Biomarkers of Clot Activation and Degradation and Risk of Future Major Cardiovascular Events in Acute Exacerbation of COPD: A Cohort Sub-Study in a Randomized Trial Population
, Jannie Marie Bülow Sand 2,†, Charlotte Suppli Ulrik 3,4, Julie Janner 3, Christian Philip Rønn 1, Sarah Rank Rønnow 2, Diana Julie Leeming 2, Sidse Graff Jensen 1, Torgny Wilcke 1,4, Alexander G. Mathioudakis 5,6, Marc Miravitlles 7, Therese Lapperre 8,9, Elisabeth Bendstrup 10,11, Ruth Frikke-Schmidt 4,12, Daniel D. Murray 13, Theis Itenov 13, Apostolos Bossios 14,15, Susanne Dam Nielsen 4,16, Jørgen Vestbo 5,6, Tor Biering-Sørensen 17,18, Jens-Ulrik Jensen 1,4,13,‡ and add
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Round 1
Reviewer 1 Report
Table 1 presents data only for males? Were there any female patients in the cohort?
Middle part of Table 1 (Biomarkers) should be presented in a figure
In discussion: Paragraph 1 has a conclusion. Which data supports that conclusion? Also, in the discussion indicate whether there was a postive or negative correlation, weak or strong.
Clinically, how is this manuscript relevant?
Author Response
Please see the attachment. In the attachment is a point-to-point response. The comments are listed C1, C2, C3, etc. Responses correspond to this and are listed e.g. R_C1, R_C2, R_C3 etc.
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Reviewer 2 Report
this is an interesting study exploring the association of clotting related biomarkers during AECOPD with subsequent MACE at 36 m follow up
comments:
1. the conclusion that VWF-N is associated with subsequent MACE appears to based on marginal statistical significance. The unadjusted hazard ratio had p value > 0.05. Adjust HR said to be 0.05.
2. Table 2 should include overall MACE with corresponding values included.
3. For death in table two, it appears that the high vWF-N group had lower mortality than the high group, which contradicts the text
Author Response
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Reviewer 3 Report
The current study confirmed an association between VWF-N and future MACE, but without significant. Concering MACE is the primary outcome, some vital confounder factors such as peripheral arterial disease history, stain treatment were not included in a multivariable Cox proportional hazard regression analysis.
Author Response
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Round 2
Reviewer 1 Report
V2 is a great version of the manuscript.
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Reviewer 2 Report
Figure 4 needs labels for the two panels. I assume the top is unadjusted cox regression HR and bottom one is adjusted. also legend should stat the outcome is MACE
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Reviewer 3 Report
The current study confirmed an association between VWF-N and future MACE, both in unadjusted and adjusted models. The discussion part is short and need more information, such as potential mechanisms and impact of public health or clinical practice.
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