Global burden of 288 causes of death and life expectancy decomposition in 204 countries and territories and 811 subnational locations, 1990–2021

For more than three decades, the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) has been systematically and comprehensively recording and analysing causes of human death stratified by age, sex, and time across the world., This information has been used to guide policy solutions, reduce modifiable risk factors, monitor and evaluate national and sub-national health interventions, and ultimately improve health recommendations at both regional and local levels. Assessing trends in cause-specific mortality is essential to inform health policy that must continuously evolve to account for rapid changes to the global health landscape, such as the COVID-19 pandemic. Comprehensive updates to levels and trends in causes of death give insight into emerging global health challenges and can facilitate benchmarking in the case of a new pandemic or other events that can lead to a staggering loss of life. Therefore, documenting novel changes to mortality, such as an emerging pandemic, in real time, is important.

Causes of death are not uniformly distributed between populations; rather, large variability in the leading causes often reflects important social and geographical differences. These differences can include access to and quality of health care, timeliness of health system responsiveness, and exposure to causes that are endemic to specific geographical locations. Mortality patterns continually evolve, as some areas become successful in their reduction efforts, whereas other causes persist within specific locations. The past 30 years have seen improvements among many causes of mortality, some of which have considerably narrowed in geographical range and are now concentrated within smaller areas worldwide. This change enables us to identify the resulting areas of concentrated mortality—areas where deaths from that cause are occurring within a limited subset of the global population. Our analysis provides an opportunity to answer important epidemiological questions that have been at the forefront of global and public health discourse—eg, which causes have contributed to the largest increase or decrease in life expectancy, which locations are experiencing greater concentrations of preventable causes of death, and how has COVID-19 and other pandemic-related mortality (OPRM) affected life expectancy and the overall fatal burden of diseases? Regional variation in many of the leading causes of death remains evident in these most recent estimates, representing important opportunities for creating tailored health policy to improve disparities and alleviate concentrations of mortality.

GBD 2021 provides an updated, comprehensive set of the fatal burden of disease summarised with cause-specific mortality metrics and years-of-life-lost (YLLs) metrics for 288 causes by age and sex across 204 countries and territories from 1990 to 2021, an update from the previously published estimates covering 1990–2019. In this study, we present mortality concentrations and a decomposition analysis of life expectancy due to different causes of death and illustrate the impact of causes of death on global, regional, and country-specific life expectancy, as well as highlighting locations that are most affected by concentrated geographical mortality burden. As with previous iterations of GBD, this cycle incorporates newly available data sources and improved methodological approaches to re-estimate the entire time series, providing updated estimates that supersede all previous GBD cause-of-death publications. GBD 2021 includes an estimation of several different models for disease and injury outcomes. This manuscript was produced as part of the GBD Collaborator Network and in accordance with the GBD Protocol.

Research in context

Evidence before this study

The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) has provided regular updates on the complex patterns and trends in population health around the world since the first GBD publication in 1993. With each subsequent iteration, there have been important methodological updates, new datasets included, and an expanded list of causes, risk factors, and locations for which estimates of the burden of disease are produced. In 1993, mortality and years of life lost (YLLs) were reported for 107 categories of diseases that covered all possible causes of death, for eight regions. In the last GBD cycle—GBD 2019—estimates of mortality and YLLs were produced for 286 causes of death in 204 countries and territories, including all WHO member states, and for subnational locations in 21 countries and territories, for every year from 1990 to 2019. Although many groups have reported on national-level, cause-specific mortality and other population-health metrics, including the WHO World Health Statistics reports, GBD is the most detailed and transparent research effort to date. Further, estimates of COVID-19-related deaths in 2020 and 2021 have been reported by several sources, including GBD studies that have quantified excess mortality due to the pandemic within a subset of GBD locations. However, no previous publications have quantified the effect of COVID-19 on life expectancy, while considering the full spectrum of disease mortality over the past three decades, across all countries and territories. This study presents, for the first time, 288 causes of death from 1990 to 2021, complementary to the all-cause mortality findings presented in the GBD 2021 Demographics analysis. Combined, these studies provide a comprehensive view of all-cause and cause-specific mortality from 1990 to 2021.

Added value of this study

Alongside the all-cause mortality and life-expectancy assessments in companion publications for GBD 2021, this analysis delineates cause-specific mortality and its effect on life expectancy. This study includes a comprehensive decomposition analysis elucidating the primary cause of death influencing life expectancy on a global, regional, and national level. Additionally, we present causes of death and YLLs for all countries and territories, providing policy makers with valuable insights into variations in cause-specific mortality. This study is also the first of its kind to publish 2021 estimates of COVID-19-related deaths and YLLs for 204 countries and territories in the context of the global burden of disease. Although other publications have estimated deaths due to COVID-19, those deaths have not previously been compared with deaths from other causes. By modelling COVID-19 deaths within a hierarchy of mutually exclusive and collectively exhaustive causes of death, this study provides policy makers with information that is essential for setting health priorities around the world. To obtain more comprehensive insights from life expectancy, it is necessary to break it down into age-specific mortality, which is influenced by cause-specific mortality rates. We examined the effect of COVID-19 and other causes of death on life expectancy by decomposing death counts into different cause-specific mortality rates across various dimensions, including country or territory, region, super-region, and five distinct time periods: 1990–2000, 2000–2010, 2010–2019, 2019–2021, and 1990–2021. We could therefore systematically calibrate the COVID-19 pandemic against other causes of mortality over the period 1990–2021. Finally, our study identified several causes of death that exhibited increased geographical concentration over time—ie, causes with a disproportionate impact within a specific geographical area compared with the rest of the global observations. This analysis provides policy makers important information on regional variation and inequalities in cause-specific mortality. Also new to GBD 2021, we report on 12 additional causes of death: COVID-19 and other pandemic-related mortality, pulmonary arterial hypertension, and nine cancer types—hepatoblastoma, Burkitt lymphoma, other non-Hodgkin lymphoma, eye cancer, retinoblastoma, other eye cancers, soft tissue and other extraosseous sarcomas, malignant neoplasm of bone and articular cartilage, and neuroblastoma and other peripheral nervous-cell tumours. Granularity of the estimation of deaths in children younger than 5 years was enhanced by the addition of four new age groups: 1–5 months, 6–11 months, 12–23 months, and 2–4 years.

Implications of all the available evidence

Our study provides a full analysis of causes of death worldwide and across time, alongside the changing patterns in life expectancy precipitated by those causes. Increasing geographical concentration of mortality was observed for many causes of death, highlighting disparities between regions and substantial differences in cause-specific contributions to life expectancy. On a global scale, this information provides an opportunity to examine whether reductions in mortality were resilient to the onset of a novel pandemic. On a regional level, the estimates generated by our study provide important detail on the evolving impact of causes of death among countries, allowing crucial insight into differential success by geography, time, and cause. The comprehensive nature of GBD 2021 cause-of-death estimation provides valuable opportunities to learn from mortality gains and losses, helping to accelerate progress in reducing mortality.