PONE-D-23-23654Ambient Air Pollution and Subclinical Carotid Atherosclerosis Measured by Magnetic Resonance Imaging: A Prospective Cohort Study

PLOS ONE

Dear Dr. de Souza,

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.

==============================

Dear Authors,

I have reviewed your manuscript detailing the association between air pollution and subclinical atherosclerosis in a Canadian cohort. Below, I outline both the strengths of your work and areas that require attention and revision.

Strengths:

Subject Matter: The topic of your study is highly relevant and timely, addressing an important public health concern.

Methodology: The use of MRI-characterized CWV to assess atherosclerosis is innovative and provides a more precise measurement.

Please address reviewer comments made by the two reviewers.

Furthermore, Areas for Revision:

Exposure Misclassification: Please provide a more detailed explanation of how individual-level exposures were estimated based on residence address. Consideration of participants' time away from residence and residential history could enhance the accuracy of the exposure assessment.

Inconsistent Exposure Window: The fixed 5-year pollutant exposure period for all participants may introduce bias. Please discuss this limitation and consider conducting sensitivity analyses to assess its impact.

Unexpected Findings: The negative association of NO2 with CWV and the lack of association with PM2.5 were unexpected. A more comprehensive discussion of these findings and potential underlying factors is needed.

Resolution of O3 Data: The spatial resolution of O3 data (10 km) may not be fine enough to capture local variations. Please discuss this limitation and its potential impact on the findings related to O3.

Lack of Consideration for Intraplaque Hemorrhage: Please discuss the limitation of not being able to look at intraplaque hemorrhage and its potential significance in understanding the relationship between air pollution and atherosclerosis.

Additional Limitations: Consider addressing other potential limitations such as selection bias, lack of longitudinal data, potential confounding variables, measurement error in pollution data, limited geographic scope, and potential interaction effects.

Your study has the potential to make a significant contribution to the field. However, the above concerns need to be addressed to enhance the robustness and credibility of the findings. I recommend a minor revision that includes a more detailed analysis of the exposure assessment, consideration of additional confounding variables, and a more comprehensive discussion of the unexpected findings and other limitations.

I look forward to seeing the revised manuscript.

==============================

Please submit your revised manuscript by Oct 06 2023 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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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.

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We look forward to receiving your revised manuscript.

Kind regards,

Sabeena Jalal, MBBS, MSc, MSc, SM

Academic Editor

PLOS ONE

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3. Thank you for stating the following in the Competing Interests section: 

"I have read the journal's policy and the authors of this manuscript have the following competing interests:

RJ de Souza has served as an external resource person to the World Health Organization’s Nutrition Guidelines Advisory Group on trans fats, saturated fats, and polyunsaturated fats.  The WHO paid for his travel and accommodation to attend meetings from 2012-2017 to present and discuss this work.  He has presented updates of this work to the WHO in 2022. He has also done contract research for the Canadian Institutes of Health Research’s Institute of Nutrition, Metabolism, and Diabetes, Health Canada, and the World Health Organization for which he received remuneration.  He has received speaker’s fees from the University of Toronto, and McMaster Children’s Hospital. He has held grants from the Canadian Institutes of Health Research, Canadian Foundation for Dietetic Research, Population Health Research Institute, and Hamilton Health Sciences Corporation as a principal investigator, and is a co-investigator on several funded team grants from the Canadian Institutes of Health Research. He has served as an independent director of the Helderleigh Foundation (Canada). He serves as a member of the Nutrition Science Advisory Committee to Health Canada (Government of Canada), and a co-opted member of the Scientific Advisory Committee on Nutrition (SACN) Subgroup on the Framework for the Evaluation of Evidence (Public Health England). Dr Anand reported receiving grants from Canadian Partnership Against Cancer, Heart and Stroke Foundation of Canada, and Canadian Institutes of Health Research, and a Canadian Institutes of Health Research Foundation grant during the conduct of the study and serving as the Tier 1 Canada Research Chair Ethnicity and Cardiovascular Disease and as the Michael G Degroote Heart and Stroke Foundation Chair in Population Health Research, and receiving grants from Heart and Stroke Foundation of Canada and Canadian Institutes of Health Research, and receiving personal fees from Bayer outside the submitted work. Dr Friedrich reported receiving personal fees from Circle CVI Inc for serving as a board member and adviser and being a shareholder outside the submitted work. Dr Dummer reported receiving grants from Canadian Partnership Against Cancer during the conduct of the study. Dr Lear reported receiving grants from the Canadian Institutes of Health Research and grants from Michael Smith Foundation for Health Research during the conduct of the study and personal fees from Curatio Inc outside the submitted work. Dr Tardif reported receiving grants from Amarin, Ceapro, Esperion, Ionis, Novartis, Pfizer, RegenXBio, Sanofi, AstraZeneca, and DalCor Pharmaceuticals, receiving personal fees from AstraZeneca, HLS Pharmaceuticals, Pendopharm, and DalCor Pharmaceuticals, and having a minor equity interest in DalCor Pharmaceuticals Minor outside the submitted work. In addition, Dr Tardif had a patent for Pharmacogenomics-Guided CETP Inhibition issued by DalCor Pharmaceuticals, a patent for Use of Colchicine After Myocardial Infarction pending, and a patent for Genetic Determinants of Response to Colchicine pending. No other disclosures were reported. Dr Brauer served on the WHO Guideline Development Group (no remuneration was provided but travel costs to meetings were covered). "

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Additional Editor Comments:

Dear Authors,

I have reviewed your manuscript detailing the association between air pollution and subclinical atherosclerosis in a Canadian cohort. Below, I outline both the strengths of your work and areas that require attention and revision.

Strengths:

Subject Matter: The topic of your study is highly relevant and timely, addressing an important public health concern.

Methodology: The use of MRI-characterized CWV to assess atherosclerosis is innovative and provides a more precise measurement.

Areas for Revision:

Exposure Misclassification: Please provide a more detailed explanation of how individual-level exposures were estimated based on residence address. Consideration of participants' time away from residence and residential history could enhance the accuracy of the exposure assessment.

Inconsistent Exposure Window: The fixed 5-year pollutant exposure period for all participants may introduce bias. Please discuss this limitation and consider conducting sensitivity analyses to assess its impact.

Unexpected Findings: The negative association of NO2 with CWV and the lack of association with PM2.5 were unexpected. A more comprehensive discussion of these findings and potential underlying factors is needed.

Resolution of O3 Data: The spatial resolution of O3 data (10 km) may not be fine enough to capture local variations. Please discuss this limitation and its potential impact on the findings related to O3.

Lack of Consideration for Intraplaque Hemorrhage: Please discuss the limitation of not being able to look at intraplaque hemorrhage and its potential significance in understanding the relationship between air pollution and atherosclerosis.

Additional Limitations: Consider addressing other potential limitations such as selection bias, lack of longitudinal data, potential confounding variables, measurement error in pollution data, limited geographic scope, and potential interaction effects.

Conclusion:

Your study has the potential to make a significant contribution to the field. However, the above concerns need to be addressed to enhance the robustness and credibility of the findings. I recommend a minor revision that includes a more detailed analysis of the exposure assessment, consideration of additional confounding variables, and a more comprehensive discussion of the unexpected findings and other limitations.

I look forward to seeing the revised manuscript.

Thank you.

[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: Partly

**********

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

Reviewer #1: Yes

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: Hello,

The study presents valuable insights into the relationship between air pollution and subclinical atherosclerosis, utilizing a large sample size and advanced MRI techniques. The geographical diversity and comprehensive analysis add to the study's strengths.

However, there are areas that require clarification and improvement:

Exposure Assessment: The authors should provide a more detailed explanation of the exposure misclassification risk and how the fixed 5-year pollutant exposure period might have affected the results. Clarifying these aspects would enhance the paper's transparency and allow readers to better assess the findings' validity.

Unexpected Findings: The unexpected negative association with NO2 and the lack of association with PM2.5 should be discussed more thoroughly. The authors should explore potential reasons for these findings and compare them more extensively with existing literature.

Resolution of O3 Data: The authors should discuss the limitations of the O3 spatial resolution and how it might have influenced the results.

Additional Analyses (Optional): If possible, further analyses could be conducted to address some of the limitations, such as considering participants' time away from residence or exploring the relationship with intraplaque hemorrhage.

The paper's contributions are significant, and the limitations do not undermine the overall value of the research. However, addressing these minor revisions would enhance the paper's clarity, coherence, and impact. Therefore, acceptance with minor revisions seems the most appropriate recommendation.

Thank you.

Reviewer #2: Mention the limitations

Selection Bias: If the study's participants were not randomly selected or if there was a lack of diversity in the sample (e.g., age, gender, geographic location), this could introduce selection bias, limiting the generalizability of the findings.

Lack of Longitudinal Data: If the study was cross-sectional in nature, the lack of longitudinal data might hinder the ability to establish causal relationships between air pollution and atherosclerosis.

Potential Confounding Variables: If not all relevant confounding variables were controlled for, such as diet, lifestyle factors, or pre-existing health conditions, this could affect the validity of the associations found.

Measurement Error in Pollution Data: If there were inaccuracies in the measurement of pollution levels, such as reliance on satellite data or modeling without sufficient ground-truthing, this could lead to misestimation of exposure levels.

Lack of Sensitivity Analysis: If sensitivity analyses were not conducted to assess the robustness of the findings to different modeling assumptions or potential outliers, this could raise questions about the stability of the results.

Concerns Regarding Exposure Assessment: The methodology used to gauge individual-level exposures, relying solely on residence addresses, might lead to inaccuracies in exposure classification. The failure to account for variations in participants' locations and their residential histories could compromise the integrity of the exposure evaluation.

Inconsistency in Exposure Time Frame: The application of a uniform 5-year window for pollutant exposure across all participants, irrespective of their specific enrollment dates, could introduce an element of bias, potentially skewing the assessment of exposure.

Unanticipated Results: The findings that NO2 was inversely associated with CWV and that there was no discernible connection with PM2.5 were surprising and at odds with certain existing studies. These outcomes prompt questions about possible unaccounted confounding variables or other hidden factors that might have shaped the results.

Limitations in O3 Data Resolution: The 10 km spatial resolution used for O3 data might be insufficient to detect localized fluctuations, which could have an impact on the precision of the conclusions drawn regarding O3.

Omission of Intraplaque Hemorrhage Analysis: The study's inability to examine intraplaque hemorrhage, owing to its limited scope, might overlook a crucial aspect in unraveling the complex relationship between air pollution and atherosclerosis. This limitation could be significant in the overall interpretation of the findings.

**********

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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

**********

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PONE-D-23-23654R1Ambient Air Pollution and Subclinical Carotid Atherosclerosis Measured by Magnetic Resonance Imaging: A Prospective Cohort StudyPLOS ONE

Dear Dr. de Souza,

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.

==============================

ACADEMIC EDITOR: 

1. Although "air pollution" is cited in the study title, "air pollutants exposure" is explicitly addressed in the findings. Therefore, the study should use more precise language to avoid drawing readers' attention away from the discrepancy between the title and the findings. Suggested Title: Exposure to Air Pollutants and Subclinical Carotid Atherosclerosis Measured by Magnetic Resonance Imaging: A Prospective Cohort Study

2. Tables S4 through S8 appear to include the study's most significant findings. Given that these are the most significant findings, why are these tables listed in the supplementary materials? These should be mentioned in the main manuscript.

3. Please take into account the feedback from the reviewers and thoroughly proofread the study for errors and grammatical flaws.

4. The manuscript may be accepted after minor revisions.

==============================

Please submit your revised manuscript by Apr 22 2024 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: https://journals.plos.org/plosone/s/submission-guidelines#loc-laboratory-protocols. Additionally, PLOS ONE offers an option for publishing peer-reviewed Lab Protocol articles, which describe protocols hosted on protocols.io. Read more information on sharing protocols at https://plos.org/protocols?utm_medium=editorial-email&utm_source=authorletters&utm_campaign=protocols.

We look forward to receiving your revised manuscript.

Kind regards,

Muhammad Maaz Arif, M.B.B.S, M.Phil

Academic Editor

PLOS ONE

Journal Requirements:

Please review your reference list to ensure that it is complete and correct. If you have cited papers that have been retracted, please include the rationale for doing so in the manuscript text, or remove these references and replace them with relevant current references. Any changes to the reference list should be mentioned in the rebuttal letter that accompanies your revised manuscript. If you need to cite a retracted article, indicate the article’s retracted status in the References list and also include a citation and full reference for the retraction notice.

Additional Editor Comments (if provided):

ACADEMIC EDITOR Comments:

Following changes are the top-most priority considering the reviewers comments:

1. Although "air pollution" is cited in the study title, "air pollutants exposure" is explicitly addressed in the findings. Therefore, the study should use more precise language to avoid drawing readers' attention away from the discrepancy between the title and the findings. Suggested Title: Exposure to Air Pollutants and Subclinical Carotid Atherosclerosis Measured by Magnetic Resonance Imaging: A Prospective Cohort Study.

2. Tables S4 through S8 appear to include the study's most significant findings. Given that these are the most significant findings, why are these tables listed in the supplementary materials? These should be mentioned in the main manuscript.

3. Please take into account the feedback from the reviewers and thoroughly proofread the study for errors and grammatical flaws.

4. The manuscript may be accepted after minor revisions.

Reviewer's Comments:

The study aimed to investigate the effect of long-term exposure to air pollution on cardiovascular mortality. Therefore, the authors used data from a cohort study of 6,645 individuals recruited from previous Canadian cohort studies. The strength of this study is the well assessed outcome of carotid vessel wall volume (CWV) by MRI, the four-year average duration of air pollution exposure, and the extensive adjustment for confounders including walkability and neighborhood socioeconomic status.

Interestingly, PM2.5 and NO2 were not or negatively associated with CVW, which requires further investigation.

The reviewers' comments were understandable, and the authors responded to and addressed all comments thoroughly. Furthermore, the feedback has been extensively implemented, including additional sensitivity analyses, resulting in a substantial improvement of the manuscript, which adequately discusses the present limitations. However, there are still a few minor points that need to be addressed:

## Minor

- Abstract

o for the effect of NO2, a “minus” is missing in the 95%-CI, it must be -7.32

- Methods

o More description is needed on the exclusion criterion of "known CVD history". Is this validated or self-reported? And what diseases were included in the CVD history?

o For clarification: add a sentence describing whether residential addresses were only available on a postcode grid. If so, then PM2.5 available on a 1km*1km grid was probably averaged over the postcode area? This is not clearly described in the methods section.

o As an additional analysis, the ratio of wall volume to total vessel volume (Normalized wall index) should be used instead of using maximum wall volume [e.g. PMID: 33183741]. This would account for individual variation in overall vessel size.

- Results:

o Information in the text do not match the information in the table, e.g., in the Results - participant characteristics section it says "54.8% of participants were women", but in Table 1 it says 56%. Same section: "92% of cohort postcodes were in urban areas", but in Table 3 it is 96.2%. It seems that information in the text was mixed up with the “British Columbia” column. Authors should double-check tables and text to correct any discrepancies.

- Discussion

o Any clinically relevant cut-off values for CWV? Is the mean value high (900 mm³)? Could be more addressed in the discussion and may help to contextualize the results and health of study participants to previous studies.

o I agree with Reviewer 2 that the study was rather cross-sectional in nature than longitudinal. The authors argue “Exposure to air pollution values represented a time frame prior to knowledge of the outcome for each participant, i.e., the air pollution data collected for the 5-year period prior to the MRI. We are therefore comfortable describing this as a prospective association, despite the lack of longitudinal follow-up.” However, since no information exists on the CVW thickness before the exposure window, one cannot argue that the thickness was not present at this exposure window or even before. Therefore, I suggest revising this sentence and to name it a cross-sectional association.

- Optional: instead of A, B, C, in the plots, naming the air pollutants would improve the readability of the plots.

[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 #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 #3: Yes

**********

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

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 #3: No

**********

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 #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 #3: The study aimed to investigate the effect of long-term exposure to air pollution on cardiovascular mortality. Therefore, the authors used data from a cohort study of 6,645 individuals recruited from previous Canadian cohort studies. The strength of this study is the well assessed outcome of carotid vessel wall volume (CWV) by MRI, the four-year average duration of air pollution exposure, and the extensive adjustment for confounders including walkability and neighborhood socioeconomic status.

Interestingly, PM2.5 and NO2 were not or negatively associated with CVW, which requires further investigation.

The reviewers' comments were understandable, and the authors responded to and addressed all comments thoroughly. Furthermore, the feedback has been extensively implemented, including additional sensitivity analyses, resulting in a substantial improvement of the manuscript, which adequately discusses the present limitations. However, there are still a few minor points that need to be addressed:

## Minor

- Abstract

o for the effect of NO2, a “minus” is missing in the 95%-CI, it must be -7.32

- Methods

o More description is needed on the exclusion criterion of "known CVD history". Is this validated or self-reported? And what diseases were included in the CVD history?

o For clarification: add a sentence describing whether residential addresses were only available on a postcode grid. If so, then PM2.5 available on a 1km*1km grid was probably averaged over the postcode area? This is not clearly described in the methods section.

o As an additional analysis, the ratio of wall volume to total vessel volume (Normalized wall index) should be used instead of using maximum wall volume [e.g. PMID: 33183741]. This would account for individual variation in overall vessel size.

- Results:

o Information in the text do not match the information in the table, e.g., in the Results - participant characteristics section it says "54.8% of participants were women", but in Table 1 it says 56%. Same section: "92% of cohort postcodes were in urban areas", but in Table 3 it is 96.2%. It seems that information in the text was mixed up with the “British Columbia” column. Authors should double-check tables and text to correct any discrepancies.

- Discussion

o Any clinically relevant cut-off values for CWV? Is the mean value high (900 mm³)? Could be more addressed in the discussion and may help to contextualize the results and health of study participants to previous studies.

o I agree with Reviewer 2 that the study was rather cross-sectional in nature than longitudinal. The authors argue “Exposure to air pollution values represented a time frame prior to knowledge of the outcome for each participant, i.e., the air pollution data collected for the 5-year period prior to the MRI. We are therefore comfortable describing this as a prospective association, despite the lack of longitudinal follow-up.” However, since no information exists on the CVW thickness before the exposure window, one cannot argue that the thickness was not present at this exposure window or even before. Therefore, I suggest revising this sentence and to name it a cross-sectional association.

- Optional: instead of A, B, C, in the plots, naming the air pollutants would improve the readability of the plots.

**********

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 #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.

PONE-D-23-23654R2Exposure to Air Pollutants and Subclinical Carotid Atherosclerosis Measured by Magnetic Resonance Imaging: A cross-sectional analysisPLOS ONE

Dear Dr. de Souza,

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.

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ACADEMIC EDITOR: The authors have addressed many changes as advised and have improved the article. The article may be accepted after these last few recommendations. Following issue still needs to be addressed:May be accepted after minor revisions:Editor's comment last time: "Tables S4 through S8 appear to include the study's most significant findings. Given that these are the most significant findings, why are these tables listed in the supplementary materials? These should be mentioned in the main manuscript."   The author responded that the tables are summarized in a few figures. I would strongly advise you to include all of those tables (S4 through S8) in the manuscript. These tables are closely related to the manuscript's actual objective.    Please also consider the reviewer's remarks and final checks for proofreading issues.

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Kind regards,

Muhammad Maaz Arif, M.B.B.S, M.Phil

Academic Editor

PLOS ONE

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Additional Editor Comments:

May be accepted after minor revisions.

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Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

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Reviewer #4: (No Response)

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Reviewer #4: Yes

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

Reviewer #4: Yes

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Reviewer #4: Yes

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Reviewer #4: Yes

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Reviewer #4: This article was well performed and suggested to be published soon, while there were some additional information should be disclosed:

1. the sensitive of Subclinical Carotid Atherosclerosis Measured by Magnetic Resonance Imaging.How is it varied by time? it is an important basis for the observation period.

2.the difinition of Carotid artery vessel wall volume should be described more minutely.

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Reviewer #4: Yes: Minjin Peng, Taihe Hospital, Hubei University of Medicine, https://orcid.org/0000-0002-1350-4780

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Exposure to Air Pollutants and Subclinical Carotid Atherosclerosis Measured by Magnetic Resonance Imaging: A cross-sectional analysis

PONE-D-23-23654R3

Dear Dr. de Souza,

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.

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Kind regards,

Muhammad Maaz Arif, M.B.B.S, M.Phil

Academic Editor

PLOS ONE

Additional Editor Comments (optional):

Accept. Manuscript should be thoroughly checked for proofreading errors before the final galley proof.