Global burden of 369 diseases and injuries in 204 countries and territories, 1990–2019: a systematic analysis for the Global Burden of Disease Study 2019

Background: In an era of shifting global agendas and expanded emphasis on non-communicable diseases and injuries along with communicable diseases, sound evidence on trends by cause at the national level is essential. The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) provides a systematic scientific assessment of published, publicly available, and contributed data on incidence, prevalence, and mortality for a mutually exclusive and collectively exhaustive list of diseases and injuries. Methods: GBD estimates incidence, prevalence, mortality, years of life lost (YLLs), years lived with disability (YLDs), and disability-adjusted life-years (DALYs) due to 369 diseases and injuries, for two sexes, and for 204 countries and territories. Input data were extracted from censuses, household surveys, civil registration and vital statistics, disease registries, health service use, air pollution monitors, satellite imaging, disease notifications, and other sources. Cause-specific death rates and cause fractions were calculated using the Cause of Death Ensemble model and spatiotemporal Gaussian process regression. Cause-specific deaths were adjusted to match the total all-cause deaths calculated as part of the GBD population, fertility, and mortality estimates. Deaths were multiplied by standard life expectancy at each age to calculate YLLs. A Bayesian meta-regression modelling tool, DisMod-MR 2.1, was used to ensure consistency between incidence, prevalence, remission, excess mortality, and cause-specific mortality for most causes. Prevalence estimates were multiplied by disability weights for mutually exclusive sequelae of diseases and injuries to calculate YLDs. We considered results in the context of the Socio-demographic Index (SDI), a composite indicator of income per capita, years of schooling, and fertility rate in females younger than 25 years. Uncertainty intervals (UIs) were generated for every metric using the 25th and 975th ordered 1000 draw values of the posterior distribution. Findings: Global health has steadily improved over the past 30 years as measured by age-standardised DALY rates. After taking into account population growth and ageing, the absolute number of DALYs has remained stable. Since 2010, the pace of decline in global age-standardised DALY rates has accelerated in age groups younger than 50 years compared with the 1990–2010 time period, with the greatest annualised rate of decline occurring in the 0–9-year age group. Six infectious diseases were among the top ten causes of DALYs in children younger than 10 years in 2019: lower respiratory infections (ranked second), diarrhoeal diseases (third), malaria (fifth), meningitis (sixth), whooping cough (ninth), and sexually transmitted infections (which, in this age group, is fully accounted for by congenital syphilis; ranked tenth). In adolescents aged 10–24 years, three injury causes were among the top causes of DALYs: road injuries (ranked first), self-harm (third), and interpersonal violence (fifth). Five of the causes that were in the top ten for ages 10–24 years were also in the top ten in the 25–49-year age group: road injuries (ranked first), HIV/AIDS (second), low back pain (fourth), headache disorders (fifth), and depressive disorders (sixth). In 2019, ischaemic heart disease and stroke were the top-ranked causes of DALYs in both the 50–74-year and 75-years-and-older age groups. Since 1990, there has been a marked shift towards a greater proportion of burden due to YLDs from non-communicable diseases and injuries. In 2019, there were 11 countries where non-communicable disease and injury YLDs constituted more than half of all disease burden. Decreases in age-standardised DALY rates have accelerated over the past decade in countries at the lower end of the SDI range, while improvements have started to stagnate or even reverse in countries with higher SDI. Interpretation: As disability becomes an increasingly large component of disease burden and a larger component of health expenditure, greater research and developm nt investment is needed to identify new, more effective intervention strategies. With a rapidly ageing global population, the demands on health services to deal with disabling outcomes, which increase with age, will require policy makers to anticipate these changes. The mix of universal and more geographically specific influences on health reinforces the need for regular reporting on population health in detail and by underlying cause to help decision makers to identify success stories of disease control to emulate, as well as opportunities to improve. Funding: Bill & Melinda Gates Foundation. © 2020 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 licens

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

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

Defining Abdominal Obesity as a Risk Factor for Coronary Heart Disease in the US Hispanic Community Health Study/Study Of Latinos (HCHS/SOL)

It is now well established that pronounced differences exist in prevalence of abdominal obesity across gender and ethnicity. Hispanic/Latinos, in particular, have been shown to have markedly distinct prevalence when compared to other ethnic populations around the world. Various organizations have highlighted the need to examine whether overall abdominal obesity cut points are appropriate for the use in this ethnic minority, particular highlighting the need of research among Hispanic/Latino residing in Western countries. This study used data from the Hispanic Community Health Study/Study of Latinos (HCHS/SOL), the largest study of Hispanic/Latinos in the US, to: (1) establish optimal definitions for abdominal obesity among Hispanic/Latino adults, (2) determine the level of agreement between the presence of the metabolic syndrome diagnosed by the current Joint Interim Statement (IJS) definition and an updated definition with optimal abdominal obesity cut points, and (3) examine the association between the presence of the metabolic syndrome, diagnosed by both the IJS and our updated definition, and coronary heart disease (CHD). The sample was comprised of 16,289 individuals (59.94% female). Our results indicate than among US Hispanic/Latino adults, waist circumference cut points of \u3e102 cm in men and \u3e97 cm in women provide optimal discrimination for cardiovascular risk as judged by the presence of CHD. When using these cut points to create an updated metabolic syndrome definition among women, we found disagreement between our updated definition and the current IJS criteria for metabolic syndrome. The prevalence of the metabolic syndrome was overestimated by about 5% points among women based on IJS criteria when compared to our updated definition. Further, we determined that the performance of our updated metabolic syndrome definition as predictor of CHD was comparable to that of the IJS definition. In this paper, we provide for the first time an empirically-derived definition of abdominal obesity for use among Hispanic/Latino adults in the US. Future reports should examine our recommended waist circumference definition cut points and the performance of our updated metabolic syndrome definition as a predictor of cardiovascular risk among US Hispanic/Latinos in prospective designs

Leptin as a Novel Predictor of Somatic Depressive Symptoms in Hispanics with the Metabolic Syndrome

The association between depression and the Metabolic Syndrome (MetS) has been extensively investigated, and inflammation has been identified as an underlying link. Recent reports, however, indicate a possible role of leptin in modulating the immune response, yielding increases in inflammatory markers. The literature suggests this hormone may not only explain the metabolic abnormalities associated with depression but may also act as a biomarker of depression itself. This study aimed to determine the association between circulating leptin and total depressive symptoms and depressive symptom dimensions (cognitive and somatic) after controlling for important confounding factors such as age, gender, insulin resistance, body mass index (BMI) and inflammation. We studied 119 Hispanic participants, 60 women and 59 men, recruited for the Community Health and Risk-reduction for the Metabolic Syndrome (CHARMS) study. Depression was measured using the Beck Depression Inventory (BDI). Somatic and Cognitive subscale scores were calculated. Leptin was measured using a leptin-specific enzyme immunoassay. Inflammation was assessed using C-reactive protein (CRP) measured with a high-sensitivity assay. Participants with CRP levels greater than 10 mg/L were excluded from analysis. CRP and leptin levels were log transformed to achieve a normal distribution. Median BDI total score, BDI cognitive score and BDI somatic score were 8, 3 and 5, respectively. Median circulating leptin levels were 30.6 ng/ml. In univariate regression, leptin levels were significantly associated with total (β =0.36, P=.000), cognitive (β =0.24, P=.011) and somatic depressive symptoms (β =0.48, P=.000). After controlling for age, gender, insulin resistance, BMI and inflammation, circulating leptin levels remained significantly associated with somatic depressive symptoms only (β =.41, P=.004). Another important predictor of somatic depressive symptoms was age (β=0.23; P=0.004). The model accounted for 31% of the variance in somatic depression scores. Leptin is significantly associated with somatic depressive symptoms in Hispanics with the MetS. This association was independent of important confounding factors such as gender, age, BMI, insulin resistance and inflammation. Further research is needed to elucidate the complex pathways linking depression and the MetS while incorporating the potential role of leptin

Metabolic Syndrome in Andean Populations

The metabolic syndrome, a cluster of metabolic abnormalities, has been linked to both cardiovascular disease and type 2 diabetes mellitus risk. Several studies have shown that ethnicity is an important determinant for risk of developing the metabolic syndrome; therefore, further understanding of the prevalence and presentation of the metabolic syndrome in various ethnic groups is needed. Latin American communities, and particularly Andean countries, are largely understudied in relation to the metabolic syndrome and until recently, the prevalence of this metabolic disturbance in Andean Hispanics was unknown. Nonetheless, recent (and ongoing) population studies are providing important data regarding the prevalence and patterns of the metabolic syndrome in various Andean countries. This review aims to summarize and interpret the information provided by these studies in an effort to better characterize the metabolic syndrome in Andean Hispanics

Prevalence of lifestyle-related cardiovascular risk factors in Peru: the PREVENCION study Prevalencia de factores de riesgo cardiovascular relacionados con el estilo de vida en Perú: el estudio PREVENCIÓN

OBJECTIVES: To estimate the prevalence of lifestyle-related cardiovascular risk factors in the adult population of Arequipa, the second largest city in Peru. METHODS: The prevalence and patterns of smoking, alcohol drinking, lack of physical activity, high-fat diet, and low fruit and vegetable intake were evaluated among 1 878 subjects (867 men and 1 011 women) in a population-based study. RESULTS: The age-standardized prevalence of current smoking, former smoking, and never smoking were 21.6%, 14.3%, and 64.1%, respectively. The prevalence of current smoking was significantly higher in men than women (31.1% vs. 12.1%; P OBJETIVOS: Estimar la prevalencia de factores de riesgo cardiovascular relacionados con el estilo de vida de adultos de Arequipa, la segunda mayor ciudad de Perú. MÉTODOS: Se realizó un estudio de base poblacional para evaluar la prevalencia y los patrones de consumo de tabaco y bebidas alcohólicas, la falta de actividad física, la dieta rica en grasas y el bajo consumo de frutas y vegetales en 1 878 personas (867 hombres y 1 011 mujeres). RESULTADOS: Las prevalencias estandarizadas por la edad de los fumadores actuales, pasados y de los que nunca fumaron fueron 21,6%, 14,3% y 64,1%, respectivamente. La prevalencia de tabaquismo fue significativamente mayor en los hombres que en las mujeres (31,1% frente a 12,1%; P < 0,01). La prevalencia del consumo de bebidas alcohólicas fue de 37,7%, significativamente mayor en los hombres que en las mujeres (55,5% frente a 19,7%; P < 0,01). La prevalencia del consumo excesivo de alcohol fue de 21,1%, mayor en los hombres que en las mujeres (36,1% frente a 6,4%; P < 0,01). La gran mayoría de los bebedores presentó un patrón de consumo concentrado fundamentalmente en los fines de semana y los días feriados, más que el consumo habitual con las comidas en los días laborables. La proporción de personas con insuficiente actividad fue de 57,6%, significativamente mayor en las mujeres que en los hombres (63,3% frente a 51,9%; P < 0,01). En general, 42,0% de los adultos informaron consumir dietas ricas en grasas, 34,5% dijo tener un bajo consumo de frutas y 33,3% un bajo consumo de vegetales. CONCLUSIONES: La alta prevalencia de factores de riesgo cardiovascular relacionados con el estilo de vida encontrada en esta población de los Andes es preocupante. Se deben implementar urgentemente programas preventivos para resolver este creciente problema

Prevalence of lifestyle-related cardiovascular risk factors in Peru: the PREVENCION study

OBJECTIVES: To estimate the prevalence of lifestyle-related cardiovascular risk factors in the adult population of Arequipa, the second largest city in Peru. METHODS: The prevalence and patterns of smoking, alcohol drinking, lack of physical activity, high-fat diet, and low fruit and vegetable intake were evaluated among 1 878 subjects (867 men and 1 011 women) in a population-based study. RESULTS: The age-standardized prevalence of current smoking, former smoking, and never smoking were 21.6%, 14.3%, and 64.1%, respectively. The prevalence of current smoking was significantly higher in men than women (31.1% vs. 12.1%; P < 0.01). The prevalence of current alcohol use was 37.7% and significantly higher in men than women (55.5% vs. 19.7%; P < 0.01). Similarly, the prevalence of binge drinking was 21.2%, and the percentage of men who binge drink (36.1%) was significantly higher than for women (6.4%; P < 0.01). The vast majority of alcohol drinkers reported a pattern of alcohol consumption mainly on weekends and holidays rather than regular drinking with meals during the week. The proportion of insufficiently active people was 57.6% and was significantly higher in women than men (63.3% vs. 51.9%; P < 0.01). Overall, 42.0% of adults reported consuming high-fat diets, 34.5% reported low fruit intake, and 33.3% reported low vegetable intake. CONCLUSIONS: The high prevalence of lifestyle-related cardiovascular risk factors found in this Andean population is of concern. Preventive programs are urgently needed to deal with this growing problem

Normative values and correlates of carotid artery intima-media thickness and carotid atherosclerosis in Andean-Hispanics: The Prevencion Study

Carotid intima-media thickness (cIMT) is an independent predictor of cardiovascular risk. Furthermore, ethnicity and gender-specific normative data are required to assess cIMT, which are not available for Andean-Hispanics. In addition, data regarding correlates of subclinical atherosclerosis in ethnic population are needed. We studied 1448 adults enrolled in a population-based study in Peru. cIMT and carotid plaque were measured with high-resolution ultrasonography. A healthy reference sample ( n = 472) with no cardiovascular disease, normal weight and normal metabolic parameters was selected to establish normative cIMT values. Correlates of abnormal cIMT and carotid plaque were assessed in the entire population. In the reference sample, 95th-percentile cIMT values were both age and gender-dependent. In stepwise regression, selected predictors of increasing cIMT were: older age, impaired fasting glucose, diabetes mellitus, higher systolic blood pressure, higher LDL-cholesterol, smoking and male gender. Predictors of carotid plaque included older age, male gender, higher systolic blood pressure, lower diastolic blood pressure and higher LDL-cholesterol. HDL-cholesterol and C-reactive protein were not associated with cIMT or carotid plaque. The lack of association with HDL-cholesterol was confirmed using high performance liquid chromatography. We present ethnic-specific cut-offs for abnormal cIMT applicable to Andean-Hispanics and correlates of subclinical atherosclerosis in this population. Pending longitudinal studies, our data supports several risk associations seen in other populations and can be used to identify Andean-Hispanics at increased risk for atherosclerotic cardiovascular disease. The lack of association between HDL-C and cIMT or carotid plaque in this population requires further investigation