PONE-D-19-34971

Untreated hypertension in Russian 35-69 year olds – a cross-sectional study

PLOS ONE

Dear Dr. PETERSEN,

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.

I agree with both reviewers your manuscript can benefit from subheadings and better structuring of the Methods section.

Also provide more details on study population selection and expand the discussion section on how to make inferences about generalizability of odds ratios given the difference in participation rates between the two urban populations. Are these still valid or would the estimation of odds ratios be affected due to the selection process? 

Reviewer 2 makes an important point about including psychosocial CVD risk factors such as depression, anxiety and stress. These variables should be included in the multivariable analysis when available.

Please also provide results from a logistic regression model including all variables (not only adjusted for age and CVD, but adjusting with all other variables) and test for interaction by gender (within one comprehensive model, not separated by gender). 

We would appreciate receiving your revised manuscript by Apr 02 2020 11:59PM. When you are 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.

If you would like to make changes to your financial disclosure, please include your updated statement in your cover letter.

To enhance the reproducibility of your results, we recommend that if applicable you deposit your laboratory protocols in protocols.io, where a protocol can be assigned its own identifier (DOI) such that it can be cited independently in the future. For instructions see: http://journals.plos.org/plosone/s/submission-guidelines#loc-laboratory-protocols

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). This letter should be uploaded as separate file and labeled 'Response to Reviewers'.
• A marked-up copy of your manuscript that highlights changes made to the original version. This file should be uploaded as separate file and labeled 'Revised Manuscript with Track Changes'.
• An unmarked version of your revised paper without tracked changes. This file should be uploaded as separate file and labeled 'Manuscript'.

Please note while forming your response, if your article is accepted, you may have the opportunity to make the peer review history publicly available. The record will include editor decision letters (with reviews) and your responses to reviewer comments. If eligible, we will contact you to opt in or out.

We look forward to receiving your revised manuscript.

Kind regards,

Bart Ferket

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

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

2. In ethics statement in the manuscript and in the online submission form, please provide additional information about what type of informed consent you obtained (for instance, written or verbal, and if verbal, how it was documented and witnessed).

3. We note that you have indicated that data from this study are available upon request. PLOS only allows data to be available upon request if there are legal or ethical restrictions on sharing data publicly. For information on unacceptable data access restrictions, please see http://journals.plos.org/plosone/s/data-availability#loc-unacceptable-data-access-restrictions.

In your revised cover letter, please address the following prompts:

a) If there are ethical or legal restrictions on sharing a de-identified data set, please explain them in detail (e.g., data contain potentially identifying or sensitive patient information) and who has imposed them (e.g., an ethics committee). Please also provide contact information for a data access committee, ethics committee, or other institutional body to which data requests may be sent.

b) If there are no restrictions, please upload the minimal anonymized data set necessary to replicate your study findings as either Supporting Information files or to a stable, public repository and provide us with the relevant URLs, DOIs, or accession numbers. Please see http://www.bmj.com/content/340/bmj.c181.long for guidelines on how to de-identify and prepare clinical data for publication. For a list of acceptable repositories, please see http://journals.plos.org/plosone/s/data-availability#loc-recommended-repositories.

We will update your Data Availability statement on your behalf to reflect the information you provide.

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

Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. Is the manuscript technically sound, and do the data support the conclusions?

The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented.

Reviewer #1: Partly

Reviewer #2: Partly

**********

2. Has the statistical analysis been performed appropriately and rigorously?

Reviewer #1: Yes

Reviewer #2: I Don't Know

**********

3. Have the authors made all data underlying the findings in their manuscript fully available?

The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). 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

**********

4. 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: No

Reviewer #2: Yes

**********

5. Review Comments to the Author

Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #1: The aim of the study is not clearly stated. I just assume it was (1) to determine the prevalence of untreated hypertension in population samples of Arkhangelsk and Novosibirsk and (2) to identify factors to be associated with untreated hypertension in the two population samples.

Section Materials and methods should be clearly structured having the following subsections:

Population – this should also include how the individuals were selected

Screening examination – should be briefly described, including blood pressure measurement

Definition of risk factors, incl. hypertension. The definition of hypertension used on lines 117 and 118 does not seem to include values equal to 140/90 mmHg, which is not in agreement with the quoted European guidelines on hypertension.

Statistical analysis

In conclusion, it is an important study which has to be published, however, the current version needs a major revision.

Reviewer #2: The submitted manuscript assesses the rate of untreated hypertension based on the «Know Your Heart» study and is carried out in two Russian cities, namely Novosibirsk and Arkhangelsk. The aim was also to provide further insights into the country-specific factors contributing to the fact that far too many hypertensive men and women currently remain untreated. However, there are a number of points, which need clarifications and revision.

1) The Materials and Methods section is not enough conclusive. It is difficult to understand the methodology of the study. Although authors provided a reference to their comprehensive paper on the «Know Your Heart» study design [Cook S, Malyutina S, Kudryavtsev AV, et al. Know Your Heart: Rationale, design and conduct of a cross-sectional study of cardiovascular structure, function and risk factors in 4500 men and women aged 35-69 years from two Russian cities, 2015-18. Wellcome Open Res. 2018;3:67.], it is not enough. I recommend to give in the current paper at least basic explanations on how the study population was selected.

2) The description of statistical methods is very scarce; they are presented literally in a couple of sentences and are not allocated in a separate subsection.

3) The robustness of results seems doubtful due to a low response rate. Moreover, the response rate in Novosibirsk, which is a developed city with a population of more than 1.5 million people, was more than two times lower than in Arkhangelsk (22% vs 51%, respectively). This issue must be addressed in some way.

4) Within the scope of the studied problems, the psychosocial CVD risk factors such as depression, anxiety and stress are shown to be of great importance for the Russian population. These factors serve as barriers for traditional risk factors modification and CVD treatment, including hypertension treatment, and they are also known to independently affect long-term health outcomes in CVD patients. According to the design paper, the “Know Your Heart” study encompassed assessment of anxiety and depression (using validated questionnaires), as well as assessment of self-reported social support. It is not clear, why these data were not used in the multivariate logistic regression models of untreated vs treated hypertension in this paper. The inclusion of these data into the models may provide more accurate and comprehensive information on factors, associated with lack of antihypertensive treatment, specifically relevant for the Russian population.

5) I would recommend avoiding inappropriate slang expressions like antihypertensives instead of antihypertensive drugs or medicines or treatment.

Given all of the above, this article needs a major revision before publication.

**********

6. 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: Yes: Renata Cifkova

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 to be viewed.]

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 us at figures@plos.org. Please note that Supporting Information files do not need this step.

Untreated hypertension in Russian 35-69 year olds – a cross-sectional study

PONE-D-19-34971R1

Dear Dr. PETERSEN,

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

Within one week, you will receive an e-mail containing information on the amendments required prior to publication. When all required modifications have been addressed, you will receive a formal acceptance letter and your manuscript will proceed to our production department and be scheduled for publication.

Shortly after the formal acceptance letter is sent, an invoice for payment will follow. To ensure an efficient production and billing process, please log into Editorial Manager at https://www.editorialmanager.com/pone/, click the "Update My Information" link at the top of the page, and update your user information. 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 enable them to help maximize its impact. If they will be preparing press materials for this manuscript, you must inform our press team as soon as possible and 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.

With kind regards,

Bart Ferket

Academic Editor

PLOS ONE

Additional Editor Comments (optional):

Reviewers' comments: