Title: High muscular fitness has a powerful protective cardiometabolic effect in adults: Influence of weight status

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Author s response to reviews Title: High muscular fitness has a powerful protective cardiometabolic effect in adults: Influence of weight status Authors: Robinson Ramírez-Vélez (robin640@hotmail.com) Jorge Correa-Bautista (jorge.correa@urosario.edu.co) Felipe Lobelo (flobelo@hotmail.com) Mikel Izquierdo (mikel.izquierdo@gmail.com) Alicia Alonso-Martínez (amalonsoma@gmail.com) Fernando Rodríguez-Rodríguez (fernando.rodriguez@ucv.cl) Carlos Cristi-Montero (carlos.cristi.montero@gmail.com) Version: 1 Date: 30 Aug 2016 Author s response to reviews: Bogota 30th August 2016 Dr. Hossein Khosravi Boroujeni BMC Public Health Ref. Reply Editor. BMC Public Health - PUBH-D-16-02197

Dear Dr. Hossein: We are re-submitting a revised version of our manuscript after addressing the areas of concern highlighted by the reviewers and taking into account their suggestions and comments. The changes of the manuscript are visible by using red highlighted text. In this cover letter the reviewer s comments are answered point-by-point. We appreciate the thoroughness with which the reviewers regarded our paper and hope that the article may now be suitable for publication in the BMC Public Health Journal. We look forward to your reply. Yours sincerely. The authors Reviewer #1: Paper on the association of muscular strength with several metabolic and anthropometric variables in a Latin American population. I have some considerations, which I would like the authors to address: Major points: 1. The population is stated in the title of the paper and in the conclusions as "young university students". However, there is no mentioning of the population being university students in the Methods section. Also the populations mean age is stated as app. 30 years in the Methods section (range 18-40 years). This can hardly be labelled "young" and I believe it is an unusually high age for university students. Could the authors please elaborate on this matter in the Methods section, or remove "young university students" from the title and conclusion.

A: Thank you for the positive feedback regarding our study, as well as the constructive input. We agree with this comment and we have removed this sentence "young university students" from title and conclusion. Also, we have left only university student in the rest of the document. 2. Muscular fitness is used interchangeably with muscular strength in this paper, and in the Discussion section "strength training" and its effect on health is mentioned. According to the Methods section, muscular strength is measured as hand grip strength. Very few people will probably actively train their hand grip strength, and hand grip strength may in my opinion be seen merely as an indication of good health / muscular strength - and not important on its own. I believe that the Discussion section would benefit from a more clear distinction between handgrip strength (which is measured in this study) and muscular fitness per se. A: A brief clarification has been added in discussion as well as a new reference (Wind, 2010) which explains the relationship between Handgrip strength and overall strength. 3. Minor points: Abstract, L. 7: Please state the abbreviation of body mass index here insted of in line 17. 4. L. 56: I do not understand the meaning of this line - could you please rephrase. A: Thank you, we have rephrased the line 56. 5. Methods, p. 5, L. 12: Please state if the subjects were compensated for their participation in any way. "methods" section. Volunteers were not compensated for their participation. 6. Measures, p. 7: Please move the description of z-scores to the statistical analysis section.

A: Thank you for this recommendation. We have included the description of z-scores to the statistical analysis section. 7. Discussion in general: Please state what ethnic group the studies that you refer to are from. "methods" section. This sentence is now on Page 11, line 14 to 18. 8. Discussion, p.9, L. 3: Please omit "the importance of" in the first sentence. You have demonstrated an association - not that it is an important one in any respect. 9. p. 11, L. 39: Please elaborate on the "... present a series of indices that favor their health,..." - it is unclear what you mean. A: Thank you, this sentence have been clarified. 10. Table 1: Please explain the abbreviation MBP. 11. Please give the smoking prevalence (%) for the three groups. Reviewer #2: The paper addresses a topic of interest, however, with the available data a more robust data analysis could be performed. In some aspects the paper also lacks clarity. Here are some issues that may improve the manuscript quality:

1. The paper needs an English language editing. There are some wrong sentences - just as an example, the conclusion in the abstract (page 2, lines 53-56). A: Thank you for this recommendation. English style was revised. Plase see Reading- Service.com Editorial Certification 2. Along the manuscript authors sometimes refer to the strength relative to the body weight (MF/BM) simply as MF. Does the tertiles of MF refer to the MF/BF tertiles? Please correct that along to text for coherence and accuracy. A: Thanks for detecting this inconsistency. We have checked to maintain consistency throughout the manuscript. 3. In the abstract, should the abbreviation FM/BM be MF/BM (page 2, lines 41-47)? A: Thanks for detecting this inconsistency. We have checked to maintain consistency throughout the manuscript. 4. The objective described at the end of the introduction (page 4, lines 27-32) is not completely in accordance to the one presented in the abstract. There is no reference to the role of BMI. A: Thanks for detecting this inconsistency. We have rephrased the objective. 5. I think table 1 should just be mentioned in the results section, and not in the methods (page 5, lines 10-12). 6. Please revise the description about LDL-c estimation. "400mg/dL"??

7. About CMRSI, authors refer that "The odds ratio for elevated metabolic risk score - "clustered risk" - was defined as 1 SD above the age and sex-specific meanš", but any analysis with ORs is presented in the paper. A: Thanks for detecting this inconsistency. The sentence has been removed. 8. Regarding the statistical analysis, it is not clear how the ANCOVA model was performed. Was the model run in each of the BMI strata, testing the effect of MF/BF on each of the outcomes (CMRSI and LMCRI)?? Or was it computed in each strata of MF/BF? In the abstract results for both comparisons are presented, but it is not clear for what comparison does the p- values in table 2 refer to. And why are P<0.001 presented in the abstract, and in the results section and Table 2 only p<0.05 are described? A: Thanks. The P<0.05 has been changed by P<0.001 A: We have rephrased the ANCOVA model. 9. The test used for comparisons in table 1 is not described in the statistical analysis section. "methods" section. ANOVA test was used to examine any significant difference by BMI group. 10. Results section is not well presented. Please provide a proper description of the results in table 1. A more clear presentation of the results in table 2 is also required. A: Thank you. We have rephrased the results section.

11. If two scores about cardiometabolic health were computed (LMCRI and CMRSI), why using the specific components in all analyses? The advantages and limitations of these scores should be also discussed. A: Thank you. We have included the following sentence in the "discussion" section. This sentence is now on Page 10, line 13 to 21. 12. Did the authors considered to run a linear regression model for the two outcomes (LMCRI and CMRSI)? Or a binary logistic regression? And did the authors test the effect of other potential confounders, such as sex, family history of CVD, etcš? A: Thank you for this recommendation. We appreciate you suggest to use linear regression/binary logistic model controlling for the potential confounding such as sex, family history of CVD, but not is the objective in this paper. 13. Since tertiles of muscular fitness were based on the MF corrected for body weight, please discuss the advantages and the rationale for also stratifying the analyses by BMI. Although BMI is also an indicator of adiposity, it is highly correlated with weight. So please discuss the rationale for the way the analysis were conducted. "discussion" section. This sentence is now on Page 14-15. We thank the reviewers and the editor for taking the time to review our manuscript and look forward to your response. Very sincerely yours, Mikel Izquierdo PhD.