PONE-D-20-07641

Impact of Calculated Plasma Volume Status on All-cause and Cardiovascular Mortality: 4-year Nationwide Community-Based Prospective Cohort Study

PLOS ONE

Dear Tetsu Watanabe

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.

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Kind regards,

Anderson Saranz Zago, PhD

Academic Editor

PLOS ONE

Additional Editor Comments (if provided):

According to the opinion of the reviewers, the manuscript brings an interesting subject, however, it needs to be reviewed on several topics. After all these changes, the authors can resubmit the manuscript for a new evaluation.

Sincerely

Anderson Saranz Zago, PhD.

Academic editor

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https://doi.org/10.1253/circj.CJ-18-0721

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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: No

Reviewer #2: Yes

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

Reviewer #1: Yes

Reviewer #2: Yes

**********

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: Yes

Reviewer #2: Yes

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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: Yes

Reviewer #2: Yes

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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 present study aimed to examine whether PVS is a novel risk factor for all-cause and cardiovascular deaths in the general population. It's an interesting study due to the variety of factors that could be related to cardiovascular mortality. However, the topic should be better explored.

The introduction section is really poor. It's not clear the relationship between plasma volume and mortality. What are the physiological mechanism that can explain this relationship ?

Why PVS is associated with cardiac events and mortality in patients with heart failure ?

Why is this discussion important and what are the hypothesis of the study?

Methods. What changes is expected during the aging process in the PVS ? This answer can explain if the age range (40 to 74 years old) is too high (or not).

In the “definition of PVS” section it is not clear where the values reported comes from (Men: a = 1530; b = 41; 3; c = 39 / women, a = 864; b = 47.9; c = 40). No reference is cited.

Is the authors used some statistical model to define the PVS range (7 and -13.3) ?

Is it possible a negative plasma volume ? It should be better explained.

How blood pressure were measured ?

Endpoint and follow-up section - All subjects were prospectively followed for a period of 914,292 person-years. (???????? Period should be in years/months/days). Participants were followed for 4 years. However the table one present the subject characteristics of the first year. How about the others ?

The results were presented in a difficult way understand.

In the page 7 the authors comment: higher PVS - older and low risk / low PVS - younger and high risk. However, in page 8 and 9, high PVS was significantly associated with all-cause, cardiovascular and non-cardiovascular deaths / page 10 - low PVS was significantly associated with all-cause and cardiovascular deaths, but not non-cardiovascular deaths.

Which is better ? High or low ?

The legend of figures are really poor. What does it means each line in the graphic ?

The interpretation of the graphics are really difficult. The legends do not provide such informations.

The first paragraph of discussion section shows a summary of the results. However the follow explanation it's not clean to a complete understanding of the relationship between PVS and cardiovascular risk.

Reviewer #2: The study now submitted is of good technical quality, its design was well prepared, presents extreme originality and offers great contributions to the application in the clinical area, including: early diagnosis, prognosis, emergency care and choices in making therapeutic decisions.

In addition, for a prospective epidemiological study, the Japanese territorial coverage was quite significant, Including more distant areas such as Okinawa, but no less important than the central areas.

However, on this point I have my first question: why did the researchers not include parts north of Honshu Island, in the representative Tohoku region, between Aomori and Fukoshima?

The second issue concerns possible differences in PVS between higher altitude regions. As is well known, the plasma volume as well as the hematocrit may vary significantly between inhabitants of regions close to sea level and mountainous regions. This could interfere with the PVS values, the mean PVS obtained, over or underestimating mean values, as well as interfere with the inference of the analogies.

In the case of a Japanese archipelago with a wide variation in altitude, the authors do not point out such aspects, homogeneity or not of the altitude of the regions covered by the study and also what measures were taken to minimize possible errors.

Another important question is, why were the mean PVS values of a random sample obtained from healthy people in the same age group and distributed in the regions of the study not obtained?

Finally, how do the authors justify the absence of the inclusion of the state of physical fitness or regular practice of physical activity or sedentary sedentary lifestyle among the variables analyzed and associated with PLWHA and its variations, since the regular practice of physical activity is recognized and widely used in the treatment of heart patients?

Could its effects on the patient's clinical status and consequently on PLWHA not interfere in the discussion of the results?

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Reviewer #1: No

Reviewer #2: Yes: Cassiano Merussi Neiva

[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.

PONE-D-20-07641R1

Impact of Calculated Plasma Volume Status on All-cause and Cardiovascular Mortality: 4-year Nationwide Community-Based Prospective Cohort Study

PLOS ONE

Dear Dr. Tetsu Watanabe

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.

As you can see both reviewer pointed that all comment were addressed. However, one of them made a comment about the legend of figure 1.

Please submit your revised manuscript by July 06th. 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

We look forward to receiving your revised manuscript.

Kind regards,

Anderson Saranz Zago, PhD

Academic Editor

PLOS ONE

Additional Editor Comments (if provided):

Both reviewer pointed that all comment were addressed. However, one of them made a comment about the legend of figure 1.

After all these changes, you can resubmit the manuscript for the final decision.

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Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. If the authors have adequately addressed your comments raised in a previous round of review and you feel that this manuscript is now acceptable for publication, you may indicate that here to bypass the “Comments to the Author” section, enter your conflict of interest statement in the “Confidential to Editor” section, and submit your "Accept" recommendation.

Reviewer #1: All comments have been addressed

Reviewer #2: All comments have been addressed

**********

2. 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: Yes

Reviewer #2: Yes

**********

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

Reviewer #1: Yes

Reviewer #2: Yes

**********

4. 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: Yes

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. 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 manuscript has substantially improved after review. It can be observed that all comments have been addressed. However, I would make a last suggestion, given the changes made in the legend of the figures.

In the legend of figure 1, the authors included the following sentence: “We collected data from 230,989 subjects (aged 40–74 years) who participated in the health check-ups of 2008–2011. Among them, 107 were excluded from this study due to lack of essential data. During the median follow-up period of four years, there were 586 cardiovascular deaths, 2,552 non-cardiovascular deaths, and 3,138 all-cause deaths” This sentence should not be included in the legend since it represent a description and it is already included in the study population section.

Reviewer #2: I have no further questions and consider that the authors have answered satisfactorily the questions asked previously, as well as the suggested corrections.

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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: Yes: Anderson Saranz Zago

Reviewer #2: Yes: Cassiano Merussi Neiva

[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.

Impact of Calculated Plasma Volume Status on All-cause and Cardiovascular Mortality: 4-year Nationwide Community-Based Prospective Cohort Study

PONE-D-20-07641R2

Dear Dr. Watanabe,

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.

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Kind regards,

Anderson Saranz Zago, PhD

Academic Editor

PLOS ONE

Additional Editor Comments (optional):

I am pleased to inform you that your manuscript has been deemed suitable for publication in PLOS ONE. Congratulations!

Sincerely

Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. If the authors have adequately addressed your comments raised in a previous round of review and you feel that this manuscript is now acceptable for publication, you may indicate that here to bypass the “Comments to the Author” section, enter your conflict of interest statement in the “Confidential to Editor” section, and submit your "Accept" recommendation.

Reviewer #1: All comments have been addressed

**********

2. 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: Yes

**********

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

Reviewer #1: Yes

**********

4. 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: 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

**********

6. 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: (No Response)

**********

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: Yes: Anderson Saranz Zagp