中国成年人肥胖相关体格测量指标、吲哚类分子与动脉粥样硬化性心血管疾病的前瞻性队列研究

司佳卉; 程思; 余灿清; 孙点剑一; 庞元捷; 裴培; 杜怀东; 陈君石; 陈铮鸣; 李立明; 吕筠

Abstract

司佳卉,程思,余灿清,孙点剑一,庞元捷,裴培,杜怀东,陈君石,陈铮鸣,李立明,吕筠.中国成年人肥胖相关体格测量指标、吲哚类分子与动脉粥样硬化性心血管疾病的前瞻性队列研究[J].Chinese journal of Epidemiology,2025,46(1):65-72

中国成年人肥胖相关体格测量指标、吲哚类分子与动脉粥样硬化性心血管疾病的前瞻性队列研究

Adiposity-related anthropometric parameters, indoles and atherosclerotic cardiovascular disease in Chinese adults: a prospective cohort study

Received:June 03, 2024

DOI：10.3760/cma.j.cn112338-20240603-00325

KeyWord: 动脉粥样硬化性心血管疾病体格测量指标吲哚类分子

English Key Word: Atherosclerotic cardiovascular disease Anthropometric measurement Indoles

FundProject:国家自然科学基金（82404348，82192901，82192900，82388102）；重大疾病流行病学教育部重点实验室（北京大学）开放基金（2024102）；英国Wellcome Trust （212946/Z/18/Z，202922/Z/16/Z，104085/Z/14/Z，088158/Z/09/Z）；中国香港Kadoorie Charitable基金

Author Name	Affiliation	E-mail
Si Jiahui	CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences (CAS), Beijing 100101, China
Cheng Si	Department of Epidemiology and Biostatistics, School of Public Health, Peking University, Beijing 100191, China
Yu Canqing	Department of Epidemiology and Biostatistics, School of Public Health, Peking University, Beijing 100191, China Peking University Center for Public Health and Epidemic Preparedness & Response, Beijing 100191, China Key Laboratory of Epidemiology of Major Diseases (Peking University), Ministry of Education, Beijing 100191, China
Sun Dianjianyi	Department of Epidemiology and Biostatistics, School of Public Health, Peking University, Beijing 100191, China Peking University Center for Public Health and Epidemic Preparedness & Response, Beijing 100191, China Key Laboratory of Epidemiology of Major Diseases (Peking University), Ministry of Education, Beijing 100191, China
Pang Yuanjie	Department of Epidemiology and Biostatistics, School of Public Health, Peking University, Beijing 100191, China Peking University Center for Public Health and Epidemic Preparedness & Response, Beijing 100191, China Key Laboratory of Epidemiology of Major Diseases (Peking University), Ministry of Education, Beijing 100191, China
Pei Pei	Peking University Center for Public Health and Epidemic Preparedness & Response, Beijing 100191, China
Du Huaidong	Clinical Trial Service Unit and Epidemiological Studies Unit, Nuffield Department of Population Health, University of Oxford, Oxford OX3 7LF, United Kingdom
Chen Junshi	China National Center for Food Safety Risk Assessment, Beijing 100022, China
Chen Zhengming	Clinical Trial Service Unit and Epidemiological Studies Unit, Nuffield Department of Population Health, University of Oxford, Oxford OX3 7LF, United Kingdom
Li Liming	Department of Epidemiology and Biostatistics, School of Public Health, Peking University, Beijing 100191, China Peking University Center for Public Health and Epidemic Preparedness & Response, Beijing 100191, China Key Laboratory of Epidemiology of Major Diseases (Peking University), Ministry of Education, Beijing 100191, China
Lyu Ju	Department of Epidemiology and Biostatistics, School of Public Health, Peking University, Beijing 100191, China Peking University Center for Public Health and Epidemic Preparedness & Response, Beijing 100191, China Key Laboratory of Epidemiology of Major Diseases (Peking University), Ministry of Education, Beijing 100191, China State Key Laboratory of Vascular Homeostasis and Remodeling, Peking University, Beijing 100191, China	lvjun@bjmu.edu.cn

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Abstract:

目的探讨中国成年人肥胖相关体格测量指标（BMI、腰围、腰臀比及体脂率）与血浆中吲哚类分子以及吲哚类分子与新发动脉粥样硬化性心血管疾病（ASCVD）的关联。方法基于中国慢性病前瞻性研究（CKB），利用其中2 183名研究对象在2008年第一次重复调查时采集的血样检测吲哚类分子。测量研究对象2004年基线及2008年重复调查时的体重、身高、腰围、臀围及体脂率，BMI和腰臀比通过标准方法进行计算。对所有研究对象的长期随访自2008年重复调查完成开始，直到出现新发ASCVD、死亡、失访或到2018年12月31日为止。CKB通过多种途径获取发病和死亡信息，包括死亡和常规疾病监测系统、医疗保险数据库以及主动的定向监测。利用多元线性回归模型估计基线、第一次重复调查及基线至第一次重复调查体格测量指标的变化率与3种吲哚类分子（吲哚、3-吲哚乙酸、3-吲哚丙酸）的关联；利用Cox比例风险回归模型估计3种吲哚类分子与ASCVD发病风险的关联。结果基线或第一次重复调查的体格测量指标与血浆3-吲哚丙酸呈负相关，基线BMI每增加1.0 kg/m²与3-吲哚丙酸每增加0.1个标准差关联的回归系数（β）值（95%CI）为-0.23（-0.36~-0.10）（错误发现率=0.004）。调整基线BMI后，基线腰围、腰臀比及体脂率每增加1个单位与3-吲哚丙酸每增加0.1个标准差关联的β值（95%CI）依次为-0.09（-0.18~-0.01）、-0.12（-0.19~-0.05）及-0.20（-0.32~-0.08）。BMI变化率（2008年与2004年BMI之差除以调查间隔）与吲哚及3-吲哚乙酸每增加0.1个标准差关联的β值（95%CI）为1.40（0.58~2.21）及-1.07（-1.91~-0.23）。研究对象随访时间M（Q₁，Q₃）为10.46（10.36，10.53）年，新发ASCVD 236名。3-吲哚乙酸及3-吲哚丙酸与ASCVD发病风险存在负关联，3-吲哚乙酸及3-吲哚丙酸每增加1个标准差，ASCVD发病的HR值（95%CI）为0.87（0.76~0.99）及0.84（0.73~0.96）。结论体格测量指标及其变化影响血浆中吲哚类分子水平，3-吲哚乙酸和3-吲哚丙酸水平降低与ASCVD发病风险增加有关，3-吲哚乙酸、3-吲哚丙酸可能是肥胖导致ASCVD的中介因素。

English Abstract:

Objective To investigate the relationship of several adiposity-related anthropometric parameters, including BMI, waist circumference (WC), waist-to-hip ratio (WHR), body fat percentage (BFP) and indoles in plasma with the incidence of atherosclerotic cardiovascular disease (ASCVD) in adults in China. Methods In China Kadoorie Biobank (CKB) study, blood samples were collected from 2 183 participants in the first resurvey in 2008 to detect indoles. Participants' body weight, body height, WC, hip circumference, and BFP were measured at baseline survey in 2004 and resurvey in 2008, the BMI and WHR were calculated with standardized methods. The long-term follow-up of all participants started from the completion of the resurvey in 2008 until the occurrence of incident ASCVD, death, loss to follow-up or until December 31, 2018. CKB ascertained outcome status (incident ASCVD) through death and disease registries and national health insurance databases, supplemented by active follow-up. Multivariate linear regression model was used to estimate the associations of anthropometric measurements at baseline survey and the first resurvey, and changes in these measurements with 3 indoles [indole, indole-3-acetic acid (IAA), and indole-3-propionic acid (IPA)]. Cox proportional hazard regression model was used to estimate the associations between indoles and the risk for ASCVD. Results Anthropometric measurements at baseline survey or the first resurvey were negatively associated with plasma IPA level. The regression coefficient (β) of baseline BMI (per 1.0 kg/m²) with 0.1 standard deviation (SD) IPA was -0.23 (95%CI: -0.36 - -0.10) (false discovery rate=0.004). After adjusting for baseline BMI, the β of baseline WC, WHR and BFP with 0.1 SD IPA were -0.09 (95%CI: -0.18 - -0.01), -0.12 (95%CI: -0.19 - -0.05), and -0.20 (95%CI: -0.32 - -0.08), respectively. The annual change in BMI (difference between BMI in 2008 and 2004 divided by the time interval) was associated with indole and IAA, with β of 1.40 (95%CI: 0.58 - 2.21) and -1.07 (95%CI: -1.91 - -0.23), respectively, at each 0.1 increase of SD. Over a median (Q₁, Q₃) follow-up of 10.46 (10.36, 10.53) years after 2008 resurvey, 236 cases of ASCVD were recorded. IAA and IPA levels were negatively associated with the risk for ASCVD, with hazard ratios for one SD increase of IAA and IPA of 0.87 (95%CI: 0.76 - 0.99) and 0.84 (95%CI: 0.73 - 0.96), respectively. Conclusions Our results suggested that anthropometric measurements and their changing trends affect the levels of plasma imicrobial tryptophan metabolite levels, decreased levels of IAA and IPA levels are associated with increased risk of ASCVD and indoles in plasma including IPA and IAA might be the mediating factors for adiposity-induced ASCVD.

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