Meng Gao, Jun Lv, Canqing Yu, Yu Guo, Zheng Bian, Ruotong Yang, Huaidong Du, Ling Yang, Yiping Chen, Zhongxiao Li, Xi Zhang, Junshi Chen, Lu Qi, Zhengming Chen, Tao Huang , Liming Li
Metabolically healthy obesity (MHO) and its transition to unhealthy metabolic status have been associated with risk of cardiovascular disease (CVD) in Western populations. However, it is unclear to what extent metabolic health changes over time and whether such transition affects risks of subtypes of CVD in Chinese adults. We aimed to examine the association of metabolic health status and its transition with risks of subtypes of vascular disease across body mass index (BMI) categories.
Cardiovascular disease (CVD) is a leading cause of death and disability worldwide and contributes to more than 17 million deaths annually, especially 8.4 million CVD deaths across Brazil, Russia, India, China, and South Africa (BRICS) in 2016. Obesity and its related metabolic disorders have been major risk factors for CVD globally, including in China. However, people with obesity have variability in metabolic factors. It has been reported that a subset of individuals with obesity do not develop metabolic disorders and are described as having metabolically healthy obesity (MHO), though most Western studies suggested MHO is not an absolute healthy status for diabetes and CVD.
The CKB cohort was established in 10 (5 urban and 5 rural) regions geographically spread across China. The study design, methods, and participants have been described in detail previously. Briefly, a total of 512,715 participants aged 30 to 79 years old were enrolled in the study during 25 June 2004 to 15 July 2008, and the participation rate was about 30%. Two periodic resurveys were conducted in 2008 and during 4 August 2013 to 18 September 2014, on approximately 5% of randomly chosen surviving participants using administrative unit as the basic sampling unit
Our findings show that in Chinese adults, MHO individuals had an 8% higher risk of developing MVE, 34% higher risk of IHD, and 11% higher risk of stroke, with no association found with MCE. Our data show that the risk of all types of vascular disease in metabolically unhealthy individuals was much higher across BMI categories. These associations were similar in male and female but slightly attenuated in older people. These results supported the notion that obesity remains an independent risk factor for vascular disease. Our data further suggest that metabolic health changes over time across BMI categories. Particularly, stable unhealthy obesity substantially increased the risks of all types of vascular disease, with much higher risk than did the transition from healthy to unhealthy obesity.
In summary, our study shows that obesity, even without metabolic syndrome, is still an important risk factor for major vascular disease independent of these common metabolic disorders in Chinese adults. Our findings also support that recommendations for vascular prevention should highlight the importance of metabolic health maintenance across all BMI groups among Chinese adults. Importantly, our data suggest that metabolic health is a transient state for a large proportion of Chinese adults, with highest vascular risk for those who remain unhealthily obese. Closer attention should be paid to definition of metabolic health and its transition over time.
The most important acknowledgment is to the participants in the study and the members of the survey teams in each of the 10 regional centers, as well as to the project development and management teams based at Beijing, Oxford, and the 10 regional centers. The members of the CKB collaborative group are as follows: International Steering Committee: Junshi Chen, Zhengming Chen (PI), Robert Clarke, Rory Collins, Yu Guo, Liming Li (PI), Jun Lv, Richard Peto, Robin Walters. International Coordinating Centre, Oxford: Daniel Avery, Ruth Boxall, Derrick Bennett, Yumei Chang, Yiping Chen, Zhengming Chen, Robert Clarke, Huaidong Du, Simon Gilbert, Alex Hacker, Mike Hill, Michael Holmes, Andri Iona, Christiana Kartsonaki, Rene Kerosi, Ling Kong, Om Kurmi, Garry Lancaster, Sarah Lewington, Kuang Lin, John McDonnell, Iona Millwood, QunhuaNie, JayakrishnanRadhakrishnan, Paul Ryder, Sam Sansome, Dan Schmidt, Paul Sherliker, RajaniSohoni, Becky Stevens, Iain Turnbull, Robin Walters, Jenny Wang, Lin Wang, Neil Wright, Ling Yang, Xiaoming Yang. National Coordinating Centre, Beijing: Zheng Bian, Yu Guo, Xiao Han, Can Hou, Jun Lv, Pei Pei, Chao Liu, Canqing Yu. 10 Regional Coordinating Centers: Qingdao CDC: Zengchang Pang, Ruqin Gao, Shanpeng Li, Shaojie Wang, Yongmei Liu, Ranran Du, YajingZang, Liang Cheng, Xiaocao Tian, Hua Zhang, YaomingZhai, Feng Ning, Xiaohui Sun, Feifei Li. Licang CDC: SiluLv, Junzheng Wang, Wei Hou. Heilongjiang Provincial CDC: Mingyuan Zeng, Ge Jiang, Xue Zhou. Nangang CDC: Liqiu Yang, Hui He, Bo Yu, Yanjie Li, QinaiXu,Quan Kang, ZiyanGuo. Hainan Provincial CDC: Dan Wang, Ximin Hu, Jinyan Chen, Yan Fu, Zhenwang Fu, Xiaohuan Wang. Meilan CDC: Min Weng, ZhendongGuo, ShukuanWu,Yilei Li, Huimei Li, Zhifang Fu. Jiangsu Provincial CDC: Ming Wu, Yonglin Zhou, Jinyi Zhou, Ran Tao, Jie Yang, Jian Su. Suzhou CDC: Fang liu, Jun Zhang, Yihe Hu, Yan Lu, Liangcai Ma, Aiyu Tang, Shuo Zhang, JianrongJin, Jingchao Liu. Guangxi Provincial CDC: Zhenzhu Tang, Naying Chen, Ying Huang. Liuzhou CDC: Mingqiang Li, JinhuaiMeng, Rong Pan, Qilian Jiang, Jian Lan,Yun Liu, Liuping Wei, Liyuan Zhou, Ningyu Chen Ping Wang, FanwenMeng, Yulu Qin, Sisi Wang. Sichuan Provincial CDC: Xianping Wu, Ningmei Zhang, XiaofangChen,Weiwei Zhou. Pengzhou CDC: Guojin Luo, Jianguo Li, Xiaofang Chen, XunfuZhong, Jiaqiu Liu, Qiang Sun. Gansu Provincial CDC: Pengfei Ge, Xiaolan Ren, Caixia Dong. Maiji CDC: Hui Zhang, Enke Mao, Xiaoping Wang, Tao Wang, Xi zhang. Henan Provincial CDC: Ding Zhang, Gang Zhou, Shixian Feng, Liang Chang, Lei Fan. Huixian CDC: YulianGao, Tianyou He, Huarong Sun, Pan He, Chen Hu, Xukui Zhang, Huifang Wu, Pan He. Zhejiang Provincial CDC: Min Yu, Ruying Hu, Hao Wang. Tongxiang CDC: Yijian Qian, Chunmei Wang, KaixuXie, Lingli Chen, Yidan Zhang, Dongxia Pan, QijunGu. Hunan Provincial CDC: Yuelong Huang, Biyun Chen, Li Yin, Huilin Liu, Zhongxi Fu, Qiaohua Xu. Liuyang CDC: Xin Xu, Hao Zhang, Huajun Long, Xianzhi Li, Libo Zhang, ZheQiu.
Citation: Gao M, Lv J, Yu C, Guo Y, Bian Z, Yang R, et al. (2020) Metabolically healthy obesity, transition to unhealthy metabolic status, and vascular disease in Chinese adults: A cohort study. PLoS Med 17(10): e1003351. https://doi.org/10.1371/journal.pmed.1003351
Editor: WeipingJia, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, CHINA
Received: February 26, 2020; Accepted: September 11, 2020; Published: October 30, 2020
Copyright: © 2020 Gao et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Data Availability: Details of how to access China Kadoorie Biobank data and details of the data release schedule are available from www.ckbiobank.org/site/Data+Access.
Funding: LL and JL received grants (2016YFC0900500, 2016YFC0900501, 2016YFC0900504, 2016YFC1303904) from the National Key R&D Program of China. TH received grants (2019YFC2003400) from the National Key R&D Program of China. ZMC received grants from the UK Wellcome Trust (212946/Z/18/Z, 202922/Z/16/Z, 104085/Z/14/Z, 088158/Z/09/Z); LL and JL received grants from National Natural Science Foundation of China (91846303, 91843302, 81390540, 81390541, 81390544), and Chinese Ministry of Science and Technology (2011BAI09B01). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Competing interests: The authors have declared that no competing interests exist.
Abbreviations: BMI, body mass index; BRICS, Brazil, Russia, India, China, and South Africa; CDC, Center for Disease Control and Prevention; CI, confidence interval; CKB, China Kadoorie Biobank; CVD, cardiovascular disease; HR, hazard ratio; IHD, ischemic heart disease; MCE, major coronary event; MHN, metabolically healthy normal weight; MHO, metabolically healthy obesity; MHOO, metabolically healthy overweight or obesity; MUN, metabolically unhealthy normal weight; MUO, metabolically unhealthy obesity; MUOO, metabolically unhealthy overweight or obesity; MVE, major vascular events; RPG, random plasma glucose.