PONE-D-22-29922Association of total cholesterol variability with risk of venous thrombosis: a nationwide cohort studyPLOS ONE

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Reviewer #1: Yes

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

Reviewer #1: Yes

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Reviewer #1: Yes

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Reviewer #1: No

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5. Review Comments to the Author

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Reviewer #1: This manuscript reports on a population study on the association between variability of total cholesterol (TC) variability over time and the risk for venous thromboembolism (VTE). TC variability was measured using the coefficient of variation (CV), standard deviation (SD), and variability independent of mean (VIM). All these parameters were consistently and independently associated with a 15% increased risk for VTE.

This is an interesting manuscript. Prior to publication, I suggest the authors to address the following:

1) the age of the target population ranged from 40 to 79 years (line 90). How do the authors explain that the mean age of the studied population was only 43.8±10.1? The age distribution looks very close to the lower end of the targeted population and the results may only apply to a younger population as compared with older, which is at higher risk for both VTE and high TC.

2) have the authors considered separating analysis according to sex (as sex is an important risk factor for cardiovascular diseases)?

3) CV, SD, and VIM are collinear and based on the same parameters (mean, SD). It lead to the same risk estimates for each parameter. Could this be discussed?

4) the article needs editing throughout:

First, I suggest using “VTE” instead of “VT” for venous thromboembolism, as it is a more common abbreviation. Also, please use “DVT” for deep vein thrombosis and “PE” for pulmonary embolism.

The manuscript is sometimes unclear or imprecise, particularly the introduction (the first sentence is hard to understand, second paragraph on risk factors should be edited (major risk factors for VTE are surgery, immobilisation/fracture of lower limbs, cancer, APS; all other risk factors are at intermediate risk for VTE; I would tone done the association between AFib, renal insufficiency and VTE as well in paragraph 3).

Consider putting all criteria for definition of cardiovascular risk factors and diseases in an appendix instead of listing all ICD codes etc.

Line 274 to 296 should be rephrased. Line 290 to 293: it is not clear whether the authors refer to their papers or others.

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Reviewer #1: No

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Association of total cholesterol variability with risk of venous thromboembolism: a nationwide cohort study

PONE-D-22-29922R1

Dear Dr. Song,

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,

Christophe Leroyer

Academic Editor

PLOS ONE