Relationship between Pulse Pressure and Handgrip Strength in the Korean Population: A Nationwide Cross-Sectional Study

Round 1

Reviewer 1 Report

Comments and Suggestions for Authors

Abstract – Background – as there are very few data available on the relation between pulse pressure and sarcopenia (Coelho Jùnior et al, Ohara et al) , and the logical connection is far from evident, the last sentence of the paragraph should rather state that the purpose of the study is to assess if this relationship does exist.

Line 131 – in descriptive statistics standard deviation, not standard error should be used.

Line 140 – as subjects were excluded according to study criteria, the Authors can say that 54.668 were evaluated, but only 29.482 participated in the study. So this number should appear at line 74. However the interpretation is further complicated by the fact that no one of these numbers appear in figure 1, where participants are no longer 29.482, but 17.397. The Authors should clarify and make coherent the report of numbers.

Line 157 – no percentage of patients with metabolic syndrome is reported in table 1 (even if the components are there) – see also line 221

Figure 1 – in the text the values of PP are characterized as PP<40 - 40≤PP<60 - PP≥60: why here only two group are described?

Line 174 – overall percentage of weak and strong patients should be reported; it would be useful to add this information in table 1, beyond maximum HGS.

Legend to table 2 – the exact value of p is to be reported, in place of p<0.05. Odd should be corrected to odds. It should be explicitly indicated that the handgrip strength is number of weak HGS and not a continuous variable.

Lines 241-4 – we were not able to find any data concerning relationship between handgrip strength and arterial stiffness neither in Bohannon [23] nor in Shim [24] papers.

Line 267 – “Comprehensively, the association between PP and HGS can serve as a clinically valuable method for PP monitoring, which is an inexpensive and noninvasive measurement 268 tool for identifying people with low muscular strength” – measurement of handgrip strength is inexpensive and noninvasive, so it is difficult to propose pulse pressure as a surrogate.

The discussion emphasizes the role of pulse pressure as useful functional and prognostic variable. In similar fashion the role of handgrip strength is reported. The discussion would result easier for the reader if the two topics were included in separated paragraphs, and then a further paragraph was to describe the relationship between pulse pressure and handgrip strength. The latter is in fact the subject of the paper. Both the two variables increase with aging, but even Authors do not consider this as the only explanation. It should be emphasized that few previous references are reported (Coelho [37], Ohara [38]), and probably the discussion on the potential mechanism should be more detailed.

Line 397 – the full citation is: Healthcare (Basel) 2020;8:458

 

Comments on the Quality of English Language

The quality of English language is almost appropriate

Author Response

Reviewer 1

 

1. Minor editing of English language required
   Answer: Thank you. I have checked the English language.

 

 

2. Abstract – Background – as there are very few data available on the relation between pulse pressure and sarcopenia (Coelho Jùnior et al, Ohara et al), and the logical connection is far from evident, the last sentence of the paragraph should rather state that the purpose of the study is to assess if this relationship does exist.

Answer: We agree your comment. We have revised the 3^rd paragraph in the introduction section.

Line 60-64: The purpose of the present study is to determine if PP and HGS are associated using data from the Korea National Health and Nutrition Examination Survey (KNHANES). To do this, the relationship between PP and clinical characteristics was examined, and changes in PP and the prevalence of weak HGS according to age and sex were identified. Finally, the correlation between PP and the prevalence of weak HGS was assessed.

 

 

3. Line 131 – in descriptive statistics standard deviation, not standard error should be used.

Answer: We appreciate your confirmation. The Korea National Health and Nutrition Examination Survey (KNHANES) is data composed of a complex sampling design including variance estimation, stratification variables, and sample weights. So, the mean and standard error was calculated instead of the commonly used mean and standard deviation.

Line 69-71: This study was conducted using data from the 2014-2020 KNHANES, which is data composed of a complex sampling design including variance estimation, stratification variables, and sample weights.

 

 

4. Line 140 – as subjects were excluded according to study criteria, the Authors can say that 54.668 were evaluated, but only 29.482 participated in the study. So this number should appear at line 74. However the interpretation is further complicated by the fact that no one of these numbers appear in figure 1, where participants are no longer 29.482, but 17.397. The Authors should clarify and make coherent the report of numbers.

Answer: We appreciate your confirmation. The figure from another paper prepared on a similar topic was mistakenly uploaded. I have replaced it with the original Figure 1.

5. Line 157 – no percentage of patients with metabolic syndrome is reported in table 1 (even if the components are there) – see also line 221

Answer: We appreciate your observation. We have added metabolic syndrome as a variable in Table 1. However, we did not used data of metabolic syndrome as a confounding factor in Table 2 because hypertension, diabetes, and hyperlipidemia were considered overlapping with metabolic syndrome.   The table below shows the results of analysis including metabolic syndrome data.

	Model 1	Model 2	Model 3
Pulse pressure  < 40 ≥ 40, < 60  ≥ 60	Reference 1.639 (1.440-1.865)a 6.346 (5.529-7.284)a	Reference 0.950 (0.840-1.075) 1.550 (1.325-1.815)a	Reference 0.933 (0.728-1.197) 1.576 (1.121-2.215)a

 

 

 

 

 

 

Values are presented as odds ratio (95% CI); ^a: p value < 0.05; Model 1 was unadjusted; Model 2 was adjusted for age and sex; Model 3 was adjusted for age, sex, BMI, smoking status, drinking, physical activity, hypertension, diabetes, hyperlipidemia, and metabolic syndrome. Abbreviation: CI, confidence Intervals; BMI, body mass index

 

 

6. Figure 1 – in the text the values of PP are characterized as PP<40 - 40≤PP<60 - PP≥60: why here only two group are described?

Answer: Thank you for your finding. Similar to response 4, there was a mistake in uploading Figure 1. This has been corrected.

 

7. Line 174 – overall percentage of weak and strong patients should be reported; it would be useful to add this information in table 1, beyond maximum HGS.

Answer: Thank you for the comment. Reflecting your opinion, we replaced maximum HGS with the percentage of HGS in Table 1.

	PP < 40	40≤PP<60	PP ≥ 60	p value
HGS, n (%) weak normal	670 (6.6) 13591 (93.4)	1071 (11.1) 10860 (88.9)	747 (23.5) 2543 (76.5)	< 0.001

                                                      

 

8. Legend to table 2 – the exact value of p is to be reported, in place of p<0.05. Odd should be corrected to odds. It should be explicitly indicated that the handgrip strength is number of weak HGS and not a continuous variable.

Answer: Thank you for your confirming. We have added p-values in Table 2 using SPSS software.

9. Lines 241-4 – we were not able to find any data concerning relationship between handgrip strength and arterial stiffness neither in Bohannon [23] nor in Shim [24] papers.

Answer: Thank you for your observation. References [31-33] are studies of the relationship between handgrip strength and arterial stiffness. We have revised it in our manuscript. 

Line 249-252: Among these, HGS, which indicates skeletal muscle strength [2], is a key factor of sarcopenia and is used as a biomarker, which is consistent in explaining bone mineral density, fracture, quality of life, diabetes, arterial stiffness, cardiovascular disease, and all-cause mortality [23-34].

 

 

10. Line 267 – “Comprehensively, the association between PP and HGS can serve as a clinically valuable method for PP monitoring, which is an inexpensive and noninvasive measurement 268 tool for identifying people with low muscular strength” – measurement of handgrip strength is inexpensive and noninvasive, so it is difficult to propose pulse pressure as a surrogate. The discussion emphasizes the role of pulse pressure as useful functional and prognostic variable. In similar fashion the role of handgrip strength is reported. The discussion would result easier for the reader if the two topics were included in separated paragraphs, and then a further paragraph was to describe the relationship between pulse pressure and handgrip strength. The latter is in fact the subject of the paper. Both the two variables increase with aging, but even Authors do not consider this as the only explanation. It should be emphasized that few previous references are reported (Coelho [37], Ohara [38]), and probably the discussion on the potential mechanism should be more detailed.

Answer: We appreciate your comments. As you mentioned, we described that PP may be a useful functional and prognostic variable in low muscle strength, and we divided the HGS and PP sections and discussed the relationship between PP and HGS in the PP section. We also emphasized that few studies have yet confirmed the relationship between PP and HGS. In addition, the potential mechanism for the relationship between PP and HGS could not be described in more detail due to the lack of evidence supporting it. Lastly, we have discussed that muscle strength is influenced not only by PP but also by aging, poor nutrition, lack of exercise, and hormone deficiency. Thus, longitudinal study is required to determine the causal relationship of muscle strength caused by PP.

Line 264-279: High PP, which is strongly correlated with arterial stiffness and predicts atheroscle-rosis-related complications, is also positively correlated with coronary heart disease, heart failure, overall cardiovascular events, and cardiovascular mortality [10, 35, 36]. Although both PP and sarcopenia are associated with cardiovascular disease, few studies have yet confirmed the relationship between PP and HGS [37, 38]. It found that in comparison to older women without sarcopenia, high PP in those with sarcopenia was related to poor muscle function and high cardiovascular risk [37]. Ohara et al. found a significant negative correlation between PP and HGS in 1,593 middle-aged to older participants without a history of symptomatic cardiovascular events such as coronary heart disease, peripheral arterial disease, stroke, or congestive heart failure [38]. Consistent with these findings, high PP was associated with weak HGS in the Korean population (Table 2). Therefore, high PP may be a risk factor for sarcopenia.

Comprehensively, the association between PP and HGS indicates that PP may be a useful functional and prognostic variable in low muscle strength. Early detection of in-creased PP may allow for intervention at the right time, including the management of malnutrition and exercise, to prevent sarcopenia and improve overall health.

Line 306-308: Muscle strength is influenced not only by PP but also by aging, poor nutrition, lack of exercise, frailty syndrome [42-44], and hormone deficiency. Therefore, longitudinal study is required to determine the causal relationship of muscle strength caused by PP.

 

12. Line 397 – the full citation is: Healthcare (Basel) 2020;8:458 (4):458

Answer: Thank you for your comment. We have revised it.

 

 

13. Comments on the Quality of English Language The quality of English language is almost appropriate.

Answer: Thank you. We have checked the English language.

Author Response File: Author Response.docx

Reviewer 2 Report

Comments and Suggestions for Authors

The paper exhibits quite good writing quality and reader engagement. Both the title and abstract succinctly summarize the research's essence with relevant details. The introduction provides essential context, while the methods section is delineated for reproducibility. The authors present data that aligns with their approach, supported by appropriate tables. The article maintains a cohesive structure, making it easily comprehensible. Conclusions are well-founded on evidence and reasoning. Additionally, the references are thorough and current. Noteworthy aspects of the paper include its compelling topic, concise yet informative introduction, transparent methodology, clear presentation of results, a discussion that situates findings within the existing literature, and conclusions firmly based on the obtained results.

The only remarks:

Did you estimate Frail syndrome in your patients? Please discuss it; it has been noticed that subjects with Frailty have increased cardiovascular mortality; one marker of this syndrome is handgrip strength (please cite PMID: 33327401; PMID: 36121826

 

2.     How many subjects have metabolic syndrome please add that data to the table

3.     How many subjects had sarcopenia? Male or female more often presented sarcopenia in your study?

4.     How many subjects had falls?

5.     Please add the section future directions of studies  

Author Response

Reviewer 2

 

1. Did you estimate Frail syndrome in your patients? Please discuss it; it has been noticed that subjects with Frailty have increased cardiovascular mortality; one marker of this syndrome is handgrip strength (please cite PMID: 33327401; PMID: 36121826)

Answer: Thank you for your advice. We mentioned frailty syndrome in the discussion section and added references related to it.

Line 306-311: Muscle strength is influenced not only by PP but also by aging, poor nutrition, lack of exercise, frailty syndrome [42-44], and hormone deficiency. Therefore, longitudinal study is required to determine the causal relationship of muscle strength caused by PP. In addition, examining physiological pathways, such as arterial stiffness and endothelial function, will be able to deepen our comprehension of the association between these two parameters.

 

42. Cesari, M.; Leeuwenburgh, C.; Lauretani, F.; Onder, G.; Bandinelli, S.; Maraldi, C.; Guralnik, J.M.; Pahor, M.; Ferrucci, L. Frailty syndrome and skeletal muscle: results from the Invecchiare in Chianti study. Am J Clin Nutr 2006, 83, 1142-1148
43. Jakubiak, G.K.; Pawlas, N.; Cieślar, G.; Stanek, A. Chronic Lower Extremity Ischemia and Its Association with the Frailty Syn-drome in Patients with Diabetes. Int J Environ Res Public Health 2020, 17, doi:10.3390/ijerph17249339.
44. Liu, X.; Tou, N.X.; Gao, Q.; Gwee, X.; Wee, S.L.; Ng, T.P. Frailty and risk of cardiovascular disease and mortality. PLoS One 2022, 17, e0272527

 

2. How many subjects have metabolic syndrome please add that data to the table.

Answer: Thank you for your comment. We have added and analyzed data of metabolic syndrome in Table 1.

 

3. How many subjects had sarcopenia? Male or female more often presented sarcopenia in your study?

Answer:

	Male	Female	p value
Weak HGS, n (%)	712 (8.3)	1779 (11.5)	< 0.001

Chi-share test, Values are presented as number (weighted percentage)

4. How many subjects had falls?

Answer: We appreciated your comment. This study collected and analyzed information from the years 2014-2020. In the survey conducted in 2019-2020, participants were asked if they had experienced repetitive falls. However, as the survey only asked about repetitive falls and not about any falls experienced, it is considered insufficient to evaluate falls comprehensively. Nevertheless, within the subset of participants from 2019-2020, those who experienced repetitive falls are as follows.

	PP < 40	40≤PP<60	PP ≥ 60	p value
Recurrent falls, n (%)	7 (0.2)	19 (0.7)	10 (1.5)	< 0.001

 

5. Please add the section future directions of studies  

Answer: Thank you for your comment. We have added future directions of studies in the manuscript.

Line 305-311: 4.3. Future directions of studies

Muscle strength is influenced not only by PP but also by aging, poor nutrition, lack of exercise, frailty syndrome [42-44], and hormone deficiency. Therefore, longitudinal study is required to determine the causal relationship of muscle strength caused by PP. In addi-tion, examining physiological pathways, such as arterial stiffness and endothelial func-tion, will be able to deepen our comprehension of the association between these two pa-rameters.

Author Response File: Author Response.docx