Global burden of 288 causes of death and life expectancy decomposition in 204 countries and territories and 811 subnational locations, 1990–2021: a systematic analysis for the Global Burden of Disease Study 2021

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Abstract

BACKGROUND: Regular, detailed reporting on population health by underlying cause of death is fundamental for public health decision making. Cause-specific estimates of mortality and the subsequent effects on life expectancy worldwide are valuable metrics to gauge progress in reducing mortality rates. These estimates are particularly important following large-scale mortality spikes, such as the COVID-19 pandemic. When systematically analysed, mortality rates and life expectancy allow comparisons of the consequences of causes of death globally and over time, providing a nuanced understanding of the effect of these causes on global populations. METHODS: The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2021 cause-of-death analysis estimated mortality and years of life lost (YLLs) from 288 causes of death by age-sex-location-year in 204 countries and territories and 811 subnational locations for each year from 1990 until 2021. The analysis used 56 604 data sources, including data from vital registration and verbal autopsy as well as surveys, censuses, surveillance systems, and cancer registries, among others. As with previous GBD rounds, cause-specific death rates for most causes were estimated using the Cause of Death Ensemble model-a modelling tool developed for GBD to assess the out-of-sample predictive validity of different statistical models and covariate permutations and combine those results to produce cause-specific mortality estimates-with alternative strategies adapted to model causes with insufficient data, substantial changes in reporting over the study period, or unusual epidemiology. YLLs were computed as the product of the number of deaths for each cause-age-sex-location-year and the standard life expectancy at each age. As part of the modelling process, uncertainty intervals (UIs) were generated using the 2·5th and 97·5th percentiles from a 1000-draw distribution for each metric. We decomposed life expectancy by cause of death, location, and year to show cause-specific effects on life expectancy from 1990 to 2021. We also used the coefficient of variation and the fraction of population affected by 90% of deaths to highlight concentrations of mortality. Findings are reported in counts and age-standardised rates. Methodological improvements for cause-of-death estimates in GBD 2021 include the expansion of under-5-years age group to include four new age groups, enhanced methods to account for stochastic variation of sparse data, and the inclusion of COVID-19 and other pandemic-related mortality-which includes excess mortality associated with the pandemic, excluding COVID-19, lower respiratory infections, measles, malaria, and pertussis. For this analysis, 199 new country-years of vital registration cause-of-death data, 5 country-years of surveillance data, 21 country-years of verbal autopsy data, and 94 country-years of other data types were added to those used in previous GBD rounds. FINDINGS: The leading causes of age-standardised deaths globally were the same in 2019 as they were in 1990; in descending order, these were, ischaemic heart disease, stroke, chronic obstructive pulmonary disease, and lower respiratory infections. In 2021, however, COVID-19 replaced stroke as the second-leading age-standardised cause of death, with 94·0 deaths (95% UI 89·2-100·0) per 100 000 population. The COVID-19 pandemic shifted the rankings of the leading five causes, lowering stroke to the third-leading and chronic obstructive pulmonary disease to the fourth-leading position. In 2021, the highest age-standardised death rates from COVID-19 occurred in sub-Saharan Africa (271·0 deaths [250·1-290·7] per 100 000 population) and Latin America and the Caribbean (195·4 deaths [182·1-211·4] per 100 000 population). The lowest age-standardised death rates from COVID-19 were in the high-income super-region (48·1 deaths [47·4-48·8] per 100 000 population) and southeast Asia, east Asia, and Oceania (23·2 deaths [16·3-37·2] per 100 000 population). Globally, life expectancy steadily improved between 1990 and 2019 for 18 of the 22 investigated causes. Decomposition of global and regional life expectancy showed the positive effect that reductions in deaths from enteric infections, lower respiratory infections, stroke, and neonatal deaths, among others have contributed to improved survival over the study period. However, a net reduction of 1·6 years occurred in global life expectancy between 2019 and 2021, primarily due to increased death rates from COVID-19 and other pandemic-related mortality. Life expectancy was highly variable between super-regions over the study period, with southeast Asia, east Asia, and Oceania gaining 8·3 years (6·7-9·9) overall, while having the smallest reduction in life expectancy due to COVID-19 (0·4 years). The largest reduction in life expectancy due to COVID-19 occurred in Latin America and the Caribbean (3·6 years). Additionally, 53 of the 288 causes of death were highly concentrated in locations with less than 50% of the global population as of 2021, and these causes of death became progressively more concentrated since 1990, when only 44 causes showed this pattern. The concentration phenomenon is discussed heuristically with respect to enteric and lower respiratory infections, malaria, HIV/AIDS, neonatal disorders, tuberculosis, and measles. INTERPRETATION: Long-standing gains in life expectancy and reductions in many of the leading causes of death have been disrupted by the COVID-19 pandemic, the adverse effects of which were spread unevenly among populations. Despite the pandemic, there has been continued progress in combatting several notable causes of death, leading to improved global life expectancy over the study period. Each of the seven GBD super-regions showed an overall improvement from 1990 and 2021, obscuring the negative effect in the years of the pandemic. Additionally, our findings regarding regional variation in causes of death driving increases in life expectancy hold clear policy utility. Analyses of shifting mortality trends reveal that several causes, once widespread globally, are now increasingly concentrated geographically. These changes in mortality concentration, alongside further investigation of changing risks, interventions, and relevant policy, present an important opportunity to deepen our understanding of mortality-reduction strategies. Examining patterns in mortality concentration might reveal areas where successful public health interventions have been implemented. Translating these successes to locations where certain causes of death remain entrenched can inform policies that work to improve life expectancy for people everywhere. FUNDING: Bill & Melinda Gates Foundation.

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The record

Venue

The Lancet

Topic

COVID-19 and healthcare impacts

Field

Medicine

Canadian institutions

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Funders

Division of Cardiothoracic Surgery, University of Colorado School of Medicine, Anschutz Medical CampusCilagPrecursory Research for Embryonic Science and TechnologyEunice Kennedy Shriver National Institute of Child Health and Human DevelopmentNational Institute on Drug AbuseNational Institute of Mental HealthNational Institute on AgingNorwegian Institute of Public HealthFaculty of Medicine and Health, University of SydneyBiotechnology Industry Research Assistance CouncilErasmus Universitair Medisch Centrum RotterdamRobarts Research InstituteQueensland Brain InstituteInstituto de Salud Carlos IIIRussian Academy of SciencesFundação para a Ciência e a TecnologiaJapan Society for the Promotion of ScienceNational Health and Medical Research CouncilMedical Research CouncilMusculoskeletal Research Center, Washington University in St. LouisNovo Nordisk PharmaDepartment of Global Health and Population, Harvard T.H. Chan School of Public HealthSchool of Medicine, Indiana UniversityNovartis PharmaUniversity of North Carolina at Chapel HillLoyola University Chicago Stritch School of MedicineUniversity of California, Los AngelesCollege of Engineering, Michigan State UniversityScience and Engineering Research BoardDuke Global Health Institute, Duke UniversityCanadian Institutes of Health ResearchDirectorate for Computer and Information Science and EngineeringNational Institutes of HealthStatistical Society of AustraliaWolkite UniversityUniversity of Health and Allied SciencesUniversidade Federal do Espírito SantoDilla UniversityUniversity of West AtticaDebre Markos UniversityMadda Walabu UniversityNorth South UniversityAjman UniversityPirogov Russian National Research Medical UniversityAlfaisal UniversityLaboratório Associado para a Química VerdeRede de Química e TecnologiaWestern Sydney UniversityCorporación colombiana de investigación agropecuariaHomi Bhabha National InstituteCentro de Investigação em Tecnologias e Serviços de SaúdeDivision of Mathematical SciencesUniversitatea SapientiaIdorsia PharmaceuticalsUniversity of Asia PacificDuke Kunshan UniversityCochrane South AfricaJenderal Soedirman UniversityUniwersytet Śląski w KatowicachTabriz University of Medical SciencesSouthwest Medical UniversityEuropean Regional Development FundLingnan UniversityShahid Beheshti University of Medical SciencesMinistry of Science and ICT, South KoreaKing Abdullah International Medical Research CenterUniversity of OxfordLorestan University of Medical SciencesUniversity of NicosiaImperial College LondonSouthern University of Science and TechnologySwedish Orphan BiovitrumHealth CanadaChettinad Academy of Research and EducationIndian Institute of Science Education and Research MohaliPeking Union Medical CollegeUniversitas HasanuddinICAR-Indian Veterinary Research InstituteCentre for Heart Rhythm Disorders, University of AdelaideEnvironmental Defense FundAustralian Catholic UniversityŚląski Uniwersytet Medyczny w KatowicachNational Center of Neurology and PsychiatryUniversity of RochesterDebreceni EgyetemUniversität UlmUniversity of South AfricaUniversidade Federal de PernambucoThe Wellcome Trust DBT India AllianceEmory UniversityNanjing UniversityFondation BotnarNational Nutrition and Food Technology Research InstituteLebanese American UniversityTanta UniversityAddis Ababa UniversityMadras Diabetes Research FoundationUniversitas Sebelas MaretUniversitat Rovira i VirgiliUniversitas MataramShaqra UniversityAllerganUniversity of AlbertaInternational Medical UniversityUniversidade Federal de Minas GeraisBharathiar UniversityYasuj University of Medical SciencesUniversity of Cape TownSouthern Medical UniversityZagazig UniversityUniversity of PatrasNazarbayev UniversityServierWuhan UniversityAfrican Population and Health Research CenterTechnische Universität BerlinCenter for Drug Use and HIV ResearchUniversidade do PortoUniversity College LondonCooperativa de Ensino Superior Politécnico e UniversitárioFundação Oswaldo CruzNational Taiwan UniversityI.M. Sechenov First Moscow State Medical UniversityUniversité de GenèveUniversitas IndonesiaManagement and Science UniversityOulun YliopistoBangladesh University of Health SciencesUniversitatea de Medicină şi Farmacie "Carol Davila" BucureştiNIHR Sheffield Biomedical Research CentreUniversity of HailFasa University of Medical SciencesJames Madison UniversityGuilan University of Medical SciencesUniversitat de BarcelonaNational Taiwan University HospitalGöteborgs UniversitetSemnan UniversityMinistry of Health and Medical EducationUniversità Cattolica del Sacro CuoreNational Research University Higher School of EconomicsUniversidad Nacional Autónoma de MéxicoUniversity of Florida HealthUniversity of JordanUniwersytet ŁódzkiUniversidade de São PauloTehran Heart CenterWuhan University of Science and TechnologyNanjing University of Science and TechnologyChinese Academy of Medical SciencesInjury Prevention Research CenterBirjand University of Medical SciencesUniversitair Medisch Centrum GroningenUniversidade Federal de Santa CatarinaShiraz UniversityKeele UniversityUniversitetet i BergenAmerican Heart AssociationSüleyman Demirel ÜniversitesiDepartment of Radiology and Biomedical Imaging, University of California, San FranciscoH. Lundbeck A/SCasen RecordatiUniversity of ColomboHouston Methodist HospitalSabzevar University of Medical SciencesUniversidade Federal do Rio Grande do SulLondon School of Economics and Political ScienceUmeå UniversitetGeorge Institute for Global HealthWestfälische Wilhelms-Universität MünsterZahedan University of Medical SciencesTribhuvan UniversityQueensland University of TechnologyZhejiang UniversityInyuvesi Yakwazulu-NataliShahroud University of Medical SciencesUniversité de BourgogneUniversidad Autónoma de MadridUniversity of WaterlooKuwait UniversityMajmaah UniversityDalian University of TechnologyUniversiteit StellenboschUniversity of CreteNational Drug and Alcohol Research CentreAcademia SinicaUniversiti MalayaSultan Qaboos UniversityMcGill UniversityStockholms Läns LandstingJomo Kenyatta University of Agriculture and TechnologyIntas PharmaceuticalsNovo NordiskUniversitas Gadjah MadaUniversidad Autónoma MetropolitanaKhalifa University of Science, Technology and ResearchKarolinska InstitutetJordan University of Science and TechnologyUniversity of St AndrewsPatuakhali Science and Technology UniversityUniversità di BolognaIsfahan University of Medical SciencesDepartment of Health and Aged Care, Australian GovernmentCentro de Investigación Biomédica en Red de Salud MentalHjärt-LungfondenA.T. Still UniversityNational Research Foundation of KoreaNational Science and Technology CouncilImam Abdulrahman Bin Faisal UniversityUniversity of the Western CapeHuazhong University of Science and TechnologyGazi ÜniversitesiQueen's UniversityMinistero della SaluteU.S. Department of Veterans AffairsBundesministerium für GesundheitMinistry of Trade, Industry and EnergyKorea Institute for Advancement of TechnologyDalhousie UniversityLa Trobe UniversityHellenic Foundation for Research and InnovationChandigarh UniversityKwame Nkrumah University of Science and TechnologyDanoneChulalongkorn UniversityChalmers Tekniska HögskolaCleveland ClinicGeneralitat de CatalunyaSydney Medical SchoolKing Abdullah University of Science and TechnologyCapital Medical UniversityUniversity of AberdeenWashington University in St. LouisUniversidad Nacional de ColombiaDaiichi Sankyo EuropeWellcome TrustYunnan UniversityKorea UniversityMongolian National University of Medical SciencesSeoul National UniversityVirginia Commonwealth UniversityUniversiti Brunei DarussalamTaibah UniversityBauman Moscow State Technical UniversityAustralian Mathematical Sciences InstituteUniversitat Pompeu FabraSun Yat-sen UniversityAmerican University of SharjahUniversity of CanberraCairo UniversityMurdoch UniversityUniversity of TehranOttawa Hospital Research InstituteMonash UniversityKing Saud UniversityHelmholtz Zentrum MünchenKing Faisal Specialist Hospital and Research CentreUniversiti Kebangsaan MalaysiaNorth Dakota State UniversityJames Cook UniversitySemmelweis EgyetemUnited Arab Emirates UniversitySanofiUniversity of ThessalyAXA Research FundNelson Mandela African Institution of Science and TechnologyNational Natural Science Foundation of ChinaAhmadu Bello UniversityUniversity of South AustraliaFlorida Department of HealthSingapore Eye Research InstituteAmity UniversityPublic Health Foundation of IndiaMahidol UniversityIndian Council of Medical ResearchNanjing University of Chinese MedicineSouth African Medical Research CouncilNorges Teknisk-Naturvitenskapelige UniversitetNational Research FoundationFresenius Medical Care North AmericaChinese University of Hong KongShandong UniversityAustralian Academy of ScienceKing's College LondonUniversity of TorontoJackson State UniversityUniversity of SouthamptonAdamas UniversityMashhad University of Medical SciencesUniversity of New South WalesBGI GroupHumanitas UniversityNational Institute of Mental Health and NeurosciencesUniversity of TabrizBadan Riset dan Inovasi NasionalJapan Science and Technology AgencyTamilnadu State Council For Science And TechnologyAin Shams UniversityMenzies Centre for Australian Studies, King's College London, University of LondonPasteur Institute of IranBudapesti Corvinus EgyetemMinistry of Education, Culture, Sports, Science and TechnologyUniversity of ZanjanZanjan University of Medical SciencesMorehouse School of MedicineDezful University of Medical SciencesSRM Institute of Science and TechnologySoutheast UniversityWollega UniversityEuropean CommissionUniwersytet Medyczny im. Karola Marcinkowskiego w PoznaniuKasturba Medical College, ManipalYarmouk UniversityUniversiteit AntwerpenTehran University of Medical Sciences and Health ServicesCalifornia Department of Public HealthYork UniversityUniversity of Technology SydneyAgios PharmaceuticalsConselho Nacional de Desenvolvimento Científico e TecnológicoQueen Elizabeth Hospital Birmingham CharityVictoria UniversityUniversity of TabukUniversiteit UtrechtDuke-NUS Medical SchoolNational Heart, Lung, and Blood InstituteDire Dawa UniversityUniversidad de ChileDepartment of Biotechnology, Ministry of Science and Technology, IndiaBrown UniversityNord universitetIstituto di Ricerche Farmacologiche Mario Negri - IRCCSAksum UniversityUniversitas AirlanggaCOMSATS Institute of Information TechnologyUniversity of QueenslandNational Institute for Health and Care ResearchUniversidade de LisboaIslamic Azad UniversityUniversity of KelaniyaAmgenAmarin CorporationInternational Society of NephrologyUnited Nations Population FundBaqiyatallah University of Medical SciencesUK Research and InnovationQassim UniversityUmm Al-Qura UniversityBroad InstituteBrigham and Women's HospitalHögskolan DalarnaTulane UniversityUniversidad de ColimaVanderbilt University Medical CenterYale UniversityBirzeit UniversityHebei UniversityNational Defense Medical CollegeOhio State UniversityJohns Hopkins UniversityNorthwell HealthUniversidade Federal de SergipeMassachusetts Eye and EarQueensland HealthUniversità degli Studi di UdineSheffield Hallam UniversityUniversity of LeicesterMcMaster UniversityMinisterul Cercetării, Inovării şi DigitalizăriiBirmingham City UniversityUnited States Agency for International DevelopmentJimma UniversityUniversity of HullMinistry of EducationUniversity Of Nigeria NsukkaUniversity of Nevada, Las VegasUniversity of Science and Technology of ChinaJapan Aerospace Exploration AgencyUniversity of the RyukyusTsinghua UniversityUniversity of PennsylvaniaNaresuan UniversityUniversiti Sains MalaysiaAlexandria UniversityHaramaya UniversitySchool of Medicine, Case Western Reserve UniversityEli Lilly and CompanyIndian Institute of ScienceFlinders UniversityRajarata University of Sri LankaUniversidade de CoimbraBoston Scientific CorporationEast Carolina UniversityDeutsches KrebsforschungszentrumAmicus TherapeuticsUniversidad El BosqueUniversität BaselUniversity of California, San DiegoUniversità di CataniaInternational Parkinson and Movement Disorder SocietyAuckland University of Technology, New ZealandUniversità degli Studi di MilanoHamad Medical CorporationUniversity of OtagoDirectorate for Biological SciencesUniversité de BordeauxKorean Diabetes AssociationIndian Council of Agricultural ResearchGastrointestinal and Liver Diseases Research CenterSalahaddin University-ErbilMassachusetts General HospitalUniversity of MontanaIran University of Medical SciencesHallym UniversityAhvaz Jundishapur University of Medical SciencesJazan UniversityGriffith UniversityXiamen UniversityChildren's Hospital of PhiladelphiaNational Institute of Pharmaceutical Education and Research, RaebareliCentral Taiwan University of Science and TechnologyUniversiti Putra MalaysiaShiraz University of Medical SciencesU.S. Environmental Protection AgencyPfizerWachemo UniversityApplied Molecular Biosciences UnitDepartment of Science and Technology, Ministry of Science and Technology, IndiaFondazione CariploAstellas PharmaMichigan State UniversityAstraZenecaEdwards LifesciencesLoyola University ChicagoUniversidade da Beira InteriorLilly DeutschlandAlexion PharmaceuticalsShanghai Jiao Tong UniversityUniverzita Komenského v BratislaveJamia Millia IslamiaGeorge Mason UniversityWenzhou Medical UniversityUniversidad Peruana Cayetano HerediaUniversità degli Studi di GenovaHarvard Business SchoolUniversità degli Studi del Piemonte OrientaleMansoura UniversityWayne State UniversityHarvard UniversityPhilipps-Universität MarburgItä-Suomen YliopistoUniversity of MissouriInstitute for Health Metrics and EvaluationFudan UniversityCase Western Reserve UniversityTeva Pharmaceutical IndustriesKurdistan University Of Medical SciencesUniversidade de PernambucoBrody School of MedicineCity University of Hong KongHouston Methodist Research InstituteVanderbilt UniversityArizona State UniversityAgenzia Sanitaria e Sociale Regionale, Regione Emilia-RomagnaCincinnati Children's Hospital Medical CenterUniversity of Texas Health Science Center at HoustonRijksuniversiteit GroningenUniversità degli Studi dell'AquilaUniversity of WashingtonAlberta Health ServicesBill and Melinda Gates FoundationKuopion Yliopistollinen SairaalaUniversity of Southern CaliforniaCoventry UniversityHelsingin YliopistoKaiser PermanenteFederation University AustraliaInstitució Catalana de Recerca i Estudis AvançatsAarhus UniversitetCharles Sturt UniversityVictoria University of WellingtonGAVI AllianceDepartment of Health and Social CareMazandaran University of Medical SciencesTrinity College DublinNorthwestern UniversityBabcock UniversityAmerican Diabetes Association

Keywords

Life expectancyBurden of diseaseDisease burdenDiseaseEnvironmental healthMedicineDevelopment economicsEconomicsPopulation

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