Short-term excess mortality following tropical cyclones in the United States.

Knowledge of excess deaths after tropical cyclones is critical to understanding their impacts, directly relevant to policies on preparedness and mitigation. We applied an ensemble of 16 Bayesian models to 40.7 million U.S. deaths and a comprehensive record of 179 tropical cyclones over 32 years (1988-2019) to estimate short-term all-cause excess deaths. The deadliest tropical cyclone was Hurricane Katrina in 2005, with 1491 [95% credible interval (CrI): 563, 3206] excess deaths (>99% posterior probability of excess deaths), including 719 [95% CrI: 685, 752] in Orleans Parish, LA (>99% probability). Where posterior probabilities of excess deaths were >95%, there were 3112 [95% CrI: 2451, 3699] total post-hurricane force excess deaths and 15,590 [95% CrI: 12,084, 18,835] post-gale to violent storm force deaths; 83.1% of post-hurricane force and 70.0% of post-gale to violent storm force excess deaths occurred more recently (2004-2019); and 6.2% were in least socially vulnerable counties.

Estimates of excess mortality for the five Nordic countries during the COVID-19 pandemic 2020-2021.

BACKGROUND: Excess mortality during the COVID-19 pandemic is of major scientific and political interest. METHODS: We critically reviewed different estimates of all-cause excess mortality for the five Nordic countries (Denmark, Finland, Iceland, Norway and Sweden), which have been much studied during the COVID-19 pandemic, using the latest register data to discuss uncertainties and implications. RESULTS: We show using back-calculation of expected deaths from Nordic all-cause deaths that the Institute for Health Metrics and Evaluation model is a clear outlier in the compared estimates and likely substantially overestimates excess mortality of Finland and Denmark, and probably Sweden. Our review suggests a range of total Nordic excess deaths of perhaps 15 000-20 000, but results are sensitive to assumptions in the models as shown. CONCLUSIONS: We document substantial heterogeneity and uncertainty in estimates of excess mortality. All estimates should be taken with caution in their interpretation as they miss detailed account of demographics, such as changes in the age group populations over the study period.

Lessons learned and lessons missed: impact of the coronavirus disease 2019 (COVID-19) pandemic on all-cause mortality in 40 industrialised countries and US states prior to mass vaccination.

Background: Industrialised countries had varied responses to the coronavirus disease 2019 (COVID-19) pandemic, and how they adapted to new situations and knowledge since it began. These differences in preparedness and policy may lead to different death tolls from COVID-19 as well as other diseases. Methods: We applied an ensemble of 16 Bayesian probabilistic models to vital statistics data to estimate the impacts of the pandemic on weekly all-cause mortality for 40 industrialised countries from mid-February 2020 through mid-February 2021, before a large segment of the population was vaccinated in these countries. Results: Over the entire year, an estimated 1,410,300 (95% credible interval 1,267,600-1,579,200) more people died in these countries than would have been expected had the pandemic not happened. This is equivalent to 141 (127-158) additional deaths per 100,000 people and a 15% (14-17) increase in deaths in all these countries combined. In Iceland, Australia and New Zealand, mortality was lower than would be expected if the pandemic had not occurred, while South Korea and Norway experienced no detectable change in mortality. In contrast, the USA, Czechia, Slovakia and Poland experienced at least 20% higher mortality. There was substantial heterogeneity across countries in the dynamics of excess mortality. The first wave of the pandemic, from mid-February to the end of May 2020, accounted for over half of excess deaths in Scotland, Spain, England and Wales, Canada, Sweden, Belgium, the Netherlands and Cyprus. At the other extreme, the period between mid-September 2020 and mid-February 2021 accounted for over 90% of excess deaths in Bulgaria, Croatia, Czechia, Hungary, Latvia, Montenegro, Poland, Slovakia and Slovenia. Conclusions: Until the great majority of national and global populations have vaccine-acquired immunity, minimising the death toll of the pandemic from COVID-19 and other diseases will require actions to delay and contain infections and continue routine health care.

Magnitude, demographics and dynamics of the effect of the first wave of the COVID-19 pandemic on all-cause mortality in 21 industrialized countries.

The Coronavirus Disease 2019 (COVID-19) pandemic has changed many social, economic, environmental and healthcare determinants of health. We applied an ensemble of 16 Bayesian models to vital statistics data to estimate the all-cause mortality effect of the pandemic for 21 industrialized countries. From mid-February through May 2020, 206,000 (95% credible interval, 178,100-231,000) more people died in these countries than would have had the pandemic not occurred. The number of excess deaths, excess deaths per 100,000 people and relative increase in deaths were similar between men and women in most countries. England and Wales and Spain experienced the largest effect: ~100 excess deaths per 100,000 people, equivalent to a 37% (30-44%) relative increase in England and Wales and 38% (31-45%) in Spain. Bulgaria, New Zealand, Slovakia, Australia, Czechia, Hungary, Poland, Norway, Denmark and Finland experienced mortality changes that ranged from possible small declines to increases of 5% or less in either sex. The heterogeneous mortality effects of the COVID-19 pandemic reflect differences in how well countries have managed the pandemic and the resilience and preparedness of the health and social care system.

Anomalously warm temperatures are associated with increased injury deaths.

Temperatures that deviate from the long-term local norm affect human health, and are projected to become more frequent as the global climate changes1. There are limited data on how such anomalies affect deaths from injuries. In the present study, we used data on mortality and temperature over 38 years (1980-2017) in the contiguous USA and formulated a Bayesian spatio-temporal model to quantify how anomalous temperatures, defined as deviations of monthly temperature from the local average monthly temperature over the entire analysis period, affect deaths from unintentional (transport, falls and drownings) and intentional (assault and suicide) injuries, by age group and sex. We found that a 1.5 °C anomalously warm year, as envisioned under the Paris Climate Agreement2, would be associated with an estimated 1,601 (95% credible interval 1,430-1,776) additional injury deaths. Of these additional deaths, 84% would occur in males, mostly in adolescence to middle age. These would comprise increases in deaths from drownings, transport, assault and suicide, offset partly by a decline in deaths from falls in older ages. The findings demonstrate the need for targeted interventions against injuries during periods of anomalously warm temperatures, especially as these episodes are likely to increase with global climate change.

Three Public Health Interventions Could Save 94 Million Lives in 25 Years.

BACKGROUND: Preventable noncommunicable diseases, mostly cardiovascular diseases, are responsible for 38 million deaths annually. A few well-documented interventions have the potential to prevent many of these deaths, but a large proportion of the population in need does not have access to these interventions. We quantified the global mortality impact of 3 high-impact and feasible interventions: scaling up treatment of high blood pressure to 70%, reducing sodium intake by 30%, and eliminating the intake of artificial trans fatty acids. METHODS: We used global data on mean blood pressure levels and sodium and trans fat intake by country, age, and sex from a pooled analysis of population health surveys, and regional estimates of current coverage of antihypertensive medications, and cause-specific mortality rates in each country, as well, with projections from 2015 to 2040. We used the most recent meta-analyses of epidemiological studies to derive relative risk reductions for each intervention. We estimated the proportional effect of each intervention on reducing mortality from related causes by using a generalized version of the population-attributable fraction. The effect of antihypertensive medications and lowering sodium intake were modeled through their impact on blood pressure and as immediate increase/reduction to the proposed targets. RESULTS: The combined effect of the 3 interventions delayed 94.3 million (95% uncertainty interval, 85.7-102.7) deaths during 25 years. Increasing coverage of antihypertensive medications to 70% alone would delay 39.4 million deaths (35.9-43.0), whereas reducing sodium intake by 30% would delay another 40.0 million deaths (35.1-44.6) and eliminating trans fat would delay an additional 14.8 million (14.7-15.0). The estimated impact of trans fat elimination was largest in South Asia. Sub-Saharan Africa had the largest proportion of premature delayed deaths out of all delayed deaths. CONCLUSIONS: Three effective interventions can save almost 100 million lives globally within 25 years. National and international efforts to scale up these interventions should be a focus of cardiovascular disease prevention programs.

Investing in non-communicable disease risk factor control among adolescents worldwide: a modelling study.

INTRODUCTION: Exposure to non-communicable disease (NCD) risk factors is increasing among adolescents in most countries due to demographic, economic and epidemiological forces. We sought to analyse the potential health impact and costs of implementing NCD risk reduction interventions among adolescents worldwide. METHODS: We identified six interventions targeted at adolescent tobacco smoking, heavy episodic drinking and obesity and supported by effectiveness and cost-effectiveness evidence. Based on a population-level cohort of adolescents in 70 representative countries, we assessed the global mortality consequences of fully implementing these interventions over 2020-2070 using the potential impact fraction approach. We calculated the economic benefits of reduced mortality and estimated the required financial costs, discounting both at 3% annually. We also conducted best-case and worst-case scenario analyses. RESULTS: Full implementation of these interventions worldwide could avert nearly 10% of premature deaths among this cohort, translating to about US$400 billion in cumulative economic benefits. Cumulatively, the required costs would be about US$85 billion, suggesting that every US$1 of public money invested would generate US$5 in increased human capital. Tobacco taxes generally conferred the highest economic returns; however, an in-depth analysis of three countries illustrated the potential for different priorities, such as alcohol control, to emerge. CONCLUSION: From a life course perspective, implementation of a package of interventions to reduce NCD risk among adolescents worldwide would substantially reduce premature mortality at reasonable costs. Our analysis illustrates the importance of integrating NCD prevention policies into the emerging global agenda for adolescent health and well-being.

Contributions of diseases and injuries to widening life expectancy inequalities in England from 2001 to 2016: a population-based analysis of vital registration data.

BACKGROUND: Life expectancy inequalities in England have increased steadily since the 1980s. Our aim was to investigate how much deaths from different diseases and injuries and at different ages have contributed to this rise to inform policies that aim to reduce health inequalities. METHODS: We used vital registration data from the Office for National Statistics on population and deaths in England, by underlying cause of death, from 2001 to 2016, stratified by sex, 5-year age group, and decile of the Index of Multiple Deprivation (based on the ranked scores of Lower Super Output Areas in England in 2015). We grouped the 7·65 million deaths by their assigned International Classification of Diseases (10th revision) codes to create categories of public health and clinical relevance. We used a Bayesian hierarchical model to obtain robust estimates of cause-specific death rates by sex, age group, year, and deprivation decile. We calculated life expectancy at birth by decile of deprivation and year using life-table methods. We calculated the contributions of deaths from each disease and injury, in each 5-year age group, to the life expectancy gap between the most deprived and affluent deciles using Arriaga's method. FINDINGS: The life expectancy gap between the most affluent and most deprived deciles increased from 6·1 years (95% credible interval 5·9-6·2) in 2001 to 7·9 years (7·7-8·1) in 2016 in females and from 9·0 years (8·8-9·2) to 9·7 years (9·6-9·9) in males. Since 2011, the rise in female life expectancy has stalled in the third, fourth, and fifth most deprived deciles and has reversed in the two most deprived deciles, declining by 0·24 years (0·10-0·37) in the most deprived and 0·16 years (0·02-0·29) in the second-most deprived by 2016. Death rates from every disease and at every age were higher in deprived areas than in affluent ones in 2016. The largest contributors to life expectancy inequalities were deaths in children younger than 5 years (mostly neonatal deaths), respiratory diseases, ischaemic heart disease, and lung and digestive cancers in working ages, and dementias in older ages. From 2001 to 2016, the contributions to inequalities declined for deaths in children younger than 5 years, ischaemic heart disease (for both sexes), and stroke and intentional injuries (for men), but increased for most other causes. INTERPRETATION: Recent trends in life expectancy in England have not only resulted in widened inequalities but the most deprived communities are now seeing no life expectancy gain. These inequalities are driven by a diverse group of diseases that can be effectively prevented and treated. Adoption of the principle of proportionate universalism to prevention and health and social care can postpone deaths into older ages for all communities and reduce life expectancy inequalities. FUNDING: Wellcome Trust.

Worldwide burden of cancer attributable to diabetes and high body-mass index: a comparative risk assessment.

BACKGROUND: Diabetes and high body-mass index (BMI) are associated with increased risk of several cancers, and are increasing in prevalence in most countries. We estimated the cancer incidence attributable to diabetes and high BMI as individual risk factors and in combination, by country and sex. METHODS: We estimated population attributable fractions for 12 cancers by age and sex for 175 countries in 2012. We defined high BMI as a BMI greater than or equal to 25 kg/m2. We used comprehensive prevalence estimates of diabetes and BMI categories in 2002, assuming a 10-year lag between exposure to diabetes or high BMI and incidence of cancer, combined with relative risks from published estimates, to quantify contribution of diabetes and high BMI to site-specific cancers, individually and combined as independent risk factors and in a conservative scenario in which we assumed full overlap of risk of diabetes and high BMI. We then used GLOBOCAN cancer incidence data to estimate the number of cancer cases attributable to the two risk factors. We also estimated the number of cancer cases in 2012 that were attributable to increases in the prevalence of diabetes and high BMI from 1980 to 2002. All analyses were done at individual country level and grouped by region for reporting. FINDINGS: We estimated that 5·7% of all incident cancers in 2012 were attributable to the combined effects of diabetes and high BMI as independent risk factors, corresponding to 804 100 new cases. 187 600 (24·5%) of 766 000 cases of liver cancer and 121 700 (38·4%) of 317 000 cases of endometrial cancer were attributable to these risk factors. In the conservative scenario, about 4·5% (629 000 new cases) of all incident cancers assessed were attributable to diabetes and high BMI combined. Individually, high BMI (544 300 cases) was responsible for almost twice as many cancer cases as diabetes (293 300 cases). 25·8% of diabetes-related cancers (equating to 75 600 new cases) and 31·9% of high BMI-related cancers (174 040 new cases) were attributable to increases in the prevalence of these risk factors from 1980 to 2002. INTERPRETATION: A substantial number of cancer cases are attributable to diabetes and high BMI. As the prevalence of these cancer risk factors increases, clinical and public health efforts should focus on identifying optimal preventive and screening measures for whole populations and individual patients. FUNDING: NIHR and Wellcome Trust.

Worldwide burden of cancer attributable to diabetes and high body-mass index: a comparative risk assessment.

BACKGROUND: Diabetes and high body-mass index (BMI) are associated with increased risk of several cancers, and are increasing in prevalence in most countries. We estimated the cancer incidence attributable to diabetes and high BMI as individual risk factors and in combination, by country and sex. METHODS: We estimated population attributable fractions for 12 cancers by age and sex for 175 countries in 2012. We defined high BMI as a BMI greater than or equal to 25 kg/m2. We used comprehensive prevalence estimates of diabetes and BMI categories in 2002, assuming a 10-year lag between exposure to diabetes or high BMI and incidence of cancer, combined with relative risks from published estimates, to quantify contribution of diabetes and high BMI to site-specific cancers, individually and combined as independent risk factors and in a conservative scenario in which we assumed full overlap of risk of diabetes and high BMI. We then used GLOBOCAN cancer incidence data to estimate the number of cancer cases attributable to the two risk factors. We also estimated the number of cancer cases in 2012 that were attributable to increases in the prevalence of diabetes and high BMI from 1980 to 2002. All analyses were done at individual country level and grouped by region for reporting. FINDINGS: We estimated that 5·6% of all incident cancers in 2012 were attributable to the combined effects of diabetes and high BMI as independent risk factors, corresponding to 792 600 new cases. 187 600 (24·5%) of 766 000 cases of liver cancer and 121 700 (38·4%) of 317 000 cases of endometrial cancer were attributable to these risk factors. In the conservative scenario, about 4·5% (626 900 new cases) of all incident cancers assessed were attributable to diabetes and high BMI combined. Individually, high BMI (544 300 cases) was responsible for twice as many cancer cases as diabetes (280 100 cases). 26·1% of diabetes-related cancers (equating to 77 000 new cases) and 31·9% of high BMI-related cancers (174 040 new cases) were attributable to increases in the prevalence of these risk factors from 1980 to 2002. INTERPRETATION: A substantial number of cancer cases are attributable to diabetes and high BMI. As the prevalence of these cancer risk factors increases, clinical and public health efforts should focus on identifying optimal preventive and screening measures for whole populations and individual patients. FUNDING: NIHR and Wellcome Trust.

Future life expectancy in 35 industrialised countries: projections with a Bayesian model ensemble.

BACKGROUND: Projections of future mortality and life expectancy are needed to plan for health and social services and pensions. Our aim was to forecast national age-specific mortality and life expectancy using an approach that takes into account the uncertainty related to the choice of forecasting model. METHODS: We developed an ensemble of 21 forecasting models, all of which probabilistically contributed towards the final projections. We applied this approach to project age-specific mortality to 2030 in 35 industrialised countries with high-quality vital statistics data. We used age-specific death rates to calculate life expectancy at birth and at age 65 years, and probability of dying before age 70 years, with life table methods. FINDINGS: Life expectancy is projected to increase in all 35 countries with a probability of at least 65% for women and 85% for men. There is a 90% probability that life expectancy at birth among South Korean women in 2030 will be higher than 86·7 years, the same as the highest worldwide life expectancy in 2012, and a 57% probability that it will be higher than 90 years. Projected female life expectancy in South Korea is followed by those in France, Spain, and Japan. There is a greater than 95% probability that life expectancy at birth among men in South Korea, Australia, and Switzerland will surpass 80 years in 2030, and a greater than 27% probability that it will surpass 85 years. Of the countries studied, the USA, Japan, Sweden, Greece, Macedonia, and Serbia have some of the lowest projected life expectancy gains for both men and women. The female life expectancy advantage over men is likely to shrink by 2030 in every country except Mexico, where female life expectancy is predicted to increase more than male life expectancy, and in Chile, France, and Greece where the two sexes will see similar gains. More than half of the projected gains in life expectancy at birth in women will be due to enhanced longevity above age 65 years. INTERPRETATION: There is more than a 50% probability that by 2030, national female life expectancy will break the 90 year barrier, a level that was deemed unattainable by some at the turn of the 21st century. Our projections show continued increases in longevity, and the need for careful planning for health and social services and pensions. FUNDING: UK Medical Research Council and US Environmental Protection Agency.

Worldwide Exposures to Cardiovascular Risk Factors and Associated Health Effects: Current Knowledge and Data Gaps.

Information on exposure to, and health effects of, cardiovascular disease (CVD) risk factors is needed to develop effective strategies to prevent CVD events and deaths. Here, we provide an overview of the data and evidence on worldwide exposures to CVD risk factors and the associated health effects. Global comparative risk assessment studies have estimated that hundreds of thousands or millions of CVD deaths are attributable to established CVD risk factors (high blood pressure and serum cholesterol, smoking, and high blood glucose), high body mass index, harmful alcohol use, some dietary and environmental exposures, and physical inactivity. The established risk factors plus body mass index are collectively responsible for ≈9.7 million annual CVD deaths, with high blood pressure accounting for more CVD deaths than any other risk factor. Age-standardized CVD death rates attributable to established risk factors plus high body mass index are lowest in high-income countries, followed by Latin America and the Caribbean; they are highest in the region of central and eastern Europe and central Asia. However, estimates of the health effects of CVD risk factors are highly uncertain because there are insufficient population-based data on exposure to most CVD risk factors and because the magnitudes of their effects on CVDs in observational studies are likely to be biased. We identify directions for research and surveillance to better estimate the effects of CVD risk factors and policy options for reducing CVD burden by modifying preventable risk factors.

Regional contributions of six preventable risk factors to achieving the 25 × 25 non-communicable disease mortality reduction target: a modelling study.

BACKGROUND: Countries have agreed to reduce premature mortality from the four main non-communicable diseases (NCDs) by 25% from 2010 levels by 2025 (referred to as the 25 × 25 target). Countries also agreed on a set of global voluntary targets for selected NCD risk factors. Previous analyses have shown that achieving the risk factor targets can contribute substantially towards meeting the 25 × 25 mortality target at the global level. We estimated the contribution of achieving six of the globally agreed risk factor targets towards meeting the 25 × 25 mortality target by region. METHODS: We estimated the effect of achieving the targets for six risk factors (tobacco and alcohol use, salt intake, obesity, and raised blood pressure and glucose) on NCD mortality between 2010 and 2025. Our methods accounted for multicausality of NCDs and for the fact that, when risk factor exposure increases or decreases, the harmful or beneficial effects on NCDs accumulate gradually. We used data for risk factor and mortality trends from systematic analyses of available country data. Relative risks for the effects of individual and multiple risks, and for change in risk after decreases or increases in exposure, were from reanalyses and meta-analyses of epidemiological studies. FINDINGS: The probability of dying between the ages 30 years and 70 years from the four main NCDs in 2010 ranged from 19% in the region of the Americas to 29% in southeast Asia for men, and from 13% in Europe to 21% in southeast Asia for women. If current trends continue, the probability of dying prematurely from the four main NCDs is projected to increase in the African region but decrease in the other five regions. If the risk factor targets are achieved, the 25 × 25 target will be surpassed in Europe in both men and women, and will be achieved in women (and almost achieved in men) in the western Pacific; the regions of the Americas, the eastern Mediterranean, and southeast Asia will approach the target; and the rising trend in Africa will be reversed. In most regions, a more ambitious approach to tobacco control (50% reduction relative to 2010 instead of the agreed 30%) will contribute the most to reducing premature NCD mortality among men, followed by addressing raised blood pressure and the agreed tobacco target. For women, the highest contributing risk factor towards the premature NCD mortality target will be raised blood pressure in every region except Europe and the Americas, where the ambitious (but not agreed) tobacco reduction would have the largest benefit. INTERPRETATION: No WHO region will meet the 25 × 25 premature mortality target if current mortality trends continue. Achieving the agreed targets for the six risk factors will allow some regions to meet the 25 × 25 target and others to approach it. Meeting the 25 × 25 target in Africa needs other interventions, including those addressing infection-related cancers and cardiovascular disease. FUNDING: UK Medical Research Council.

The future of life expectancy and life expectancy inequalities in England and Wales: Bayesian spatiotemporal forecasting.

BACKGROUND: To plan for pensions and health and social services, future mortality and life expectancy need to be forecast. Consistent forecasts for all subnational units within a country are very rare. Our aim was to forecast mortality and life expectancy for England and Wales' districts. METHODS: We developed Bayesian spatiotemporal models for forecasting of age-specific mortality and life expectancy at a local, small-area level. The models included components that accounted for mortality in relation to age, birth cohort, time, and space. We used geocoded mortality and population data between 1981 and 2012 from the Office for National Statistics together with the model with the smallest error to forecast age-specific death rates and life expectancy to 2030 for 375 of England and Wales' 376 districts. We measured model performance by withholding recent data and comparing forecasts with this withheld data. FINDINGS: Life expectancy at birth in England and Wales was 79·5 years (95% credible interval 79·5-79·6) for men and 83·3 years (83·3-83·4) for women in 2012. District life expectancies ranged between 75·2 years (74·9-75·6) and 83·4 years (82·1-84·8) for men and between 80·2 years (79·8-80·5) and 87·3 years (86·0-88·8) for women. Between 1981 and 2012, life expectancy increased by 8·2 years for men and 6·0 years for women, closing the female-male gap from 6·0 to 3·8 years. National life expectancy in 2030 is expected to reach 85·7 (84·2-87·4) years for men and 87·6 (86·7-88·9) years for women, further reducing the female advantage to 1·9 years. Life expectancy will reach or surpass 81·4 years for men and reach or surpass 84·5 years for women in every district by 2030. Longevity inequality across districts, measured as the difference between the 1st and 99th percentiles of district life expectancies, has risen since 1981, and is forecast to rise steadily to 8·3 years (6·8-9·7) for men and 8·3 years (7·1-9·4) for women by 2030. INTERPRETATION: Present forecasts underestimate the expected rise in life expectancy, especially for men, and hence the need to provide improved health and social services and pensions for elderly people in England and Wales. Health and social policies are needed to curb widening life expectancy inequalities, help deprived districts catch up in longevity gains, and avoid a so-called grand divergence in health and longevity. FUNDING: UK Medical Research Council and Public Health England.

Contribution of six risk factors to achieving the 25×25 non-communicable disease mortality reduction target: a modelling study.

BACKGROUND: Countries have agreed to reduce premature mortality (defined as the probability of dying between the ages of 30 years and 70 years) from four main non-communicable diseases (NCDs)--cardiovascular diseases, chronic respiratory diseases, cancers, and diabetes--by 25% from 2010 levels by 2025 (referred to as 25×25 target). Targets for selected NCD risk factors have also been agreed on. We estimated the contribution of achieving six risk factor targets towards meeting the 25×25 mortality target. METHODS: We estimated the impact of achieving the targets for six risk factors (tobacco and alcohol use, salt intake, obesity, and raised blood pressure and glucose) on NCD mortality between 2010 and 2025. Our methods accounted for multi-causality of NCDs and for the fact that when risk factor exposure increases or decreases, the harmful or beneficial effects on NCDs accumulate gradually. We used data for risk factor and mortality trends from systematic analyses of available country data. Relative risks for the effects of individual and multiple risks, and for change in risk after decreases or increases in exposure, were from re-analyses and meta-analyses of epidemiological studies. FINDINGS: If risk factor targets are achieved, the probability of dying from the four main NCDs between the ages of 30 years and 70 years will decrease by 22% in men and by 19% in women between 2010 and 2025, compared with a decrease of 11% in men and 10% in women under the so-called business-as-usual trends (ie, projections based on current trends with no additional action). Achieving the risk factor targets will delay or prevent more than 37 million deaths (16 million in people aged 30-69 years and 21 million in people aged 70 years or older) from the main NCDs over these 15 years compared with a situation of rising or stagnating risk factor trends. Most of the benefits of achieving the risk factor targets, including 31 million of the delayed or prevented deaths, will be in low-income and middle-income countries, and will help to reduce the global inequality in premature NCD mortality. A more ambitious target on tobacco use (a 50% reduction) will almost reach the target in men (>24% reduction in the probability of death), and enhance the benefits to a 20% reduction in women. INTERPRETATION: If the agreed risk factor targets are met, premature mortality from the four main NCDs will decrease to levels that are close to the 25×25 target, with most of these benefits seen in low-income and middle-income countries. On the basis of mortality benefits and feasibility, a more ambitious target than currently agreed should be adopted for tobacco use. FUNDING: UK MRC.