Heart Dysfunction in Essential Hypertension Depends on Systemic Proinflammatory Influences: A Retrospective Clinical Pathophysiological Study

Round 1

Reviewer 1 Report

The topic of the manuscript by Barsukov at al. is still actual and interesting. Unfortunatelly, there are some issues which needs to be addressed:

Introduction: definition of metabolic syndrome included hypertension, obesity and diabetes. In line 43 authors listed metabolic syndrome as well as its components – must be chosen one

Methods: add numbers of patiens with HTN 1st or 2nd grade

Results: in main group, results of heart geometry parameters (LVMI, LAVI and so) are listed in table 1, however in table 2 and 3 those parameters are missing. All of them should be listed.

For better orientation comparison between groups should be in table

Authors mentioned that most of the hypertensive patients used different antihypertensive drugs, it is very well known, that some of them has also positive effect on heart function – how did you evaluate this effect? Must be explain

Literature should be updated – 2 paper are from 2021, 3 from 2020, none from 2022   

Author Response

The term «metabolic syndrome» is deleted on line 43.
The «Methods» section indicates the number of patients in the main group with 1 and 2 degrees of hypertension.
Tables 1, 2 and 3 are supplemented with necessary baseline indicators for better orientation. Information about the medications taken is reflected in the «Discussion» section.
Updates have been made to 7 sources in the bibliography.

Author Response File: Author Response.doc

Reviewer 2 Report

The manuscript intends to find out the changes of serum proinflammatory indicators in patients with essential hypertension and heart failure with preserved LV ejection fraction. The authors used patients with essential hypertension but no heart failure as the comparison group, and healthy individuals as the control group. They compared the results between patients at either stage 1 or stage 2 LV diastolic dysfunction, and between males and females. Their results strongly indicate a higher level of proinflammatory indicators in patients at stage 2 compared to patients at stage 1, and in male than in female.

Overall, the results are robust and scientifically sound. However, the background is not detailed enough. The link among essential hypertension, heart failure, LV ejection fraction and LVDD is not clear. Previous research about the role of inflammation in hypertension was not discussed in depth. It is hard to understand why CRP, IL-6 and TNF-ɑ are chosen to be tested in the study. The same problem exists in the discussion part. 34 out of 48 references used in the paper are not within the recent 5 years. According to their conclusions, it is highly recommended that the authors discuss the gender difference, inflammation, especially CRP, IL-6, TNF-ɑ, in hypertension, inflammation and LVDD in sequence and in detail.  Additionally, although CRP, IL-6 and TNF-ɑ data from the three groups were listed in table 1, table 2 and table 3 respectively, there is no statistical comparison among them. The authors did do the statistics for groups Without LVDD, LVDD 1 stage, LVDD 2 stage and Healthy, and presented the results in the main context. However, only p values between LVDD 1 stage and LVDD 2 stage were reported. How about the p values of Without LVDD compared with all the other groups? How about the Healthy group? Is there any gender difference within Without LVDD and Healthy group? All statistical results need to be available. Moreover, when the p values were reported in the main context, there was no indication about which figure they were discussing. Figure number need to be labelled at the place where it is discussed. Plus, the format of the figure, simple bar plots, is not acceptable. Please add the individual data point to the plot.

Specific comments:

1.       Abstract and the first paragraph of Discussion are not well structured. Usually, people follow the pattern of Background, Aims, Method, Results, and Conclusions.

2.       Methods, there is no description about how the 6-min walking test was conducted. 

3.       Method, Line 119, the blood levels of several parameters were determined, why? Are these parameters related to the results reported in the manuscript? If they are related, where is the data?

4.       Table 1, reference range needs to be in the table. When describing the table content, please explain the indication of each parameter and how the males and females look like (are they normal? If not, what that mean) in a clear way. A simple summary as Line 192 is hard to read.

5.       Line 197, non-significant data also need to be reported. Please put the data of LVIDD, LVISD, LVEF, RWT and LAVI in table 1 or in supplementary material. Please explain the meaning of this non-significance as well.

6.       Statistics about data in table 1, table 2 and table 3 are required. Please discuss the results. It is also very interesting to see the gender difference only exist in the main group, but not in comparison and healthy group. Please discuss as well.

7.       Figure 3 – 5, comparisons among Without LVDD to all the other groups, and Healthy to all the other groups are missing. The figure needs to contain individual data point and significance.

8.       Figure 6 and 7, it is better to have r values indicated in the figures. The meaning of each dot in the figure needs a description. Is a dot representing a participant?

9.       Line 255, what is the meaning of results? In general, the authors reported results without discussing the indication, which needs to be corrected.

Author Response

Abstract structuring done.
The 6-minute walk test methodology is given. Reference ranges for pro-inflammatory biomarkers are given.
The content of tables 1-3 has been supplemented, deciphered.
Figures 3-5 are supplemented with the interpretation of the data in the text for healthy and non-LVDD patients.
The interpretation of the results in the discussion section has been improved (with respect to the data in line 255 and others).
Figures 6 and 7 have been corrected, additions have been made to their description.
Several references refreshed for recent ones.

Round 2

Reviewer 1 Report

accept in present form without further comments

Author Response

Text improved taking into account the comments

Author Response File: Author Response.docx