PONE-D-25-15914Assessing Stroke Risk Disparities: Analysis of Lifestyle and Vascular Factors in Transgender Stroke SurvivorsPLOS ONE

Dear Dr. Zand,

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.

I commend the authors for their hard work. The reviewers have graciously made some suggestions, many of which were comments I had myself.Please address them thoroughly in the manuscript and in your written responses. 

Please submit your revised manuscript by Jul 06 2025 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.

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Daniel Antwi-Amoabeng, MD, MSc

Academic Editor

PLOS ONE

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Additional Editor Comments:

I commend the authors for their hard work. The reviewers have graciously made some suggestions, many of which were comments I had myself. Please address them thoroughly.

Thank you.

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Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. Is the manuscript technically sound, and do the data support the conclusions?

The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented.

Reviewer #1: Yes

Reviewer #2: Partly

Reviewer #3: Yes

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

Reviewer #1: Yes

Reviewer #2: Yes

Reviewer #3: Yes

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3. Have the authors made all data underlying the findings in their manuscript fully available?

The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified.

Reviewer #1: Yes

Reviewer #2: Yes

Reviewer #3: Yes

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4. Is the manuscript presented in an intelligible fashion and written in standard English?

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Reviewer #1: Yes

Reviewer #2: Yes

Reviewer #3: No

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5. Review Comments to the Author

Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #1: Summary of the Study

This manuscript addresses an important and under-researched topic: stroke risk disparities among transgender individuals.

Using data from the Behavioral Risk Factor Surveillance System (BRFSS) from 2020 to 2022, the authors compare stroke risk factors between transgender and cisgender stroke survivors.

The study highlights significant disparities in lifestyle and vascular risk factors, socioeconomic status, and mental health, emphasizing the need for targeted interventions to improve post-stroke outcomes in transgender populations.

Strengths of the Study

Novelty and Relevance: The study fills a critical gap in stroke research by focusing on transgender individuals, a population often overlooked in cardiovascular studies.

Robust Methodology: The use of propensity score matching (PSM) to reduce bias and ensure comparability between transgender and cisgender groups is commendable.

Comprehensive Analysis: The study examines a wide range of risk factors, including lifestyle, vascular, socioeconomic, and demographic variables, providing a holistic view of disparities.

Publicly Available Data: The use of BRFSS data ensures transparency and replicability, and the authors clearly state the limitations of the dataset.

Actionable Insights: The findings highlight modifiable risk factors, such as smoking and alcohol use, which can inform targeted interventions.

Weaknesses and Suggestions for Improvement

Lack of Data on Hormone Therapy:

Issue: The study does not include data on hormone therapy, which is a significant factor influencing stroke risk in transgender individuals.

Suggestion: Acknowledge this limitation more explicitly in the discussion and suggest future studies to investigate the role of hormone therapy in stroke risk.

Limited Data on Healthcare Access:

Issue: The manuscript does not explore disparities in healthcare access, which could influence post-stroke outcomes.

Suggestion: Include a discussion on how healthcare access barriers may exacerbate stroke risk and outcomes in transgender individuals.

Mental Health Analysis:

Issue: While trends in depression and poor mental health are noted, they are not statistically significant.

Suggestion: Consider exploring qualitative data or longitudinal studies to better understand the relationship between mental health and stroke risk in transgender populations.

Classification Bias:

Issue: Stroke diagnoses in the BRFSS dataset are self-reported, which may introduce classification bias.

Suggestion: Discuss how this limitation could impact the findings and suggest validation through clinical data in future research.

Sample Size:

Issue: The sample size for transgender stroke survivors is relatively small (n=189), which may limit the generalizability of the findings.

Suggestion: Highlight the need for larger, more representative studies to confirm these results.

Discussion of E-Cigarette Use:

Issue: The manuscript notes a significant disparity in e-cigarette use but does not delve into its implications for stroke risk.

Suggestion: Expand the discussion on the cardiovascular risks associated with e-cigarette use and its potential role in stroke prevention strategies.

Figures and Tables:

Issue: Some tables (e.g., Table 3) are dense and difficult to interpret.

Suggestion: Simplify the presentation of key findings by summarizing them in a more reader-friendly format, such as bullet points or visual aids.

Future Directions:

Issue: The manuscript does not provide specific recommendations for future research.

Suggestion: Include a dedicated section outlining areas for further investigation, such as the impact of hormone therapy, healthcare access, and longitudinal studies on post-stroke outcomes.

Recommendation

Decision: Revise and Resubmit

While the study addresses a critical topic and provides valuable insights, the limitations in data (e.g., lack of hormone therapy and healthcare access variables) and the small sample size warrant further refinement. The manuscript should be revised to:

Strengthen the discussion of limitations.

Provide clearer recommendations for future research.

Simplify the presentation of results for better readability.

Once these revisions are made, the manuscript would be a strong candidate for acceptance, as it contributes significantly to the understanding of stroke risk disparities in transgender populations.

Reviewer #2: This study compared the post-stroke survivors characteristics of cisgender and transgenders using a national database, and the results are striking for the need of further researches in this topic. The results are showing that transgender stroke survivors are vulnerable in mental, physical and also social dimensions compared to cisgender stroke survivors. stud results is important to raise awareness to provide proactive health enhancing practices to this vulnerable patient groups.

I have some suggestions;

-As authors mentioned in the discussion, the results of this study describes the comparison of characteristics of post-stroke residents in two groups. so using "stroke risk factor" phrase is not applicable for topic. They search DM, HT, HL, behavioral risk factors but, it i not evident that these factors were present before stroke. So I suggest to change the Title "Assessing stroke risk disparities" as it sounds that you designed the study to find out the preexisting risk factors fro stroke in transgender groups.

2. There are some punctuation and font size discordance, please check for them.

3. Please check for reference style, and correct.

Best Regards,

Reviewer #3: This a good manuscript that highlights the neglected group for health access. The scientific approach of obtaining the results is varied.

The comparison is powerful and informative. I commend your work.

Although you may not determine causation in such a cross-sectional study, but such strong associations are important in the world of science ,one as a baseline, but also as an eye opener for more investigation in the future experiments.

There are a few typos and clarity issues that i outline in the attached word document for your attention to improve the manuscript.

thank you for your efforts and scientific endeavors.

regards

petit

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Reviewer #1: Yes:  Pranav Barve MD MPH

Reviewer #2: No

Reviewer #3: No

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Attachments

Attachment

Submitted filename: review notes PLOS.docx

PONE-D-25-15914R1Post-Stroke Health Disparities: Comparative Analysis of Lifestyle and Vascular Profiles in Transgender and Cisgender Stroke SurvivorsPLOS ONE

Dear Dr. Zand,

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: I acknowledge the revisions made based on the external reviewer’s comments. However, my reading of the revised manuscript reveals persistent unresolved issues. In addition to the punctuation and font size/type face discordance mentioned by Reviewer 2, which was not resolved, I provide additional comments below to guide your next iteration of revisions. Despite these current limitations, the manuscript examines an important and understudied population, and with careful revision addressing the concerns outlined in my review, it could make a valuable contribution to our understanding of health disparities in transgender stroke survivors. 

Please submit your revised manuscript by Sep 12 2025 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,

Daniel Antwi-Amoabeng, MD, MSc

Academic Editor

PLOS ONE

Journal Requirements:

If the reviewer comments include a recommendation to cite specific previously published works, please review and evaluate these publications to determine whether they are relevant and should be cited. There is no requirement to cite these works unless the editor has indicated otherwise. 

Additional Editor Comments:

I acknowledge the revisions made based on the external reviewer’s comments. However, my reading of the revised manuscript reveals persistent unresolved issues. In addition to the punctuation and font size/type face discordance mentioned by Reviewer 2, which was not resolved. I provide additional comments below to guide your next iteration of revisions.

Title:

This has several issues.

What is meant by “vascular profiles”? It is vague and misleading. The study examines specific cardiovascular risk factors (CAD, HTN, DM, HLD) and not comprehensive vascular profiles, which would include imaging data, biomarkers or physiological measurements none of which was included.

Using disparities in the title and eliminating race and income level from your matched analysis is problematic as these are known drivers of healthcare disparities.

The title does not clarify that the study is about risk factors present in stroke survivors and not necessarily factors that developed after stroke or preceded stroke, which a cross-sectional design cannot determine.

I suggest an alternative title:

Lifestyle behaviors and cardiovascular risk factors in transgender versus cisgender stroke survivors.

Abstract:

The matching was 189 transgender to 378 cisgender (from the methods section). The total sample size stated in the abstract can be misleading, as you only analyzed 567 individuals. Please edit this to avoid confusion.

Highlights:

• The statement that transgender individuals showed 70% higher prevalence of stroke is misleading. Please interpret odds ratios appropriately.

• Smoking and alcohol: Please do not conflate likelihood and odds ratio. Again, interpret this properly

• E-cigarette: I suggest a review of the proper interpretation of odds ratios and proper reporting here.

Introduction:

This section needs to be improved. Are there putative mechanisms (beyond hormone therapy) that adversely increase the risk of strokes in transgender patients. This may be obvious to the authors but must be clearly stated as it forms that bases of the scientific value of your investigations. A focused survey of the current literature on disparities in risk factors and cardiovascular disease outcomes is needed.

Please frame the distinction between pre-stroke risk factors and post-stroke characteristics.

Methods:

Study population: were nonbinary individuals classified as cisgender or transgender?

“Their birth gender determined the gender of respondents”: Please edit it for clarity.

Please report on the BMI cut-offs for the nominal scale introduced.

Statistical analysis: Thank you for including information on why race and income level were not included in the list of variables on which your participants were matched. However, this justification is problematic, and this approach may introduce substantial bias and limits the representativeness of findings. If you can provide evidence from literature, especially from studies that use the BRFSS, your justification may be strengthened.

Results:

There are several instances where the authors conflate odds ratios with likelihood. This needs to be corrected.

Some adjusted ORs show dramatic changes from crude ORs, suggesting potential overadjustment or multicollinearity. Please consider pre-estimation multicollinearity checks such as correlation matrix or post-estimation checks such as VIF to inform which variables you include in your final model.

Table 1: Sex (please show that this is as assigned at birth)

Table 2:

• Please state currency for income level. Are these median household incomes or unadjusted reports by the respondents? State clearly that these are US Dollars.

• Please explain why you include this table and caption indicating PS matching when the methods say the variables were excluded from PS matching.

Table 3:

No correction for multiple testing despite numerous comparisons increasing Type I error risk. Please apply appropriate multiple comparison corrections or acknowledge this limitation and interpret p-values more cautiously.

Lifestyle Risk Factors:

Did you check for collinearity. Binge drinking and alcohol consumption appear to be collinear intuitively. Including both in your models may be concerning on the surface. Please provide post estimation tests such as VIF.

Discussion and Conclusions:

The 3rd sentence of the second paragraph is misleading.

I advise caution in interpreting the findings of the small sample cross-sectional study. Avoid language that suggests causal implications.

Please discuss why aORs differ so much from cORs.

Please explore alternative explanations for your findings.

Please acknowledge that self-reported diagnosis without independent validation introduces potential bias, particularly for stigmatized factors. Discuss this as a limitation.

Discuss potential survivor bias.

Paragraph 11: the study did not study post-stroke outcomes. Please correct this.

Final comment:

Despite the limitations above and those raised by the external reviewers, the study provides valuable preliminary data on this underserved population. The manuscript STILL REQUIRES MAJOR revisions before publication. The most critical issues are misinterpretation of statistical measures and overstatement of causal implications. With appropriate careful revisions, this could be a valuable contribution to our understanding of health disparities in transgender populations.

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[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.

Lifestyle Behaviors and Cardiovascular Risk Factors in Transgender Versus Cisgender Stroke Survivors

PONE-D-25-15914R2

Dear Dr. Zand,

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.

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Kind regards,

Daniel Antwi-Amoabeng, MD, MSc

Academic Editor

PLOS ONE

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