Association of sleep apnea with outcomes in peripheral artery disease: Insights from the PORTRAIT study

Qurat-ul-ain Jelani; Carlos Mena-Hurtado; Kensey Gosch; Moghniuddin Mohammed; Clementine Labrosciano; Christopher Regan; Lindsey E. Scierka; John A. Spertus; Sameer Nagpal; Kim G. Smolderen

doi:10.1371/journal.pone.0256933

Peer Review History

Original SubmissionApril 7, 2021
17 Jun 2021 Decision Letter - Carmine Pizzi, Editor PONE-D-21-11479 Association of Sleep Apnea with Outcomes in Peripheral Artery Disease: Insights from the PORTRAIT Study PLOS ONE Dear Dr. Scierka, 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. Please submit your revised manuscript by Aug 01 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, Carmine Pizzi Academic Editor PLOS ONE 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 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 2. Thank you for including your ethics statement: "This study was conducted in accordance with the Declaration of Helsinki. The Institutional Review Board of each participating site provided study approval and all patients provided informed consent before enrollment in the study. The Strengthening the Reporting of Observational Studies in Epidemiology guidelines for reporting observational studies were used.". a.) Please amend your current ethics statement to include the full name of the ethics committee/institutional review board(s) that approved your specific study. b.) Please provide additional details regarding participant consent. In the ethics statement in the Methods and online submission information, please ensure that you have specified what type you obtained (for instance, written or verbal, and if verbal, how it was documented and witnessed). If your study included minors, state whether you obtained consent from parents or guardians. If the need for consent was waived by the ethics committee, please include this information. Once you have amended this/these statement(s) in the Methods section of the manuscript, please add the same text to the “Ethics Statement” field of the submission form (via “Edit Submission”). For additional information about PLOS ONE ethical requirements for human subjects research, please refer to http://journals.plos.org/plosone/s/submission-guidelines#loc-human-subjects-research. 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. 4. Thank you for stating the following in the Competing Interests section: 'Dr. Smolderen is supported by an unrestricted research grant from Merck, Boston Scientific, Abbott Vascular and Terumo, and she is a consultant for Optum Labs. Dr. Spertus provides consultative services to Amgen, Merck, AstraZeneca, Novartis, Bayer, Janssen and United Healthcare. He has an equity interest in Health Outcomes Sciences and serves on the Board of Blue Cross Blue Shield of Kansas City. He owns the copyright to the Peripheral Artery Questionnaire, the Seattle Angina Questionnaire and the Kansas City Cardiomyopathy Questionnaire. Dr. Mena-Hurtado is a consultant for Bard, Cook, Medtronic, Abbott, Boston Scientific and Cardinal Health. Other authors report no disclosure.' Please confirm that this does not alter your adherence to all PLOS ONE policies on sharing data and materials, by including the following statement: "This does not alter our adherence to PLOS ONE policies on sharing data and materials.” (as detailed online in our guide for authors http://journals.plos.org/plosone/s/competing-interests). If there are restrictions on sharing of data and/or materials, please state these. Please note that we cannot proceed with consideration of your article until this information has been declared. Please include your updated Competing Interests statement in your cover letter; we will change the online submission form on your behalf. Please know it is PLOS ONE policy for corresponding authors to declare, on behalf of all authors, all potential competing interests for the purposes of transparency. PLOS defines a competing interest as anything that interferes with, or could reasonably be perceived as interfering with, the full and objective presentation, peer review, editorial decision-making, or publication of research or non-research articles submitted to one of the journals. Competing interests can be financial or non-financial, professional, or personal. Competing interests can arise in relationship to an organization or another person. Please follow this link to our website for more details on competing interests: http://journals.plos.org/plosone/s/competing-interests Reviewer #1: To: Title: “Association of Sleep Apnea with Outcomes in Peripheral Artery Disease: Insights from the PORTRAIT Study” - The use of questionnaires can be considered as a limitation of the study. Please discuss this point into a dedicated limitation section. - The authors can also consider the impact of CPAP therapy on PAD outcomes. This would be really interesting as Ciccone et al. [Int J Cardiol. 2012 Jul 26;158(3):383-6] previously demonstrated the reversibility of endothelial function after CPAP therapy. - The duration of sleep apnea may impact on the severity of the PAD. Please discuss such a point in relation to the paper from Ciccone MM et al. Respir Med. 2012 May;106(5):740-6. Reviewer #2: This is an interesting and original study; however, as often happens in studies analyzing big data, the results should be addressed in a more specific way. I have some questions for the authors: 1. Methods page 5 line 18: please provide the reference about Rutherford Classification 2. Could you please provide a comparison between patients with different Rutherford classes (3,4,5 and 6) with and without sleep apnea? PAD includes very different patterns of disease which can not be put together in the same analysis. 3. The authors should also stratify the results between patients who were revascularized and those who were not in order to make the results more homogeneous. https://doi.org/10.1371/journal.pone.0256933.r001
Revision 1
29 Jul 2021 Author Response Responses to Reviewer #1 – 1. The use of questionnaires can be considered as a limitation of the study. Please discuss this point into a dedicated limitation section. We respectfully disagree with the reviewer on this comment. As research and clinical management of chronic disease populations shifts away from focusing only biomedical factors, methods have been developed to capture more patient-centered information. Validated patient reported outcomes measures (including the PAQ, EQ5D, GAD, PHQ etc used in this study) are high quality and rigorously tested tools developed using the classic test theory and also adopted by standards set by the FDA for the measurements of patient reported outcomes. These validated instruments are the gold standard for capturing patient reported outcomes and are a reliable and valid way to collect and study disease-specific health status and psychological constructs assessed in this study. 2. The authors can also consider the impact of CPAP therapy on PAD outcomes. This would be really interesting as Ciccone et al. [Int J Cardiol. 2012 Jul 26;158(3):383-6] previously demonstrated the reversibility of endothelial function after CPAP therapy. We agree that adding the implications of treatment with CPAP to the discussion would add to the manuscript. We have added the following commend and citation to the Discussion section [page 16, line 274]: “Regardless of whether sleep apnea can be considered an independent risk factor of adverse outcomes for PAD or whether it is a marker of underlying atherosclerotic risk, it is important to emphasize that treatment of sleep apnea (weight loss, behavioral therapy including alcohol cessation, CPAP and surgical correction) [56] can potentially lead to improved outcomes, including patients’ health status and psychological outcomes such as depressive symptoms in patient with hypertension, atrial fibrillation and heart failure [40-42]. In addition, CPAP treatment has also been shown to improve endothelial function after initiation [57].” 3. The duration of sleep apnea may impact on the severity of the PAD. Please discuss such a point in relation to the paper from Ciccone MM et al. Respir Med. 2012 May;106(5):740-6. We agree that the duration of sleep apnea may have an impact on the severity of PAD. We have added this as a limitation in the Discussion section [page 17, line 313] as our study is unable to associate the duration of sleep apnea with features of the patient’s PAD as follows: “We were unable to assess whether the duration of having comorbid sleep apnea was associated with the severity of PAD, as increased duration of disease has been linked with increasing intima thickness in carotid stenosis [76].” Responses to Reviewer #2 – 1. Methods page 5 line 18: please provide the reference about Rutherford Classification. The citation for the Rutherford Classification (Rutherford, 1997) has been added. 2. “Could you please provide a comparison between patients with different Rutherford classes (3,4,5 and 6) with and without sleep apnea? PAD includes very different patterns of disease which can not be put together in the same analysis.” We agree that there is variation in PAD by Rutherford Classification, however we are unable to provide the analysis requested as the PORTRAIT Registry only included patients with symptomatic claudication (Rutherford Class 1, 2, and 3), and Rutherford 4-6 was an exclusion criterion. In our results, we have included a comparison between those with and without sleep apnea by symptom severity (mild, moderate, and severe claudication symptoms), and we found this association to not be statistically significant (p = 0.55). The Rutherford Classification labels corresponding to those symptoms (Class 1, 2, and 3 respectively) have been added to Table 1 for clarity [page 9-10 with changes on page 10 and 11]. 3. “The authors should also stratify the results between patients who were revascularized and those who were not in order to make the results more homogeneous.” We stratified the health status outcomes by management strategy (revascularization versus conservative management without revascularization) and did not find a statistically significant difference. This information was added to the manuscript as follows: Methods [page 8, line 166] “We also tested the interaction between sleep apnea and two other variables: (1) CPAP use (yes versus no) and (2) initial management strategy (revascularization versus conservative management without revascularization) to the unadjusted models to verify whether differences in health status outcomes existed for those who were treated with CPAP or revascularization versus those who were not.” Results [page 13, line 226] “There were no differences in health status outcomes between sleep apnea patients using CPAP versus those with sleep apnea without CPAP treatment or between sleep apnea patients treated with revascularization versus those with sleep apnea who were managed conservatively (without revascularization) in the unadjusted model so no further modeling including these interaction terms was performed.” Attachments Attachment Submitted filename: Response to Reviewers 7-26-2021.docx https://doi.org/10.1371/journal.pone.0256933.r002
19 Aug 2021 Decision Letter - Carmine Pizzi, Editor Association of sleep apnea with outcomes in peripheral artery disease: Insights from the PORTRAIT study PONE-D-21-11479R1 Dear Dr. Smolderen, 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, Carmine Pizzi Academic Editor PLOS ONE https://doi.org/10.1371/journal.pone.0256933.r003
Formally Accepted
31 Aug 2021 Acceptance Letter - Carmine Pizzi, Editor PONE-D-21-11479R1 Association of sleep apnea with outcomes in peripheral artery disease: Insights from the PORTRAIT study Dear Dr. Smolderen: 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 Prof Carmine Pizzi Academic Editor PLOS ONE https://doi.org/10.1371/journal.pone.0256933.r004

Open letter on the publication of peer review reports

PLOS recognizes the benefits of transparency in the peer review process. Therefore, we enable the publication of all of the content of peer review and author responses alongside final, published articles. Reviewers remain anonymous, unless they choose to reveal their names.

We encourage other journals to join us in this initiative. We hope that our action inspires the community, including researchers, research funders, and research institutions, to recognize the benefits of published peer review reports for all parts of the research system.

Learn more at ASAPbio .