Modification effect of ideal cardiovascular health metrics on genetic association with incident heart failure in the China Kadoorie Biobank and the UK Biobank
Authors: Yang Ruotong , Lv Jun , Yu Canqing , Guo Yu , Pei Pei , Huang Ninghao , Yang Ling , Millwood Iona Y. , Walters Robin G. , Chen Yiping , Du Huaidong , Tao Ran , Chen Junshi , Chen Zhengming , Clarke Robert , Huang Tao , Li Liming ,   on behalf of the China Kadoorie Biobank Collaborative Group, Chen Junshi , Chen Zhengming , Clarke Robert , Collins Rory , Guo Yu , Li Liming , Lv Jun , Peto Richard , Walters Robin , Avery Daniel , Boxall Ruth , Bennett Derrick , Chang Yumei , Chen Yiping , Chen Zhengming , Clarke Robert , Du Huaidong , Gilbert Simon , Hacker Alex , Hill Mike , Holmes Michael , Iona Andri , Kartsonaki Christiana , Kerosi Rene , Kong Ling , Kurmi Om , Lancaster Garry , Lewington Sarah , Lin Kuang , McDonnell John , Millwood Iona , Nie Qunhua , Radhakrishnan Jayakrishnan , Ryder Paul , Sansome Sam , Schmidt Dan , Sherliker Paul , Sohoni Rajani , Stevens Becky , Turnbull Iain , Walters Robin , Wang Jenny , Wang Lin , Wright Neil , Yang Ling , Yang Xiaoming , Guo Yu , Han Xiao , Hou Can , Lv Jun , Pei Pei , Liu Chao , Yu Canqing , Pang Zengchang , Gao Ruqin , Li Shanpeng , Wang Shaojie , Liu Yongmei , Du Ranran , Zang Yajing , Cheng Liang , Tian Xiaocao , Zhang Hua , Zhai Yaoming , Ning Feng , Sun Xiaohui , Li Feifei , Lv Silu , Wang Junzheng , Hou Wei , Zeng Mingyuan , Jiang Ge , Zhou Xue , Yang Liqiu , He Hui , Yu Bo , Li Yanjie , Xu Qinai , Kang Quan , Guo Ziyan , Wang Dan , Hu Ximin , Chen Jinyan , Fu Yan , Fu Zhenwang , Wang Xiaohuan , Weng Min , Guo Zhendong , Wu Shukuan , Li Yilei , Li Huimei , Fu Zhifang , Wu Ming , Zhou Yonglin , Zhou Jinyi , Tao Ran , Yang Jie , Su Jian , Liu Fang , Zhang Jun , Hu Yihe , Lu Yan , Ma Liangcai , Tang Aiyu , Zhang Shuo , Jin Jianrong , Liu Jingchao , Tang Zhenzhu , Chen Naying , Huang Ying , Li Mingqiang , Meng Jinhuai , Pan Rong , Jiang Qilian , Lan Jian , Liu Yun , Wei Liuping , Zhou Liyuan , Wang Ningyu Chen Ping , Meng Fanwen , Qin Yulu , Wang Sisi , Wu Xianping , Zhang Ningmei , Chen Xiaofang , Zhou Weiwei , Luo Guojin , Li Jianguo , Chen Xiaofang , Zhong Xunfu , Liu Jiaqiu , Sun Qiang , Ge Pengfei , Ren Xiaolan , Dong Caixia , Zhang Hui , Mao Enke , Wang Xiaoping , Wang Tao , Zhang Xi , Zhang Ding , Zhou Gang , Feng Shixian , Chang Liang , Fan Lei , Gao Yulian , He Tianyou , Sun Huarong , He Pan , Hu Chen , Zhang Xukui , Wu Huifang , He Pan , Yu Min , Hu Ruying , Wang Hao , Qian Yijian , Wang Chunmei , Xie Kaixu , Chen Lingli , Zhang Yidan , Pan Dongxia , Gu Qijun , Huang Yuelong , Chen Biyun , Yin Li , Liu Huilin , Fu Zhongxi , Xu Qiaohua , Xu Xin , Zhang Hao , Long Huajun , Li Xianzhi , Zhang Libo , Qiu Zhe 
Published: October 2021

Abstract
Background
Both genetic and cardiovascular factors contribute to the risk of developing heart failure (HF), but whether idea cardiovascular health metrics (ICVHMs) offset the genetic association with incident HF remains unclear.

Objectives
To investigate the genetic association with incident HF as well as the modification effect of ICVHMs on such genetic association in Chinese and British populations.

Methods
An ICVHMs based on smoking, drinking, physical activity, diets, body mass index, waist circumference, blood pressure, blood glucose, and blood lipids, and a polygenic risk score (PRS) for HF were constructed in the China Kadoorie Biobank (CKB) of 96,014 participants and UK Biobank (UKB) of 335,782 participants which were free from HF and severe chronic diseases at baseline.

Results
During the median follow-up of 11.38 and 8.73 years, 1451 and 3169 incident HF events were documented in CKB and UKB, respectively. HF risk increased monotonically with the increase of PRS per standard deviation (CKB: hazard ratio [HR], 1.19; 95% confidence interval [CI], 1.07, 1.32; UKB: 1.07; 1.03, 1.11; P for trend < 0.001). Each point increase in ICVHMs was associated with 15% and 20% lower risk of incident HF in CKB (0.85; 0.81, 0.90) and UKB (0.80; 0.77, 0.82), respectively. Compared with unfavorable ICVHMs, favorable ICVHMs was associated with a lower HF risk, with 0.71 (0.44, 1.15), 0.41 (0.22, 0.77), and 0.48 (0.30, 0.77) in the low, intermediate, and high genetic risk in CKB and 0.34 (0.26, 0.44), 0.32 (0.25, 0.41), and 0.37 (0.28, 0.47) in UKB (P for multiplicative interaction > 0.05). Participants with low genetic risk and favorable ICVHMs, as compared with high genetic risk and unfavorable ICVHMs, had 56~72% lower risk of HF (CKB 0.44; 0.28, 0.70; UKB 0.28; 0.22, 0.37). No additive interaction between PRS and ICVHMs was observed (relative excess risk due to interaction was 0.05 [−0.22, 0.33] in CKB and 0.04 [−0.14, 0.22] in UKB).

Conclusions
In CKB and UKB, genetic risk and ICVHMs were independently associated with the risk of incident HF, which suggested that adherence to favorable cardiovascular health status was associated with a lower HF risk among participants with all gradients of genetic risk.