http://circres.ahajournals.org/content/120/3/439?etoc=
Abstract
On
the basis of the GBD (Global Burden of Disease) 2013 Study, this
article provides an overview of the global, regional, and
country-specific burden of stroke by sex and age groups, including
trends in stroke burden from 1990 to 2013, and outlines recommended
measures to reduce stroke burden. It shows that although stroke
incidence, prevalence, mortality, and disability-adjusted life-years
rates tend to decline from 1990 to 2013, the overall stroke burden in
terms of absolute number of people affected by, or who remained disabled
from, stroke has increased across the globe in both men and women of
all ages. This provides a strong argument that “business as usual” for
primary stroke prevention is not sufficiently effective. Although
prevention of stroke is a complex medical and political issue, there is
strong evidence that substantial prevention of stroke is feasible in
practice. The need to scale-up the primary prevention actions is urgent.
Introduction
Evidence-based
approaches to organization and planning of stroke care and services
require accurate ongoing data on stroke incidence, prevalence, and
outcomes. The best sources of such data are population-based studies
that meet “gold-standard” criteria and are continuously repeated over
time,1 as stroke epidemiology is changing rapidly.2
However, such studies are expensive and require expertise for their
proper design and execution. That is why no such studies have been done
in most countries, especially in the developing countries and over a
long period of time. From the public health perspective, there is also a
need to monitor stroke burden on a global scale and compare burden
between different countries and regions over time, including trends and
projections relative to other major diseases. To address these issues
and fill the gaps in disease burden estimates across all countries, the
GBD (Global Burden of Disease) Study was set up in 1992 within the
Institute for Health Metrics and Evaluation of the University of
Washington.3
During the period of time from 1990 to present, the GBD Study has
developed (and continuously updated) a large database and advanced
methodologies for modeling the burden of a wide range of diseases and
their risk factors in 188 countries.4–6
This article summarizes GBD 2013 Study findings on stroke burden
recently published in the special open access issue of the journal Neuroepidemiology7
and outlines recommended measures to reduce stroke burden. In these
publications, stroke burden is reported in terms of incidence of
first-ever stroke (ischemic stroke [IS] and hemorrhagic stroke [HS]
separately, and total stroke), prevalence, mortality, and
disability-adjusted life-years (DALYs) in children (0–19 years of age),8 young to middle-aged adults (20–64 years of age),9 and overall for all ages combined2 and by sex10
from 1990 to 2013. All burden estimates were reported with
corresponding 95% uncertainty intervals (UI). In lay terms, DALYs mean
the number of years lost because of disability. The diagnostic criteria
for stroke used in the GBD analyses are based on the World Health
Organization (WHO) definition of stroke.11
Details on the methodology of the GBD stroke burden estimates,
including diagnostic criteria and data sources, have been published
elsewhere.12,13
Overall Overview of the Global, Regional, and Country-Specific Burden of Stroke, Including Trends in stroke Burden From 1990 to 2013
In
2013, stroke was the second most common cause of deaths (11.8% of all
deaths [95% UI, 10.9–13.0%]) worldwide, after ischemic heart disease
(14.8% of all deaths [95% UI, 13.4–15.8]), and the third most common
cause of disability (4.5% of DALYs from all cause [95% UI, 4.1–5.2])
after ischemic heart disease (6.1% [95% UI, 5.5–6.8]). Overall, the GBD
2013 stroke burden estimates confirmed previous observations about the
significant increase in stroke burden in the world over the last two and
half decades,14 especially in developing countries,14,15 and substantial geographical variations in stroke burden.14,15 As shown in Figure 1, the highest stroke DALYs and mortality rates in 2013 were observed in Russia and Eastern European countries.
Figure 1.
Age-standardized
stroke disability-adjusted life-years (DALYs) and mortality rates per
100,000 person-years in various regions of the world in 2013 (both
sexes, all ages)
Although
stroke mortality and DALYs rates have declined from 142/100,000
person-years (95% UI, 129–154) and 2431/100,000 person-years (95% UI,
2224–2631), respectively, in 1990 to 110/100,000 person-years (95% UI,
102–122) and 1807 person-years (95% UI, 1667–1992), in 2013 the absolute
number of people who died from stroke, remained disabled from stroke
(as measured by DALYs), affected by stroke (as measured by incidence of
new strokes), or survived stroke has increased statistically significant
(1.4- to 1.8-folds for IS and 1.2- to 1.9-folds for HS). Globally, in
2013 there were almost 25.7 million stroke survivors (71% with IS), 6.5
million deaths from stroke (51% died from IS), 113 million DALYs due to
stroke (58% due to IS), and 10.3 million new strokes (67% IS). Improved
stroke care, aging, and growth of the population combined with the
increased prevalence of many modifiable stroke risk factors16 are likely to be the main drivers in the increased number of stroke survivors and people affected by stroke.
Proportional (%) contribution of DALYs from stroke to DALYs from all other causes in 2013 (Figure 2)
varied between different countries but was largest in developing
countries, especially Russia, Eastern European countries, and East Asian
countries, ranging from 11.6% to 12.7% in North Korea, Macedonia,
Bulgaria, and Georgia to 8.4% to 9.7% in China and Indonesia. As also
shown in Figure 2,
proportional contribution of stroke-related DALYs compared with 10
other leading causes of DALYs in 2013 was the second highest and not
statistically significantly different from ischemic heart disease,
especially in developed countries.
Figure 2.
Proportional
contribution (%) of age-standardized disability-adjusted life-years
(DALYs) from stroke to DALYs in 2013. COPD indicates chronic obstructive
pulmonary disease.
The
proportional contribution of stroke-related DALYs and deaths due to
stroke compared with all diseases also increased from 1990 (3.5% [95%
UI, 3.1–4.0] and 9.7% [95% UI, 8.5–10.7], respectively) to 2013 (4.6%
[95% UI, 4.0–5.3] and 11.8% [95% UI, 10.5–13.3], respectively), but
there was a diverging trend in developed and developing countries with a
significant increase in DALYs and deaths in developing countries (from
0.9 [95% UI, 0.8–1.0] and 2.1 [95% UI, 1.9–2.4] for DALYs and 3.0 [95%
UI, 2.6–3.4] and 5.2 [95% UI, 4.6–5.8] for deaths in 1990 to 1.7 [95%
UI, 1.3–1.9], 2.8 [95% UI, 2.5–3.3] for DALYs and 5.2 [95% UI, 4.2–5.7],
6.4 [95% UI 5.8–7.5] for IS and HS deaths, respectively, in 2013).
There was no measurable change in the proportional contribution of DALYs
and deaths from stroke in developed countries over the 23-year study
period.
This GBD and other reports17,18
indicate that stroke in the young and middle-aged adults are not
decreasing or may even be increasing, likely because of increase in
metabolic risk factors, including obesity and diabetes mellitus, among
the young. The GBD findings also suggest that stroke should no longer be
regarded as a disease of the elderly: two thirds of all strokes occur
among persons <70 age.="" of="" p="" years="">
Sex Differences in Stroke Burden in the World, Including Trends From 1990 to 2013
The
GBD 2013 Study identified significant disparities in stroke burden
between men and women, with men having consistently greater incidence of
IS than women (133/100,000 person-years [95% UI, 125–143] and
99/100,000 person-years [95% UI, 92–107], respectively). Although
incidence rates of both IS and HS in 2013 were lower than that in 1990
for both men and women, the number of incident and prevalent strokes was
significantly greater in 2013 compared with 1990 for both men and
women, IS and HS (Table).
The risk (rate of stroke) and absolute number of IS and HS events (both
incident and prevalent strokes) in 2013 were significantly greater in
men than in women (except no statistically significant excess of
incident IS events in men), suggesting changes in the sex distribution
of stroke burden in the world. Age-adjusted incidence rates seemed to be
declining worldwide at a faster rate in women than in men, but the
reasons for that remain unclear.
Table.
Absolute
Number of Women and Men With Stroke (in Millions) in the World by
Stroke Type in 1990 and 2013 (95% Uncertainty Limits Are in Brackets)
In 2013, proportional (%) contribution of stroke-related deaths to deaths from all causes (Figure 3)
in women was greater than in men and highest in Eastern European
countries, Asia East, and North Africa, where it ranged from 35% (95%
UI, 29–38) in Macedonia and 32% (95% UI, 28–35) in Vietnam to 16% to 18%
in North Africa (95% UI, 14–20), and lowest in Sub-Saharan Africa
(range from 3 to 11) and Papua New Guinea (2% [95% UI, 1–3]).
Figure 3.
Proportional (%) contribution of stroke-related deaths to deaths from all causes in men and women in 2013.
There were also noticeable sex differences in the proportional contribution of stroke-related DALYs to DALYs from all causes (Figure 4).
Although in men it was highest in Bulgaria, Macedonia, Georgia, China,
and North Korea (11%–12%), in women it was not high in China (9% [95%
UI, 7–10]).
Figure 4.
Proportional
contribution (%) of age-standardized disability-adjusted life-years
(DALYs) from stroke to DALYs from all causes in 2013 by sex.
Overview of the Global, Regional, and Country-Specific Burden of Stroke in Adults, Including Trends in Stroke Burden From 1990 to 2013
Globally,
between 1990 and 2013, there were significant increases in prevalent
cases, total deaths, and DALYs because of HS and IS in younger adults
aged 20 to 64 years. In 2013, in younger adults aged 20 to 64 years, the
global prevalence of HS was 3.7 million cases [95% UI, 3.5–3.9] and IS
was 7.3 million cases [95% UI, 7.0–7.6]. Globally, between 1990 and
2013, there were significant increases in absolute numbers and
prevalence rates of both HS and IS for younger adults. There were 1.5
million [95% UI, 1.3–1.7] stroke deaths globally among younger adults,
but the number of deaths from HS (1.0 [95% UI, 0.9–1.2]) was
significantly higher than the number of deaths from IS (0.4 million
[0.4–0.5]).
Death and DALY rates declined in both
developed and developing countries, but a significant increase in
absolute numbers of stroke deaths among younger adults was detected in
developing countries, where most of the burden of stroke resided. There
was a 20.1% [95% UI, −23.6 to 10.3] decline in the number of total
stroke deaths among younger adults in developed countries, but a 36.7%
[95% UI, 26.3–48.5] increase in developing countries. Percentage changes
in deaths and DALYs in younger adults between 1990 and 2013 in
developed and developing countries by 5-year age group also showed
diverging trends (Figure 5),
that is, increase of the percentage change toward greater burden with
aging in developing countries and decrease of the percentage change
toward the reduction of the burden with aging in developed countries.
Death rates for all strokes among younger adults declined significantly
in developing countries from 47/100,00 person-years [95% UI, 42.6–51.7]
in 1990 to 39/100,000 person-years [95%UI, 35.0–43.8] in 2013. Death
rates for all strokes among younger adults also declined significantly
in developed countries from 33.3 [95% UI, 29.8–37.0] in 1990 to 23.5
[95% UI, 21.1–26.9] in 2013. Although the trends in declining death and
DALY rates in developing countries are encouraging, these regions still
fall far behind developed regions of the world.
Figure 5.
Percentage
change in age-standardized death and disability-adjusted life-year
rates in younger adults between 1990 and 2013 by 5-year age group in
developed and developing countries.
In
2013, the greatest burden of stroke among younger adults was because of
HS. A significant decrease in HS death rates for younger adults was
seen only in developed countries between 1990 and 2013 (19.8 [95% UI,
16.9–22.6] and 13.7 [95% UI, 12.1–15.9]) per 100,000). No significant
change was detected in IS death rates among younger adults. The total
DALYs from all strokes in 20 to 64 year olds were 51.0 million [95% UI,
46.6–57.3]. Globally, there was a 24.4% [95%UI, 16.6–33.8] increase in
total DALYs for this age group, with a 20% [95% UI, 11.7–31.1] and 37.3%
[95% UI, 23.4–52.2] increase in HS and IS numbers, respectively.
Overview of the Global, Regional, and Country-Specific Burden of Stroke in Children, Including Trends in Stroke Burden From 1990 to 2013
Globally,
between 1990 and 2013, there was a significant increase in the absolute
number of prevalent childhood strokes while absolute numbers and rates
of both deaths and DALYs declined significantly. In 2013, there were
almost 100,000 prevalent cases [95% UI, 91,000–106,000] of childhood IS
and 68,000 [95% UI, 63,000–72,000] prevalent cases of childhood HS,
reflecting an increase of ≈35% in the absolute numbers of prevalent
childhood strokes since 1990. There were ≈33,000 [95% UI, 29,000–39,000]
deaths and 2.6 million [95% UI, 2.3–3.1] DALYs because of childhood
stroke in 2013 globally, reflecting ≈200% decrease in the absolute
numbers of death and DALYs in childhood stroke since 1990. Between 1990
and 2013, there were significant increases in the global prevalence
rates of childhood IS, as well as significant decreases in the global
death and DALY rates of all strokes in 0 to 19 year olds. Males showed a
trend toward higher childhood stroke death rates (1.5/100,000
person-years [1.3–1.8]) than females (1.1/100,000 person-years [0.9–1.5]
per 100,000) and higher childhood stroke DALYs rates (120.1/100,000
person-years [100.8–143.4]) than females (90.9/100,000 person-years
[74.6–122.4]) globally in 2013.
Although the gap in childhood stroke burden between developed and developing countries is closing (Figure 6),
the 2013 childhood stroke burden in terms of absolute numbers of
prevalent strokes, deaths, and DALYs remained much higher in developing
countries. Although prevalence rates for childhood IS and HS decreased
significantly in developed countries, in developing countries, a decline
was seen only in HS, with no change in IS prevalence rates. The
childhood stroke DALY rates in 2013 were 13.3/100,000 person-years [95%
UI, 10.6–17.1] for IS and 92.7/100,000 person-years [95% UI, 80.5–109.7]
for HS. Although globally the prevalence of childhood IS compared with
childhood HS was similar, the death rate and DALYs rate of HS was 6- to
7-fold higher than that of IS. In 2013, the prevalence rate of childhood
IS and HS was significantly higher in developed countries than that in
developing countries. Conversely, both death and DALY rates for all
strokes were significantly lower in developed countries than in
developing countries in 2013.
Figure 6.
Trends
in age-standardized death and disability-adjusted life-year (DALY)
rates (per 100,000 people per year) in childhood stroke between 1990 and
2013 in developed and developing countries.
Call for Action
The
patterns of the main categories of diseases have shifted considerably
during the last few decades. The GBD project and other studies have
shown a decline in infectious and nutritional disorders, and a rise in
noncommunicable diseases (NCD), such as stroke, heart disease, cancer,
diabetes mellitus, and chronic obstructive pulmonary disease.6
The most recent GBD estimates showed that during the last two and half
decades, the number of stroke survivors and people with incident stroke
have increased 50% to 100%, thus indicating that currently used primary
stroke prevention strategies are not sufficiently effective and require a
serious revision. Projections demonstrate that the NCDs will be
increasingly prevalent in the next decades and will reach epidemic
proportions, which will seriously influence global public health, and
furthermore have substantial effects on social and economic
development—unless urgent actions are undertaken. Fortunately, the core
NCDs share one important element: they are all highly preventable. In
the past, epidemiological global data on stroke have often been included
under the term “cardiovascular disease” without further subdivision
into the 2 main constituents, such as heart disease and stroke. The
major implications of each of these disorders for global health warrant
their recognition as stand-alone diseases that should be accounted for
separately, rather than embedded under an umbrella term that is often
not well understood.
A key to reducing the global burden
of stroke is renewed emphasis on stroke prevention. Whereas each of the
NCDs require specific management and treatment when they occur, the
prevention of NCDs share many common features because the main risk
factors are mostly similar. For stroke, heart disease, diabetes
mellitus, cancer, and pulmonary diseases, 4 modifiable lifestyle risk
factors are of major importance: tobacco use, unhealthy diet, physical
inactivity, and harmful use of alcohol. The WHO has established the “4
by 4” principle of 4 core NCDs (cardiovascular disease, cancer, diabetes
mellitus, pulmonary diseases) and 4 major modifiable risk factors in
their list of “best buys”: (mass actions on the lifestyle risk factors
are the most cost- effective means of prevention).19 This cluster of diseases and risk factors are prioritized by the WHO in its Global Action Plan on NCDs.20 For stroke, other major risk factors include hypertension, which is twice as important for stroke as for coronary heart disease21; and atrial fibrillation, which increases in importance with increasing age.
The
major threat to global health and the implications for society was
increasingly recognized from around the year 2000 onwards and lead to
the landmark event of the adoption of the United Nations (UN)
declaration on NCDs in September 2011.22
This event clearly marked that stroke and NCDs not only constitute a
medical but also a political and developmental issue of global
importance. With the political declaration, the UN member states
committed to take strong action on the NCDs. The task to lead the
implementation and monitoring of the UN declaration was given to the
WHO, who issued the WHO Global Action plan that included a set of global
targets for lifestyle risk factors and health system improvements to
achieve the overall goal of a 25% reduction in premature NCD mortality
by the year 2025. Stroke prevention should not be a stand-alone isolated
issue, but be a part of the common actions now in progress on the major
NCD risk factors. Only by joining forces with other initiatives for
NCDs prevention will stroke prevention have its full impact. The major
principles in prevention are similar for stroke and other types of
cardiovascular disease.23
The
UN declaration called for a 25% relative reduction in premature
mortality from NCDs, including stroke, by the year 2025. However, the
other stroke epidemiological metrics should not be forgotten. The most
important primary health goal for stroke is clearly a reduction in
stroke incidence—prevention is always better than cure. However, the
need for effective therapies in the acute phase (stroke unit management,
thrombolytic, and other reperfusion therapies), as well as
rehabilitation and long-term follow-up efforts to prevent stroke
recurrence and improve functional outcomes should be recognized as
important measures to substantially reduce the burden of stroke in
people who have developed or survived stroke. As one-third of all
strokes occur in persons who have had a previous cerebrovascular event,
adequate attention should be paid to secondary stroke prevention. This
should include measures to ensure adherence to the recommended (evidence
based) poststroke and transient ischemic attack surgical management (if
indicated), medications, and lifestyle modifications. The world’s first
global stroke services guidelines (The World Stroke Organization Global
Stroke Services Guidelines and Action Plan) have recently been
published and provide a listing of essential components of care at
different levels of services.24
The document recognizes 3 levels of stroke care: minimal (stroke care
delivery is based at a local clinic staffed predominantly by
nonphysicians, and much of the emphasis is placed bedside clinical
skills, on teaching, and prevention; there is a lack of diagnostics,
such as computed tomographic scan, stroke units, thrombolytic therapies,
basic secondary stroke prevention, and rehabilitation), essential
(offers access to a computed tomographic scan, physicians, and the
potential for acute thrombolytic therapy; however, stroke expertise may
still be difficult to access; the bulk of evidence-based therapies for
stroke is available at that level), and advanced (availability of
multidisciplinary stroke expertise, multimodal imaging, and
comprehensive therapies, eg, neurosurgical interventions and
thrombectomy). The world map of stroke services is not precisely known
at present, but a high proportion of populations is estimated to have
access only to minimal stroke services. It is now urgent to change
minimal services to essential services in all regions.
Several
actors are responsible for ensuring that the call for action on stroke
will be effective and lead to improvements in stroke metrics.
Governments have the main responsibility and have the power to influence
environmental (eg, air pollution), social (eg, poverty, racial/ethnic
inequality in health care, education, employment, housing, etc.),
medical (provision of adequate health services), and lifestyle factors
(eg, smoking, nutrition, and physical activity) through legislation and
taxation of tobacco, alcohol, and food contents (salt, sugar, and
saturated fats). One still unmet need also within the responsibility of
governments is adequate funding of stroke research, including primary
stroke prevention research. However, in spite of stroke being a leading
cause of death and disability, the volume of funding for stroke research
(including primary stroke prevention research) is low in comparison
with that spent on cancer or coronary heart disease.25
Health systems have the responsibility to identify risk factors that
require medical contacts for their detection and treatment (eg, elevated
blood pressure, atrial fibrillation, and symptomatic carotid artery
stenosis) to influence risk factors for the substantial part of the
population that already have an NCD or a risk factor that requires
regular medical contacts. Nongovernmental organizations, such as the
World Stroke Organisation and academia, have important responsibilities
in providing adequate scientifically based advice on prevention,
practices, management, and therapies. Academia also has the
responsibility to develop technological advances, such as the Stroke
Riskometer app,26
to help individuals to recognize their own risk factors, calculate the
future risk of stroke, and provide targeted advice on how to lower the
risk.27 Thus, the responsibilities to a decreased global burden of stroke are shared.
It has been estimated that with effective actions on common lifestyle factors, at least half of all strokes may be prevented.28
Prevention of stroke is a complex medical and a political issue—but
there is strong evidence that substantial prevention of stroke is
feasible in practice. The need to scale-up the actions is urgent. Stroke
prevention has entered a new era, with stroke being identified as one
of the prioritized NCDs in the WHO and UN actions on NCDs.
Sources of Funding
This
article and some reported figures were based on research supported by
the Bill and Melinda Gates Foundation; Prof Feigin was partly funded by
the Health Research Council of New Zealand, the Brain Research New
Zealand Centre of Research Excellence and Ageing Well Programme of the
National Science Challenge, Ministry of Business, Innovation and
Employment of New Zealand.
Disclosures
None.
Footnotes
- The views expressed in this article are those of the authors and do not necessarily represent the views of the National Heart, Lung, and Blood Institute, National Institutes of Health, or the US Department of Health and Human Services.
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