Conventional and genetic associations of BMI with major vascular and non-vascular disease incidence and mortality in a relatively lean Chinese population: U-shaped relationship revisited
Authors: Iona Andri , Bragg Fiona , Fairhurst-Hunter Zammy , Millwood Iona Y , Wright Neil , Lin Kuang , Yang Ling , Du Huaidong , Chen Yiping , Pei Pei , Cheng Liang , Schmidt Dan , Avery Daniel , Yu Canqing , Lv Jun , Clarke Robert , Walters Robin , Li Liming , Parish Sarah , Chen Zhengming ,   China Kadoorie Biobank Collaborative Group, Chen Junshi , Chen Zhengming , Clarke Robert , Collins Rory , Guo Yu , Li Liming , Wang Chen , Lv Jun , Peto Richard , Walters Robin , Avery Daniel , Bennett Derrick , Boxall Ruth , Chan Ka Hung , Chang Yumei , Chen Yiping , Chen Zhengming , Clarke Johnathan , Clarke Robert , Du Huaidong , Mohamed Ahmed Edris , Fairhurst-Hunter Zammy , Fry Hannah , Gilbert Simon , Hacker Alex , Hill Mike , Holmes Michael , Im Pek Kei , Iona Andri , Kakkoura Maria , Kartsonaki Christiana , Lin Kuang , Mazidi Mohsen , Millwood Iona , Morris Sam , Nie Qunhua , Pozarickij Alfred , Ryder Paul , Said Saredo , Sansome Sam , Schmidt Dan , Sherliker Paul , Sohoni Rajani , Stevens Becky , Turnbull Iain , Walters Robin , Wang Lin , Wright Neil , Yang Ling , Yang Xiaoming , Yao Pang , Guo Yu , Han Xiao , Hou Can , Xia Qingmei , Liu Chao , Lv Jun , Pei Pei , Yu Canqing , Chen Naying , Liu Duo , Tang Zhenzhu , Chen Ningyu , Jiang Qilian , Lan Jian , Li Mingqiang , Liu Yun , Meng Fanwen , Meng Jinhuai , Pan Rong , Qin Yulu , Wang Ping , Wang Sisi , Wei Liuping , Zhou Liyuan , Dong Caixia , Ge Pengfei , Ren Xiaolan , Li Zhongxiao , Mao Enke , Wang Tao , Zhang Hui , Zhang Xi , Chen Jinyan , Hu Ximin , Wang Xiaohuan , Guo Zhendong , Li Huimei , Li Yilei , Weng Min , Wu Shukuan , Yan Shichun , Zou Mingyuan , Zhou Xue , Guo Ziyan , Kang Quan , Li Yanjie , Yu Bo , Xu Qinai , Chang Liang , Fan Lei , Feng Shixian , Zhang Ding , Zhou Gang , Gao Yulian , He Tianyou , He Pan , Hu Chen , Sun Huarong , Zhang Xukui , Chen Biyun , Fu Zhongxi , Huang Yuelong , Liu Huilin , Xu Qiaohua , Yin Li , Long Huajun , Xu Xin , Zhang Hao , Zhang Libo , Su Jian , Tao Ran , Wu Ming , Yang Jie , Zhou Jinyi , Zhou Yonglin , Hu Yihe , Hua Yujie , Liu Jianrong Jin Fang , Liu Jingchao , Lu Yan , Ma Liangcai , Tang Aiyu , Zhang Jun , Cheng Liang , Du Ranran , Gao Ruqin , Li Feifei , Li Shanpeng , Liu Yongmei , Ning Feng , Pang Zengchang , Sun Xiaohui , Tian Xiaocao , Wang Shaojie , Zhai Yaoming , Zhang Hua , Hou Wei , Lv Silu , Wang Junzheng , Chen Xiaofang , Wu Xianping , Zhang Ningmei , Zhou Weiwei , Chen Xiaofang , Li Jianguo , Liu Jiaqiu , Luo Guojin , Sun Qiang , Zhong Xunfu , Gong Weiwei , Hu Ruying , Wang Hao , Wan Meng , Yu Min , Chen Lingli , Gu Qijun , Pan Dongxia , Wang Chunmei , Xie Kaixu , Zhang Xiaoyi , Li Shuya , Qin Haiqiang , Wang Yongjun , Chen Qiling , Wang Jihua , Sun Xiaojia , Wang Lei , Wang Xun , Zhang Liming , Zhou Shanshan , Chen Hongyuan , Chen Li , Gou Haiyan , Wang Weizhi , Zhu Yanmei , Zhu Yulan , Zhang Ning , Cheng Xin , Dong Qiang , Dong Yi , Fang Kun , Mao Yiting , An Yu , Chen Peiling , Chen Yinghua , Liu Zhihong , Chen Lihua Zhang Xiaohong , Jv Naixin , Li Xiaojiu , Liu Liyang , Lu Yun , Xing Xiaona , You Shihao , Cheng Xiaoli , Gua Chaojun , Jiang Jinping , Liu Jingyi , Ma Shumei , Yang Xuefeng , Du Xiaomo , Xu Jian , Yang Xuecheng , Zhao Xiaodi , Hao Zilong , Liu Ming , Wang Deren , Li Xiaoting , Hui Lili , Liao Zhanling , Liu Feng , Feng Chunning , Ji Dejiang , Qu Fengxia , Yuan Wenwen , Fu Xin , Ding Jing , Du Peng , Jin Lirong , Mao Yueshi , Wang Xin 
Published: October 2024

Abstract

Background
Higher body mass index (BMI) is associated with higher incidence of cardiovascular and some non-cardiovascular diseases (CVDs/non-CVDs). However, uncertainty remains about its associations with mortality, particularly at lower BMI levels.

Methods
The prospective China Kadoorie Biobank recruited &gt;512 000 adults aged 30–79 years in 2004–08 and genotyped a random subset of 76 000 participants. In conventional and Mendelian randomization (MR) analyses, Cox regression yielded adjusted hazard ratios (HRs) associating measured and genetically predicted BMI levels with incident risks of major vascular events (MVEs; conventional/MR 68 431/23 621), ischaemic heart disease (IHD; 50 698/12 177), ischaemic stroke (IS; 42 427/11 897) and intracerebral haemorrhage (ICH; 7644/4712), and with mortality risks of CVD (15 427/6781), non-CVD (26 915/4355) and all causes (42 342/6784), recorded during ∼12 years of follow-up.

Results
Overall, the mean BMI was 23.8 (standard deviation: 3.2) kg/m2 and 13% had BMIs of &lt;20 kg/m2. Measured and genetically predicted BMI showed positive log-linear associations with MVE, IHD and IS, but a shallower positive association with ICH in conventional analyses. Adjusted HRs per 5 kg/m2 higher genetically predicted BMI were 1.50 (95% CI 1.41–1.58), 1.49 (1.38–1.61), 1.42 (1.31–1.54) and 1.64 (1.58–1.69) for MVE, IHD, IS and ICH, respectively. These were stronger than associations in conventional analyses [1.21 (1.20–1.23), 1.28 (1.26–1.29), 1.31 (1.29–1.33) and 1.14 (1.10–1.18), respectively]. At BMIs of ≥20 kg/m2, there were stronger positive log-linear associations of BMI with CVD, non-CVD and all-cause mortality in MR than in conventional analyses.

Conclusions
Among relatively lean Chinese adults, higher genetically predicted BMI was associated with higher risks of incident CVDs. Excess mortality risks at lower BMI in conventional analyses are likely not causal and may reflect residual reverse causality.