and the Research Department of Primary Care and Population Health (S.G.W.), University College London, London, the Centre for Public Health, Queens University Belfast, Belfast (F.K.), and the Cardiovascular Epidemiology Unit, Institute of Cardiovascular Research, University of Dundee, Dundee (H.T.-P.) - all in the United Kingdom; the Emory Global Diabetes Research Center and Hubert Department of Global Health, Rollins School of Public Health, Emory University, Atlanta (R.M.C.-L.); the School of Public Health, University of Queensland, Brisbane (A.D.), the Division of Cancer Epidemiology, Cancer Council Victoria (A.M.H.), the Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, the University of Melbourne (A.M.H.), and Baker Heart and Diabetes Institute (J.E.S.), Melbourne, the Sydney School of Public Health, Faculty of Medicine and Health, University of Sydney (J.J.M.), and the George Institute for Global Health (A.E.S.), Sydney, and the School of Population Health (A.E.S.), University of New South Wales, Kensington (L.A.S.) - all in Australia; the Department of Cardiovascular and Endocrine-Metabolic Diseases and Aging, Istituto Superiore di Sanità, Rome (C.D., L.P.), the Research Center in Epidemiology and Preventive Medicine, Department of Medicine and Surgery, University of Insubria, Varese (M.M.F., L.I., G.V.), the Department of Epidemiology and Prevention, IRCCS Neuromed, Pozzilli (G. de Gaetano, L.I.), Clinica Medica, University of Milano-Bicocca, Milan (G. Grassi), and the MONICA (Monitoring Cardiovascular Diseases)-Friuli Study Group, Udine (D.V.) - all in Italy; the Department of Epidemiology, Cardiovascular Disease Prevention and Health Promotion, National Institute of Cardiology, and Lazarski University, Warsaw (W.D.), and the Department of Epidemiology and Population Studies, Institute of Public Health, Faculty of Health Sciences, Jagiellonian University Medical College, Krakow (A. Pajak) - all in Poland; the Department of Endocrinology, University Medical Center Groningen, University of Groningen, Groningen (R.P.D.), and the Departments of Neurology (M.K.I.) and Epidemiology (M.K.I., M.K.), Erasmus University Medical Center Rotterdam, Rotterdam - both in the Netherlands; the Department of Clinical Sciences Malmö, Lund University, Malmö (G.E., O.M.), the Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism, Uppsala University (U.R.), and the Department of Medical Sciences, Uppsala University, Uppsala (L.L.), and the Department of Public Health and Clinical Medicine, University of Umea, Umea (S. Söderberg) - all in Sweden; the Department of Epidemiology, Tel Aviv University School of Public Health, Tel Aviv, Israel (U.G.); HUNT (Trøndelag Health Study) Research Center, Department of Public Health and Nursing, Norwegian University of Science and Technology, Levanger (K.H.), the K.G. Jebsen Center for Genetic Epidemiology, Department of Public Health and Nursing, Trondheim(K.H.), the Department of Cardiology, Division of Medicine, Akershus University Hospital, Lørenskog (M.N.L.), the K.G. Jebsen Center for Cardiac Biomarkers, Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo (M.N.L.), and the Department of Clinical Medicine, University of Tromsø the Arctic University of Norway, Tromsø (E.B.M.) - all in Norway; the Department of Chronic Diseases, Institute for Clinical Effectiveness and Health Policy, Buenos Aires (V.I.); Medical Research Council Unit The Gambia at London School of Hygiene and Tropical Medicine, Banjul, Gambia (M.J., A.M.P.); the Department of Public Health and Welfare, Finnish Institute for Health and Welfare, Helsinki (P.J., K.K., V.S.); Medical Research Council-Uganda Virus Research Institute and London School of Hygiene and Tropical Medicine Uganda Research Unit, Entebbe, Uganda (P.K., J.M.); the Prevention of Metabolic Disorders Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences (D.K.), the Liver and Pancreaticobiliary Disease Research Center (R.M.), the Digestive Oncology Research Center (R.M., H.P.), and the Digestive Disease Research Center (R.M., M.N., H.P., S.G.S.), Digestive Disease Research Institute, Shariati Hospital, Tehran University of Medical Sciences - all in Tehran, Iran; the National Research Center for Therapy and Preventive Medicine, Ministry of Healthcare of the Russian Federation, Moscow (A.K.), and the Research Institute of Internal and Preventive Medicine-Branch of the Federal Research Center Institute of Cytology and Genetics, Siberian Branch of Russian Academy of Sciences, Novosibirsk (S.M.) - both in Russia; the Department of Clinical Medicine, Faculty of Health and Medical Sciences (A.L.), and the Department of Cardiology, Bispebjerg Hospital (E.P.), University of Copenhagen, and the Center for Clinical Research and Prevention, Bispebjerg and Frederiksberg Hospital (A.L.) - both in Copenhagen; the Estonian Genome Center, Institute of Genomics, University of Tartu, Tartu, Estonia (A.M.); the Department of Epidemiology and Public Health, Graduate School of Medical Sciences, Kyushu University, Fukuoka (T.N., S. Sakata), and the Global Center of Excellence Program Study Group, Yamagata University School of Medicine, Yamagata (M.W.) - both in Japan; the School of Medicine, University of Passo Fundo, Passo Fundo (K.O.), and the Department of Public Health, Postgraduate Program in Public Health, Federal University of Santa Catarina, Florianopolis (E.O.) - both in Brazil; the School of Health Sciences and Education, Harokopio University, Athens, Greece (D.P.); the National Council of Applied Economic Research, Delhi (A. Perianayagam), and the International Institute for Population Sciences, Mumbai (A. Perianayagam) - both in India; the Catalan Department of Health, Barcelona (S. Sans); the Hypertension in Africa Research Team, South African Medical Research Council Unit for Hypertension and Cardiovascular Disease, North-West University, Potchefstroom (A.E.S.), and the School of Mathematics, Statistics, and Computer Science, University of KwaZulu-Natal, Pietermaritzburg (A.Z.) - both in South Africa; the Department of Internal Medicine, B.P. Koirala Institute of Health Sciences, Dharan, Nepal (S.K.S.); the Laboratory of Population Studies, Institute of Cardiology, and the Department of Preventive Medicine, Faculty of Public Health, Lithuanian University of Health Sciences, Kaunas, Lithuania (A.T.); the China Center for Health Development Studies (Y.Y.) and Center for Healthy Aging and Development Studies, National School of Development (Y.Z.), Peking University, and the Key Laboratory of Epidemiology of Major Diseases, Peking University, Ministry of Education (Y.Y.) - both in Beijing; the Center for the Study of Aging and Human Development and Geriatrics Division, Medical School of Duke University, Durham, NC (Y.Z.); and Cardio-CARE, Davos (A.Z., S.B.), and the Swiss Institute of Bioinformatics, Lausanne (A.Z.) - both in Switzerland.

PMID: 37632466
PMCID: PMC10589462
DOI: 10.1056/NEJMoa2206916

Abstract

Background: Five modifiable risk factors are associated with cardiovascular disease and death from any cause. Studies using individual-level data to evaluate the regional and sex-specific prevalence of the risk factors and their effect on these outcomes are lacking.

Methods: We pooled and harmonized individual-level data from 112 cohort studies conducted in 34 countries and 8 geographic regions participating in the Global Cardiovascular Risk Consortium. We examined associations between the risk factors (body-mass index, systolic blood pressure, non-high-density lipoprotein cholesterol, current smoking, and diabetes) and incident cardiovascular disease and death from any cause using Cox regression analyses, stratified according to geographic region, age, and sex. Population-attributable fractions were estimated for the 10-year incidence of cardiovascular disease and 10-year all-cause mortality.

Results: Among 1,518,028 participants (54.1% of whom were women) with a median age of 54.4 years, regional variations in the prevalence of the five modifiable risk factors were noted. Incident cardiovascular disease occurred in 80,596 participants during a median follow-up of 7.3 years (maximum, 47.3), and 177,369 participants died during a median follow-up of 8.7 years (maximum, 47.6). For all five risk factors combined, the aggregate global population-attributable fraction of the 10-year incidence of cardiovascular disease was 57.2% (95% confidence interval [CI], 52.4 to 62.1) among women and 52.6% (95% CI, 49.0 to 56.1) among men, and the corresponding values for 10-year all-cause mortality were 22.2% (95% CI, 16.8 to 27.5) and 19.1% (95% CI, 14.6 to 23.6).

Conclusions: Harmonized individual-level data from a global cohort showed that 57.2% and 52.6% of cases of incident cardiovascular disease among women and men, respectively, and 22.2% and 19.1% of deaths from any cause among women and men, respectively, may be attributable to five modifiable risk factors. (Funded by the German Center for Cardiovascular Research (DZHK); ClinicalTrials.gov number, NCT05466825.).

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Figures

**Figure 1.**
Associations of continuous risk factors with cardiovascular disease and all-cause mortality allowing for non-linear effects. Global analyses. Individuals with cardiovascular disease at baseline were excluded. Age was used as the time scale. All five risk factors considered were included in the models together with use of antihypertensive medications. A one-year landmark analysis was performed. Confidence interval widths have not been adjusted for multiplicity and should not be used in place of hypothesis testing. To convert the values for non-HDL cholesterol from milligrams per deciliter (mg/dL) to millimoles per liter (mmol/L), multiply by 0.02586.

**Figure 2.**
Associations of risk factors with cardiovascular disease and all-cause mortality allowing for effects to change with age. Global analyses. Individuals with cardiovascular disease at baseline were excluded. Age was used as the time scale. All five risk factors considered were included in the models together with use of antihypertensive medications. A one-year landmark analysis was performed. Global estimates are presented. Confidence interval widths have not been adjusted for multiplicity and should not be used in place of hypothesis testing. To convert the values for non-HDL cholesterol from milligrams per deciliter (mg/dL) to millimoles per liter (mmol/L), multiply by 0.02586.

**Figure 3.**
Population-attributable fractions of risk factors for 10-year cardiovascular disease and all-cause mortality. Models were computed using a one-year landmark analysis. (A) Aggregate global population-attributable fractions. (B) Population-attributable fractions for aggregate risk factors by geographic region. (C) Population-attributable fractions for single risk factors in direct regional comparison.

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Comment in

Modifiable Risk Factors and Cardiovascular Outcomes.
Ou D, Hu C, Huang S. Ou D, et al. N Engl J Med. 2023 Dec 21;389(25):2400. doi: 10.1056/NEJMc2312596. N Engl J Med. 2023. PMID: 38118038 No abstract available.
Modifiable Risk Factors and Cardiovascular Outcomes.
Mei Z, Pu J, Zheng D. Mei Z, et al. N Engl J Med. 2023 Dec 21;389(25):2400-2401. doi: 10.1056/NEJMc2312596. N Engl J Med. 2023. PMID: 38118039 No abstract available.
Modifiable Risk Factors and Cardiovascular Outcomes.
Figtree GA, Gray MP, Channon KM. Figtree GA, et al. N Engl J Med. 2023 Dec 21;389(25):2401. doi: 10.1056/NEJMc2312596. N Engl J Med. 2023. PMID: 38118040 No abstract available.
Modifiable Risk Factors and Cardiovascular Outcomes. Reply.
Magnussen C, Leong DP, Blankenberg S. Magnussen C, et al. N Engl J Med. 2023 Dec 21;389(25):2401-2402. doi: 10.1056/NEJMc2312596. N Engl J Med. 2023. PMID: 38118041 No abstract available.
Modifizierbare Risikofaktoren verursachen jeden fünften Tod.
Wirth A. Wirth A. MMW Fortschr Med. 2024 Apr;166(7):24-25. doi: 10.1007/s15006-024-3841-3. MMW Fortschr Med. 2024. PMID: 38637375 Review. German. No abstract available.

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1. Joseph P, Leong D, McKee M, et al. Reducing the Global Burden of Cardiovascular Disease, Part 1: The Epidemiology and Risk Factors. Circulation research 2017;121(6):677–694. (In eng). DOI: 10.1161/circresaha.117.308903. - DOI - PubMed
1. Yusuf S, Hawken S, Ounpuu S, et al. Effect of potentially modifiable risk factors associated with myocardial infarction in 52 countries (the INTERHEART study): case-control study. Lancet 2004;364(9438):937–52. DOI: 10.1016/S0140-6736(04)17018-9. - DOI - PubMed
1. Yusuf S, Joseph P, Rangarajan S, et al. Modifiable risk factors, cardiovascular disease, and mortality in 155 722 individuals from 21 high-income, middle-income, and low-income countries (PURE): a prospective cohort study. Lancet 2020;395(10226):795–808. DOI: 10.1016/S0140-6736(19)32008-2. - DOI - PMC - PubMed
1. collaboration SwgaECr. SCORE2 risk prediction algorithms: new models to estimate 10-year risk of cardiovascular disease in Europe. European heart journal 2021;42(25):2439–2454. (In eng). DOI: 10.1093/eurheartj/ehab309. - DOI - PMC - PubMed
1. Yadlowsky S, Hayward RA, Sussman JB, McClelland RL, Min YI, Basu S. Clinical Implications of Revised Pooled Cohort Equations for Estimating Atherosclerotic Cardiovascular Disease Risk. Annals of internal medicine 2018;169(1):20–29. (In eng). DOI: 10.7326/m17-3011. - DOI - PubMed

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[1] Joseph P, Leong D, McKee M, et al. Reducing the Global Burden of Cardiovascular Disease, Part 1: The Epidemiology and Risk Factors. Circulation research 2017;121(6):677–694. (In eng). DOI: 10.1161/circresaha.117.308903. - DOI - PubMed

[2] Joseph P, Leong D, McKee M, et al. Reducing the Global Burden of Cardiovascular Disease, Part 1: The Epidemiology and Risk Factors. Circulation research 2017;121(6):677–694. (In eng). DOI: 10.1161/circresaha.117.308903. - DOI - PubMed

[3] Yusuf S, Hawken S, Ounpuu S, et al. Effect of potentially modifiable risk factors associated with myocardial infarction in 52 countries (the INTERHEART study): case-control study. Lancet 2004;364(9438):937–52. DOI: 10.1016/S0140-6736(04)17018-9. - DOI - PubMed

[4] Yusuf S, Hawken S, Ounpuu S, et al. Effect of potentially modifiable risk factors associated with myocardial infarction in 52 countries (the INTERHEART study): case-control study. Lancet 2004;364(9438):937–52. DOI: 10.1016/S0140-6736(04)17018-9. - DOI - PubMed

[5] Yusuf S, Joseph P, Rangarajan S, et al. Modifiable risk factors, cardiovascular disease, and mortality in 155 722 individuals from 21 high-income, middle-income, and low-income countries (PURE): a prospective cohort study. Lancet 2020;395(10226):795–808. DOI: 10.1016/S0140-6736(19)32008-2. - DOI - PMC - PubMed

[6] Yusuf S, Joseph P, Rangarajan S, et al. Modifiable risk factors, cardiovascular disease, and mortality in 155 722 individuals from 21 high-income, middle-income, and low-income countries (PURE): a prospective cohort study. Lancet 2020;395(10226):795–808. DOI: 10.1016/S0140-6736(19)32008-2. - DOI - PMC - PubMed

[7] collaboration SwgaECr. SCORE2 risk prediction algorithms: new models to estimate 10-year risk of cardiovascular disease in Europe. European heart journal 2021;42(25):2439–2454. (In eng). DOI: 10.1093/eurheartj/ehab309. - DOI - PMC - PubMed

[8] collaboration SwgaECr. SCORE2 risk prediction algorithms: new models to estimate 10-year risk of cardiovascular disease in Europe. European heart journal 2021;42(25):2439–2454. (In eng). DOI: 10.1093/eurheartj/ehab309. - DOI - PMC - PubMed

[9] Yadlowsky S, Hayward RA, Sussman JB, McClelland RL, Min YI, Basu S. Clinical Implications of Revised Pooled Cohort Equations for Estimating Atherosclerotic Cardiovascular Disease Risk. Annals of internal medicine 2018;169(1):20–29. (In eng). DOI: 10.7326/m17-3011. - DOI - PubMed

[10] Yadlowsky S, Hayward RA, Sussman JB, McClelland RL, Min YI, Basu S. Clinical Implications of Revised Pooled Cohort Equations for Estimating Atherosclerotic Cardiovascular Disease Risk. Annals of internal medicine 2018;169(1):20–29. (In eng). DOI: 10.7326/m17-3011. - DOI - PubMed

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Global Effect of Modifiable Risk Factors on Cardiovascular Disease and Mortality

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