PONE-D-19-14921

Anxiety and Depression Relationship with Coronary Slow Flow

PLOS ONE

Dear Dr. Elamragy,

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PLOS ONE

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Reviewer #1: In this study, the authors aimed to assess the possible relation of psychiatric disorders, such as depression and anxiety status, with the coronary flow pattern in patients with angiographically normal coronary arteries. The TIMI frame count (TFC) has been used for definition of coronary slow flow (CSF) phenomenon and psychiatric interviews were performed to assess severity of anxiety and depression using the BAI and BDI scales. The results show that patients with CSF had significantly higher anxiety and depression scores, irrespective of gender. The authors also found a strong correlation between the BAI score and CSF severity.

We thank the authors for this interesting study. The pathophysiologic hypothesis is intriguing and the study design is fitting. However, this reviewer has several concerns:

Major comments

- The authors should give detailed information about the clinical findings of CSF patients and control patients. In particular, the symptomatic burden, including duration of the angina pattern, as well as frequency and severity of angina attacks should be reported and compared.

- The use of beta-blockers, vasodilators or other anti-ischemic drugs might have affected the detection of CSF. The authors should at least comment this point as a limitation of the study.

- If possible, the authors should report the educational and socioeconomic status of patients of the 2 groups, as possible factors influencing depression or anxiety status.

Minor comments

- The analysis of this study doesn’t account for the use of psychiatric drugs or other medication. Although none of the antidepressant drugs is known to cause CSF, as the authors say in the text, the answers of patients to the interviews might have been influenced by their use.

- Have the authors tried to exclude patients with possible “secondary form” of CSF (i.e. coronary artery ectasia, coronary artery spasm, pulmonary arterial hypertension, etc...)?

- The depression and anxiety rating scales (BAI and BDI), used to assess the severity of the psychiatric disorder, are two self-report scales. Thus, they depend on patients’ reliability, time and context of interview administration.

Reviewer #2: The study is focused on a large-scale problem that is the increasing prevalence of patients with both coronary artery disease (CAD) and depression or anxiety, that, to date, are probably not well diagnosed and treated for the underlying psychological conditions despite growing evidences that these conditions play an important role in provoking and modifying the prognosis in cardiovascular diseases. The study, taking into account the intrinsic limitations of a cross sectional study, shows significant and independent association between depression and coronary slow flow (CSF) as well as with male gender or triglyceride serum levels (association already demonstrated by other authors) and significant but dependent association with anxiety and other classical cardiovascular risk factors. The paper, sustaining the role of psychological conditions together with classical cardiovascular risk factors in determining CSF, wants to stress the importance of an accurate global (physical and psychological) assessment of the patient. An interesting point of the paper is the exclusion of patients with a coronary artery stenosis > 20%, in fact even mild-to-moderate stenosis could affect CSF and could have represented a selection bias.

However, this manuscript had some issues that deserve clarifications.

Major comments

1. The study population is composed by consecutive patients who underwent coronary angiography due to ‘objective evidence of ischemia’. What do the Authors mean with that sentence? It is necessary to provide a clear definition of ischemia and a standardized diagnosis.

2. Diabetes, one of the most important cardiovascular risk factors and strongly related to endothelial dysfunction, seems not to be associated with CSF. The authors should be discussing this point

3. Another point is the definition of the ex-smoker status. The Authors have provided an arbitrary definition of former smoker (only the patients who have stopped > 2 years), not shared by the principal National Health Systems. This gross classification of patients probably leads to some bias in defining the relationship between smoking and CSF because the toxic substances contained in cigarettes act in a short/medium period of time in causing endothelial dysfunction and inflammation.

4. It is well established that depression and anxiety are twice as high in females than in males, in this study the mean BDI and BAI scores are lower in women. Maybe these scores should be integrated with a clinical evaluation of symptoms by a psychiatrist to avoid the subjective influence of the patients and on the physician in interpreting the answers. It would also be useful to provide the complete data of the prevalence and of the degree of anxiety and depression adjusted for gender.

5. One major problem of this work is that it does not evaluate the role of psychoactive drugs. For example, it is not well established if the antidepressants play a role in unmasking endothelial dysfunction or platelet adhesion and it is still a matter of debate the role of these drugs in improving symptoms and prognosis in patients with cardiovascular diseases. It would be interesting to have some data regarding this issue in the study population.

Minor comments

1. Please check the references. For example, references 10-15 refer to articles that do not match with the text.

2. Try to make the ‘Result Section’ more uniform. There are many tables that can be merged into one single table. This solution will help in improving paper’s structure: more logical and fluid to read and understand.

Anxiety and Depression Relationship with Coronary Slow Flow

PONE-D-19-14921R1

Dear Dr. Elamragy,

We are pleased to inform you that your manuscript has been judged scientifically suitable for publication and will be formally accepted for publication once it complies with all outstanding technical requirements.

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With kind regards,

Carmine Pizzi

Academic Editor

PLOS ONE