PONE-D-20-05576

Long-term trajectories of arterial stiffness in obese CPAP-treated obstructive sleep apnea

PLOS ONE

Dear Dr Galerneau,

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.

Both reviewers raised several concerns that need to be addressed. Also, the reviewer listed a list of comments that require to be revised. 

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We look forward to receiving your revised manuscript.

Kind regards,

Yu Ru Kou, PhD

Academic Editor

PLOS ONE

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2. During your revisions, please clarify the wording in the title and update it in the manuscript file and online submission information. Specifically, we suggest the title to be modified as follows: "Long-term trajectories of arterial stiffness in patients with obesity and obstructive sleep apnea treated with continuous positive airway  pressure.

3. Throughout the manuscript, please avoid the use of potentially stigmatising language. For example, please replace 'obese patients' with 'patients with obesity'.

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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: Partly

Reviewer #2: Yes

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

Reviewer #1: Yes

Reviewer #2: Yes

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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: No

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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: I’ve read with interest the manuscript entitled „Long-term trajectories of arterial stiffness in obese CPAP-treated obstructive sleep apnea”. Authors of this study compared arterial stiffness at the time of OSA diagnosis and several years later with CPAP treatment. Authors concluded arterial stiffness progresses despite CPAP treatment. I think the study is well done and the manuscript very well written. I have a few comments/suggestions:

Major:

Why was a second PSG not done during the follow up visit? Or at least the Epworth questionnaire? I think this has to be discussed as a study limitation. We do not know what happened with OSA severity of the treated subjects (it might have been worse over the years in some of the patients with not known CPAP adherence).

Have you compared those patients with known CPAP adherence of at least 4 hours with the rest? What happened with arterial stiffness in just those patients with known CPAP adherence > 4 hours?

Were there any patients with CSA? Please show more PSG parameters.

Minor:

The follow up visit was not the same for all of the patients. What was the reason?

Reviewer #2: General comment

This is an interesting article dealing with an important aspect of sleep apnea morbidity that is not study enough in the litterature

Major Comments

1. In the title, the use of « trajectories » is not appropriate. As written, the goal seems to be to draw the fluctuations of the arterial stiffness over a period. But in this study, there is a comparison of the PWV before and after at least 4 years of CPAP therapy. This term need to be changed into “variations” or “deterioration” for example

2. In the abstract

a. Precise the goal of the study: PWV variation and determinants of increased PWV

b. The methods section is not complete: write a sentence about the analysis done in the study

3. In the analysis, it is interesting and important to know if there is a statistical difference between PWV before and after CPAP therapy.

Minor Comments

Abstract

Line 50: delete “a high”

Line 51: Difficult to understand “and/or current or past smoking”

Introduction

Line 124: As said before, “long term longitudinal trajectories of arterial stiffness”

Line 126: reformulate: “assess the longitudinal changes in PWV”

Methods

Line 144: “full respiratory polysomnography”: restrict it to polysomnography, it already include the respiratory recordings

Line 145: “AHI was calculated from the number of apnea and hypopnea events per hour of sleep” : AHI was calculated “as” not “from”

Line 149 : “Overnight sleep studies were scored according to international guidelines” : precise which ones , references, they differ over years

Line 155: “the ratio of distance to transit time”: it is the ratio of distance “on” not of

Line 175: FEV1/FVC<70%, according to standard definitions : normally you should use FEV1/FVC< lower limit of the normal (LIN), this is the standard definition, according to anthropometric parameters as stipulated by GLI

Line 179-180: “Adherence was defined as a mean CPAP use of at least 4 hours per night.”: generally adherence is evaluated over a period, here was it during the 4-9 years of follow up or only during the last year before the 2nd measurement of PWV?

Line 183 : It is important to be precise about the delay after which the new PWV was measured. 4 to 9 years is too large, even more than the double the 4 years. There may be a difference in PWV according to time (4 and 9 years) in the same patients. Here precise if it was only one measurement of PWV or more after that 4 years of CPAP therapy. This part need to be more precise!!!

Line 193: “univariable analysis”: it is univariate analysis same for multivariable, It is multivariate

Line 195 : Multivariate analysis was compute via which type of regression model?

Line 196: “Age, sex and CPAP treatment were included in the final multivariable model independently of the results of the univariable analysis”: this is called ajustement for age, sex and CPAP treatment

Line 201: “Due to the low number of missing values, a simple imputation method was used to impute missing data: quantitative variables were imputed using the median and qualitative variables were imputed using the most frequent value”: why was there missing values of PWV? This was a prospective study and the primary outcome was PWV, how missing values can be explained only on 107 patients?

Line 203-204: “Statistical analyses were performed with SAS v9.4 software (SAS Institute Inc., Cary, NC, United States)”: this is at the beginning of the section statistical analysis

Line 205: A p-value < 0.05 not “A p-value of < 0.05”

Results

Figure 1:

- Put the n of patients without OSA or with CSA

- As asked before, I don’t understand how 19 patients did not have data on PWV at follow up : Was it a retrospective study?

- Why are you dividing patients at the end into 2 groups according to the CPAP adherence? It is not necessary here to tell us how patients were included in the study. The outcome is changes in PWV not the adherence to CPAP therapy

Line 212: write median (IQR)

Line 214: “Patients commonly exhibited hypertension (58.3% of the population)” rephrase: delete commonly exhibited and of the population

Line 215: remove frequently; in the methods there is no mention about how a patients was characterized as current or former smoker!

Table 1:

- It is not possible to put n (%) in column + Median (IQR) and the same n (%) in lines and at the end “Categorical variables are expressed as a percentage and quantitative variables as the median (25th, 75th percentiles)”. This is repetition!!! . Normally n (%) on the head of the column and median (25th, 75th percentiles) on line for only qualitative variables. And if it is like that, it is not necessary to add as footnotes “Categorical variables are expressed as a percentage and quantitative variables as the median (25th, 75th percentiles)”

- In the bracket of IQR, hyphen not semi column

- Add comma after the name of the variable, eg: Age, (years)- BMI, (Kg/m²)….

- FEV1/ FVC < 70% (%) ; it is n (%)

- It is Fasting “blood”Glucose

- Footnotes: FEV1 is forced expiratory volume during the first second; add SBP, PaCO2, PaO2, SpO2

Line 221:

It is “Determinants of arterial stiffness deterioration” not Determinants deterioration in arterial stiffness

The title of this section don’t fit the results presented. In that part there is a description of Arterial stiffness in the studied population. Please, give another title.

It is after that there the title “Determinants of arterial stiffness deterioration” which will include 2 sections: univariate and multivariate analysis

Line 224: the expression “over the whole period” is not appropriate

Table 2

- Commas after the name of the variable

- Footnotes: remove “a” after as; TLC is not on this table; the expression of median should be uniform over the manuscript, chose between IQR and (25th-75th percentile) even if they express the same thing

Line 230 : remove figure on the title of the section

Figure 2: it is 95% CI not the CI95% and precise the definitions of abbreviations used there somewhere

Line 232: what is the definition of hypertension in the work? is it elevated blood pressure during the investigation or a notion of Hypertension treated or not before? Important to precise it in methods. In that way we will really interpret the results.

Line 234-235: “There was a trend toward a significant association between increase in PWV and COPD (P=0.10)” not well said. The p value is superior from your cut off but this potential associated factor can be included in the final model of multivariate analysis.

Line 240: really good the adjustment

Line 243-244: “The multivariable analysis did not demonstrate a long-term impact of CPAP adherence on PWV evolution”: I am not convinced. CPAP adherence here is evaluated when? Is it the mean or median of CPAP adherence measured each year?

Line 248: To the best of our knowledge instead of to our knowledge; review the expression long term trajectories

Line 251 : dependent of not on

Line 252: “with trends suggesting the influence of type 2 diabetes and COPD comorbidities” : no, not to considered as a major result. The p value is not significant

Line 253: “Neither indices of OSA severity at diagnosis or CPAP adherence” , better to say “Neither indices of OSA severity at diagnosis nor CPAP adherence”

Line 255: “Sleep apnea is known as impacting vascular “ better to say “Sleep apnea is known to impact vascular …

Line 255-261: “our obese OSA population (median age 55 years) showed greater arterial stiffness at baseline, as assessed by PWV, compared to the same age group in the general population”: this assertion have not been verified in your results, you have not compare those groups and had a statistical significant difference. Please rephrase all that

Line 269 : Had been not has been

Line 299-301: no, data shown in this study don’t confirm independent association between COPD and PWV because the P value in multivariate analysis is not significant

The conclusion and perspective section is only talking about perspective. Add a first part that summary your main pertinent results.

Figure 3: same remarks as figure 2

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Reviewer #1: No

Reviewer #2: No

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PONE-D-20-05576R1

Long-term variations of arterial stiffness in patients with obesity and obstructive sleep apnea treated with continuous positive airway pressure

PLOS ONE

Dear Dr. Galerneau,

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.

One reviewer still had some suggestions. Particularly, he/she did not find one sentence in the revised manuscript that was indicated in your response..

Please submit your revised manuscript by Jul 06 2020 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

We look forward to receiving your revised manuscript.

Kind regards,

Yu Ru Kou, PhD

Academic Editor

PLOS ONE

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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: (No Response)

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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: I would like to thank the authors for revising the manuscript. I think it substantially improved. I have no further comments/questions.

Reviewer #2: Authors have addressed the major part of our recommendations.

But some few corrections need to be done:

Line 153: the reference of AASM need to be in the reference list

Line 178: if “FEV1/FVC<70% was one pre-specified inclusion criteria” you should write it in the section participant as an inclusion criteria. Also, if you write according to standard definitions, we need to have a reference.

Line 180-183: “We thank the reviewer for asking for clarification on this. CPAP adherence used for data analysis was corresponding to objective compliance measured in the 3 to 6 months preceding follow-up visit. This sentence has been added in the methods section.” I am not seeing that sentence in the section on CPAP treatment

Line 243: delete “figure 3” in the title of the section “multivariate analysis” and put it in the text below

Line 311: please, in the conclusion it is not appropriate to write details as “1.34 [0.10; 2.37] m/s” … etc. You can write: “there is an increase in PWV over the study period. Determinants of PWV progression are old age and hypertension”

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Reviewer #1: No

Reviewer #2: Yes: Virginie Poka-Mayap

[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.

Long-term variations of arterial stiffness in patients with obesity and obstructive sleep apnea treated with continuous positive airway pressure

PONE-D-20-05576R2

Dear Dr. Galerneau,

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,

Yu Ru Kou, PhD

Academic Editor

PLOS ONE

Additional Editor Comments (optional):

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 #2: All comments have been addressed

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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 #2: Yes

**********

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

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 #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 #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 #2: (No Response)

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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 #2: Yes: Virginie Poka-Mayap