Global Epidemiology Compressed

Reviews
Global epidemiology, health burden

and effective interventions for elevated
blood pressure and hypertension
Bin Zhou 1,2,3
, Pablo Perel4, George A. Mensah 5
and Majid Ezzati 1,2,3,6 ✉
Abstract | High blood pressure is one of the most important risk factors for ischaemic heart
disease, stroke, other cardiovascular diseases, chronic kidney disease and dementia. Mean blood
pressure and the prevalence of raised blood pressure have declined substantially in high-income
regions since at least the 1970s. By contrast, blood pressure has risen in East, South and Southeast
Asia, Oceania and sub-Saharan Africa. Given these trends, the prevalence of hypertension is now
higher in low-income and middle-income countries than in high-income countries. In 2015, an
estimated 8.5 million deaths were attributable to systolic blood pressure >115 mmHg, 88% of
which were in low-income and middle-income countries. Measures such as increasing the
availability and affordability of fresh fruits and vegetables, lowering the sodium content of
packaged and prepared food and staples such as bread, and improving the availability of dietary
salt substitutes can help lower blood pressure in the entire population. The use and effectiveness
of hypertension treatment vary substantially across countries. Factors influencing this variation
include a country’s financial resources, the extent of health insurance and health facilities, how
frequently people interact with physicians and non-physician health personnel, whether a clear
and widely adopted clinical guideline exists and the availability of medicines. Scaling up
treatment coverage and improving its community effectiveness can substantially reduce the
health burden of hypertension.
High blood pressure is one of the most important risk of early research. We then review the data on worldwide
factors for ischaemic heart disease, stroke, other cardio levels and trends in blood pressure and hypertension,
vascular diseases (CVDs), chronic kidney disease and effects on mortality, and major causes of high and low
dementia1–10. Elevated blood pressure is a leading pre blood pressure. We also review how blood pressure
ventable cause of CVD mortality and disease burden, might be lowered in different populations, emphasizing
globally and in most regions of the world11–13. One of how epidemiological evidence can be used in real-world
the global non-c ommunicable disease (NCD) tar conditions. Finally, we briefly present issues related to
gets adopted by the World Health Assembly in 2013 the global epidemiology of hypertension and its man
is to lower the prevalence of raised blood pressure by agement in the context of the coronavirus disease 2019
25% by 2025 compared with its 2010 level12,14. Raised (COVID-19) pandemic.
blood pressure is defined as systolic blood pressure
(SBP) ≥140 mmHg or diastolic blood pressure (DBP) History of blood pressure and hypertension
≥90 mmHg. Early knowledge and measurements. In the Yellow
In this Review, we summarize the current data on Emperor’s Classic of Medicine (first written approxi
the global epidemiology of blood pressure and hyperten mately 200–400 BCE), the Yellow Emperor of China
sion and evaluate how they have changed over time. We (approximately 2600–2700 BCE) was believed to have
also present estimates of the mortality effects of elevated talked about the so-called ‘hard pulse disease’, claiming
blood pressure and summarize interventions that can that ‘if too much salt is used in food, the pulse hardens’
✉e-mail: majid.ezzati@ reduce the burden of high blood pressure. To begin, we and suggested the use of venesection for treatment15,16.
imperial.ac.uk give a brief historical overview of how blood pressure Physicians in ancient Egypt (approximately 1500 BCE)
https://doi.org/10.1038/ came to be established as an important risk factor for and India (approximately 150 BCE) also noted the rela
s41569-021-00559-8 CVDs and other diseases, emphasizing the global nature tionship between pulse quality and the development
NATure RevIewS | CArDIology volume 18 | November 2021 | 785
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Key points In 1905, Nikolai Korotkoff, a Russian surgeon, reported

a method that uses the tapping sounds detected through a
• Hypertension is more prevalent in low-income and middle-income countries than stethoscope at different phases during the deflation of
in high-income countries. the cuff to determine the pressure at which blood flow
• In 2015, 8.5 million deaths were associated with high blood pressure, 88% of which was completely blocked, that is, SBP, and the pressure
were in low-income and middle-income countries. at which blood flow was no longer restrained, that is,
• Population-level measures, such as increasing the availability and affordability of fresh DBP22,23. Together, Korotkoff ’s auscultatory technique
fruits and vegetables and lowering the sodium content of packaged and prepared and Rocci’s cuff formed the basis of modern blood
foods, can lower blood pressure in the entire population. pressure measurement devices.
• Effective use of pharmacological treatment for people with hypertension varies
substantially globally and is particularly low in low-income and middle-income Blood pressure as a risk factor. The quantitative connec
countries.
tion between high blood pressure and mortality was first
• Scaling up treatment coverage and improving its effectiveness can substantially revealed in studies with the use of insurance data at the
reduce the health burden of hypertension.
beginning of the twentieth century24,25. These data also
revealed that blood pressure rises with age and is higher
of afflictions of the heart and brain17. Pulse also had in those who have higher weight for their height26.
an essential role in ancient Greek medicine, and its The Framingham Heart Study27 showed a greater risk of
relationship with environment and disease was dis coronary heart disease in men and women with hyper
cussed at length by physicians including Hippocrates tension (defined as SBP ≥160 mmHg or DBP ≥95 mmHg)
(460–370 BCE), Erasistratus (304–250 BCE) and Galen than in individuals with SBP <140 mmHg and DBP
(130–210 CE)16–19. However, these physicians did not <90 mmHg. The study also showed an increased risk
note the connection between apoplexy and high blood of CVD in those with high-normal blood pressure,
pressure or hardening of the pulse16. that is, 130–139 mmHg for SBP and 85–89 mmHg for
In 1628, William Harvey described the process of DBP, compared with those with optimal blood pressure,
blood flowing out of the heart and then returning to defined as SBP <120 mmHg and DBP <80 mmHg (ref.28).
the heart via arteries, peripheries and veins17,20. Nearly The Prospective Studies Collaboration pooled 61 pro
300 years later, blood pressure was discovered, and a spective observational studies with 1 million participants
reliable method for its measurement was devised. Even in Asia, Australasia, Canada, Europe and the USA and
before this technology was developed, the work of a found a doubling of the risk of ischaemic heart disease
few physicians, including Richard Bright and Frederick and stroke with every 20 mmHg and 10 mmHg increase
Akbar Mahomed, led to the first description of essen in SBP and DBP, respectively, starting from as low as
tial hypertension in the nineteenth century, for example, 115 mmHg for SBP and 75 mmHg for DBP5. The Asia
hypertension in the absence of renal disease16,17,21. Pacific Cohort Studies Collaboration found similar asso
The first accurate, direct measurement of human ciations in Asian and Australasian populations6,8. On the
blood pressure was performed by the surgeon Faivre basis of observational studies, each 10 mmHg increase
with the use of a mercury manometer during a limb in SBP is associated with a 45% higher risk of ischaemic
amputation in 1856, with a reported arterial blood pres heart disease and about a 65% higher risk of ischaemic or
sure of 115–120 mmHg (refs22,23). Devices for the indi haemorrhagic stroke in those aged 55–64 years5,8. The
rect measurement of blood pressure (that is, to measure relative risk is inversely associated with age8.
the counter-pressure needed to stop the blood flow in The observational results were confirmed by data
an artery) evolved from the first sphygmograph to visu from clinical trials that lowered blood pressure. These
alize pulse waves, invented by Karl Vierordt in 1855, to trials included the VA Cooperative Trials, Multiple
Samuel Siegfried Ritter von Basch’s sphygmomanometer Risk Factor Intervention Trial (MRFIT), and those
in 1880 (ref.23). In 1896, Scipione Riva Rocci invented included in the Blood Pressure Lowering Treatment
an inflatable cuff that compressed around the whole Trialists’ Collaboration7,29–34. Other trials, including the
circumference of the arm to apply uniform pressure. Systolic Blood Pressure Intervention Trial (SPRINT),
The cuff size was later changed to 12 cm in 1901 from the and meta-analyses of trials further showed reductions
original 5 cm (refs22,23), and it became the prototype in CVD events but mixed results for cardiovascular
of cuffs that continue to be used in modern devices. and all-cause mortality with intensive blood pressure
lowering to levels below the conventional cut-off for
hypertension of 140/90 mmHg, for example, SBP of
Author addresses
120–130 mmHg (refs2–4,35–37). However, most of the trials
1
Department of Epidemiology and Biostatistics, School of Public Health, Imperial College have been performed in Western populations, and trial
London, London, UK. evidence is especially scarce for Africa, Latin America
2
MRC Centre for Environment and Health, School of Public Health, Imperial College and South Asia.
London, London, UK.
3
The Abdul Latif Jameel Institute for Disease and Emergency Analytics, School of Public
Global, regional and national levels
Health, Imperial College London, London, UK.
4
Department of Non-communicable Disease Epidemiology, London School of Hygiene National and multi-country studies. Supplementary
& Tropical Medicine, London, UK. Table 1 summarizes the studies that investigated
5
Center for Translation Research and Implementation Science, National Heart, Lung, blood pressure and hypertension trends in individual
and Blood Institute, National Institutes of Health, Bethesda, MD, USA. countries38–67 for a period of ≥20 years. The studies that
6
Regional Institute for Population Studies, University of Ghana, Accra, Ghana. compared multiple countries68–95 are summarized in
786 | November 2021 | volume 18 www.nature.com/nrcardio
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Men Mean systolic blood pressure (mmHg) Mean diastolic blood pressure (mmHg)
Central Europe
Southern Latin America
Eastern Europe
Central Asia
Polynesia and Micronesia
East Africa
Central Africa
West Africa
Southern Africa
Melanesia
Southwestern Europe
Northwestern Europe
Southeast Asia
World
South Asia
Central Latin America
Caribbean
East Asia
Middle East and North Africa
Andean Latin America
High-income English-speaking
High-income Asia Pacific
115 120 125 130 135 70 75 80 85
Women Mean systolic blood pressure (mmHg) Mean diastolic blood pressure (mmHg)
East Africa
Central Africa
Central Asia
Melanesia
West Africa
Polynesia and Micronesia
Central Europe
Southern Africa
South Asia
Eastern Europe
Southeast Asia
World
East Asia
Caribbean
Northwestern Europe
Southwestern Europe
115 120 125 130 135 70 75 80 85
Central and Eastern Europe East and Southeast Asia High−income Western Oceania Sub−Saharan Africa
Central Asia, Middle East and North Africa High−income Asia Pacific Latin America and Caribbean South Asia World
Fig. 1 | Changes in blood pressure by region. Changes in age-standardized mean systolic and diastolic blood pressure
between 1975 and 2015 by region. The start and end points of each arrow represent the levels of blood pressure in 1975
and 2015, respectively. Rightward arrows indicate an increase in blood pressure, and leftward arrows indicate a decrease.
Supplementary Table 2. These studies show that blood Global studies. Beginning in the 2000s, some stud
pressure has declined in high-income countries and ies pooled multiple data sources to understand the
in some middle-income countries. By contrast, blood global patterns of blood pressure and hypertension
pressure and the prevalence of hypertension have been (Supplementary Table 2). Kearney and colleagues96,97
rising or at best stagnating in the other middle-income used data from 32 studies and estimated the global
and low-income countries, including the world’s most hypertension prevalence in 2000. Mills and co-workers98
populous countries, China and India. pooled 135 studies with 970,000 participants from
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Mean systolic blood pressure, men 2015
Age-standardized
mean systolic
blood pressure
(mmHg)
140
135
130
125
Caribbean
120
115
110
American Samoa Bahrain Bermuda Brunei Darussalam Cabo Verde Comoros Cook Islands
Fiji French Polynesia F.S. Micronesia Kiribati Maldives Marshall Islands Mauritius
Montenegro Nauru Niue Palau Samoa Sao Tome and Seychelles
Solomon Islands Tokelau Tonga Tuvalu Vanuatu Principe
Mean systolic blood pressure, women 2015
Age-standardized
mean systolic
blood pressure
(mmHg)
140
135
130
Caribbean
125
120
115
110
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◀ and the Caribbean, Central and Eastern Europe, Central

Fig. 2 | Worldwide systolic blood pressure. Age-standardized mean systolic blood pressure
by country in 2015. Adapted from (ref.102), CC BY 4.0 (https://creativecommons.org/ Asia, the Middle East and North Africa. Elsewhere,
licenses/by/4.0/). the age-standardized prevalence of raised blood pres
sure remained unchanged, despite rising mean blood
90 countries and estimated the worldwide prevalence pressure.
of hypertension for two time points in 2000 and 2010. South Korea and Canada had the lowest age-
Another study99 pooled 237 data sources with >660,000 standardized mean SBP in 2015 for both men
participants in a statistical model to generate global and (117–118 mmHg) and women (~111 mmHg) (Fig. 2). The
regional estimates of mean SBP. This study also reported highest mean SBPs in men were reported in countries
county results from national studies, which was possi in Central and Eastern Europe (for example, Croatia,
ble for only eight of the 191 countries included in the Lithuania and Slovenia), Oceania, Central Asia and
analysis. sub-Saharan Africa, with an age-standardized mean SBP
Danaei and colleagues100 reported the first set of reaching 137.5 mmHg (131.2–143.8 mmHg) in Slovenia.
consistent and comparable country-level estimates Women in countries in sub-Saharan Africa (for example,
of blood pressure trends. This study pooled 786 studies Guinea, Malawi, Mozambique and Niger) had the high
with 5.4 million participants with the use of a Bayesian est levels of mean SBP, surpassing 132 mmHg. Countries
meta-regression model to estimate year-on-year trends with the lowest mean DBP were Peru and several
in mean SBP for 199 countries from 1980 to 2008. high-income countries, including Australia, Canada,
Forouzanfar and co-workers101 pooled 844 studies with New Zealand, Singapore and the UK (Fig. 3). DBP was
8.7 million participants to estimate trends in mean SBP high throughout Central and Eastern Europe, South Asia
for 195 countries from 1990 to 2015. The most compre and sub-Saharan Africa, with the age-standardized mean
hensive estimates were produced by the NCD Risk Factor surpassing 85 mmHg in Lithuanian men.
Collaboration (NCD-RisC)102, which pooled 1,479 stud Australia, Canada, Peru, Singapore, South Korea, the
ies with 19.1 million participants and estimated trends UK and the USA had the lowest prevalence of raised blood
in mean SBP, mean DBP and the prevalence of raised pressure in 2015 for both sexes, with an age-standardized
blood pressure — defined as SBP ≥140 mmHg or DBP prevalence of <13% in women and <19% in men (Fig. 4).
≥90 mmHg — for 200 countries from 1975 to 2015. At the other extreme, the age-standardized prevalence
In the next section, we use the results from NCD-RisC surpassed 35% among men in some countries in Central
to summarize the worldwide trends in blood pressure. and Eastern Europe, including Croatia, Latvia, Lithuania,
Hungary and Slovenia. The prevalence of raised blood
Worldwide trends in blood pressure. The global age- pressure was >33% among women in some countries in
standardized mean SBP in 2015 among men ≥18 years West Africa.
of age was 127.0 mmHg, largely unchanged since 1975.
SBP declined slightly among women in the same period Blood pressure and national characteristics. Although
(from 123.9 mmHg to 122.3 mmHg) (Fig. 1). Trends in the determinants and correlates of high versus low blood
the age-standardized mean DBP, which was 78.7 mmHg pressure at the individual level are well-established103,
for men and 76.7 mmHg for women in 2015, were sim less is known about the association between popula
ilar. The age-standardized prevalence of raised blood tion blood pressure and national characteristics such
pressure declined globally in both sexes, from 29.5% as national income, urbanization, diet and BMI. Two
to 24.1% among men and from 26.1% to 20.1% among studies examined the association between population
women. mean SBP and some national characteristics, including
Mean SBP and DBP declined substantially in the national income, a measure of the Western diet, the pro
high-income regions, from the highest in the world in portion of the national population living in urban areas
1975 to the lowest in 2015 (Fig. 1). The largest decline and food share of household expenditure104,105. Next, we
in mean SBP occurred in the high-income Asia Pacific examine the association between mean SBP and DBP
region, by 3.2 mmHg and 2.4 mmHg per decade among and the per capita gross domestic product (GDP), the
women and men, respectively. The largest decline in proportion of the population living in urban areas and
mean DBP occurred in the high-income Western region: the age-standardized mean BMI.
1.8 mmHg per decade among women and 1.5 mmHg per Figure 5 shows the associations between SBP and per
decade among men. Mean SBP declined among women capita GDP, urbanization and BMI in 1975 and 2015.
in Central and Eastern Europe, Latin America and the In 1975, mean SBP and DBP were positively associated
Caribbean and possibly in Central Asia, the Middle East with per capita GDP, urbanization and BMI. By 2015, the
and North Africa, albeit with larger uncertainty than in correlation between mean SBP and these factors dimin
high-income regions. Similarly, mean DBP decreased ished in men and reversed in women. Correlations for
in women in these regions, but the reduction was mean DBP changed similarly, but the negative correlation
smaller than in high-income regions. Men had little or for women was weaker than that for mean SBP.
no change in mean SBP or DBP in these regions. In con The changing association of mean SBP and DBP
trast to these declines, mean SBP and DBP have risen with GDP and urbanization indicates that hypertension
among men and women in East, South and Southeast is not a ‘disease of affluence’ but one of poverty at the
Asia, Oceania and sub-Saharan Africa. The largest global level. The weakening of associations with BMI
regional decrease in raised blood pressure was reported (Fig. 5) suggests that other dietary, environmental and
in the high-income regions, followed by Latin America health-care factors that also influence blood pressure are
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Mean diastolic blood pressure, men 2015
Age-standardized
mean diastolic
blood pressure
(mmHg)
85
80
Caribbean
75
70
Mean diastolic blood pressure, women 2015
Age-standardized
mean diastolic
blood pressure
(mmHg)
85
80
Caribbean
75
70
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◀ Fig. 3 | Worldwide diastolic blood pressure. Age-standardized mean diastolic blood regions131. Similarly, alcohol consumption has also had
pressure by country in 2015 (ref.102). mixed trends across countries and regions132. In high-
income countries, the decline in blood pressure has
counteracting the effects of BMI. For example, higher occurred despite rising BMI, an established risk factor for
income and more year-round availability of fruits and high blood pressure, whereas both BMI and blood pres
vegetables have increased their availability in most sure are rising in most low-income and middle-income
countries106. Similarly, at least in high-income countries, countries110. Other potential population-wide determi
more people with hypertension are treated95, especially nants of blood pressure include increased availability
individuals with a high BMI107. Some low-income and and consumption of fruits and vegetables through better
middle-income countries with high blood pressure lev year-round availability106,108, central heating at home and
els (for example, those in South Asia and sub-Saharan work, which would lower winter blood pressure133–135,
Africa) had one or more adverse factors, including and improvements in early childhood and adolescent
low consumption of fresh fruits, high consumption nutrition, as seen in greater adulthood body height
of salt, and a high prevalence of maternal and child in successive birth cohorts112. Blood pressure is also
hood undernutrition106,108–112. The changing association decreasing in adolescents in high-income countries
between blood pressure and these country character and possibly some middle-income countries93,136–139,
istics highlights the need to understand what factors suggesting a role of the life-course effects from these
drive the changes in high-income countries and in population-wide determinants.
low-income and middle-income countries.
Within country patterns
Changes in blood pressure distributions. Blood pressure Blood pressure in men and women. Men are known to
is affected by nutritional, environmental and behavioural have a higher blood pressure than women140, but this
factors throughout the life course, including fetal and relationship could vary by age and geography. According
early childhood nutrition and growth113, adiposity103, diet to NCD-RisC data, in 2015, men had a higher age-
(particularly sodium and potassium)114,115, alcohol use116, standardized mean SBP than women in most countries.
smoking117, physical activity118, air pollution119, noise120, Men also had higher DBP and prevalence of raised
psychosocial stress121 and the use of blood-pressure- blood pressure than women in most countries, except
lowering medicines. Changes in some of these determi in sub-Saharan Africa and a few countries in Oceania
nants, such as an increase in BMI and better nutrition in and Asia, where the sex-specific pattern was reversed.
childhood and adolescence, can shift the entire popula The male–female differences in the age-standardized
tion distribution of blood pressure and thereby change mean and prevalence were mainly owing to sex-specific
both the mean value and the prevalence of raised blood differences before the age of 50 years. Men and women
pressure. By contrast, medication and lifestyle change aged ≥50 years had more similar mean SBP and DBP
in those with elevated blood pressure would reduce and prevalence of raised blood pressure, with countries
the prevalence of raised blood pressure by affecting the divided into some with lower and others with higher
high-blood-pressure tail of the distribution, with a fairly blood pressure in men (Fig. 6). The male–female differ
small effect on the mean blood pressure value. ence in blood pressure in 2015 was on average larger in
An analysis of multi-country data from the WHO high-income countries and those in Central and Eastern
MONICA project revealed that different percentiles of Europe than in countries in other regions.
population blood pressure distribution changed as much
as its mean in most populations throughout the study Subnational patterns of blood pressure. Several studies
period, which was about 10 years from the 1980s to the have considered differences in blood pressure between
1990s; nonetheless, the upper percentile changed by a rural and urban populations or in relation to socio
larger amount in some communities71. The NCD-RisC economic status (SES). In high-income countries, blood
found that from 1985 to 2016, in most regions where pressure has consistently been reported to be higher
the prevalence of raised blood pressure decreased, the in low-SES groups than in high-SES groups and higher in
decline in mean blood pressure was the main driver of poorer and more rural areas of countries than in richer
the decline in prevalence, contributing to at least half urban centres141–145. The observed decline in blood pres
of the total decline122. In regions where the prevalence of sure in high-income countries benefited all SES groups;
raised blood pressure increased or remained unchanged, however, the inverse SES gradient has persisted for as
the increase was driven entirely by a rise in mean blood long as data have been available146–153.
pressure. Data from studies on geographical and socio
The behavioural, nutritional and environmental economic patterns of blood pressure and hypertension
drivers of the shift in the population distribution of in low-income and middle-income countries are more
blood pressure remain uncertain largely because these mixed than in high-income nations74,142,154–165. A review
determinants are poorly measured. Salt intake might of early data from Africa and Asia led to the conclusion
have declined in some countries where blood pressure that “there are communities, in whom blood pressure
declined123–125, but it has discordant trends with blood does not rise with age and in whom the problem of
pressure in other countries109,126–130. The prevalence of essential hypertension and its complications appears to
smoking has declined in most high-income countries be virtually non-existent. I must emphasize that in the
and some middle-income countries, but remains high vast majority of tropical communities blood pressure
or is increasing in other low-income and middle-income patterns are similar to those seen in the economically
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Raised blood pressure, men 2015
Age-standardized
adult prevalence of
raised blood pressure
55%
45%
35%
Caribbean
25%
15%
5%
Raised blood pressure, women 2015
Age-standardized
adult prevalence of
raised blood pressure
55%
45%
35%
Caribbean
25%
15%
5%
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◀ Fig. 4 | Worldwide prevalence of raised blood pressure. Age-standardized prevalence At the population level, several interventions and strat
of raised blood pressure by country in 2015 (ref.102). egies are effective in reducing the risk of hypertension.
Examples of effective population-based interventions
advanced countries of the world”166. Meta-analyses include increasing the availability and affordability of
and re-analyses of health survey data have concluded fresh fruits and vegetables through pricing and targeted
that groups with lower SES have a higher prevalence of subsidies for low-income families, lowering the sodium
hypertension in countries across all income levels except content of packaged and prepared food and staples such
those in Africa167,168. The multicentre PURE study73 also as bread by influencing food reformulation and regu
found that high-education groups have a lower preva latory and voluntary mechanisms and making dietary
lence of hypertension in all countries except those in salt substitutes readily available and accessible1,174–176,179.
low-income nations. The success of these strategies requires active and sus
tained collaboration among global, regional, national and
Mortality local governments, myriad government agencies, and
A few studies have combined data on the population health promotion and disease prevention experts179–181.
mean blood pressure with risk ratios from epidemio Implementation research is needed to identify what indi
logical studies to estimate the number of deaths attrib vidual and population-level interventions and strategies
utable to high blood pressure11,169–172. The focus of these work best and can be sustained in each setting and any
calculations was initially on CVDs and was subsequently unintended consequences1,182. In particular, studies in
extended to include chronic kidney disease11,171,172. low-income and middle-income countries are needed
According to data from these studies, an estimated to identify and evaluate effective population-level inter
7.7–10.4 million annual deaths are attributable to ventions in settings with limited resources available to
elevated blood pressure levels11,172. individuals, families and governments, and with limited
Figure 7 shows the number of deaths from CVDs and infrastructure, and in different social contexts.
chronic kidney disease attributable to all levels of high
blood pressure by region and cause of death. In 2015, Pharmacological treatment. Progress in the pharmaco
an estimated 4.5 million deaths in men and 4.0 million logical treatment of hypertension in the past 50 years
deaths in women were attributable to SBP higher than is among the most remarkable in medicine. With hun
the optimal level of 115 mmHg, 88% of which were in dreds of thousands of patients recruited into trials since
low-income and middle-income regions. This figure the landmark VA Cooperative Study29, a wide portfolio
represents an increase of 1.6 million and 0.9 million for now exists of cost-effective and safe pharmacological
men and women, respectively, compared with 1990. The options to treat people with hypertension. The evi
increase was a result of doubling of deaths attributable to dence is among the most robust in clinical medicine
high blood pressure in East, South and Southeast Asia and supported by the largest number of outcome-based
and sub-Saharan Africa. By contrast, in high-income randomized clinical trials178. Systematic reviews and
Western and Asia Pacific regions, the number of deaths meta-analyses of trials have shown that a 10 mmHg
attributable to high blood pressure declined by 20–30% reduction in SBP or a 5 mmHg reduction in DBP is
despite a larger and older population. In relative terms, associated with substantial reductions in all major
deaths from chronic kidney disease attributable to cardiovascular events (about 40% in heart failure, 35%
high blood pressure increased more than deaths from in stroke, 15% in coronary heart disease, 20% in cardio
CVDs (Fig. 7). vascular mortality and 10% in all-cause mortality)183.
Importantly, these relative risk reductions are consis
Prevention and management tent across baseline levels of blood pressure and absolute
Non-pharmacological interventions. Successful control of disease risk and comorbidities4,7,33.
hypertension should entail a comprehensive strategy Many hypertension clinical guidelines exist worldwide,
of prevention at the individual and population levels, including the 2018 guidelines by the European Society of
with the use of non-pharmacological interventions Cardiology and the European Society of Hypertension178
throughout the life course1,103,173. Although a large num and the 2020 guidelines by the International Society of
ber of studies have established risk factors for hyper Hypertension184. Several national guidelines have been
tension, fewer studies have evaluated the effectiveness developed within the past 5 years, including guidelines
of non-pharmacological interventions for hyperten from Canada177, China185, India186, Kenya187, the UK188 and
sion prevention, especially in global or multi-country the USA189. WHO is also working on its first hypertension
contexts. Studies that have evaluated the effectiveness clinical guideline, which is expected to be ready in 2021.
of non-pharmacological interventions for hyperten Although guidelines can differ in certain features, such as
sion prevention include some of the Lancet Series in the blood pressure threshold value required to start treat
NCDs174, the Disease Control Priorities study175, the ment or the target blood pressure for those on treatment,
Lancet Commission on Hypertension1, and the WHO a clear consensus exists about the strong evidence for the
Action Plan for the Prevention and Control of NCDs176. effectiveness of four major classes of pharmacotherapies,
Prevention of hypertension is also addressed in some including blockers of the renin–angiotensin–aldosterone
national and regional guidelines177–179. Effective inter system (RAAS), calcium channel blockers, β-blockers
ventions at the individual level include advice from and thiazide or thiazide‐like diuretics. Although specific
physicians and nurses to reduce dietary sodium and indications exist for some of the pharmacological groups,
increase the consumption of fruits and vegetables. such as β-blockers for patients with coronary artery
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Mean systolic blood pressure Mean diastolic blood pressure
a Per capita GDP

140 Men 1975 Women 1975 Men 1975 Women 1975
85
130 80
75
120
70
mmHg

85
130
80
120 75
70
110
6 8 10 12 6 8 10 12 6 8 10 12 6 8 10 12
Natural logarithm of GDP per capita (2011 Int$) Natural logarithm of GDP per capita (2011 Int$)
b Proportion of the population living in urban areas
85
130 80
75
120
70
mmHg

85
130
80
120 75
70
110
0 25 50 75 100 0 25 50 75 100 0 25 50 75 100 0 25 50 75 100
Proportion of population living in urban area (%) Proportion of population living in urban area (%)
c Mean BMI
85
130 80
75
120
70
mmHg

85
130
80
120 75
70
110
20 25 30 20 25 30 35 20 25 30 20 25 30 35
Mean BMI (kg/m2) Mean BMI (kg/m2)
Central and Eastern Europe East and Southeast Asia High-income Western Oceania Sub-Saharan
Central Asia, Middle East High-income Asia Pacific Latin America and South Asia Africa
and North Africa Caribbean
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◀ Fig. 5 | Association between country characteristics and blood pressure. which can be combined statistically into risk scores192.
a | Relationship between mean systolic and diastolic blood pressure and per capita gross In addition to the content of guidelines, recognition of
domestic product (GDP) for 1975 and 2015. b | Relationship between mean systolic and the importance of delivery approaches for successful
diastolic blood pressure and the proportion of the population living in urban areas for guideline implementation has increased. Some of the
1975 and 2015. c | Relationship between mean systolic and diastolic blood pressure and
effective implementation approaches include task shift
mean BMI for 1975 and 2015. In 1975, mean systolic and diastolic blood pressure were
positively correlated with GDP, the proportion of the population living in urban areas
ing, electronic decision-support tools and simplification
and mean BMI. In 2015, mean blood pressure was no longer correlated with these of guidelines193,194. The increasing recognition of the need
country characteristics for men and negatively correlated with GDP and the proportion to simplify guidelines has influenced global hypertension
of the population living in urban areas for women. Each point shows one country, programmes, such as the programmes by the Resolve To
coloured by region. Save Lives initiative and the Global Standardization of
Hypertension Treatment Project, which have adopted
disease or heart failure and RAAS blockers for patients simplified treatment protocols guided by local circum
with chronic kidney disease, a consensus has been estab stances to improve compliance195,196. Finally, although
lished that all antihypertensive drugs have a similar effect antihypertensive treatment counts among the most
on major cardiovascular outcomes, including mortality178. remarkable achievements in clinical medicine, and now
Fixed-dose combination therapy, with two or more agents many antihypertensive drugs are cost-effective, safe and
in a single pill, is a crucial component of the current med off-patent, the availability and affordability of antihyper
ical management of hypertension. This approach has sev tensive drugs are limited, and their use is still low, as we
eral advantages, including pharmacological (synergies of discuss in the next section197.
mechanisms of action and fewer adverse effects owing to
lower doses) and practical (increasing adherence) aspects, Global variations in treatment. The extent to which
and is currently recommended as initial therapy in most patients with hypertension are treated and whether their
guidelines190,191. blood pressure is lowered to levels below the threshold
Another crucial pillar of antihypertensive treatment for hypertension (that is, controlled) varies substantially
is the overall risk approach. The relative effect of anti across countries. A regional hypertension programme by
hypertensive treatment is approximately constant across Kaiser Permanente Northern California and the nation
baseline cardiovascular risks. Therefore, individuals at wide Canadian Hypertension Education Program have
higher risk benefit more in absolute terms33. In addi achieved some of the best performances in hyperten
tion to blood pressure levels, most current guidelines sion control, with 70–90% of individuals with hyper
consider the overall cardiovascular risk of treatment tension having their blood pressure controlled198,199. This
recommendations. The overall risk can be estimated achievement demonstrates that high levels of hyperten
by considering age and other cardiovascular risk fac sion control are feasible through improving health-care
tors such as lipid levels, diabetes mellitus and smoking, provider and patient compliance with evidence-based
Systolic blood pressure Diastolic blood pressure

90
Central and Eastern Europe
150 Central Asia, Middle East and North Africa
Male age-standardized mean blood pressure (mmHg)
East and Southeast Asia

High-income Western
Latin America and Caribbean
Oceania 85
140 South Asia

Sub-Saharan Africa
18−49 years
≥50 years
80
130
75
120
70
110 120 130 140 150 70 75 80 85

Female age-standardized mean blood pressure (mmHg)
Fig. 6 | Comparison of female and male blood pressures. Comparison of female and male blood pressures in people
aged 18–49 years and ≥50 years in 2015. Each point shows one country, coloured by region. The interaction between sex
and age group was significant (P < 0.0001 for systolic and diastolic blood pressure) in an analysis of variance in a model
with blood pressure as a dependent variable and sex, age group and their interaction as independent variables. Men aged
18–49 years have higher blood pressure levels than women of the same age in most countries, and men and women aged
≥50 years have on average similar blood pressure levels.
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a Men West Africa

Central Africa
1990
Southern Africa
East Africa
Central Asia
South Asia
2015 Southeast Asia
East Asia
Melanesia
Women Polynesia and Micronesia
Caribbean
1990
Northwestern Europe
2015 Southwestern Europe
Central Europe
Eastern Europe
0 1 2 3 4
Deaths attributable to SBP >115 mmHg (millions)
b Men
1990
2015
Women
1990
Cause of death
Ischaemic heart disease
Haemorrhagic stroke
2015 Ischaemic stroke
Other cardiovascular diseases
Chronic kidney disease
0 1 2 3 4
Deaths attributable to SBP >115 mmHg (millions)
Fig. 7 | Deaths attributable to high blood pressure. Deaths attributable to high systolic blood pressure (SBP) in 1990 and
2015, coloured by region (part a) and cause of death (part b).
guidelines, updating recommendations annually, estab had the lowest. Even in the best-performing countries,
lishing a hypertension registry, monitoring physician treatment coverage for hypertension was at most 80%
performance and providing feedback, implementing and control rates were <70%, with treatment and con
regular blood pressure measurements and single-pill trol rates being as low as 40% and 20%, respectively, in
combination therapy, tailored knowledge dissemination the worst-performing countries95. The study also found
and national leadership198,200. that hypertension treatment and control rates have pla
National coverage and effectiveness of hypertension teaued since ~2010 (ref.95). Another study used data from
treatment vary substantially. A 2019 study used national 90 countries worldwide and found that, between 2000
data from 44 low-income and middle-income countries and 2010, the percentage of people with hypertension
and found that only 30% of people with hypertension who were being treated increased both in high-income
are receiving pharmacological treatment and only 10% and in low-income and middle-income countries, but
have their blood pressure controlled below the hyper the gap between them widened98.
tension threshold level92. High-income countries gen Some studies have identified factors that affect the
erally perform better, but treatment and control rates in treatment of hypertension. The implementation of
most countries are lower than those with high-quality universal health coverage, the extent of out-of-pocket
hypertension programmes. Another 2019 study used spending for care and medicines, and the number
national data on hypertension treatment from the 1970s and location of health facilities influence access to
in 12 high-income countries95. The study showed that health-care. The extent of diagnosis and appropriate
Canada, Germany, South Korea and the USA had the treatment of hypertension are influenced by the number
highest rates of awareness, treatment and control of of health personnel and mechanisms such as task sharing
hypertension, whereas Finland, Ireland, Japan and Spain with non-physician health workers and well-developed
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clinical guidelines for hypertension management201,202. of telemedicine in improving blood pressure control211–213.
Well-developed supply chains ensure regular availabil Other approaches are emerging, including smartphone-
ity of antihypertensive medicine, which, together with based apps for self-management and tracking and wear
their cost and the extent of the out-of-pocket payment, able devices (for example, smartwatches) that measure
determine whether patients can obtain and afford the blood pressure. Although these approaches look promis
medicine197. In addition, mechanisms such as m-health ing, the evidence is limited to support their effectiveness
(for example, text message reminders), home visits by in improving blood pressure control214–216. By providing
community health workers and other community-based remote access to health care, these approaches might
health promotion programmes improve patient adher partly overcome the obstacles posed by limited health
ence to treatment203–208. Similarly, the use of combination infrastructure for hypertension control in low-income
therapy improves both adherence to treatment and treat and middle-income countries. Conversely, they might
ment effectiveness190,209,210. Evidence from trials supports create new barriers for some caused by the increased
the effectiveness of improving many of these factors, demand for new technology that might be available only
but macrosocial and macroeconomic factors, includ to those with higher income and education. Therefore,
ing insurance, procurement and personnel, affect how a need exists to conduct implementation research on
interventions can be scaled up regionally and nationally. these approaches to identify the populations and contexts
Information technology has brought new approaches in which they work, and to determine how they work and
to hypertension management. Telemedicine might help their effects on inequalities.
overcome physical barriers to accessing health care,
including for remote and disparate populations and at Global hypertension initiatives. The public health
times of restricted population mobility. However, the evi importance of hypertension is recognized in several
dence from clinical trials is mixed on the effectiveness global initiatives. Global Hearts, led by WHO, includes
Table 1 | Features of global initiatives and programmes for hypertension treatment

Initiative or Target Key areas of action
programme regions
Global Hearts NA HEARTS (six technical packages for the prevention and control of cardiovascular
(WHO) disease): training health-care workers to counsel on behavioural risk factors and
healthy lifestyles; simple, standardized and evidence-based treatment protocols
for hypertension and diabetes mellitus; ensuring access to essential medicines
and technology; risk-based approach to the management of cardiovascular
disease, including country-specific risk charts; implementing team-based care
and task shifting; and improved monitoring system with standardized indicators
(for example, hypertension control rate) and data collection tools
WHF Hypertension NA Opportunistic screening; promoting use of inexpensive, good-quality generic
Roadmap medications for hypertension; education on adherence to lifestyle modification
and medication use
Pan-African Society Sub-Saharan A ten-point action plan for African ministries of health, including: creating or
of Cardiology Africa adopting simple and practical clinical evidence-based hypertension management
Roadmap guidelines; annual monitoring and report of the detection, treatment and control
rates of hypertension, with a clear target for improvement by 2025, with use of the
WHO STEPwise approach to surveillance; integrating hypertension management
within existing health services such as disease-specific vertical programmes
(for example, HIV and tuberculosis); task-sharing with trained community health
workers; and ensuring availability of essential equipment and medicines
Resolve To Save China, India, Practical treatment protocols with specific medications, dosages and steps
Lives Thailand to take if blood pressure is not controlled; adopting community-based care and
task sharing; ensuring supply of medications; adopting easy-to-take medicine
regimens, using free or low-cost medications and follow-up visits, and making
blood pressure monitoring readily available; and leveraging technology to
develop information systems that allow for continuous, real-time improvement
Global Barbados, Using nationally relevant, evidence-based and implementable treatment
Standardization Malawi protocols that are endorsed by key stakeholders; identifying a core set of widely
of Hypertension available medications that are safe and effective; ensuring the quality, safety
Treatment Project and consistent supply of the core set of medications; developing hypertension
registries and monitoring targets (for example, blood pressure control) within a
care system or programme to evaluate the efficacy of the system or programme
and make adjustments accordingly; empowering patients by involving them in
decisions related to their treatment, creating a physician–patient relationship on
the basis of mutual respect, and utilizing educational materials and peer-support
groups to improve the knowledge, attitude and adherence to treatment of
the patients; use of team‐based care that coordinates care delivery within the
team (task sharing) and ensures continuity of care; and use of community-based
settings for services such as blood pressure checks and education and engaging
community partners (for example, civil society organizations and media)
NA, not applicable; WHF, World Heart Federation.
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two specific components related to hypertension; the especially where national or local lockdowns have been
SHAKE package (salt reduction) and the HEARTS tech implemented255–258. The reduced contact with health-care
nical package (strengthening the management of CVDs services might delay the diagnosis of hypertension and
in primary health care)217. The World Heart Federation disrupt the treatment of hypertension. A WHO survey
Hypertension Roadmap, and its regional adaptations revealed that 53% of countries have reported disruptions
such as the one developed by the Pan-African Society in hypertension management256, but the precise effect of
of Cardiology, aims to provide a framework for coun this disruption remains unknown. The COVID-19 pan
tries and regions to implement policy and health system demic might also affect social networks and interactions,
solutions for hypertension control218,219. The Resolve To physical activity, smoking, mental stress, alcohol use and
Save Lives initiative aims to prevent 100 million deaths diet259,260, all of which influence hypertension directly or
globally and has two hypertension-related components indirectly. Together with other disruptions in care, these
(salt reduction and hypertension control)220. The global issues might have already contributed to excess deaths
importance of hypertension is also recognized because beyond those caused by COVID-19 directly261.
hypertension treatment coverage is considered a tracer What long-term effect the COVID-19 pandemic
indicator in the WHO universal health coverage index221. will have on hypertension management remains uncer
The key features of global hypertension initiatives and tain. For example, there might be an increased uptake
programmes are summarized in Table 1. of telemedicine or remote consultation with general
practitioners243,253. In the short term, efforts should be
Hypertension and the COVID-19 pandemic. Hyper focused on ensuring that all social groups, particularly
tension has emerged as a common comorbidity in poor and vulnerable groups, have opportunities and sup
patients hospitalized with COVID-19 (refs 222–230) . port to access healthy foods and to have outdoor time,
Studies in China, Italy, the UK and the USA found a and that preventive and treatment care continues to be
strong association between pre-existing hypertension available.
and disease severity and mortality. However, findings
were mixed after accounting for age and other comor Conclusions
bidities and risk factors, particularly obesity and diabe This Review demonstrates that hypertension has always
tes, which often co-occur with hypertension222,223,230–237. been present in low-income populations throughout
Therefore, at the time of this Review, insufficient evi the world to varying degrees. After decades of decline
dence exists to establish hypertension or high blood in high-income countries and an increase in some
pressure as a risk factor for hospitalization with, or low-income and middle-income regions, blood pressure
prognosis of, COVID-19 independent of age and other levels are now much higher in lower-income countries,
conditions. especially in sub-Saharan Africa and South Asia, and in
Severe acute respiratory syndrome coronavirus 2 Central and Eastern Europe. Consequently, now 88% of
(SARS-CoV-2) binds to angiotensin-converting enzyme 2 the mortality attributable to high blood pressure is out
receptors to gain access to cells238. Therefore, concerns side high-income regions. We have also found that the
existed about the safety of RAAS inhibitors for patients evidence on whether blood pressure and hypertension
with COVID-19 (ref.239). However, a growing body of are higher in rural or urban populations is equivocal.
evidence has emerged to allay this concern231,240,241, and The reasons for the massive declines in blood pres
clinical groups have recommended the continued use sure in high-income countries are probably multifaceted
of RAAS inhibitors in these patients242–248. In addition, and include both general economic and infrastructural
studies have shown a potential protective effect of RAAS development and specific actions in the health systems
inhibitors in patients with COVID-19 with or without towards prevention and treatment71,122. Although over
hypertension249–252, but data are limited beyond recom all economic and health development over the coming
mending that patients receiving RAAS inhibitors should decades might replicate these achievements elsewhere,
continue with their medication as usual. the large and globally inequitable burden of high blood
At the time of this Review, the COVID-19 pandemic pressure should motivate the use of the personal and
has also had an important indirect effect on hyper population-based interventions reviewed here so that
tension and CVDs243,253,254. Elective patient care and rising trends are reversed and declines are accelerated.
routine contact with health-care services, including
hypertension care, has plummeted since the outbreak, Published online 28 May 2021
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Reviews

Global epidemiology, health burden

NATure RevIewS | CArDIology volume 18 | November 2021 | 785

Key points In 1905, Nikolai Korotkoff, a Russian surgeon, reported

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Mean systolic blood pressure, men 2015

Mean systolic blood pressure, women 2015

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◀ and the Caribbean, Central and Eastern Europe, Central

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Mean diastolic blood pressure, men 2015

Mean diastolic blood pressure, women 2015

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Raised blood pressure, men 2015

Raised blood pressure, women 2015

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Mean systolic blood pressure Mean diastolic blood pressure

a Per capita GDP

140 Men 2015 Women 2015 Men 2015 Women 2015

140 Men 2015 Women 2015 Men 2015 Women 2015

140 Men 2015 Women 2015 Men 2015 Women 2015

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Systolic blood pressure Diastolic blood pressure

East and Southeast Asia

140 South Asia

110 120 130 140 150 70 75 80 85

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a Men West Africa

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Table 1 | Features of global initiatives and programmes for hypertension treatment

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