PONE-D-21-07004

Incidence and Risk Factors of Hypertension: A Multicentre Retrospective Cohort Study in Tabuk, Saudi Arabia

PLOS ONE

Dear Dr. Mohamed,

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Academic Editor

PLOS ONE

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"The study was fully funded by Research Unit, Academic Affairs Department, King Salman Armed Forces Hospital Tabuk, Saudi Arabia."

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Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. Is the manuscript technically sound, and do the data support the conclusions?

The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented.

Reviewer #1: Yes

Reviewer #2: Partly

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

Reviewer #1: Yes

Reviewer #2: No

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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: No

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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: No

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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: Thank you for a thorough study of the epidemiology of hypertension in an understudied population. I have a few comments:

-First of all, the paper needs thorough language editing.

-In the methodology, it is stated that patients were included with hypertension diagnosed according to ICD-10. ICD-10 is a disease coding/classification system, not a set of diagnostic criteria. The criteria used (ACC/AHA 2017) should be mentioned instead.

-I couldn't find a clear mention of how long the (mean) follow up interval was anywhere. Please include, because a short interval would be a limitation that needs mentioning.

-References should be provided for the parameters used in the sample size calculation such as the odds ratio, risk/prevalence ratio, etc, or at least some justification for their choice if arbitrary.

-Since this is effectively a time-series analysis, I think a multivariate cox proportionate hazards model would be appropriate to include to help disentangle the effect of confounding variables.

-In the results, I couldn't help but notice that so few patients are over 47, which is not very representative of the hypertensive patient population. The reason for this should be clarified.

-Some essential data such as the presence and type of antihypertensive treatment are not included in the analysis. This should at least be mentioned in the limitations. It would also be useful to mention the reason for presentation, e.g. checkup visit, symptoms, etc if possible.

Overall, the study provides much needed data about hypertensive risk factors in the Saudi Arabian population, and would be useful to publish after the above considerations.

Reviewer #2: 1- GENERAL COMMENT

The strength of the current research is studying all the stages of hypertension aiming to identify the incidence rate and the predictors associated with hypertension, which is an interesting subject. There are very few studies dealing with the incidence of hypertension and changes in blood pressure over time. although the difficulty of studying the incidence rate of hypertension lie in the diversity of the incidence rate of hypertension with the regions.

The manuscript needs English editing since there are several typos and grammatical errors.

2- INTRODUCTION

2.1. The authors should elaborate more on the previous research that includes the incidence of hypertension in different ethnicities. For example, the CARLA-Cohort study.

Lacruz ME, Kluttig A, Hartwig S, Löer M, Tiller D, Greiser KH, Werdan K, Haerting J. Prevalence and Incidence of Hypertension in the General Adult Population: Results of the CARLA-Cohort Study. Medicine (Baltimore). 2015 Jun;94(22):e952. doi: 10.1097/MD.0000000000000952. PMID: 26039136

2.2. It is advised to cite previous studies about the incidence rate of hypertension in the Gulf area.

3. MATERIALS AND METHODS

3.1. The methods were not written in sufficient detail to allow the study to be replicated. The study design was reported as a retrospective cohort, therefore this should be explained, and the two cohorts should be defined; the exposed cohort and the non-exposed one.

3.1. The recruitment of the patients was described as from the nephrology, cardiology and internal medicine departments. Was the recruitment from the outpatient clinics or the inpatient department? This issue was not clear.

3.2. The patients had three blood pressure measurements, if the patient has more than 3 measurements, what did the authors do? It should be stated that the last three measurements were used in the methods section. Did you mean these measurements? What is the minimum interval allowed between these three measurements? All these details should be mentioned in the methods section.

3.3. Why did the authors exclude the diagnosis of hypertension in less than 6 months? This might bias the results.

3.4. Regarding the operational definitions, the referee suggests removing the paragraph that defines the blood pressure, which is found on page 2, line 41-44.

3.5. The inclusion criteria were not clear in the Methods section. It should be written in details.

3.6. How did the authors adjust for the change of age overtime of the study of one year?

3.7. Regarding the calculation of the incidence rate,

• The equations of incidence rate and relative risk should be supported by the related references.

• The way of calculation of the incidence rate should be written in the methods more comprehensively, and in the results as well. For example, how did the authors diagnose the new cases of hypertension? How many new cases did the authors diagnose? Then, put the incidence rate equation defining both the numerator and denominator, to find out the incidence rate.

3.8. All the risk factors should be defined and cited. For example, the physical activity was defined but not referenced, while the family history of hypertension, smoking status were not defined nor referenced. The referee suggests applying these in the operational definition.

4. RESULTS

4.1. The stage of elevated BP according to ACC guidelines 2017, is stated in different contexts of the manuscript as ELEVATED HYPERTENSION, which needs to be corrected through the manuscript to THE STAGE OF ELEVATED BP, because it does not fulfil the criteria of hypertension. The same error was found in figure 1.

4.2. In all stages of BP STATED in figure 1, the total cases were demonstrated. The new cases should be mentioned as well.

4.3. The legend of Table 2 stated the mean systolic and diastolic BP and the incidence of hypertension. There is no incidence of hypertension in this table.

4.4. In Figure 2, it is advised to highlight the equation of each stage defining the numerator and denominator till you calculate the incidence rate. Importantly, mention the new cases.

4.5. On page 7, it was mentioned that there is an increasing risk of stage 2 with age. Nevertheless, not only stage 2, but also stage 1 and the hypertensive crisis.

4.6. Table 4 needs important modifications:

4.6.1. It is very important to mention the p-value for each relation of the table, and highlighting the significant ones.

4.6.2. The table depicted 4 relationships as significant, meanwhile, they need to be double-checked for the significance because the CI of the odds ratio (OR) ranging from below 1 to above 1, which in many situations refers to a non-significant relationship. It is advised to consult a statistician to solve this issue. The four relations are the marital status and stage 1, the marital status and hypertensive crisis, the current smoking and stage one, and the current smoking and stage 2.

4.6.3. Why the elevated BP stage was not included in table 3 and 4. It is better to be added.

5. DISCUSSION

5.1. It needs to be comprehensive.

5.2. All the risk factors should be discussed in more details. As unemployment and nationality/race were not mentioned.

5.3. It will be valuable to mention the black race as an important subgroup.

5.4. All the references used in the discussion should be explained in detail trying to explain the similarities and differences with the current study.

6. CONCLUSION

6.1. It should be reconstructed to highlight the main findings and support the study results. The conclusion in the abstract should be matched with the manuscript conclusion.

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Reviewer #1: No

Reviewer #2: Yes: Hussein M. Ismail

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Investigating the incidence and risk factors of hypertension: a multicentre retrospective cohort study in Tabuk, Saudi Arabia

PONE-D-21-07004R1

Dear Dr. Mohamed,

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,

Manal S. Fawzy, Ph.D., M.D.

Academic Editor

PLOS ONE

Additional Editor Comments (optional):

The authors have adequately addressed the concerns raised by the reviewers. Thank you

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: All comments have been addressed

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: Yes

Reviewer #2: Yes

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

Reviewer #1: Yes

Reviewer #2: Yes

**********

4. Have the authors made all data underlying the findings in their manuscript fully available?

The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified.

Reviewer #1: Yes

Reviewer #2: Yes

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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

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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: (No Response)

Reviewer #2: (No Response)

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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: Yes: Hussein M. Ismail