PONE-D-20-20980

Psychosocial job exposure and risk of coronary artery calcification

PLOS ONE

Dear Dr.  Eriksson

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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We look forward to receiving your revised manuscript.

Kind regards,

Xianwu Cheng, M.D., Ph.D., FAHA

Academic Editor

PLOS ONE

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Reviewers' comments:

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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

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

Reviewer #1: No

Reviewer #2: 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: No

Reviewer #2: Yes

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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: This ms reports results of analyses of the associations of established measures of stress at work (high job strain, active job and passive job) with coronary artery calcium score (CACS, an established measure of coronary atherosclerosis) in a sample of healthy Swedes on whom they also have measures of the metabolic syndrome (waist circumference, triglycerides, HDL cholesterol, blood pressure and fasting glucose). They report in men non-significant associations of high job strain and active job with higher prevalence ratios (PR) of CACS >100 and in women non-significant association of passive job with higher PR of CACS >100. There are several concerns regarding the statistical analyses the authors used that need to be addressed before a final decision can be reached regarding this ms.

Rather than only doing Cox regression analyses evaluating associations between the job stress measures with PR of CACS 1-99 or CACS > 100 with only age-adjustment or age-adjustment and adjustment for education, smoking, SES area and metabolic syndrome, they need to do more comprehensive analyses that take into account associations of the job stress and CACS measures with the variables they adjust for. In Table 1, for example, men with CACS >100 appear to have higher level of metabolic syndrome (52%) than men with CACs=0 (21%), they also have higher smoking rate (70%) than men with CACS=0(41%). There is no mention in the Results of whether these associations of CACS>100 with increased metabolic syndrome and smoking are statistically significant. It could also be informative if they carried out analyses of the associations between CACs and the components of the metabolic syndrome. That is, are some of the components of the metabolic syndrome – e.g. glucose, triglycerides and BP – accounting for the association of the metabolic syndrome with CACS>100.

They also need to evaluate associations between the job stress measures and all the variables they adjust for in the regression analyses. If, for example, higher job strain is associated with the same factors—i.e., smoking and metabolic syndrome – that appear to be associated with CACS>100, it could be the case that there is a statistically significant indirect pathway from high job strain à metabolic syndrome (or some of its components) and smoking àincreased CACS. They do cite a paper (30) in the Discussion that found job strain associated with increased risk of metabolic syndrome. They also cite a paper in the Introduction (11, Nyborg et al.) that found increased job strain associated with increased diabetes, smoking, physical inactivity and obesity. A paper by Jensen et al. (Circ Cardiovasc Imaging Epub, July 14, 2020) found obesity associated with increased CAC and increased CHD and all cause mortality over a follow-up period.

They could test this pathway using structural equation modeling. If this indirect pathway from job stress indices to increased CACS is found significant, this paper would be making a far greater contribution to our understanding of the impact of increased stress at work on mechanisms involved in the development of coronary artery disease.

There is another measure of stress at work, effort/reward imbalance (ERI), that might be worth evaluating using the same approach (especially as expanded in line with concerns above).

Reviewer #2: The authors provide an interesting and potential important manuscript describing "psychosocial job exposure and risk of coronary artery calcification", The main issues concerning this paper are those concerning the potential associations between psychosocial exposures and coronary calcium.

There are some weak points that need to be addressed by the authors.

Major

1. The author should supplement CACS, the Swedish Demand-Control-Support Questionnaire, the specific evaluation criteria for calcification and working stress。

2. I think the direction chosen in this paper is very good. But the conclusion is bad supported by the data in this paper. First the conclusion say “exposure to a high strain or active job situation could potentially increase the risk of CACS in men”, We don't know if these people are representative of people in social groups who work under different pressures. Second in 384 men, there are 59 people in low strain job, 58 people in active job,111 people in high strain job,156 people in passive job, We can see that most people live in stressful jobs, so it is unscientific to conclude that stressed people have more calcification.

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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.

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Reviewer #1: No

Reviewer #2: No

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PONE-D-20-20980R1

Psychosocial job exposure and risk of coronary artery calcification

PLOS ONE

Dear Dr.  Eriksson

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 %March 2, 2021. 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,

Xianwu Cheng, M.D., Ph.D., FAHA

Academic Editor

PLOS ONE

Additional Editor Comments (if provided):

One original reviewer has still concerned that the authors did not satisfactory addressed most of original comments. Thus, this is last chance to revise your manuscript for pulication in PONE.

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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

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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: Partly

Reviewer #2: Yes

**********

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

Reviewer #1: No

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: The authors have not responded adequately to my concerns regarding the original version of this ms. With a sample of 384 men and 393 women, there is ample power for them to conduct and report results of exploratory tests of associations between the variables adjusted for in the analyses of associations between job stress measures and CACS and the job stress measures and CACS levels themselves. They do note in Methods (lines 153-156) that the covariates (age, smoking, education, socioeconomic area and metabolic syndrome) were “all P< 0.05 when adding one by one to the first model for CACS > 100..” If I interpret this correctly, this means that all these covariates were significantly associated significantly with severe CACS > 100. There is no reason they should not report these associations in a table – or indicate in Table 1 that the 52% of men with CACS >100 is significantly different from the 21% of men with metabolic syndrome in those with CACS of 0, with similar indicates for the other covariates.

In addition to these presumed associations of the covaried risk factors with CACS, attention also needs to be given to their associations with the job stress measures. If, as I noted in my review of the original ms, there is a significant association of high job strain with high levels of metabolic syndrome, it would suggest the possibility, even if they do not provide a direct test of metabolic syndrome as a mediator, that the increased CACS in men with high job strain may be the result of their higher level of metabolic syndrome. Given that prior research (ref 30) has found an association between high job strain and metabolic syndrome, there is every reason to expect they will be able to replicate that finding in the current study. I don’t disagree with their point that using SEM to assess possible pathways is now considered to require the temporal aspect to be conclusive with respect to causation. It might still be informative, however, even with the current cross-sectional data, to perform SEM pathway analysis, as an exploratory way of seeing if there might be a pathway from job strain to higher CACS via metabolic syndrome. Even though it could not be considered definitive (which the authors would note in a revised ms), if such an SEM path analysis did identify a statistically significant indirect pathway from high job strain to high metabolic syndrome (or other covariates or metabolic syndrome components per below) and from there to high CACS, it would be encouraging that, despite their failure to find a significant association between job strain and CACS, there is reason to continue to pursue ongoing research (including longitudinal) to evaluate job stress measures as risk factors for CACS (and CVD events). Moreover, finding such a significant indirect pathway could also help identify intervention targets in men in high strain jobs – e.g., if there’s a significant indirect pathway from job strain via smoking to CACS, that would suggest stopping smoking as an important preventive approach in men in high strain jobs.

Speaking of exploratory analyses, there is no reason, given a total sample of 777 men and women, for them to assert that “the study is too small to go into details of the components of the metabolic syndrome.” If the metabolic syndrome itself (and other covariates) are significantly associated with CACS (and job stress measures?), it should be possible to determine whether the association of metabolic syndrome itself with CADS is due to one or more specific components of the metabolic syndrome.

They conclude that “Our results indicate that exposure for high strain job or active job could increase the risk of CAC in men, but in women, it could rather be exposure for passive job that increases the risk. However, there was a lack of power in the study.” Given that the associations of job stress measures with CACS in men and women were not statistically significant, I believe it would behoove the authors to perform exploratory analyses as outlined in my comments above to take maximum advantage of the extensive data they have on this sample of 384 men and 393 women.

Reviewer #2: Dear author

Thank you very much for providing the supplement CACS and explain the categorization of participants. This paper may highlight the psychological factor on vascular calcification, which may notice people care for the work stress.

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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

[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.

Attachments

Attachment

Submitted filename: Response-PONE-D-20-20980_R1.doc

PONE-D-20-20980R2

Psychosocial job exposure and risk of coronary artery calcification

PLOS ONE

Dear Dr Eriksson

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 March30, 2021. 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,

Xianwu Cheng, M.D., Ph.D., FAHA

Academic Editor

PLOS ONE

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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: Partly

Reviewer #2: Yes

**********

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

Reviewer #1: No

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: No

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: The authors have responded to my request to include indication of significant differences comparing CACS 1-99 and >100 groups with the CACs 0 group with respect to job stress measures, ever smoker, SES area, and Metabolic Syndrome measures in Table 1. And it is interesting to observe that in men only ever smoker and MetSyn are higher in CACS 1-99 and CACS >100 than CACS 0, and in women only No University and SES area are higher in CACS >100 and MetSyn is higher in CACS 1-99, but not CACS >100 – likely due to small N (7) in that group. They need to include these statistically significant differences in the Results section.

Despite the fact that none of the tests of associations between job stress and other measures with CACS were significant in either men or women, they still conclude that, despite “a lack of power in the study,” “Our results indicate that exposure for high strain job or active job could increase the risk of CAC in men, but in women, it could rather be exposure for passive job that increases the risk.” Given this lack of significant effects for the job stress measures, a strong case can be made that they should undertake exploratory analyses in this sample of 777 healthy middle-aged men and women to evaluate associations between job stress measures and other factors they find associated with increased CACS – i.e., ever smoker and MetSyn in men and No University, SES area and MetSyn in women – to determine whether these other factors that are associated with CACS and, therefore, at least potential mediators of effects of job stress on CACS, are increased in men and women with high job stress. If these potential mediators are significantly increased in men and women with high levels of job stress measures, it would at least enable the authors to suggest – even if they do not perform SEM path analyses, that these factors (especially ever smoked and MetSyn) could be mediators of associations between job stress and CACS.

A similar argument can be made for them to perform exploratory analyses to determine whether it is possible to identify specific components of the MetSyn that are accounting for the association between MetSyn and increased CACS in both men and women, and, if so, whether these MetSyn components are also elevated in men and/or women with high levels of job stress.

It is not clear how doing stratified analyses of job stress associations with CACS in men with MetSyn vs men with no MetSyn – all nonsignificant – addresses the question of mediation of job stress impact on CACS.

Reviewer #2: Dear author

The paper entitled with Psychosocial job exposure and risk of coronary artery calcification show an interesting study to identify psychological stress on CVD disease, the detail mechanism for calcification need to further explore, but this phenomenon need our of us to notice.

Thank you very much to made a meaningful research.

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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

[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-20-20980R3

Psychosocial job exposure and risk of coronary artery calcification

PLOS ONE

Dear Dr. Eriksson

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 April 30, 2021. 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,

Xianwu Cheng, M.D., Ph.D., FAHA

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.

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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)

**********

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: Partly

**********

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

Reviewer #1: 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: 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 #1: Yes

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6. Review Comments to the Author

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Reviewer #1: In this R3 draft the authors have made some constructive changes in response to my earlier reviews, but there are still some areas where improvement would be good.

They have included some reference to the univariate Fischer’s exact tests of differences in Table 1’s work variables and their chosen covariates in the first paragraph of the Results section, but I believe they need to include more details – i.e., in men with CACS >100 the 38% percent with high strain job was NOT significantly different from the 25% in men with CACS of 0. In contrast, Table 1 shows that in men with CASC > 100 or 1-99 both % Ever smoker and Metabolic syndrome were significantly elevated compared to men with CACS of 0; and in women those with CACS >100 had significantly higher % with No University and living in Low SES area than those with CADS 0, and those with CACS 1-99 had significantly higher % with metabolic syndrome. The higher % in passive work conditions in those women with CACS > 100 is NOT significant. I believe that the significant associations between CACS levels and % with Metabolic syndrome and Ever smoker in men and between CACS levels and No university and low status SES area and Metabolic syndrome in women should be reported in more detail – e.g., 83% of women with CACS >100 had No university vs only 48% of women with CACS of 0, and give the P-values (e.g., P<0.05) for each significant one.

They say they have moderated the conclusion to take into account that none of the tests of associations between job stress and other measures with CACS were significant, but the conclusion of the R3 draft is the same as that of the R2 draft. I suggest that they do not assert “Our results indicate…” – I suggest the say instead, “Our results suggest the possibility that exposure ….” They should also include some details of the significant associations in Table 1 of job stress measures and covaried factors with CACS in the conclusion.

In response to my suggestion that they test whether factors they found associated with increased CACS in Table 1 are also associated with job stress measures, they say they have “checked this and none of the adjustment factors was significantly related to high strain jobs, among neither men nor women.” And “However we will not include this in the results section since this is not our research question.” I disagree and recommend they include that these associations were tested and all were nonsignificant.

They also say they did not explore associations between components of the metabolic syndrome that are accounting for the association between metabolic syndrome and increased CACS in both men and women because “This study was not an exploratory study…We do not believe it is correct to set up a new research question within the same study when finding out that we have insignificant results.” I also disagree with this argument – indeed, when one has insignificant results, it can be considered appropriate to carry out additional analyses to try to contribute something more than failure to confirm their hypothesis that job stress would be associated with increased CACS.

In response to my concern that it is not clear how doing stratified analyses of job stress associations with CACS in men with MetSyn vs those with no MetSyn addresses the question of mediation of job stress impact on CACS, they say they therefore did the stratified analyses, but say nothing regarding implications of these analyses being nonsignifcant.

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Reviewer #1: No

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Psychosocial job exposure and risk of coronary artery calcification

PONE-D-20-20980R4

Dear Dr. Eriksson

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Reviewer #1: All comments have been addressed

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Reviewer #1: No

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Reviewer #1: Yes

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Reviewer #1: (No Response)

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Reviewer #1: No