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Global Theme Article on Poverty and Human Development
The Burden of Blood Pressure-Related Disease
A Neglected Priority for Global Health
Vlado Perkovic, Rachel Huxley, Yangfeng Wu, Dorairaj Prabhakaran, Stephen MacMahon
T
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he importance of high blood pressure as a major cause
of common serious diseases has been recognized in
most Western countries for ⬇50 years. Before that, malignant hypertension was a frequent reason for hospital
admission and a common cause of death.1 Safe and
effective antihypertensive drugs were first developed in
the 1960s and were shown to dramatically improve the
prognosis associated with malignant hypertension.2,3 Over
the next few decades, the widespread use of an expanding
armamentarium of blood pressure–lowering drugs to patients at risk of malignant hypertension effectively eradicated this condition from most developed countries. Subsequently, the provision of blood pressure–lowering
treatments to a much broader group of patients at risk of
serious cardiovascular diseases, such as stroke and coronary heart disease, among whom blood pressure levels
were often only modestly elevated, contributed importantly to the declines in stroke and coronary disease deaths
rates experienced by most Western populations.4
However, the situation in higher-income countries stands
in stark contrast to that experienced by their lower-income
neighbors. The overall burden of blood pressure–related
diseases is rapidly rising in countries such as India and China
as a consequence of the aging population, increasing urbanization, and increases in age-specific rates of conditions such
as stroke.5,6 Even war-torn countries and those ravaged by
HIV/AIDS, such as some in sub-Saharan Africa, incur a huge
burden of blood pressure–related diseases. In several such
populations, cerebral hemorrhage is the leading cause of
death in adults.7 Although safe and effective antihypertensive
treatment could be provided in these regions with a range of
generic products from ⬍1 cent per person per day, the reality
is that most people for whom such drugs are clearly indicated
receive no treatment whatsoever. In this regard, the antihypertensive care available for a large proportion of the world’s
population remains much as it was in the 1950s before the
development of diuretics and ␤-blockers. In this review, we
describe the global burden of blood pressure–related diseases,
discuss some of the barriers to the implementation of effec-
tive preventive programs, and consider practical solutions
that could be implemented in resource-poor settings.
Prevalence of High Blood Pressure in
Higher- and Lower-Income Regions
There is now compelling evidence that the level of systolic
blood pressure at which the risks of stroke and coronary heart
disease begin to increase is ⬇115 mm Hg.8 –10 On this basis,
the majority of adults in most higher- and lower-income
populations have nonoptimal blood pressure.11,12 However,
there are important regional variations in blood pressure
distributions, even taking into account potential differences in
the technique of blood pressure measurement. For example,
in both sexes, for all ages ⬎45 years, average blood pressure
levels are highest in populations from Eastern Europe and
Russia. Average levels are also particularly high in the
Middle East, North Africa, and parts of sub-Sahara Africa.12
Classifications of hypertension vary, but on the basis of a
single blood pressure measurement ⬎140 mm Hg systolic or
90 mm Hg diastolic, ⬇1 in 4 adults, worldwide, would be so
classified (Table 1).13 Currently, this equates to ⬇1 billion
individuals, and this number is expected to grow to ⬎1.5
billion (⬇30% of the global population) by 2025, solely as a
consequence of increases in both total population size and the
proportions within populations reaching older ages. In higherincome regions, the number of hypertensive individuals is
predicted to grow by 70 million people from 2000 to 2025,
whereas in lower-income regions, the number is predicted to
grow by ⬎500 million over the same period. In China and
India alone, the total number with a systolic blood pressure
⬎140 mm Hg or a diastolic blood pressure ⬎90 mm Hg is
expected to increase to ⬎500 million by 2025.
Although demographic changes in populations will have
the greatest short-term consequences for changes in population blood pressure distributions and hypertension prevalence, other factors are likely to augment these changes. In
particular, progress in economic development, with consequent increases in obesity because of greater food availability
and choice, and a reduction in physical activity can be
expected to further increase mean blood pressure levels and
Received August 21, 2007; first decision August 31, 2007; revision accepted September 25, 2007.
From the George Institute for International Health (V.P., R.H., S.M.), University of Sydney, Sydney, Australia; Department of Nephrology (V.P.),
Royal North Shore Hospital, Sydney, Australia; George Institute for International Health (Y.W.), Peking University Health Science Centre, Beijing,
China; Department of Cardiology (D.P.), All India Institute of Medical Sciences, New Delhi, India; and Royal Prince Alfred Hospital (S.M.), Sydney,
Australia.
Correspondence to Vlado Perkovic, George Institute for International Health, University of Sydney, PO Box M201, Level 10, King George V Building,
Royal Prince Alfred Hospital, Missenden Rd, Sydney, NSW 2050, Australia. E-mail [email protected]
(Hypertension. 2007;50:1-2.)
© 2007 American Heart Association, Inc.
Hypertension is available at http://hyper.ahajournals.org
DOI: 10.1161/HYPERTENSIONAHA.107.095497
1
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Hypertension
December 2007
Table 1. Estimated Number of Individuals Aged >20 Years With Blood Pressure
>140/90 mm Hg in 2000 and Predicted Number of Affected Individuals in 2025
Region
Prevalence 2000,
Millions
Predicted Prevalence
2025, Millions
Increase,
Millions
Established market economies
239.5
309.7
70.2
Latin America and the Caribbean
114.3
200.6
86.3
Former socialist economies
93.1
103.7
10.6
Middle East crescent
73.8
152.6
78.8
China
181.6
299.2
117.6
India
118.2
213.5
95.3
Other Asia and islands
71.4
129.4
58.0
Sub-Saharan Africa
79.8
150.7
70.9
971.7
1559.4
587.7
Total
Adapted from Kearney et al13 with permission from Elsevier.
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the proportion with high blood pressure in lower income
regions such as China and India.14 –16
Effects of Blood Pressure on Disease Burden
in Higher- and Lower-Income Regions
Large-scale epidemiological studies have clearly demonstrated the enormous impact of nonoptimal blood pressure
levels on the risks of major cardiovascular events in both
higher- and lower-income regions.8,9,17 The Asia Pacific
Cohort Studies Collaboration, which involved ⬎500 000
individuals followed for several years on average, has demonstrated direct continuous associations of usual levels of
systolic and diastolic blood pressure with the risks of coro-
nary heart disease and stroke in both white and Asian
populations.9,18
Overall, the association of blood pressure with stroke risk
was about twice as steep as that with coronary disease risk,
and whereas the association with coronary risk was identical
in the Asian and white populations, the association with
stroke risk was steeper among Asians (Figure 1). This
appeared, in part, to be the consequence of the greater
proportion of strokes that were hemorrhagic in the Asian
population and the steeper association of blood pressure with
hemorrhagic rather than ischemic stroke. There was also
evidence of a steeper association of blood pressure with
hemorrhagic stroke among Asians compared with whites.10
Figure 1. The higher risk of (A) fatal and
nonfatal coronary heart disease and (B)
stroke, associated with higher systolic
blood pressure (SBP) levels by age and
region in the Asia Pacific Cohort Studies
Collaboration.
Perkovic et al
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There is little direct evidence about the effects of blood
pressure on cardiovascular disease risks in other lowerincome regions outside of Asia. However, on the basis of
regional evidence about blood pressure distributions and the
burden of death and disability from cardiovascular disease,
the contribution of blood pressure to total cardiovascular
disease burden can been estimated for all regions of the
world.11,19 Those analyses showed that approximately two
thirds of all stroke and half of all coronary disease can be
attributed to nonoptimal blood pressure. This represents ⬇7
million deaths and 64 million disability-adjusted life years
each year. Lower-income countries suffered approximately
two thirds of the total burden of blood pressure–related
disease. The 2 countries experiencing the greatest burden of
blood pressure–related diseases were India and China. However, whereas stroke was the most common type of blood
pressure–related disease in China, coronary disease was more
common in India. Compared with higher-income regions,
these and other lower-income regions had a greater proportion of blood pressure–related disease occur among people of
middle age. In the poorest regions, including many in Africa,
most blood pressure–related disease occurred among individuals aged 40 to 59 years.11
The relationship between blood pressure levels and noncardiovascular diseases risk has been less well defined, although
similar relationships between blood pressure levels and the
risk of end-stage kidney disease have been described in large
studies of white20 and Asian populations.21 Given the very
large increases in diabetes (and the inevitable attendant
increases in diabetic kidney disease) being experienced
across the developing world,22,23 it is likely that nonoptimal
blood pressure will be responsible for a large proportion of
the resulting disease burden.
Effects of Blood Pressure Lowering on Disease
Risks in Higher- and Lower-Income Regions
The effects of blood pressure lowering with a range of drug
therapies have been demonstrated in a large series of clinical
trials. Evidence from these trials has been synthesized by the
Blood Pressure Lowering Treatment Trialists’ Collaboration
and others, demonstrating that the magnitude of the blood
pressure reduction achieved is a more important predictor
of the cardiovascular benefits obtained than the choice of
drug.24 –26 In a wide variety of patient populations, blood
pressure lowering reduced the risk of coronary heart disease
and stroke by roughly the magnitude predicted from the
observational evidence about the association of blood pressure with cause-specific cardiovascular events. In general, a
10-mm Hg reduction in systolic blood pressure produced
approximately a 20% to 25% reduction in major cardiovascular events, with larger effects on stroke than coronary
outcomes.
There was some evidence of relatively minor differences
between drug classes in their effects on some cause-specific
outcomes. For example, for any given blood pressure reduction, there appeared to be an ⬇10% greater reduction in
coronary heart disease risk with angiotensin-converting enzyme inhibitor treatment than with other therapy.27 However,
overall the net effects on total cardiovascular disease risk of
Blood Pressure as a Global Priority
3
Figure 2. The effects of a perindopril-based blood pressure–
lowering regimen on the risk of subsequent stroke among Asian
and Caucasian participants in the Perindopril Protection Against
Recurrent Stroke Study. Reproduced from Rodgers et al.29
all of the common drug classes were broadly equivalent.
Indeed, treatment based on a diuretic, one of the least
expensive drug classes, produced as much reduction in
overall risk as did treatment based on any of the other more
expensive drug classes. Because diuretics are available for as
little as a few cents per week, they provide the most
affordable basis for antihypertensive therapy in resource-poor
settings.
Most trials have been conducted in higher-income countries, and few have recruited enough patients from lowerincome regions to provide reliable evidence about the effects
of treatment in resource-poor settings. However, 2 studies
have recruited large numbers of patients from Asia, in
particular, China, as well as Western countries. In the
Perindopril Protection Against Recurrent Stroke Study Trial28
of blood pressure lowering among patients with a history of
cerebrovascular disease, participants recruited from Asian
countries derived at least an equivalent benefit from the study
therapy as did participants from Western countries (Figure
2).29 Similarly, in the Action in Diabetes and Vascular
Disease Trial30 of blood pressure lowering among patients
with type 2 diabetes, the effects of treatment were the same
among participants recruited from Asia and those recruited
from elsewhere. A few trials have been conducted exclusively
in Asian populations (eg, the Felodipine Event Reduction
Trial31), and these studies have generally reported benefits
that are similar to those typically observed in studies conducted in Western populations.
Although some higher-income countries may have the
resources required to provide blood pressure–lowering treatment to most or all of those with hypertension, this is not
affordable or practical for most lower-income countries. For
example, for India or China to provide treatment for all of
those with hypertension would require each of these countries
to deliver such care to a population of ⬇200 million.13 For
such countries, it is essential that treatment policy targets
those most in need, for whom benefits will be greatest and
costs easiest to justify. One approach that has been widely
promulgated by the World Health Organization32 and European33 guidelines is to base treatment policies on estimated
absolute disease risk rather than on blood pressure levels
alone. If the target for blood pressure–lowering therapy was a
25% 10-year risk of a major cardiovascular event, then this
4
Hypertension
December 2007
Figure 3. Total number of individuals (in
millions) with an estimated 10-year risk of
cardiovascular disease of ⱖ25% according to World Health Organization region.
AFR indicates Africa; AMR, the Americas;
EMR, Eastern Mediterranean; EUR,
Europe; SEAR, Southeast Asia; WPR,
Western Pacific Region; A, very low child
mortality and very low adult mortality; B,
low child mortality and low adult mortality;
C, low child mortality and high adult mortality; D, high child mortality and high
adult mortality; E, high child mortality and
very high adult mortality. Developed by Dr
A. Rodgers from data collected for Ezzati
et al.19
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would imply the provision of treatment to ⬇50 million people
in of each China and India and ⬇20 million people in each of
Africa and South America (Figure 3). Such a treatment
strategy has been assessed as being cost-effective for many
lower-income regions.34 However, for some of the poorest
countries, blood pressure–lowering treatment may need to be
restricted to even higher-risk individuals, perhaps only those
who have moderate-to-severe hypertension or a history of
significant cardiovascular or renal disease.
Barriers to the Prevention of Blood
Pressure–Related Diseases in
Lower-Income Regions
Drug Costs
There are many barriers to the provision of appropriate blood
pressure–lowering therapy in resource-poor settings, but drug
costs should not be one of them. For example, the diuretic
hydrochlorothiazide can be purchased internationally for
⬇0.3 cents per 25-mg tablet, the ␤-blocker atenolol for ⬇1
cent per 100-mg tablet, and the angiotensin-converting enzyme inhibitor enalapril for 2 to 3 cents per 20-mg tablet35
(Table 2). On this basis, 1 year’s supply of hydrochlorothiazide should cost approximately $1 per person, and the total
annual cost of purchasing drug for all of those with a 25%
10-year risk of a major cardiovascular event would be
approximately $50 million in each of China and India and
approximately $20 million in each of Africa and South
Table 2. International Median Supplier Reference Cost of
Selected Blood Pressure–Lowering Agents
Drug Class
␤-Blocker
Calcium channel blocker
Diuretic
ACE inhibitor
Example Agent,
Dose, mg
Median Supplier
Price, US Cents
per Dose
Atenolol, 50
1.1
Nifedipine sustained
release, 20
1.9
Hydrochlorothiazide, 25
0.3
Enalapril, 20
4.5
Data are from McFadyen. ACE indicates angiotensin-converting enzyme.
35
America. Assuming that such treatment reduced the 10-year
risk of a major cardiovascular event from 25% to 20%, the
drug costs for the prevention of each fatal or serious event
would be approximately $200. Such costs are within the
financial capacity of all but the very poorest countries.
However, as experience in sub-Saharan Africa has shown
with respect to donated or heavily subsidized antiretroviral
drugs, the absence of functional primary health care services
in many countries means that even a free or inexpensive drug
cannot be reliably provided to those in need.36 In addition,
whereas the cost of some generic drugs from wholesalers may
be low, the price at which the same drug is provided to a
patient is often grossly inflated. Moreover, there are often
financial incentives for healthcare providers to selectively
prescribe more expensive drugs despite there being no clear
advantage over cheaper drugs, such as diuretics.
Structural Barriers
The prevention of blood pressure–related diseases requires a
primary health care system that can identify those at high risk,
ensure regular monitoring of their health status, and provide
an uninterrupted appropriate and affordable treatment supply.
Each of these poses its own unique challenges in many
lower-income regions. With respect to identifying those at
high risk, algorithms developed for Western populations
typically require laboratory blood tests for total, low-density
lipoprotein, and high-density lipoprotein cholesterol and fasting blood glucose.37 In many resource-poor settings, laboratory access can be difficult and expensive. In regions in which
HIV and hepatitis B infection are common, there may also be
professional and community concerns about screening programs that involve phlebotomy. Therefore, screening algorithms are required that take special account of these factors.
For example, a screening algorithm that includes gender, age,
cardiovascular disease history, blood pressure, weight and
height, and a urine dipstick test for glucose and protein is
likely to be more practical and may well provide much of the
predictive value of more complex blood-based assessments.32
In addition, such algorithms should, wherever possible, use
regional data on morbidity and mortality, because background rates vary considerably between regions.38 Although
Perkovic et al
Table 3. Prevalence, Awareness, and Treatment Status of
Hypertension (>140/90 mm Hg) in Studies Conducted Among
Nonrepresentative Indian Subpopulations
Prevalence, Awareness, % Treatment, %
%
of Prevalent
of Prevalent
Study
Reddy et al, 200640
27.7
37.3
Prabhakaran et al, 200541
30.0
31.5
22.1
37.3
18.7
Urban
70
46.6
41.6
Rural
55
61.4
53.0
30.9
13.1
8.0
Deepa et al, 200342
30.3
Hypertension Study Group, 2001
39
Gupta et al, 199543
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there are few data available about the proportion of high-risk
individuals who are aware of their status, there are more data
available about the proportion aware of having high blood
pressure. For example, in lower-income regions such as India,
only a minority of all those with high blood pressure are
aware of their condition (Table 3).39 – 43 Improving the identification of individuals at high risk of blood pressure–related
diseases will require educational programs aimed at both
healthcare providers and consumers. The provision of provider incentives for screening and risk assessment is likely to
be an important determinant of success.
The capacity to provide long-term monitoring of those at
high risk is an essential criterion for the effective prevention
of blood pressure–related diseases. In many situations, primary healthcare services have provided only episodic care
with little record kept of previous visits.44 In part, this reflects
the priority given to the management of acute conditions,
such as infections, trauma, and childbirth, over chronic
conditions that require treatment over many years. It is now
clear that primary healthcare services in resource-poor settings must be adapted to provide long-term care, not only for
the management of cardiovascular and other serious noncommunicable diseases but also for the management of HIV
infection with long-term antiretroviral therapy.44 Central to
this is an improvement in the quality of medical charts, which
are required for continuity of care. Once again, provider
incentives are likely to be helpful in achieving acceptable
levels of monitoring and follow-up.
Continuity of care also requires access to an uninterrupted
and affordable drug supply. In many situations, neither is
available. Drug distribution chains in many rural regions can
be unreliable, to the degree that even hospitals can often be
without blood pressure–lowering drugs for the treatment of
hypertensive emergencies. In other regions, drug distribution
chains are more reliable, but the involvement of several
distributors can inflate costs significantly. Finally, in many
lower-income countries, there is no separation between prescription and supply, resulting in perverse incentives to
prescribe higher-cost drugs and to add profit margins on top
of supply costs. In such circumstances there is a need to
regulate drug supply such that continuity is assured and
charges to patients are kept within reasonable limits. There is
also a need to separate prescription and supply to avoid drug
selection being affected by financial rewards to the pre-
Blood Pressure as a Global Priority
5
scriber. In these circumstances, practical guidelines designed
specifically for use in resource-poor settings are required in
place of the complex and largely impractical international
guidelines developed primarily with higher-income countries
in mind. Guidelines for lower-income regions should be
developed with due regard to the important role played by
nonphysician health workers, who provide a large proportion
of primary healthcare services in countries such as China.
Again, incentives to reward the prescription of guidelinebased blood pressure–lowering therapy are likely to be
helpful.
Policy Barriers
In many countries there are policy barriers to the implementation of blood pressure–lowering treatment programs. Most
common is the restrictive focus of prevention programs on
infectious disease and sometimes on HIV/AIDS alone. Many
lower-income countries face a double burden of communicable and noncommunicable disease, yet few allocate resources
to demands on the basis of cost-effectiveness or even disease
burden. Multilateral organizations, such as the World Health
Organization and the World Bank, have been partly responsible for this unbalanced approach through the setting of
Millennium Development Goals45 that excluded any mention
of chronic disease prevention and through the setting of
implausibly high targets for antiretroviral therapy implementation.46 Notably, the failure to achieve these targets47 at least
in part reflected the failure to deploy effective strategies to
create the primary healthcare networks required to deliver
any form of chronic care.
Fortunately, in recent years both World Health Organization48 and the World Bank49 have recognized the importance of chronic diseases, including blood pressure–related
diseases, as a cause not only of premature death and
disability but also as a threat to social and economic
development. This may herald the beginning of a rebalancing of investment priorities for health care in at least
some lower-income countries. However, the prioritization of
blood pressure control as a strategy to improve health status
will require evidence that worthwhile benefits can be
achieved at a price that is affordable. This requires a markedly different approach to that adopted in higher-income
countries in which treatment programs are primarily physician centered and often use expensive diagnostic procedures
(eg, 24-hour blood pressure measurement or echocardiography) and on-patent drugs. As indicated above, lower-income
regions require approaches that can be implemented by
nonphysician healthcare workers using simple assessment
tools and low-cost drugs. They also require a targeted focus
on a select group of individuals at particularly high risk of
cardiovascular or renal diseases. Goals that involve the
identification and treatment of all of those who might be
classified as hypertensive, irrespective of disease risk, are
unrealistic and, as a consequence, counterproductive. Different strategies are probably required in urban and rural areas,
but both require outreach programs to access disadvantaged
population subgroups.
6
Hypertension
December 2007
Research Relevant to the Prevention of
Blood Pressure–Related Diseases in
Lower-Income Regions
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Strategies to reduce the burden of blood pressure–related
diseases in lower-income countries requires research. Although most requirements are for operational research, there
is still a need for research that will provide evidence about the
effects of novel interventions for disease prevention that may
be of special relevance to particular populations. Research
into region-specific strategies targeting important determinants of blood pressure, such as salt intake or obesity, may
yield useful information. However, the greatest current need
is for operational research to determine how best to implement affordable drug-based preventive programs that have
proven effective in reducing blood pressure–related diseases,
such as stroke and coronary heart disease. Novel approaches
are required, because the models developed for use in
higher-income countries are neither affordable nor practical
given current and foreseeable resource constraints.
One research strategy that may have particular merit is the
conduct of cluster-randomized trials of new healthcare delivery strategies for the prevention of blood pressure–related
diseases. This could involve the development of regionally
tailored packages of interventions targeted to healthcare
providers and designed to increase the identification of
high-risk individuals and to improve their treatment according to evidence-based, resource-sensitive algorithms. Key
components of such a package would need to include healthcare provider training, simple algorithms for screening, treatment and follow-up, and reliable drug supply. Intervention
packages targeted to consumers could also be assessed.
Components might include free or subsidized drugs, health
education about blood pressure and cardiovascular disease,
and community programs aimed at increasing self-referral for
risk assessment. Although such research programs are challenging to implement and require significant resources, they
are still likely to be much less expensive than the trial
programs required for the development and registration of
new antihypertensive drugs and of much greater potential
benefit for the prevention of blood pressure–related diseases
globally.
Perspectives
Nonoptimal blood pressure is the leading cause of death
globally, responsible for 7 million deaths annually. Most of
these deaths and most of the disability caused by blood
pressure–related diseases are suffered by people in lowerincome countries. The resulting burden threatens already
fragile health systems, as well as social and economic
development. Yet, very few people receive blood pressure–
lowering therapy in many lower-income countries. The reasons for this are complex but largely involve the limitations
of primary healthcare systems to deliver effective and affordable care. The solutions are also complex and will not be
easily found in the approaches adopted by most higherincome countries given the costs involved. Specific solutions
are required for different regional circumstances. These need
to reflect competing disease burdens, financial resources,
human resources, and cultural and societal values regarding
the relative importance of strategies focused on disease
prevention as opposed to treatment. Novel research strategies
are required to identify the optimal path toward this goal.
Acknowledgment
We gratefully acknowledge the contribution of Associate Professor
Bruce Neal to this work.
Sources of Funding
This work was supported in part by a program grant from the
National Health and Medical Research Council of Australia. V.P. is
a recipient of a National Heart Foundation of Australia Astra Zeneca
Fellowship and a Royal Australasian College of Physicians Pfizer
Cardiovascular Research Fellowship.
Disclosures
None.
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The Burden of Blood Pressure-Related Disease: A Neglected Priority for Global Health
Vlado Perkovic, Rachel Huxley, Yangfeng Wu, Dorairaj Prabhakaran and Stephen MacMahon
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