Derivation and validation of a predictive model for chronic stress in patients with cardiovascular disease

Ali O. Malik; Philip G. Jones; Carlos Mena-Hurtado; Matthew M. Burg; Mehdi H. Shishehbor; Vittal Hejjaji; Andy Tran; John A. Spertus; Kim G. Smolderen

doi:10.1371/journal.pone.0275729

Peer Review History

Original SubmissionApril 19, 2021
17 Mar 2022 Decision Letter - M. Harvey Brenner, Editor PONE-D-21-13011 Derivation and Validation of a Predictive Model for Chronic Stress in Patients with Cardiovascular Disease PLOS ONE Dear Dr. Smolderen, 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 revise your manuscript in accordance with the reviewer's comments: It is of course elegant to establish the prediction model in one cohort and then apply it on another one. However, I feel that the authors have not discussed the significance of the obvious differences between the two cohorts. The PAD cohort is older and among participants only one fourth are working whereas in the TRIUMPH CAD cohort the participants are younger and half them are working. Coronary heart disease is associated with threat to life whereas PAD is associated with pain suffering and severe limitations in movement ability. However for those who are working (in both groups) working conditions are an important potential source of chronic stress. A substantial part of the literature on psychosocial prediction of CAD is based upon stress at work studies. This pertains for instance to the review by Kivimäki and Steptoe that the authors refer to. In fact most of the studies that they refer to deal with stress at work. In addition the international IPD study fairly recently reported from a prospective study that job strain significantly predicts development of PAD (Heikkilä et al 2020). It is odd to see the complete lack of reference to this whole literature. I can see a point in using the short four-item stress questionnaire for screening purposes, with subsequent more detailed discussion regarding working conditions in individual cases. The authors mention that the questionnaire captures factors associated with both environmental and individual (coping) factors. For less informed readers it may be helpful to explain that follow-up interviews may help in determining a strategy for dealing with the patient´s chronic stress and that things to do might have to do either with coping strategies or family/work organization questions. The authors hint at the possibility that chronic stress during the follow-up period might have been a consequence of medical procedures and changes in disease course. I think that point needs to be developed because it would be of interest to clinicians reading the paper. Conversely, another topic the authors do not discuss is the potential role of adverse psychosocial conditions in aggravating the clinical course Despite your professional efforts to explore effects of drop-out on different levels I still think you should discuss more openly the fact that a lot of subjects have fallen behind in several drop-out steps. The ones remaining are likely to be under less chronic stress than others. Please submit your revised manuscript by April 28, 2022. 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). 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We noticed you have some minor occurrence of overlapping text with the following previous publication(s), which needs to be addressed: - https://mospace.umsystem.edu/xmlui/handle/10355/71054 - https://linkinghub.elsevier.com/retrieve/pii/S0022399920308758 In your revision ensure you cite all your sources (including your own works), and quote or rephrase any duplicated text outside the methods section. Further consideration is dependent on these concerns being addressed. [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: Yes ******** 2. Has the statistical analysis been performed appropriately and rigorously? Reviewer #1: 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: No ****** 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 ****** 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: It is of course elegant to establish the prediction model in one cohort and then apply it on another one. However, I feel that the authors have not discussed the significance of the obvious differences between the two cohorts. The PAD cohort is older and among participants only one fourth are working whereas in the TRIUMPH CAD cohort the participants are younger and half them are working. Coronary heart disease is associated with threat to life whereas PAD is associated with pain suffering and severe limitations in movement ability. However for those who are working (in both groups) working conditions are an important potential source of chronic stress. A substantial part of the literature on psychosocial prediction of CAD is based upon stress at work studies. This pertains for instance to the review by Kivimäki and Steptoe that the authors refer to. In fact most of the studies that they refer to deal with stress at work. In addition the international IPD study fairly recently reported from a prospective study that job strain significantly predicts development of PAD (Heikkilä et al 2020). It is odd to see the complete lack of reference to this whole literature. In view of the great importance of working conditions you might in the future use one questionnaire for working and a slightly different one for a non-working group. I can see a point in using the short four-item stress questionnaire for screening purposes, with subsequent more detailed discussion regarding working conditions in individual cases. The authors mention that the questionnaire captures factors associated with both environmental and individual (coping) factors. For less informed readers it may be helpful to explain that follow-up interviews may help in determining a strategy for dealing with the patient´s chronic stress and that things to do might have to do either with coping strategies or family/work organization questions. The authors hint at the possibility that chronic stress during the follow-up period might have been a consequence of medical procedures and changes in disease course. I think that point needs to be developed because it would be of interest to clinicians reading the paper. Conversely, another topic the authors do not discuss is the potential role of adverse psychosocial conditions in aggravating the clinical course Despite your professional efforts to explore effects of drop-out on different levels I still think you should discuss more openly the fact that a lot of subjects have fallen behind in several drop-out steps. The ones remaining are likely to be under less chronic stress than others. ****** 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:** Tores Theorell [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. https://doi.org/10.1371/journal.pone.0275729.r001
Revision 1
3 Jun 2022 Author Response Please note: Below, we have copied the reviewers’ comments (in bold) and provided our responses in plain text. Sentences added to the manuscript in response to an editor or reviewer comment are indented and placed in italic font. ________________________________________ Reviewer Comments: It is of course elegant to establish the prediction model in one cohort and then apply it on another one. However, I feel that the authors have not discussed the significance of the obvious differences between the two cohorts. The PAD cohort is older and among participants only one fourth are working whereas in the TRIUMPH CAD cohort the participants are younger and half them are working. Coronary heart disease is associated with threat to life whereas PAD is associated with pain suffering and severe limitations in movement ability. RESPONSE# 1: These are important points. The reviewer is correct in pointing out the differences between the derivative cohort (TRIUMPH study) and validation cohort (PORTRAIT study), with the obvious difference of vascular bed involved, coronary in TRIUMPH cohort and peripheral in PORTRAIT cohort. From a pathophysiological standpoint, the two conditions coronary artery disease (CAD) and peripheral artery disease (PAD) have the same underlying etiology, i.e., atherosclerosis as a generalized process. Even though the manifestation of symptoms is different, prior work has demonstrated that the clinical event burden in terms of future risk of myocardial infarction and stroke, is similar, if not greater amongst those with PAD vs. CAD (JAMA. 2007 Mar 21;297(11):1197-206). So even though the cohorts represent different arterial beds that got affected, they all represent manifestations of the same underlying disease. It is reassuring to know that the performance of the models across these populations is comparable, which would accommodate screening for high levels of chronic stress throughout atherosclerotic disease trajectories that patients may face. This point is underscored by the c-statistic for our 6-item model which was comparable in both cohorts, 0.75 in TRIUMPH cohort and 0.77 in the PORTRAIT cohort. The following sentences have been added to the discussion section. Page 12 Line 22-23, Page 13 Line 1-5 “Fourth, the derivative and validation cohorts differed in terms of demographics, socioeconomic conditions and vascular disease (coronary artery disease vs PAD). However, both disease processes are a manifestation of the same pathophysiological mechanism of atherosclerosis. Moreover, patients with PAD have a similar risk of adverse cardiovascular events (myocardial infarction, stroke), compared with patients affected by coronary artery disease.42 Our model had good predictive ability in both cohorts, underscoring the value of our model in screening for higher levels of stress in patients across the spectrum of cardiovascular disease. “ However for those who are working (in both groups) working conditions are an important potential source of chronic stress. A substantial part of the literature on psychosocial prediction of CAD is based upon stress at work studies. This pertains for instance to the review by Kivimäki and Steptoe that the authors refer to. In fact most of the studies that they refer to deal with stress at work. In addition the international IPD study fairly recently reported from a prospective study that job strain significantly predicts development of PAD (Heikkilä et al 2020). It is odd to see the complete lack of reference to this whole literature. In view of the great importance of working conditions you might in the future use one questionnaire for working and a slightly different one for a non-working group. RESPONSE# 2: We agree with the reviewer. Certainly, some of the literature exploring the impact of stress on development and progression of cardiovascular disease pertains to stress at the workplace. We have acknowledged this in our revision and referred to the work by Heikkilä et al. It is indeed important to understand sources of stress for patients with cardiovascular disease. Stress at workplace is indeed an important consideration. However other sources of stress such as economic hardship, lack of social support also contribute to the overall burden of stress in these patients (J Am Coll Cardiol. 2018 Jun 5;71(22):2585-2597, Heart. 2020 Sep;106(18):1394-1399). Future work should focus on identifying these causes of stress to help identify interventions to help patients cope, as a strategy to improve outcomes, in addition to identifying policy measures that could address some of the more systematic root causes of stress. While we did not explore source of stress with aim of formulating actionable coping mechanisms, this remains an area for future work. The following sentences have been added to the discussion section. Page 13 Line 5-13 “Fifth, it is known that factors at the workplace are associated with risk of experiencing chronic stress and have been associated with development and progression of CVD.1 Stress at the work-place along with other factors such as economic hardship, lack of social support etc., are important sources of stress for patients with CVD.43,44 Our aim was to identify patients who are at risk of CVD, and we did not further explore individual sources of stress. Indeed, identifying unique sources of stress in patients with CVD, with the aim of formulating actionable coping strategies, in addition to identifying policy measures that could address some of the more systematic root causes of stress remain areas for future work”. I can see a point in using the short four-item stress questionnaire for screening purposes, with subsequent more detailed discussion regarding working conditions in individual cases. The authors mention that the questionnaire captures factors associated with both environmental and individual (coping) factors. For less informed readers it may be helpful to explain that follow-up interviews may help in determining a strategy for dealing with the patient´s chronic stress and that things to do might have to do either with coping strategies or family/work organization questions. RESPONSE# 3: This is a very important point. As next steps, we will need to further identify the sources of stress patients affected by cardiovascular disease are dealing with (e. g. work stress, loneliness, economic hardship, as well as stress from navigating the disease and its management itself etc.) and develop tailored interventions to manage or mitigate sources of stress. This remains an area of future work. Please see RESPONSE# 2. The authors hint at the possibility that chronic stress during the follow-up period might have been a consequence of medical procedures and changes in disease course. I think that point needs to be developed because it would be of interest to clinicians reading the paper. Conversely, another topic the authors do not discuss is the potential role of adverse psychosocial conditions in aggravating the clinical course. RESPONSE# 4: The reviewer is correct. We were cognizant of this issue and agree that stress during follow-up could be due to medical procedures and changes in disease course. To account for this bias, we excluded baseline stress assessment from the definition of chronic stress. We had mentioned that in the methods section and have clarified this further in the revised version of the manuscript. For TRIUMPH study (derivation cohort), follow-up assessments were at 1,6- and 12-month follow-up intervals. For the PORTRAIT study (validation cohort) follow-up assessments were at 3,6 and 12-month follow-up intervals. We defined chronic stress as two or more follow-up assessments with PSS-4 score ≥ 6. The following sentences were added/modified to the manuscript. Page 6 Line 2-7 “We wanted to quantify a patient’s exposure to chronic stress, during the 12-months of follow-up. Therefore, to provide more stable categorization of stress levels at follow-up we defined chronic stress as 2 or more follow-up PSS-4 assessments of �6, after the initial baseline assessment. As the initial event (AMI or worsening PAD symptoms) could contribute to the patient’s stress in the first few days, baseline PSS-4 assessments were not included in the definition.” Page 10 Line 10-11 “This was after the initial event (AMI, worsening symptoms of PAD), which could contribute to stress in the first few days.” Despite your professional efforts to explore effects of drop-out on different levels I still think you should discuss more openly the fact that a lot of subjects have fallen behind in several drop-out steps. The ones remaining are likely to be under less chronic stress than others. RESPONSE# 5: Thank you for the suggestion. We agree that missing data is a big limitation. Even though we used multiple imputations by chained equations (MICE) [Journal of statistical software 2010: 1-68], with predictive mean matching to account for any bias, this remains an important limitation of our work. We have highlighted this further in the limitations section of our revised manuscript. The following sentences have been added to the manuscript. Page 13 Line 15-16 “We used multiple imputation to account for missing data, but there remains potential for bias. However, this still remains an important limitation of our work” Attachments Attachment Submitted filename: Response Letter v6.docx https://doi.org/10.1371/journal.pone.0275729.r002
23 Sep 2022 Decision Letter - Xianwu Cheng, Editor Derivation and Validation of a Predictive Model for Chronic Stress in Patients with Cardiovascular Disease PONE-D-21-13011R1 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, Xianwu Cheng, M.D., Ph.D., FAHA Academic Editor PLOS ONE Additional Editor Comments (optional): Authors have adressed all original concerns. 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: The authors have been honest about weaknesses and discuss them adequately. They do contribute to the literature ****** 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: Tores Theorell ******** https://doi.org/10.1371/journal.pone.0275729.r003
Formally Accepted
7 Oct 2022 Acceptance Letter - Xianwu Cheng, Editor PONE-D-21-13011R1 Derivation and Validation of a Predictive Model for Chronic Stress in Patients with Cardiovascular Disease 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 Associate Prof. Xianwu Cheng Academic Editor PLOS ONE https://doi.org/10.1371/journal.pone.0275729.r004

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