ORIGINAL ARTICLE

Ultra-Processed Foods Consumption Increases the Risk

of Hypertension in Adults: A Systematic Review and
Meta-Analysis
Mei Wang,1,2,3,4,* Xinyi Du,1,2,3,4,* Wei Huang,1,2,3,4 and Yong Xu1,2,3,4,

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BACKGROUND ratio: 1.23; 95% CI: 1.11, 1.37; P = 0.034). Furthermore, analyses were
Effect of ultra-processed foods (UPFs) consumption on health has performed based on gender, study design, exposure assessment,
attracted widespread attention in recent years. However, the re- outcome assessment, body mass index, energy intake, and phys-
lationship between UPFs consumption and hypertension is un- ical activity, which suggested that the results remained statistically
clear. This meta-analysis was conducted to analyze the above significant.
association.
CONCLUSIONS
METHODS Our findings suggested that UPFs might have detrimental effects on
We systematically searched PubMed, Embase, and Cochrane Library the incidence of hypertension in the general population. Although
for all relevant studies published up to 31 January 2022 without lan- current evidence is limited, it cannot be denied that reducing con-
guage limitation. The random-effects model was selected to pool the sumption of UPFs may contribute to decrease the risk of chronic
effect sizes and 95% confidence intervals (CIs). noncommunicable diseases.

RESULTS Keywords: blood pressure; hypertension; systematic review and meta-

Nine observational studies involving 111,594 participants were in- analysis; ultra-processed foods.
cluded. Results from this meta-analysis showed that higher UPFs
consumption significantly increased the risk of hypertension (odds https://doi.org/10.1093/ajh/hpac069

With the rapid development in the technology related to as oils, butter, sugar, and salt; (iii) processed foods, such as bottled
food production and processing, the global food system has vegetables, canned fish, fruits in syrup, cheeses, and freshly made
undergone significant changes in the past decades.1,2 Ultra- breads; (iv) UPFs, such as sausages, savory packaged snacks,
processed foods (UPFs) rich in sugar and saturated fats domi- reconstituted meat products.4 At the highest end of the pro-
nate the food supplies of high-income countries, and that UPFs cessing spectrum, UPFs are characteristically energy dense, high
consumption is now rapidly increasing in middle-income in unhealthy types of fat, refined starches, free sugars and salt,
countries, which might attribute to its availability, afforda- and poor sources of protein, dietary fiber, and micronutrients,5,6
bility, and marketability.3 Additionally, UPFs are considered many of these nutritional features being directly related to ad-
to be the major source of energy in most countries.2 verse health. Moreover, ultra-processed products are made to
To study the effect of food processing on nutritional quality and be hyperpalatable and attractive, with long shelf-life, and able to
health, the NOVA classification system, most widely used system be consumed anywhere, anytime.7 Therefore, UPFs have almost
for studying food processing, classifies foods into 4 groups based replaced the minimally processed food and freshly prepared
on the extent and purpose of food processing: (i) unprocessed dishes, and are high popularity worldwide.8
or minimally processed foods, such as fruits, offal, eggs, milk, The evidence so far has demonstrated that UPFs are asso-
fungi, algae, and water; (ii) processed culinary ingredients, such ciated with unhealthy dietary nutrient profiles and several

1Department of Endocrinology and Metabolism, Affiliated Hospital of

*These authors have contributed equally to this work and share first
authorship. Southwest Medical University, Luzhou, Sichuan, China; 2Luzhou Key
Laboratory of Cardiovascular and Metabolic Diseases, Department of
Correspondence: Yong Xu ([email protected]). Endocrinology and Metabolism, the Affiliated Hospital of Southwest
Medical University, Luzhou, Sichuan, China; 3Sichuan Clinical
Initially submitted April 22, 2022; accepted for publication June 18, Research Center for Nephropathy, Department of Endocrinology and
2022; online publication June 24, 2022. Metabolism, Luzhou, Sichuan, China; 4Metabolic Vascular Disease Key
Laboratory of Sichuan Province, Department of Endocrinology and
Metabolism, Luzhou, Sichuan, China.

© The Author(s) 2022. Published by Oxford University Press on

behalf of American Journal of Hypertension, Ltd. All rights reserved.
For permissions, please e-mail: [email protected]

892 American Journal of Hypertension 35(10) October 2022

 Ultra-processed Foods and Hypertension

noncommunicable chronic diseases.8 Several observational Exclusion criteria

studies have found that UPFs significantly increase the risk
of cardiovascular diseases,9,10 all-cause mortality,11,12 over- The exclusion criteria were as follows: (i) duplicate
weight and obesity,13,14 cancers,15,16 and depression.17,18 reports; (ii) not population-based studies; (iii) case
In contrast, there is evidence that consumption of cer- reports, comments, reviews, and conference summary;
tain unprocessed or minimally processed foods, such as (iv) nonobservational design; (v) not examined the associ-
whole grains, fruits, and vegetables, is inversely associated ation between UPFs and the risk of hypertension; (vi) not
with weight gain.19–21 Recently, possible relationships be- provided the relevant effect sizes and corresponding 95%
tween UPFs and hypertension are being more widespread confidence; and (vii) unavailable full text or incomplete
concerns. Some studies assessed the association between data.
intake of UPFs and hypertension,22–30 but the findings are
inconsistent. Therefore, a full understanding of the effect of Selection and data extraction
UPFs consumption on hypertension is greatly necessary.

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Although 2 recent systematic reviews assessed the asso- The titles and abstracts were screened independently
ciation between UPFs consumption and hypertension,31,32 by 2 authors (MW and XYD). Then the full texts were
some limitations would not be ignored. The results of reviewed based on inclusion and exclusion criteria. Any
previous studies showed that there was no statistically disagreement was resolved by the third party through ne-
significant association between UPFs consumption and hy- gotiation. Studies would be included in this meta-analysis if
pertension,31 or it only reviewed the studies on UPFs con- they examined the relationship between UPFs and the risk
sumption and hypertension without quantitative analysis.32 of hypertension in populations, and provided outcomes of
As a result, the association between UPFs consumption and hypertension and their risk estimates and 95% CIs. The fol-
hypertension remains unclear. Therefore, we aimed to con- lowing data from eligible published articles were extracted:
duct a comprehensive meta-analysis and systematic review (i) first author’s last name; (ii) year of publication; (iii)
of observational studies to assess the relationship between type of study design; (iv) study location; (v) number of
UPFs consumption and hypertension in adults. participants; (vi) age range and gender; (vii) duration of
follow-up for cohort studies; (viii) primary outcomes; (ix)
the most adjusted risk estimates (risk ratio, hazard ratio,
METHODS and OR) and corresponding 95% CIs; and (x) the covariates
This meta-analysis was conducted based on the Preferred used for adjustment.
Reporting Items for Systematic Reviews and Meta-Analyses
(PRISMA) guideline33 (Supplementary Table S1 online). Assessment of study quality
Ethical approval was not necessary because this study was
meta-analysis of published studies. Two investigators (MW and XYD) separately assessed
the quality of included articles using the Newcastle-Ottawa
scale (NOS) which was adapted for cross-sectional and co-
Search strategy and study selection hort studies. The NOS includes selection, comparability, and
We conducted a comprehensive literature search for outcome. Studies with NOS scores 1–3 stars indicated poor
all potentially relevant observational studies in PubMed, quality, NOS scores 4–6 stars indicated fair quality, and NOS
Embase, and Cochrane Library up to 31 January 2022 with scores 7–9 stars indicated high quality.34
no restriction on language. The search-relevant keywords
are as follows: ([Ultra processed foods OR Ultraprocessed Statistical analysis
foods OR Ultra-processed foods OR Processed foods] AND
[Hypertension OR Blood pressure]). We also examined rel- We equated hazard ratio and risk ratio with OR in this
evant original studies and review articles to search for other meta-analysis.35 The potential sources of heterogeneity
eligible studies. The search strategy is given in detail in between studies were assessed by using the Q test and I2
Supplementary Table S2 online. statistics,36 and I2 > 50% or P < 0.05 indicated significant het-
erogeneity. The random-effect model would be selected to
Inclusion criteria pool the effect sizes and corresponding 95% CIs if there was
significant heterogeneity. Otherwise, the fixed-effect model
Studies were included if they met the following explicit was employed. In order to further investigate whether the
criteria: (i) the type of research was observational studies relationship between UPFs and incidence of diabetes mel-
(such as cohort, cross-sectional, and case–control studies); litus and hypertension was biased by some specific factors
(ii) they were population-based studies; (iii) participants (e.g., study design, type of diseases, gender, continent, expo-
were ≥18 years old at baseline; (iv) the exposure interested sure assessment, outcome assessment, sample size, follow-up
was UPFs (as defined by the NOVA classification system); time, and adjustments [such as body mass index, energy in-
(v) the primary outcome of interest was hypertension; and take, and physical activity]), we conducted the subgroup
(vi) data provided as risk ratio, hazard ratio, or odds ratio analyses based on above factors. All statistical analyses were
(OR) and corresponding 95% confidence intervals (CIs) for conducted with Stata software (version 12.0, Stata Corp LP,
the risk of hypertension. College Station, TX).

American Journal of Hypertension 35(10) October 2022 893

Wang et al.

RESULTS Sensitivity analysis

Literature search and study characteristics Sensitivity analysis indicated that none of the included
studies had significant impact on the results of the meta-
We initially identified 1004 relevant articles from analysis (Figure 3).
PubMed, Embase, and Cochrane Library database. Finally,
9 articles met the inclusion criteria were included in this
meta-analysis after excluding duplicates, unrelated arti- Publication bias
cles, reviews, meta-analyses, and other studies. The pro- The Begg’s rank correlation test and the Egger’s regression
cess of literature screening is provided in the flow chart test confirmed that there was no publication bias for hyper-
(Figure 1). All of the included studies were observational, tension (P = 0.348 and P = 0.247, respectively). As shown in
including 4 cohort studies25,26,29,30 and 5 cross-sectional Figure 4, the funnel plots were symmetrical, which revealed
studies.22–24,27,28 Two studies were conducted in the United no clear publication bias.
States,22,24 2 in Canada,23,27 2 in Brazil,29,30 1 in Spain,25 1

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in Mexico,26 and 1 in Lebanon.28 Eight studies included
both men and women, 1 study only included women. DISCUSSION
For exposure assessment, 6 studies used food-frequency
questionnaire as exposure assessment tools,22,25,26,28–30 In our meta-analysis, we systematically summarized
while 3 studies were based on 24-hour dietary recall or the current published observational studies examining the
records.23,24,27 The characteristics of all included studies association between UPFs consumption and the risk of
are shown in Table 1. hypertension.
The result suggested that higher consumption of UPFs
significantly increased the risk of hypertension in adults.
UPFs consumption and the risk of hypertension Subgroup analyses, conducted based on study design, sample
size, geographical location, body mass index, energy intake,
Nine studies, including 4 cohort studies and 5 cross-sec- and physical activity, indicated that the results remained re-
tional studies, explored the effect of UPFs consumption on markable correlation between UPFs consumption and risk
the incidence of hypertension. Results of the meta-analysis of hypertension.
of 9 studies indicated that higher consumption of UPFs As the subgroup analysis showed, there was no association
was significantly associated with incidence of hypertension between UPFs consumption and hypertension in females,
(pooled OR: 1.23; 95% CI: 1.11, 1.37; I2 = 51.9%, P = 0.034), although based on only 1 study.26 The potential explana-
and the statistical heterogeneity was moderate with an I2 of tion may be that the ratio of energy contribution of UPFs
51.9% (Figure 2). Furthermore, analyses were performed in different countries may variable. For instance, the ratio
based on gender, study design, exposure assessment, out- of energy contribution of UPFs is 62% in the United States
come assessment, body mass index, energy intake, and but 29% in Chile, which perhaps causes the difference of in-
physical activity, which suggested that the results remained cidence of hypertension related to UPFs consumption.7,37
statistically significant (Table 2). Besides, the effect of UPFs on health may be cumulative
outcome over a long period of time but not captured in
short term. Moreover, education and income may also be
important factors to influence the result because the study
was conducted based on Mexican Teachers’ Cohort. Future
studies are needed to explore the effect of UPF consumption
on hypertension of different genders.
Our findings of a positive association between higher in-
take of UPFs and hypertension are consistent with previous
studies. A recent meta-analysis of observational studies
showed that sugar-sweetened beverages, which are part of
the definition of UPFs, are considered to be significantly as-
sociated with hypertension, as well as obesity, T2DM, and
all-cause mortality.38 It is reported that participants with
higher intake of UPFs had a greater risk of overweight and
obesity compared with participants with lower intake of
UPFs.39 And it is well known that obesity is considered as an
important risk factor for hypertension.
Recently, several potential mechanisms have been suggested
to explain the association between UPFs intake and the risk of
hypertension. As we mentioned earlier, UPFs are nutritionally
unbalanced due to high levels of free/added sugars, saturated
Figure 1. Flow diagram for the selection of eligible observational and trans-fatty acids, and low levels of protein, dietary fiber,
articles. and micronutrients. These differences in nutrient content of

894 American Journal of Hypertension 35(10) October 2022

 Table 1. Characteristics of included studies in this meta-analysis

Study Sample Exposure Diagnostic criteria for Study

Study ID Country design size Age Sex Comparison Exposure Reference assessment hypertension quality Adjustment

Nardocci Canada Cross- 13,608 ≥19 M + F Q3 vs. Q1 ≥58.7% of ≤38.5% of 24-Hour Self-declared AH— 7 stars Age, sex, smoking
et al.27 sectional TE TE dietary answer to question status, physical
recall on long-term activity, education,
health conditions income, residential
diagnosed by area, immigrant status,
healthcare provider: alcohol consumption,
“Do you have residential area, and
diabetes/ indigenous identity.
high blood
pressure?”
Rezende- Brazil Cohort 1,221 35.2 M + F Q5 vs. Q1 34.6%– 0.8%– FFQ Self-declared medical 8 stars Gender, age, marital
Alves 76.2% 16.6% of diagnosis or use of status, skin color, per
et al.29 of TE TE antihypertensive or capita income, physical
self-declared high activity, smoking,
BP (≥130/80 mm obesity, family history
Hg) according to of hypertension, and
recent cutoff points energy intake.
proposed by ACC/
AHA.
Mendonça Spain Cohort 14,790 36.3 M + F Q3 vs. Q1 NR NR FFQ Self-declared medical 8 stars Sex, age, physical
et al.25 diagnosis. activity, hours of TV
watching, baseline
BMI, smoking status,
use of analgesics,
following a special
diet at baseline, family
history of hypertension,
hypercholesterolemia,
alcohol consumption,
total energy intake,
olive oil intake,
consumption of fruits,
and vegetables.
Ivancovsky- United Cross- 789 58.83 ± 6.58 M + F Q4 vs. Q1 NR NR FFQ Systolic BP/diastolic 8 stars Age, gender, BMI, saturate
Wajcman States sectional BP ≥130/80 mm Hg fatty acids and protein
et al. 22 and/or medication. intake, physical activity,
coffee, and fibers.
Scaranni Brazil Cohort 8,754 35–74 M + F Q3 vs. Q1 15% of TE 35% of TE FFQ Measurement of BP 8 stars Age, sex, color or race,
et al.30 (SBP ≥140 mm Hg education, physical
or DBP ≥90 mm activity, smoking, alcohol
Hg) and use of consumption, Na intake
antihypertensive in measured by 12-hour
previous 2 weeks. urine sample, total daily
energy intake.
Lavigne- Canada Cross- 811 ≥18 M + F Q5 vs. Q1 83% of TE 21.1% of 24-Hour Measurement of BP 7 stars Age, sex, area of
Robichaud sectional TE dietary (SBP ≥130 mm Hg residence, current
et al. 23 recall or DBP ≥85 mm smoker, alcohol drinker,
Hg). and total dietary energy
intake.

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896
Wang et al.

Table 1. Continued

Study Sample Exposure Diagnostic criteria for Study

Study ID Country design size Age Sex Comparison Exposure Reference assessment hypertension quality Adjustment

Nasreddine Lebanon Cross- 302 ≥18 M + F Q4 vs. Q1 NR NR FFQ Measurement of BP 8 stars Age, gender, marital
et al.28 sectional (SBP ≥130 mm Hg status, BMI, area of
or DBP ≥85 mm residence, level of
Hg). education, income,
smoking status,
physical activity,
and total energy
intake.

American Journal of Hypertension 35(10) October 2022

Martínez United Cross- 6,385 ≥20 M + F Q5 vs. Q1 >71% of <40% of 24-Hour Measurement of BP 7 stars Sex, age, race/ethnicity,
Steele States sectional TE TE dietary (SBP ≥130 mm ratio of family income to
et al.24 recall Hg and/or DBP poverty and educational
≥85 mm Hg) or attainment + current
currently taking smoking status, and
antihypertensive physical activity.
medication.
Monge Mexico Cohort 64,934 ≥25 F Q5 vs. Q1 ≤20% of >45% of FFQ Self-declared medical 7 stars Age, indigenous,
et al.26 TE TE diagnosis or use of internet access,
antihypertensive. insurance, family
history of hypertension,
menopausal status,
smoking, physical
activity, energy intake,
and multivitamin
intake.

Abbreviations: AH, arterial hypertension; BMI, body mass index; BP, blood pressure; DBP, diastolic blood pressure; F, females; FFQ, food-frequency questionnaire; M, males; NR, not
reported; SBP, systolic blood pressure; TE, total energy.

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 Ultra-processed Foods and Hypertension

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Figure 2. Forest plot of the association between consumption of ultra-processed foods (UPFs) and hypertension using a random-effects model. Meta-
analysis of the data from the 9 included studies demonstrated that higher consumption of UPFs significantly increased the risk of hypertension.

UPFs may play an important role in these mechanisms. Firstly, vitamins, and minerals,53 which may also contribute to the de-
highly processed foods tend to have higher levels of refined velopment of diabetes mellitus and hypertension.
carbohydrates, which are quickly absorbed into the blood- Another potential mechanism may be associated with
stream, leading to high glycemic load (GL),40 the latter may the wide range of additives added to UPFs and chem-
activate return-related neural circuits (such as the striatum) ical compounds formed during their manufacturing
similar to addictive substances and increase cravings and processes or released from their packaging materials. For
hunger, thereby leading to an increase in energy intake,41–43 example, emulsifiers (e.g., carboxymethylcellulose and
which is associated with higher hypertension prevalence, in- polysorbate-80), detergent-like molecules that are a ubiq-
cidence, and greater increases in blood pressure. Besides, uitous component of processed foods, may affect the
diets high in carbohydrate might elevate insulin secretion and gut microbiome and promote colitis and metabolic syn-
promote the partitioning of energy toward storage as fat; in drome.54 Long-term consumption of artificial sweeteners
response, hunger and appetite increases.44 And excessive in- might accelerate atherosclerosis and senescence via impair-
take of fat also contributes to weight gain and the risk of over- ment of function and structure of apolipoprotein A–I and
weight or obesity, the latter being recognized as an important high-density lipoprotein.55 High levels of polycyclic aro-
risk factor for cardiovascular diseases. Several studies have matic hydrocarbons have also been shown to be positively
shown that UPFs and beverages (e.g., confectionery snacks, associated with hypertension.56,57 Acrylamide and acrolein
sugar-sweetened beverages, and cakes) might contain rela- produced during food heat treatments were linked to an
tively high levels of glucose-derived advanced glycation end increased risk of cardiovascular diseases.58,59 However, it still
products, the latter enhancing oxidative stress and initiating remains unclear what plays a leading role in the association.
inflammatory responses, which over time could lead to or ac- It is urgent to need a better understanding of what really
celerate vascular diseases.9,45–47 Moreover, data from animal matters and how various aspects influence those impacts.
experimental studies suggested that fructose may increase Our study provided comprehensive evidence of the nega-
blood pressure by stimulating uric acid,48 inhibiting endothe- tive influence of UPFs intake on hypertension. The findings
lial nitric oxide synthase system,49,50 stimulating sympathetic indicate that more efforts should be put into reducing the
nervous system,51 or directly increasing sodium absorption in high consumption of UPFs, and attach importance to
the intestinal tract.52 Additionally, sodium is one of the main promoting healthy and sustainable dietary habits.
ingredients added in the process of producing ready-to-eat
food such as processed meat,4,29,53 and it is well established that Strengths and limitations
avoiding excessive sodium consumption is crucial to prevent
hypertension and to reduce cardiovascular risk. Furthermore, Our meta-analysis provides the most comprehensive as-
intake of UPFs is associated with low intake of protein, fiber, sessment on the associations of UPFs consumption with

American Journal of Hypertension 35(10) October 2022 897

Wang et al.

Table 2. Subgroup analyses of consumption of ultra-processed

foods (UPFs) and risk of hypertension

No. of
Subgroups studies OR (95% CI) I2 % P

All 9 1.23 (1.11–1.37) 51.9 0.034

Design
Cohort 4 1.16 (1.03–1.32) 55.20 0.082
Cross-sectional 5 1.35 (1.11–1.64) 44.30 0.127
Sex
M+F 8 1.27 (1.17–1.38) 14.50 0.317

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M — — — —
F 1 0.98 (0.84–1.14) — —
Sample size Figure 3. Sensitivity analysis of all included studies.
≥10,000 3 1.22 (0.96–1.54) 83.4 0.002
<10,000 6 1.24 (1.13–1.36) 0.00 0.576
Exposure assessment
FFQ 6 1.20 (1.06–1.37) 51.00 0.069
Food record 3 1.29 (1.01–1.65) 61.8 0.073
Continent
Europe 1 1.21 (1.06–1.38) — —
Asia 1 3.10 (0.58–16.61) — —
North America 5 1.23 (1.01–1.50) 72.20 0.006
South America 2 1.26 (1.10–1.44) 0.00 0.580
Outcome assessment
Measured 5 1.23 (1.11–1.35) 0.00 0.486
Self-reported 4 1.24 (1.02–1.51) 76.80 0.005
BMI
Yes 2 1.58 (1.11–2.24) 0.00 0.420 Figure 4. Funnel plot evaluating the publication bias for associa-
tion between the intake of ultra-processed foods (UPFs) and the risk of
No 7 1.21 (1.08–1.35) 55.80 0.035 hypertension.
Energy intake
Yes 6 1.16 (1.03–1.30) 40.20 0.137 UPFs consumption was not exactly the same in the included
No 3 1.39 (1.12–1.72) 60.60 0.079 studies of this meta-analysis, which made these comparisons
less straightforward; thus, we could only obtain a quantita-
Physical activity
tive rate of the association between the UPFs consumption
Yes 8 1.24 (1.11–1.39) 56.50 0.024 and hypertension but not a specific range. Finally, subgroup
No 1 0.99 (0.59–1.67) — — meta-analyses by common study characteristic do not com-
pletely eliminate substantial heterogeneity across studies.
Abbreviations: BMI, body mass index; CI, confidence interval; F, Improved analyses should be carried out as more informa-
females; FFQ, food-frequency questionnaire; M, males; OR, odds tion becomes available in the future.
ratio. Based on our findings, consumption of UPFs is signifi-
cantly associated with an increased risk of hypertension in
hypertension. Moreover, studies involving a large number adults. As the current evidence is limited, more longitudinal
of participants are expected to provide sufficient statis- studies and intervention studies are needed in the future to
tical power to examine the relationship between UPF and further explore the potential association between UPFs con-
hypertension. Nevertheless, there are also several limita- sumption and hypertension.
tions to be acknowledged. Firstly, our meta-analysis was
based on observational studies and thus some unmeasured
confounding factors may have various degrees of influence SUPPLEMENTARY MATERIAL
on the results. Secondly, the studies included in this meta-
analysis were used to assess UPFs consumption through Supplementary data are available at American Journal of
food-frequency questionnaire, food recording, and 24-hour Hypertension online.
recall, which are likely to recall bias. Thirdly, the definition of Supplementary Table 1. PRISMA checklist.

898 American Journal of Hypertension 35(10) October 2022

 Ultra-processed Foods and Hypertension

Supplementary Table 2. Search strategy to identify ob- 8. Forouzanfar MH, Afshin A, Alexander LT, Anderson HR, Bhutta ZA,
servational studies reporting the association between ultra- Biryukov S, Brauer M, Burnett R, Cercy K, Charlson FJ, Cohen AJ,
Dandona L, Estep K, Ferrari AJ, Frostad JJ, Fullman N, Gething PW,
processed foods (UPFs) consumption and hypertension. Godwin WW, Griswold M, Hay SI, Kinfu Y, Kyu HH, Larson HJ,
Liang X, Lim SS, Liu PY, Lopez AD, Lozano R, Marczak L, Mensah GA,
Mokdad AH, Moradi-Lakeh M, Naghavi M, Neal B, Reitsma MB,
Roth GA, Salomon JA, Sur PJ, Vos T, Wagner JA, Wang H, Zhao Y,
FUNDING
Zhou M, Aasvang GM, Abajobir AA, Abate KH, Abbafati C, Abbas KM,
Abd-Allah F, Abdulle AM, Abera SF, Abraham B, Abu-Raddad LJ,
This study was supported by the Sichuan Science and Abyu GY, Adebiyi AO, Adedeji IA, Ademi Z, Adou AK, Adsuar JC,
Technology Program, Sichuan, China (grant numbers: Agardh EE, Agarwal A, Agrawal A, Kiadaliri AA, Ajala ON,
2020YFS0456 and 2019YFS0537) and the Luzhou-Southwest Akinyemiju TF, Al-Aly Z, Alam K, Alam NKM, Aldhahri SF,
Medical University cooperation project, Luzhou, Sichuan, Aldridge RW, Alemu ZA, Ali R, Alkerwi Aa, Alla F, Allebeck P,
Alsharif U, Altirkawi KA, Martin EA, Alvis-Guzman N, Amare AT,
China (grant number: 2018LZXNYD—PT01). Amberbir A, Amegah AK, Amini H, Ammar W, Amrock SM,
Andersen HH, Anderson BO, Antonio CAT, Anwari P, Ärnlöv J,

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Artaman A, Asayesh H, Asghar RJ, Assadi R, Atique S, Avokpaho EFGA,
Awasthi A, Quintanilla BPA, Azzopardi P, Bacha U, Badawi A,
Bahit MC, Balakrishnan K, Barac A, Barber RM, Barker-Collo SL,
ACKNOWLEDGMENTS Bärnighausen T, Barquera S, Barregard L, Barrero LH, Basu S, Batis C,
Bazargan-Hejazi S, Beardsley J, Bedi N, Beghi E, Bell B, Bell ML,
We thank all participants from the Department of Bello AK, Bennett DA, Bensenor IM, Berhane A, Bernabé E, Betsu BD,
Endocrinology and Metabolism, the Affiliated Hospital Beyene AS, Bhala N, Bhansali A, Bhatt S, Biadgilign S, Bikbov B,
of Southwest Medical University for their assistance and Bisanzio D, Bjertness E, Blore JD, Borschmann R, Boufous S,
Bourne RRA, Brainin M, Brazinova A, Breitborde NJK, Brenner H,
support. Broday DM, Brugha TS, Brunekreef B, Butt ZA, Cahill LE, Calabria B,
Campos-Nonato IR, Cárdenas R, Carpenter DO, Carrero JJ, Casey DC,
Castañeda-Orjuela CA, Rivas JC, Castro RE, Catalá-López F, Chang J-
AUTHORS’ CONTRIBUTIONS C, Chiang PP-C, Chibalabala M, Chimed-Ochir O, Chisumpa VH,
Chitheer AA, Choi J-YJ, Christensen H, Christopher DJ, Ciobanu LG,
Coates MM, Colquhoun SM, Manzano AGC, Cooper LT,
Y.X. and W.H. were involved in the whole conception and Cooperrider K, Cornaby L, Cortinovis M, Crump JA, Cuevas-Nasu L,
design process of the study. M.W. and X.D. contributed to Damasceno A, Dandona R, Darby SC, Dargan PI, das Neves J, Davis AC,
the selection of literature and participated in the process Davletov K, de Castro EF, De la Cruz-Góngora V, De Leo D,
of literature quality evaluation, data extraction, and anal- Degenhardt L, Del Gobbo LC, del Pozo-Cruz B, Dellavalle RP,
ysis. M.W. wrote the paper. Y.X. and W.H. commented on Deribew A, Jarlais DCD, Dharmaratne SD, Dhillon PK, Diaz-Torné C,
Dicker D, Ding EL, Dorsey ER, Doyle KE, Driscoll TR, Duan L,
the manuscript. All authors read and approved the final Dubey M, Duncan BB, Elyazar I, Endries AY, Ermakov SP, Erskine HE,
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Gessner BD, Giref AZ, Giroud M, Gishu MD, Giussani G, Goenka S,
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