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PONE-D-21-04254

Long-term Risk of Death and Recurrent Cardiovascular Events Following Acute Coronary Syndromes

PLOS ONE

Dear Dr. Welsh,

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.

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Yoshihiro Fukumoto

Academic Editor

PLOS ONE

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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: Yes

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

Reviewer #1: I Don't Know

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: Yes

Reviewer #2: Yes

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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

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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: The authors tried to show the long-term cardiovascular (CV) event risk in patients with acute coronary syndrome (ACS) and the factors that were associated with the risk. The results indicated that patients with NSTEMI, rather than those with STEMI or unstable angina, were at a higher risk for major adverse cardiac events (MACE) defined by a composite of all-cause death, hospitalization for stroke, and re-hospitalization for MI. The incremental presence of comorbidities was associated with worse long-term outcomes in the study patients with ACS. Thus, the authors’ observations agreed with previous reports and added valuable data.

The strength of the current study is the large number of study patients and the data of mortality might be accurate, while the weaknesses of the study include the lack of information about the status of risk management, adherence to the medical therapies and detailed information (such as severity) of other endpoints and comorbidities.

Because the study patients were those with ACS presentation and diabetes and hypertension were included in the comorbidity count variables, another common risk factor for coronary artery disease, dyslipidemia or hyper-LDL cholesterolemia should be included in the variables as well. Why the authors excluded this factor from the comorbidity count variables? If the reason was that hyper-LDL cholesterolemia was not a significant risk factor for future CV events in this study, the use of statins in patients with hyper-LDL cholesterolemia and non-use in those without hyper-LDL cholesterolemia might cancel the significance of this risk factor. Thus, the lack of information of control status of each risk factor could affect the results. Please consider adding hyper-LDL cholesterolemia to the comorbidity count variables, if the data are available.

Use of the term “residual risk” in the current study seems somewhat strange to me. Residual risks may be defined as risks remained after intensive or at least standard risk control was achieved, but the risk management status was uncertain.

Reviewer #2: This is an interesting study reporting the impact of the comorbidities on residual CV risk in a large, inclusive population of patients following an ACS. The sample size is large. The paper is well-written. I have only one comment to the authors.

What is the novelty of this study? I think several reports have already shown clinical significance of the comorbidities in ACS patients. Could the authors highlight novelty of this study in discussion?

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Reviewer #1: No

Reviewer #2: No

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Long-term Risk of Death and Recurrent Cardiovascular Events Following Acute Coronary Syndromes

PONE-D-21-04254R1

Dear Dr. Welsh,

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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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,

Yoshihiro Fukumoto

Academic Editor

PLOS ONE

Additional Editor Comments (optional):

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: I Don't Know

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

**********

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 adequately addressed my comments and described difficult issues to be revised as study limitations. I have no further comments.

Reviewer #2: (No Response)

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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