Correlation of Sarcopenia with Coronary Artery Disease Severity and Pericoronary Adipose Tissue Attenuation: A Coronary CT Study

Round 1

Reviewer 1 Report

Comments and Suggestions for Authors

We would like to thank the authors for submitting their manuscript to our journal. The article focuses on the use of coronary CT in evaluating the impact of sarcopenia on coronary artery disease and pericoronary adipose tissue attenuation. Below are some minor revisions required for improvement:

1) It is recommended to reference the modern application of photon counting CT within coronary CT angiography in the introduction. The following article should be cited: Trimarchi, Giancarlo et al. “Charting the Unseen: How Non-Invasive Imaging Could Redefine Cardiovascular Prevention.” Journal of Cardiovascular Development and Disease vol. 11, no. 8, 245, 9 Aug. 2024, doi:10.3390/jcdd11080245.

2) In the tables, please include explanations for abbreviations such as pCAD-RADS and pROI, enhancing clarity for readers.

3) We advise creating a graphical abstract that effectively summarizes the study's findings and key messages, facilitating a more accessible understanding of the research.

4) Finally, it would be beneficial to discuss other cardiological settings, such as in patients undergoing pre-TAVI or left atrial appendage closure (LAAC), where preoperative CT could be utilized for sarcopenia assessment.

These revisions aim to strengthen the article's contribution to the field and provide readers with a comprehensive understanding of the study's implications.

Author Response

R1.1: It is recommended to reference the modern application of photon counting CT within coronary CT angiography in the introduction. The following article should be cited: Trimarchi, Giancarlo et al. “Charting the Unseen: How Non-Invasive Imaging Could Redefine Cardiovascular Prevention.” Journal of Cardiovascular Development and Disease vol. 11, no. 8, 245, 9 Aug. 2024, doi:10.3390/jcdd11080245.

Reply: We thank the Reviewer for their suggestion. We cited the referenced article in the Introduction, which now reads:

“Recently, the updated version of CAD-RADS reporting system has been published to provide a standardized classification of CAD on CCTA evaluating coronary stenosis, plaque burden and modifiers such as patients having undergone prior procedures, along with evidence-based recommendations for patient management [20]. Moreover, novel applications such as photon counting CT could potentially unlock new potential for CCTA, adding to the list of biomarkers which can be derived from such techniques [21].”

R1.2: In the tables, please include explanations for abbreviations such as pCAD-RADS and pROI, enhancing clarity for readers.

Reply: We thank the Reviewer for their query. We did include explanations for abbreviations in the table captions

R1.3: We advise creating a graphical abstract that effectively summarizes the study's findings and key messages, facilitating a more accessible understanding of the research.

Reply: We thank the Reviewer for their advice. While we recognize the value of graphical abstracts in enhancing the accessibility of research, we have decided not to include one in this particular submission. Our study's findings are nuanced and multi-dimensional, and we feel that a graphical abstract might oversimplify the complexity of the data and the key messages we wish to convey. Additionally, the detailed visualizations and explanations provided within the manuscript already offer a clear and comprehensive summary of the results.

R1.4: Finally, it would be beneficial to discuss other cardiological settings, such as in patients undergoing pre-TAVI or left atrial appendage closure (LAAC), where preoperative CT could be utilized for sarcopenia assessment.

Reply: We thank the Reviewer for their comment. We added a brief discussion of this issue in the Discussion section, which now reads:

“This might lead to the lack of significant correlations between CT muscle metrics and cardiovascular risk biomarkers. Last, we did not appraise the role of the assessment of sarcopenia from CCTA specifically in patients referred to procedures such as transcatheter aortic valve replacement, or left atrial appendage closure, especially in the preoperative settings. Future studies could be aimed at performing such evaluations, to better define the role of such analyses in the preprocedural setting.”

Reviewer 2 Report

Comments and Suggestions for Authors

Sarcopenia is an important player is current daily clinical practice, both in malnutriced and obese patients.  Current  study was aimed to  analyse association between sarcopenia and  CAD  via  CTA.  The  topic as  actual  and  important.  The  paper could  be  reccommende  to the  Journal after several clarifications.

 

1.          The title  represents  the  study. However,  I recommend  to  make  it more précised (eg… impact of sarcopemia on CAD severity…)

2.          Abstract is  brief, however  acceptable. 

3.           Introduction  represents current concept of sarcopenia and  link with  CAD.  The aim of the study is clear.

6. Materials and  methods section is well written. Study  design is sufficient. CT protocol is well-described and  illustrated.

7. Statistic section  is ok.

8. Lines 164-178 are technical. Should be  delated.

9. Result section  requires several corrections.

Before regression analysis, several issues have to be  clarified, even in supplementary data

 

1)      Patients characteristics

2)      Epidemiology of sarcopenia in entire cohort

3)      CTCA data, more précised.

Then regression analysis could  be  presented.

Of interest, is  to compare CAD-RAD and pericoronary  adipose tissue between sarcopenic patients and  controls with correction to age, sex and risk factors.

 

1.       Discussion section is good.

11.        References are updated.

Comments on the Quality of English Language

English is fine

Author Response

R2.1: The title represents the study. However, I recommend to make it more précised (eg… impact of sarcopenia on CAD severity…)

Reply: We thank the Reviewer for their comment. We edited the title to “Correlation of sarcopenia with coronary artery disease severity and pericoronary tissue attenuation: a coronary CT study”

R2.2: Lines 164-178 are technical. Should be delated.

Reply: We thank the Reviewer for their suggestion. We deleted the referenced lines.

R2.3: Result section requires several corrections. Before regression analysis, several issues have to be clarified, even in supplementary data

• Patients characteristics
• Epidemiology of sarcopenia in entire cohort
• CTCA data, more précised.

Then regression analysis could be presented.

Of interest, is to compare CAD-RAD and pericoronary adipose tissue between sarcopenic patients and controls with correction to age, sex and risk factors.

Reply: We thank the Reviewer for their remark. We did include age and sex of included patients, as patients characteristics, in the manuscript. As sarcopenia cutoffs are not strictly defined for the referenced spine levels we used for muscle measurements, we did not classify patients with regards to whether or not they presented with sarcopenia. Concerning CTCA data, we reported patients’ CAD-RADS scores in the manuscript.

Reviewer 3 Report

Comments and Suggestions for Authors

The paper by Albano et al. investigates the association between sarcopenia and CAD using coronary CT angiography. The study aimed to evaluate the relationship between sarcopenia indicators, such as muscle metrics, and cardiovascular metrics like CAD-RADS and pericoronary adipose tissue attenuation. While the findings revealed weak correlations between sarcopenia and cardiovascular risk markers, traditional factors like age and other cardiovascular risks overshadowed sarcopenia’s impact.

 

The study has several limitations: The small, single-center sample size limits the generalizability of the findings, making it difficult to draw broad conclusions about the relationship between sarcopenia and cardiovascular disease. Additionally, the muscle measurements were taken at the T6 and T8 levels, which are not standard for sarcopenia assessment; the L3 level is widely accepted as the most accurate site for estimating overall skeletal muscle mass. This raises concerns about whether the chosen muscle groups adequately represent sarcopenia in this population. The retrospective design further introduces potential biases. While the paper provides some insights, it falls short in terms of offering strong, actionable conclusions. It contributes to the ongoing conversation but is unlikely to have a major impact on the field.

 

Major Comments:

 

Introduction:

More details about previous studies specifically investigating the relationship between sarcopenia and CAD should be included, as this is a central theme of the paper. Add more in-depth references to studies linking sarcopenia with CAD or cardiovascular outcomes, or provide a rationale for the limited literature.

 

Methods:

While using T6 and T8 may offer advantages specific to coronary CT angiography scans, these levels are less validated for the assessment of sarcopenia compared to L3. The L3 level is traditionally used in sarcopenia research, particularly for muscle mass assessment, as it correlates well with whole-body muscle mass and has been widely validated in both clinical and research settings. The authors should explicitly acknowledge that the use of T6 and T8 for muscle measurements may limit the comparability of their results to other sarcopenia studies that use L3. If T6 and T8 have been validated for sarcopenia in other contexts, they should cite relevant literature. If not, they should mention the need for further validation of these levels as accurate indicators of sarcopenia. Additionally, the authors should check for any abdominal CT scans taken around the same time as the coronary CT angiography. If available, they should use these abdominal scans to measure muscle areas (M. psoas) at the L3 level, which is the standard reference for assessing skeletal muscle mass.

 

Results:

The authors mention several weak correlations, but the clinical significance of these weak correlations is not fully explored. They should provide more interpretation of the borderline significant findings and what they mean clinically. Additionally, consider adding visual representations (e.g., correlation matrices or scatter plots) to make it easier for readers to understand the relationships between muscle metrics and cardiovascular risk markers.

 

Conclusion:

The conclusions are somewhat aligned with the results, particularly regarding the weak correlations found. However, the conclusion fails to fully discuss the limited predictive value of sarcopenia in relation to traditional risk factors. The authors conclude that sarcopenia might still be valuable for cardiovascular risk assessment, but the data do not strongly support this assertion. The conclusion should be revised to reflect the limited significance of sarcopenia in predicting cardiovascular disease, emphasizing that age and traditional factors are more powerful predictors.

Comments on the Quality of English Language

Some grammatical errors.

Author Response

R3.1: More details about previous studies specifically investigating the relationship between sarcopenia and CAD should be included, as this is a central theme of the paper. Add more in-depth references to studies linking sarcopenia with CAD or cardiovascular outcomes, or provide a rationale for the limited literature.

Reply: We thank the Reviewer for their advice. We understand the importance of providing a robust background, particularly on the relationship between sarcopenia and coronary artery disease (CAD), which is indeed a central theme of the paper. However, we aimed to keep the introduction concise, as overly long introductions can detract from the focus of a scientific article. In this case, we sought to highlight the key relevant studies while avoiding redundancy with the more detailed discussion in later sections.

R3.2: While using T6 and T8 may offer advantages specific to coronary CT angiography scans, these levels are less validated for the assessment of sarcopenia compared to L3. The L3 level is traditionally used in sarcopenia research, particularly for muscle mass assessment, as it correlates well with whole-body muscle mass and has been widely validated in both clinical and research settings. The authors should explicitly acknowledge that the use of T6 and T8 for muscle measurements may limit the comparability of their results to other sarcopenia studies that use L3. If T6 and T8 have been validated for sarcopenia in other contexts, they should cite relevant literature. If not, they should mention the need for further validation of these levels as accurate indicators of sarcopenia. Additionally, the authors should check for any abdominal CT scans taken around the same time as the coronary CT angiography. If available, they should use these abdominal scans to measure muscle areas (M. psoas) at the L3 level, which is the standard reference for assessing skeletal muscle mass.

Reply: We thank the Reviewer for their comment. Naturally, were L3 levels available in our CT datasets, we would have opted for performing sarcopenia measurements at such level. However, as this was not the case for our CCTA datasets, we aimed for T6 and T8 measurements, which have occasionally been studied in previous literature, and were feasible in all instances. We added a reference from a work by Brath et al. (10.1186/s41747-023-00340-1), which states that “Any thoracic level can be used to assess thoracic muscle mass”. Thus, the Methods section now reads:

“The measurement of skeletal muscle area was conducted at T8 pedicle level, noting the attenuation in Hounsfield units and the cross-sectional area (CSA) of the paravertebral skeletal muscles on both sides of the spine, including the erector spinae muscle, longissimus thoracis muscle, spinalis thoracis muscle, and iliocostalis lumborum muscle. Such level was chosen due to its widespread representation throughout the study sample, along with the fact that measurements at T6-T8 have been validated to assess sarcopenia [34].”

R3.3: The authors mention several weak correlations, but the clinical significance of these weak correlations is not fully explored. They should provide more interpretation of the borderline significant findings and what they mean clinically. Additionally, consider adding visual representations (e.g., correlation matrices or scatter plots) to make it easier for readers to understand the relationships between muscle metrics and cardiovascular risk markers.

Reply: We thank the Reviewer for their suggestion. We did add to the interpretation of results in the Discussion section. However, we did not include visual representations such as scatter plots, as they may not represent the best way to report such analyses in cases of weak correlations. The Discussion now reads:

“Similarly, the very weak, albeit significant, positive correlations between PM muscle metrics, namely density, CSA and nCSA, and LAD pCAT (ρ=0.220 p=0.001, ρ=0.240 p<0.001, and ρ=0.229 p<0.001, respectively), indicate that decreased PM muscle density and area, again related to sarcopenia, are, too, linked to lower adipose tissue attenuation. The same may be true for borderline correlations, which still indicate the same trend for muscle density and pCAT.”

R3.4: The conclusions are somewhat aligned with the results, particularly regarding the weak correlations found. However, the conclusion fails to fully discuss the limited predictive value of sarcopenia in relation to traditional risk factors. The authors conclude that sarcopenia might still be valuable for cardiovascular risk assessment, but the data do not strongly support this assertion. The conclusion should be revised to reflect the limited significance of sarcopenia in predicting cardiovascular disease, emphasizing that age and traditional factors are more powerful predictors.

Reply: We thank the Reviewer for their comment. We edited the Conclusion so to match results more closely, toning down the potential role of sarcopenia in cardiovascular disease, and the passage now reads:

“In conclusion, results from our study show that muscle metrics derived from CCTA may be tare related to cardiovascular risk, albeit weakly, linking cardiovascular risk and sarcopenia. Still, traditional risk factors yield a higher impact on the overall cardiovascular risk evaluation. As such, these metrics might be considered when other more robust parameters clinical/imaging parameters are not available. Further studies on larger populations are warranted to review the role of skeletal muscle evaluation from CCTA.”

 

Round 2

Reviewer 2 Report

Comments and Suggestions for Authors

The paper is improved  and could  be  recommened  to the  Journal

Author Response

We thank the reviewer for his positive comment

Reviewer 3 Report

Comments and Suggestions for Authors

Dear Authors!

 

Thank you for your comments, you adressed all concerns and made adjustments to the manuscript. 

 

Best regards!

Author Response

We thank the reviewer for his positive comment