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BMJ Open Is Committed to Open Peer Review. As Part of This Commitment We Make the Peer Review History of Every Article We Publish Publicly Available BMJ Open: first published as 10.1136/bmjopen-2019-029179 on 7 November 2019. Downloaded from BMJ Open is committed to open peer review. As part of this commitment we make the peer review history of every article we publish publicly available. When an article is published we post the peer reviewers’ comments and the authors’ responses online. We also post the versions of the paper that were used during peer review. These are the versions that the peer review comments apply to. The versions of the paper that follow are the versions that were submitted during the peer review process. They are not the versions of record or the final published versions. They should not be cited or distributed as the published version of this manuscript. BMJ Open is an open access journal and the full, final, typeset and author-corrected version of record of the manuscript is available on our site with no access controls, subscription charges or pay-per-view fees (http://bmjopen.bmj.com). If you have any questions on BMJ Open’s open peer review process please email [email protected] http://bmjopen.bmj.com/ on September 26, 2021 by guest. Protected copyright. BMJ Open BMJ Open: first published as 10.1136/bmjopen-2019-029179 on 7 November 2019. Downloaded from Contribution of serum lipids as effect modifiers to a relationship between mean arterial pressure and coronary heart disease in Chinese rural population: The Henan Rural Cohort Study ForJournal: peerBMJ Open review only Manuscript ID bmjopen-2019-029179 Article Type: Research Date Submitted by the 15-Jan-2019 Author: Complete List of Authors: Zhang, Xia ; College of Public Health, Zhengzhou University, Department of Epidemiology and Biostatistics Li, Yuqian; Department of Clinical Pharmacology, School of Pharmaceutical Science, Zhengzhou University, Zhengzhou, Henan, PR. China, Wang, Yanhua; The First Affiliated Hospital of Henan University of Traditional Chinese Medicine Encephalopathy District Hu, Kai ; Henan Academy of Medical Sciences Tu, Runqi ; College of Public Health, Zhengzhou University, Department of Epidemiology and Biostatistics Zhang, Haiqing; College of Public Health, Zhengzhou University, Department of Epidemiology and Biostatistics http://bmjopen.bmj.com/ Tian, zhongyan; College of Public Health, Zhengzhou University, Department of Epidemiology and Biostatistics Qiao, Dou ; Department of Epidemiology and Biostatistics, College of Public Health, Zhengzhou University Zhang, Gongyuan ; Department of Epidemiology and Biostatistics, College of Public Health, Zhengzhou University Wang, Chongjian; Zhengzhou University, Department of Epidemiology and Biostatistics, College of Public Health on September 26, 2021 by guest. Protected copyright. Coronary heart disease < CARDIOLOGY, Mean arterial pressure, Serum Keywords: lipids, Rural population For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml Page 1 of 23 BMJ Open 1 2 3 BMJ Open: first published as 10.1136/bmjopen-2019-029179 on 7 November 2019. Downloaded from 4 Title: 5 6 Contribution of serum lipids as effect modifiers to a relationship between mean arterial pressure 7 8 and coronary heart disease in Chinese rural population: The Henan Rural Cohort Study 9 Short title: 10 11 Mean arterial pressure and coronary heart disease 12 13 Authors: 14 15 Xia Zhang1†, Yuqian Li2†, Yanhua Wang3, Kai Hu4, Runqi Tu1, Haiqing Zhang1, Zhongyan Tian1, 16 17 Dou Qiao1, Gongyuan Zhang1, Chongjian Wang1* 18 For peer review only 19 Authors affiliations: 20 21 1 Department of Epidemiology and Biostatistics, College of Public Health, Zhengzhou University, 22 23 Zhengzhou, Henan, PR China. 24 25 2 Department of Clinical Pharmacology, School of Pharmaceutical Science, Zhengzhou University, 26 27 Zhengzhou, Henan, PR China. 28 29 3 Department of encephalopathy, The First Affiliated Hospital of Henan University of 30 31 Traditional Chinese Medicine, Zhengzhou, Henan, PR China. 32 33 4 Henan Academy of Medical Sciences, Zhengzhou, Henan, PR China. 34 35 † Xia Zhang and Yuqian Li contributed equally to this work. 36 37 http://bmjopen.bmj.com/ 38 * Correspondence author 39 40 Dr. Chongjian Wang 41 42 Department of Epidemiology and Biostatistics 43 44 College of Public Health, Zhengzhou University 45 on September 26, 2021 by guest. Protected copyright. 46 100 Kexue Avenue, Zhengzhou, 450001, Henan, PR China 47 48 Phone: +86 371 67781452; 49 50 Fax: +86 371 67781919 51 52 E-mail: [email protected] 53 54 55 56 57 58 59 60 1 For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml BMJ Open Page 2 of 23 1 2 3 BMJ Open: first published as 10.1136/bmjopen-2019-029179 on 7 November 2019. Downloaded from 4 Ethics approval 5 6 Ethics approval was obtained from the “Zhengzhou University Life Science Ethics Committee”, 7 8 and written informed consent was obtained for all participants. Ethic approval code: [2015] MEC 9 (S128) 10 11 12 13 Competing interests 14 15 The authors have declared that no competing interests exist. 16 17 18 For peer review only 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 http://bmjopen.bmj.com/ 38 39 40 41 42 43 44 45 on September 26, 2021 by guest. Protected copyright. 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 2 For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml Page 3 of 23 BMJ Open 1 2 3 BMJ Open: first published as 10.1136/bmjopen-2019-029179 on 7 November 2019. Downloaded from 4 Abstract 5 6 Objectives: The aim was to evaluate the relationship between mean arterial pressure (MAP) and 7 8 coronary heart disease (CHD) in Chinese rural population. In addition, we hypothesized that this 9 10 relationship might be mediated by some degree of serum lipids. 11 12 Design: Cross-sectional study. 13 14 Setting: The participants were originated from The Henan Rural Cohort Study, which was 15 16 launched in five rural areas (Tongxu county of Kaifeng city, Yima county of Sanmenxia city, 17 18 Suiping county ofFor Zhumadian peer city, Xinxiang review county of Xinxiang only city and Yuzhou county of 19 20 Xuchang city) in Henan province, China, during July 2015 and September 2017. 21 22 Participants: Including 39020 subjects aged 18 to 79 years as present research population. 23 24 Outcome measures: Systolic blood pressure (SBP) and diastolic blood pressure (DBP) was 25 26 measured by using electronic sphygmomanometer. MAP was calculated by one-third SBP plus 27 28 two thirds DBP. Restricted cubic splines and logistic regression models were used to evaluate the 29 30 odds ratios (ORs) and 95% confidence intervals (CIs). Mediation analysis using bootstrap was 31 32 performed to examine the contribution of serum lipids to MAP - related CHD. 33 34 Results: The adjusted OR (95%CI) for the highest MAP quartile with the risk of CHD was 35 1.45(1.24-1.69) compared with the lowest quartile. Simultaneously, each 1 standard deviation 36 37 http://bmjopen.bmj.com/ increment in MAP was significantly associated with a 12% increased risk of CHD. A linear 38 39 dose-response relationship between MAP and CHD as was found (P for non-linear =0.1169) in 40 41 the fully adjusted model. We further reported that 36.07% proportion explained risk of CHD was 42 43 mediated through serum lipids. 44 45 Conclusions: Increased MAP was a significant marker of CHD in Chinese rural population. on September 26, 2021 by guest. Protected copyright. 46 47 Meanwhile, the relationship was mediated by some degree of serum lipids, and triglyceride was a 48 49 main mediator. 50 51 Clinical Trial Registration 52 53 The Henan Rural Cohort study has been registered at Chinese Clinical Trial Register (Registration 54 55 number: ChiCTR-OOC-15006699). http://www.chictr.org.cn/showproj.aspx?proj=11375 56 57 Keywords: Coronary heart disease; Mean arterial pressure; Serum lipids; Rural population 58 59 60 3 For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml BMJ Open Page 4 of 23 1 2 3 BMJ Open: first published as 10.1136/bmjopen-2019-029179 on 7 November 2019. Downloaded from 4 Strengths and limitations of this study 5 6 Focusing on the rural population includes the relatively large sample size. 7 8 The present study had rigorous design and various statistical methods. 9 10 11 Elevated MAP was significantly associated with the risk of CHD. 12 13 14 The first one to explore the association was mediated by some degree of serum lipids. 15 16 The causal association between MAP and CHD was not established in this cross-sectional 17 18 analysis. For peer review only 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 http://bmjopen.bmj.com/ 38 39 40 41 42 43 44 45 on September 26, 2021 by guest. Protected copyright. 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 4 For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml Page 5 of 23 BMJ Open 1 2 3 BMJ Open: first published as 10.1136/bmjopen-2019-029179 on 7 November 2019. Downloaded from 4 Introduction 5 6 Cardiovascular diseases (CVDs) are the major challenge for sustainable human development 1. 7 8 Globally, the number of deaths attributed to CVD has been increased from 12.59 million to 17.92 9 10 million from 1990 to 2015 2. In China, there were around 42% increasing within 25 years 3. 11 12 Studies have shown that coronary heart disease (CHD) accounts for a large proportion of all CVD 13 14 cases 2. According to the “China Health and Family Planning Statistical Yearbook 2016”, in 2015, 15 16 the mortality of CHD has increased significantly in rural areas, which was slightly higher than that 17 18 in urban areas by 2015For 4.
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