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      Global Impact of Modifiable Risk Factors on Cardiovascular Disease and Mortality

      research-article
      , M.D. 1 , 2 , 3 , , Ph.D. 1 , 3 , , Ph.D. 4 , , M.D. 5 , , M.D. Ph.D. 6 , , M.D. 7 , , Ph.D. 8 , , M.D. 9 , , M.D. Ph.D. 10 , , Ph.D. 11 , , M.D. 12 , 13 , , M.D. Ph.D. 14 , , M.D. 15 , , Ph.D. 16 , , M.D. 17 , 18 , , Ph.D. 19 , , M.D. Ph.D. 20 , 21 , , M.D. Ph.D. 22 , , M.D. Ph.D. 23 , , M.D. Ph.D. 24 , , M.D. Ph.D. 25 , , M.D. Ph.D. 26 , , Ph.D. 27 , , M.D. 28 , , M.D. 29 , , Ph.D. 30 , 31 , , M.D. Ph.D. 32 , 33 , , M.D. Ph.D. 24 , 26 , , M.D. Ph.D. 34 , , Ph.D. 35 , , M.D. 36 , , M.D. Ph.D. 37 , , M.D. Ph.D. 38 , , M.D. Ph.D. 39 , , M.D. 40 , , Ph.D. 41 , , M.D. 42 , 43 , 44 , , M.D. Ph.D. 45 , , Ph.D. 37 , , M.D. 46 , 47 , , M.D. 48 , , M.D. Ph.D. 49 , , M.D. Ph.D. 50 , 51 , , M.A. 1 , 2 , 3 , , M.D. Ph.D. 52 , 53 , , M.D. 54 , 55 , 56 , , M.D. Ph.D. 57 , , M.D. Ph.D. 58 , , M.D. Ph.D. 23 , , M.D. Ph.D. 59 , , M.D. Ph.D. 10 , 60 , , M.D. 61 , , Ph.D. 38 , , M.D. Ph.D. 56 , 62 , , M.D. Ph.D. 63 , , M.D. Ph.D. 64 , , M.D. Ph.D. 65 , , Ph.D. 66 , , M.D. Ph.D. 67 , , Ph.D. 19 , , M.D. Ph.D. 68 , , Ph.D. 69 , 70 , , M.D. 71 , 72 , 42 , , M.D. Ph.D. 55 , 56 , , Ph.D. 36 , , M.D. 73 , , M.D. Ph.D. 74 , , M.D. Ph.D. 37 , , M.D. Ph.D 75 , , M.D. Ph.D. 64 , , Ph.D. 12 , 13 , , Ph.D. 76 , 77 , , Ph.D. 56 , , M.D. 78 , , M.D. 79 , , M.D. 80 , , M.D. Ph.D. 81 , , M.D. 82 , , Ph.D. 71 , 83 , , M.D. 84 , , M.D. 1 , 2 , 3 , , M.D. 85 , , Ph.D. 24 , , M.Sc. 1 , 2 , 3 , , Ph.D. 86 , , M.D. Ph.D. 87 , , M.D. 88 , , M.D. Ph.D. 89 , 90 , , M.D. 89 , 91 , , Ph.D. 1 , 3 , 92 , 93 , 94 , , M.D. 1 , 2 , 3 , 92
      The New England journal of medicine

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          Abstract

          Background:

          Five modifiable risk factors are associated with cardiovascular disease (CVD) and all-cause mortality. The regional and sex-specific prevalence of these modifiable risk factors and their impact on CVD and all-cause mortality have not been evaluated using individual-level data.

          Methods:

          The Global Cardiovascular Risk Consortium harmonized individual-level data from 112 cohort studies conducted in 34 countries and 8 geographic regions. Associations between body-mass index, systolic blood pressure, non-high-density lipoprotein cholesterol, smoking, and diabetes with incident CVD and all-cause mortality were examined using Cox regression analyses and stratified by geographic region, age and sex. Population-attributable fractions were estimated for 10-year incident CVD and all-cause mortality.

          Results:

          Among 1,518,028 individuals (54.1% women, median age 54.4 years), there were regional variations in the prevalence of the five modifiable risk factors. Incident CVD occurred in 80,596 individuals (median and maximum follow-up, 7.3 and 47.3 years, respectively) and 177,369 individuals died (median and maximum follow-up, 8.7 and 47.6 years, respectively). Aggregate global CVD population-attributable fractions were 57.2% (95% confidence interval [CI], 52.4 to 62.1) in women and 52.6% (95% CI, 49.0 to 56.1) in men for all risk factors combined. Aggregate global all-cause mortality population-attributable fractions were 22.2% in women and 19.1% in men.

          Conclusions:

          Harmonized individual-level data from a global cohort found that 57.2% of incident CVD in women and 52.6% in men, and 22.2% of deaths in women and 19.1% in men may be attributable to five modifiable risk factors. The prevalence and impact of these risk factors on incident CVD and all-cause mortality varies by sex and across geographic regions.

          ClinicalTrials.gov number NCT05466825

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          mice: Multivariate Imputation by Chained Equations inR

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            Global Burden of Cardiovascular Diseases and Risk Factors, 1990–2019

            Cardiovascular diseases (CVDs), principally ischemic heart disease (IHD) and stroke, are the leading cause of global mortality and a major contributor to disability. This paper reviews the magnitude of total CVD burden, including 13 underlying causes of cardiovascular death and 9 related risk factors, using estimates from the Global Burden of Disease (GBD) Study 2019. GBD, an ongoing multinational collaboration to provide comparable and consistent estimates of population health over time, used all available population-level data sources on incidence, prevalence, case fatality, mortality, and health risks to produce estimates for 204 countries and territories from 1990 to 2019. Prevalent cases of total CVD nearly doubled from 271 million (95% uncertainty interval [UI]: 257 to 285 million) in 1990 to 523 million (95% UI: 497 to 550 million) in 2019, and the number of CVD deaths steadily increased from 12.1 million (95% UI:11.4 to 12.6 million) in 1990, reaching 18.6 million (95% UI: 17.1 to 19.7 million) in 2019. The global trends for disability-adjusted life years (DALYs) and years of life lost also increased significantly, and years lived with disability doubled from 17.7 million (95% UI: 12.9 to 22.5 million) to 34.4 million (95% UI:24.9 to 43.6 million) over that period. The total number of DALYs due to IHD has risen steadily since 1990, reaching 182 million (95% UI: 170 to 194 million) DALYs, 9.14 million (95% UI: 8.40 to 9.74 million) deaths in the year 2019, and 197 million (95% UI: 178 to 220 million) prevalent cases of IHD in 2019. The total number of DALYs due to stroke has risen steadily since 1990, reaching 143 million (95% UI: 133 to 153 million) DALYs, 6.55 million (95% UI: 6.00 to 7.02 million) deaths in the year 2019, and 101 million (95% UI: 93.2 to 111 million) prevalent cases of stroke in 2019. Cardiovascular diseases remain the leading cause of disease burden in the world. CVD burden continues its decades-long rise for almost all countries outside high-income countries, and alarmingly, the age-standardized rate of CVD has begun to rise in some locations where it was previously declining in high-income countries. There is an urgent need to focus on implementing existing cost-effective policies and interventions if the world is to meet the targets for Sustainable Development Goal 3 and achieve a 30% reduction in premature mortality due to noncommunicable diseases.
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              Evolocumab and Clinical Outcomes in Patients with Cardiovascular Disease

              Evolocumab is a monoclonal antibody that inhibits proprotein convertase subtilisin-kexin type 9 (PCSK9) and lowers low-density lipoprotein (LDL) cholesterol levels by approximately 60%. Whether it prevents cardiovascular events is uncertain.
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                Author and article information

                Journal
                0255562
                5985
                N Engl J Med
                N Engl J Med
                The New England journal of medicine
                0028-4793
                1533-4406
                6 October 2023
                05 October 2023
                26 August 2023
                21 October 2023
                : 389
                : 14
                : 1273-1285
                Affiliations
                [1 ]University Heart and Vascular Center Hamburg, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
                [2 ]German Centre for Cardiovascular Disease (DZHK), Partner site Hamburg/Kiel/Luebeck, Hamburg, Germany
                [3 ]Center for Population Health Innovation (POINT), University Heart and Vascular Center Hamburg, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
                [4 ]Department of Medicine (Cardiology), McMaster University, Hamilton, Canada
                [5 ]Experimental Medicine Research Unit from the School of Medicine, National Autonomous University of Mexico (UNAM), Mexico City
                [6 ]Univ. Lille, Inserm, Centre Hosp. Univ Lille, Institut Pasteur de Lille, UMR1167 - RID-AGE LabEx DISTALZ - Risk factors and molecular determinants of aging-related diseases, F-59000 Lille, France
                [7 ]Division of Clinical and Health Services Research, National Institute on Minority Health and Health Disparities at the National Institutes of Health, Bethesda, MD, USA
                [8 ]Department of Public Health and Primary Care, Ghent University, Ghent, Belgium
                [9 ]Department of Medicine, Baylor College of Medicine, USA
                [10 ]CRONICAS Center of Excellence in Chronic Diseases, Universidad Peruana Cayetano Heredia, Lima, Peru
                [11 ]Department of Epidemiology and Public Health, University College London, London, UK
                [12 ]Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg, Germany
                [13 ]Network Aging Research (NAR), Heidelberg University, Heidelberg, Germany
                [14 ]Emory Global Diabetes Research Center and Hubert Department of Global Health Rollins School of Public Health, Emory University, Atlanta, USA
                [15 ]Division of Cardiology, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, USA
                [16 ]School of Public Health, University of Queensland, Brisbane, QLD, Australia
                [17 ]Department of Internal Medicine B, University Medicine Greifswald, Greifswald, Germany
                [18 ]German Centre for Cardiovascular Disease (DZHK), Partner Site Greifswald, Greifswald, Germany Cardiovascular Disease (DZD), Site Greifswald, Greifswald, Germany
                [19 ]Department of Cardiovascular, Endocrine-metabolic Diseases and Aging, Istituto Superiore di Sanità-ISS, Rome, Italy
                [20 ]Department of Epidemiology, Cardiovascular Disease Prevention and Health Promotion, National Institute of Cardiology, Warsaw, Poland
                [21 ]Lazarski University, Warsaw, Poland
                [22 ]Department of Endocrinology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands
                [23 ]Lund University, Department of Clinical Sciences Malmö, Malmö, Sweden
                [24 ]Research Center in Epidemiology and Preventive Medicine, Department of Medicine and Surgery, University of Insubria, Varese, Italy
                [25 ]Department of Cardiology, INSERM UMR 1295, Toulouse Rangueil University Hospital, 31059 Toulouse, France
                [26 ]Department of Epidemiology and Prevention, IRCCS Neuromed, Pozzilli (IS), Italy
                [27 ]Tel Aviv University School of Public Health department of Epidemiology Tel Aviv University School of Public Health department of Epidemiology
                [28 ]Centro de Estudios en Diabetes AC. Centro de Investigacion en Salud Poblacional. Instituto Nacional de Salud Publica
                [29 ]Clinica Medica, University of Milano-Bicocca, Milan, Italy
                [30 ]Cancer Epidemiology Division, Cancer Council Victoria, 615 St Kilda Road, Melbourne, Victoria 3004, Australia
                [31 ]Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Victoria 3010, Australia
                [32 ]HUNT Research Center, Department of Public Health and Nursing, Norwegian University of Science and Technology (NTNU), Levanger, Norway
                [33 ]K.G. Jebsen Center for Genetic Epidemiology, Department of Public Health and Nursing, Norwegian University of Science and Technology (NTNU), Trondheim, Norway
                [34 ]Departments of Neurology & Epidemiology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands
                [35 ]Department of Chronic Diseases, Institute for Clinical Effectiveness and Health Policy, Buenos Aires, Argentina
                [36 ]MRC Unit The Gambia @ London School of Hygiene & Tropical Medicine, Banjul, The Gambia
                [37 ]Department of Public Health and Welfare, Finnish Institute for Health and Welfare (THL), Helsinki, Finland
                [38 ]MRC/UVRI and LSHTM Uganda Research Unit
                [39 ]Department of Epidemiology, Erasmus MC University Medical Center Rotterdam, Rotterdam, The Netherlands
                [40 ]Centre for Public Health, Queens University Belfast
                [41 ]Prevention of Metabolic Disorders Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran
                [42 ]German Centre for Cardiovascular Research (DZHK), partner site Munich Heart Alliance, Munich, Germany
                [43 ]German Heart Centre, Technical University of Munich, Munich, Germany
                [44 ]Institute of Epidemiology and Medical Biometry, University of Ulm, Ulm, Germany
                [45 ]National research center for therapy and preventive medicine of the Ministry of Healthcare of the Russian Federation, Moscow, Russia
                [46 ]Institute of Clinical Chemistry and Laboratory Medicine, University Medical Center of the Johannes Gutenberg-University Mainz, Mainz, Germany
                [47 ]DZHK (German Center for Cardiovascular Research), partner site RhineMain, Mainz, Germany
                [48 ]University Heart & Vascular Center Frankfurt, Frankfurt/Main, Germany and German Centre for Cardiovascular Disease (DZHK), Partner site Rhein/Main, Frankfurt, Germany
                [49 ]Department of Medical Sciences, Uppsala, Sweden
                [50 ]Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
                [51 ]Center for Clinical Research and Prevention, Bispebjerg/Frederiksberg Hospital, Copenhagen, Denmark
                [52 ]Department of Cardiology, Division of Medicine, Akershus University Hospital, Lørenskog, Norway
                [53 ]K.G. Jebsen Center for Cardiac Biomarkers, Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway
                [54 ]Liver and Pancreaticobiliary Disease Research Center, Digestive Disease Research Institute, Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran
                [55 ]Digestive Oncology Research Center, Digestive Disease Research Institute, Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran
                [56 ]Digestive Disease Research Center, Digestive Disease Research Institute, Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran
                [57 ]Research Institute of Internal and Preventive Medicine, Branch of ‘Federal Research Center Institute of Cytology and Genetics’ (IC&G), Siberian Branch of RAS, Novosibirsk, Russia
                [58 ]Department of Clinical Medicine, UiT The Arctic University of Norway, Tromsø, Norway
                [59 ]Estonian Genome Center, Institute of Genomics, University of Tartu, Tartu, Estonia
                [60 ]Sydney School of Public Health, Faculty of Medicine and Health, University of Sydney, Sydney, Australia
                [61 ]Department of Public health, Strasbourg University Hospital, University of Strasbourg, Strasbourg, France
                [62 ]Metabolic Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, Bethesda, Maryland, USA
                [63 ]Michael E DeBakey Veterans Affairs hospital and Baylor College of Medicine, Houston, USA
                [64 ]Department of Epidemiology and Public Health, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
                [65 ]Medicine School, University of Passo Fundo, Passo Fundo, Rio Grande do Sul, Brazil
                [66 ]Department of Public Health, Postgraduate Program in Public Health, Federal University of Santa Catarina, Florianopolis, Brazil
                [67 ]Department of Epidemiology and Population Studies, Institute of Public Health, Faculty of Health Sciences, Jagiellonian University Medical College, Poland
                [68 ]School of Health Sciences and Education, Harokopio University, Athens, Greece
                [69 ]National Council of Applied Economic Research (NCAER), Delhi, India
                [70 ]International Institute for Population Sciences, Mumbai, India
                [71 ]Institute of Epidemiology, Helmholtz Zentrum München - German Research Center for Environmental Health, Neuherberg, Germany
                [72 ]Chair of Epidemiology, Institute for Medical Information Processing, Biometry and Epidemiology, Medical Faculty, Ludwig-Maximilians-Universität München, Munich, Germany
                [73 ]Department of Cardiology, Bispebjerg Hospital, University of Copenhagen, Denmark
                [74 ]Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism, Uppsala University, Uppsala, Sweden
                [75 ]Catalan Department of Health, Barcelona, Spain
                [76 ]The School of Population Health, University of New South Wales; The George Institute for Global Health, Sydney, Australia
                [77 ]Hypertension in Africa Research Team (HART), SAMRC Unit for Hypertension and Cardiovascular Disease, North-West University, Potchefstroom, South Africa
                [78 ]Department of Internal Medicine, BP Koirala Institute of Health Sciences, Dharan, Nepal
                [79 ]Baker Heart and Diabetes Institute, Melbourne, Australia
                [80 ]University of New South Wales, Australia
                [81 ]Department of Public Health and Clinical Medicine, University of Umea, Umea, Sweden
                [82 ]Laboratory of Population Studies, Institute of Cardiology, Kaunas, Lithuania; Department of Preventive Medicine, Faculty of Public Health, Lithuanian University of Health Sciences, Kaunas, Lithuania
                [83 ]German Center for Diabetes Research (DZD), Partner Munich-Neuherberg, Neuherberg, Germany
                [84 ]Cardiovascular Epidemiology Unit, Institute of Cardiovascular Research, University of Dundee, Dundee, Scotland, UK
                [85 ]MONICA-FRIULI Study Group, Udine, Italy
                [86 ]Research Department of Primary Care and Population Health, University College London, London, UK
                [87 ]Global Center of Excellence Program Study Group, Yamagata University School of Medicine, Yamagata, Japan
                [88 ]University Medical Center of the Johannes Gutenberg-University Mainz, Mainz, Germany
                [89 ]China Center for Health Development Studies, Peking University, Beijing, China
                [90 ]Key Laboratory of Epidemiology of Major Diseases (Peking University), Ministry of Education, Beijing, China
                [91 ]Center for the Study of Aging and Human Development and Geriatrics Division, Medical School of Duke University, Durham, NC, US
                [92 ]Cardio-CARE, Davos, Switzerland
                [93 ]School of Mathematics, Statistics and Computer Science, University of KwaZulu-Natal, Pietermaritzburg, South Africa
                [94 ]Swiss Institute of Bioinformatics, Lausanne, Switzerland
                Author notes
                [*]

                contributed equally

                [#]

                Member of The Global Cardiovascular Risk Consortium (GCVRC) Management Group

                Corresponding Author: Stefan Blankenberg, University Heart and Vascular Center, Department for Cardiology, Center of Population Health Innovation, University Medical Center Hamburg (UKE), Medizincampus Davos, Cardio-CARE, Davos, Switzerland, Martinistraße 52, 20246 Hamburg, Fon: +49 40 7410 56800, Fax: +49 40 7410 5, s.blankenberg@ 123456uke.de
                Article
                NIHMS1931665
                10.1056/NEJMoa2206916
                10589462
                37632466
                6ecb8a21-e455-45b0-937c-5c0619f0ac1b

                This Author Accepted Manuscript is licensed for use under the CC-BY license.

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