Longitudinal trajectories of blood lipid levels in an ageing population sample of Russian Western-Siberian urban population

Jaroslav A. Hubacek; Yuri Nikitin; Yulia Ragino; Ekaterina Stakhneva; Hynek Pikhart; Anne Peasey; Michael V. Holmes; Denes Stefler; Andrey Ryabikov; Eugeny Verevkin; Martin Bobak; Sofia Malyutina

doi:10.1371/journal.pone.0260229

Peer Review History

Original SubmissionJune 29, 2021
23 Aug 2021 Decision Letter - Paolo Magni, Editor PONE-D-21-21255 Longitudinal trajectories of blood lipid levels in an ageing population sample of Russian Western-Siberian urban population PLOS ONE Dear Dr. Hubacek, 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. Please consider all the reviewer's comments and address properly all of them. Please submit your revised manuscript by Oct 07 2021 11:59PM. If you will need more time than this to complete your revisions, please reply to this message or contact the journal office at plosone@plos.org. When you're ready to submit your revision, log on to https://www.editorialmanager.com/pone/ and select the 'Submissions Needing Revision' folder to locate your manuscript file. 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Please include captions for your Supporting Information files at the end of your manuscript, and update any in-text citations to match accordingly. Please see our Supporting Information guidelines for more information: http://journals.plos.org/plosone/s/supporting-information. [Note: HTML markup is below. Please do not edit.] 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 ******** 2. Has the statistical analysis been performed appropriately and rigorously? Reviewer #1: Yes ****** 3. 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Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here. Reviewer #1: Yes ****** 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 manuscript is written in clear English. For achieving the aim of the study (evaluation of changes in blood lipid concentrations associated with age in a Russian West-Siberian Caucasian population) adequate statistical methods for calculations and sample size are used. The idea of the manuscript is structured and logical based on the purpose declared. However, it could be considered as a one part of a project aiming to reclassify current cardiovascular risk scores as - it does not take into account a range of other confounding factors (diet particularities, other medications that may affect lipid blood levels, physical activity etc) that may affect the curve of the blood lipid changes, - the mendelian randomization data about the life-time cardiovascular risk impact has to be taken into account, - the results presented in the manuscript have to be supported by the data about the logic association of the blood lipid changes curve in different age groups with the prevalence of cardiovascular events in these groups. ****** 6. 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. 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Revision 1
3 Nov 2021 Author Response Comments to the Author 1/ - it does not take into account a range of other confounding factors (diet particularities, other medications that may affect lipid blood levels, physical activity etc) that may affect the curve of the blood lipid changes RE: We agree that in addition to lipid lowering treatment, age, sex and smoking, there are other factors that could influence plasma lipid levels in study participants. Concerning the lipid lowering treatment, as mentioned in the discussion, our subjects were almost exclusively treated by statins (no subjects on PCSK9 inhibitors or ezetimibe were included; see now added information at lines 460 - 463). In terms of other medications – unfortunately in the HAPIEE study we have no data available on specific medication of participants apart from lipid-lowering drugs, antihypertensive drugs or sugar lowering drugs (on dosage or regiment of intake). We have described this limitation of our data in the Discussion section of the revised manuscript. In additional sensitivity analyses, we have further adjusted the models for fruit or vegetables intakes (by tertiles); total energy intake (centered at 10.6 MJ/day); and leisure time physical activity (less than 3 MET-hours/day; 3-10 MET hours/day; more than 10 MET hours/day). These adjustments did not materially change the results, including the direction of trajectories. We have added the description of additional adjustments to the revised paper (lines 353 - 366). Unfortunately, available data about dietary habits and/or general physical activities of examined subjects were not known in sufficient details at all three examinations to perform adequate analyses of effects. This is now listed between the study weaknesses (lines 414-416). 2/ - the mendelian randomization data about the life-time cardiovascular risk impact has to be taken into account RE: Thank you for this comment raising the issue of Mendelian randomisation that we have now incorporated to the Discussion. We agree that Mendelian randomisation data could be of interest for the estimation of life exposure to the distinct risk factors and their life-time impact on CVD risk. However, such analysis has not been performed in our study, mainly because of unavailable genotyping data due to the shortage of funding, and this approach is out of the scope of present paper. Nevertheless, it is merit to refer the recent papers which used the randomization by genetic score based on polymorphisms associated with LDL-C (known from GWAS), and reported the association between life-long LDL-C lowering and reduced CVD risk [Ference et al., 2019; Lind et al., 2021, ref list under 23 and 24]. In revised manuscript we have widened Discussion taking into account these findings (lines 384 - 389). 3/ - the results presented in the manuscript have to be supported by the data about the logic association of the blood lipid changes curve in different age groups with the prevalence of cardiovascular events in these groups. RE: Thank you for this comment. In our analysis, we have taken into account CVD of participants by adjusting for CVD mortality rather than prevalence. As mentioned in the Methods (lines – 161 - 162), Results (Table 4 and lines 242 - 247) and Discussion (lines – 337 - 345) sections, both total and cardiovascular mortality has been taken into account during the calculations – we have adjusted our results on these parameters. Two sensitivity analyses also suggest that the effect of CVD mortality on lipid trajectories is small and did not affect the observed trajectories substantially (see lines 340 - 345). Unadjusted and fully adjusted results are presented in Tables 2 and 4. In Tables 2, 3, 4 and wide list of supplementary figures, data are also presented for different age groups (as suggested by reviewer). Attachments Attachment Submitted filename: Response to Reviewers.docx https://doi.org/10.1371/journal.pone.0260229.r002
5 Nov 2021 Decision Letter - Paolo Magni, Editor Longitudinal trajectories of blood lipid levels in an ageing population sample of Russian Western-Siberian urban population PONE-D-21-21255R1 Dear Dr. Hubacek, 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. An invoice for payment will follow shortly after the formal acceptance. To ensure an efficient process, please log into Editorial Manager at http://www.editorialmanager.com/pone/, click the 'Update My Information' link at the top of the page, and double check that your user information is up-to-date. If you have any billing related questions, please contact our Author Billing department directly at authorbilling@plos.org. 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, Paolo Magni Academic Editor PLOS ONE https://doi.org/10.1371/journal.pone.0260229.r003
Formally Accepted
17 Nov 2021 Acceptance Letter - Paolo Magni, Editor PONE-D-21-21255R1 Longitudinal trajectories of blood lipid levels in an ageing population sample of Russian Western-Siberian urban population Dear Dr. Hubacek: I'm pleased to inform you that your manuscript has been deemed suitable for publication in PLOS ONE. Congratulations! Your manuscript is now with our production department. If your institution or institutions have a press office, please let them know about your upcoming paper now to help maximize its impact. If they'll be preparing press materials, please inform our press team within the next 48 hours. 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. If we can help with anything else, please email us at plosone@plos.org. Thank you for submitting your work to PLOS ONE and supporting open access. Kind regards, PLOS ONE Editorial Office Staff on behalf of Prof. Paolo Magni Academic Editor PLOS ONE https://doi.org/10.1371/journal.pone.0260229.r004

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