25 research outputs found
Molecular genetics of paediatric versus adult brain tumours
Tese de doutoramento em Ciências da Saúde (especialidade de Ciências da Saúde)Brain
tumours
are
the
leading
cause
of
cancer-‐related
death
in
paediatric
patients
and
are
responsible
for
the
greater
part
of
the
cancer-‐related
years
of
life
lost
across
all
age
groups.
The
more
malignant
histologies
are
the
major
contributors
to
the
high-‐rates
of
mortality
and
morbidity
of
brain
tumours.
In
the
present
thesis
we
focused
our
studies
on
high-‐grade
gliomas
and
medulloblastomas,
the
most
common
malignant
brain
tumours
of
adults
and
childhood
patients,
respectively.
Childhood
and
adult
patients
share
most
of
the
different
brain
tumours’
histological
types,
despite
a
large
variation
in
frequency
across
specific
age
groups.
Nevertheless,
there
is
increasing
evidence
that,
despite
being
histologically
similar,
childhood
and
adult
tumours
have
key
clinical
and
molecular
differences.
The
work
summarized
in
this
thesis
aims
to
disclose
molecular
mechanisms
particular
to
paediatric
and
adult
high-‐grade
gliomas
and
medulloblastomas,
attempting
to
better
understand
the
biology
of
age-‐specific,
histologically
identical,
tumours.
Brain
tumours
are
characterized
by
multiple
genetic
alterations
affecting
receptor
tyrosine
kinase
(RTK)
pathways.
As
the
EGFR
RTK
pathway
is
one
of
the
most
important
signalling
networks
in
high-‐grade
gliomas,
we
aimed
to
study
EGFR
molecular
aberrations
involved
in
protein
activation,
potentially
relevant
for
tumour’s
response
to
EGFR-‐targeted
therapy.
The
role
of
EGFR
in
adult
high-‐grade
gliomas
is
well-‐characterized,
and
in
the
present
thesis
we
studied
a
unique
series
of
Portuguese
patients,
aiming
to
understand
whether
the
EGFR
molecular
alterations
of
these
patients
were
in
line
with
other
populations
in
terms
of
potential
biomarkers
of
EGFR-‐targeted
therapy.
On
the
other
hand,
EGFR
is
thought
to
be
less
significant
in
childhood
tumours,
although
there
is
limited
published
data.
Accordingly,
we
aimed
to
study
the
frequency
and
role
of
EGFR
molecular
alterations
in
paediatric
high-‐grade
gliomas,
aiming
to
evaluate
the
presence
of
molecular
signatures
of
response
to
existing
drugs
in
these
patients.
We
confirmed
that
EGFR
represents
one
of
the
most
frequently
altered
molecules
in
high-‐grade
glioma,
particularly
in
adult
glioblastoma,
and
that
it
is
also
true
for
Portuguese
patients.
In
addition
some
paediatric
tumours,
particularly
anaplastic
oligodendrogliomas,
frequently
presented
EGFR
aberrations
and
therefore
are
also
potential
candidates
for
EGFR-‐targeted
therapy. Microsatellite
instability
(MSI)
frequency
in
brain
tumours
remains
a
controversial
research
topic,
and
there
is
a
lack
of
clarity
in
the
published
literature.
In
this
context,
we
aimed
to
study
MSI
in
high-‐grade
gliomas
and
medulloblastoma
from
adult
and
paediatric
patients
and
identify
MSI
target
genes
potentially
involved
in
MSI-‐related
tumorigenesis.
Our
findings
show
the
presence
of
MSI
in
a
fraction
of
medulloblastoma
and
high-‐grade
gliomas.
Age-‐specific
differences
in
MSI
frequency
were
not
present
in
medulloblastoma,
however
MSI
was
significantly
more
frequent
in
paediatric
high-‐grade
gliomas
than
in
adults
tumours.
Moreover
MSI-‐positivity
was
associated
with
a
stable
genomic
profile.
Overall,
of
the
18
MSI
target-‐genes
studied,
only
three
were
mutated,
all
in
paediatric
in
MSI
tumours,
MBD4
in
one
medulloblastoma,
and
MSH6
and
DNAPKcs
in
high-‐grade
glioma
As
we
failed
to
find
the
MMR
alteration
responsible
for
the
MSI
phenotype,
further
research
is
critical
to
clarify
this
topic.
Nevertheless,
our
studies
provided
evidence
for
a
potential
novel
molecular
pathway
in
a
proportion
of
medulloblastoma
and
paediatric
high-‐grade
gliomas,
associated
with
the
presence
of
MSI.
Overall,
the
work
summarized
in
this
thesis
contributed
to
the
knowledge
of
the
molecular
mechanisms
involved
in
the
development
of
childhood
and
adult
brain
tumours,
and
confirms
that,
despite
being
histologically
indistinguishable,
these
tumours
can
be
molecularly
distinctive.Os
tumores
cerebrais
são
a
principal
causa
de
morte
por
cancro
em
crianças,
sendo
também
os
principais
responsáveis
na
diminuição
de
anos
de
vida
em
doentes
oncológicos
de
todas
as
faixas
etárias.
Os
tumores
de
maior
malignidade
sãos
que
mais
contribuem
para
as
altas
taxas
de
mortalidade
e
morbilidade
características
dos
tumores
cerebrais.
Nesta
tese,
centramos
os
nossos
estudos
em
gliomas
de
alto
grau
e
meduloblastomas,
os
tumores
cerebrais
malignos
mais
frequentes
em
doentes
adultos
e
pediátricos,
respectivamente.
Apesar
dos
diversos
tipos
histológicos
de
tumores
cerebrais
serem
comuns
a
doentes
de
diferentes
idades,
existe
uma
significativa
diferença
na
frequência
com
que
ocorrem
em
adultos
e
crianças.
Além
disso,
há
cada
vez
mais
indícios
de
que,
tumores
histologicamente
semelhantes,
apresentam
diferenças
fundamentais
a
nível
clínico
e
molecular,
dependendo
da
idade
dos
doentes.
Os
tumores
cerebrais
são
caracterizados
por
diversas
alterações
genéticas
que
afectam
os
receptores
de
tirosina
cinase
(RTK).
Sendo
a
via
de
sinalização
do
RTK
EGFR
uma
das
mais
importantes
em
gliomas
de
alto
grau,
estudámos
alterações
moleculares
envolvidas
na
sua
activação
e
potencialmente
importantes
na
resposta
tumoral
à
terapia
dirigida.
O
papel
desta
molécula
em
gliomas
de
alto
grau
de
doentes
adultos
tem
sido
amplamente
descrito,
pelo
que
avaliámos
uma
série
de
tumores
de
doentes
Portugueses
adultos.
Neste
trabalho
pretendemos
perceber
se
as
alterações
de
EGFR
nos
tumores
Portugueses
se
assemelham
às
descritas
noutras
populações,
de
forma
a
avaliar
o
seu
potencial
papel
como
biomarcador
de
terapia
dirigida
ao
EGFR.
Por
outro
lado,
,
apesar
da
escassez
de
dados
publicados,
pensa-‐se
que
a
importância
do
EGFR
em
tumores
pediátricos
seja
limitada.
Para
melhor
esclarecer
este
assunto,
estudámos
a
presença
de
alterações
moleculares
do
EGFR
em
gliomas
pediátricos
de
alto
grau,
com
o
objectivo
de
avaliar
quais
os
potenciais
biomarcadores
na
resposta
a
fármacos
anti-‐EGFR.
Confirmámos
que
o
EGFR
é
uma
das
moléculas
mais
frequentemente
alteradas
em
gliomas
de
alto
grau,
particularmente
em
tumores
adultos,
sendo
isto
também
verdade
para
os
doentes
Portugueses.
Igualmente
os
tumores
pediátricos,
em
particular,
os
oligodendrogliomas
anaplásicos,
apresentam
alterações
nesta
molécula
e
consequentemente,
são
também
potenciais
candidatos
ao
uso
de
fármacos
anti-‐EGFR. A
ocorrência
de
instabilidade
de
microssatélites
(MSI)
em
tumores
cerebrais
é
um
tópico
de
investigação
controverso,
sendo
a
literatura
existente
insuficiente
para
a
esclarecer
este
assunto.
Neste
contexto,
estudámos
a
presença
de
MSI
em
gliomas
de
alto
grau
e
meduloblastomas
de
doentes
adultos
e
pediátricos,
assim
como
os
genes-‐alvo
potencialmente
envolvidos
na
tumorigénese
relacionada
com
MSI.
Os
nossos
resultados
demonstram
a
presença
de
MSI
numa
fracção
de
meduloblastomas
e
gliomas
de
alto
grau.
Em
meduloblastomas
não
se
observaram
variações
na
presença
de
MSI
em
doentes
de
diferentes
idades,
no
entanto
em
gliomas
de
alto
grau,
a
frequência
de
MSI
é
estatisticamente
mais
elevada
nos
tumores
pediátricos
.
Além
disso,
em
gliomas,
a
presença
de
MSI
foi
associada
a
um
perfil
genómico
estável.
Dos
mais
de
18
genes-‐alvo
analisados,
foram
encontradas
mutações
apenas
em
três
e
somente
em
tumores
pediátricos:
MBD4
num
meduloblastoma
e
MSH6
e
DNAPKcs
em
gliomas
de
alto
grau.
.
O
estudo
das
moléculas
de
“mismatch
repair”
não
clarificou
qual
o
seu
papel
no
fenótipo
de
MSI,
observado
nestes
doentes.
No
entanto,
os
nossos
estudos
evidenciam
a
presença
de
uma
potencial
nova
via
molecular
em
alguns
meduloblastomas
e
gliomas
de
alto
grau
associada
à
presença
de
MSI.
Concluindo,
o
trabalho
resumido
nesta
tese,
contribuiu
para
o
conhecimento
das
mecanismos
molecular
envolvidos
no
desenvolvimento
de
tumores
cerebrais
pediátricos
e
adultos,
e
confirma
que
apesar
de
histologicamente
semelhantes,
podem
ser
molecularmente
distintos
Analysis of microsatellite instability in medulloblastoma
Medulloblastoma is the most common malignant brain tumor in children. The presence of microsatellite instability (MSI) in brain tumors, particularly medulloblastomas, has not been properly addressed. The aim of the present study was to evaluate the role of MSI in medulloblastoma carcinogenesis. MSI status was determined in 36 patients using a pentaplex PCR of quasimonomorphic markers (NR27, NR21, NR24, BAT25, and BAT26). Methylation status of mismatch repair (MMR) genes was achieved by methylation-specific multiplex ligation-dependent probe amplification (MLPA). In addition, MutS homolog 6 (MSH6) expression was determined by immunohistochemistry. Mutations of 10 MSI target genes (TCF4, XRCC2, MBD4, MRE11, ATR, MSH3, TGFBR2, RAD50, MSH6, and BAX) were studied by pentaplex PCR followed by analysis with GeneScan 3.7 software. Mutation analysis of hotspot regions of beta-catenin (CTNNB1) and BRAF (v-raf murine sarcoma viral oncogene homolog B1) oncogenes was performed by PCR single-strand conformation polymorphism analysis followed by direct sequencing. Among the 36 tumors, we found four (11%) cases with instability, one with high MSI and three with low MSI. Methylation analysis of MMR genes in cases presenting shifts on the MSI markers revealed mild hypermethylation of MSH6 in 75% of cases, yet MSH6 was expressed in all the tumors. The MSI target genes MBD4 (methyl-CpG binding domain protein 4) and MRE11 (meiotic recombination 11 homolog A) were mutated in two different tumors. No CTNNB1 or BRAF mutations were found. This study is the most comprehensive analysis of MSI in medulloblastomas to date. We observed the presence of MSI together with mutations of MSI target genes in a small fraction of cases, suggesting a new genetic pathway for a role in medulloblastoma development.M.V.-P. is the recipient of a Ph.D. fellowship (SFRH/BD/29145/2006), and I.A. is the recipient
of a research fellowship (SFRH/BI/33160/2007) from
Fundação para a Ciência e Tecnologia, Portugal. This
study was partially supported by a grant from Clinical
de Radioterapia do Porto, Portugal
Study of hTERT and Histone 3 Mutations in Medulloblastoma
CNPq/Universal
(475358/2011-2), Fundação de Amparo à Pesquisa do Estado de
São Paulo (FAPESP; 2012/19590-0) and Fundação para a Ciência
e Tecnologia (FCT; PTDC/SAU-ONC/115513/2009) grants to
R.M.R. The project was cofinanced by Programa Operacional
Regional do Norte (ON.2-O Novo Norte), Quadro de Referência
Estratégico Nacional (QREN) and Fundo Europeu de Desenvol-
vimento Regional (FEDER). M.V.-P. is the recipient of an FCT
Post-Doctorate Research Fellowship (SFRH/BPD/104290/2014)Hotspot activating mutations of the telomerase reverse transcriptase (hTERT) promoter region were recently described in several tumor types. These mutations lead to enhanced expression of telomerase, being responsible for telomere maintenance and allowing continuous cell division. Additionally, there are alternative telomere maintenance mechanisms, associated with histone H3 mutations, responsible for disrupting the histone code and affecting the regulation of transcription. Here, we investigated the clinical relevance of these mechanistically related molecules in nnedulloblastoma. Sixty-nine medulloblastomas, formalin fixed and paraffin embedded, from a cohort of patients aged 1.5-70 years, were used to investigate the hotspot mutations of the hTERT promoter region, i.e. H3F3A and HIST1H3B, using Sanger sequencing. We successfully sequenced hTERT in all 69 medulloblastoma samples and identified a total of 19 mutated cases (27.5%). c.-124:G>A and c.-146:G>A mutations were detected, respectively, in 16 and 3 samples. Similar to previous reports, hTERT mutations were more frequent in older patients (p < 0.0001), being found only in 5 patients <20 years of age. In addition, hTERT-mutated tumors were more frequently recurrent (p = 0.026) and hTERT mutations were significantly enriched in tumors located in the right cerebellar hemisphere (p = 0.039). No mutations were found on the H3F3A or HIST1H3B genes. hTERT promoter mutations are frequent in medulloblastoma and are associated with older patients, prone to recurrence and located in the right cerebellar hemisphere. On the other hand, histone 3 mutations do not seem to be present in nnedulloblastoma.This study was partially supported by CNPq/Universal (475358/2011-2), Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP; 2012/19590-0) and Fundacao para a Ciencia e Tecnologia (FCT; PTDC/SAU-ONC/115513/2009) grants to R.M.R. The project was cofinanced by Programa Operacional Regional do Norte (ON.2-O Novo Norte), Quadro de Referencia Estrategico Nacional (QREN) and Fundo Europeu de Desenvolvimento Regional (FEDER). M.V.-P. is the recipient of an FCT Post-Doctorate Research Fellowship (SFRH/BPD/104290/2014).info:eu-repo/semantics/publishedVersio
Genetic variants of vascular endothelial growth factor predict risk and survival of gliomas
The vascular endothelial growth factor regulates angiogenesis that is increased in glioma. VEGF polymorphisms are thought to modulate vascular endothelial growth factor plasma levels and therefore may be implicated in glioma risk. We aimed to clarify the role of VEGF and von Willebrand factor polymorphisms in glioma susceptibility and prognosis. A case-control study of 126 glioma patients and 180 cancer-free controls was performed. Using Sequenom MassARRAY platform, 11 VEGF and 1 VWF polymorphisms were genotyped. Unconditional multivariate logistic regression models were used to calculate odds ratios and 95% confidence intervals. The associations between polymorphisms and survival were evaluated using a Cox regression model. Bonferroni's adjustment was used to correct for multiple testing. The VEGF polymorphism rs833061 was strongly associated with increased risk for glioma (odds ratio = 164.85) and glioblastoma (odds ratio = 155.66), confirmed after Bonferroni correction. Also, the VEGF polymorphisms rs3024994, rs2010963, and particularly the homozygous carriers of rs1005230 were associated with a worse prognosis for glioma and glioblastoma. Our data support a role of VEGF and VWF polymorphisms as glioma biomarkers, with additional potential relevance for molecular stratification of patients for anti-angiogenic therapies.FCT -Fundação para a Ciência e a Tecnologia(NORTE-01-0145-FEDER-000013)info:eu-repo/semantics/publishedVersio
A distinct spectrum of copy number aberrations in pediatric high-grade gliomas
As genome-scale technologies begin to unravel the complexity of the equivalent tumors in adults, we can attempt detailed characterization of high-grade gliomas in children, that have until recently been lacking. Toward this end, we sought to validate and extend investigations of the differences between pediatric and adult tumors. Purpose: As genome-scale technologies begin to unravel the complexity of the equivalent tumors in adults, we can attempt detailed characterization of high-grade gliomas in children, that have until recently been lacking. Toward this end, we sought to validate and extend investigations of the differences between pediatric and adult tumors.
Experimental Design: We carried out copy number profiling by array comparative genomic hybridization using a 32K bacterial artificial chromosome platform on 63 formalin-fixed paraffin-embedded cases of high-grade glioma arising in children and young people (<23 years).
Results: The genomic profiles of these tumors could be subclassified into four categories: those with stable genomes, which were associated with a better prognosis; those with aneuploid and those with highly rearranged genomes; and those with an amplifier genotype, which had a significantly worse clinical outcome. Independent of this was a clear segregation of cases with 1q gain (more common in children) from those with concurrent 7 gain/10q loss (a defining feature of adults). Detailed mapping of all the amplification and deletion events revealed numerous low-frequency amplifications, including IGF1R, PDGFRB, PIK3CA, CDK6, CCND1, and CCNE1, and novel homozygous deletions encompassing unknown genes, including those at 5q35, 10q25, and 22q13. Despite this, aberrations targeting the “core signaling pathways” in adult glioblastomas are significantly underrepresented in the pediatric setting.
Conclusions: These data highlight that although there are overlaps in the genomic events driving gliomagenesis of all ages, the pediatric disease harbors a distinct spectrum of copy number aberrations compared with adults.National Health Service funding to the NIHR
Biomedical Research Centre. This work was supported by The Royal
Marsden Children's Department Fund, Fundação para a Ciência e Tecnologia, Portugal, and Breakthrough Breast Cance
Height and body-mass index trajectories of school-aged children and adolescents from 1985 to 2019 in 200 countries and territories: a pooled analysis of 2181 population-based studies with 65 million participants
Summary Background Comparable global data on health and nutrition of school-aged children and adolescents are scarce. We aimed to estimate age trajectories and time trends in mean height and mean body-mass index (BMI), which measures weight gain beyond what is expected from height gain, for school-aged children and adolescents. Methods For this pooled analysis, we used a database of cardiometabolic risk factors collated by the Non-Communicable Disease Risk Factor Collaboration. We applied a Bayesian hierarchical model to estimate trends from 1985 to 2019 in mean height and mean BMI in 1-year age groups for ages 5–19 years. The model allowed for non-linear changes over time in mean height and mean BMI and for non-linear changes with age of children and adolescents, including periods of rapid growth during adolescence. Findings We pooled data from 2181 population-based studies, with measurements of height and weight in 65 million participants in 200 countries and territories. In 2019, we estimated a difference of 20 cm or higher in mean height of 19-year-old adolescents between countries with the tallest populations (the Netherlands, Montenegro, Estonia, and Bosnia and Herzegovina for boys; and the Netherlands, Montenegro, Denmark, and Iceland for girls) and those with the shortest populations (Timor-Leste, Laos, Solomon Islands, and Papua New Guinea for boys; and Guatemala, Bangladesh, Nepal, and Timor-Leste for girls). In the same year, the difference between the highest mean BMI (in Pacific island countries, Kuwait, Bahrain, The Bahamas, Chile, the USA, and New Zealand for both boys and girls and in South Africa for girls) and lowest mean BMI (in India, Bangladesh, Timor-Leste, Ethiopia, and Chad for boys and girls; and in Japan and Romania for girls) was approximately 9–10 kg/m2. In some countries, children aged 5 years started with healthier height or BMI than the global median and, in some cases, as healthy as the best performing countries, but they became progressively less healthy compared with their comparators as they grew older by not growing as tall (eg, boys in Austria and Barbados, and girls in Belgium and Puerto Rico) or gaining too much weight for their height (eg, girls and boys in Kuwait, Bahrain, Fiji, Jamaica, and Mexico; and girls in South Africa and New Zealand). In other countries, growing children overtook the height of their comparators (eg, Latvia, Czech Republic, Morocco, and Iran) or curbed their weight gain (eg, Italy, France, and Croatia) in late childhood and adolescence. When changes in both height and BMI were considered, girls in South Korea, Vietnam, Saudi Arabia, Turkey, and some central Asian countries (eg, Armenia and Azerbaijan), and boys in central and western Europe (eg, Portugal, Denmark, Poland, and Montenegro) had the healthiest changes in anthropometric status over the past 3·5 decades because, compared with children and adolescents in other countries, they had a much larger gain in height than they did in BMI. The unhealthiest changes—gaining too little height, too much weight for their height compared with children in other countries, or both—occurred in many countries in sub-Saharan Africa, New Zealand, and the USA for boys and girls; in Malaysia and some Pacific island nations for boys; and in Mexico for girls. Interpretation The height and BMI trajectories over age and time of school-aged children and adolescents are highly variable across countries, which indicates heterogeneous nutritional quality and lifelong health advantages and risks
Worldwide trends in underweight and obesity from 1990 to 2022: a pooled analysis of 3663 population-representative studies with 222 million children, adolescents, and adults
Background Underweight and obesity are associated with adverse health outcomes throughout the life course. We
estimated the individual and combined prevalence of underweight or thinness and obesity, and their changes, from
1990 to 2022 for adults and school-aged children and adolescents in 200 countries and territories.
Methods We used data from 3663 population-based studies with 222 million participants that measured height and
weight in representative samples of the general population. We used a Bayesian hierarchical model to estimate
trends in the prevalence of different BMI categories, separately for adults (age ≥20 years) and school-aged children
and adolescents (age 5–19 years), from 1990 to 2022 for 200 countries and territories. For adults, we report the
individual and combined prevalence of underweight (BMI <18·5 kg/m2) and obesity (BMI ≥30 kg/m2). For schoolaged children and adolescents, we report thinness (BMI <2 SD below the median of the WHO growth reference)
and obesity (BMI >2 SD above the median).
Findings From 1990 to 2022, the combined prevalence of underweight and obesity in adults decreased in
11 countries (6%) for women and 17 (9%) for men with a posterior probability of at least 0·80 that the observed
changes were true decreases. The combined prevalence increased in 162 countries (81%) for women and
140 countries (70%) for men with a posterior probability of at least 0·80. In 2022, the combined prevalence of
underweight and obesity was highest in island nations in the Caribbean and Polynesia and Micronesia, and
countries in the Middle East and north Africa. Obesity prevalence was higher than underweight with posterior
probability of at least 0·80 in 177 countries (89%) for women and 145 (73%) for men in 2022, whereas the converse
was true in 16 countries (8%) for women, and 39 (20%) for men. From 1990 to 2022, the combined prevalence of
thinness and obesity decreased among girls in five countries (3%) and among boys in 15 countries (8%) with a
posterior probability of at least 0·80, and increased among girls in 140 countries (70%) and boys in 137 countries (69%)
with a posterior probability of at least 0·80. The countries with highest combined prevalence of thinness and
obesity in school-aged children and adolescents in 2022 were in Polynesia and Micronesia and the Caribbean for
both sexes, and Chile and Qatar for boys. Combined prevalence was also high in some countries in south Asia, such
as India and Pakistan, where thinness remained prevalent despite having declined. In 2022, obesity in school-aged
children and adolescents was more prevalent than thinness with a posterior probability of at least 0·80 among girls
in 133 countries (67%) and boys in 125 countries (63%), whereas the converse was true in 35 countries (18%) and
42 countries (21%), respectively. In almost all countries for both adults and school-aged children and adolescents,
the increases in double burden were driven by increases in obesity, and decreases in double burden by declining
underweight or thinness.
Interpretation The combined burden of underweight and obesity has increased in most countries, driven by an
increase in obesity, while underweight and thinness remain prevalent in south Asia and parts of Africa. A healthy
nutrition transition that enhances access to nutritious foods is needed to address the remaining burden of
underweight while curbing and reversing the increase in obesit
Rising rural body-mass index is the main driver of the global obesity epidemic in adults
Body-mass index (BMI) has increased steadily in most countries in parallel with a rise in the proportion of the population who live in cities(.)(1,2) This has led to a widely reported view that urbanization is one of the most important drivers of the global rise in obesity(3-6). Here we use 2,009 population-based studies, with measurements of height and weight in more than 112 million adults, to report national, regional and global trends in mean BMI segregated by place of residence (a rural or urban area) from 1985 to 2017. We show that, contrary to the dominant paradigm, more than 55% of the global rise in mean BMI from 1985 to 2017-and more than 80% in some low- and middle-income regions-was due to increases in BMI in rural areas. This large contribution stems from the fact that, with the exception of women in sub-Saharan Africa, BMI is increasing at the same rate or faster in rural areas than in cities in low- and middle-income regions. These trends have in turn resulted in a closing-and in some countries reversal-of the gap in BMI between urban and rural areas in low- and middle-income countries, especially for women. In high-income and industrialized countries, we noted a persistently higher rural BMI, especially for women. There is an urgent need for an integrated approach to rural nutrition that enhances financial and physical access to healthy foods, to avoid replacing the rural undernutrition disadvantage in poor countries with a more general malnutrition disadvantage that entails excessive consumption of low-quality calories.Peer reviewe
Worldwide trends in hypertension prevalence and progress in treatment and control from 1990 to 2019: a pooled analysis of 1201 population-representative studies with 104 million participants.
BACKGROUND: Hypertension can be detected at the primary health-care level and low-cost treatments can effectively control hypertension. We aimed to measure the prevalence of hypertension and progress in its detection, treatment, and control from 1990 to 2019 for 200 countries and territories. METHODS: We used data from 1990 to 2019 on people aged 30-79 years from population-representative studies with measurement of blood pressure and data on blood pressure treatment. We defined hypertension as having systolic blood pressure 140 mm Hg or greater, diastolic blood pressure 90 mm Hg or greater, or taking medication for hypertension. We applied a Bayesian hierarchical model to estimate the prevalence of hypertension and the proportion of people with hypertension who had a previous diagnosis (detection), who were taking medication for hypertension (treatment), and whose hypertension was controlled to below 140/90 mm Hg (control). The model allowed for trends over time to be non-linear and to vary by age. FINDINGS: The number of people aged 30-79 years with hypertension doubled from 1990 to 2019, from 331 (95% credible interval 306-359) million women and 317 (292-344) million men in 1990 to 626 (584-668) million women and 652 (604-698) million men in 2019, despite stable global age-standardised prevalence. In 2019, age-standardised hypertension prevalence was lowest in Canada and Peru for both men and women; in Taiwan, South Korea, Japan, and some countries in western Europe including Switzerland, Spain, and the UK for women; and in several low-income and middle-income countries such as Eritrea, Bangladesh, Ethiopia, and Solomon Islands for men. Hypertension prevalence surpassed 50% for women in two countries and men in nine countries, in central and eastern Europe, central Asia, Oceania, and Latin America. Globally, 59% (55-62) of women and 49% (46-52) of men with hypertension reported a previous diagnosis of hypertension in 2019, and 47% (43-51) of women and 38% (35-41) of men were treated. Control rates among people with hypertension in 2019 were 23% (20-27) for women and 18% (16-21) for men. In 2019, treatment and control rates were highest in South Korea, Canada, and Iceland (treatment >70%; control >50%), followed by the USA, Costa Rica, Germany, Portugal, and Taiwan. Treatment rates were less than 25% for women and less than 20% for men in Nepal, Indonesia, and some countries in sub-Saharan Africa and Oceania. Control rates were below 10% for women and men in these countries and for men in some countries in north Africa, central and south Asia, and eastern Europe. Treatment and control rates have improved in most countries since 1990, but we found little change in most countries in sub-Saharan Africa and Oceania. Improvements were largest in high-income countries, central Europe, and some upper-middle-income and recently high-income countries including Costa Rica, Taiwan, Kazakhstan, South Africa, Brazil, Chile, Turkey, and Iran. INTERPRETATION: Improvements in the detection, treatment, and control of hypertension have varied substantially across countries, with some middle-income countries now outperforming most high-income nations. The dual approach of reducing hypertension prevalence through primary prevention and enhancing its treatment and control is achievable not only in high-income countries but also in low-income and middle-income settings. FUNDING: WHO