Risk factors in adolescents as predictors of arterial hypertension in adults: Protocol for a systematic review.

This is a protocol of a review paper, and there is no abstract. This review is part of a doctoral project that aims to develop a discrete event simulation model to predict how many adolescents may become hypertensive in adulthood. We will use data from the Brazilian study of cardiovascular risks in adolescents, called ERICA (Portuguese acronym). This study may help promote adherence to disease prevention protocols.

Introduction

Cardiovascular diseases have been the leading cause of death in Brazil for more than three decades. Early control of high blood pressure (HBP), smoking, hypercholesterolemia, and obesity may contribute to the reduction of cardiovascular morbidity and mortality [1].

HBP is defined by sustained blood pressure (BP) levels above systolic 140 or diastolic 90 mmHg (millimeters of mercury), or both for adults, according to the 7th Brazilian Guidelines for Hypertension [1]. It is a multifactorial clinical condition often associated with functional or structural alterations of the target organs (heart, brain, kidneys, and blood vessels); and metabolic changes, with a consequent increase in the risk of fatal and non-fatal cardiovascular events [1, 2]. HBP affects 30% of the adult population, and about one third do not know their condition. According to the World Health Organization (WHO) [2], 17 million people die each year worldwide due to cardiovascular diseases. HBP increases the risk of myocardial infarction, stroke, and renal failure, and can cause heart failure. It is an asymptomatic disease, and many individuals are diagnosed only when the first complication arises. Factors associated with the development of hypertension include age, sex, ethnicity, body weight, salt and alcohol intake, lifestyle, socioeconomic status, and genetic factors [3].

Interest in the assessment of BP in children and adolescents began in the 1960s. The first recommendations for routine BP measurement in this age group appeared only in the 1970s. Until then, only secondary changes in BP were identified. New studies have emerged to understand the behavior of BP in this age group, its determining factors, its relationship with future HBP or cardiovascular disease, and to adopt primary prevention measures [4].

Aspects such as eating habits, lifestyle, and high blood pressure in childhood and adolescence, are important in the occurrence of cardiovascular diseases in adults [5]. Some risk factors, such as overweight, physical inactivity, and inadequate diet, are now more prevalent than in previous times in children and adolescents [5].

A systematic review estimated the pooled prevalence of HBP in Latin America in 6.2% (95% CI 3.1–10.6) [6]. Another study estimated the pooled prevalence of HBP in Brazilian adolescents in 8.12% (95% CI 6.24–10.52) [7].

It is essential to highlight the difference between association and prediction. An association indicates whether the exposition is more likely to be present in individuals who have hypertension, but doesn’t necessarily imply that it is a causal risk factor. More important, if it is not causal, then measures to control it will have no effect [8].

It has been shown that HBP in childhood can be a predictive factor for systemic arterial hypertension in adulthood. Several cohort studies have found a significant correlation between HBP in children and adolescents and hypertension in adulthood [9, 10]. Children with blood pressure above the 90th percentile are 2.4 times more likely to be hypertensive adults [11]. Although essential hypertension in children is not a risk factor for cardiovascular events in childhood, cardiovascular and hemodynamic changes can be seen in these individuals from the second decade of life or even earlier [12].

Question to be answered: What are the predictors in childhood of HBP in adulthood.

The objective of this review is to assess the published evidence on risk factors for HBP present in adolescents and their contribution to the development of the disease in adulthood.

Materials and methods

This systematic review was registered in PROSPERO ID: CRD42020172254. This protocol for systematic review follows the principles recommended in PRISMA-P for protocols [13] (S1 Checklist).

Eligibility criteria

The studies will be selected according to the following criteria:

Types of studies

Cohort studies. We will include prospective and retrospective cohort studies that measured risk factors in adolescence and document their long-term association with HBP occurring in adulthood.

Participants

Studies examining adolescents (aged 12 to 17 years), in general population.

Outcome measure

The outcome is the relative risk (RR) or other measure of association (OR, HR) of HBP in adulthood (age over 18 years). for each of the risk factors in adolescence. If the outcome measure is another (OR, for example), the results will be grouped according to the measure presented, or converted to RR.

Exclusion criteria

Studies focused on specific populations known to have a higher incidence of HBP (such as diabetics, adolescents who are obese, or have cardiac, or renal diseases).

Search methods for identification of studies

The databases to be searched will include Embase, LILACS, ADOLEC, MEDLINE, Cochrane Library, and references of selected articles that meet the inclusion criteria. There will be no restriction on language and date. The terms (and respective entry terms) used will be: risk factor, adolescent, trends, hypertension, high blood pressure, adults, middle aged, epidemiologic studies, cohort studies, follow-up studies, longitudinal studies.

Data collection and analysis

Selection of studies. Two reviewers will independently screen identified titles and abstracts applying the eligibility criteria described above. Full texts will then be analyzed to determine which studies meet the defined inclusion criteria. The selection will be made using Rayyan QCRI [14], which is a 100% free web/mobile application. Disagreements at this stage will be resolved by consensus or by involving a third reviewer.

Data extraction and management. The extraction will be carried out by two peers independently using a standard form. When more than one publication of a study is available, the most recent data will be used, unless relevant results were published in an earlier version. Disagreements will be resolved by consensus or by involving a third reviewer.

Predictive factors

The potential predictive factors are defined by the guidelines for hypertension of the Brazilian Society of Cardiology [1]: sex, ethnicity, body weight (overweight and obesity), salt and alcohol intake, physical activity, family history and socioeconomic factors. If found in a paper reported other factors not listed with a strong association for adolescents, these will be included.

Quality assessment. The methodological quality of potential studies will be assessed using the Newcastle-Ottawa scale (NOS) for non-randomized studies. We will use the “Quality In Prognosis Studies” (QUIPS) [15] tool that consists of several prompting items categorized into six domains ((1) study participation, (2) study attrition, (3) prognostic factor measurement, (4) outcome measurement, (5) study confounding, and (6) statistical analysis and reporting), and each domain is judged on a three-grade scale (low, moderate or high risk of bias).

Data analysis and statistical considerations

Data synthesis and analyses will be done using the Cochrane Review Manager software, RevMan 5.4. When possible (depending on the number of studies), studies will be combined in a meta-analysis. For variables, the association will be expressed as RR, or some other measure, for occurrence of HBP in adults. Uncertainty will be quantified with a 95% CI. The heterogeneity between the studies will be assessed using the I2 statistic. When I2 <50%, we will use the fixed-effect model. In the event of significant inconsistency, possible causes will be assessed on a case-by-case basis and, when necessary, subgroup analysis will be carried out. We will use funnel plots to assess the potential existence of reporting bias. If there is evidence of effect modification, the analysis will be stratified by sex, ethnicity, and socioeconomic factors.

The status of the study

The study is in the data collection and analysis phase. The initial deadline for completion is October2021.

PRISMA-P-checklist RS risk factors.

(DOCX)

Click here for additional data file.

12 Feb 2021

Submitted filename: Response to editor.docx

Click here for additional data file.

24 Jun 2021

PONE-D-21-04728

Risk factors in adolescents as predictors of arterial hypertension in adults: protocol for a systematic review

PLOS ONE

Dear Dr. Costa,

Thank you for submitting your manuscript to PLOS ONE. After careful consideration, we feel that it has merit but does not fully meet PLOS ONE’s publication criteria as it currently stands. Therefore, we invite you to submit a revised version of the manuscript that addresses the points raised during the review process.

The Study Protocol format aims to support a strong methodological approach, increase the reproducibility of results, and address publication bias. Authors first submit a Study Protocol that should include a study’s rationale, its timeline, and proposed methodology for data collection and analysis; this article type does not include results, although it may report pilot data. The authors may disregard reviewer 1’s comments regarding lack of results. They need to carefully address the other reviewer comments.

Please submit your revised manuscript by Aug 08 2021 11:59PM. If you will need more time than this to complete your revisions, please reply to this message or contact the journal office at plosone@plos.org. When you're ready to submit your revision, log on to https://www.editorialmanager.com/pone/ and select the 'Submissions Needing Revision' folder to locate your manuscript file.

Please include the following items when submitting your revised manuscript:

A rebuttal letter that responds to each point raised by the academic editor and reviewer(s). You should upload this letter as a separate file labeled 'Response to Reviewers'.

A marked-up copy of your manuscript that highlights changes made to the original version. You should upload this as a separate file labeled 'Revised Manuscript with Track Changes'.

An unmarked version of your revised paper without tracked changes. You should upload this as a separate file labeled 'Manuscript'.

If you would like to make changes to your financial disclosure, please include your updated statement in your cover letter. Guidelines for resubmitting your figure files are available below the reviewer comments at the end of this letter.

If applicable, we recommend that you deposit your laboratory protocols in protocols.io to enhance the reproducibility of your results. Protocols.io assigns your protocol its own identifier (DOI) so that it can be cited independently in the future. For instructions see: http://journals.plos.org/plosone/s/submission-guidelines#loc-laboratory-protocols. Additionally, PLOS ONE offers an option for publishing peer-reviewed Lab Protocol articles, which describe protocols hosted on protocols.io. Read more information on sharing protocols at https://plos.org/protocols?utm_medium=editorial-email&utm_source=authorletters&utm_campaign=protocols.

We look forward to receiving your revised manuscript.

Kind regards,

Johannes Vogel

Academic Editor

PLOS ONE

Journal Requirements:

When submitting your revision, we need you to address these additional requirements.

1. Please ensure that your manuscript meets PLOS ONE's style requirements, including those for file naming. The PLOS ONE style templates can be found at

and

https://journals.plos.org/plosone/s/file?id=ba62/PLOSOne_formatting_sample_title_authors_affiliations.pdf

2. Please review your reference list to ensure that it is complete and correct. If you have cited papers that have been retracted, please include the rationale for doing so in the manuscript text, or remove these references and replace them with relevant current references. Any changes to the reference list should be mentioned in the rebuttal letter that accompanies your revised manuscript. If you need to cite a retracted article, indicate the article’s retracted status in the References list and also include a citation and full reference for the retraction notice.

3. We note that you have stated that you will provide repository information for your data at acceptance. Should your manuscript be accepted for publication, we will hold it until you provide the relevant accession numbers or DOIs necessary to access your data. If you wish to make changes to your Data Availability statement, please describe these changes in your cover letter and we will update your Data Availability statement to reflect the information you provide.

4. Please include captions for your Supporting Information files at the end of your manuscript, and update any in-text citations to match accordingly. Please see our Supporting Information guidelines for more information: http://journals.plos.org/plosone/s/supporting-information.

[Note: HTML markup is below. Please do not edit.]

Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. Does the manuscript provide a valid rationale for the proposed study, with clearly identified and justified research questions?

The research question outlined is expected to address a valid academic problem or topic and contribute to the base of knowledge in the field.

Reviewer #1: Yes

Reviewer #2: Yes

**********

2. Is the protocol technically sound and planned in a manner that will lead to a meaningful outcome and allow testing the stated hypotheses?

The manuscript should describe the methods in sufficient detail to prevent undisclosed flexibility in the experimental procedure or analysis pipeline, including sufficient outcome-neutral conditions (e.g. necessary controls, absence of floor or ceiling effects) to test the proposed hypotheses and a statistical power analysis where applicable. As there may be aspects of the methodology and analysis which can only be refined once the work is undertaken, authors should outline potential assumptions and explicitly describe what aspects of the proposed analyses, if any, are exploratory.

Reviewer #1: Partly

Reviewer #2: Yes

**********

3. Is the methodology feasible and described in sufficient detail to allow the work to be replicable?

Descriptions of methods and materials in the protocol should be reported in sufficient detail for another researcher to reproduce all experiments and analyses. The protocol should describe the appropriate controls, sample size calculations, and replication needed to ensure that the data are robust and reproducible.

Reviewer #1: No

Reviewer #2: Yes

**********

4. Have the authors described where all data underlying the findings will be made available when the study is complete?

The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception, at the time of publication. The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified.

Reviewer #1: No

Reviewer #2: Yes

**********

5. Is the manuscript presented in an intelligible fashion and written in standard English?

PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here.

Reviewer #1: Yes

Reviewer #2: Yes

**********

6. Review Comments to the Author

Please use the space provided to explain your answers to the questions above and, if applicable, provide comments about issues authors must address before this protocol can be accepted for publication. You may also include additional comments for the author, including concerns about research or publication ethics.

You may also provide optional suggestions and comments to authors that they might find helpful in planning their study.

(Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #1: This manuscript contains a plan to review literature to identify childhood predictors of adult hypertension. However, no data was presented. I am unclear as to the rationale for submitting this preliminary work for publication given that there are no results and nothing meaningful will be contributed to the published literature on this subject.

Reviewer #2: Pg 1 – Please explain numbers 1 and 3 in the affiliation - for the first and last authors.

Pg 2- Background – P 2 – “HBP is defined by sustained blood pressure (BP) levels above systolic 140 or diastolic 90 mmHg (millimeters of mercury), or both.” – Please review the definition.

In accordance with most major guidelines it is recommended that hypertension be diagnosed when a person’s systolic blood pressure in the office is ≥ 140 mm Hg and/or their diastolic blood pressure is ≥ 90 mm Hg. This definition does not apply to the United States. In the 2017 ACC/AHA guideline, hypertension is defined as BP ≥130 and / or ≥80 mm Hg.

Another important thing is that these definitions apply to adults ≥ 18 years of age.

For the adolescents, what definition do you intend to use?

Pg 5 - If the included population consists of adolescents aged between 12 to 17 years and the outcomes are measured at adulthood (age over 19 years), how are considered subjects aged 18 years – adolescents or adults?

Pg 5 row 108 – a bracket is missing

Pg 5 row 113 – a space and a comma in addition

Pg 5 – Search methods – “The databases to be searched will include Embase, LILACS, ADOLEC, MEDLINE, Cochrane Library, and bibliographic citations. “ What will be the selection criteria for “bibliographic citations” ?

Pg 5 - There may be too many search terms.

I recommend not using the term “skin pigmentation” ; this is not a risk factor for the purpose of this review.

Pg 7 – “The initial deadline for completion is April 2021.”

A new deadline must be set.

**********

7. PLOS authors have the option to publish the peer review history of their article (what does this mean?). If published, this will include your full peer review and any attached files.

If you choose “no”, your identity will remain anonymous but your review may still be made public.

Do you want your identity to be public for this peer review? For information about this choice, including consent withdrawal, please see our Privacy Policy.

Reviewer #1: No

Reviewer #2: No

[NOTE: If reviewer comments were submitted as an attachment file, they will be attached to this email and accessible via the submission site. Please log into your account, locate the manuscript record, and check for the action link "View Attachments". If this link does not appear, there are no attachment files.]

While revising your submission, please upload your figure files to the Preflight Analysis and Conversion Engine (PACE) digital diagnostic tool, https://pacev2.apexcovantage.com/. PACE helps ensure that figures meet PLOS requirements. To use PACE, you must first register as a user. Registration is free. Then, login and navigate to the UPLOAD tab, where you will find detailed instructions on how to use the tool. If you encounter any issues or have any questions when using PACE, please email PLOS at figures@plos.org. Please note that Supporting Information files do not need this step.

4 Aug 2021

Response to Reviewers

1. Please ensure that your manuscript meets PLOS ONE's style requirements, including those for file naming. The PLOS ONE style templates can be found at

https://journals.plos.org/plosone/s/file?id=wjVg/PLOSOne_formatting_sample_main_body.pdf and https://journals.plos.org/plosone/s/file?id=ba62/PLOSOne_formatting_sample_title_authors_affiliations.pdf

Response: done.

2. Please review your reference list to ensure that it is complete and correct. If you have cited papers that have been retracted, please include the rationale for doing so in the manuscript text, or remove these references and replace them with relevant current references. Any changes to the reference list should be mentioned in the rebuttal letter that accompanies your revised manuscript. If you need to cite a retracted article, indicate the article’s retracted status in the References list and also include a citation and full reference for the retraction notice.

Response: reference 4 corrected.

3. We note that you have stated that you will provide repository information for your data at acceptance. Should your manuscript be accepted for publication, we will hold it until you provide the relevant accession numbers or DOIs necessary to access your data. If you wish to make changes to your Data Availability statement, please describe these changes in your cover letter and we will update your Data Availability statement to reflect the information you provide.

Response: Please make the following change regarding the availability of data: The results of this study will be available in article format to be submitted for publication.

4. Please include captions for your Supporting Information files at the end of your manuscript, and update any in-text citations to match accordingly. Please see our Supporting Information guidelines for more information: http://journals.plos.org/plosone/s/supporting-information.

Response: done (page 4, line 92 and after references).

Reviewer #1:

This manuscript contains a plan to review literature to identify childhood predictors of adult hypertension. However, no data was presented. I am unclear as to the rationale for submitting this preliminary work for publication given that there are no results and nothing meaningful will be contributed to the published literature on this subject.

Response written by the editor: Authors first submit a Study Protocol that should include a study’s rationale, its timeline, and proposed methodology for data collection and analysis; this article type does not include results, although it may report pilot data. The authors may disregard reviewer 1’s comments regarding lack of results.

Reviewer #2:

Pg 1 – Please explain numbers 1 and 3 in the affiliation - for the first and last authors.

Response: We apologize for the typo. The first and last authors are from the same institution. Affiliation has been corrected (number 3 has been removed and inserted number 1 for last author)

Pg 2- Background – P 2 – “HBP is defined by sustained blood pressure (BP) levels above systolic 140 or diastolic 90 mmHg (millimeters of mercury), or both.” – Please review the definition.

In accordance with most major guidelines it is recommended that hypertension be diagnosed when a person’s systolic blood pressure in the office is ≥ 140 mm Hg and/or their diastolic blood pressure is ≥ 90 mm Hg. This definition does not apply to the United States. In the 2017 ACC/AHA guideline, hypertension is defined as BP ≥130 and / or ≥80 mm Hg.

Another important thing is that these definitions apply to adults ≥ 18 years of age.

For the adolescents, what definition do you intend to use?

Response: We use the definition of HBP according to the 7th Brazilian Guidelines for Hypertension for adults (included in the text). For the adolescents, in this review we will identify the definition used by the authors of each selected study.

Pg 5 - If the included population consists of adolescents aged between 12 to 17 years and the outcomes are measured at adulthood (age over 19 years), how are considered subjects aged 18 years – adolescents or adults?

Response: This has been corrected as the subjects aged 18 years will be considered adults (included in line 104 page 5).

Pg 5 row 108 – a bracket is missing

Response: corrected

Pg 5 row 113 – a space and a comma in addition

Response: corrected

Pg 5 – Search methods – “The databases to be searched will include Embase, LILACS, ADOLEC, MEDLINE, Cochrane Library, and bibliographic citations. “ What will be the selection criteria for “bibliographic citations” ?

Response: Bibliographic citations refers to the references provided in the articles that meet the inclusion criteria. Corrected in the text.

Pg 5 - There may be too many search terms.

I recommend not using the term “skin pigmentation”; this is not a risk factor for the purpose of this review.

Response: We agree and removed this term from the search.

Pg 7 – “The initial deadline for completion is April 2021.” A new deadline must be set.

Response: Amended to October

Submitted filename: Response to Reviewers.docx

Click here for additional data file.

11 Aug 2021

Risk factors in adolescents as predictors of arterial hypertension in adults: protocol for a systematic review

PONE-D-21-04728R1

Dear Dr. Costa,

We’re pleased to inform you that your manuscript has been judged scientifically suitable for publication and will be formally accepted for publication once it meets all outstanding technical requirements.

Within one week, you’ll receive an e-mail detailing the required amendments. When these have been addressed, you’ll receive a formal acceptance letter and your manuscript will be scheduled for publication.

An invoice for payment will follow shortly after the formal acceptance. To ensure an efficient process, please log into Editorial Manager at http://www.editorialmanager.com/pone/, click the 'Update My Information' link at the top of the page, and double check that your user information is up-to-date. If you have any billing related questions, please contact our Author Billing department directly at authorbilling@plos.org.

If your institution or institutions have a press office, please notify them about your upcoming paper to help maximize its impact. If they’ll be preparing press materials, please inform our press team as soon as possible -- no later than 48 hours after receiving the formal acceptance. Your manuscript will remain under strict press embargo until 2 pm Eastern Time on the date of publication. For more information, please contact onepress@plos.org.

Kind regards,

Johannes Vogel

Academic Editor

PLOS ONE

Additional Editor Comments (optional):

Reviewers' comments:

12 Aug 2021

PONE-D-21-04728R1

Risk factors in adolescents as predictors of arterial hypertension in adults: protocol for a systematic review

Dear Dr. Costa:

I'm pleased to inform you that your manuscript has been deemed suitable for publication in PLOS ONE. Congratulations! Your manuscript is now with our production department.

If your institution or institutions have a press office, please let them know about your upcoming paper now to help maximize its impact. If they'll be preparing press materials, please inform our press team within the next 48 hours. Your manuscript will remain under strict press embargo until 2 pm Eastern Time on the date of publication. For more information please contact onepress@plos.org.

If we can help with anything else, please email us at plosone@plos.org.

Thank you for submitting your work to PLOS ONE and supporting open access.

Kind regards,

PLOS ONE Editorial Office Staff

on behalf of

Professor Johannes Vogel

Academic Editor

PLOS ONE