PONE-D-20-39440

Obesity and Mortality after the First Ischemic Stroke: Is Obesity Paradox Real?

PLOS ONE

Dear Dr. Zand,

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Aristeidis H. Katsanos, MD, PhD

Academic Editor

PLOS ONE

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[This study had no specific funding. VA had financial research support from the Defense Threat Reduction Agency (DTRA) grant No. HDTRA1-18-1-0008 sub-awarded to Geisinger and funds from the National Institute of Health (NIH) grant No. R56HL116832 sub-awarded to Geisinger during the study period. RZ had financial research support from Bucknell University Initiative Program, Roche – Genentech Biotechnology Company, the Geisinger Health Plan Quality fund, and receives institutional support from Geisinger Health System during the study period.]

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Reviewers' comments:

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Comments to the Author

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Reviewer #1: Yes

Reviewer #2: Yes

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

Reviewer #1: Yes

Reviewer #2: Yes

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Reviewer #1: Yes

Reviewer #2: No

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Reviewer #1: Yes

Reviewer #2: Yes

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5. Review Comments to the Author

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Reviewer #1: This is a retrospective, cohort study of consecutive first-ever ischemic stroke patients with the aim to investigate the association between baseline BMI and all-cause mortality after stroke. This is a well-designed study, based on high quality data derived from GNSIS database, assessed with robust statistical analyses, producing well-presented results supporting the obesity paradox which has been questioned in previous studies. What is more, the authors have already adequately discussed all potential limitations.

For further discussion and due to the existence of data of such a high quality, it would be of interest if an association could be presented between the obesity and mortality among specific ischemic stroke subtypes.

Reviewer #2: The study by Chaudhary et al. provides evidence in support of the “obesity paradox” in ischemic stroke patients. In this retrospective cohort of 6,703 first-time ischemic stroke patients, overweight and obese patients were found to have statistically decreased hazard ratio for one-year mortality in comparison to non-overweight patients. The manuscript is very well written, the methods and statistical analyses are adequately presented. The authors could consider few suggestions that might further improve the results/discussion.

1. Are underlying stroke etiologies captured in the GNSIS database? Considering the noted differences in cardiovascular risk factors in obese/overweight vs. non-overweight patients (as shown in Table 1), it would be interesting to assess whether small vessel disease or other underlying stroke etiologies might differ between obese/overweight vs. non-overweight patients (i.e., with subsequent implications in the functional recovery after stroke).

2. Could the authors discuss on whether ischemic/hypoxic preconditioning might be associated with improved functional outcome in obese/overweight patients? Can the rates of concomitant Obesity hypoventilation syndrome (OHS) be retrieved for included patients?

Minor

- Line 256, p 12: “has” should be corrected to “have”.

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Reviewer #1: No

Reviewer #2: Yes: Maria-Ioanna Stefanou

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Obesity and mortality after the first ischemic stroke: Is obesity paradox real?

PONE-D-20-39440R1

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,

Aristeidis H. Katsanos, MD, PhD

Academic Editor

PLOS ONE

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Reviewers' comments: