Meta-analysis of the correlation between serum uric acid level and carotid intima-media thickness

Mingzhu Ma; Liangxu Wang; Wenjing Huang; Xiaoni Zhong; Longfei Li; Huan Wang; Bin Peng; Min Mao

doi:10.1371/journal.pone.0246416

Peer Review History

Original SubmissionSeptember 13, 2020
6 Nov 2020 Decision Letter - Giuseppina Novo, Editor PONE-D-20-28226 Meta-analysis of the correlaion between serum uric acid level and carotid intima-media thickness PLOS ONE Dear Dr. Mao, 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 Dec 21 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 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: Partly Reviewer #2: Yes Reviewer #3: Partly ******** 2. Has the statistical analysis been performed appropriately and rigorously? Reviewer #1: I Don't Know Reviewer #2: Yes Reviewer #3: No ****** 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 Reviewer #3: 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: No Reviewer #2: Yes Reviewer #3: No ****** 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: I think I made a mistake accepting the revision of this article whose validity is substantially linked to the soundness of its statistical approach that goes, unfortunately, beyond my level knowledge. Topic is certainly interesting but, given the ambiguity about this subject, as reported in the literature, I think that a sound statistical check (that goes beyond my capacity) is necessary. There are a few grammatical errors in the text. The style of references is not uniform across the list Reviewer #2: In this paper, authors analyze through meta-analysis the relationship between serum uric acid level and carotid intimal thickness.The paper is well designed and the conclusion, such as that there is a significant correlation between serum uric acid level and carotid intima-media thickness, and a high concentration of serum uric acid is related to carotid artery intima-media thickness are beliavable. I would suggest some revisions as follows: - in the abstract, I suggest to better explicate these sentence that was repeated: "Meta-analysis showed that carotid intimal thickness in the high uric acid group was significantly higher than that in the control group [...] The results showed that the carotid intimal thickness of the high uric acid group was still significantly higher than that of the control group, and the difference was statistically significant". - the 15 articles selected for the meta-analysis have not been cited; please add the references of these articles to allow readers to know them, maybe it would be added in the Table 1; - Figure 5 contains a mistake in the author "Francesco Antonini-Canterin" that was wrongly written. Reviewer #3: This is a meta-analysis study focus on the relationship between serum uric acid level the carotid intima-media thickness. Previous studies have shown that CIMT is the main risk factor and main pathophysiological basis of ASCVD. However, the correlation between hyperuricemia and ASCVD is still controversial. In current study contain some serious flaws and some concerns need to be addressed, 1. CIMT determination uses different B-ultrasound equipment in different research centers, and uses different operating procedures, how to evaluate the differences between centers? 2. The population included in the study is biased, and there are high-risk groups of ASCVD such as diabetes, which requires further subgroup analysis. 3. Other influencing factors of ASCVD such as blood lipid level, BP, medication status, BMI, etc. may be alternative in different studies. This will ultimately affect the value of CMIT and should be included in the analysis. 4. The mechanism of the effect of hyperuricemia on CIMT and even atherosclerosis is not sufficiently explained in the discussion section, and further elucidation is needed. 5. The normal value of CMIT is generally considered to be below 1.0mm, 1.0-1.2mm is considered to be thickened, and 1.2mm or more is considered abnormal. Can the CIMT value be subdivided into different subgroups for analysis and discuss the relationship between hyperuricemia and the abnormal rate of CMIT? 6. Professional language editing must be done prior to re-submission. ****** 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: Yes:** Concetta Di Nora Reviewer #3: 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. Then, login and navigate to the UPLOAD tab, where you will find detailed instructions on how to use the tool. If you encounter any issues or have any questions when using PACE, please email PLOS at figures@plos.org. Please note that Supporting Information files do not need this step. https://doi.org/10.1371/journal.pone.0246416.r001
Revision 1
9 Dec 2020 Author Response Editor: Any new text in the revised manuscript has been noted below in bold font. 1. In accordance with PLOS ONE’s style requirements, we have updated the file names and manuscript title, as well as the references. 2. Search terms used for the systematic review have been added to the Methods section, and PRISMA checklist has been updated in accordance with PLOS guidelines. 3. Statements of funding information have been included at the cover letter. 4. Description of competing Interests has been included at the cover letter. 5. The title in the manuscript has been modified according to the title of the online submission system. 6. Supporting Information files have been included at the end of the manuscript, and in-text citations have been updated in accordance with PLOS guidelines. Reviewer #1: We thank Reviewer #1 for the significant feedback. We strongly agree with the reviewer's opinion that a statistical check should be conducted on ambiguous subjects, which is also the purpose of our meta-analysis: we conducted a comprehensive analysis of the existing research with a statistical review to expand the sample size and better explore the correlation between serum uric acid level and carotid intimal thickness. The revised article was submitted after careful language review, and the style of references has been uniformly modified in accordance with PLOS guidelines. Thanks for your correction! Reviewer #2: We thank Reviewer #2 for the important suggestion to explicate the sentence that was repeated. The second half of the repeated part in the abstract is actually the conclusion of the subgroup analysis. We have made the following corrections (Abstract, lines 17-26): “Meta-analysis showed that CIMT in the high uric acid group was significantly higher than that in the control group (SMD = 0.53, 95% CI: [0.38, 0.68]), and the difference was significant (z = 6.98, P < 0.00001). The heterogeneity among the 15 articles was obvious (I2 = 89%, P < 0.00001). Subgroup analysis by disease status illustrated a positive relationship between SUA and CIMT in healthy people and people with diseases. SUA was shown to be positively correlated with CIMT in people aged 45-60 years and ≥60 years by subgroup analysis by age. SUA was also found to be positively correlated with CIMT in a population with BMI>24 kg/m2 by subgroup analysis by BMI. In addition, subgroup analysis of other risk factors for CIMT, including TC, SBP, DBP, triglycerides, and LDL-C, all showed a positive correlation between SUA and CIMT.” We thank Reviewer #2 for the suggestion to add the 15 articles selected for the meta-analysis to the references. We have added these 15 articles to the reference section ([20-34]) and added the "Author" column in Table 1, with references to the corresponding literature after the author's name. The mistake in Figure 5 has been corrected. Reviewer #3: We thank reviewer #3 for the extensive feedback, and we have incorporated most of it. Based on that, we think our paper has improved to a great extent. It also became more comprehensible for the reader. Thank you. 1. We would like to thank the Reviewer for raising the question of different instruments and procedures for measuring CIMT between studies. In the process of measurement, random error is inevitable due to different operators and instruments. However, the measurement methods of each research centre are strictly in accordance with the medical testing guidelines and consensus [1-4] and control the error within the acceptable range. Thus, the difference is subtle. 2. We agree with the Reviewer that further subgroup analysis is necessary. We conducted a subgroup analysis between healthy people and people at high risk of cardiovascular and cerebrovascular disease. The results are shown in Table 2, and the heterogeneity of subgroups is shown in Table 3. The following text was added to the Results section (Results, lines 156-164): “Because the correlation between SUA and CIMT is affected by population characteristics and may be affected by other risk factors for CIMT, we conducted subgroup analyses. Initially, we divided the population into two groups and found that CIMT levels were higher in the high uric acid group than in the control group, both in healthy people and in people with diseases. (Healthy people: SMD = 0.29, 95% CI: [0.17, 0.42]; people with diseases: SMD = 0.73, 95% CI: [0.52, 0.95]). The differences were statistically significant (P < 0.00001), as shown in Fig 4, which meant that SUA levels were positively correlated with CIMT. In addition, the heterogeneity of the two subgroups decreased but was still significant (I2 = 78%, P = 0.0001; I2 = 73%, P = 0.0005).” We also added the results of subgroup analysis to the Abstract (Abstract, lines 20-21): “Subgroup analysis by disease status illustrated a positive relationship between SUA and CIMT in healthy people and people with diseases.” 3. We strongly agree with the opinion that confounding factors should be considered when researching the correlation between SUA and CIMT. We have added some subgroup analyses of cardiovascular and cerebrovascular disease risk factors that may influence CIMT thickness (age, BMI, TC, SBP, DBP, LDL-C and triglyceride) and added the following content to the Results section (Results, lines 165-173): “To further control for confounders, we performed an age-based subgroup analysis and found a positive correlation between SUA and CIMT in people aged 45-60 years and ≥60 years (Fig 4), but no correlation was found in people between the ages of 18 and 45. We also performed a subgroup analysis based on BMI. The SUA level was significantly positively correlated with CIMT in people with BMI>24 kg/m2. In addition, we performed subgroup analysis on other risk factors for CIMT: TC, SBP, DBP, triglycerides and LDL-C (the forest plots are shown in S1 Appendix). The results showed that the carotid intimal thickness of the high uric acid group was higher than that of the control group, and the difference was statistically significant (Table 2). The heterogeneity of each subgroup is shown in Table 3.” We also added the results of subgroup analysis to the Abstract (Abstract, lines 22-26): “SUA was shown to be positively correlated with CIMT in people aged 45-60 years and ≥60 years by subgroup analysis by age. SUA was also found to be positively correlated with CIMT in a population with BMI>24 kg/m2 by subgroup analysis by BMI. In addition, subgroup analysis of other risk factors for CIMT, including TC, SBP, DBP, triglycerides, and LDL-C, all showed a positive correlation between SUA and CIMT.” However, because the number of included studies was limited and the confounders included in each study were not exactly the same (we added the confounders of each article to S2 Table), some confounders were included in too few articles. We were unable to conduct an adequate combinatorial analysis during the subgroup analysis, nor were we able to analyse many other important factors that might affect CIMT, which may result in confusion in relation to the conclusion. This is also one of the limitations of our research. We have added this information to the limitations of the article (Discussion, lines 276-279): “Third, the analysis was also limited by the number of included studies and the quality of individual studies. We were unable to conduct an adequate combinatorial analysis during the subgroup analysis, and many other important factors affecting CIMT could not be analysed.” 4. We appreciate the suggestion by Reviewer #3 to further discuss the mechanisms of hyperuricaemia in CIMT and atherosclerosis. We have added to the Discussion section a description of how hyperuricaemia affects CIMT and atherosclerosis (Discussion, lines, 204-223): “The destruction of the vascular wall and endothelial cell function are direct causes of atherosclerosis. As an end product of purine metabolism in humans and higher primates, uric acid can damage the integrity of the vascular surface and affect the function of endothelial cells through direct or indirect effects on the vascular endothelium. The mechanism of this process is as follows: uric acid can promote the proliferation and migration of vascular smooth muscle cells and even lead to vascular remodelling, affecting its normal function. When the concentration of uric acid in the blood reaches a certain level, it will deposit into the tissue in the form of urate crystals and damage the vascular endothelium. The occurrence of hyperuricaemia aggravates abnormalities in metabolites and affects the vascular endothelium and haemodynamics [23]. Oxidative stress is the key link in endothelial dysfunction caused by hyperuricaemia and is related to the increased risk of cardiovascular and cerebrovascular disease [39]. However, there is another effect of uric acid level on carotid atherosclerosis. When blood vessels are in the atherosclerotic state, the pro-oxidant state will inactivate some superoxide dismutases (e.g., NOS1 and NOS3, etc.) and reduce the scavenging of free radicals in blood vessels, thus increasing the oxygen level [40]. Uric acid protects the activity of these inactivated enzymes and may counteract the harmful effects of hyperuricaemia in some areas of the vascular system [26]. Because uric acid is generally considered to have more harmful than protective effects, it is considered to be a risk factor for CIMT and atherosclerosis [36, 37, 42], but the clinical relevance of the two has been controversial.” 5. We thank Reviewer #3 very much for posing this important question, which is what we want to solve. However, most of the literature measured only CIMT thickness and did not classify the population according to the status of CIMT (thickened, abnormal or plaque), so we failed to explore the relationship between hyperuricaemia and the abnormal rate of CIMT through subgroup analysis. We have added the following to illustrate these limitations in the discussion section (Discussion, lines 273-276): “Second, similarly, different conditions of CIMT (thickened, abnormal and plaque, etc.) were not distinguished in the included literature, resulting in the inability to conduct subgroup analysis on the correlation between SUA and different types of CIMT abnormalities.” 6. Professional language editing has been completed. Reference: 1. Management of Atherosclerotic Carotid and Vertebral Disease: 2017 Clinical Practice Guidelines of the European Society for Vascular Surgery (ESVS):http://sr.xingshulin.com/view/guide.html?id=13703&share_ticket=code%3D-1%26version%3D7.16.0%26os%3Da 2. Saba L, Yuan C, Hatsukami TS, Balu N, Qiao Y, DeMarco JK, et al. Carotid Artery Wall Imaging: Perspective and Guidelines from the ASNR Vessel Wall Imaging Study Group and Expert Consensus Recommendations of the American Society of Neuroradiology. AJNR Am J Neuroradiol. 2018;39(2):E9-e31. Epub 2018/01/13. doi: 10.3174/ajnr.A5488. PubMed PMID: 29326139; PubMed Central PMCID: PMCPMC7410574. 3. Xiaoying Li, Heng Guan, Tingshu Yang, Wei Guo, Shuxia Wang. Chinese experts suggest the diagnosis and treatment of atherosclerotic diseases in the limbs of the elderly (2012). Chinese Journal of Geriatrics. 2013;(02):121-31.(in Chinese) 4. Chinese guidelines for interventional diagnosis and treatment of carotid artery stenosis: http://sr.xingshulin.com/view/guide.html?id=7150&share_ticket=code%3D-1%26version%3D7.16.0%26os%3Da Attachments Attachment Submitted filename: Response to Reviewers.docx* https://doi.org/10.1371/journal.pone.0246416.r002
8 Jan 2021 Decision Letter - Giuseppina Novo, Editor PONE-D-20-28226R1 Meta-analysis of the correlation between serum uric acid level and carotid intima-media thickness PLOS ONE Dear Dr. Mao, 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. Particularly revise the discussion according to one of the reviewers suggestions. Afterwards there are no more comments to be addressed. Please submit your revised manuscript by Feb 22 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. Please include the following items when submitting your revised manuscript: A rebuttal letter that responds to each point raised by the academic editor and reviewer(s). You should upload this letter as a separate file labeled 'Response to Reviewers'. A marked-up copy of your manuscript that highlights changes made to the original version. You should upload this as a separate file labeled 'Revised Manuscript with Track Changes'. An unmarked version of your revised paper without tracked changes. You should upload this as a separate file labeled 'Manuscript'. If you would like to make changes to your financial disclosure, please include your updated statement in your cover letter. Guidelines for resubmitting your figure files are available below the reviewer comments at the end of this letter. If applicable, we recommend that you deposit your laboratory protocols in protocols.io to enhance the reproducibility of your results. Protocols.io assigns your protocol its own identifier (DOI) so that it can be cited independently in the future. For instructions see: http://journals.plos.org/plosone/s/submission-guidelines#loc-laboratory-protocols We look forward to receiving your revised manuscript. Kind regards, Giuseppina Novo Academic Editor PLOS ONE [Note: HTML markup is below. Please do not edit.] 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 #2: All comments have been addressed Reviewer #3: 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 #2: Yes Reviewer #3: Yes ****** 3. Has the statistical analysis been performed appropriately and rigorously? Reviewer #2: Yes Reviewer #3: 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 #2: Yes Reviewer #3: 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 #2: Yes Reviewer #3: 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 #2: In this paper, authors analyze through meta-analysis the relationship between serum uric acid level and carotid intimal thickness. The paper is well designed and the conclusion, such as that there is a significant correlation between serum uric acid level and carotid intima-media thickness, and a high concentration of serum uric acid is related to carotid artery intima-media thickness are beliavable. All the previous concerns have been adequately addressed by the authors. Reviewer #3: The discussion could be more concise and highlight its clinical significance, in addition, there is a little no more revision needed. ****** 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 #2: Yes:** Concetta Di Nora Reviewer #3: 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. Then, login and navigate to the UPLOAD tab, where you will find detailed instructions on how to use the tool. If you encounter any issues or have any questions when using PACE, please email PLOS at figures@plos.org. Please note that Supporting Information files do not need this step. https://doi.org/10.1371/journal.pone.0246416.r003
Revision 2
13 Jan 2021 Author Response Editor: Any new text in the revised manuscript has been noted below in bold font. The Discussion section has been modified according to the suggestions of reviewers. RESPONSE TO REVIEWER’S COMMENTS: Reviewer #3: The discussion could be more concise and highlight its clinical significance, in addition, there is a little no more revision needed. Reply: We appreciate the excellent observation from Reviewer #3 regarding the Discussion section. We adopted the suggestions of reviewers, revised the discussion and added the following contents to highlight the clinical significance (Discussion, lines 244-251): “Therefore, this study revealed that a high level of SUA may be a predictor of atherosclerosis, and strengthening the control of serum uric acid levels in early prevention is helpful to reduce the risk of atherosclerosis. These findings proved that the rising level of SUA could pose an increased risk of cardiovascular and cerebrovascular diseases, provided a potential therapeutic target and new ideas for further clinical researches. It was suggested that decreasing level of uric acid could be an adjunctive therapy for cardiovascular and cerebrovascular diseases, and the atherosclerosis diagnosis and treatment also could be supported by testing the level of SUA in clinic.” Attachments Attachment Submitted filename: Response to Reviewers.docx* https://doi.org/10.1371/journal.pone.0246416.r004
20 Jan 2021 Decision Letter - Giuseppina Novo, Editor Meta-analysis of the correlation between serum uric acid level and carotid intima-media thickness PONE-D-20-28226R2 Dear Dr. Mao, 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, Giuseppina Novo 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 #2: All comments have been addressed Reviewer #3: 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 #2: (No Response) Reviewer #3: Yes ****** 3. Has the statistical analysis been performed appropriately and rigorously? Reviewer #2: (No Response) Reviewer #3: N/A ****** 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 #2: (No Response) Reviewer #3: 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 #2: (No Response) Reviewer #3: 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 #2: ---------------------------------------------------------------------------------------------------- Reviewer #3: The author has rigorously answered the reviewer's questions and made corresponding modifications. Now it could be accepted for publication. ****** 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 #2: Yes:** CONCETTA DI NORA Reviewer #3: No https://doi.org/10.1371/journal.pone.0246416.r005
Formally Accepted
22 Jan 2021 Acceptance Letter - Giuseppina Novo, Editor PONE-D-20-28226R2 Meta-analysis of the correlation between serum uric acid level and carotid intima-media thickness Dear Dr. Mao: 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 Professor Giuseppina Novo Academic Editor PLOS ONE https://doi.org/10.1371/journal.pone.0246416.r006

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