Valery L. Feigin

Global and regional burden of stroke during 1990–2010: findings from the Global Burden of Disease Study 2010

BACKGROUND Although stroke is the second leading cause of death worldwide, no comprehensive and comparable assessment of incidence, prevalence, mortality, disability, and epidemiological trends has been estimated for most regions. We used data from the Global Burden of Diseases, Injuries, and Risk Factors Study 2010 (GBD 2010) to estimate the global and regional burden of stroke during 1990-2010. METHODS We searched Medline, Embase, LILACS, Scopus, PubMed, Science Direct, Global Health Database, the WHO library, and WHO regional databases from 1990 to 2012 to identify relevant studies published between 1990 and 2010.We applied the GBD 2010 analytical technique (DisMod-MR), based on disease-specific, pre-specified associations between incidence, prevalence, and mortality, to calculate regional and country-specific estimates of stroke incidence, prevalence, mortality, and disability-adjusted life-years (DALYs) lost by age group (<75 years, ≥ 75 years, and in total)and country income level (high-income, and low-income and middle-income) for 1990, 2005, and 2010. FINDINGS We included 119 studies (58 from high-income countries and 61 from low-income and middle-income countries). From 1990 to 2010, the age-standardised incidence of stroke significantly decreased by 12% (95% CI 6-17)in high-income countries, and increased by 12% (-3 to 22) in low-income and middle-income countries, albeit nonsignificantly. Mortality rates decreased significantly in both high income (37%, 31-41) and low-income and middle income countries (20%, 15-30). In 2010, the absolute numbers of people with fi rst stroke (16・9 million), stroke survivors (33 million), stroke-related deaths (5・9 million), and DALYs lost (102 million) were high and had significantly increased since 1990 (68%, 84%, 26%, and 12% increase, respectively), with most of the burden (68・6% incident strokes, 52・2% prevalent strokes, 70・9% stroke deaths, and 77・7% DALYs lost) in low-income and middle-income countries. In 2010, 5・2 million (31%) strokes were in children (aged <20 years old) and young and middle-aged adults(20-64 years), to which children and young and middle-aged adults from low-income and middle-income countries contributed almost 74 000 (89%) and 4・0 million (78%), respectively, of the burden. Additionally, we noted significant geographical differences of between three and ten times in stroke burden between GBD regions and countries. More than 62% of new strokes, 69・8% of prevalent strokes, 45・5% of deaths from stroke, and 71・7% of DALYs lost because of stroke were in people younger than 75 years. INTERPRETATION Although age-standardised rates of stroke mortality have decreased worldwide in the past two decades,the absolute number of people who have a stroke every year, stroke survivors, related deaths, and the overall global burden of stroke (DALYs lost) are great and increasing. Further study is needed to improve understanding of stroke determinants and burden worldwide, and to establish causes of disparities and changes in trends in stroke burden between countries of different income levels. FUNDING Bill & Melinda Gates Foundation.

Worldwide stroke incidence and early case fatality reported in 56 population-based studies: a systematic review

This systematic review of population-based studies of the incidence and early (21 days to 1 month) case fatality of stroke is based on studies published from 1970 to 2008. Stroke incidence (incident strokes only) and case fatality from 21 days to 1 month post-stroke were analysed by four decades of study, two country income groups (high-income countries and low to middle income countries, in accordance with the World Banks country classification) and, when possible, by stroke pathological type: ischaemic stroke, primary intracerebral haemorrhage, and subarachnoid haemorrhage. This Review shows a divergent, statistically significant trend in stroke incidence rates over the past four decades, with a 42% decrease in stroke incidence in high-income countries and a greater than 100% increase in stroke incidence in low to middle income countries. In 2000-08, the overall stroke incidence rates in low to middle income countries have, for the first time, exceeded the level of stroke incidence seen in high-income countries, by 20%. The time to decide whether or not stroke is an issue that should be on the governmental agenda in low to middle income countries has now passed. Now is the time for action.

Stroke epidemiology: a review of population-based studies of incidence, prevalence, and case-fatality in the late 20th century

This overview of population-based studies of incidence, prevalence, mortality, and case-fatality of stroke was based on studies from 1990. Incidence (first stroke in an individuals lifetime) and prevalence were computed by age, sex, and stroke type. Age-standardised incidence and prevalence with the corresponding 95% CI were plotted for each study to facilitate comparisons. The review shows that the burden of stroke is high and is likely to increase in future decades as a result of demographic and epidemiological transitions in populations. The main features of stroke epidemiology include modest geographical variation in incidence, prevalence, and case-fatality among the--predominantly white--populations studied so far, and a stabilisation or reversal in the declining secular trends in the pre-1990s rates, especially in older people. However, further research that uses the best possible methods to study the incidence, risk factors, and outcome of stroke are urgently needed in other populations of the world, especially in less developed countries where the risk of stroke is high, lifestyles are changing rapidly, and population restructuring is occurring.

Blood Pressure and Stroke An Overview of Published Reviews

Background— The last few years have seen a considerable increase in the amount of information available concerning blood pressure (BP) and stroke associations. This article provides an overview of published reviews of the effects on stroke seen in trials of BP-lowering drugs and compares these with the results available from cohort studies. Summary of Review— We present a review of major overviews of prospective cohort studies and an updated meta-analysis of >40 randomized controlled trials of BP lowering, which included >188 000 participants and approximately 6800 stroke events. Cohort studies now indicate that in the Asia Pacific region as well as in North America and Western Europe, each 10 mm Hg lower systolic BP is associated with a decrease in risk of stroke of approximately one third in subjects aged 60 to 79 years. The association is continuous down to levels of at least 115/75 mm Hg and is consistent across sexes, regions, and stroke subtypes and for fatal and nonfatal events. The proportional association is age dependent but is still strong and positive in those aged 80 years. Data from randomized controlled trials, in which mean age at event was approximately 70 years, indicate that a 10 mm Hg reduction in systolic BP is associated with a reduction in risk of stroke of approximately one third. Per mm Hg systolic BP reduction, the relative benefits for stroke appear similar between agents, by baseline BP levels, and whether or not individuals have a past history of cardiovascular disease. There is, however, evidence of greater benefit with a larger BP reduction. Conclusions— The epidemiologically expected benefits of BP lowering for stroke risk reduction are broadly consistent across a range of different population subgroups. There are greater benefits from larger BP reductions, and initiating and maintaining BP reduction for stroke prevention is a more important issue than choice of initial agent.

Risk factors for subarachnoid hemorrhage : An updated systematic review of epidemiological studies

Background and Purpose— After a 1996 review from our group on risk factors for subarachnoid hemorrhage (SAH), much new information has become available. This article provides an updated overview of risk factors for SAH. Methods— An overview of all longitudinal and case-control studies of risk factors for SAH published in English from 1966 through March 2005. We calculated pooled relative risks (RRs) for longitudinal studies and odds ratios (ORs) for case-control studies, both with corresponding 95% CIs. Results— We included 14 longitudinal (5 new) and 23 (12 new) case-control studies. Overall, the studies included 3936 patients with SAH (892 cases in 14 longitudinal studies and 3044 cases in 23 case-control studies) for analysis. Statistically significant risk factors in longitudinal and case-control studies were current smoking (RR, 2.2 [1.3 to 3.6]; OR, 3.1 [2.7 to 3.5]), hypertension (RR, 2.5 [2.0 to 3.1]; OR, 2.6 [2.0 to 3.1]), and excessive alcohol intake (RR, 2.1 [1.5 to 2.8]; OR, 1.5 [1.3 to 1.8]). Nonwhite ethnicity was a less robust risk factor (RR, 1.8 [0.8 to 4.2]; OR, 3.4 [1.0 to 11.9]). Oral contraceptives did not affect the risk (RR, 5.4 [0.7 to 43.5]; OR, 0.8 [0.5 to 1.3]). Risk reductions were found for hormone replacement therapy (RR, 0.6 [0.2 to 1.5]; OR, 0.6 [0.4 to 0.8]), hypercholesterolemia (RR, 0.8 [0.6 to 1.2]; OR, 0.6 [0.4 to 0.9]), and diabetes (RR, 0.3 [0 to 2.2]; OR, 0.7 [0.5 to 0.8]). Data were inconsistent for lean body mass index (RR, 0.3 [0.2 to 0.4]; OR, 1.4 [1.0 to 2.0]) and rigorous exercise (RR, 0.5 [0.3 to 1.0]; OR, 1.2 [1.0 to 1.6]). In the studies included in the review, no other risk factors were available for the meta-analysis. Conclusions— Smoking, hypertension, and excessive alcohol remain the most important risk factors for SAH. The seemingly protective effects of white ethnicity compared to nonwhite ethnicity, hormone replacement therapy, hypercholesterolemia, and diabetes in the etiology of SAH are uncertain.

Global and regional burden of first-ever ischaemic and haemorrhagic stroke during 1990–2010: findings from the Global Burden of Disease Study 2010

Summary Background The burden of ischaemic and haemorrhagic stroke varies between regions and over time. With differences in prognosis, prevalence of risk factors, and treatment strategies, knowledge of stroke pathological type is important for targeted region-specific health-care planning for stroke and could inform priorities for type-specific prevention strategies. We used data from the Global Burden of Diseases, Injuries, and Risk Factors Study 2010 (GBD 2010) to estimate the global and regional burden of first-ever ischaemic and haemorrhagic stroke during 1990–2010. Methods We searched Medline, Embase, LILACS, Scopus, PubMed, Science Direct, Global Health Database, the WHO library, and regional databases from 1990 to 2012 to identify relevant studies published between 1990 and 2010. We applied the GBD 2010 analytical technique (DisMod-MR) to calculate regional and country-specific estimates for ischaemic and haemorrhagic stroke incidence, mortality, mortality-to-incidence ratio, and disability-adjusted life-years (DALYs) lost, by age group (aged <75 years, ≥75 years, and in total) and country income level (high-income and low-income and middle-income) for 1990, 2005, and 2010. Findings We included 119 studies (58 from high-income countries and 61 from low-income and middle-income countries). Worldwide, the burden of ischaemic and haemorrhagic stroke increased significantly between 1990 and 2010 in terms of the absolute number of people with incident ischaemic and haemorrhagic stroke (37% and 47% increase, respectively), number of deaths (21% and 20% increase), and DALYs lost (18% and 14% increase). In the past two decades in high-income countries, incidence of ischaemic stroke reduced significantly by 13% (95% CI 6–18), mortality by 37% (19–39), DALYs lost by 34% (16–36), and mortality-to-incidence ratios by 21% (10–27). For haemorrhagic stroke, incidence reduced significantly by 19% (1–15), mortality by 38% (32–43), DALYs lost by 39% (32–44), and mortality-to-incidence ratios by 27% (19–35). By contrast, in low-income and middle-income countries, we noted a significant increase of 22% (5–30) in incidence of haemorrhagic stroke and a 6% (–7 to 18) non-significant increase in the incidence of ischaemic stroke. Mortality rates for ischaemic stroke fell by 14% (9–19), DALYs lost by 17% (–11 to 21%), and mortality-to-incidence ratios by 16% (–12 to 22). For haemorrhagic stroke in low-income and middle-income countries, mortality rates reduced by 23% (–18 to 25%), DALYs lost by 25% (–21 to 28), and mortality-to-incidence ratios by 36% (–34 to 28). Interpretation Although age-standardised mortality rates for ischaemic and haemorrhagic stroke have decreased in the past two decades, the absolute number of people who have these stroke types annually, and the number with related deaths and DALYs lost, is increasing, with most of the burden in low-income and middle-income countries. Further study is needed in these countries to identify which subgroups of the population are at greatest risk and who could be targeted for preventive efforts.

Estimates and 25-year trends of the global burden of disease attributable to ambient air pollution: an analysis of data from the Global Burden of Diseases Study 2015.

Summary Background Exposure to ambient air pollution increases morbidity and mortality, and is a leading contributor to global disease burden. We explored spatial and temporal trends in mortality and burden of disease attributable to ambient air pollution from 1990 to 2015 at global, regional, and country levels. Methods We estimated global population-weighted mean concentrations of particle mass with aerodynamic diameter less than 2·5 μm (PM2·5) and ozone at an approximate 11 km × 11 km resolution with satellite-based estimates, chemical transport models, and ground-level measurements. Using integrated exposure–response functions for each cause of death, we estimated the relative risk of mortality from ischaemic heart disease, cerebrovascular disease, chronic obstructive pulmonary disease, lung cancer, and lower respiratory infections from epidemiological studies using non-linear exposure–response functions spanning the global range of exposure. Findings Ambient PM2·5 was the fifth-ranking mortality risk factor in 2015. Exposure to PM2·5 caused 4·2 million (95% uncertainty interval [UI] 3·7 million to 4·8 million) deaths and 103·1 million (90·8 million 115·1 million) disability-adjusted life-years (DALYs) in 2015, representing 7·6% of total global deaths and 4·2% of global DALYs, 59% of these in east and south Asia. Deaths attributable to ambient PM2·5 increased from 3·5 million (95% UI 3·0 million to 4·0 million) in 1990 to 4·2 million (3·7 million to 4·8 million) in 2015. Exposure to ozone caused an additional 254 000 (95% UI 97 000–422 000) deaths and a loss of 4·1 million (1·6 million to 6·8 million) DALYs from chronic obstructive pulmonary disease in 2015. Interpretation Ambient air pollution contributed substantially to the global burden of disease in 2015, which increased over the past 25 years, due to population ageing, changes in non-communicable disease rates, and increasing air pollution in low-income and middle-income countries. Modest reductions in burden will occur in the most polluted countries unless PM2·5 values are decreased substantially, but there is potential for substantial health benefits from exposure reduction. Funding Bill & Melinda Gates Foundation and Health Effects Institute.

Incidence of traumatic brain injury in New Zealand: a population-based study

BACKGROUND Traumatic brain injury (TBI) is the leading cause of long-term disability in children and young adults worldwide. However, accurate information about its incidence does not exist. We aimed to estimate the burden of TBI in rural and urban populations in New Zealand across all ages and TBI severities. METHODS We did a population-based incidence study in an urban (Hamilton) and rural (Waikato District) population in New Zealand. We registered all cases of TBI (admitted to hospital or not, fatal or non-fatal) that occurred in the population between March 1, 2010, and Feb 28, 2011, using multiple overlapping sources of information. We calculated incidence per 100,000 person-years with 95% CIs using a Poisson distribution. We calculated rate ratios [RRs] to compare the age-standardised rates between sex, ethnicity, and residency (urban, rural) groups. We used direct standardisation to age-standardise the rates to the world population. RESULTS The total incidence of TBI per 100,000 person-years was 790 cases (95% CI 749-832); incidence per 100,000 person-years of mild TBI was 749 cases (709-790) and of moderate to severe TBI was 41 cases (31-51). Children (aged 0-14 years) and adolescents and young adults (aged 15-34 years) constituted almost 70% of all TBI cases. TBI affected boys and men more than women and girls (RR 1·77, 95% CI 1·58-1·97). Most TBI cases were due to falls (38% [516 of 1369]), mechanical forces (21% [288 of 1369]), transport accidents (20% [277 of 1369]), and assaults (17% [228 of 1369]). Compared with people of European origin, Maori people had a greater risk of mild TBI (RR 1·23, 95% CI 1·08-1·39). Incidence of moderate to severe TBI in the rural population (73 per 100,000 person-years [95% CI 50-107) was almost 2·5 times greater than in the urban population (31 per 100 000 person-years [23-42]). INTERPRETATION Our findings suggest that the incidence of TBI, especially mild TBI, in New Zealand is far greater than would be estimated from the findings of previous studies done in other high-income countries. Our age-specific and residency-specific data for TBI incidence overall and by mechanism of injury should be considered when planning prevention and TBI care services. FUNDING Health Research Council of New Zealand.

Demographic and Epidemiologic Drivers of Global Cardiovascular Mortality

BACKGROUND Global deaths from cardiovascular disease are increasing as a result of population growth, the aging of populations, and epidemiologic changes in disease. Disentangling the effects of these three drivers on trends in mortality is important for planning the future of the health care system and benchmarking progress toward the reduction of cardiovascular disease. METHODS We used mortality data from the Global Burden of Disease Study 2013, which includes data on 188 countries grouped into 21 world regions. We developed three counterfactual scenarios to represent the principal drivers of change in cardiovascular deaths (population growth alone, population growth and aging, and epidemiologic changes in disease) from 1990 to 2013. Secular trends and correlations with changes in national income were examined. RESULTS Global deaths from cardiovascular disease increased by 41% between 1990 and 2013 despite a 39% decrease in age-specific death rates; this increase was driven by a 55% increase in mortality due to the aging of populations and a 25% increase due to population growth. The relative contributions of these drivers varied by region; only in Central Europe and Western Europe did the annual number of deaths from cardiovascular disease actually decline. Change in gross domestic product per capita was correlated with change in age-specific death rates only among upper-middle income countries, and this correlation was weak; there was no significant correlation elsewhere. CONCLUSIONS The aging and growth of the population resulted in an increase in global cardiovascular deaths between 1990 and 2013, despite a decrease in age-specific death rates in most regions. Only Central and Western Europe had gains in cardiovascular health that were sufficient to offset these demographic forces. (Funded by the Bill and Melinda Gates Foundation and others.).

The Global Burden of Mental, Neurological and Substance Use Disorders: An Analysis from the Global Burden of Disease Study 2010

Background The Global Burden of Disease Study 2010 (GBD 2010), estimated that a substantial proportion of the world’s disease burden came from mental, neurological and substance use disorders. In this paper, we used GBD 2010 data to investigate time, year, region and age specific trends in burden due to mental, neurological and substance use disorders. Method For each disorder, prevalence data were assembled from systematic literature reviews. DisMod-MR, a Bayesian meta-regression tool, was used to model prevalence by country, region, age, sex and year. Prevalence data were combined with disability weights derived from survey data to estimate years lived with disability (YLDs). Years lost to premature mortality (YLLs) were estimated by multiplying deaths occurring as a result of a given disorder by the reference standard life expectancy at the age death occurred. Disability-adjusted life years (DALYs) were computed as the sum of YLDs and YLLs. Results In 2010, mental, neurological and substance use disorders accounted for 10.4% of global DALYs, 2.3% of global YLLs and, 28.5% of global YLDs, making them the leading cause of YLDs. Mental disorders accounted for the largest proportion of DALYs (56.7%), followed by neurological disorders (28.6%) and substance use disorders (14.7%). DALYs peaked in early adulthood for mental and substance use disorders but were more consistent across age for neurological disorders. Females accounted for more DALYs in all mental and neurological disorders, except for mental disorders occurring in childhood, schizophrenia, substance use disorders, Parkinson’s disease and epilepsy where males accounted for more DALYs. Overall DALYs were highest in Eastern Europe/Central Asia and lowest in East Asia/the Pacific. Conclusion Mental, neurological and substance use disorders contribute to a significant proportion of disease burden. Health systems can respond by implementing established, cost effective interventions, or by supporting the research necessary to develop better prevention and treatment options.