Supplementary material Heart 1 Members of the China Kadoorie Biobank collaborative group 2 International Steering Committee: Junshi Chen, Zhengming Chen (PI), Robert Clarke, Rory 3 Collins, Yu Guo, Liming Li (PI), Jun Lv, Richard Peto, Robin Walters. International Co- 4 ordinating Centre, Oxford: Daniel Avery, Ruth Boxall, Derrick Bennett, Yumei Chang, Yiping 5 Chen, Zhengming Chen, Robert Clarke, Huaidong Du, Simon Gilbert, Alex Hacker, Mike 6 Hill, Michael Holmes, Andri Iona, Christiana Kartsonaki, Rene Kerosi, Ling Kong, Om 7 Kurmi, Garry Lancaster, Sarah Lewington, Kuang Lin, John McDonnell, Iona Millwood, 8 Qunhua Nie, Jayakrishnan Radhakrishnan, Paul Ryder, Sam Sansome, Dan Schmidt, Paul 9 Sherliker, Rajani Sohoni, Becky Stevens, Iain Turnbull, Robin Walters, Jenny Wang, Lin 10 Wang, Neil Wright, Ling Yang, Xiaoming Yang. National Co-ordinating Centre, Beijing: 11 Zheng Bian, Yu Guo, Xiao Han, Can Hou, Jun Lv, Pei Pei, Chao Liu, Yunlong Tan, Canqing 12 Yu. 10 Regional Co-ordinating Centres: Qingdao CDC: Zengchang Pang, Ruqin Gao, 13 Shanpeng Li, Shaojie Wang, Yongmei Liu, Ranran Du, Yajing Zang, Liang Cheng, Xiaocao 14 Tian, Hua Zhang, Yaoming Zhai, Feng Ning, Xiaohui Sun, Feifei Li. Licang CDC: Silu Lv, 15 Junzheng Wang, Wei Hou. Heilongjiang Provincial CDC: Mingyuan Zeng, Ge Jiang, Xue 16 Zhou. Nangang CDC: Liqiu Yang, Hui He, Bo Yu, Yanjie Li, Qinai Xu,Quan Kang, Ziyan 17 Guo. Hainan Provincial CDC: Dan Wang, Ximin Hu, Jinyan Chen, Yan Fu, Zhenwang Fu, 18 Xiaohuan Wang. Meilan CDC: Min Weng, Zhendong Guo, Shukuan Wu,Yilei Li, Huimei Li, 19 Zhifang Fu. Jiangsu Provincial CDC: Ming Wu, Yonglin Zhou, Jinyi Zhou, Ran Tao, Jie Yang, 20 Jian Su. Suzhou CDC: Fang liu, Jun Zhang, Yihe Hu, Yan Lu, , Liangcai Ma, Aiyu Tang, 21 Shuo Zhang, Jianrong Jin, Jingchao Liu. Guangxi Provincial CDC: Zhenzhu Tang, Naying 22 Chen, Ying Huang. Liuzhou CDC: Mingqiang Li, Jinhuai Meng, Rong Pan, Qilian Jiang, Jian 23 Lan,Yun Liu, Liuping Wei, Liyuan Zhou, Ningyu Chen Ping Wang, Fanwen Meng, Yulu Qin,, 24 Sisi Wang. Sichuan Provincial CDC: Xianping Wu, Ningmei Zhang, Xiaofang Chen,Weiwei 25 Zhou. Pengzhou CDC: Guojin Luo, Jianguo Li, Xiaofang Chen, Xunfu Zhong, Jiaqiu Liu, 26 Qiang Sun. Gansu Provincial CDC: Pengfei Ge, Xiaolan Ren, Caixia Dong. Maiji CDC: Hui 27 Zhang, Enke Mao, Xiaoping Wang, Tao Wang, Xi zhang. Henan Provincial CDC: Ding 1 Meng R, et al. Heart 2020; 106:213–220. doi: 10.1136/heartjnl-2019-315750 Supplementary material Heart 1 Zhang, Gang Zhou, Shixian Feng, Liang Chang, Lei Fan. Huixian CDC: Yulian Gao, Tianyou 2 He, Huarong Sun, Pan He, Chen Hu, Xukui Zhang, Huifang Wu, Pan He. Zhejiang Provincial 3 CDC: Min Yu, Ruying Hu, Hao Wang. Tongxiang CDC: Yijian Qian, Chunmei Wang, Kaixu 4 Xie, Lingli Chen, Yidan Zhang, Dongxia Pan, Qijun Gu. Hunan Provincial CDC: Yuelong 5 Huang, Biyun Chen, Li Yin, Huilin Liu, Zhongxi Fu, Qiaohua Xu. Liuyang CDC: Xin Xu, 6 Hao Zhang, Huajun Long, Xianzhi Li, Libo Zhang, Zhe Qiu. 7 2 Meng R, et al. Heart 2020; 106:213–220. doi: 10.1136/heartjnl-2019-315750 Supplementary material Heart 1 Figure Legends 2 Supplementary figure 1. Assessment of famine exposure 3 The upper and lower time axes show the definitions of the Chinese Great famine and famine 4 exposure subgroups (based on birth), separately. Lines between two time axes present a nine- 5 month gestation period. 6 7 Pre-famine Famine Post-famine 1/1/1956-12/31/1957 1/1/1959-12/31/1960 1/1/1962-12/31/1963 1956 1957 1958 1959 1960 1961 1962 1963 1964 1965 1955 1965 1956 1957 1958 1959 1960 1961 1962 1963 1964 1965 1955 1965 Pre-famine births Famine births Post-famine births 10/1/1956-9/30/1958 10/1/1959-9/30/1961 10/1/1965-9/30/1964 Non-famine births (10/1/1956-9/30/1958 & 10/1/1965-9/30/1964) 8 9 10 3 Meng R, et al. Heart 2020; 106:213–220. doi: 10.1136/heartjnl-2019-315750 Supplementary material Heart 1 Supplementary table 1. Baseline characteristics of 92,284 participants according to three 2 famine exposure subgroups Post-famine Famine Pre-famine births births births No. of participants 39,698 19,794 32,792 Age at baseline, year 43.0 46.0 48.9 Men, % 37.8 39.1 40.2 Rural area, % 56.5 50.1 54.4 Middle school and above, % 77.8 69.6 56.5 Married, % 95.4 94.8 94.5 Daily smoking, % 27.6 29.1 29.4 Daily alcohol consumption, % 8.0 9.3 10.0 Physical activity, MET-hour/day 25.9 25.2 23.9 Average weekly consumption*, day Red meat 4.0 3.9 3.8 Fresh vegetables 6.9 6.9 6.9 Fresh fruits 2.8 2.7 2.6 Family history of, % Heart attack 3.8 4.1 4.1 Stroke 18.3 20.3 20.6 Cancer 16.9 18.6 18.9 Postmenopausal women, % 4.4 12.1 35.1 BMI, kg/m2 23.8 24.0 24.0 WHR 0.87 0.88 0.88 Hypertension, % 21.1 25.1 29.9 Diabetes, % 2.9 4.4 4.4 3 Abbreviations: MET indicates metabolic equivalent of task; BMI, body mass index; WHR, 4 Meng R, et al. Heart 2020; 106:213–220. doi: 10.1136/heartjnl-2019-315750 Supplementary material Heart 1 waist-to-hip ratio. 2 The results are presented as adjusted means or percentages, with adjustment for sex and study 3 area, as appropriate. 4 *Average weekly consumptions of fresh fruits, vegetables, and red meat were calculated by 5 assigning participants to the midpoint of their consumption category. 6 5 Meng R, et al. Heart 2020; 106:213–220. doi: 10.1136/heartjnl-2019-315750 Supplementary material Heart 1 Supplementary table 2. HRs (95% CIs) for association between early famine exposure and 2 ischemic heart disease according to potential baseline risk factors Non-famine Famine births births Pinteraction Cases HR Cases HR (95% CIs) Ischemic heart disease Daily smoking 0.953 No 2,430 1.00 794 1.07 (0.98, 1.16) Yes 1,045 1.00 357 1.07 (0.94, 1.21) Daily alcohol consumption 0.843 No 3,196 1.00 1,054 1.07 (0.99, 1.15) Yes 279 1.00 97 1.05 (0.82, 1.34) Physical activity, MET-hour/day 0.003 <22.7 1,978 1.00 682 1.15 (1.05, 1.26) ≥22.7 1,497 1.00 469 0.97 (0.87, 1.08) BMI, kg/m2 0.623 <24.0 1,538 1.00 500 1.09 (0.98, 1.21) ≥24.0 1,937 1.00 651 1.05 (0.96, 1.15) WHR 0.148 Men <0.90, women <0.85 1,430 1.00 472 1.01 (0.91, 1.13) Men ≥0.90, women ≥0.85 2,045 1.00 679 1.10 (1.01, 1.21) Hypertension 0.509 No 2,214 1.00 744 1.04 (0.96, 1.14) Yes 1,261 1.00 407 1.10 (0.98, 1.24) Diabetes 0.459 No 3,239 1.00 1,065 1.07 (1.00, 1.15) Yes 236 1.00 86 1.05 (0.80, 1.36) 6 Meng R, et al. Heart 2020; 106:213–220. doi: 10.1136/heartjnl-2019-315750 Supplementary material Heart Non-famine Famine births births Pinteraction Cases HR Cases HR (95% CIs) Major coronary events Daily smoking 0.966 No 165 1.00 51 1.09 (0.79, 1.52) Yes 225 1.00 74 1.12 (0.85, 1.48) Daily alcohol consumption 0.205 No 337 1.00 102 1.06 (0.84, 1.34) Yes 53 1.00 23 1.41 (0.84, 2.38) Physical activity, MET-hour/day 0.286 <22.7 198 1.00 69 1.22 (0.92, 1.64) ≥22.7 192 1.00 56 1.00 (0.73, 1.37) BMI, kg/m2 0.973 <24.0 178 1.00 54 1.13 (0.82, 1.56) ≥24.0 212 1.00 71 1.11 (0.83, 1.47) WHR 0.046 Men <0.90, women <0.85 143 1.00 32 0.74 (0.50, 1.11) Men ≥0.90, women ≥0.85 247 1.00 93 1.32 (1.03, 1.70) Hypertension 0.870 No 197 1.00 65 1.10 (0.82, 1.49) Yes 193 1.00 60 1.11 (0.82, 1.50) Diabetes 1.000 No 352 1.00 110 1.12 (0.89, 1.40) Yes 38 1.00 15 1.09 (0.57, 2.08) 1 Abbreviations: HR indicates hazard ratio; CI, confidence interval; and MET, metabolic 2 equivalent of task, BMI, body mass index; WHR, waist-to-hip ratio. 7 Meng R, et al. Heart 2020; 106:213–220. doi: 10.1136/heartjnl-2019-315750 Supplementary material Heart 1 Multivariable model was adjusted for sex (men or women), education (no formal school, 2 primary school, middle school, high school, college, or university or higher), marital status 3 (married, widowed, divorced or separated, or never married), smoking (never smoker, former 4 smoker who had quit for reasons other than illness, current smoker or former smoker who had 5 quit because of illness: 1-14, 15-24, or ≥25 cigarettes or equivalent tobacco per day), alcohol 6 consumption (non-weekly drinker, former weekly drinker, weekly drinker, daily drinker: <15, 7 15-29, 30-59, or ≥60 grams of pure alcohol), physical activity (MET-hour/day), intakes of 8 fruits, vegetables, and red meat (day/week; calculated by assigning participants to the 9 midpoint of their consumption category), family history of heart attack, stroke, or cancer 10 (presence or absence; only adjusted for in corresponding analysis of specific diseases), 11 menopausal status (premenopausal, perimenopausal, or postmenopausal; for women only), 12 BMI, WHR, and prevalent hypertension and diabetes at baseline (presence or absence), as 13 appropriate.