Sleep Quality as a Predictor of Coronary Artery Disease Severity in Geriatric Acute Coronary Syndrome
Round 1
Reviewer 1 Report
Comments and Suggestions for Authors1. Brief manuscript summary
This prospective observational study examined the relationship between sleep quality, measured by validated subjective questionnaires (PSQI) and objective assessments (actigraphy), and angiographic severity of coronary artery disease (CAD), measured by Gensini and SYNTAX scores. The study compares sleep habits, nocturnal desaturation measures, and cardiometabolic risk factors. Poor sleep quality may be a non-invasive, cost-effective diagnostic for high-risk individuals and independently connected to more severe coronary atherosclerosis.
2. Key manuscript strengths
1. A clinically important, developing subject
Sleep difficulties are widely recognized as cardiometabolic risk factors, and understanding their relationship to coronary atherosclerotic burden advances preventive cardiology.
2. Combining subjective and objective sleep assessment tools
PSQI, actigraphy, and oxygen desaturation indicators make the technique stronger than self-reported surveys.
3. Use reliable angiographic scoring systems (SYNTAX, Gensini).
Using anatomical and weighted stenosis grading methods helps assess CAD severity.
4. Multivariable analysis
The attempt to adjust for age, diabetes, hypertension, and smoking tries to determine sleep characteristics' independent effects.
Big Issues (Many Changes)
1. Methodological clarity is lacking—important information is missing.
The Methods section lacks crucial medical clinical study information:
The patient selection criteria are unclear. The inclusion/exclusion criteria must expressly exclude shift workers, OSA patients, heart failure patients, and sedative/hypnotic users.
I worry about statistical power since the sample size calculation is lacking.
Sleep characteristics may have been gathered before or after angiography. OSA's potential impact is also ignored. Because OSA is intimately associated to CAD, not identifying or ruling out OSA may cloud the results.
Recommendation: Add explicit qualifying criteria, sample size, measurement sequence, and OSA reduction strategies to the Methods section.
2. The sleep test lacks depth and validity.
The study discusses actigraphy but does not specify device kind, sample frequency, or sleep efficiency constraints.
• No explanation provided for PSQI scoring. • No mention of night-to-night fluctuations; actigraphy should span three to seven nights.
Suggestion: Explain actigraphy, PSQI categories, and why single-night recordings are preferable than multi-night recordings.
3. Overthinking causality
The report commonly claims that poor sleep predicts CAD severity.
But: • Cross-sectional designs prevent cause identification.
• More severe CAD patients may have nocturnal angina, dyspnea, or decreased autonomic tone, making sleep difficult.
Change "causal" to "association" and state that the data don't reveal predictive or causal associations.
4. Insufficient multivariable modeling knowledge
The authors claim that sleep quality was "independently associated" but do not provide all multivariate model factors.
• No collinearity analyses reported.
• Depression, anxiety, BMI, and alcohol consumption were excluded.
Please provide multivariable regression tables with β coefficients, adjusted OR/HR, 95% CI, and variance inflation factors.
5. No description of angiographic assessment reliability
Different individuals need expertise with SYNTAX and Gensini scores.
The document does not say:
• If two inexperienced reviewers assessed angiograms.
Kappa statistics show observer agreement.
Whether disputes were resolved.
Consider adding scorers' training, blinding, and repeatability measurements.
6. The debate fails to identify limits.
This limitations section is insufficient. Important limitations include: OSA is not regularly tested.
Sedatives, obesity, and autonomic dysfunction may confuse.
No inflammatory signs (CRP, IL-6) to support a mechanism.
Small sample and single-center design.
Cross-sectional design limits inference.
Without these caveats, the Discussion exaggerates clinical importance.
4. Small Issues
1. English editing
The content is readable but requires style:
• Move "significant relation" a "significant association."
• Avoid subjective phrasing like "interesting finding" and "important impact."
• Remove unnecessary words to improve flow.
2. Charts and tables
Some figures lack axes or unit labels, and table abbreviations (AHI, ODI, SE, PSG, etc.) must be explained.
3. Sources
Key clinical sleep references are lacking, including:
• AHA/ACC scientific statement on sleep and heart health • Key cohort studies (MESA, Nurses' Health Study)
Updating the reference list improves the review's science.
Author Response
Comment 1: "The Methods section lacks crucial medical clinical study information: The patient selection criteria are unclear. The inclusion/exclusion criteria must expressly exclude shift workers, OSA patients, heart failure patients, and sedative/hypnotic users. I worry about statistical power since the sample size calculation is lacking. Sleep characteristics may have been gathered before or after angiography. OSA's potential impact is also ignored. Because OSA is intimately associated to CAD, not identifying or ruling out OSA may cloud the results."
Response: We thank the reviewer for this important observation. We have made the following changes: We have enhanced exclusion criteria, sample size explanation and timing of sleep assessment, OSA screening parts.
Comment 2: "The study discusses actigraphy but does not specify device kind, sample frequency, or sleep efficiency constraints. No explanation provided for PSQI scoring. No mention of night-to-night fluctuations; actigraphy should span three to seven nights."
Response: We thank the reviewer for this comment and would like to clarify a potential misunderstanding. Our study did not use actigraphy or any objective sleep measurement devices. We relied exclusively on the Pittsburgh Sleep Quality Index (PSQI), a well-validated subjective questionnaire. We have enhanced the PSQI methodology section to provide complete details about scoring and validation.
Comment 3: "The report commonly claims that poor sleep predicts CAD severity. But: Cross-sectional designs prevent cause identification. More severe CAD patients may have nocturnal angina, dyspnea, or decreased autonomic tone, making sleep difficult. Change 'causal' to 'association' and state that the data don't reveal predictive or causal associations."
Response: We completely agree with this critical observation and have made extensive revisions: We have changed title and we have systematically revised all language throughout the manuscript to use "association," "correlation," and "linked to" rather than "predictor," "predicts," or other causal terminology.
Comment 4: "The authors claim that sleep quality was 'independently associated' but do not provide all multivariate model factors. No collinearity analyses reported. Depression, anxiety, BMI, and alcohol consumption were excluded. Please provide multivariable regression tables with β coefficients, adjusted OR/HR, 95% CI, and variance inflation factors."
Response: We appreciate this important methodological concern. We have enhanced statistical methods part. Table 2 already presents the complete multivariable logistic regression results including β coefficients, standard errors, p-values, odds ratios (Exp(β)), and 95% confidence intervals for all variables in the model.
Comment 5: "Different individuals need expertise with SYNTAX and Gensini scores. The document does not say: If two inexperienced reviewers assessed angiograms. Kappa statistics show observer agreement. Whether disputes were resolved. Consider adding scorers' training, blinding, and repeatability measurements."
Response: We thank the reviewer for highlighting this important methodological detail. Our manuscript already included inter-observer reliability assessment. The Section 2.6 (Coronary Artery Disease Management and Severity Assessment) states: "The extent and severity of CAD were quantified using the SYNTAX score, calculated from coronary angiography images by two blinded interventional cardiologists using the online SYNTAX calculator (version 2.11). Interobserver variability was assessed via Cohen's kappa, yielding substantial agreement (κ=0.78). In cases of discrepancy, a third cardiologist reviewed the images for final adjudication."
Both cardiologists were experienced interventional cardiologists (>5 years of experience each), were blinded to patients' sleep quality assessments and clinical outcomes, and used the standardized online SYNTAX calculator to ensure consistency.
Comment 6: "This limitations section is insufficient. Important limitations include: OSA is not regularly tested. Sedatives, obesity, and autonomic dysfunction may confuse. No inflammatory signs (CRP, IL-6) to support a mechanism. Small sample and single-center design. Cross-sectional design limits inference. Without these caveats, the Discussion exaggerates clinical importance."
Response: We completely agree and have substantially expanded the Limitations section to address all these concerns.
Comment 7: "The content is readable but requires style: Move 'significant relation' to 'significant association.' Avoid subjective phrasing like 'interesting finding' and 'important impact.' Remove unnecessary words to improve flow."
Response: We have revised language throughout the manuscript to use "significant association" rather than "significant relation," removed subjective phrases, and improved conciseness. We appreciate the attention to precise academic language.
Comment 8: "Some figures lack axes or unit labels, and table abbreviations (AHI, ODI, SE, PSG, etc.) must be explained."
Response: We have verified that all figures have properly labeled axes with units. All tables now include comprehensive footnotes defining all abbreviations used.
Comment 9: "Key clinical sleep references are lacking, including: AHA/ACC scientific statement on sleep and heart health. Key cohort studies (MESA, Nurses' Health Study). Updating the reference list improves the review's science."
Response: We thank the reviewer for this excellent suggestion. We have incorporated these authoritative references to strengthen the scientific foundation of our work:
The AHA Scientific Statement on Sleep and Cardiovascular Health has been cited in the Introduction to establish the importance of sleep as a recognized cardiovascular health component.
The Multi-Ethnic Study of Atherosclerosis (MESA) reference has been added when discussing the prospective evidence linking sleep parameters to cardiovascular outcomes.
The Nurses' Health Study reference has been incorporated to provide context from one of the largest cohort studies demonstrating the sleep-coronary heart disease relationship.
Reviewer 2 Report
Comments and Suggestions for AuthorsMajor Point
- Throughout the article, there is an inconsistent use of acronyms such as ACS (Acute Coronary Syndrome) and CAD (Coronary Artery Disease). These terms should be defined when first mentioned and consistently used throughout the paper. For example, you could mention ACS in the Introduction, then define it fully as Acute Coronary Syndrome before proceeding with the acronym.
Additionally, make sure that all acronyms, such as PSQI (Pittsburgh Sleep Quality Index), are introduced with their full forms the first time they appear.
- In the Methods section, it would be beneficial to clarify the statistical methods used, particularly in relation to:The multivariable logistic regression model: While you explain that significant variables were included, it would be helpful to state the specific criteria for inclusion and provide a more detailed explanation of the rationale behind the selection of the covariates. This would enhance the reproducibility and clarity of the statistical analysis.
- Authors should reference the following studies in the context of arrhythmic risk and sudden cardiac death prevention in patients with CAD, especially those who have been treated with empagliflozin and dapagliflozin: Impact of empagliflozin and dapagliflozin on sudden cardiac death: A systematic review and meta-analysis of adjudicated randomized evidence. Heart Rhythm. 2025 Sep 17:S1547-5271(25)02890-5 and Electrocardiographic modifications and cardiac involvement in COVID-19 patients: results from an Italian cohort. J Cardiovasc Med (Hagerstown). 2021 Mar 1;22(3):190-196.
These studies provide critical insights into the relationship between pharmacological interventions, arrhythmic events, and sudden cardiac death in particularly for geriatric patients with pneumonia disorders. Ensure to incorporate these references in the Introduction or Discussion sections, elaborating on their relevance to your study’s findings.
Minor Point
- Introduction (Page 4, Lines 91-94): Original: "The mechanisms of increased severity include endothelial dysfunction, chronic inflammation, and polypharmacy, which necessitate careful consideration of risks in this population [5]." Suggested: "The mechanisms contributing to increased severity include endothelial dysfunction, chronic inflammation, and polypharmacy, which require careful consideration of risks in this population [5]."
The phrase “necessitate careful consideration” may sound more formal than needed. "Require careful consideration" provides a clearer and more concise meaning.
- Methodology (Page 6, Line 142):Original: "Inclusion criteria were as follows: adult patients aged 65 years or older with confirmed ACS; at least 6 months of follow-up post-procedure; PSQI assessment recorded at the 6-month control visit..." Suggested: "Inclusion criteria were as follows: adult patients aged 65 years or older with confirmed ACS, at least 6 months of follow-up post-procedure, and PSQI assessment recorded at the 6-month follow-up visit..."
The word "control visit" might be misinterpreted. Using "follow-up visit" ensures consistency with the typical phrasing used in clinical research.
- Results (Page 13, Lines 242-245): Original: "Patients with intermediate/high SYNTAX scores had significantly poorer sleep quality, shorter sleep duration, and lower sleep efficiency compared to those with low SYNTAX scores." Suggested: "Patients with intermediate/high SYNTAX scores had significantly poorer sleep quality, shorter sleep duration, and lower sleep efficiency than those with low SYNTAX scores."
The use of "compared to" is technically not incorrect, but "than" is typically preferred when comparing two distinct groups.
- In the Conclusions section (Page 16, Line 341), you mention: "These findings underscore the need for routine sleep assessments in elderly ACS management..." You might also want to briefly mention how your findings might inform clinical practice in terms of interventions (such as sleep improvement strategies) to reduce the cardiovascular burden in elderly ACS patients. This minor clarification would strengthen the conclusion by providing more actionable insights for practitioners in the field.
Author Response
Comment 1: "Throughout the article, there is an inconsistent use of acronyms such as ACS (Acute Coronary Syndrome) and CAD (Coronary Artery Disease). These terms should be defined when first mentioned and consistently used throughout the paper."
Response: We have carefully reviewed the entire manuscript to ensure that all acronyms are properly defined at first use in both the Abstract and the main text, and are used consistently thereafter.
Comment 2: "In the Methods section, it would be beneficial to clarify the statistical methods used, particularly in relation to: The multivariable logistic regression model: While you explain that significant variables were included, it would be helpful to state the specific criteria for inclusion and provide a more detailed explanation of the rationale behind the selection of the covariates."
Response: We appreciate this recommendation for enhanced methodological transparency. We have expanded Section 2.9 (Statistical Analysis) .
Comment 3: "Authors should reference the following studies in the context of arrhythmic risk and sudden cardiac death prevention in patients with CAD, especially those who have been treated with empagliflozin and dapagliflozin: [two specific references provided]"
Response: We appreciate the reviewer's suggestion to consider these studies. However, we respectfully note that our study focuses specifically on sleep quality assessment using the Pittsburgh Sleep Quality Index and its association with angiographic coronary artery disease severity (SYNTAX scores), rather than on arrhythmic outcomes, sudden cardiac death, or pharmacological interventions with SGLT2 inhibitors.
While these are undoubtedly important topics in geriatric cardiovascular care, they fall outside the primary scope of our current investigation examining the sleep quality-CAD severity relationship. Our study does not address arrhythmic burden, sudden cardiac death as an outcome, or the effects of specific pharmacological therapies.
If the reviewer could clarify the specific connection between these references and our study's findings regarding sleep quality and angiographic disease severity, we would be happy to incorporate them more meaningfully. Alternatively, if these references are considered essential by the editorial team, we could briefly mention them in a broader context of cardiovascular risk management in elderly patients, though this would be somewhat tangential to our primary findings.
Comment 4: "Introduction (Page 4, Lines 91-94): Original: 'The mechanisms of increased severity include endothelial dysfunction, chronic inflammation, and polypharmacy, which necessitate careful consideration of risks in this population [5].' Suggested: 'The mechanisms contributing to increased severity include endothelial dysfunction, chronic inflammation, and polypharmacy, which require careful consideration of risks in this population [5].'"
Response: The sentence has been changed as suggested.
Comment 5: "Methodology (Page 6, Line 142): Change 'control visit' to 'follow-up visit'"
Response: All instances of "control visit" have been changed to "follow-up visit" throughout the manuscript.
Comment 6: "Results: Change 'compared to those with' to 'than those with'"
Response: We agree this is grammatically more precise. We have reviewed the Results section and changed "compared to" to "than" in comparison contexts.
Comment 7: "In the Conclusions section, you might also want to briefly mention how your findings might inform clinical practice in terms of interventions (such as sleep improvement strategies) to reduce the cardiovascular burden in elderly ACS patients."
Response: We have enhanced the Conclusions section to include specific clinical implications and potential interventions.
Round 2
Reviewer 1 Report
Comments and Suggestions for AuthorsAll requests were promptly addressed.
Reviewer 2 Report
Comments and Suggestions for Authors
