White blood cell count and incidence of hypertension in the general Japanese population: ISSA-CKD study

Shintaro Ishida; Seiji Kondo; Shunsuke Funakoshi; Atsushi Satoh; Toshiki Maeda; Miki Kawazoe; Chikara Yoshimura; Kazuhiro Tada; Koji Takahashi; Kenji Ito; Tetsuhiko Yasuno; Kosuke Masutani; Hitoshi Nakashima; Hisatomi Arima

doi:10.1371/journal.pone.0246304

Peer Review History

Original SubmissionJuly 4, 2020
6 Oct 2020 Decision Letter - Tatsuo Shimosawa, Editor PONE-D-20-20652 White blood cell count and incidence of hypertension in the general Japanese population: ISSA-CKD study PLOS ONE Dear Dr. Ishida, 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 submit your revised manuscript by Nov 20 2020 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 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 Reviewer #2: Yes ******** 2. Has the statistical analysis been performed appropriately and rigorously? Reviewer #1: No Reviewer #2: Yes ****** 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 ****** 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 ****** 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: Although it is a retrospective analysis, it is an interesting study that analyzes the association between the development of hypertension and white blood cell(WBC) count in many subjects. However, more detail discussion should be given to the causal relationship between WBC count and hypertension. For example, if it is reported that the number of WBC decreases due to improvement of obesity and lipid abnormalities, it becomes easier to support the results of this study. Finally, it is necessary to correct LDH cholesterol to LDL cholesterol in Table 2. Reviewer #2: Using a population-based retrospective cohort study in Iki-City, Nagasaki Prefecture, Japan, authors evaluated the relationship between the WBC count and hypertension in the general Japanese population. They demonstrated that the WBC count was associated with future development of hypertension. It should be recommended to add some explanations and/or interpretation. 1. Iki-City is considered to be an aging society compared to the national average in Japan. It may affect as selection bias. 2. A number of previous observational studies reported associated between indicators of inflammation and incidence of hypertension. A prospective cohort study of a Japanese population was also reported. What is the novelty in the present study? ****** 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. 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 [NOTE: If reviewer comments were submitted as an attachment file, they will be attached to this email and accessible via the submission site. Please log into your account, locate the manuscript record, and check for the action link "View Attachments". If this link does not appear, there are no attachment files.] While revising your submission, please upload your figure files to the Preflight Analysis and Conversion Engine (PACE) digital diagnostic tool, https://pacev2.apexcovantage.com/. PACE helps ensure that figures meet PLOS requirements. To use PACE, you must first register as a user. Registration is free. 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Revision 1
8 Jan 2021 Author Response Response to Reviewer #1 Thank you for your useful suggestions. We have attempted to address your suggestions as follows: Major comment 1. Although it is a retrospective analysis, it is an interesting study that analyzes the association between the development of hypertension and white blood cell (WBC) count in many subjects. However, more detail discussion should be given to the causal relationship between WBC count and hypertension. For example, if it is reported that the number of WBC decreases due to improvement of obesity and lipid abnormalities, it becomes easier to support the results of this study. Response. Thank you for your advice. (1) We could not find a paper that reported that WBC decreased due to improvement of obesity but there was a cross sectional study that reported the association between obesity and higher WBC counts. Because weight gain has been shown to be associated with increase in blood pressure levels, WBC counts may in part be associated with hypertension in part as a maker of obesity. We have added this the 3rd paragraph of the Discussion section (lines 167 to 170, page 8) as follows: “Another possibility is that WBC count may in part be associated with hypertension in part as a maker of obesity, because obesity is associated with higher WBC count [25] and weight gain [26] has been shown to be associated with increasing levels in blood pressure levels. “ (2) We could find papers which reported that WBC decreased due to lipid lowering treatment using statins. However, because statins have anti-inflammatory effects, it is not clear whether lowering lipid abnormalities lowering itself reduces WBC counts or not. Therefore, we are not sure whether lipids are involved in the link between WBC counts and hypertension. Major comment 2. It is necessary to correct LDH cholesterol to LDL cholesterol in Table 2. Response. Thank you for your advice. We suppose that the typo you pointed out is in Table1 instead of Table2. We corrected “LDH cholesterol” to “LDL cholesterol” in the revised Table1. Response to Reviewer #2 Thank you for your useful suggestions. We have attempted to address your suggestions as follows: Major comment 1. Iki-City is considered to be an aging society compared to the national average in Japan. It may affect as selection bias. Response. As you pointed out, frequency of people aged 65 years or older (“aging rate”) was 35.5% in the Iki City in 2015, which was higher than that of the total Japan (26.5%in 2015). As a result, findings of this study with higher frequency of elderly may not be applicable to other regions of Japan with lower aging rates. We have added this limitation to the 4th paragraph of the Discussion section (lines 176 to 178, page 8) as follows: “Third, because frequency of people aged 65 years or older (“aging rate”) was higher in the Iki City (35.5% in 2015) than that of the total Japan (26.5%in 2015), our findings may not be applicable to other regions of Japan with lower aging rates.” Major comment 2. A number of previous observational studies reported associated between indicators of inflammation and incidence of hypertension. A prospective cohort study of a Japanese population was also reported. What is the novelty in the present study? Response. Thank you for your advice. A novelty of the present study is the fact that this is a population-based study in current Japan. Although one longitudinal study investigated the association between white blood cell counts and incidence of hypertension among Japanese, their participants were atomic bomb survivors in the Hiroshima and the Nagasaki Prefectures. Furthermore, baseline assessment of white blood cells counts were conducted in 1960’s. In contrast, participants of this study were general Japanese people and baseline assessment was conducted after 2006. Yours sincerely Shintaro Ishida Attachments Attachment Submitted filename: Response to Reviewers 2.docx https://doi.org/10.1371/journal.pone.0246304.r002
18 Jan 2021 Decision Letter - Tatsuo Shimosawa, Editor White blood cell count and incidence of hypertension in the general Japanese population: ISSA-CKD study PONE-D-20-20652R1 Dear Dr. Ishida, 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, Tatsuo Shimosawa, M.D., Ph.D. 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: (No Response) Reviewer #2: All comments have been addressed ******** 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: Yes 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: I confirmed the detail discussion about causal relationship between WBC count and hypertension. I was satisfied with your response and revised manuscript. I decided to accept this paper. Reviewer #2: This second version of the paper has been much improved. The responses to the comments and the added description are adequate. ****** 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 https://doi.org/10.1371/journal.pone.0246304.r003
Formally Accepted
22 Jan 2021 Acceptance Letter - Tatsuo Shimosawa, Editor PONE-D-20-20652R1 White blood cell count and incidence of hypertension in the general Japanese population: ISSA-CKD study Dear Dr. Ishida: 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. Tatsuo Shimosawa Academic Editor PLOS ONE https://doi.org/10.1371/journal.pone.0246304.r004

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