Socioeconomic and behavioral determinants of cardiovascular diseases among older adults in Belgium and France: A longitudinal analysis from the SHARE study

Hamid Yimam Hassen; Hilde Bastiaens; Kathleen Van Royen; Steven Abrams

doi:10.1371/journal.pone.0243422

Peer Review History

Original SubmissionJuly 9, 2020
23 Sep 2020 Decision Letter - Luisa N. Borrell, Editor PONE-D-20-21259 Socioeconomic and behavioral determinants of cardiovascular diseases among older adults in Belgium and France: a longitudinal analysis from the SHARE study PLOS ONE Dear Dr. Hassen, 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. ============================== ACADEMIC EDITOR: While both reviewers found the study relevant and important, Reviewer 2 has underscored several methodological issues. Please pay careful attention to these issues as addressing them could improve the message of the paper. ============================== Please submit your revised manuscript by Nov 07 2020 11:59PM. 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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. Please provide additional details regarding participant consent. In the ethics statement in the Methods and online submission information, please ensure that you have specified (1) whether consent was informed and (2) 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. [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 Reviewer #2: Partly ******** 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 ****** 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 ****** 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 revised work is very well conducted, the ideas are original and relevant. The results are very interesting and will be very beneficial for the scientific community. Additionally, I find it well written and easy to understand. I would just like to comment that in table 1 in the Sex (Female) variable, I noticed that there is a typo: you need to close the parentheses. Reviewer #2: The authors conducted a large cohort study evaluating socioeconomic determinants and cardiovascular disease using data collected from several waves of the SHARE study. By using marginal GEE models the investigators were able to account for between- and within- subject effects of social determinants. The paper was well thought out in many ways but there are some areas for improvement. Suggested edits/comments could be found below: 1. Please provide some analysis of individuals for which the outcomes of interest were missing. The authors state in line 108-109 that only persons with outcome data were contained in the sample but it is not clear how not including these persons may have biased the results. Even some descriptive analyses among persons with missing outcome data would be helpful. This is exceptionally important for the outcome which may be missing a large proportion of individuals who are deceased and therefore were not included in the sample. 2. Related to this point, proportions of missingness in tables 3-4 were helpful, however, in general it would be helpful to know more about the multiple imputations models. How were variables selected and were there auxillary variables used to specify the missing model? 3. Please clarify if any of the "multivariate". This appears to be used interchangeably but it seems as though "multivariable" may be the correct wording. The different types of models have very different implications. 4. While the authors allude to some of the limitations of using self-reported data, it might be helpful to include some more discussion of how measurement error may have biased some of these findings (e.g., low SES underreporting certain social behaviors such as alcohol/tobacco use/abuse, how does self-reporting CV events limit this analysis?). 5. The mediation analysis was well thought out but since this contains so many similar social constructs, the authors may benefit from removing it from the main text and supplement. It can be explored in future work when developing a causal model rather than the present predictive one. Collinearity also may be an issue between some of the crudely defined socioeconomic factors. 6. A similar analysis looking at incident CVD cases would be interesting either for this study or in the future. Is there a way to exclude persons with prevalent CVD events from earlier waves and at baseline of this study to understand if one of these factors (i.e., retirement status, depression) cause CVD in this population? 7. Reporting variability within and between countries is an advantage of using hierarchical models such as the one employed in this study but there is no mention of it in the text. Only descriptive results were presented between the countries. Please include more information on how these countries differ. 8. It will be generally important to state whether this is a predictive model that identifies risk factors and not a causal model which may be limited to confounding and selection biases. ****** 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:** MIREYA MARTÍNEZ-GARCÍA 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.] 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. 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Revision 1
20 Oct 2020 Author Response Response to Reviewers PONE-D-20-21259 Socioeconomic and behavioral determinants of cardiovascular diseases among older adults in Belgium and France: a longitudinal analysis from the SHARE study PLOS ONE First of all, I wish to thank the editor and the reviewers, also on behalf of all authors, for their valuable and constructive comments to improve our manuscript. We revised the manuscript based on the comments and issues raised by the editor and the reviewers. We are confident that we have addressed all these comments adequately and we therefore hope that the manuscript is accepted for publication. Find hereunder a point by point reply to the comments and questions raised by the editor and the two reviewers. Editor 1. Please ensure that your manuscript meets PLOS ONE's style requirements, including those for file naming. Response: Thank you for your suggestions. We have reviewed the manuscript to meet the journal requirements and we hope that the manuscript in its current form does so. 2. Please provide additional details regarding participant consent. In the ethics statement in the Methods and online submission information, please ensure that you have specified (1) whether consent was informed and (2) 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. Response: Thank you for your suggestions. We used publicly available data (available via the website http://www.share-project.org/data-documentation/data-documentation-tool.html) for a secondary data analysis. In order to clarify this, we have added the following sentences in line 208 - 214 of the revised version of the manuscript: “We used publicly available data (available via the website http://www.share-project.org/data-documentation/data-documentation-tool.html) for a secondary data analysis. SHARE underwent a review of ethical standards by the University of Mannheim's internal review board (IRB). Ethical considerations including written informed consent has been taken care of by another institution. Details on the conduct of the study including the ethical approval can be found elsewhere (Alcser, Benson et al. 2005).” Reviewer # 1 1. The work is very well conducted, the ideas are original and relevant. The results are very interesting and will be very beneficial for the scientific community. Additionally, I find it well written and easy to understand. I would just like to comment that in table 1 in the Sex (Female) variable, I noticed that there is a typo: you need to close the parentheses. Response: Thank you for your feedback and appreciation for our work. We corrected the typo accordingly. Reviewer # 2 1. The authors conducted a large cohort study evaluating socioeconomic determinants and cardiovascular disease using data collected from several waves of the SHARE study. By using marginal GEE models the investigators were able to account for between- and within- subject effects of social determinants. The paper was well thought out in many ways but there are some areas for improvement. Suggested edits/comments could be found below. Response: Thank you for your feedback. The comments were very helpful and we revised the manuscript thoroughly. We hope that we addressed all your concerns in the revised manuscript. 2. Please provide some analysis of individuals for which the outcomes of interest were missing. The authors state in line 108-109 that only persons with outcome data were contained in the sample but it is not clear how not including these persons may have biased the results. Even some descriptive analyses among persons with missing outcome data would be helpful. This is exceptionally important for the outcome which may be missing a large proportion of individuals who are deceased and therefore were not included in the sample. Response: Thank you for your feedback. As we mentioned in line 108 to 110, we excluded individuals who are aged < 50 years, individuals that already have CVD at enrollment and those that did not have information on the CVD outcome variables at enrollment. Participants with intermediate missingness in terms of the outcome variables are included in the analysis and managed using the MI technique. The main reason to exclude individuals with no CVD outcome information at enrollment is to make sure that the individuals that are included are free from CVD events prior to study initiation. In total, 467 participants were excluded (108 being aged below 50 years, 117 with missing outcome values at enrollment and 242 individuals that already had a history of CVD at enrollment). Although we assume missingness of CVD outcomes at enrollment to be completely at random (MCAR) by not including those 117 participants, the percentage of missing outcome data is below 0.8% and we therefore believe that the impact on the inference is limited when the underlying missingness mechanism is mis-specified. Nevertheless, we do agree with the reviewer that a descriptive analysis to deal with the baseline missingness could be explored. As recommended by the reviewer, we performed a descriptive analysis to compare the included individuals and the individuals that were excluded due to missing outcome values (n=117) in terms of a set of covariates. The descriptive results thereof are presented in table 1 of the supplementary material. The results show that individuals who were included are comparable with the excluded ones in terms of socioeconomic characteristics. We also added a description in line 166 to 171 of the revised manuscript. 3. Related to this point, proportions of missingness in tables 3-4 were helpful, however, in general it would be helpful to know more about the multiple imputations models. How were variables selected and were there auxiliary variables used to specify the missing model? Response: Thank you for this comment. Indeed, we used auxiliary variables in combination with the covariate information used in the substantive model(s) in order to specify the imputation models. Examples of such auxiliary variables include family size, activities of daily living, limitation of activities, self-perceived health, among other variables. The perspective taken in the Multiple Imputation by Chained Equations (MICE) approach, also referred to as full conditional specification, is one of a specification of several imputation models which sequentially imputed missing values for a given variable when regressed against all other covariates available. For more details regarding this approach and the justification of full conditional specification, we refer the reader to (Van Buuren 2018). We revised the description in line 194 to 200 of the analysis section in order to clarify this. Moreover, more details concerning the imputation models and the covariates included therein are included in page 6 of the supplementary material. In general, the inclusion of auxiliary variables in the imputation models, next to the covariates present in the substantive model(s), albeit potentially unimportant from an explanatory perspective, leads to a more precision in terms of estimation of the model parameters in the final substantive model. 4. Please clarify if any of the "multivariate". This appears to be used interchangeably but it seems as though "multivariable" may be the correct wording. The different types of models have very different implications. Response: We agree with the reviewer that a multivariate analysis is different from a multiple or multivariable one, the latter being the analysis that has been conducted in our manuscript. Therefore, we revised the manuscript to consistently use ‘multivariable’ throughout the manuscript. 5. While the authors allude to some of the limitations of using self-reported data, it might be helpful to include some more discussion of how measurement error may have biased some of these findings (e.g., low SES underreporting certain social behaviors such as alcohol/tobacco use/abuse, how does self-reporting CV events limit this analysis?). Response: We kindly agree with the reviewer that those in low socioeconomic status usually have a higher likelihood of under-reporting CVD status, risks and other health related issues, which might nullify the effect size of SES on CVD. This indicates the effect of SES on CVD could be even more than what we found. We elaborated more extensively on the limitation of the self-reported data and discussed this in view of the reviewer’s comment in line 367 to 374 of the revised manuscript. 6. The mediation analysis was well thought out but since this contains so many similar social constructs, the authors may benefit from removing it from the main text and supplement. It can be explored in future work when developing a causal model rather than the present predictive one. Collinearity also may be an issue between some of the crudely defined socioeconomic factors. Response: We agree that the mediation analysis needs more exploration. We accept that this study and more importantly its design did not fully comply with nor allow for a formal and in-depth mediation analysis as we have a number of related determinants and mediators. Separate mediation analyses are needed, principally for each determinant-mediator-outcome relationship. We will consider to perform an extensive mediation analysis in the continuing analysis. Initially, we believed that this mediation analysis would provide some indications for future studies. However, to avoid confusion and mis-understanding for readers, we removed it from the main text and the supplement. 7. A similar analysis looking at incident CVD cases would be interesting either for this study or in the future. Is there a way to exclude persons with prevalent CVD events from earlier waves and at baseline of this study to understand if one of these factors (i.e., retirement status, depression) cause CVD in this population? Response: Thank you for your feedback. In fact, we excluded those individuals with CVD during the first wave of their enrollment as we mentioned in line 108 to 110 of the methods section. However, in this study, as the survey is every two years, we could not ascertain the exact number of CVD events (MI, stroke, etc..) and the exact date of such an event in between the waves. This made the incidence analysis somewhat complicated. Nevertheless, we do believe that this is very interesting and a potential avenue for further research. As suggested, we will consider to perform incidence analysis in the future. 8. Reporting variability within and between countries is an advantage of using hierarchical models such as the one employed in this study but there is no mention of it in the text. Only descriptive results were presented between the countries. Please include more information on how these countries differ. Response: Thank you for your comment. We explored the difference between two countries extensively in the revised version. Besides the descriptive statistics, we also compared the difference between countries in several ways. Firstly, we compared both countries using differences in socioeconomic as well as the outcome variable. Secondly, as we have mentioned in line 187 to 190, we developed a separate GEE model for the two countries to assess whether the determinants vary across countries. However, the results showed no significant difference in the effect sizes of determinants between countries (detailed results are indicated in table 7 and 8 of the supplementary material). Thirdly, we performed a combined analysis without the inclusion of country-specific determinants under the assumption that such differences were unimportant based on our earlier stratified analysis. Hence, we finally preferred to present the results of the (combined) GEE model, for both countries combined. 9. It will be generally important to state whether this is a predictive model that identifies risk factors and not a causal model which may be limited to confounding and selection biases. Response: Thank you for your feedback. We do agree that the aim of this study is to identify risk factors for the occurrence of CVD, i.e. a so-called risk factor identification study. We stated this explicitly in the discussion section and indicated that our model is not a causal one, rather one that focuses on association and not on (the establishment of) causality. We believe that this study would provide overall insight for further individual causal study. References Alcser, K. H., G. Benson, A. Börsch-Supan, A. Brugiavini, D. Christelis, E. Croda, M. Das, G. de Luca, J. Harkness and P. Hesselius (2005). "The survey of health, aging, and retirement in Europe—Methodology." Mannheim Mannheim Research Institute for the Economics of Aging (MEA). Van Buuren, S. (2018). Flexible imputation of missing data, CRC press. Hamid Y. Hassen Hamid.hassen@uantwerpen.be Attachments Attachment Submitted filename: Response to Reviewers.docx https://doi.org/10.1371/journal.pone.0243422.r002
23 Nov 2020 Decision Letter - Luisa N. Borrell, Editor Socioeconomic and behavioral determinants of cardiovascular diseases among older adults in Belgium and France: a longitudinal analysis from the SHARE study PONE-D-20-21259R1 Dear Dr. Hassen, 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, Luisa N. Borrell, DDS, PhD Academic Editor PLOS ONE Additional Editor Comments (optional): You have addressed the reviewer's comments. However, I have some suggestions for the tables as they should stand alone. 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 ******** 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: The authors adequately addressed all comments posed to them from the first round of reviews. Thank you for providing me with an opportunity to review this work. ****** 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: No Attachments Attachment Submitted filename: PONE-D-20-21259_R1 LNB.pdf https://doi.org/10.1371/journal.pone.0243422.r003
Formally Accepted
26 Nov 2020 Acceptance Letter - Luisa N. Borrell, Editor PONE-D-20-21259R1 Socioeconomic and behavioral determinants of cardiovascular diseases among older adults in Belgium and France: a longitudinal analysis from the SHARE study Dear Dr. Hassen: 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 Dr. Luisa N. Borrell Academic Editor PLOS ONE https://doi.org/10.1371/journal.pone.0243422.r004

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