Peripheral Artery Disease in Asian Ischaemic Stroke Patients—A Cross-Sectional Study
Round 1
Reviewer 1 Report
Comments and Suggestions for AuthorsThank you for the opportunity to review this manuscript examines the prevalence of peripheral artery disease (PAD) in 150 patients admitted with acute ischaemic stroke. PAD is common in Asian stroke patients and that clinicians should consider targeted PAD screening, especially in non-lacunar stroke.
Several important issues should be noted.
Major comments:
1. The manuscript includes a long comparison with prior Asian studies and shows that PAD in stroke patients has already been reported across several Asian populations, including Singapore, with prevalence figures in a similar range.
2. The logistic models include multiple covariates despite only 33 PAD events. That is a difficult ratio for stable multivariable analysis. The shift from ischaemic heart disease in one model to non-lacunar infarction in the final model suggests model sensitivity.
3. Patients who were aphasic or drowsy throughout admission were excluded. The paper itself notes that such patients may include those with large artery occlusion, who could be more likely to have PAD.
4. The study measures PAD and stroke features at the same time. It cannot determine whether PAD predicts stroke subtype, future vascular events, or treatment response.
5. Stroke was divided into lacunar and non-lacunar infarction on imaging, rather than using a more detailed etiologic classification throughout the study population. Non-lacunar infarction is a broad category and does not map cleanly to large artery atherosclerosis.
6. Risk factors were defined largely by history or medication use. The study did not assess duration, severity, control, or treatment intensity, and smoking was categorized as ever-smoked.
I recommend major revision, and I encourage you to continue this important line of work.
The English could be improved to more clearly express the research.
Author Response
Reviewer 1
Thank you for the opportunity to review this manuscript examines the prevalence of peripheral artery disease (PAD) in 150 patients admitted with acute ischaemic stroke. PAD is common in Asian stroke patients and that clinicians should consider targeted PAD screening, especially in non-lacunar stroke.
Several important issues should be noted.
Major comments:
- The manuscript includes a long comparison with prior Asian studies and shows that PAD in stroke patients has already been reported across several Asian populations, including Singapore, with prevalence figures in a similar range.
Reply – thank you, the consistency of the results with other Asian studies supports the reliability of the fundings.
- The logistic models include multiple covariates despite only 33 PAD events. That is a difficult ratio for stable multivariable analysis. The shift from ischaemic heart disease in one model to non-lacunar infarction in the final model suggests model sensitivity.
Reply – thank you, this important point has now been added to the study Limitations section (lines 334-353).
- Patients who were aphasic or drowsy throughout admission were excluded. The paper itself notes that such patients may include those with large artery occlusion, who could be more likely to have PAD.
Reply - thank you. As only 3 patients were excluded for this reason, the overall result is unlikely to have been affected. This point has now been added to the study Results and also to the study Limitations section (lines 216-218, 334-353).
- The study measures PAD and stroke features at the same time. It cannot determine whether PAD predicts stroke subtype, future vascular events, or treatment response.
Reply – thank you, this important point has now been added to the study Limitations section (lines 334-353).
- Stroke was divided into lacunar and non-lacunar infarction on imaging, rather than using a more detailed etiologic classification throughout the study population. Non-lacunar infarction is a broad category and does not map cleanly to large artery atherosclerosis.
Reply – thank you, this important point has now been added to the study Limitations section (lines 334-353).
- Risk factors were defined largely by history or medication use. The study did not assess duration, severity, control, or treatment intensity, and smoking was categorized as ever-smoked.
Reply - thank you, this important point which was already briefly mentioned before in the study Limitations section, has now been expanded with these new inputs (lines 334-353).
I recommend major revision, and I encourage you to continue this important line of work.
Reply – thank you so much for your kind encouragement.
Thank you for your most insightful comments. I hope I have adequately addressed your concerns.
Reviewer 2 Report
Comments and Suggestions for AuthorsGeneral Comment
Consider dividing the sections into some subheading for easier reading navigation.
It will be beneficial from a practical point of view to provide CT/MRI figures for each Model group, as well as carotid sonograms of the plaque cases.
Abstract
Comment: Provide the number of your sample size.
Line-28 "Further studies with larger patient numbers are needed to corroborate these findings": Comment: rudimentary statement, I suggest removing it.
Introduction
Comment: Consider adding pathology brief background of lacunar versus non-lacunar infarction.
Methods
Line 101 "The overall study methods have been previously described Relevant to this study": Comment: Substitute this statement with a description that assure reproducibility of the method by other researcher.
Comment: Provide the The Ethical Institutional Review Board (IRB) Approval.
Comment: Include the sample size and its demography (Lines 156-160) here under the methods sections, not the results. What was the original screened sample size of the selected 150?
Results
Lines 156-160: Comment: This belongs to the methods section.
Comment: Consider incorporating graphical illustrations of your results/analysis out come.
Comment: Provide the data of the infarctions size or by the clinical grading system.
Comment: Provide data on the carotid plaque size/grading indexing the occlusions severity. Analyze its statistical correlations with the infarction grades. What is the statistical associations percentages by severity? How much of a risk factor it could had contributed in comparison to non-occluded carotid arteries.
Discussion
Comment: several associations were addressed and elaborated on but lacks graphical illustrations. Provide graphs for each major found association representing each of your models.
Conclusion
Line 271 "This study adds valuable new information to this field of PAD in IS patients" Comment: rudimentary statement, I suggest removing it.
Author Response
Reviewer 2
General Comment
Consider dividing the sections into some subheading for easier reading navigation.
Reply – thank you, headings have now been added (lines 36, 50, 65, 83, 104, 109, 114, 131, 178, 188, 200, 205, 215, 226, 229, 238, 246, 262, 269, 278, 315, 333).
It will be beneficial from a practical point of view to provide CT/MRI figures for each Model group, as well as carotid sonograms of the plaque cases.
Reply - Thank you, figures/sonograms have now been added – please see Figs 1a, 1b, 2a, 2b.
Abstract
Comment: Provide the number of your sample size.
Reply – thank you, this information has now been added: ‘The estimated sample size was 150 subjects.’ (Lines 17-18).
Line-28 "Further studies with larger patient numbers are needed to corroborate these findings": Comment: rudimentary statement, I suggest removing it.
Reply – thank you, this sentence has now been removed.
Introduction
Comment: Consider adding pathology brief background of lacunar versus non-lacunar infarction.
Reply – thank you, this important information has now been added to the Methods section to expand on LI and NLI (lines 147-153).
Methods
Line 101 "The overall study methods have been previously described Relevant to this study": Comment: Substitute this statement with a description that assure reproducibility of the method by other researcher.
Reply – I apologise for the lack of clarity. These 2 phrases have now been removed, and the Methods section enhanced to allow reproducibility by other researchers (lines 114-186).
Comment: Provide the The Ethical Institutional Review Board (IRB) Approval.
Reply – thank you, this already appeared in the Institutional Review Board Statement after the main text of the paper. It is now also added the Methods section too (lines 206-208, 370-371).
Comment: Include the sample size and its demography (Lines 156-160) here under the methods sections, not the results.
Reply – Thank you, sample size estimate already appears in Methods – I am sorry it was not clear before, the heading has now been added (line 200). I apologise, but as I believe demography are Results, i was following the instructions to authors from the journal and placed the information in Results:
‘Results: Provide a concise and precise description of the experimental results’ (https://www.mdpi.com/journal/neurosci/instructions). I am sorry if I have misunderstood
What was the original screened sample size of the selected 150?
Reply – thank you, 153 subjects were screened - 3 were excluded as they remained drowsy and aphasic throughout their hospital stay and consent was not obtainable. This information now appears in the Results section (lines 216-218).
Results
Lines 156-160: Comment: This belongs to the methods section.
Reply – I apologise, but i was following the instructions to authors from the journal: ‘Results: Provide a concise and precise description of the experimental results’ (https://www.mdpi.com/journal/neurosci/instructions). I am sorry if I have misunderstood
Comment: Consider incorporating graphical illustrations of your results/analysis out come.
Reply – thank you, figures have now been added – please see Figs 1a, 1b, 2a, 2b.
Comment: Provide the data of the infarctions size or by the clinical grading system.
Reply – thank you for this important point. Unfortunately, volumetric determination of infarct size was not performed, stroke severity by the National Institute of Health Stroke Scale (NIHSS) was not consistently recorded and thus unavailable for analysis. This issue has now been added to the study Limitations section (lines 334-353).
Comment: Provide data on the carotid plaque size/grading indexing the occlusions severity. Analyze its statistical correlations with the infarction grades. What is the statistical associations percentages by severity? How much of a risk factor it could had contributed in comparison to non-occluded carotid arteries.
Reply – thank you, unfortunately data on carotid plaque size/grading was not collected, but degree of stenosis was collected – only 8% had stenosis >50% - this has now been added to the Results. Analysis was not performed on correlation with infarction grades due to the small proportion. No significant association was found with PAD on logistic regression. To avoid double counting, only the association of presence of plaques with PAD was analysed – as reported, no significant association was found with PAD on logistic regression.
Discussion
Comment: several associations were addressed and elaborated on but lacks graphical illustrations. Provide graphs for each major found association representing each of your models.
Reply – thank you, please see Figs 1a, 1b, 2a, 2b.
Conclusion
Line 271 "This study adds valuable new information to this field of PAD in IS patients" Comment: rudimentary statement, I suggest removing it.
Reply – thank you, this sentence has now been removed.
Thank you for your most insightful comments. I hope I have adequately addressed your concerns.
Round 2
Reviewer 1 Report
Comments and Suggestions for AuthorsI have no further question.
Comments on the Quality of English LanguageI have no further question.
Reviewer 2 Report
Comments and Suggestions for AuthorsThe presentation of the study had improved.
The remaining shortcoming is the not provided infarctions size and its clinical grading system. However, it was addressed in the limitation.
