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1. One-size-fits-all versus risk-category-based screening interval strategies for cardiovascular disease prevention in Chinese adults: a prospective cohort studyResearch in context

Author

Zhijia Sun, Yu Ma, Canqing Yu, Dianjianyi Sun, Yuanjie Pang, Pei Pei, Ling Yang, Yiping Chen, Huaidong Du, Hao Zhang, Xiaoming Yang, Maxim Barnard, Robert Clarke, Junshi Chen, Zhengming Chen, Liming Li, Jun Lv, Rory Collins, Richard Peto, Robin Walters, Daniel Avery, Derrick Bennett, Lazaros Belbasis, Ruth Boxall, Ka Hung Chan, Charlotte Clarke, Johnathan Clarke, Ahmed Edris Mohamed, Hannah Fry, Simon Gilbert, Pek Kei Im, Andri Iona, Maria Kakkoura, Christiana Kartsonaki, Hubert Lam, Kuang Lin, James Liu, Mohsen Mazidi, Iona Millwood, Sam Morris, Qunhua Nie, Alfred Pozarickij, Maryanm Rahmati, Paul Ryder, Saredo Said, Dan Schmidt, Becky Stevens, Iain Turnbull, Baihan Wang, Lin Wang, Neil Wright, Pang Yao, Xiao Han, Can Hou, Qingmei Xia, Chao Liu, Lang Pan, Zengchang Pang, Ruqin Gao, Shanpeng Li, Haiping Duan, Shaojie Wang, Yongmei Liu, Ranran Du, Yajing Zang, Liang Cheng, Xiaocao Tian, Hua Zhang, Yaoming Zhai, Feng Ning, Xiaohui Sun, Feifei Li, Silu Lv, Junzheng Wang, Wei Hou, Wei Sun, Shichun Yan, Xiaoming Cui, Chi Wang, Zhenyuan Wu, Yanjie Li, Quan Kang, Huiming Luo, Tingting Ou, Xiangyang Zheng, Zhendong Guo, Shukuan Wu, Yilei Li, Huimei Li, Ming Wu, Yonglin Zhou, Jinyi Zhou, Ran Tao, Jie Yang, Jian Su. Fang Liu, Jun Zhang, Yihe Hu, Yan Lu, Liangcai Ma, Aiyu Tang, Shuo Zhang, Jianrong Jin, Jingchao Liu, Mei Lin, Zhenzhen Lu, Lifang Zhou, Changping Xie, Jian Lan, Tingping Zhu, Yun Liu, Liuping Wei, Liyuan Zhou, Ningyu Chen, Yulu Qin, Sisi Wang, Xianping Wu, Ningmei Zhang, Xiaofang Chen, Xiaoyu Chang, Mingqiang Yuan, Xia Wu, Wei Jiang, Jiaqiu Liu, Qiang Sun, Faqing Chen, Xiaolan Ren, Caixia Dong, Hui Zhang, Enke Mao, Xiaoping Wang, Tao Wang, Xi Zhang, Kai Kang, Shixian Feng, Huizi Tian, Lei Fan, XiaoLin Li, Huarong Sun, Pan He, Xukui Zhang, Min Yu, Ruying Hu, Hao Wang, Xiaoyi Zhang, Yuan Cao, Kaixu Xie, Lingli Chen, Dun Shen, Xiaojun Li, Donghui Jin, Li Yin, Huilin Liu, Zhongxi Fu, Xin Xu, Jianwei Chen, Yuan Peng, Libo Zhang, and Chan Qu

Subjects
Cardiovascular disease, Screening, Primary prevention, Public aspects of medicine, RA1-1270
Abstract

Summary: Background: In non-high-risk individuals, risk-category-based atherosclerotic cardiovascular disease (ASCVD) screening strategies may be more cost-effective than one-size-fits-all approaches. However, current decisions are constrained by a lack of research evidence. We aimed to explore appropriate risk-category-based screening interval strategies for non-high-risk individuals in ASCVD primary prevention in the Chinese population. Methods: We used data from 28,624 participants in the China Kadoorie Biobank (CKB) who had completed at least two field surveys. The risk assessment tools were the 10-year ASCVD risk prediction models developed based on the CKB cohort. We constructed multistate Markov models to model disease progression and estimate transition probabilities between different risk categories. The total person-years spent unidentified in the high-risk state over a 10-year period were calculated for each screening interval protocol. We also estimated the number of ASCVD events prevented, quality-adjusted life years (QALYs) gained, and costs saved when compared to the 3-yearly screening protocol. Findings: When compared to the uniform 3-yearly protocol, most risk-category-based screening interval protocols would identify more high-risk individuals timely, thus preventing more ASCVD events and gaining QALYs. A few of them would reduce total health-care costs. The protocol, which used 6-year, 3-year, and 2-year screening intervals for low-risk, intermediate-low-risk, and intermediate-high risk individuals, was optimal, and would reduce the person-years spent unidentified in the high-risk category by 17.9% (95% CI: 13.1%–21.9%), thus preventing an estimated 113 thousand (95% CI: 83–138) hard ASCVD events for Chinese adults aged 30–79 over a 10-year period. When using a lower cost of statin therapy, more screening protocols would gain QALYs while saving costs. Interpretation: For the primary prevention of ASCVD, risk-category-based screening protocols outperformed the one-size-fits-all approach in the Chinese population. Funding: This work was supported by National Natural Science Foundation of China (82192904, 82388102, 82192900) and grants (2023YFC2509400) from the National Key R&D Program of China. The CKB baseline survey and the first re-survey were supported by a grant from the Kadoorie Charitable Foundation in Hong Kong. The long-term follow-up is supported by grants from the UK Wellcome Trust (212946/Z/18/Z, 202922/Z/16/Z, 104085/Z/14/Z, 088158/Z/09/Z), grants (2016YFC0900500) from the National Key R&D Program of China, National Natural Science Foundation of China (81390540, 91846303, 81941018), and Chinese Ministry of Science and Technology (2011BAI09B01).

Published
2024
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2. Association between health insurance cost-sharing and choice of hospital tier for cardiovascular diseases in China: a prospective cohort studyResearch in context

Author

Muriel Levy, John Buckell, Robert Clarke, Nina Wu, Pei Pei, Dianjianyi Sun, Daniel Avery, Hua Zhang, Jun Lv, Canqing Yu, Liming Li, Zhengming Chen, Winnie Yip, Yiping Chen, Borislava Mihaylova, Junshi Chen, Rory Collins, Chen Wang, Richard Peto, Robin Walters, Maxim Barnard, Derrick Bennett, Ruth Boxall, Kahung Chan, Johnathan Clarke, Huaidong Du, Ahmed Edris Mohamed, Hannah Fry, Simon Gilbert, Pek Kei Im, Andri Iona, Maria Kakkoura, Christiana Kartsonaki, Hubert Lam, Kuang Lin, James Liu, Mohsen Mazidi, Iona Millwood, Sam Morris, Qunhua Nie, Alfred Pozaricki, Paul Ryder, Saredo Said, Dan Schmidt, Becky Stevens, Iain Turnbull, Baihan Wang, Lin Wang, Neil Wright, Ling Yang, Xiaoming Yang, Pang Yao, Xiao Han, Can Hou, Qingmei Xia, Chao Liu, Naying Chen, Duo Liu, Zhenzhu Tang, Ningyu Chen, Qilian Jiang, Jian Lan, Mingqiang Li, Yun Liu, Fanwen Meng, Jinhuai Meng, Rong Pan, Yulu Qin, Ping Wang, Sisi Wang, Liuping Wei, Liyuan Zhou, Caixia Dong, Pengfei Ge, Xiaolan Ren, Zhongxiao Li, Enke Mao, Tao Wang, Hui Zhang, Xi Zhang, Jinyan Chen, Ximin Hu, Xiaohuan Wang, Zhendong Guo, Huimei Li, Yilei Li, Min Weng, Shukuan Wu, Shichun Yan, Mingyuan Zou, Xue Zhou, Ziyan Guo, Quan Kang, Yanjie Li, Bo Yu, Qinai Xu, Liang Chang, Lei Fan, Shixian Feng, Ding Zhang, Gang Zhou, Yulian Gao, Tianyou He, Pan He, Chen Hu, Huarong Sun, Xukui Zhang, Biyun Chen, Zhongxi Fu, Yuelong Huang, Huilin Liu, Qiaohua Xu, Li Yin, Huajun Long, Xin Xu, Hao Zhang, Libo Zhang, Jian Su, Ran Tao, Ming Wu, Jie Yang, Jinyi Zhou, Yonglin Zhou, Yihe Hu, Yujie Hua, Jianrong Jin, Fang Liu, Jingchao Liu, Yan Lu, Liangcai Ma, Aiyu Tang, Jun Zhang, Liang Cheng, Ranran Du, Ruqin Gao, Feifei Li, Shanpeng Li, Yongmei Liu, Feng Ning, Zengchang Pang, Xiaohui Sun, Xiaocao Tian, Shaojie Wang, Yaoming Zhai, Wei Hou, Silu Lv, Junzheng Wang, Xiaofang Chen, Xianping Wu, Ningmei Zhang, Xiaoyu Chang, Jianguo Li, Jiaqiu Liu, Guojin Luo, Qiang Sun, Xunfu Zhong, Weiwei Gong, Ruying Hu, Hao Wang, Meng Wang, Min Yu, Lingli Chen, Qijun Gu, Dongxia Pan, Chunmei Wang, Kaixu Xie, Xiaoyi Zhang, Hongyuan Chen, Liyang Liu, Haiyan Gou, Xun Wang, Jing Ding, Ning Zhang, Yueshi Mao, Shanshan Zhou, Lirong Jin, Xin Cheng, Yun Lu, Li Chen, Zilong Hao, Xiaona Xing, Lei Wang, Naixin Ju, Yiting Mao, Shuya Li, Peng Du, Deren Wang, Xiaojia Sun, Shihao You, Weizhi Wang, Yanmei Zhu, Xiaojiu Li, and Yi Dong

Subjects
Hospital type, Cardiovascular diseases, Healthcare seeking behaviour, China, Public aspects of medicine, RA1-1270
Abstract

Summary: Background: Hospitals in China are classified into tiers (1, 2 or 3), with the largest (tier 3) having more equipment and specialist staff. Differential health insurance cost-sharing by hospital tier (lower deductibles and higher reimbursement rates in lower tiers) was introduced to reduce overcrowding in higher tier hospitals, promote use of lower tier hospitals, and limit escalating healthcare costs. However, little is known about the effects of differential cost-sharing in health insurance schemes on choice of hospital tiers. Methods: In a 9-year follow-up of a prospective study of 0.5 M adults from 10 areas in China, we examined the associations between differential health insurance cost-sharing and choice of hospital tiers for patients with a first hospitalisation for stroke or ischaemic heart disease (IHD) in 2009–2017. Analyses were performed separately in urban areas (stroke: n = 20,302; IHD: n = 19,283) and rural areas (stroke: n = 21,130; IHD: n = 17,890), using conditional logit models and adjusting for individual socioeconomic and health characteristics. Findings: About 64–68% of stroke and IHD cases in urban areas and 27–29% in rural areas chose tier 3 hospitals. In urban areas, higher reimbursement rates in each tier and lower tier 3 deductibles were associated with a greater likelihood of choosing their respective hospital tiers. In rural areas, the effects of cost-sharing were modest, suggesting a greater contribution of other factors. Higher socioeconomic status and greater disease severity were associated with a greater likelihood of seeking care in higher tier hospitals in urban and rural areas. Interpretation: Patient choice of hospital tiers for treatment of stroke and IHD in China was influenced by differential cost-sharing in urban areas, but not in rural areas. Further strategies are required to incentivise appropriate health seeking behaviour and promote more efficient hospital use. Funding: Wellcome Trust, Medical Research Council, British Heart Foundation, Cancer Research UK, Kadoorie Charitable Foundation, China Ministry of Science and Technology, and National Natural Science Foundation of China.

Published
2024
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3. Causal association between snoring and stroke: a Mendelian randomization study in a Chinese populationResearch in context

Author

Yunqing Zhu, Zhenhuang Zhuang, Jun Lv, Dianjianyi Sun, Pei Pei, Ling Yang, Iona Y. Millwood, Robin G. Walters, Yiping Chen, Huaidong Du, Xianping Wu, Dan Schmidt, Daniel Avery, Junshi Chen, Zhengming Chen, Liming Li, Canqing Yu, Robert Clarke, Rory Collins, Yu Guo, Richard Peto, Robin Walter, Derrick Bennett, Ruth Boxall, Sue Burgess, Ka Hung Chan, Yumei Chang, Johnathan Clarke, Ahmed Edris Mohamed, Zammy Fairhurst-Hunter, Hannah Fry, Mike Hill, Michael Holmes, Pek Kei Im, Andri Iona, Maria Kakkoura, Christiana Kartsonaki, Rene Kerosi, Kuang Lin, Mohsen Mazidi, Iona Millwood, Sam Morris, Qunhua Nie, Alfred Pozarickij, Paul Ryder, Saredo Said, Paul Sherliker, Becky Stevens, Iain Turnbull, Robin Walters, Lin Wang, Neil Wright, Xiaoming Yang, Pang Yao, Xiao Han, Can Hou, Chao Liu, Qingmei Xia, Zengchang Pang, Ruqin Gao, Shanpeng Li, Haiping Duan, Shaojie Wang, Yongmei Liu, Ranran Du, Yajing Zang, Liang Cheng, Xiaocao Tian, Hua Zhang, Yaoming Zhai, Feng Ning, Xiaohui Sun, Feifei Li, Silu Lv, Junzheng Wang, Wei Hou, Wei Sun, Shichun Yan, Xiaoming Cui, Chi Wang, Zhenyuan Wu, Yanjie Li, Quan Kang, Huiming Luo, Tingting Ou, Xiangyang Zheng, Zhendong Guo, Shukuan Wu, Yilei Li, Huimei Li, Ming Wu, Yonglin Zhou, Jinyi Zhou, Ran Tao, Jie Yang, Jian Su, Fang Liu, Jun Zhang, Yihe Hu, Yan Lu, Liangcai Ma, Aiyu Tang, Shuo Zhang, Jianrong Jin, Jingchao Liu, Mei Lin, Zhenzhen Lu, Lifang Zhou, Changping Xie, Jian Lan, Tingping Zhu, Yun Liu, Liuping Wei, Liyuan Zhou, Ningyu Chen, Yulu Qin, Sisi Wang, Ningmei Zhang, Xiaofang Chen, Xiaoyu Chang, Mingqiang Yuan, Xia Wu, Wei Jiang, Jiaqiu Liu, Qiang Sun, Faqing Chen, Xiaolan Ren, Caixia Dong, Hui Zhang, Enke Mao, Xiaoping Wang, Tao Wang, Xi zhang, Kai Kang, Shixian Feng, Huizi Tian, Lei Fan, XiaoLin Li, Huarong Sun, Pan He, Xukui Zhang, Min Yu, Ruying Hu, Hao Wang, Xiaoyi Zhang, Yuan Cao, Kaixu Xie, Lingli Chen, Dun Shen, Xiaojun Li, Donghui Jin, Li Yin, Huilin Liu, Zhongxi Fu, Xin Xu, Hao Zhang, Jianwei Chen, Yuan Peng, Libo Zhang, and Chan Qu

Subjects
Snoring, Stroke, Body mass index, Mendelian randomization, Public aspects of medicine, RA1-1270
Abstract

Summary: Background: Previous observational studies established a positive relationship between snoring and stroke. We aimed to investigate the causal effect of snoring on stroke. Methods: Based on 82,339 unrelated individuals with qualified genotyping data of Asian descent from the China Kadoorie Biobank (CKB), we conducted a Mendelian randomization (MR) analysis of snoring and stroke. Genetic variants identified in the genome-wide association analysis (GWAS) of snoring in CKB and UK Biobank (UKB) were selected for constructing genetic risk scores (GRS). A two-stage method was applied to estimate the associations of the genetically predicted snoring with stroke and its subtypes. Besides, MR analysis among the non-obese group (body mass index, BMI

Published
2024
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4. Mortality and recurrent vascular events after first incident stroke: a 9-year community-based study of 0·5 million Chinese adults

Author

Yiping Chen, DPhil, Neil Wright, PhD, Yu Guo, MSc, Iain Turnbull, MRCP, Christiana Kartsonaki, DPhil, Ling Yang, PhD, Zheng Bian, MSc, Pei Pei, BSc, Dongxia Pan, MBBS, Yidan Zhang, BSc, Haiqiang Qin, MD, Yilong Wang, ProfMD, Jun Lv, ProfPhD, Ming Liu, MD, Zilong Hao, MD, Yongjun Wang, ProfMD, Canqing Yu, PhD, Richard Peto, ProfFRS, Rory Collins, ProfFRS, Liming Li, ProfMPH, Robert Clarke, ProfFRCP, Zhengming Chen, ProfDPhil, Yiping Chen, Neil Wright, Yu Guo, Iain Turnbull, Christiana Kartsonaki, Ling Yang, Zheng Bian, Pei Pei, Dongxia Pan, Yidan Zhang, Haiqiang Qin, Yilong Wang, Jun Lv, Ming Liu, Zilong Hao, Yongjun Wang, Canqing Yu, Richard Peto, Rory Collins, Liming Li, Robert Clarke, Zhengming Chen, Junshi Chen, Robin Walters, Daniel Avery, Derrick Bennett, Ruth Boxall, Fiona Bragg, Yumei Chang, Huaidong Du, Simon Gilbert, Alex Hacker, Michael Holmes, Rene Kerosi, Garry Lancaster, Kuang Lin, John McDonnell, Iona Millwood, Qunhua Nie, Paul Ryder, Sam Sansome, Dan Schmidt, Rajani Sohoni, Jenny Wang, Lin Wang, Xiaoming Yang, Xiao Han, Can Hou, Biao Jing, Chao Liu, Zengchang Pang, Ruqin Gao, Shanpeng Li, Shaojie Wang, Yongmei Liu, Ranran Du, Yajing Zang, Liang Cheng, Xiaocao Tian, Hua Zhang, Yaoming Zhai, Feng Ning, Xiaohui Sun, Feifei Li, Silu Lv, Junzheng Wang, Wei Hou, Mingyuan Zeng, Ge Jiang, Xue Zhou, Liqiu Yang, Hui He, Bo Yu, Yanjie Li, Qinai Xu, Quan Kang, Ziyan Guo, Dan Wang, Ximin Hu, Hongmei Wang, Jinyan Chen, Yan Fu, Zhenwang Fu, Xiaohuan Wang, Min Weng, Zhendong Guo, Shukuan Wu, Yilei Li, Huimei Li, Zhifang Fu, Ming Wu, Yonglin Zhou, Jinyi Zhou, Ran Tao, Jie Yang, Jian Su, Fang Liu, Jun Zhang, Yihe Hu, Yan Lu, Liangcai Ma, Aiyu Tang, Shuo Zhang, Jianrong Jin, Jingchao Liu, Zhenzhu Tang, Naying Chen, Ying Huang, Mingqiang Li, Jinhuai Meng, Rong Pan, Qilian Jiang, Jian Lan, Yun Liu, Liuping Wei, Ningyu Chen, Ping Wang, Fanwen Meng, Yulu Qin, Sisi Wang, Xianping Wu, Ningmei Zhang, Xiaofang Chen, Weiwei Zhou, Guojin Luo, Jianguo Li, Xunfu Zhong, Jiaqiu Liu, Qiang Sun, Pengfei Ge, Xiaolan Ren, Caixia Dong, Hui Zhang, Enke Mao, Xiaoping Wang, Tao Wang, Xi Zhang, Ding Zhang, Gang Zhou, Shixian Feng, Liang Chang, Lei Fan, Yulian Gao, Tianyou He, Huarong Sun, Pan He, Chen Hu, Xukui Zhang, Huifang Wu, Min Yu, Ruying Hu, Hao Wang, Yijian Qian, Chunmei Wang, Kaixu Xie, Lingli Chen, Zhongxi Fu, Qiaohua Xu, Xin Xu, Hao Zhang, Huajun Long, Xianzhi Li, Libo Zhang, and Zhe Qiu

Subjects
Public aspects of medicine, RA1-1270
Abstract

Summary: Background: Stroke is a leading cause of death and disability worldwide. Despite considerable improvements in diagnosis and treatment, little is known about the short-term and long-term prognosis after a first stroke in low-income and middle-income countries, including China. We aimed to assess the short-term and long-term risk of recurrent stroke and mortality after a first stroke for each of the major pathological stroke types. Methods: This population-based cohort study included adults aged 35–74 years without disability who were recruited to the China Kadoorie Biobank (CKB). A baseline survey was conducted in ten geographical areas (five urban, five rural) in China, and participants had clinical measurements recorded. Participants were followed up by monitoring death registries and by electronic linkage to health registries and health insurance claims databases, with follow-up until Jan 1, 2017. Participants were excluded from analyses if they had a previous history of stroke, transient ischaemic attack, or ischaemic heart disease at baseline. All incidences of fatal and non-fatal stroke during the study period were recorded by type (ischaemic stroke, intracerebral haemorrhage, subarachnoid haemorrhage, and unspecified type). Primary outcome measures were 28-day mortality, recurrent stroke, major vascular events (recurrent stroke, myocardial infarction, or vascular death), vascular mortality, and all-cause mortality. Findings: Of 512 715 individuals in the CKB, 489 586 participants without previous ischaemic heart disease and stroke at recruitment were included, of whom 45 732 (42 073 [92%] confirmed by brain imaging) had a stroke during the study period. The mean age was 59·3 years (SD 9·8) for participants who had a stroke (54% women) and 50·8 years (10·3) for participants with no stroke (60% women). 36 588 (80%) of the incident cases of stroke were ischaemic stroke, 7440 (16%) were intracerebral haemorrhage, 702 (2%) were subarachnoid haemorrhage, and 1002 (2%) were an unspecified stroke type. 28-day mortality was 3% (95% CI 3–4) for ischaemic stroke, 47% (46–48)for intracerebral haemorrhage, 19% (17–22; 52% for rural areas and 32% for urban areas) subarachnoid haemorrhage, and 24% (22–27) for unspecified stroke. Among participants who survived stroke at 28 days, 41% (41–42) had recurrent stroke at 5 years (ischaemic stroke 41% [41–42], intracerebral haemorrhage 44% [42–46], subarachnoid haemorrhage 22% [18–27], unspecified stroke type 40% [35–44]) and mortality at 5 years was 17% ([17–18] ischaemic stroke 16% [15–16], intracerebral haemorrhage 28% [26–29], subarachnoid haemorrhage 16% [12–20], unspecified stroke type 15% [12–19]). After a first ischaemic stroke, 91% of recurrent strokes were also ischaemic stroke; after an intracerebral haemorrhage, 56% of recurrent strokes were intracerebral haemorrhage, and 41% of recurrent strokes were ischaemic stroke. Interpretation: After a first stroke, the risk of recurrence or death within 5 years was high among this population of Chinese adults. Urgent improvements to secondary prevention of stroke in China are needed to reduce these risks. Funding: Wellcome Trust, Medical Research Council, British Heart Foundation, Cancer Research UK, Kadoorie Charitable Foundation, Chinese Ministry of Science and Technology, National Natural Science Foundation of China. Copyright: © 2020 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license.

Published
2020
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5. Cooking fuels and risk of all-cause and cardiopulmonary mortality in urban China: a prospective cohort study

Author

Kuai Yu, PhD, Jun Lv, PhD, Gaokun Qiu, PhD, Canqing Yu, PhD, Yu Guo, MSc, Zheng Bian, MSc, Ling Yang, PhD, Yiping Chen, DPhil, Chaolong Wang, ProfPhD, An Pan, ProfPhD, Liming Liang, ProfPhD, Frank B Hu, ProfPhD, Zhengming Chen, ProfDPhil, Liming Li, ProfMPH, Tangchun Wu, ProfPhD, Junshi Chen, Zhengming Chen, Robert Clarke, Rory Collins, Yu Guo, Liming Li, Jun Lv, Richard Peto, Robin Walters, Daniel Avery, Ruth Boxall, Yumei Chang, Yiping Chen, 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, Qunhua Nie, Jayakrishnan Radhakrishnan, Paul Ryder, Sam Sansome, Dan Schmidt, Paul Sherliker, Rajani Sohoni, Becky Stevens, Iain Turnbull, Jenny Wang, Lin Wang, Neil Wright, Ling Yang, Xiaoming Yang, Zheng Bian, Xiao Han, Can Hou, Pei Pei, Chao Liu, Yunlong Tan, Canqing Yu, Zengchang Pang, Ruqin Gao, Shanpeng Li, Shaojie Wang, Yongmei Liu, Ranran Du, Yajing Zang, Liang Cheng, Xiaocao Tian, Hua Zhang, Yaoming Zhai, Feng Ning, Xiaohui Sun, Feifei Li, Silu Lv, Junzheng Wang, Wei Hou, Mingyuan Zeng, Ge Jiang, Xue Zhou, Liqiu Yang, Hui He, Bo Yu, Yanjie Li, Qinai Xu, Quan Kang, Ziyan Guo, Dan Wang, Ximin Hu, Hongmei Wang, Jinyan Chen, Yan Fu, Zhenwang Fu, Xiaohuan Wang, Min Weng, Zhendong Guo, Shukuan Wu, Yilei Li, Huimei Li, Zhifang Fu, Ming Wu, Yonglin Zhou, Jinyi Zhou, Ran Tao, Jie Yang, Jian Su, Fang Liu, Jun Zhang, Yihe Hu, Yan Lu, Liangcai Ma, Aiyu Tang, Shuo Zhang, Jianrong Jin, Jingchao Liu, Zhenzhu Tang, Naying Chen, Ying Huang, Mingqiang Li, Jinhuai Meng, Rong Pan, Qilian Jiang, Jian Lan, Yun Liu, Liuping Wei, Liyuan Zhou, Ningyu Chen, Ping Wang, Fanwen Meng, Yulu Qin, Sisi Wang, Xianping Wu, Ningmei Zhang, Xiaofang Chen, Weiwei Zhou, Guojin Luo, Jianguo Li, Xunfu Zhong, Jiaqiu Liu, Qiang Sun, Pengfei Ge, Xiaolan Ren, Caixia Dong, Hui Zhang, Enke Mao, Xiaoping Wang, Tao Wang, Xi Zhang, Ding Zhang, Gang Zhou, Shixian Feng, Liang Chang, Lei Fan, Yulian Gao, Tianyou He, Huarong Sun, Pan He, Chen Hu, Xukui Zhang, Huifang Wu, Min Yu, Ruying Hu, Hao Wang, Yijian Qian, Chunmei Wang, Kaixu Xie, Lingli Chen, Yidan Zhang, Dongxia Pan, Qijun Gu, Yuelong Huang, Biyun Chen, Li Yin, Huilin Liu, Zhongxi Fu, Qiaohua Xu, Xin Xu, Hao Zhang, Huajun Long, Xianzhi Li, Libo Zhang, and Zhe Qiu

Subjects
Public aspects of medicine, RA1-1270
Abstract

Summary: Background: Cooking practice has transitioned from use of solid fuels to use of clean fuels, with addition of better ventilation facilities. However, the change in mortality risk associated with such a transition remains unclear. Methods: The China Kadoorie Biobank (CKB) Study enrolled participants (aged 30–79 years) from ten areas across China; we chose to study participants from five urban areas where transition from use of solid fuels to clean fuels for cooking was prevalent. Participants who reported regular cooking (weekly or more frequently) at baseline were categorised as persistent clean fuel users, previous solid fuel users, or persistent solid fuel users, according to self-reported fuel use histories. All-cause and cardiopulmonary mortality were identified through linkage to China's Disease Surveillance Point system and local mortality records. Findings: Between June 24, 2004, and July 15, 2008, 226 186 participants living in five urban areas of China were enrolled in the CKB Study. Among 171 677 participants who reported cooking regularly (weekly or more frequently), 75 785 (44%) were persistent clean fuel users, 80 511 (47%) were previous solid fuel users, and 15 381 (9%) were persistent solid fuel users. During a mean of 9·8 (SD 1·7) years of follow-up, 10 831 deaths were documented, including 3819 cardiovascular deaths and 761 respiratory deaths. Compared with persistent clean fuel users, persistent solid fuel users had significantly higher risks of all-cause mortality (hazard ratio [HR] 1·19, 95% CI 1·10–1·28), cardiovascular mortality (1·24, 1·10–1·39), and respiratory mortality (1·43, 1·10–1·85). The excess risk of all-cause and cardiopulmonary mortality fell by more than 60% in 5 years after cessation of solid fuel use and continued to decrease afterwards. Use of ventilation was associated with lower all-cause mortality risk, even among persistent clean fuel users (HR 0·78, 0·69–0·89). Interpretation: Solid fuel use for cooking is associated with a higher risk of mortality, and cessation of solid fuel use cuts excess mortality risks swiftly and substantially within 5 years. Ventilation use also lowers the risk of mortality, even among people who persistently use clean fuels. It is of prime importance for both policy makers and the public to accelerate the transition from solid fuels to clean fuels and promote efficient ventilation to minimise further adverse health effects. Funding: National Natural Science Foundation of China, Wellcome Trust, and Kadoorie Charitable Foundation.

Published
2020
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6. Adiposity and risk of ischaemic and haemorrhagic stroke in 0·5 million Chinese men and women: a prospective cohort study

Author

Zhengming Chen, ProfDPhil, Andri Iona, MSc, Sarah Parish, ProfDPhil, Yiping Chen, DPhil, Yu Guo, MSc, Fiona Bragg, DPhil, Ling Yang, PhD, Zheng Bian, MSc, Michael V Holmes, PhD, Sarah Lewington, DPhil, Ben Lacey, FFPH, Ruqin Gao, MSc, Fang Liu, MBBS, Zengzhi Zhang, MSc, Junshi Chen, ProfMD, Robin G Walters, PhD, Rory Collins, ProfFRS, Robert Clarke, ProfFRCP, Richard Peto, ProfFRS, Liming Li, ProfMPH, Junshi Chen, Zhengming Chen, Robert Clarke, Rory Collins, Yu Guo, Liming Li, Jun Lv, Richard Peto, Robin Walters, Daniel Avery, Derrick Bennett, Ruth Boxall, Fiona Bragg, Yumei Chang, Yiping Chen, Huaidong Du, Simon Gilbert, Alex Hacker, Michael Holmes, Andri Iona, Christiana Kartsonaki, Rene Kerosi, Om Kurmi, Sarah Lewington, Garry Lancaster, Kuang Lin, John McDonnell, Iona Millwood, Qunhua Nie, Jayakrishnan Radhakrishnan, Paul Ryder, Sam Sansome, Dan Schmidt, Paul Sherliker, Rajani Sohoni, Becky Stevens, Iain Turnbull, Jenny Wang, Lin Wang, Neil Wright, Ling Yang, Xiaoming Yang, Zheng Bian, Ge Chen, Xiao Han, Can Hou, Pei Pei, Shuzhen Qu, Yunlong Tan, Canqing Yu, Zengchang Pang, Ruqin Gao, Shaojie Wang, Yongmei Liu, Ranran Du, Yajing Zang, Liang Cheng, Xiaocao Tian, Hua Zhang, Silu Lv, Junzheng Wang, Wei Hou, Jiyuan Yin, Ge Jiang, Xue Zhou, Liqiu Yang, Hui He, Bo Yu, Yanjie Li, Huaiyi Mu, Qinai Xu, Meiling Dou, Jiaojiao Ren, Shanqing Wang, Ximin Hu, Hongmei Wang, Jinyan Chen, Yan Fu, Zhenwang Fu, Xiaohuan Wang, Min Weng, Xiangyang Zheng, Yilei Li, Huimei Li, Yanjun Wang, Ming Wu, Jinyi Zhou, Ran Tao, Jie Yang, Chuanming Ni, Jun Zhang, Yihe Hu, Yan Lu, Liangcai Ma, Aiyu Tang, Shuo Zhang, Jianrong Jin, Jingchao Liu, Zhenzhu Tang, Naying Chen, Ying Huang, Mingqiang Li, Jinhuai Meng, Rong Pan, Qilian Jiang, Weiyuan Zhang, Yun Liu, Liuping Wei, Liyuan Zhou, Ningyu Chen, Hairong Guan, Xianping Wu, Ningmei Zhang, Xiaofang Chen, Xuefeng Tang, Guojin Luo, Jianguo Li, Xunfu Zhong, Jiaqiu Liu, Qiang Sun, Pengfei Ge, Xiaolan Ren, Caixia Dong, Hui Zhang, Enke Mao, Xiaoping Wang, Tao Wang, Xi Zhang, Ding Zhang, Gang Zhou, Shixian Feng, Liang Chang, Lei Fan, Yulian Gao, Tianyou He, Huarong Sun, Pan He, Chen Hu, Qiannan Lv, Xukui Zhang, Min Yu, Ruying Hu, Hao Wang, Yijian Qian, Chunmei Wang, Kaixue Xie, Lingli Chen, Yidan Zhang, Dongxia Pan, Yuelong Huang, Biyun Chen, Li Yin, Donghui Jin, Huilin Liu, Zhongxi Fu, Qiaohua Xu, Xin Xu, Hao Zhang, Youping Xiong, Huajun Long, Xianzhi Li, Libo Zhang, and Zhe Qiu

Subjects
Public aspects of medicine, RA1-1270
Abstract

Summary: Background: China has high stroke rates despite the population being relatively lean. Uncertainty persists about the relevance of adiposity to risk of stroke types. We aimed to assess the associations of adiposity with incidence of stroke types and effect mediation by blood pressure in Chinese men and women. Methods: The China Kadoorie Biobank enrolled 512 891 adults aged 30–79 years from ten areas (five urban and five rural) during 2004–08. During a median 9 years (IQR 8–10) of follow-up, 32 448 strokes (about 90% confirmed by neuroimaging) were recorded among 489 301 participants without previous cardiovascular disease. Cox regression analysis was used to produce adjusted hazard ratios (HRs) for ischaemic stroke (n=25 210) and intracerebral haemorrhage (n=5380) associated with adiposity. Findings: Mean baseline body-mass index (BMI) was 23·6 kg/m2 (SD 3·2), and 331 723 (67·8%) participants had a BMI of less than 25 kg/m2. Throughout the range examined (mean 17·1 kg/m2 [SD 0·9] to 31·7 kg/m2 [2·0]), each 5 kg/m2 higher BMI was associated with 8·3 mm Hg (SE 0·04) higher systolic blood pressure. BMI was positively associated with ischaemic stroke, with an HR of 1·30 (95% CI 1·28–1·33 per 5 kg/m2 higher BMI), which was generally consistent with that predicted by equivalent differences in systolic blood pressure (1·25 [1·24–1·26]). The HR for intracerebral haemorrhage (1·11 [1·07–1·16] per 5 kg/m2 higher BMI) was less extreme, and much weaker than that predicted by the corresponding difference in systolic blood pressure (1·48 [1·46–1·50]). Other adiposity measures showed similar associations with stroke types. After adjustment for usual systolic blood pressure, the positive associations with ischaemic stroke were attenuated (1·05 [1·03–1·07] per 5 kg/m2 higher BMI); for intracerebral haemorrhage, they were reversed (0·73 [0·70–0·77]). High adiposity (BMI >23 kg/m2) accounted for 14·7% of total stroke (16·5% of ischaemic stroke and 6·7% of intracerebral haemorrhage). Interpretation: In Chinese adults, adiposity was strongly positively associated with ischaemic stroke, chiefly through its effect on blood pressure. For intracerebral haemorrhage, leanness, either per se or through some other factor (or factors), might increase risk, offsetting the protective effects of lower blood pressure. Funding: UK Wellcome Trust, UK Medical Research Council, British Heart Foundation, Cancer Research UK, Kadoorie Charitable Foundation, Chinese Ministry of Science and Technology, Chinese National Natural Science Foundation.

Published
2018
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7. Age-specific association between blood pressure and vascular and non-vascular chronic diseases in 0·5 million adults in China: a prospective cohort study

Author

Ben Lacey, FFPH, Sarah Lewington, DPhil, Robert Clarke, ProfFRCP, Xiang Ling Kong, MSc, Yiping Chen, DPhil, Yu Guo, MSc, Ling Yang, PhD, Derrick Bennett, PhD, Fiona Bragg, DPhil, Zheng Bian, MSc, Shaojie Wang, MD, Hua Zhang, MD, Junshi Chen, ProfMD, Robin G Walters, PhD, Rory Collins, ProfFRS, Richard Peto, ProfFRS, Liming Li, ProfMPH, Zhengming Chen, ProfDPhil, Junshi Chen, Zhengming Chen, Robert Clarke, Rory Collins, Yu Guo, Liming Li, Jun Lv, Richard Peto, Robin Walters, Daniel Avery, Derrick Bennett, Ruth Boxall, Fiona Bragg, Yumei Chang, Yiping Chen, Huaidong Du, Simon Gilbert, Alex Hacker, Michael Holmes, Andri Iona, Christiana Kartsonaki, Rene Kerosi, Om Kurmi, Sarah Lewington, Garry Lancaster, Kuang Lin, John McDonnell, Iona Millwood, Qunhua Nie, Jayakrishnan Radhakrishnan, Paul Ryder, Sam Sansome, Dan Schmidt, Paul Sherliker, Rajani Sohoni, Becky Stevens, Iain Turnbull, Jenny Wang, Lin Wang, Neil Wright, Ling Yang, Xiaoming Yang, Zheng Bian, Ge Chen, Xiao Han, Can Hou, Pei Pei, Shuzhen Qu, Yunlong Tan, Canqing Yu, Zengchang Pang, Ruqin Gao, Shaojie Wang, Yongmei Liu, Ranran Du, Yajing Zang, Liang Cheng, Xiaocao Tian, Hua Zhang, Silu Lv, Junzheng Wang, Wei Hou, Jiyuan Yin, Ge Jiang, Xue Zhou, Liqiu Yang, Hui He, Bo Yu, Yanjie Li, Huaiyi Mu, Qinai Xu, Meiling Dou, Jiaojiao Ren, Shanqing Wang, Ximin Hu, Hongmei Wang, Jinyan Chen, Yan Fu, Zhenwang Fu, Xiaohuan Wang, Min Weng, Xiangyang Zheng, Yilei Li, Huimei Li, Yanjun Wang, Ming Wu, Jinyi Zhou, Ran Tao, Jie Yang, Chuanming Ni, Jun Zhang, Yihe Hu, Yan Lu, Liangcai Ma, Aiyu Tang, Shuo Zhang, Jianrong Jin, Jingchao Liu, Zhenzhu Tang, Naying Chen, Ying Huang, Mingqiang Li, Jinhuai Meng, Rong Pan, Qilian Jiang, Weiyuan Zhang, Yun Liu, Liuping Wei, Liyuan Zhou, Ningyu Chen, Hairong Guan, Xianping Wu, Ningmei Zhang, Xiaofang Chen, Xuefeng Tang, Guojin Luo, Jianguo Li, Xunfu Zhong, Jiaqiu Liu, Qiang Sun, Pengfei Ge, Xiaolan Ren, Caixia Dong, Hui Zhang, Enke Mao, Xiaoping Wang, Tao Wang, Xi Zhang, Ding Zhang, Gang Zhou, Shixian Feng, Liang Chang, Lei Fan, Yulian Gao, Tianyou He, Huarong Sun, Pan He, Chen Hu, Qiannan Lv, Xukui Zhang, Min Yu, Ruying Hu, Hao Wang, Yijian Qian, Chunmei Wang, Kaixue Xie, Lingli Chen, Yidan Zhang, Dongxia Pan, Yuelong Huang, Biyun Chen, Li Yin, Donghui Jin, Huilin Liu, Zhongxi Fu, Qiaohua Xu, Xin Xu, Hao Zhang, Youping Xiong, Huajun Long, Xianzhi Li, Libo Zhang, and Zhe Qiu

Subjects
Public aspects of medicine, RA1-1270
Abstract

Summary: Background: The age-specific association between blood pressure and vascular disease has been studied mostly in high-income countries, and before the widespread use of brain imaging for diagnosis of the main stroke types (ischaemic stroke and intracerebral haemorrhage). We aimed to investigate this relationship among adults in China. Methods: 512 891 adults (59% women) aged 30–79 years were recruited into a prospective study from ten areas of China between June 25, 2004, and July 15, 2008. Participants attended assessment centres where they were interviewed about demographic and lifestyle characteristics, and their blood pressure, height, and weight were measured. Incident disease was identified through linkage to local mortality records, chronic disease registries, and claims to the national health insurance system. We used Cox regression analysis to produce adjusted hazard ratios (HRs) relating systolic blood pressure to disease incidence. HRs were corrected for regression dilution to estimate associations with long-term average (usual) systolic blood pressure. Findings: During a median follow-up of 9 years (IQR 8–10), there were 88 105 incident vascular and non-vascular chronic disease events (about 90% of strokes events were diagnosed using brain imaging). At ages 40–79 years (mean age at event 64 years [SD 9]), usual systolic blood pressure was continuously and positively associated with incident major vascular disease throughout the range 120–180 mm Hg: each 10 mm Hg higher usual systolic blood pressure was associated with an approximately 30% higher risk of ischaemic heart disease (HR 1·31 [95% CI 1·28–1·34]) and ischaemic stroke (1·30 [1·29–1·31]), but the association with intracerebral haemorrhage was about twice as steep (1·68 [1·65–1·71]). HRs for vascular disease were twice as steep at ages 40–49 years than at ages 70–79 years. Usual systolic blood pressure was also positively associated with incident chronic kidney disease (1·40 [1·35–1·44]) and diabetes (1·14 [1·12–1·15]). About half of all vascular deaths in China were attributable to elevated blood pressure (ie, systolic blood pressure >120 mm Hg), accounting for approximately 1 million deaths (

Published
2018
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8. Smoking and smoking cessation in relation to risk of diabetes in Chinese men and women: a 9-year prospective study of 0·5 million people

Author

Xin Liu, PhD, Fiona Bragg, DPhil, Ling Yang, PhD, Christiana Kartsonaki, DPhil, Yu Guo, MSc, Huaidong Du, PhD, Zheng Bian, MSc, Yiping Chen, DPhil, Canqing Yu, PhD, Jun Lv, ProfPhD, Kang Wang, BSc, Hua Zhang, MSc, Junshi Chen, ProfMD, Robert Clarke, ProfFRCP, Rory Collins, ProfFRS, Richard Peto, ProfFRS, Liming Li, ProfMPH, Zhengming Chen, ProfDPhil, Junshi Chen, Zhengming Chen, Robert Clarke, Rory Collins, Yu Guo, Liming Li, Jun Lv, Richard Peto, Robin Walters, Daniel Avery, Derrick Bennett, Ruth Boxall, Fiona Bragg, Yumei Chang, Yiping Chen, Huaidong Du, Simon Gilbert, Alex Hacker, Michael Holmes, Christiana Kartsonaki, Rene Kerosi, Garry Lancaster, Kuang Lin, John McDonnell, Iona Millwood, Qunhua Nie, Jayakrishnan Radhakrishnan, Paul Ryder, Sam Sansome, Dan Schmidt, Rajani Sohoni, Becky Stevens, Iain Turnbull, Jenny Wang, Lin Wang, Neil Wright, Ling Yang, Xiaoming Yang, Zheng Bian, Ge Chen, Xiao Han, Can Hou, Pei Pei, Shuzhen Qu, Yunlong Tan, Canqing Yu, Zengchang Pang, Ruqin Gao, Shaojie Wang, Yongmei Liu, Ranran Du, Yajing Zang, Liang Cheng, Xiaocao Tian, Hua Zhang, Silu Lv, Junzheng Wang, Wei Hou, Jiyuan Yin, Ge Jiang, Xue Zhou, Liqiu Yang, Hui He, Bo Yu, Yanjie Li, Huaiyi Mu, Qinai Xu, Meiling Dou, Jiaojiao Ren, Shanqing Wang, Ximin Hu, Hongmei Wang, Jinyan Chen, Yan Fu, Zhenwang Fu, Xiaohuan Wang, Min Weng, Xiangyang Zheng, Yilei Li, Huimei Li, Yanjun Wang, Ming Wu, Jinyi Zhou, Ran Tao, Jie Yang, Chuanming Ni, Jun Zhang, Yihe Hu, Yan Lu, Liangcai Ma, Aiyu Tang, Shuo Zhang, Jianrong Jin, Jingchao Liu, Zhenzhu Tang, Naying Chen, Ying Huang, Mingqiang Li, Jinhuai Meng, Rong Pan, Qilian Jiang, Weiyuan Zhang, Yun Liu, Liuping Wei, Liyuan Zhou, Ningyu Chen, Hairong Guan, Xianping Wu, Ningmei Zhang, Xiaofang Chen, Xuefeng Tang, Guojin Luo, Jianguo Li, Xunfu Zhong, Jiaqiu Liu, Qiang Sun, Pengfei Ge, Xiaolan Ren, Caixia Dong, Hui Zhang, Enke Mao, Xiaoping Wang, Tao Wang, Xi Zhang, Ding Zhang, Gang Zhou, Shixian Feng, Liang Chang, Lei Fan, Yulian Gao, Tianyou He, Huarong Sun, Pan He, Chen Hu, Qiannan Lv, Xukui Zhang, Min Yu, Ruying Hu, Hao Wang, Yijian Qian, Chunmei Wang, Kaixue Xie, Lingli Chen, Yidan Zhang, Dongxia Pan, Yuelong Huang, Biyun Chen, Li Yin, Donghui Jin, Huilin Liu, Zhongxi Fu, Qiaohua Xu, Xin Xu, Hao Zhang, Youping Xiong, Huajun Long, Xianzhi Li, Libo Zhang, and Zhe Qiu

Subjects
Public aspects of medicine, RA1-1270
Abstract

Summary: Background: In developed countries, smoking is associated with increased risk of diabetes. Little is known about the association in China, where cigarette consumption has increased (first in urban, then in rural areas) relatively recently. Moreover, uncertainty remains about the effect of smoking cessation on diabetes in China and elsewhere. We aimed to assess the associations of smoking and smoking cessation with risk of incident diabetes among Chinese adults. Methods: The prospective China Kadoorie Biobank enrolled 512 891 adults (59% women) aged 30–79 years during 2004–08 from ten diverse areas (five urban and five rural) across China. Participants were interviewed at study assessment clinics, underwent physical measurements, and had a non-fasting blood sample taken. Participants were separated into four categories according to smoking history: never-smokers, ever-regular smokers, ex-smokers, and occasional smokers. Incident diabetes cases were identified through linkage with diabetes surveillance systems, the national health insurance system, and death registries. All analyses were done separately in men and women and Cox regression was used to yield adjusted hazards ratios (HRs) for diabetes associated with smoking. Findings: 68% (n=134 975) of men ever smoked regularly compared with 3% (n=7811) of women. During 9 years' follow-up, 13 652 new-onset diabetes cases were recorded among 482 589 participants without previous diabetes. Among urban men, smokers had an adjusted HR of 1·18 (95% CI 1·12–1·25) for diabetes. HRs increased with younger age at first smoking regularly (1·12, 1·20, and 1·27 at ≥25 years, 20–24 years, and

Published
2018
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9. DISC1 and Huntington's disease--overlapping pathways of vulnerability to neurological disorder?

Author

Ruth Boxall, David J Porteous, and Pippa A Thomson

Subjects
Medicine, Science
Abstract

We re-annotated the interacting partners of the neuronal scaffold protein DISC1 using a knowledge-based approach that incorporated recent protein interaction data and published literature to. This revealed two highly connected networks. These networks feature cellular function and maintenance, and cell signaling. Of potentially greatest interest was the novel finding of a high degree of connectivity between the DISC1 scaffold protein, linked to psychiatric illness, and huntingtin, the protein which is mutated in Huntington's disease. The potential link between DISC1, huntingtin and their interacting partners may open new areas of research into the effects of pathway dysregulation in severe neurological disorders.

Published
2011
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10. Associations of polygenic risk scores with risks of stroke and its subtypes in Chinese

Author

Yu Guo, Derrick Bennett, Huaidong Du, Liming Li, Robert Clarke, Zhengming Chen, Junshi Chen, Ruying Hu, Kaixu Xie, Min Yu, Qiang Sun, Jun Zhang, Ling Yang, Shuo Zhang, Dianjianyi Sun, Hao Wang, Hua Zhang, Lingli Chen, Hao Zhang, Liang Cheng, Chao Liu, Hui Zhang, Fang Liu, Xin Xu, Wei Jiang, Tao Wang, Rory Collins, Jun Lv, Richard Peto, Robin Walters, Daniel Avery, Ruth Boxall, Yumei Chang, Yiping Chen, Simon Gilbert, Alex Hacker, Michael Holmes, Christiana Kartsonaki, Rene Kerosi, Kuang Lin, Iona Millwood, Qunhua Nie, Paul Ryder, Sam Sansome, Dan Schmidt, Rajani Sohoni, Becky Stevens, Iain Turnbull, Lin Wang, Neil Wright, Xiaoming Yang, Xiao Han, Can Hou, Pei Pei, Canqing Yu, Zengchang Pang, Ruqin Gao, Shanpeng Li, Shaojie Wang, Yongmei Liu, Ranran Du, Yajing Zang, Xiaocao Tian, Yaoming Zhai, Feng Ning, Xiaohui Sun, Silu Lv, Junzheng Wang, Yanjie Li, Quan Kang, Zhendong Guo, Ming Wu, Yonglin Zhou, Jinyi Zhou, Ran Tao, Jie Yang, Yihe Hu, Yan Lu, Liangcai Ma, Aiyu Tang, Jianrong Jin, Liuping Wei, Liyuan Zhou, Yulu Qin, Xianping Wu, Ningmei Zhang, Xiaofang Chen, Jiaqiu Liu, Xiaolan Ren, Enke Mao, Xiaoping Wang, Shixian Feng, Huarong Sun, Pan He, Xukui Zhang, Zhongxi Fu, Libo Zhang, Jingchao Liu, Andri Iona, Paul Sherliker, Wei Hou, Xiangyang Zheng, Yilei Li, Huimei Li, Yun Liu, Ningyu Chen, Caixia Dong, Xi Zhang, Lei Fan, Donghui Jin, Wei Sun, Jian Su, Mike Hill, Feifei Li, Shukuan Wu, Jian Lan, Sisi Wang, Kai Kang, Xiao Li, Pang Yao, Songchun Yang, Shichun Yan, Huilin Liu Li Yin, Chi Wang, Ka Hung Chan, Lifang Zhou, Xiaoyu Chang, Mohsen Mazidi, Mei Lin, Yuanjie Pang, Iona Y Millwood, Xiaoming Cui, Yuan Cao, Xia Wu, Pek Kei Im, Xiaoyi Zhang, Dong Sun, Robin G Walters, Zhijia Sun, Sushila Burgess, Sue Burgess, Johnathan Clarke, Ahmed Edris Mohamed, Zammy Fairhurst-Hunter, Hannah Fry, Maria Kakkoura, Sam Morris, Alfred Pozarickij, Saredo Said, Qingmei Xia, Haiping Duan, Zhenyuan Wu, Huiming Luo, Tingting Ou, Zhenzhen Lu, Changping Xie, Tingping Zhu, Mingqiang Yuan, Faqing Chen, Huizi Tian, Dun Shen, Xiaojun Li, Jianwei Chen, Yuan Peng, and Chan Qu

Subjects
Neurology. Diseases of the nervous system, RC346-429
Abstract

Background and purpose Previous studies, mostly focusing on the European population, have reported polygenic risk scores (PRSs) might achieve risk stratification of stroke. We aimed to examine the association strengths of PRSs with risks of stroke and its subtypes in the Chinese population.Methods Participants with genome-wide genotypic data in China Kadoorie Biobank were split into a potential training set (n=22 191) and a population-based testing set (n=72 150). Four previously developed PRSs were included, and new PRSs for stroke and its subtypes were developed. The PRSs showing the strongest association with risks of stroke or its subtypes in the training set were further evaluated in the testing set. Cox proportional hazards regression models were used to estimate the association strengths of different PRSs with risks of stroke and its subtypes (ischaemic stroke (IS), intracerebral haemorrhage (ICH) and subarachnoid haemorrhage (SAH)).Results In the testing set, during 872 919 person-years of follow-up, 8514 incident stroke events were documented. The PRSs of any stroke (AS) and IS were both positively associated with risks of AS, IS and ICH (p

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11. New genetic signals for lung function highlight pathways and chronic obstructive pulmonary disease associations across multiple ancestries

Author

Phuwanat Sakornsakolpat, James F. Wilson, María Soler Artigas, Beate Stubbe, Nicholas J. Wareham, James D. Crapo, Victoria E. Jackson, Eleftheria Zeggini, Olga G. Troyanskaya, Medea Imboden, A. Mesut Erzurumluoglu, Adam S. Butterworth, Carl A. Melbourne, Ian Sayers, Lars Lind, Stefan Weiss, Margaret M. Parker, Timmers Prhj, Edwin K. Silverman, John C. Whittaker, Ian P. Hall, Ozren Polasek, Mika Kähönen, Katherine A. Fawcett, Anna Hansell, Liming Li, David J. Porteous, Louise V. Wain, Robert A. Scott, Richard Packer, Richard J. Allen, Robin G Walters, Anna L. Guyatt, Terho Lehtimäki, Nicole Probst-Hensch, Shona M. Kerr, Christian Gieger, Matthias Wielscher, Rajesh Rawal, Jing Hua Zhao, John E. Hokanson, Holger Schulz, Nicola F. Reeve, Claudia Langenberg, Ke Hao, Corry-Anke Brandsma, Megan L. Paynton, Vitart, Dmitry Prokopenko, Jennie Hui, Eugene R. Bleecker, Ma'en Obeidat, John Danesh, Ralf Ewert, Benjamin B. Sun, Frank Dudbridge, Jian Zhou, Brian D. Hobbs, Blair H. Smith, Don D. Sin, Dawn L. DeMeo, Joseph C. Maranville, Ida Surakka, Alison Catherine Murray, Nicholas Locantore, Katherine A. Kentistou, Terri H. Beaty, Igor Rudan, Kuang Lin, Amund Gulsvik, Ian J. Deary, Ruth Tal-Singer, Kijoung Song, David C. Nickle, Michael H. Cho, Jian'an Luan, Joshua D. Hoffman, Georg Homuth, Zhengming Chen, Dandi Qiao, Heiko Runz, Per Bakke, Chiara Batini, Caroline Hayward, Stefan Karrasch, Alan James, Andrew P. Morris, Prescott G. Woodruff, Laura M Yerges Armstrong, David Sparrow, Ulf Gyllensten, James P. Cook, Jonathan Marten, Olli T. Raitakari, Nick Shrine, Deborah A. Meyers, Tobin, Ruth Boxall, Marjo-Riitta Järvelin, David P. Strachan, Sarah E. Harris, Philippe Joubert, Stefan Enroth, Xingnan Li, van den Berge M, Anubha Mahajan, Yohan Bossé, Peter K. Joshi, Shrine, Nick [0000-0003-3641-4371], Guyatt, Anna L [0000-0003-1860-6337], Hobbs, Brian D [0000-0001-9564-0745], Sakornsakolpat, Phuwanat [0000-0002-4308-0974], Obeidat, Ma'en [0000-0002-5443-2752], Weiss, Stefan [0000-0002-3553-4315], Kentistou, Katherine A [0000-0002-5816-664X], Sun, Benjamin B [0000-0001-6347-2281], Enroth, Stefan [0000-0002-5056-9137], Vitart, Veronique [0000-0002-4991-3797], Allen, Richard J [0000-0002-8450-3056], Beaty, Terri H [0000-0002-7644-1705], Bossé, Yohan [0000-0002-3067-3711], Joshi, Peter K [0000-0002-6361-5059], Mahajan, Anubha [0000-0001-5585-3420], Murray, Alison [0000-0003-4915-4847], Porteous, David J [0000-0003-1249-6106], Sayers, Ian [0000-0001-5601-5410], Smith, Blair H [0000-0002-5362-9430], Tal-Singer, Ruth [0000-0002-5275-8062], Timmers, Paul RHJ [0000-0002-5197-1267], Troyanskaya, Olga G [0000-0002-5676-5737], Rudan, Igor [0000-0001-6993-6884], Wilson, James F [0000-0001-5751-9178], Zeggini, Eleftheria [0000-0003-4238-659X], Hayward, Caroline [0000-0002-9405-9550], Morris, Andrew P [0000-0002-6805-6014], Butterworth, Adam S [0000-0002-6915-9015], Walters, Robin G [0000-0002-9179-0321], Cho, Michael H [0000-0002-4907-1657], Strachan, David P [0000-0001-7854-1366], Tobin, Martin D [0000-0002-3596-7874], Wain, Louise V [0000-0003-4951-1867], Apollo - University of Cambridge Repository, Institute for Molecular Medicine Finland, Groningen Research Institute for Asthma and COPD (GRIAC), UNIVERSITY OF OULU, and Commission of the European Communities

Subjects
Male, Smoking/genetics, LOCI, Genome-wide association study, VARIANTS, Bioinformatics, Genome-wide association studies, Pulmonary Disease, Chronic Obstructive, 0302 clinical medicine, Polymorphism (computer science), Risk Factors, GWAS, GENOME-WIDE ASSOCIATION, HERITABILITY, COPD, Lung, 11 Medical and Health Sciences, Genetics & Heredity, Aged, 80 and over, 0303 health sciences, Genetic Predisposition to Disease/genetics, Smoking, 1184 Genetics, developmental biology, physiology, Middle Aged, Polymorphism, Single Nucleotide/genetics, 3. Good health, medicine.anatomical_structure, Meta-analysis, Genome-Wide Association Study/methods, Medical genetics, Female, Life Sciences & Biomedicine, medicine.medical_specialty, Understanding Society Scientific Group, Biology, Polymorphism, Single Nucleotide, Article, 03 medical and health sciences, Genetics, medicine, Humans, Genetic Predisposition to Disease, 030304 developmental biology, Genetic association, Aged, Respiratory tract diseases, Science & Technology, Case-control study, Lung/physiopathology, 06 Biological Sciences, medicine.disease, Pulmonary Disease, Chronic Obstructive/genetics, respiratory tract diseases, Case-Control Studies, 3111 Biomedicine, 030217 neurology & neurosurgery, Developmental Biology, Genome-Wide Association Study
Abstract

Reduced lung function predicts mortality and is key to the diagnosis of chronic obstructive pulmonary disease (COPD). In a genome-wide association study in 400,102 individuals of European ancestry, we define 279 lung function signals, 139 of which are new. In combination, these variants strongly predict COPD in independent patient populations. Furthermore, the combined effect of these variants showed generalizability across smokers and never-smokers, and across ancestral groups. We highlight biological pathways, known and potential drug targets for COPD and, in phenome-wide association studies, autoimmune-related and other pleiotropic effects of lung function associated variants. This new genetic evidence has potential to improve future preventive and therapeutic strategies for COPD., Editorial summary: A genome-wide association study in over 400,000 individuals identifies 139 new signals for lung function. These variants can predict chronic obstructive pulmonary disease in independent, trans-ethnic cohorts.

Published
2019

12. Lifelong genetically lowered sclerostin and risk of cardiovascular disease

Author

Michael V. Holmes, Samantha Laber, Benjamin M. Neale, Jenny C Censin, Z Chen, Kuang Lin, Robin G. Walters, Kristi Krebs, Reedik Mägi, Jonas Bovijn, Iona Y. Millwood, Ruth Boxall, Cecilia M. Lindgren, Liheng Li, Lili Milani, Sara L. Pulit, Teresa Ferreira, Craig A. Glastonbury, and Chiao-Lin Chen

Subjects
0303 health sciences, business.industry, Disease, 030204 cardiovascular system & hematology, Bioinformatics, Appendix, 3. Good health, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, medicine.anatomical_structure, chemistry, Medicine, Sclerostin, business, 030304 developmental biology
Abstract

BackgroundInhibition of sclerostin is a novel therapeutic approach to lowering fracture risk. However, phase III randomised controlled trials (RCTs) of romosozumab, a monoclonal antibody that inhibits sclerostin, suggest an imbalance of serious cardiovascular events.MethodsWe used two independent genetic variants (rs7209826 and rs188810925) in SOST (encoding sclerostin) associated with bone mineral density (BMD) as proxies for therapeutic inhibition of sclerostin. We estimated the effects on risk of osteoporosis, fracture, coronary heart disease (CHD) and a further 22 cardiometabolic risk factors and diseases, by combining data from up to 478,967 participants of European ancestry from three prospective cohorts and up to 1,030,836 participants from nine GWAS consortia. In addition, we performed meta-analyses of cardiovascular outcome data from phase III RCTs of romosozumab.ResultsMeta-analysis of RCTs identified a higher risk of cardiac ischemic events in patients randomised to romosozumab (25 events among 4,298 individuals; odds ratio [OR] 2·98; 95% confidence interval [CI], 1·18 to 7·55; P=0·017). Scaled to the equivalent dose of romosozumab (210mg/month; 0·09 g/cm2 higher BMD), the SOST variants associated with lower risk of fracture (OR, 0·59; 95% CI, 0·54-0·66; P= 1·4×10−24), and osteoporosis (OR, 0·43; 95% CI, 0·36-0·52; P=2·4×10−18). The SOST variants associated with higher risk of myocardial infarction and/or coronary revascularisation (69,649 cases; OR, 1·18; 95% CI, 1·06-1·32; P=0·003) and type 2 diabetes (OR 1·15; 95% CI, 1·05-1·27; P=0·003), higher systolic blood pressure (1·3mmHg; 95% CI 0·8-1·9; P=5·9×10−6) and waist-to-hip-ratio adjusted for BMI (0·05 SDs; 95% CI, 0·02 to 0·08; P=8·5×10−4).ConclusionsGenetically and therapeutically lowered sclerostin leads to higher risk of cardiovascular events. Rigorous evaluation of the cardiovascular safety of romosozumab and other sclerostin inhibitors is warranted.

Published
2021

13. Evaluating the cardiovascular safety of sclerostin inhibition using evidence from meta-analysis of clinical trials and human genetics

Author

Zhengming Chen, Lili Milani, Kristi Krebs, Michael V. Holmes, Jenny C Censin, George Davey Smith, Chia-Yen Chen, Craig A. Glastonbury, Iona Y Millwood, Teresa Ferreira, Robin G. Walters, Reedik Mägi, Jonas Bovijn, Ruth Boxall, Cecilia M. Lindgren, Benjamin M. Neale, Sara L. Pulit, Liming Li, Samantha Laber, and Kuang Lin

Subjects
0301 basic medicine, Oncology, medicine.medical_specialty, Bone density, Osteoporosis, Romosozumab, 030204 cardiovascular system & hematology, Lower risk, Article, law.invention, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Randomized controlled trial, law, Internal medicine, medicine, business.industry, General Medicine, medicine.disease, Clinical trial, 030104 developmental biology, chemistry, Meta-analysis, Sclerostin, business
Abstract

Inhibition of sclerostin is a therapeutic approach to lowering fracture risk in patients with osteoporosis. However, data from phase III randomized controlled trials (RCTs) of romosozumab, a first-in-class monoclonal antibody that inhibits sclerostin, suggest an imbalance of serious cardiovascular events, and regulatory agencies have issued marketing authorizations with warnings of cardiovascular disease. Here we meta-analyze published and unpublished cardiovascular outcome trial data of romosozumab and investigate whether genetic variants that mimic therapeutic inhibition of sclerostin are associated with higher risk of cardiovascular disease. Meta-analysis of up to three RCTs indicated a probable higher risk of cardiovascular events with romosozumab. Scaled to the equivalent dose of romosozumab [210 mg/month; 0.09 g/cm2 higher bone mineral density (BMD)], the SOST genetic variants were associated with lower risk of fracture and osteoporosis (commensurate with the therapeutic effect of romosozumab), and with a higher risk of myocardial infarction (MI) and/or coronary revascularization and major adverse cardiovascular events (MACE). The same variants were also associated with increased risk of type 2 diabetes mellitus (T2D) and higher systolic blood pressure (SBP) and central adiposity. Taken together, our findings indicate that inhibition of sclerostin may elevate cardiovascular risk, warranting a rigorous evaluation of the cardiovascular safety of romosozumab and other sclerostin inhibitors.

Published
2020

14. New genetic signals for lung function highlight pathways and pleiotropy, and chronic obstructive pulmonary disease associations across multiple ancestries

Author

Nick Shrine, Anna L Guyatt, A Mesut Erzurumluoglu, Victoria E Jackson, Brian D Hobbs, Carl Melbourne, Chiara Batini, Katherine A Fawcett, Kijoung Song, Phuwanat Sakornsakolpat, Xingnan Li, Ruth Boxall, Nicola F Reeve, Ma’en Obeidat, Jing Hua Zhao, Matthias Wielscher, Understanding Society Scientific Group, Stefan Weiss, Katherine A Kentistou, James P Cook, Benjamin B Sun, Jian Zhou, Jennie Hui, Stefan Karrasch, Medea Imboden, Sarah E Harris, Jonathan Marten, Stefan Enroth, Shona M Kerr, Ida Surakka, Veronique Vitart, Terho Lehtimäki, Richard J Allen, Per S Bakke, Terri H Beaty, Eugene R Bleecker, Yohan Bossé, Corry-Anke Brandsma, Zhengming Chen, James D Crapo, John Danesh, Dawn L DeMeo, Frank Dudbridge, Ralf Ewert, Christian Gieger, Amund Gulsvik, Anna L Hansell, Ke Hao, Josh D Hoffman, John Hokanson, Georg Homuth, Peter K Joshi, Philippe Joubert, Claudia Langenberg, Xuan Li, Liming Li, Kuang Lin, Lars Lind, Nick Locantore, Jian’an Luan, Anubha Mahajan, Joseph C Maranville, Alison Murray, David C Nickle, Richard Packer, Margaret M Parker, Megan L Paynton, David Porteous, Dmitry Prokopenko, Dandi Qiao, Rajesh Rawal, Heiko Runz, Ian Sayers, Don D Sin, Blair H Smith, María Soler Artigas, David Sparrow, Ruth Tal-Singer, Paul RHJ Timmers, Maarten Van den Berge, John C Whittaker, Prescott Woodruff, Laura M Yerges Armstrong, Olga G Troyanskaya, Olli T Raitakari, Mika Kähönen, Ozren Polasek, Ulf Gyllensten, Igor Rudan, Ian J Deary, Nicole M Probst-Hensch, Holger Schulz, Alan L James, James F Wilson, Beate Stubbe, Eleftheria Zeggini, Marjo-Riitta Jarvelin, Nick Wareham, Edwin K Silverman, Caroline Hayward, Andrew P Morris, Adam S Butterworth, Robert A Scott, Robin G Walters, Deborah A Meyers, Michael H Cho, David P Strachan, Ian P Hall, Martin D Tobin, and Louise V Wain

Subjects
0303 health sciences, COPD, business.industry, Pulmonary disease, Bioinformatics, medicine.disease, 3. Good health, respiratory tract diseases, 03 medical and health sciences, 0302 clinical medicine, Pleiotropy (drugs), Medicine, business, 030217 neurology & neurosurgery, Lung function, 030304 developmental biology, Genetic association
Abstract

Reduced lung function predicts mortality and is key to the diagnosis of COPD. In a genome-wide association study in 400,102 individuals of European ancestry, we define 279 lung function signals, one-half of which are new. In combination these variants strongly predict COPD in deeply-phenotyped patient populations. Furthermore, the combined effect of these variants showed generalisability across smokers and never-smokers, and across ancestral groups. We highlight biological pathways, known and potential drug targets for COPD and, in phenome-wide association studies, autoimmune-related and other pleiotropic effects of lung function associated variants. This new genetic evidence has potential to improve future preventive and therapeutic strategies for COPD.

Published
2018
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15. Adherence to healthy lifestyle and cardiovascular diseases in the Chinese population

Author

Jun Lv, Canqing Yu, Yu Guo, Zheng Bian, Ling Yang, Yiping Chen, Xuefeng Tang, Weiyuan Zhang, Yijian Qian, Yuelong Huang, Xiaoping Wang, Junshi Chen, Zhengming Chen, Lu Qi, Liming Li, Rory Collins, Richard Peto, Daniel Avery, Ruth Boxall, Derrick Bennett, Yumei Chang, Robert Clarke, Huaidong Du, Simon Gilbert, Alex Hacker, Michael Holmes, Andri Iona, Christiana Kartsonaki, Rene Kerosi, Ling Kong, Om Kurmi, Garry Lancaster, Sarah Lewington, Kuang Lin, John McDonnell, Winnie Mei, Iona Millwood, Qunhua Nie, Jayakrishnan Radhakrishnan, Sajjad Rafiq, Paul Ryder, Sam Sansome, Dan Schmidt, Paul Sherliker, Rajani Sohoni, Iain Turnbull, Robin Walters, Jenny Wang, Lin Wang, Xiaoming Yang, Ge Chen, Bingyang Han, Can Hou, Pei Pei, Shuzhen Qu, Yunlong Tan, Caning Yu, Haiyan Zhou, Zeng hang Pang, Ruin Gao, Shoji Wang, Yong-Mei Liu, Ran ran Du, Yajing Zang, Liang Cheng, Xiaocao Tian, Hua Zhang, Silu Lv, Junzheng Wang, Wei Hou, Jiyuan Yin, Ge Jiang, Xue Zhou, Liqiu Yang, Hui He, Bo Yu, Yanjie Li, Huaiyi Mu, Qinai Xu, Meiling Dou, Jiaojiao Ren, Shanqing Wang, Ximin Hu, Hongmei Wang, Jinyan Chen, Yan Fu, Zhenwang Fu, Xiaohuan Wang, Min Weng, Xiangyang Zheng, Yilei Li, Huimei Li, Yanjun Wang, Ming Wu, Jinyi Zhou, Ran Tao, Jie Yang, Chuanming Ni, Jun Zhang, Yihe Hu, Yan Lu, Liangcai Ma, Aiyu Tang, Shuo Zhang, Jianrong Jin, Jingchao Liu, Zhenzhu Tang, Naying Chen, Ying Huang, Mingqiang Li, Jinhuai Meng, Rong Pan, Qilian Jiang, Yun Liu, Liuping Wei, Liyuan Zhou, Ningyu Chen, Hairong Guan, Xianping Wu, Ningmei Zhang, Xiaofang Chen, Guojin Luo, Jianguo Li, Xunfu Zhong, Jiaqiu Liu, Qiang Sun, Pengfei Ge, Xiaolan Ren, Caixia Dong, Hui Zhang, Enke Mao, Tao Wang, Xi zhang, Ding Zhang, Gang Zhou, Shixian Feng, Liang Chang, Lei Fan, Yulian Gao, Tianyou He, Huarong Sun, Pan He, Chen Hu, Qiannan Lv, Xukui Zhang, Min Yu, Ruying Hu, Hao Wang, Chunmei Wang, Kaixue Xie, Lingli Chen, Yidan Zhang, Dongxia Pan, Biyun Chen, Li Yin, Donghui Jin, Huilin Liu, Zhongxi Fu, Qiaohua Xu, Xin Xu, Hao Zhang, Youping Xiong, Huajun Long, Xianzhi Li, Libo Zhang, and Zhe Qiu

Subjects
Gerontology, Adult, Male, China, Health Behavior, Disease, 030204 cardiovascular system & hematology, Cohort Studies, 03 medical and health sciences, 0302 clinical medicine, Asian People, Environmental health, Diabetes mellitus, Medicine, Humans, 030212 general & internal medicine, Healthy Lifestyle, Aged, Chinese population, business.industry, Hazard ratio, Middle Aged, medicine.disease, Confidence interval, Lifestyle factors, Cardiovascular Diseases, Red meat, Patient Compliance, Female, business, Cardiology and Cardiovascular Medicine, Cohort study
Abstract

BACKGROUND: Adherence to a combination of healthy lifestyle factors has been related to a considerable reduction of cardiovascular risk in white populations; however, little is known whether such associations persist in nonwhite populations like the Asian population. OBJECTIVES: This study aimed to examine the associations of a combination of modifiable, healthy lifestyle factors with the risks of ischemic cardiovascular diseases and estimate the proportion of diseases that could potentially be prevented by adherence to these healthy lifestyle patterns. METHODS: This study examined the associations of 6 lifestyle factors with ischemic heart disease and ischemic stroke (IS) in the China Kadoorie Biobank of 461,211 participants 30 to 79 years of age who did not have cardiovascular diseases, cancer, or diabetes at baseline. Low-risk lifestyle factors were defined as nonsmoking status or having stopped smoking for reasons other than illness, alcohol consumption of

Published
2017

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