В декабре 2012 года в журнале The Lancet вышла серия статей с результатами исследования Global Burden of Disease Study 2010, которое позволило оценить основные причины смертности и потери здоровья в 187 странах за период с 1990 по 2010 года. Этот международный проект возглавляет консорциум Всемирной организации здравоохранения (World Health Organization), Института мониторинга и оценки здравоохранения Вашингтонского университета (Institute for Health Metrics and Evaluation of the University of Washington), школы общественного здравоохранения университета Квинсленда (School of Population Health of the University of Queensland), Гарвардской школы общественного здравоохранения (Harvard School of Public Health), Школы общественного здравоохранения им. Д.Хопкинса (Johns Hopkins Bloomberg School of Public Health), университет Токио (University of Tokyo) и Императорский колледж Лондона (Imperial College London). В этом исследовании приняли участие 486 врачей и ученых разных специальностей, представляющие 302 института в 50 странах мира.

Для оценки заболеваемости и смертности от патологии почек и ряда урологических заболеваний была сформирована экспертная группа под руководством профессора Д.Ремуции, и на протяжении почти пяти лет мы проделали большую работу по поиску эпидемиологических исследований, упорядочиванию этой информации и оценке различных моделей распространенности, заболеваемости, летальности. Основные индикаторы бремени нефрологических заболеваний в общемировых и региональных масштабах уже опубликованы в ряде статей. Хроническая болезнь почек являлась непосредственной причиной одной из каждых семидесяти смертей во всем мире в 2010 году, при этом вклад  хронической болезни почек в смертность увеличился по сравнению с 1990 годом намного более выражено, чем для большинства других нозологий. Эти данные подтверждают эпидемический рост нефрологических заболеваний и говорят о необходимости развития и укрепления нефрологической службы, а также активного изучения эпидемиологии хронической болезни почек и поиску оптимальных путей их лечения во всех странах, в том числе и в России.

Кроме вышедших в The Lancet материалов, нами также подготовлена и принята к публикации обзорная статья в Европейском журнале внутренней медицины, обобщающая целый ряд работ по ведущим причинам смертности в мире и методологическим аспектам Исследования глобального бремени болезней. В соответствии с редакционной политикой журнала размещаю авторскую версию статьи для возможности полнотекстового доступа к ней всех заинтересованных читателей (при просмотре широких таблиц можно использовать бегунок внизу таблицы или версию статьи для печати). При цитировании статьи следует использовать следующий формат: “Bikbov B, Perico N, Remuzzi G. Mortality landscape in the Global Burden of Diseases, Injuries and Risk Factors Study. Eur J Intern Med. 2014; 25(1): 1-5″ (published ahead of print 30 September 2013 doi: 10.1016/j.ejim.2013.09.002).

MORTALITY LANDSCAPE

IN THE GLOBAL BURDEN OF DISEASES, INJURIES AND RISK FACTORS STUDY

Boris Bikbov^1,2,3, Norberto Perico⁴, Giuseppe Remuzzi^4,5

¹ Chair of Nephrology, A.I.Evdokimov Moscow State University of Medicine and Dentistry, Moscow, Russian Federation
² Department of Nephrology Issues of Transplanted Kidney, Academician V.I.Shumakov Federal Research Center of Transplantology and Artificial Organs, Moscow, Russian Federation
³ Moscow City Nephrology Center, Moscow City Hospital 52, Moscow, Russian Federation
⁴ IRCCS – Istituto di Ricerche Farmacologiche Mario Negri, Bergamo, Italy
⁵ Unit of Nephrology, Dialysis and Transplantation, Azienda Ospedaliera Papa Giovanni XXIII, Bergamo, Italy

 

The Global Burden of Disease 2010 Study

The Global Burden of Diseases, Injuries and Risk Factors Study 2010 (GBD 2010) is an outstanding initiative that involved 486 scientists from 302 institutions in 50 countries, under the leadership of a consortium formed by the Institute for Health Metrics and Evaluation of the University of Washington, World Health Organization, the University of Queensland School of Population Health, the Harvard School of Public Health, the Johns Hopkins Bloomberg School of Public Health, the University of Tokyo and Imperial College London[1]. The study has provided a state of the art understanding of the burden of 67 risk factors and their clusters, 291 diseases and injuries on global, regional and national levels in period from 1990 to 2010 for 187 countries. GBD 2010 estimates covered both mortality (expressed in number of deaths, years of life lost due to premature mortality (YLL) and their rates per 100,000 persons) and morbidity (mainly expressed as years lived with disability (YLD)), while the incidence and prevalence were not reported for majority of causes so far, although they were accounted and used for YLD calculations. Finally, each disease and risk factor was presented in terms of the disability-adjusted years of life (DALY) that is merely a sum of YLL and YLD. The major published results of GBD 2010 cover global and regional levels for all diseases and risk factors [2-8] Reports focused on specific conditions are also available [9–16]. At country level detailed estimates are published for UK[17], China[18] and USA[19], and data on other countries are accessible only as aggregate partial representation via web-based tools[20]. It was announced that in the fall of 2013 comprehensive estimates for all diseases and risk factors both on country, regional and global levels will be put in the public domain[20].

 

Global mortality due to diseases and injuries

Mortality estimates in GBD 2010 have been developed based on a wide range of published and unpublished data of vital registration, verbal autopsy, mortality surveillance, and other sources[3]. These tremendous amounts of data were analyzed according to uniform approaches for communicable, maternal, neonatal and nutritional disorders (CMNND), non-communicable diseases (NCD) and injuries. Accounting all causes in one model aimed to prevent overestimation of mortality from separate diseases and represented the great advantage of GBD 2010 over other analyses that concentrated only on single cause of death.

The estimated worldwide number of deaths in the year 2010 was 52.8 million, most of which caused by NCD (35.5 mln deaths, 65.5% of total deaths number), followed by CMNND deaths (13.2 mln, 24.9%) and injuries (5.1 mln, 9.6%). These data emphasise the continuing epidemiological transition in the global mortality towards non-communicable diseases (that accounted to 57.1% of all deaths in 1990). Globally age- and sex-specific death rates are decreasing in comparison with 1990 (by 52.7% for CMNND, 32.1% for NCD and 16.3% for injuries), highlighting important achievements in prevention and treatment for many diseases. But due to world population growth and aging, the absolute number of deaths increased from 46.5 mln in 1990 to 52.8 mln in 2010, challenging health and social security systems in all countries. The growth in number of deaths for the past 20 years was as high as 30.0% for NCD and 24.0% for injuries, while it declined by 17.0% for CMNND. Despite the striking evidence of the relevance of NCD epidemic in all regions of the world, there is a substantial disproportion in resource allocation both on global level and inside some countries. In 2010 a total $28.2 billion were invested for development assistance for health, with the health sector support aimed for general strengthening of local health services amounted to only to $1.5 billion and for NCD to only $185 million (5.3% and 0.8% from the development assistance for health, respectively) [21]. Moreover, from the 20 countries with the highest all-cause DALYs only 12 are included in the top 20 recipients of development assistance for health, and globally the total expenditures on health sector support and NCD decreased respectively by 2.5% and 5.1% in 2010[21].

The global landscape of mortality causes has changed substantially from 1990 to 2010 by several dimensions of disease burden (table 1). Allocation of resource in public health to fight specific disorders should be based on several considerations, not only on the formal rank in the top list because the latter doesn’t reflect well the true burden. Both number of deaths and proportion of deaths in the total mortality structure indicate the relatively small differences between disorders that could be ranked as 5 or 10 leading cause of deaths (the same is true for the comparison of 20 and 25 top ranked causes). These differences loose significance especially keeping in mind the 95% uncertainty interval in estimated number of deaths and imperfection of vital statistic systems in many countries[3][22]. It should be taken into account that changes in mortality rates were extremely non-uniform for different causes (table 1), some of them being dramatically increased thus bringing intense pressure on health and economic systems, and suggesting even more prominent impact on global mortality in the nearest future. Number of deaths in comparison with 1990 are more than doubled not only for HIV/AIDS (accounting for 1.4 mln deaths in 2010), Alzheimer’s disease and other dementias (485,700 deaths) that already accounted among top 30 mortality causes, but also for atrial fibrillation and flutter (114,700 deaths), Parkinson’s disease (111,100 deaths), adverse effects of medical treatment (83,700 deaths), illicit drug use (77,600 deaths) and peripheral vascular disease (49,800 deaths). For the past 20 years the number of deaths for diabetes mellitus and chronic kidney diseases (that are already in the top 20 mortality causes) increased by 70-95% (accounting in 2010 for almost 1.3 million and 735,600 deaths respectively). Also other causes of death such as other urinary diseases (267,100 deaths), kidney and other urinary organ cancers (162,100 deaths), interstitial lung disease and pulmonary sarcoidosis (115,100 deaths) showed an increasing trend over the two decades. During the studied period the age-adjusted death rates (table 1) declined for many diseases while it substantially increased for several disorders, indicating the lack of control by current prevention and treatment strategies irrespective of population aging. These diseases need special attention from the health policy makers all over the world in order to stop the impending threat that they pose.

Table 1. Top 30 causes of global deaths for all ages and both sexes combined, ordered by the number of deaths in 2010 (modified from Lozano et al[3])

Global mortality patterns expressed in YLL differ reasonably, given more emphasis for disorders with deaths occurred in the younger age. Therefore the YLL based top ten global mortality causes accounted (in descending order) for ischemic heart disease, lower respiratory infections, cerebrovascular disease, diarrhoeal diseases, malaria, HIV/AIDS, preterm birth complications, road injury, chronic obstructive pulmonary disease, and neonatal encephalopathy [3].

 

Global mortality attributable to risk factors

GBD 2010 also estimated the influence of risk factors on global mortality and morbidity (table 2). These findings provide an important information for establishing priorities in prevention and screening programs, and also indicate a possible effect on health gain if risk factors are corrected. It should be noted that many risk factors are correlated at individual level (for example, excessive salt consumption, hypertension and high body mass index), thus the joint effect of several risk factors cannot be calculated as a simple addition of separate factor burden and is usually smaller than their sums. Dietary risk factors have striking influence on mortality. Excessive dietary sodium intake has an enormous estimated impact on health (3.1 mln deaths in 2010), followed by the consumption of processed meat (0.8 mln deaths), trans fatty acids (0.5 mln deaths) and sugar-sweetened beverages (0.3 mln deaths). Even more prominent are the estimated consequences on health of insufficient consumption of certain food types, such as fruits (attributable to 4.9 mln deaths in 2010), vegetables (1.8 mln deaths), nuts and seeds (2.5 mln deaths), whole grains (1.7 mln deaths), omega-3 fatty acids (1.4 mln deaths), fiber (0.7 mln deaths) and polyunsaturated fatty acids (0.5 mln deaths). Despite of these astonishing data, dietary guidance, regulation of food industry and measures for promotion of healthy eating are insufficiently incorporated in the health care policy, especially in developing countries[23]. The high-quality practical skills on nutrition counselling are poorly implemented in primary medical education for family physicians and referral to dieticians is largely insufficient even in developed countries[24]. No wonder that diseases related to nutrition have profound impact on mortality and morbidity in all world regions.

High blood pressure is the leading single risk factor with 9.4 mln deaths and 7.0% of all DALYs in 2010, and those indicators have rose by almost 30% from 1990. One of the most informative parameter for estimating the efficiency of risk factor correction that take into account both changes in risk factor burden and population size is the change in DALYs per 100,000 from 1990 to 2010. For high blood pressure it decreased less than 3%, indicating that the efforts to combat hypertension had scanty effects at a population level. Other risk factors closely related to high blood pressure increased or only slightly decreased in the past two decades. DALYs per 100,000 population increased by almost 40% for high body mass index and almost 20% for high fasting plasma glucose (each attributable to 3.4 mln deaths in 2010), indicating the ongoing uncontrolled obesity and diabetes epidemic with absence of effective interventions. Moreover, impaired glucose metabolism contributes even more to the global mortality burden and is associated with almost 4.6 mln deaths in 2010, because in GBD 2010 it is considered as acting indirectly as risk factor (table 2) leading to increased mortality from several causes (mainly cardiovascular diseases) and directly with mortality due to diabetes mellitus as a disease (table 1).

The burden of several other risk factors has decreased substantially, although they still contribute to more than 10 million deaths in 2010. This is an area that require further interventions. The major decrease in number of deaths or DALYs per 100,000 population was related to air pollution, some occupational risk factors, childhood underweight, suboptimal breastfeeding, unimproved sanitation, zinc, iron and vitamin A deficiency. For the past twenty years burden due to alcohol use (attributable to 4.9 mln deaths in 2010) decreased only by 1.3% expressed in DALYs per 100,000 population and due to active tobacco smoking (responsible for 5.7 mln deaths) decreased by 7.4%, while a significant success was achieved reducing deaths due to second-hand smoke (1.1 mln deaths) by almost 60%.

Table 2. Top 30 risk factors of global deaths for all ages and both sexes combined, ordered by the number of deaths in 2010 (modified from Lim et al[8])

 

Shortcomings and contradictions of current revision of the Global Burden of Disease Study

GBD 2010 has several limitations that require improvement in the future analysis of diseases, injuries and risk factors burden. The major shortcoming is the absent or the insufficient quality of data for many countries and conditions used to estimate mortality and morbidity. Only 89 of 187 countries in the world have complete vital registration systems, and even for many widespread and life threatening diseases there are only limited epidemiological data[22]. Quality and availability of data are challenging even for high-income countries with well established vital registration systems and plenty of epidemiological research. For example, the proportion of deaths assigned to causes that are unlikely to be the real underlying cause of death or to ill-defined causes is as high as 17.9% in England and 34.9% in Portugal[17]. The lack or inaccuracy of primary data was to some degree balanced in GBD 2010 by applying sophisticated and innovative methods of statistical modeling, as well as accounting for numerous country-level demographic and macroeconomic covariates from different sources[3][8][22]. Nonetheless, one of the principal requirements for robust estimates of death causes is the establishment and maintaining of appropriate vital registration systems in all countries as a part of general strengthening of health care.

Moreover, there are several important disorders and risk factors that are underrepresented in the GBD 2010. This is particularly evident for chronic kidney disease (CKD), that is included in the GBD for the first time according to its current definition. Previous GBD revisions[25] considered kidney diseases under the vintage term “nephritis and nephrosis”, a very inadequate definition. Currently CKD has a uniform definition and its classification is based on cause, level of glomerular filtration rate and albuminuria[26]. Methodology of mortality estimates in the GBD 2010 captured only the directly coded deaths due to end-stage kidney disease[3] that refers to most advanced decrease in glomerular filtration rate (CKD stage 5) but represents only a minor part of patients with CKD. That means the GBD 2010 didn’t take into account the mortality rate in patients with CKD stages 1 to 4 that affect more than 10% of general population according high-quality screenings conducted in USA[27], Norway[28], Australia[29], China[30] and many other countries. Moreover, there is a strong evidence that even from early stages of CKD there is a substantial increase in risk of cardiovascular events (coronary heart disease, cerebrovascular disease, peripheral artery disease) and mortality, that is directly attributable to CKD and independent of age, sex, race, smoking, history of cardiovascular disease, diabetes, serum cholesterol, body mass index and blood pressure[31–34]. Thus, considering cardiovascular morbidity and mortality CKD plays a role not only as disease but also as risk factor, that is recognized in the Scientific Statement of American Heart Association “Kidney Disease as a Risk Factor for Development of Cardiovascular Disease”[35] and by the European Guidelines on Cardiovascular Disease Prevention in Clinical Practice[36]. GBD 2010 didn’t assume that markers of CKD (glomerular filtration rate and albuminuria) are recognized as risk factors for cardiovascular mortality and morbidity, while it gave due relevance to impaired glucose metabolism, which was considered as a cause of both deaths due to diabetes and mortality due to other causes related to hyperglycemia. Despite these limitations, the contribution of CKD to global mortality was estimated in 735,600 deaths in 2010, one of the highest increase from 1990 among all diseases. This underlines that CKD has reached an epidemic dimension, in both developed and developing world, that is still poorly recognized by the health policy makers and general medical community [37].

Most probably, rare diseases and genetic disorders were also only partially accounted for in GBD 2010, mainly due to paucity of primary data on their epidemiology. GBD attributed only 510,400 deaths to congenital abnormalities in 2010, while other estimates suggest that as many as 7.9 million children worldwide are born each year with a serious birth defects of genetic or partially genetic origin[38]. Further, 9 out of 10 of those children live in low- and middle income countries[38], while even in the high-income countries only 11% of babies with inborn errors of metabolism could reach adulthood[39].

Diversity in sources of primary data and statistical model assumptions led to significant discrepancies between GBD 2010 estimates and previous assessments by other international research groups. Thus, prominent differences exist for number of deaths due to physical inactivity (3.2 mln by GBD 2010 vs 5.3 mln by Lancet Physical Activity Working Group), HIV/AIDS (1.47 mln by GBD 2010 vs 1.77 mln by UNAIDS), tuberculosis (1.2 mln by GBD 2010 and 1.05 mln by WHO) and malaria (1.17 mln by GBD 2010 vs 0.66 mln by WHO)[3][40-42]. There are also substantial differences between GBD 2010 and CHERG in mortality rates for children under five years of age due to lower respiratory infections, diarrhoeal diseases and malaria[3][43]. Finally, there is a discrepancy in the total number of deaths calculated by GBD 2010 and by WHO — 52.8 mln and 54.8 mln, respectively [3][44]. Although the GBD 2010 authors provided a rationale [3][45-46] for these differences, the harmonization of analytical methods and input data is required both from GBD and different scientific groups with joint collaboration on robust and relevant estimates of diseases and risk factors burden. This harmonization could be substantially accelerated by putting in the public domain primary data and detailed final estimates for all diseases and risk factors, as well as by moving to open source the programming code of DISMOD-MR and other algorithms used in GBD 2010.

While the number of risk factors in GBD 2010 was increased in comparison with previous GBD revisions, still it didn’t include risk factors for 126 of 241 causes of deaths that account for 26.3% of global disease burden[8]. Notably, such paramount risk factors as global climate change, poverty, inequality, weakness of health system, shortage of medical staff, unsafe sex that contributed substantially to major mortality causes were not considered in GBD 2010 due to the lack of data or methodological difficulties for producing robust statistical models. Obviously these important factors need to be taken into account for health policy planning and political agendas, while research for their improvement through timely and sustainable interventions is an absolute priority.

 

Conclusions

The GBD 2010 represents a tremendous achievement in understanding morbidity and mortality patterns in all world regions. GBD 2010 provides a useful tool for health care planning, setting the priorities for research, and triggering the establishment of prevention and treatment strategies for the wide range of diseases, injuries and risk factors. Indirectly, results of GBD 2010 also suggest the importance of modifying medical education system and revising current practices of medical care. Existing shortcomings should be overcome in future revision and update of GBD that, however, would require more strict cooperation in data collection and analysis between governmental and non-governmental organizations.

 

Learning Points

• GBD 2010 Study provided a state of the art understanding of the burden of 67 risk factors and their clusters, 291 diseases and injuries on global, regional and national levels in period from 1990 to 2010 for 187 countries.
• Communicable, maternal, neonatal and nutritional disorders declined over the past 20 years, but are still responsible for every fourth death in the world; injuries accounted for almost every tenth death globally.
• Non-communicable diseases accounted to almost two of every three deaths globally in 2010 (absolute increase by 30.0% in comparison with 1990), although age- and sex-specific death rates declined.
• Number of deaths for the past 20 years are almost doubled for HIV/AIDS, Alzheimer’s disease and other dementias, diabetes mellitus, chronic kidney diseases, atrial fibrillation and flutter, Parkinson’s disease, adverse effects of medical treatment, illicit drug use, peripheral vascular disease, urinary diseases, kidney and other urinary tract cancers, interstitial lung disease and pulmonary sarcoidosis.
• Chronic kidney diseases are still poorly recognized by the health policy makers and general medical community despite their high prevalence, clear diagnostic criteria and established effective treatment.
• Dietary risk factors, high blood pressure, tobacco and alcohol impact for almost half of deaths worldwide.
• Management of mortality risk factors is insufficiently incorporated in the health care policy both at population and individual levels.

 

Acknowledgments

The Authors are very grateful to Dr. Arrigo Schieppati (Unit of Nephrology, Dialysis and Transplantation, Azienda Ospedaliera Papa Giovanni XXIII, Bergamo, Italy) for helpful revision of the manuscript.

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Oct 28th, 2013

Метки: Global Burden of Disease Study, бесплатный полнотекстовый доступ, смертность, эпидемиология