PONE-D-24-19204Relationship Between Body Mass Index and Clinical Events in Patients With Atrial Fibrillation Undergoing Percutaneous Coronary InterventionPLOS ONE

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Reviewers' comments:

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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: No

Reviewer #2: Yes

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

Reviewer #1: No

Reviewer #2: 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: No

Reviewer #2: 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

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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: In the present study, the authors evaluated the relationship between BMI and clinical events in patients who underwent PCI under OAC therapy for AF. Low BMI value was independently associated with the incidence of NACE and MACE, although not with the incidence of major bleeding events. The authors concluded that BMI value may be a useful indicator to predict major adverse clinical events in this specific patient population. It is certainly informative that low BMI may be relevant to cardiovascular risk, however, the novelty of this study is rather low and significant population biases may exist. The reviewer has comments as below.

# It is obvious that the Low BMI group has more severe clinical background. It includes higher age, more cancer patients, more anemic patients, more ACS, and more mechanical supports during PCI. Thus, the main result of the study that the Low BMI group had more clinical events, seems a matter of course. Do the results unchanged if they are age-matched or those with ACS and with cancer are excluded?

# Relevance of low BMI for NACE was significant in the multivariable Cox regression model in this study. What about for MACE?

# In table 3, sum of the number of MACE and major bleeding is not equal to NACE. Why?

# If the authors has a K-M analysis of MACE, it may be provided as a supplemental figure.

# The studied patients contains a special cohort with dual anti-thrombotic therapy with prasugrel. What is the number of them? No sub-analysis for them is provided. Why?

Reviewer #2: Review Comments

1.　Selection of BMI Cut-off Values

I understand from the authors' description in the Limitations section that the cutoff value of 21.3 for BMI is based on the first quartile of the study population. However, it is unclear to what extent this value can be generalized to other studies or clinical trials. Additionally, as it differs from the WHO standards, it makes international comparisons difficult. Therefore, to further validate the appropriateness of this cutoff value, it is recommended to conduct supplementary analyses using other cutoff values (e.g., 18.5 or 25) or analyses based on the second quartile.

2.　The need for further adjustment of confounding variables

In this study, multivariable Cox regression analysis was used to adjust for confounding factors, but further subgroup analyses are needed to more precisely evaluate the impact of sex and age. Since sex and age are likely to independently affect cardiovascular events and bleeding risks apart from BMI, additional analyses considering these variables are recommended. Specifically, please conduct subgroup analyses by sex to evaluate the relationship between BMI and clinical outcomes separately for men and women. Furthermore, instead of including age only as a continuous variable, it is advisable to perform age-stratified subgroup analyses to assess the relationship between BMI and clinical outcomes within each age group. This will provide a more accurate assessment of the relevance of BMI.

3.　Table3：Adverse clinical events at 1 year

In Table 3, the incidence rates of NACE and MACE are shown, but the confidence intervals (CI) for these rates are not provided. Adding 95% confidence intervals for the incidence rates of each event would make it easier to evaluate the precision of the results. Therefore, it is desirable to include these intervals.

4.　Regarding Group Classification and Naming

Generally, a BMI of 18.5 to 24.9 is defined as normal weight. From the context of the paper, it is understood that BMI 21.3 is used as the cutoff for grouping in this study. However, classifying the groups as Low BMI group and Normal-High BMI group feels somewhat inappropriate. It would be less confusing to categorize them as Group 1 and Group 2 or Group A and Group B, for example.

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Reviewer #1: No

Reviewer #2: No

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Relationship Between Body Mass Index and Clinical Events in Patients With Atrial Fibrillation Undergoing Percutaneous Coronary Intervention

PONE-D-24-19204R1

Dear Dr. Kitahara,

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.

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Kind regards,

Yoshihiro Fukumoto

Academic Editor

PLOS ONE

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

Reviewer #2: All comments have been addressed

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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

Reviewer #2: Yes

**********

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

Reviewer #1: Yes

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 #1: Yes

Reviewer #2: Yes

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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

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 #1: The authors well responded to the reviewers' comments and significantly improved their manuscript. I appreciate a bunch of works of the authors. The reviewer has no further comments.

Reviewer #2: Dear Authors

Thank you for your thorough and thoughtful responses to my comments. I appreciate the additional analyses you have conducted, as well as the clarifications you have made throughout the manuscript. Your efforts to address the points raised have strengthened the study, and the new data and supplementary tables have provided valuable insights. I find the revisions and responses satisfactory, and I believe the manuscript is now suitable for publication.

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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: No

Reviewer #2: No

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