Sex disparities in the associations of overall versus abdominal obesity with the 10-year cardiovascular disease risk: Evidence from the Indonesian National Health Survey

Fathimah S. Sigit; Dicky L. Tahapary; Woro Riyadina; Kusharisupeni Djokosujono

doi:10.1371/journal.pone.0307944

Peer Review History

Original SubmissionApril 25, 2024
18 Jun 2024 Decision Letter - Emmanuel Kwaku Ofori, Editor PONE-D-24-16324Sex Disparities in the Associations of Overall versus Abdominal Obesity with the 10-Year Cardiovascular Disease Risk: Evidence from the Indonesian National Health SurveyPLOS ONE Dear Dr. Sigit, 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 02 2024 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: https://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, Emmanuel Kwaku Ofori, PhD Academic Editor PLOS ONE Journal Requirements: 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. We note that the grant information you provided in the ‘Funding Information’ and ‘Financial Disclosure’ sections do not match. When you resubmit, please ensure that you provide the correct grant numbers for the awards you received for your study in the ‘Funding Information’ section. 3. Thank you for stating the following financial disclosure: "The publication of this paper is funded by the Directorate of Research and Development, Universitas Indonesia, under Hibah PUTI 2024." Please state what role the funders took in the study. If the funders had no role, please state: ""The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript."" If this statement is not correct you must amend it as needed. Please include this amended Role of Funder statement in your cover letter; we will change the online submission form on your behalf. 4. In the online submission form, you indicated that "The dataset analysed in this study is available on reasonable request from the Ministry of Health, Republic of Indonesia, subject to prior review." All PLOS journals now require all data underlying the findings described in their manuscript to be freely available to other researchers, either 1. In a public repository, 2. Within the manuscript itself, or 3. Uploaded as supplementary information. This policy applies to all data except where public deposition would breach compliance with the protocol approved by your research ethics board. If your data cannot be made publicly available for ethical or legal reasons (e.g., public availability would compromise patient privacy), please explain your reasons on resubmission and your exemption request will be escalated for approval. 5. Please include captions for your Supporting Information files at the end of your manuscript, and update any in-text citations to match accordingly. Please see our Supporting Information guidelines for more information: http://journals.plos.org/plosone/s/supporting-information. 6. Please review your reference list to ensure that it is complete and correct. If you have cited papers that have been retracted, please include the rationale for doing so in the manuscript text, or remove these references and replace them with relevant current references. Any changes to the reference list should be mentioned in the rebuttal letter that accompanies your revised manuscript. If you need to cite a retracted article, indicate the article’s retracted status in the References list and also include a citation and full reference for the retraction notice. [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: Partly Reviewer #2: Yes ******** 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: No 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: Although the statistical analyses performed for this work are appropriate, it is difficult to affirm if the results support the conclusion because the authors did not report the respective p-values associated with the regression analyses. The authors need to report the p-values in order to make all the relevant data available without restriction. Reviewer #2: 1. The manuscript is technically sound using appropriate statistical analyses, including the Framingham Risk Score and sex- stratified multivariable linear regressions on nationally representative data from the Indonesian Health Survey. The conclusions are well supported by the data presented. 2. Statistical analysis have been performed appropriately and rigorously. 3. All data underlying the findings in their manuscript are available. 4. The manuscript is presented clearly and written in standard English. It follows a logical structure ensuring coherent presentation of the research. ****** 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: No Reviewer #2: Yes: Nathaniel Ebo Aidoo ******** [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. Attachments Attachment Submitted filename: PONE-D-24-16324_ob.edits.pdf https://doi.org/10.1371/journal.pone.0307944.r001
Revision 1
3 Jul 2024 Author Response We thank the editor and reviewers for the opportunity to revise and resubmit our manuscript. We found the feedback from the editor and reviewers constructive and helped us develop our manuscript further. Please find below our point-by-point responses addressing each comment raised by the reviewers. ------------------------------------------------------------------------------------------------------------------------------ Reviewer #1: 1. Although the statistical analyses performed for this work are appropriate, it is difficult to affirm if the results support the conclusion because the authors did not report the respective p-values associated with the regression analyses. The authors need to report the p-values in order to make all the relevant data available without restriction. ------ We thank Reviewer #1 for his/her thorough feedback and constructive criticism of our manuscript. However, following the STROBE guideline to report observational/epidemiological studies, we have properly presented the results of our study in regression coefficients and 95% CIs to show the magnitude of effect (effect size) and its measure of precision. The 95% CI is a robust indicator of the degree of error, as those that do not cross 0 mean they are statistically consistent (always positive if β is positive, always negative when β is negative). Using the p-value is not recommended due to its dichotomizing properties, which could potentially under- or over-estimate the results, and its lack of clinical significance (see references below). Nevertheless, to convince the reviewer of our results, we have now also included the significance of all effect sizes (p < or > 0.05). Solidifying our conclusion, we found that the majority of p-values from the linear regression analysis were <0.05. Only two crude associations had p>0.05 (in which the 95% CIs also crossed 0), and they became significant (p<0.05) when the associations were adjusted for confounding factors. Reference: • von Elm E, Altman DG, Egger M, et al. The Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) statement: guidelines for reporting observational studies. Lancet. 2007;370(9596):1453-1457. • Sullivan GM, Feinn R. Using Effect Size-or Why the P Value Is Not Enough. J Grad Med Educ. 2012;4(3):279-282. • Greenland S, Senn SJ, Rothman KJ, et al. Statistical tests, P values, confidence intervals, and power: a guide to misinterpretations. Eur J Epidemiol. 2016;31(4):337-350. • Ioannidis, J. P. A. (2019). What Have We (Not) Learnt from Millions of Scientific Papers with P Values? The American Statistician, 73(sup1), 20–25. • Wasserstein, R. L., & Lazar, N. A. (2016). The ASA Statement on p-Values: Context, Process, and Purpose. The American Statistician, 70(2), 129–133. 2. “Using the large, nationally representative data from the Indonesian National Health Survey, we analysed the population as stratified by sex, age, and urban/rural characteristics to gain insight into how these characteristics play a part in the associations between overall or abdominal obesity and CVD risks.” --> This information is better suited for the methods section. ------ Changed accordingly. We have moved this part to the Methods section and incorporated it with the ‘Statistical Analyses’. Line 183, Page 7, highlighted in yellow in the manuscript: “To examine whether the associations may differ between sexes, age groups, and urban/rural population settings, we repeated the multivariable linear regression analysis in these subgroups separately. These stratified analyses were done to gain insight into the role of these characteristics in the associations between body fat distribution and CVD risks.” 3. “The survey is held periodically every five years, with the 2018 survey being the most recent one with publicly available data, which we analysed in this study.” --> Within which period was this study carried out? ------ We have now elaborated the information in the manuscript. Line 100, Page 4, highlighted in yellow: “The survey is held periodically every five years, and in this study which was conducted in July-December 2023, we analysed the 2018 national survey as the most recent one with publicly available data.” 4. “From 1,017,290 individuals who were sampled as participants in the national health survey, in this study we only included non-pregnant individuals aged >15 years who were randomly selected for blood laboratory tests (n=33,786).” --> How did the authors arrive at this figure? What were the assumptions for sample size calculation? ------ We used the data of all participants included in the national health survey, who were already weighted and randomly sampled for blood laboratory tests, to represent the whole Indonesian population. This random sampling was done because, due to budget and logistic constraints, not all individuals enrolled in the survey underwent the blood glucose and lipid tests. Hence, the sampling design and calculation in this study follow the original national survey, which employed multi-stage systematic random sampling and probability proportional to size methods, to take into account differences in geographical density and urban-rural distribution in the 34 provinces, as we have mentioned in the manuscript. The detailed sampling steps of the Indonesian National Health Survey, including the census block selection at the regional and national level, were described in detail in the government’s official report, which we also now referenced in our manuscript. We also further clarified the sample inclusion in the study flow chart. Reference: Research & Development Organization, Ministry of Health, Republic of Indonesia (2019). Report on the national basic health research. Accessed 24 June 2024, <https://repository.badankebijakan.kemkes.go.id/id/eprint/3514/1/Laporan%20Riskesdas%202018%20Nasional.pdf>. Line 124, Page 5, highlighted in yellow in the manuscript “From 1,017,290 individuals who were sampled as participants in the national health survey, in this study we only included non-pregnant individuals aged >15 years who were randomly selected for blood laboratory tests (n=33,786). This random sampling was done because, due to budget and logistic constraints, not all individuals enrolled in the survey underwent the blood glucose and lipid tests.” 5. “We further excluded those aged <30 years and those with a prior history of CVDs (n=6,738), ...” --> Arbitrarily setting a threshold of age 30 raises the potential of bias unless the authors can provide reference(s) to support this. ------ We used the cut-off of 30 years to follow the estimation criteria of the Framingham Risk Score (FRS). According to the original publication of FRS, the risk score was meant to be used in adults >30 years, as the Framingham Heart Study only included those aged >30. Furthermore, the estimated 10-year risk of cardiovascular events can be calculated in age categories of 30-34, 35-39, 40-44, 45-49, 50-54, 55-59, 60-64, 65-69, 70-74, and >75 years, with different coefficients/points given for each age category in the prediction model. We also followed this categorization in the age-stratified analysis of our study. We have now properly cited the original publication in the manuscript. Reference: -D'Agostino RB Sr, Vasan RS, Pencina MJ, et al. General cardiovascular risk profile for use in primary care: the Framingham Heart Study. Circulation. 2008;117(6):743-753. doi:10.1161/CIRCULATIONAHA.107.699579 -Dyslipidemia Guidelines Tool, Canadian Cardiovascular Society, 2017 6. “From the national survey population, blood venous plasma samples were taken in a randomly selected and weighted subsample of participants.” --> plasma from venous blood? ------ We thank the reviewer for noticing this. We have now rephrased this sentence for better clarity. Line 156, Page 6, highlighted in yellow in the manuscript “From the national survey population, plasma samples from venous blood were taken in a randomly selected and weighted subsample of participants.” 7. “Abdominal obesity, presumably explained by visceral fat accumulation in the abdomen, was more strongly associated with an increased risk of CVD than overall adiposity, and more particularly so in women than men. Raising awareness of the importance of abdominal obesity in clinical practice may benefit in preventing CVD and its related morbidity and mortality. Further studies and public health policies to address the more damaging cardiovascular effects of abdominal/visceral adiposity in women than in men are necessary.” --> The authors must admit limitations of generalizability as the study strictly focuses on the Indonesian population. ------ We have now added the suggestion from the reviewers accordingly. Line 323, Page 12, highlighted in yellow in the manuscript “As this study is particularly relevant to the Indonesian population, similar studies in other countries may be necessary to generalize the results to the broader global population.” 8. “Data were presented as mean (SD) for continuous variables, or proportion (%) for categorical variables.” --> The authors indicated under the statistics section of the methods that descriptive statistics were presented including median (25-75th percentiles). Authors must indicate which variables were reported as such. ------ We thank the reviewer for this comment. We described all continuous variables as mean (SD) because, after inspecting the histogram, all variables were normally distributed (have a bell-shaped curve). We have added this information to the legend of Table 1. Legend of Table 1, Line 461, Page 16, highlighted in yellow in the manuscript “Data were presented as mean (SD) for continuous variables, or proportion (%) for categorical variables. All continuous variables described above were normally distributed.“ ------------------------------------------------------------------------------------------------------------------------------ Reviewer #2: 1. The manuscript is technically sound using appropriate statistical analyses, including the Framingham Risk Score and sex-stratified multivariable linear regressions on nationally representative data from the Indonesian Health Survey. The conclusions are well supported by the data presented. 2. Statistical analysis have been performed appropriately and rigorously. 3. All data underlying the findings in their manuscript are available. 4. The manuscript is presented clearly and written in standard English. It follows a logical structure ensuring coherent presentation of the research. ------ We are deeply grateful to Reviewer #2 for his/her overall positive response to our manuscript. Attachments Attachment Submitted filename: Response to Reviewers.docx https://doi.org/10.1371/journal.pone.0307944.r002
16 Jul 2024 Decision Letter - Emmanuel Kwaku Ofori, Editor Sex Disparities in the Associations of Overall versus Abdominal Obesity with the 10-Year Cardiovascular Disease Risk: Evidence from the Indonesian National Health Survey PONE-D-24-16324R1 Dear Dr. Sigit, 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 will be generated when your article is formally accepted. Please note, if your institution has a publishing partnership with PLOS and your article meets the relevant criteria, all or part of your publication costs will be covered. Please make sure your user information is up-to-date by logging into Editorial Manager at Editorial Manager® and clicking the ‘Update My Information' link at the top of the page. If you have any questions relating to publication charges, 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, Emmanuel Kwaku Ofori, PhD Academic Editor PLOS ONE Additional Editor Comments (optional): Manuscript is improved. All queries and suggestions have been effected by the authors. Reviewers' comments: https://doi.org/10.1371/journal.pone.0307944.r003
Formally Accepted
5 Aug 2024 Acceptance Letter - Emmanuel Kwaku Ofori, Editor PONE-D-24-16324R1 PLOS ONE Dear Dr. Sigit, I'm pleased to inform you that your manuscript has been deemed suitable for publication in PLOS ONE. Congratulations! Your manuscript is now being handed over to our production team. At this stage, our production department will prepare your paper for publication. This includes ensuring the following: * All references, tables, and figures are properly cited * All relevant supporting information is included in the manuscript submission, * There are no issues that prevent the paper from being properly typeset If revisions are needed, the production department will contact you directly to resolve them. If no revisions are needed, you will receive an email when the publication date has been set. At this time, we do not offer pre-publication proofs to authors during production of the accepted work. Please keep in mind that we are working through a large volume of accepted articles, so please give us a few weeks to review your paper and let you know the next and final steps. Lastly, 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 customercare@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 Emmanuel Kwaku Ofori Academic Editor PLOS ONE https://doi.org/10.1371/journal.pone.0307944.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 .