The Effect of Spiritual Orientation and Perceived Stress on Heart Rate Variability and Electrocardiographic Parameters in Hypertensive Patients

Round 1

Reviewer 1 Report

Comments and Suggestions for Authors

Suggestions for Iimprovement as follows: 

Abstract

• No effect sizes or actual values (means, SD, or correlation coefficients) are reported.

Introduction

• Provide stronger integration of spiritual orientation with ECG-based repolarization markers, not just HRV.
• Clarify how these variables interact.
• Explain why these factors would simultaneously affect both HRV and ECG parameters.

Methods

• Clarify whether there was detailed reporting or adjustment for potential confounders, including smoking, alcohol, caffeine intake, physical activity, and comorbidities (e.g., diabetes, anxiety/depression).
• The HRV methodology lacks frequency-domain or nonlinear analyses.
• Multivariate regression analysis should be performed and reported to adjust for confounders and to identify independent predictors of HRV and ECG outcomes.

Results

• Include results from regression or adjusted analyses to determine whether spirituality or stress independently predict HRV and ECG outcomes.

Discussion

• The Discussion does not adequately address how different antihypertensive medication classes (e.g., beta-blockers, calcium channel blockers) may have directly influenced HRV and repolarization parameters, potentially confounding the observed associations with psychosocial variables.
• Due to the lack of multivariate analysis, it remains unclear whether spirituality, stress, or self-efficacy are independent predictors or simply reflect underlying confounders (e.g., age, BMI, medication use).
• The Discussion treats HRV as a robust marker of autonomic function; however, the limitations of short-term HRV measurement (e.g., reduced reliability compared to 24-hour Holter monitoring) are not critically considered when interpreting the strength of the findings.

Author Response

We sincerely thank the reviewer for the thorough and constructive evaluation of our manuscript. The comments have been extremely valuable in improving the scientific rigor, clarity, and overall quality of the study. We have carefully revised the manuscript accordingly, and all changes have been incorporated into the revised version. Our point-by-point responses are provided below.

Abstract

Comment: No effect sizes or actual values (means, SD, or correlation coefficients) are reported.

Response:
Thank you for this important suggestion. The Abstract has been substantially revised to include detailed quantitative findings. Specifically, mean ± standard deviation values, effect sizes (Cohen’s d), and correlation coefficients have been incorporated. These additions provide a more transparent and informative summary of the magnitude and clinical relevance of the observed differences.

Introduction

Comment: Provide stronger integration of spiritual orientation with ECG-based repolarization markers, not just HRV.

Response:
We appreciate this insightful comment. The Introduction has been revised to better integrate psychosocial factors with both autonomic regulation and cardiac electrophysiology. A new paragraph has been added explaining the potential influence of spiritual orientation and stress on both HRV and ventricular repolarization parameters through shared neurobiological pathways.

 

Comment: Clarify how these variables interact.

Response:
We have expanded the theoretical framework to clarify the interaction between psychosocial factors and cardiovascular physiology. Specifically, we described the role of hypothalamic–pituitary–adrenal axis activation, sympathetic overactivity, and impaired baroreflex sensitivity as common mechanisms linking stress, spirituality, HRV, and repolarization dynamics.

 

Comment: Explain why these factors would simultaneously affect both HRV and ECG parameters.

Response:
This issue has been addressed by adding a mechanistic explanation emphasizing that autonomic imbalance can simultaneously influence both HRV and ventricular repolarization. The revised text highlights that these parameters reflect interconnected aspects of cardiovascular regulation rather than independent phenomena.

Methods

Comment: Clarify whether there was detailed reporting or adjustment for potential confounders (smoking, alcohol, caffeine, physical activity, comorbidities).

Response:
We thank the reviewer for highlighting this important issue. The Methods section has been revised to clarify that potential confounders, including smoking status, caffeine intake, physical activity, and comorbid conditions, were recorded during participant assessment. Furthermore, these variables were incorporated as covariates in the multivariate regression analyses where appropriate.

 

Comment: The HRV methodology lacks frequency-domain or nonlinear analyses.

Response:
We acknowledge this limitation. The Methods section has been updated to clarify that HRV assessment was based on time-domain parameters derived from resting ECG recordings. While frequency-domain and nonlinear analyses provide additional insights, time-domain indices such as SDNN and RMSSD are widely accepted and clinically validated measures of autonomic function. This limitation has also been explicitly acknowledged and discussed in the Discussion section.

 

Comment: Multivariate regression analysis should be performed.

Response:
We fully agree with this recommendation. Multivariate linear regression analyses have now been performed to identify independent predictors of HRV and ECG parameters. Spiritual orientation, perceived stress, and self-efficacy were included as primary predictors, while age, sex, BMI, and hypertension status were included as covariates. These analyses have been added to the Methods section and are presented in a newly introduced Table 5.

 

Results

Comment: Include results from regression or adjusted analyses.

Response:
Multivariate regression results have been incorporated into the Results section. These analyses demonstrate that spiritual orientation remains an independent positive predictor of HRV indices, whereas perceived stress independently predicts reduced HRV and increased repolarization parameters. These findings are presented in Table 5 and described in detail in the Results section.

 

Discussion

Comment: The Discussion does not adequately address medication effects.

Response:
We appreciate this important point. The Discussion has been revised to include a detailed evaluation of the potential influence of antihypertensive medications, particularly beta-blockers and calcium channel blockers, on both HRV and repolarization parameters. We also acknowledge that pharmacological effects may partially modulate the observed associations.

 

Comment: It is unclear whether psychosocial variables are independent predictors.

Response:
This concern has been addressed through the inclusion of multivariate regression analyses. The Discussion has been revised to clearly state that spiritual orientation and perceived stress remain independently associated with HRV and ECG parameters after adjustment for major confounders, while also acknowledging the possibility of residual confounding.

 

Comment: Limitations of short-term HRV measurement are not discussed.

Response:
We agree with this comment. The Discussion has been expanded to acknowledge that HRV was assessed using short-term ECG recordings rather than 24-hour Holter monitoring. We now emphasize that short-term HRV may have lower reproducibility and may not fully capture circadian autonomic variability; therefore, the findings should be interpreted with appropriate caution.

Conclusion

We believe that these revisions have substantially strengthened the manuscript by improving its methodological rigor, analytical depth, and physiological interpretation. We sincerely thank the reviewer again for the constructive feedback, which has significantly enhanced the quality of our work.

Reviewer 2 Report

Comments and Suggestions for Authors

Dear Authors

The article addresses an important topic linking psychological resources, stress and objective indicators of autonomic cardiac regulation in patients with hypertension, as the authors clearly explain in the introduction.

A strength of the study is its attempt to link psychosocial variables with physiological indicators, which fits well with the biopsychosocial model of hypertension. The authors formulate a meaningful research objective and identify a research gap concerning the simultaneous assessment of spirituality, stress, self-efficacy, HRV and repolarisation parameters.

At the same time, the manuscript in its current form requires significant methodological and editorial revisions. The main issues concern:

• the lack of a description of sample size calculation,
• an incomplete and at times inconsistent description of statistical analyses,
• the absence of multivariate analyses controlling for confounders,
• limited critical discussion of the authors’ own results in relation to the literature,
• an overly brief Limitations section.

Comments on methodology:

· the method of participant recruitment is not described,
· it is unclear whether selection was sequential, convenience-based or purposive,
· no information on the recruitment site, recruitment period or refusal rate,
· no control for important confounding variables, particularly the type of antihypertensive treatment, duration of illness, smoking, physical activity, diabetes, sleep or caffeine intake,
· the authors include patients on antihypertensive medication in the study but do not model the effect of pharmacotherapy, although they themselves acknowledge that medication may affect HRV and repolarisation.

If these variables were not analysed, they should be listed as limitations of the study.

Statistical methods:

- the description is too general,
- the tables show a mix of parametric and non-parametric statistics without full justification,
- there is no information on control for multiple testing,
- no multivariate analyses were performed, even though the subject clearly requires them.
Please describe in detail the process of calculating the sample size

Study results:
- descriptive results are at times repetitive and overly narrative,
- no confidence intervals for the main effects.
- Tables: some abbreviations and statistical symbols are not explained clearly enough; there are editorial errors such as double commas in SDS/ISES; in the tables, it is not always clear why t, U and Z are reported side by side.
- The description of the research results is overly simplified and not always precise. The authors describe the direction and significance of the relationships, but: they rarely provide specific correlation values in the text; they do not interpret effect sizes systematically; they do not address the clinical significance of the results; they do not discuss the risk of Type I error in multiple tests.
- The discussion is substantively sound and effectively situates the results within the context of autonomic dysfunction, stress, spirituality and repolarisation. However, its critical comparative value is limited:

• the authors mainly confirm directional consistency with the literature,
• very rarely compare their own results with specific numerical values from other studies,
• do not show whether their effects are larger, smaller or comparable,
• do not analyse discrepancies between studies,
• do not discuss population and measurement differences in greater detail.

This means that the discussion is more descriptive than critical and comparative.

- The Limitations section requires clarification. The authors list several important limitations, but the following are missing, amongst others: possible selection bias, limited description of recruitment, lack of control for comorbidities and lifestyle, risk of multiple comparison error, lack of multivariate analysis, limitations related to the construct of ‘spiritual orientation’ and its cultural specificity. The Limitations section should be expanded.
- conclusions: correct
- references: please include more references from the last 5 years



kind regards,

Reviewer

Author Response

We sincerely thank the reviewer for the detailed and constructive evaluation of our manuscript. We greatly appreciate the insightful comments, which have helped us significantly improve the methodological rigor, analytical clarity, and overall scientific quality of the study. All comments have been carefully considered, and the manuscript has been thoroughly revised accordingly. Our point-by-point responses are provided below.

General Comments

Comment: The manuscript requires significant methodological and editorial revisions.

Response:
We appreciate this overall assessment. In response, we have comprehensively revised the manuscript, including major improvements in the Methods, Results, Discussion, and Limitations sections. In particular, we strengthened the statistical methodology, added multivariate analyses, clarified recruitment procedures, expanded the Discussion with comparative interpretation, and significantly enhanced the Limitations section.

 

Methodology

Comment: The method of participant recruitment is not described.

Response:
We have revised the Methods section to clearly describe the recruitment process. Participants were recruited using a consecutive sampling approach from a tertiary care cardiology outpatient clinic over a defined study period. This information has been explicitly added to improve transparency.

 

Comment: It is unclear whether selection was sequential, convenience-based, or purposive.

Response:
We thank the reviewer for this clarification request. The recruitment strategy has now been explicitly defined as consecutive sampling, which has been stated in the Methods section.

 

Comment: No information on recruitment site, period, or refusal rate.

Response:
The recruitment site and approach have been clarified in the revised manuscript. Additionally, we have acknowledged that refusal rates were not systematically recorded, and this has been explicitly included as a limitation of the study.

 

Comment: No control for important confounders (medication, lifestyle, comorbidities, etc.).

Response:
We agree with the importance of this issue. The manuscript has been revised to clarify that potential confounding variables (e.g., smoking, caffeine intake, physical activity, and comorbid conditions) were recorded during participant assessment. Furthermore, these variables were considered in the analytical framework and included as covariates in multivariate regression analyses where appropriate. Residual confounding has also been acknowledged in the Limitations section.

 

Comment: The effect of antihypertensive medication is not modeled.

Response:
We acknowledge this important limitation. While patients receiving antihypertensive treatment were included to reflect real-world clinical conditions, detailed modeling of pharmacological effects (e.g., drug class and dosage) was not performed. This limitation has now been explicitly discussed in both the Discussion and Limitations sections.

 

Sample Size

Comment: Please describe in detail the process of calculating the sample size.

Response:
We thank the reviewer for this suggestion. A statement regarding sample size considerations has been added. Due to the observational and exploratory nature of the study, an a priori sample size calculation was not performed. However, a post hoc power analysis was conducted, demonstrating that the study had >90% statistical power to detect medium-to-large effect sizes. This has been clearly described in the Methods section.

 

Statistical Methods

Comment: The description is too general and inconsistent.

Response:
The Statistical Analysis section has been substantially revised. We now clearly describe the criteria for selecting parametric versus non-parametric tests based on data distribution. Additionally, the analytical framework has been clarified and structured to improve consistency and transparency.

 

Comment: No control for multiple testing.

Response:
We acknowledge this point. The revised manuscript now explicitly states that results were interpreted cautiously due to multiple comparisons. Although formal correction methods (e.g., Bonferroni) were not applied due to the exploratory nature of the study, emphasis was placed on effect sizes and consistency of findings across related variables.

 

Comment: No multivariate analyses were performed.

Response:
We fully agree with this recommendation. Multivariate linear regression analyses have now been performed and incorporated into the manuscript (Table 5). These analyses demonstrate that spiritual orientation and perceived stress remain independent predictors of HRV and repolarization parameters after adjustment for relevant covariates.

 

Results

Comment: Results are overly narrative and lack precision.

Response:
We have revised the Results section to include more precise quantitative reporting. Key numerical values, including means, p-values, and effect sizes, are now explicitly stated in the text in addition to the tables.

 

Comment: No confidence intervals reported.

Response:
We acknowledge this suggestion. While confidence intervals were not included in the original analysis, we strengthened the reporting by incorporating effect sizes and emphasizing the magnitude and consistency of findings. This limitation is acknowledged in the revised manuscript.

 

Comment: Tables contain unclear abbreviations and editorial errors.

Response:
All tables have been carefully revised. Abbreviations have been clarified, redundant punctuation (e.g., double commas) has been corrected, and table formatting has been improved for clarity.

 

Comment: Lack of effect size interpretation and clinical relevance.

Response:
We have revised both the Results and Discussion sections to include systematic interpretation of effect sizes and to emphasize the clinical relevance of the findings.

 

Discussion

Comment: The discussion is descriptive rather than critical and comparative.

Response:
We appreciate this important observation. The Discussion has been substantially revised to improve its critical and comparative depth. We have incorporated comparisons with previous studies, discussed differences in effect magnitude, and explored possible reasons for discrepancies, including differences in population characteristics, methodology, and measurement approaches.

 

Limitations

Comment: The Limitations section is incomplete.

Response:
The Limitations section has been significantly expanded. We now explicitly address potential selection bias, incomplete control of confounders, risk of multiple testing, limitations related to short-term HRV measurement, lack of detailed pharmacological modeling, and the cultural specificity of the spirituality construct.

 

References

Comment: Include more recent references.

Response:
We have updated the reference list by incorporating several recent studies published within the last five years to better reflect the current state of the literature.

 

Conclusion

Comment: Correct.

Response:
We thank the reviewer for this positive evaluation.

Reviewer 3 Report

Comments and Suggestions for Authors

The article “The Effect of Spiritual Orientation and Perceived Stress on Heart Rate
Variability and Electrocardiographic Parameters in Hypertensive Patients” is well written.

 

The methodology is thorough and correct.

The results reflect the objectives set

Author Response

We sincerely thank the reviewer for the positive and encouraging evaluation of our manuscript.

We greatly appreciate the reviewer’s comments regarding the clarity of the writing, the appropriateness of the methodology, and the consistency between the study objectives and the results.

Reviewer 4 Report

Comments and Suggestions for Authors

Dear Author(s), 

 

The manuscript is very interesting but there are some improvement suggestions which I would like to make. Kindly, see below:

• In the Introduction section it would be highly recommended to place the study in a context, for instance, what is the situation in Turkey regarding HT? Does this study help? Adding this information may help in filling the gap easier.
• In the Methods section, it would be highly recommended to add a paragraph in which you explain how the patients gave their informed consent. 
• The 2.3. subsection needs mandatory information to be added. Which were the scales used to measure spiritual orientation, perceived stress and self-efficacy. Were they all validated in the Turkish language? If yes, a description is necessary for each one of them, give examples of 1-2  items from the scale and include their Cronbach alpha. Right now, this information is very important for the robustness of the methodology and data collection stage. 
• Line 160, at Cohen s d, please add the thresholds and their interpretation as well as a reference for them. 
• For the Results section, when the author(s) describe the tables, even if the numbers are in the tables, they should also be included in the description paragraphs of the tables. For instance, Line 200- For SDNN and RMSSD, the mean scores of non-participants were higher than those of patient participants (SDNN- 82.85 vs. 68.73, p lower than 0.001; RMSSD- 44.17 vs. 35.55, p lower than 0.001)...
• I was wondering if the clarity of the discussion section would be improved if the author(s) restructure it on theoretical contributions and practical contributions, followed by limitations and future research directions. This way, it will be easier to follow all the information. 
• I would highly recommend extending the limitations section, by also including the limitations of the equipment used in collecting electrocardiographic evaluation parameters. 
• Future research directions should be referred in a separate subsection, apart from what has already been included by also trying to answer the questions who and how can  benefit from the findings of the study. 

Thank you and good luck!

Author Response

We sincerely thank the reviewer for the valuable and constructive suggestions on our manuscript. We appreciate the positive evaluation and the insightful recommendations, which have significantly improved the clarity, methodological robustness, and overall structure of the study. All comments have been carefully addressed, and the manuscript has been revised accordingly.

Introduction

Comment: It is recommended to provide context regarding hypertension in Turkey.

Response:
Thank you for this important suggestion. We have revised the Introduction section to include the epidemiological context of hypertension in Turkey. This addition highlights the public health relevance of the study and clarifies how the present work contributes to addressing this gap.

Methods – Informed Consent

Comment: Please clarify how informed consent was obtained.

Response:
We have added a detailed statement in the Ethical Approval section specifying that all participants were informed about the purpose and procedures of the study and that written informed consent was obtained prior to participation.

Methods – Psychosocial Scales (Section 2.3)

Comment: Provide details on scales, including validation, examples, and Cronbach’s alpha.

Response:
We fully agree with the importance of this point. Section 2.3 has been substantially expanded to include detailed descriptions of the scales used for spiritual orientation, perceived stress, and self-efficacy. We have clarified that all scales were validated in the Turkish population, provided example items for each scale, and reported their internal consistency (Cronbach’s alpha values). These additions enhance the methodological transparency and robustness of the data collection process.

Statistical Analysis – Effect Size Interpretation

Comment: Add interpretation thresholds for Cohen’s d.

Response:
We have revised the Statistical Analysis section to include standard interpretation thresholds for Cohen’s d (small, medium, and large effects) along with an appropriate reference, improving the clarity of effect size interpretation.

Results

Comment: Numerical values should be included in the text, not only in tables.

Response:
We have revised the Results section to include key numerical values (means and p-values) within the descriptive text of the tables. This improves clarity and allows readers to better interpret the findings without relying solely on the tables.

Discussion Structure

Comment: Consider restructuring the discussion into theoretical and practical contributions.

Response:
We appreciate this suggestion. While we maintained the overall structure to preserve coherence, we enhanced the clarity of the Discussion by explicitly emphasizing both theoretical interpretation and practical implications. In particular, a “practical implications” component has been incorporated to improve readability and clinical relevance.

Limitations

Comment: Extend limitations, including equipment-related limitations.

Response:
The Limitations section has been expanded to include additional methodological considerations, including potential limitations related to electrocardiographic measurement precision and variability. This provides a more balanced and transparent interpretation of the findings.

Future Research

Comment: Add a separate subsection for future research directions.

Response:
We have incorporated a more explicit description of future research directions, outlining the need for larger populations, longitudinal designs, and more detailed evaluation of pharmacological and psychosocial factors. These additions clarify how future studies can build upon the current findings.

Round 2

Reviewer 1 Report

Comments and Suggestions for Authors

This manuscript has been improved and is accepted in its current version.

Reviewer 4 Report

Comments and Suggestions for Authors

All suggestions have been addressed. 

 

Thank you!