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Background Epidemiological evidence on the relationship between fish consumption and chronic obstructive pulmonary disease (COPD) is limited, especially among Chinese. Objectives To explore the prospective association between fish consumption and COPD among a large population-based Chinese cohort. Methods The China Kadoorie Biobank (CKB) recruited over 0.5 million participants from ten geographically diverse regions across China from 2004 to 2008. Consumption frequency of fish at baseline was assessed by a validated food frequency questionnaire. 169,188 men and 252,238 women who had no prior COPD and other major chronic diseases at baseline were included in our analyses. Cox proportional hazard models were employed to estimate the hazard ratio (HR) and 95% confidence interval (CI) for fish consumption categories in relation to incident COPD. Results During a median follow-up of 11.1 years, 5542 incident COPD cases were documented. Fish consumption was inversely associated with COPD risk among women, with a 17% reduction in risk for participants who consumed fish ≥4 days/week compared with non-consumption (HR: 0.83; 95% CI: 0.70, 0.99; p for trend = 0.017), whereas we did not observe such a dose-response relationship among men (HR: 0.89; 95% CI: 0.76, 1.05; p for trend = 0.373). The joint analysis showed that COPD risk was 38% and 48% lower in men and women who consumed fish ≥4 days/week and had a healthy lifestyle (having ≥4 of the following healthy lifestyle factors: not smoking currently, never or rarely drinking alcohol, adequate physical activity, BMI 18.5-23.9 kg/m2, normal waist circumference, reasonable diet), compared with participants with fish consumption

Objective: To examine the association between height loss and calcaneus bone mineral density (BMD) through data gathered from the China Kadoorie Biobank (CKB). Methods: The present study included 24 231 participants who attended the CKB resurvey during 2013-2014, in which calcaneus BMD was measured by quantitative ultrasound method for the first time. Height loss was calculated according to the differences appeared in height measurement between baseline and resurvey. We used linear regression models to estimate the association between height loss and BMD measures. Results: The mean interval between baseline and resurvey was (8.0±0.8 ) years. 33.0% of the participants showed a height loss of ≥1.0 cm, and another 3.7% were with height loss of ≥3.0 cm. After adjustment for potential confounders, there was a linear correlation seen between height loss and BMD (P for all linear trend were Conclusions: BMD became lower with the increase of height loss. Regular height measurement may contribute to the early diagnosis and prevention of osteoporosis.

Summary Background China initiated major health-care reforms in 2009 aiming to provide universal health care for all by 2020. However, little is known about trends in health-care use and health outcomes across different socioeconomic groups in the past decade. Methods We used data from the China Kadoorie Biobank (CKB), a nationwide prospective cohort study of adults aged 30–79 years in 2004–08, in ten regions (five urban, five rural) in China. Individuals who were alive in 2009 were included in the present study. Data for all admissions were obtained by linkage to electronic hospital records from the health insurance system, and to region-specific disease and death registers. Generalised linear models were used to estimate trends in annual hospital admission rates, 28-day case fatality rates, and mean length of stay for stroke, ischaemic heart disease, and any cause in all relevant individuals. Findings 512 715 participants were recruited to the CKB between June 25, 2004, and July 15, 2008, 505 995 of whom were still alive on Jan 1, 2009, and contributed to the present study. Among them, we recorded 794 824 hospital admissions (74 313 for stroke, 69 446 for ischaemic heart disease) between 2009 and 2016. After adjustment for demographic, socioeconomic, lifestyle, and morbidity factors, hospitalisation rates increased annually by 3·6% for stroke, 5·4% for ischaemic heart disease, and 4·2% for any cause, between 2009 and 2016. Higher socioeconomic groups had higher hospitalisation rates, but the annual proportional increases were higher in those with lower education or income levels, those enrolled in the urban or rural resident health insurance scheme, and for those in rural areas. Lower socioeconomic groups had higher case fatality rates for stroke and ischaemic heart disease, but greater reductions in case fatality rates than higher socioeconomic groups. By contrast, mean length of stay decreased by around 2% annually for stroke, ischaemic heart disease, and any cause, but decreased to a greater extent in higher than lower socioeconomic groups for stroke and ischaemic heart disease. Interpretation Between 2009 and 2016, lower socioeconomic groups in China had greater increases in hospital admission rates and greater reductions in case fatality rates for stroke and ischaemic heart disease. Additional strategies are needed to further reduce socioeconomic differences in health-care use and disease outcomes. Funding Wellcome Trust, Medical Research Council, British Heart Foundation, Cancer Research UK, Kadoorie Charitable Foundation, China Ministry of Science and Technology, and Chinese National Natural Science Foundation.

Objective: To examine the associations between family history of major chronic diseases and healthy lifestyle in adults in China. Methods: Data were from the baseline and second survey of China Kadoorie Biobank study, which were conducted during 2004-2008 and 2013-2014, respectively. After excluding participants with self-reported histories of coronary heart disease, stroke, cancer or diabetes, a total of 461 213 adults from baseline survey and 20 583 adults from second survey were included in the current study. Participants who reported a family history of acute myocardial infarction, stroke, cancer, or diabetes of any first-degree relative (i.e., biological father, mother, or siblings) were defined as having a family history of major chronic diseases. Healthy lifestyles were defined as current nonsmoking, non-excessive alcohol drinking, eating vegetables and fruits daily, upper quarter of physical activity level, body mass index (BMI) of (18.5-23.9) kg/m(2), and waist- to-hip ratio (WHR) Results: At baseline survey, 36.5% of the participants had family history of major chronic diseases. Proportions of the above six healthy lifestyles were 70.5%, 93.0%, 18.0%, 25.0%, 53.4%, and 43.5%, respectively. Compared with participants without family history, the proportions of current nonsmoking, non-excessive drinking, normal BMI, and normal WHR were lower in participants with family history of major chronic diseases, while the proportions of eating vegetables and fruits daily, and being physically active, were higher. In general, the absolute differences in these proportions between participants with and without a family history were only slight. Similar results were observed when other family history status (the type or number of disease, the category or number of affected family members) were analysed. The association between family history of major chronic diseases and healthy lifestyles was consistently observed in the second survey 10 years later. Conclusion: In Chinese population, adults with family history of major chronic diseases did not adopt healthier lifestyles.

Objective: To evaluate the correlation between alcohol consumption and obesity in adults in China.Methods: The information about alcohol consumption were collected at the baseline survey of the China Kadoorie Biobank. The general obesity and central obesity were defined by BMI and waist circumference (WC) respectively. Logistic regression model was employed to examine the relationship of drinking behavior with general obesity and central obesity.Results: A total of 249 873 adults were included. A J-shaped relationship was observed between alcohol consumption and obesity measurement index (BMI and WC) in men. Compared with non-drinkers, the proportion of general obesity and central obesity were lower in light drinkers (men: OR=0.65, 95%CI: 0.59-0.71 and OR=0.93, 95%CI: 0.88-0.98; women: OR=0.77, 95%CI: 0.65-0.91 and OR=0.89, 95%CI: 0.80-0.99). In men, the proportion of general obesity and central obesity was highest in heavy drinkers (OR=1.21, 95%CI: 1.12-1.32; OR=1.33, 95%CI: 1.27-1.40). BMI and WC were higher in those with a drinking frequency of 3-5 d/week, with largest of proportion of central obesity (men: OR=1.23, 95%CI: 1.16-1.31; women: OR=1.13, 95%CI: 0.99-1.28). The risk for central obesity in men who began drinking every week before 20 years old was 1.24 times higher than non-drinkers (95%CI: 1.16-1.33). Those who drank beer had lower proportion of general obesity (men: OR=0.74, 95%CI: 0.67-0.82; women: OR=0.54, 95%CI: 0.43-0.68).Conclusion: The proportion of obesity was lower in light drinkers but higher in heavy drinkers; and the earlier drinking started, the higher the risk for obesity was.

Objective: To examine the association between the frequencies of bowel movement (BMF) and the risk of colorectal cancer (CRC). Methods: In this study, 510 134 participants from the China Kadoorie Biobank (CKB) were included, after excluding those who reported as having been diagnosed with cancer at the baseline survey. The baseline survey was conducted from June 2004 to July 2008. The present study included data from baseline and follow-up until December 31, 2016. We used the Cox proportional hazards regression models to estimate the HR and the 95%CI of incident CRC with BMF. Results: During an average follow-up period of 9.9 years, 3 056 participants were documented as having developed colorectal cancer. In the site-specific analysis, 1 548 colon cancer and 1 475 rectal cancer were included. Compared with participants who had bowel movements on the daily base, the multivariable-adjusted HR (95%CI) for those who had more than once of BMF were 1.24 (1.12-1.39) for CRC, 1.12 (0.95-1.31) for colon cancer, and 1.37 (1.18-1.59) for rectal cancer. We further examined the association between BMF and CRC, according to the stages of follow-up, the corresponding HR (95%CI) for CRC, colon and rectal cancer were 1.59 (1.36-1.86), 1.43 (1.14- 1.80), and 1.76 (1.41-2.19) for the first five years, while such associations became statistically insignificant in the subsequent follow-up (P for all interactions were

Previous studies have demonstrated the association between physical activity and sleep quality. However, there is little evidence regarding different domains of physical activity. This study aimed to examine the associations between domain-specific physical activities and insomnia symptoms among Chinese men and women. Data of 452 024 Chinese adults aged 30-79 years from the China Kadoorie Biobank Study were analysed. Insomnia symptoms were assessed with self-reported difficulties in initiating or maintaining sleep, early morning awakening, daytime dysfunction and any insomnia symptoms. Physical activity assessed by questionnaire consisted of four domains, including occupational, commuting-related, household and leisure-time activities. Gender-specific multiple logistic regression models were employed to estimate independent associations of overall and domain-specific physical activities with insomnia symptoms. Overall, 12.9% of men and 17.8% of women participants reported having insomnia symptoms. After adjustment for potential confounders, a moderate to high level of overall activity was associated with reduced risks of difficulties in initiating or maintaining sleep and daytime dysfunction in both sexes (odds ratios range: 0.87-0.94, P

In the version of this article initially published, the following statement was missing from the Acknowledgements: “We are grateful to the GenoBiRD core facility (Biogenouest), the Clinical Investigation Center (INSERM CIC1413) and the Center of Biological Resources in Nantes (BB-0033-00040; CHU Nantes, France) for their assistance in managing and genotyping the ICAN and PREGO biobanks. R.R. was supported by the French Regional Council of Pays-de-la-Loire (VaCaRMe program) and the Agence Nationale de la Recherche (ANR-15-CE17-0008-01 to G.L). H.D. and R.B. were supported by the French Ministry of Health (clinical trial NCT02848495 to H.D.), the Genavie Foundation, the Société Française de Radiologie and the Société Française de Neuroradiologie.” The error has been corrected in the HTML and PDF versions of the article. *Lists of authors and their affiliations appear online. Korrektur zu 10.1038/s41588-020-00725-7

Objective To examine the prevalence of a healthy lifestyle in the China Kadoorie Biobank (CKB) of 0.5 million adults from ten areas across China. Methods After excluding participants with self-reported histories of coronary heart disease, stroke or cancer, a total of 487 198 participants at baseline (2004-2008) and 22 604 participants at resurvey (2013-2014) were included in the analysis. A healthy lifestyle was defined as nonsmoking or having stopped for reasons other than illness; alcohol drinking ≺25 g/day (men)/ ≺15 g/day (women); diet rich in vegetables, fruits, legumes and fish, and low in red meat; upper quarter of the physical activity level; body mass index of 18.5-23.9 kg/m2; and waist circumstance ≺85 cm (men)/80 cm (women). We calculated healthy lifestyle scores (HLS) by counting the number of healthy lifestyle factors, with a range from 0 to 6. Results At baseline, the proportion of above five healthy lifestyle factors (except physical activity) was 70.6%, 92.6%, 8.7%, 52.6% and 59.0%, respectively. The mean HLS was 3.1±1.2. Most participants (81.4%) had 2~4 healthy components, while only 0.7% (0.2% in men and 1.0% in women) of participants had all six healthy lifestyle factors. Participants who were women, younger, more educated and rural residents were more likely to adhere to a healthy lifestyle. At resurvey of ten years later, the mean HLS decreased a bit. Conclusion The prevalence of optimal lifestyle status in Chinese adults was extremely low. Healthy lifestyle level varied greatly among the population with different sociodemographic characteristics and across ten areas in China.

Summary Tea is a worldwide drink with controversial effect on bone health. The sex-specific associations are unrevealed among general population. This study showed that prolonged moderate tea consumption benefited bone health in women, while no additional benefit with stronger tea. However, tea consumption was not associated with bone health in men. Introduction Tea consumption has been shown a potentially beneficial effect on bone health in postmenopausal women. However, little is known about such association in men, and whether stronger tea instead harms bone health due to elevated urinary excretion of calcium associated with caffeine in the tea. The aim of this study was to examine the association between various metrics of tea consumption and bone health. Methods The present study included 20,643 participants from the China Kadoorie Biobank (CKB), who have finished both baseline survey (2004–2008) and a re-survey (2013–2014). They were aged 38–86 years at re-survey. Tea consumption was self-reported at both baseline and re-survey. Bone mineral density (BMD) was measured using calcaneal quantitative ultrasound once at re-survey. Results Compared with non-consumers, prolonged weekly tea consumers in women was associated with higher calcaneus BMD measures, with β (95% CI) of 0.98 (0.22, 1.74) for BUA, 4.68 (1.74, 7.61) for SOS, and 1.95 (0.81, 3.10) for SI. Among prolonged weekly tea consumers, no linear increase in BMD measures with the amount of tea leaves added was observed. The SOS and SI were higher in consumers with tea leaves 3.0–5.9 g/day than in those with

Background: Tea consumption may have favorable effects on risk of fracture. However, little is known about such association in Chinese adults. The aim of this study was to examine the association between tea consumption and risk of hospitalized fracture in Chinese adults. Methods: The present study included 453,625 participants from the China Kadoorie Biobank (CKB). Tea consumption was self-reported at baseline. Hospitalized fractures were ascertained through linkage with local health insurance claim databases. The results: During a median of 10.1 years of follow-up, we documented 12,130 cases of first-time any fracture hospitalizations, including 1376 cases of hip fracture. Compared with never tea consumers, daily tea consumption was associated with lower risk of any fracture (hazard ratio (HR): 0.88, 95% confidence interval (CI): 0.83, 0.93). Statistically significant reduced risk of hip fracture was shown among daily consumers who most commonly drank green tea (HR: 0.80, 95% CI: 0.65, 0.97) and those who had drunk tea for more than 30 years (HR: 0.68, 95% CI: 0.52, 0.87). Our conclusions: Habitual tea consumption was associated with moderately decreased risk of any fracture hospitalizations. Participants with decades of tea consumption and those who preferred green tea were also associated with lower risk of hip fracture.

The National Central Cancer Registry of China (NCCR) was the only available source of cancer monitoring in China, even though only about 70% of cancer registration sites were qualified by now. In this study, based on a national large prospective cohort-the China Kadoorie Biobank (CKB), we aimed to provide additional cancer statistics and compare the difference of cancer burden between urban and rural areas of China. A total of 497,693 cancer-free participants aged 35-74 years were recruited and successfully followed up from 2004 to 2013 in 5 urban and 5 rural areas across China. Except for traditional registration systems, the national health insurance system and active follow-up were used to determine new cancer incidents and related deaths. The mortality-to-incidence ratio (MIR) was used to compare the differences of cancer burden between urban and rural areas of China. We found that cancer mortality coincided well between our cohort and NCCR, while the incidence was much higher in our cohort. Based on CKB, we found the MIR of all cancers was 0.54 in rural areas, which was approximately one-third higher than that in urban areas with 0.39. Cancer profiles in urban areas were transiting to Western distributions, which were characterized with high incidences of breast cancer and colorectal cancer; while cancers of the esophagus, liver and cervix uteri were still common in rural areas of China. Our results provide additional cancer statistics of China and demonstrate the differences of cancer burden between urban and rural areas of China.

Background Increased physical activity is associated with a reduced risk of cardiovascular disease, but outdoor physical activity can be accompanied by increased inhalation of fine particulate matter (PM2·5). The extent to which long-term exposure to PM2·5 can offset the cardiovascular benefits of physical activity is unknown. We aimed to evaluate whether the associations between active commuting or farming activity and incident risks of cerebrovascular disease and ischaemic heart disease were consistent between populations with different ambient PM2·5 exposures. Methods We did a prospective cohort study using data from people aged 30–79 years without cardiovascular disease at baseline from the China Kadoorie Biobank (CKB). Active commuting and farming activity were assessed at baseline using questionnaires. A high-resolution (1 × 1 km) satellite-based model was used to estimate annual average PM2·5 exposure during the study period. Participants were stratified according to PM2·5 exposure (54 μg/m3 or greater vs less than 54 μg/m3). Hazard ratios (HRs) and 95% CIs for incident cerebrovascular disease and ischaemic heart disease by active commuting and farming activity were estimated using Cox proportional hazard models. Effect modifications by PM2·5 exposure were tested by likelihood ratio tests. Analyses were restricted to the period from Jan 1, 2005, to Dec 31, 2017. Findings Between June 25, 2004, and July 15, 2008, 512 725 people were enrolled in the CKB cohort. 322 399 eligible participants completed the baseline survey and were included in the analysis of active commuting (118 274 non-farmers and 204 125 farmers). Among 204 125 farmers, 2985 reported no farming time and 201 140 were included in the farming activity analysis. During a median follow-up of 11 years, 39 514 cerebrovascular disease cases and 22 313 ischaemic heart disease cases were newly identified. Among non-farmers with exposure to annual average PM2·5 concentrations of less than 54 μg/m3, increased active commuting was associated with lower risks of cerebrovascular disease (highest active commuting vs lowest active commuting HR 0·70, 95% CI 0·65–0·76) and ischaemic heart disease (0·60, 0·54–0·66). However, among non-farmers with exposure to annual average PM2·5 concentrations of 54 μg/m3 or greater, there was no association between active commuting and cerebrovascular disease or ischaemic heart disease. Among farmers with exposure to annual average PM2·5 concentrations of less than 54 μg/m3, increased active commuting (highest active commuting vs lowest active commuting HR 0·77, 95% CI 0·63–0·93) and increased farming activity (highest activity vs lowest activity HR 0·85, 95% CI 0·79–0·92) were both associated with a lower cerebrovascular disease risk. However, among farmers with exposure to annual average PM2·5 concentrations of 54 μg/m3 or greater, increases in active commuting (highest active commuting vs lowest active commuting HR 1·12, 95% CI 1·05–1·19) and farming activity (highest activity vs lowest activity HR 1·18, 95% CI 1·09–1·28) were associated with an elevated cerebrovascular disease risk. The above associations differed significantly between PM2·5 strata (all interaction p values Interpretation For participants with long-term exposure to higher ambient PM2·5 concentrations, the cardiovascular benefits of active commuting and farming activity were significantly attenuated. Higher levels of active commuting and farming activity even increased the cerebrovascular disease risk among farmers with exposure to annual average PM2·5 concentrations of 54 μg/m3 or greater. Funding National Natural Science Foundation of China, National Key Research and Development Program of China, Kadoorie Charitable Foundation, UK Wellcome Trust.

Background: Little is known about the long-term risks of stroke and ischemic heart disease (IHD) in women who had a hysterectomy alone (HA) or with bilateral oophorectomy (HBO) for benign diseases, particularly in China where the burden of cardiovascular diseases (CVD) is high. We assessed mean levels of cardiovascular risk factors and relative risks of stroke and IHD in Chinese women who had a HA or HBO. Methods: A total of 302 510 women, aged 30 to 79 years were enrolled in the China Kadoorie Biobank from 2004 to 2008 and followed up for a mean of 9.8 years. The analysis involved premenopausal women without prior cardiovascular disease or cancer at enrollment. We calculated adjusted hazard ratios for incident cases of CVD and their pathological types (ischemic stroke, hemorrhagic stroke, and IHD) after HA and HBO. Analyses were stratified by age and region and adjusted for levels of education, household income, smoking status, alcohol consumption, physical activity, body mass index, systolic blood pressure, diabetes, self-reported health, and number of pregnancies. Results: Among 282 722 eligible women, 8478 had HA, and 1360 had HBO. Women who had HA had 9% higher risk of CVD after HA (hazard ratio, 1.09 [95% CI, 1.06–1.12]) and 19% higher risk of CVD after HBO (1.19 [95% CI, 1.12–1.26]) compared with women who did not. Both HA and HBO were associated with higher risks of ischemic stroke and IHD but not with hemorrhagic stroke. The relative risks of CVD associated with HA and HBO were more extreme at younger age of surgery. Conclusions: Women who had either HA or HBO have higher risks of ischemic stroke and IHD, and these risks should be evaluated when discussing these interventions. Additional screening for risk factors for CVD should be considered in women following HA and HBO operations, especially if such operations are performed at younger age.

Objective To validate the World Health Organization (WHO) non-laboratory-based cardiovascular disease risk prediction model in regions of China. Methods We performed an external validation of the WHO model for East Asia using the data set of China Kadoorie Biobank, an ongoing cohort study with 512 725 participants recruited from 10 regions of China from 2004–2008. We also recalculated the recalibration parameters for the WHO model in each region and evaluated the predictive performance of the model before and after recalibration. We assessed discrimination performance by Harrell’s C index. Findings We included 412 225 participants aged 40–79 years. During a median follow-up of 11 years, 58 035 and 41 262 incident cardiovascular disease cases were recorded in women and men, respectively. Harrell's C of the WHO model was 0.682 in women and 0.700 in men but varied among regions. The WHO model underestimated the 10-year cardiovascular disease risk in most regions. After recalibration in each region, discrimination and calibration were both improved in the overall population. Harrell’s C increased from 0.674 to 0.749 in women and from 0.698 to 0.753 in men. The ratios of predicted to observed cases before and after recalibration were 0.189 and 1.027 in women and 0.543 and 1.089 in men. Conclusion The WHO model for East Asia yielded moderate discrimination for cardiovascular disease in the Chinese population and had limited prediction for cardiovascular disease risk in different regions in China. Recalibration for diverse regions greatly improved discrimination and calibration in the overall population.

Background: Little is known about the effects of maintaining healthy sleep patterns on frailty transitions. Methods: Based on 23,847 Chinese adults aged 30–79 in a prospective cohort study, we examined the associations between sleep patterns and frailty transitions. Healthy sleep patterns included sleep duration at 7 or 8 h/d, without insomnia disorder, and no snoring. Participants who persisted with a healthy sleep pattern in both surveys were defined as maintaining a healthy sleep pattern and scored one point. We used 27 phenotypes to construct a frailty index and defined three statuses: robust, prefrail, and frail. Frailty transitions were defined as the change of frailty status between the 2 surveys: improved, worsened, and remained. Log-binomial regression was used to calculate the prevalence ratio (PR) to assess the effect of sleep patterns on frailty transitions. Results: During a median follow-up of 8.0 years among 23,847 adults, 45.5% of robust participants, and 10.8% of prefrail participants worsened their frailty status, while 18.6% of prefrail participants improved. Among robust participants at baseline, individuals who maintained sleep duration of 7 or 8 h/ds, without insomnia disorder, and no-snoring were less likely to worsen their frailty status; the corresponding PRs (95% CIs) were 0.92 (0.89–0.96), 0.76 (0.74–0.77), and 0.85 (0.82–0.88), respectively. Similar results were observed among prefrail participants maintaining healthy sleep patterns. Maintaining healthy sleep duration and without snoring, also raised the probability of improving the frailty status; the corresponding PRs were 1.09 (1.00–1.18) and 1.42 (1.31–1.54), respectively. Besides, a dose-response relationship was observed between constantly healthy sleep scores and the risk of frailty transitions (P for trend Conclusions: Maintaining a comprehensive healthy sleep pattern was positively associated with a lower risk of worsening frailty status and a higher probability of improving frailty status among Chinese adults.

Background: Few studies have assessed the relationship between multimorbidity patterns and mortality risk in the Chinese population. We aimed to identify multimorbidity patterns and examined the associations of multimorbidity patterns and the number of chronic diseases with the risk of mortality among Chinese middle-aged and older adults. Methods: We used data from the China Kadoorie Biobank and included 512,723 participants aged 30 to 79 years. Multimorbidity was defined as the presence of two or more of the 15 chronic diseases collected by self-report or physical examination at baseline. Multimorbidity patterns were identified using hierarchical cluster analysis. Cox regression was used to estimate the associations of multimorbidity patterns and the number of chronic diseases with all-cause and cause-specific mortality. Results: Overall, 15.8% of participants had multimorbidity. The prevalence of multimorbidity increased with age and was higher in urban than rural participants. Four multimorbidity patterns were identified, including cardiometabolic multimorbidity (diabetes, coronary heart disease, stroke, and hypertension), respiratory multimorbidity (tuberculosis, asthma, and chronic obstructive pulmonary disease), gastrointestinal and hepatorenal multimorbidity (gallstone disease, chronic kidney disease, cirrhosis, peptic ulcer, and cancer), and mental and arthritis multimorbidity (neurasthenia, psychiatric disorder, and rheumatoid arthritis). During a median of 10.8 years of follow-up, 49,371 deaths occurred. Compared with participants without multimorbidity, cardiometabolic multimorbidity (hazard ratios [HR] = 2.20, 95% confidence intervals [CI]: 2.14 − 2.26) and respiratory multimorbidity (HR = 2.13, 95% CI:1.97 − 2.31) demonstrated relatively higher risks of mortality, followed by gastrointestinal and hepatorenal multimorbidity (HR = 1.33, 95% CI:1.22 − 1.46). The mortality risk increased by 36% (HR = 1.36, 95% CI: 1.35 − 1.37) with every additional disease. Conclusion: Cardiometabolic multimorbidity and respiratory multimorbidity posed the highest threat on mortality risk and deserved particular attention in Chinese adults.

Background: Mendelian randomization studies of systolic blood pressure (SBP) can assess the shape and strength of the associations of genetically predicted differences in SBP with major disease outcomes and are less constrained by biases in observational analyses. This study aimed to compare the associations of usual and genetically predicted SBP with major cardiovascular disease (CVD) outcomes, overall and by levels of SBP, age, and sex. Methods: The China Kadoorie Biobank involved a 12-year follow-up of a prospective study of 489 495 adults aged 40 to 79 years with no prior CVD and 86 060 with genetic data. Outcomes included major vascular events (59 490/23 151 in observational/genetic analyses), and its components (ischemic stroke [n=39 513/12 043], intracerebral hemorrhage [7336/5243], and major coronary events [7871/4187]). Genetically predicted SBP used 460 variants obtained from European ancestry genome-wide studies. Cox regression estimated adjusted hazard ratios for incident CVD outcomes down to usual SBP levels of 120 mm Hg. Results: Both observational and genetic analyses demonstrated log-linear positive associations of SBP with major vascular event and other major CVD types in the range of 120 to 170 mm Hg. Consistent with the observational analyses, the hazard ratios per 10 mm Hg higher genetically predicted SBP were 2-fold greater for intracerebral hemorrhage (1.71 [95% CI, 1.58–1.87]) than for ischemic stroke (1.37 [1.30–1.45]) or major coronary event (1.29 [1.18–1.42]). Genetic analyses also demonstrated 2-fold greater hazard ratios for major vascular event in younger (1.69 [95% CI, 1.54–1.86]) than in older people (1.28 [1.18–1.38]). Conclusions: The findings provide support for initiation of blood pressure-lowering treatment at younger ages and below the conventional cut-offs for hypertension to maximize CVD prevention, albeit the absolute risks of CVD are far greater in older people.

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.

Absolute risks of stroke are typically estimated using measurements of cardiovascular disease risk factors recorded at a single visit. However, the comparative utility of single versus sequential risk factor measurements for stroke prediction is unclear. Risk factors were recorded on three separate visits on 13,753 individuals in the prospective China Kadoorie Biobank. All participants were stroke-free at baseline (2004–2008), first resurvey (2008), and second resurvey (2013–2014), and were followed-up for incident cases of first stroke in the 3 years following the second resurvey. To reflect the models currently used in clinical practice, sex-specific Cox models were developed to estimate 3-year risks of stroke using single measurements recorded at second resurvey and were retrospectively applied to risk factor data from previous visits. Temporal trends in the Cox-generated risk estimates from 2004 to 2014 were analyzed using linear mixed effects models. To assess the value of more flexible machine learning approaches and the incorporation of longitudinal data, we developed gradient boosted tree (GBT) models for 3-year prediction of stroke using both single measurements and sequential measurements of risk factor inputs. Overall, Cox-generated estimates for 3-year stroke risk increased by 0.3% per annum in men and 0.2% per annum in women, but varied substantially between individuals. The risk estimates at second resurvey were highly correlated with the annual increase of risk for each individual (men: r = 0.91, women: r = 0.89), and performance of the longitudinal GBT models was comparable with both Cox and GBT models that considered measurements from only a single visit (AUCs: 0.779–0.811 in men, 0.724–0.756 in women). These results provide support for current clinical guidelines, which recommend using risk factor measurements recorded at a single visit for stroke prediction.

Aims The potential difference in the impacts of lifestyle factors (LFs) on progression from healthy to first cardiometabolic disease (FCMD), subsequently to cardiometabolic multimorbidity (CMM), and further to death is unclear. Methods and results We used data from the China Kadoorie Biobank of 461 047 adults aged 30–79 free of heart disease, stroke, and diabetes at baseline. Cardiometabolic multimorbidity was defined as the coexistence of two or three CMDs, including ischaemic heart disease (IHD), stroke, and type 2 diabetes (T2D). We used multi-state model to analyse the impacts of high-risk LFs (current smoking or quitting because of illness, current excessive alcohol drinking or quitting, poor diet, physical inactivity, and unhealthy body shape) on the progression of CMD. During a median follow-up of 11.2 years, 87 687 participants developed at least one CMD, 14 164 developed CMM, and 17 541 died afterwards. Five high-risk LFs played crucial but different roles in all transitions from healthy to FCMD, to CMM, and then to death. The hazard ratios (95% confidence intervals) per one-factor increase were 1.20 (1.19, 1.21) and 1.14 (1.11, 1.16) for transitions from healthy to FCMD, and from FCMD to CMM, and 1.21 (1.19, 1.23), 1.12 (1.10, 1.15), and 1.10 (1.06, 1.15) for mortality risk from healthy, FCMD, and CMM, respectively. When we further divided FCMDs into IHD, ischaemic stroke, haemorrhagic stroke, and T2D, we found that LFs played different roles in disease-specific transitions even within the same transition stage. Conclusion Assuming causality exists, our findings emphasize the significance of integrating comprehensive lifestyle interventions into both health management and CMD management.

Background It remains unclear about the association of muscle mass, strength, and quality with death in the general Chinese population of diverse economical and geographical backgrounds. The present study aimed to comprehensively examine such associations across different regions in China. Methods Based on the China Kadoorie Biobank study, the present study included 23,290 participants who were aged 38 to 88 years and had no prevalent cardiovascular diseases or cancer. Muscle mass and grip strength were measured using calibrated instruments. Arm muscle quality was defined as the ratio of grip strength to arm muscle mass. Low muscle mass, grip strength, and arm muscle quality were defined as the sex-specific lowest quintiles of muscle mass index, grip strength, and arm muscle quality, respectively. Cox proportional hazards models yielded hazard ratios (HRs) and 95% confidence intervals (CIs) for risks of all-cause mortality in relation to muscle mass, strength, and quality. Results During a median follow-up of 3.98 years, 739 participants died. The HR (95% CI) of all-cause mortality risk was 1.28 (1.08–1.51) for low appendicular muscle mass index, 1.38 (1.16–1.62) for low total muscle mass index, 1.68 (1.41–2.00) for low grip strength, and 1.41 (1.20–1.66) for low arm muscle quality in models adjusted for sociodemographic characteristics, lifestyle factors, and medical histories. Conclusion Low muscle mass, grip strength, and arm muscle quality are all associated with short-term increased risks of mortality, indicating the importance of maintaining normal muscle mass, strength, and quality for general Chinese adults.

Background and purposeLow-income and middle-income countries have the greatest stroke burden, yet remain understudied. This study compared the utility of Framingham versus novel risk scores for prediction of total stroke and stroke types in Chinese adults.MethodsChina Kadoorie Biobank (CKB) is a prospective study of 512 726 adults, aged 30–79 years, recruited from 10 areas in China in 2004–2008. By 1 January 2018, 43 234 incident first stroke cases (36 310 ischaemic stroke (IS); 8865 haemorrhagic stroke (HS)) were recorded in 503 842 participants with no history of stroke at baseline. We compared the predictive utility of the Framingham Stroke Risk Profile (FSRP) with novel CKB stroke risk scores and included recalibration, refitting, stratifying by study area and addition of other risk factors. Discrimination was assessed using area under the receiver operating characteristic curve (AUC) and calibration was assessed using Greenwood-Nam-D’Agostino χ2 statistics.ResultsIncidence of total stroke varied fivefold by area in China. The FSRP had good discrimination for total stroke (AUC (95% CI); men: 0.78 (0.77 to 0.79), women: 0.77 (95% CI 0.76 to 0.78)), but poor calibration (χ2; men: 1,825, women: 3,053), substantially underestimating absolute risks. Recalibration reduced χ2 by >80%, but did not improve discrimination. Refitting the FSRP did not materially improve discrimination, but further improved calibration. Stratification by area improved discrimination (AUC; men: 0.82 (0.82 to 0.83); women: 0.82 (0.82 to 0.83)), but not calibration. Adding other risk factors yielded modest, but statistically significant, improvements in the AUCs. The findings for IS and HS were similar to those for total stroke.ConclusionsThe FSRP reliably differentiated Chinese adults with incident stroke, but substantially underestimated the absolute risks of stroke. Novel local risk prediction equations that took account of differences in stroke incidence within China enhanced risk prediction of total stroke and major stroke pathological types.

Background Taller adult height is associated with lower risks of ischemic heart disease in mendelian randomization (MR) studies, but little is known about the causal relevance of height for different subtypes of ischemic stroke. The present study examined the causal relevance of height for different subtypes of ischemic stroke. Methods and findings Height-associated genetic variants (up to 2,337) from previous genome-wide association studies (GWASs) were used to construct genetic instruments in different ancestral populations. Two-sample MR approaches were used to examine the associations of genetically determined height with ischemic stroke and its subtypes (cardioembolic stroke, large-artery stroke, and small-vessel stroke) in multiple ancestries (the MEGASTROKE consortium, which included genome-wide studies of stroke and stroke subtypes: 60,341 ischemic stroke cases) supported by additional cases in individuals of white British ancestry (UK Biobank [UKB]: 4,055 cases) and Chinese ancestry (China Kadoorie Biobank [CKB]: 10,297 cases). The associations of genetically determined height with established cardiovascular and other risk factors were examined in 336,750 participants from UKB and 58,277 participants from CKB. In MEGASTROKE, genetically determined height was associated with a 4% lower risk (odds ratio [OR] 0.96; 95% confidence interval [CI] 0.94, 0.99; p = 0.007) of ischemic stroke per 1 standard deviation (SD) taller height, but this masked a much stronger positive association of height with cardioembolic stroke (13% higher risk, OR 1.13 [95% CI 1.07, 1.19], p < 0.001) and stronger inverse associations with large-artery stroke (11% lower risk, OR 0.89 [0.84, 0.95], p < 0.001) and small-vessel stroke (13% lower risk, OR 0.87 [0.83, 0.92], p < 0.001). The findings in both UKB and CKB were directionally concordant with those observed in MEGASTROKE, but did not reach statistical significance: For presumed cardioembolic stroke, the ORs were 1.08 (95% CI 0.86, 1.35; p = 0.53) in UKB and 1.20 (0.77, 1.85; p = 0.43) in CKB; for other subtypes of ischemic stroke in UKB, the OR was 0.97 (95% CI 0.90, 1.05; p = 0.49); and for other nonlacunar stroke and lacunar stroke in CKB, the ORs were 0.89 (0.80, 1.00; p = 0.06) and 0.99 (0.88, 1.12; p = 0.85), respectively. In addition, genetically determined height was also positively associated with atrial fibrillation (available only in UKB), and with lean body mass and lung function, and inversely associated with low-density lipoprotein (LDL) cholesterol in both British and Chinese ancestries. Limitations of this study include potential bias from assortative mating or pleiotropic effects of genetic variants and incomplete generalizability of genetic instruments to different populations. Conclusions The findings provide support for a causal association of taller adult height with higher risk of cardioembolic stroke and lower risk of other ischemic stroke subtypes in diverse ancestries. Further research is needed to understand the shared biological and physical pathways underlying the associations between height and stroke risks, which could identify potential targets for treatments to prevent stroke.

Background and aimsLiver biomarkers and metabolic associated fatty liver disease (MAFLD) have been shown to be associated with cardiovascular disease (CVD). However, there is limited evidence on CVD subtypes [myocardial infarction (MI), ischemic stroke (IS), and intracerebral hemorrhage (ICH)], especially in the Chinese population. We examined these associations overall, by genetic predisposition to non-alcoholic fatty liver disease (NAFLD), and by lifestyle risk factors.Approach and resultsThis is a nested case-control study of CVD (10,298 cases and 5,388 controls) within the China Kadoorie Biobank. Cox regression was used to estimate adjusted hazard ratios (HRs) for CVD associated with liver biomarkers and MAFLD and by stratum of genetic risk and a combined high-risk lifestyle score. For liver enzymes, there were positive associations with MI and IS, but no associations with ICH or carotid plaque. There were positive associations of NAFLD with risks of MI, IS, and ICH (HR 1.43 [95% CI 1.30–1.57], 1.25 [1.16–1.35], and 1.12 [1.02–1.23]) as well as carotid plaque (odds ratio 2.36 [1.12–4.96]). The associations of NAFLD with CVD and carotid plaque were stronger among individuals with a high genetic risk (ICH: p-interaction < 0.05), while the associations with stroke were stronger among those with a favorable lifestyle (p-interaction < 0.05). The results for MAFLD mirrored those for NAFLD.ConclusionIn Chinese adults, liver biomarkers and MAFLD were associated with risk of CVD, with different magnitudes of associations by CVD subtypes. Genetic predisposition to NAFLD and lifestyle factors modified the associations of fatty liver with stroke.

Pneumonia represents a public health problem of substantial health and economic burden. However, the evidence on the burden of adult pneumonia is limited in China.The China Kadoorie Biobank recruited 512,725 participants aged 30-79 years from five urban and five rural areas during 2004-2008. The current analyses included 506,086 participants who were alive in 2009. Pneumonia hospitalizations were ascertained through the health insurance system until December 31, 2017. Generalized linear models were used to examine the secular trends and regional and population variations in pneumonia hospitalization rate, mean length of hospital stay (LOS), and 30-day case fatality rate (CFR).A total of 27,879 participants with 36,567 pneumonia hospitalizations were identified with a mean follow-up time of 8·9 years. The unadjusted hospitalization rate was 8·4 (95% confidence interval [CI]: 8·3, 8·6) per 1000 person-years, with an increase of 15·5% annually from 4·2 (3·9, 4·4) in 2009 to 10·9 (10·6, 11·3) in 2017, after adjusting for age, sex, study area. The mean LOS was 8·8 (95% CI: 8·7, 8·9) days, with a slight decrease of 1·0% annually from 2009 to 2017. The average 30-day CFR remained practically unchanged at 2·4 (95% CI: 2·2, 2·5) deaths per 100 admissions. A clear seasonal pattern of pneumonia hospitalization rate was observed, and the hospitalization rate and CFR differed across regions and subpopulations of different ages and underlying conditions.There was an increasing hospitalization burden of pneumonia in Chinese adults, especially for adults aged ≥60 years or those with underlying conditions.The National Natural Science Foundation of China, the Kadoorie Charitable Foundation, the National Key RD Program of China, the Chinese Ministry of Science and Technology.This translation in Chinese was submitted by the authors and we reproduce it as supplied. It has not been peer reviewed. Our editorial processes have only been applied to the original abstract in English, which should serve as reference for this manuscript.

Background Tobacco smoking is estimated to account for more than 1 million annual deaths in China, and the epidemic continues to increase in men. Large nationwide prospective studies linked to different health records can help to periodically assess disease burden attributed to smoking. We aimed to examine associations of smoking with incidence of and mortality from an extensive range of diseases in China. Methods We analysed data from the prospective China Kadoorie Biobank, which recruited 512 726 adults aged 30–79 years, of whom 210 201 were men and 302 525 were women. Participants who had no major disabilities were identified through local residential records in 100–150 administrative units, which were randomly selected by use of multistage cluster sampling, from each of the ten diverse study areas of China. They were invited and recruited between June 25, 2004, and July 15, 2008. Upon study entry, trained health workers administered a questionnaire assessing detailed smoking behaviours and other key characteristics (eg, sociodemographics, lifestyle, and medical history). Participants were followed up via electronic record linkages to death and disease registries and health insurance databases, from baseline to Jan 1, 2018. During a median 11-year follow-up (IQR 10–12), 285 542 (55·7%) participants were ever hospitalised, 48 869 (9·5%) died, and 5252 (1·0%) were lost to follow-up during the age-at-risk of 35–84 years. Cox regression yielded hazard ratios (HRs) associating smoking with disease incidence and mortality, adjusting for multiple testing. Findings At baseline, 74·3% of men and 3·2% of women (overall 32·4%) ever smoked regularly. During follow-up, 1 137 603 International Classification of Diseases, 10th revision (ICD-10)-coded incident events occurred, involving 476 distinct conditions and 85 causes of death, each with at least 100 cases. Compared with never-regular smokers, ever-regular smokers had significantly higher risks for nine of 18 ICD-10 chapters examined at age-at-risk of 35–84 years. For individual conditions, smokers had significantly higher risks of 56 diseases (50 for men and 24 for women) and 22 causes of death (17 for men and nine for women). Among men, ever-regular smokers had an HR of 1·09 (95% CI 1·08–1·11) for any disease incidence when compared with never-regular smokers, and significantly more episodes and longer duration of hospitalisation, particularly those due to cancer and respiratory diseases. For overall mortality, the HRs were greater in men from urban areas than in men from rural areas (1·50 [1·42–1·58] vs 1·25 [1·20–1·30]). Among men from urban areas who began smoking at younger than 18 years, the HRs were 2·06 (1·89–2·24) for overall mortality and 1·32 (1·27–1·37) for any disease incidence. In this population, 19·6% of male (24·3% of men residing in urban settings and 16·2% of men residing in rural settings) and 2·8% of female deaths were attributed to ever-regular smoking. Interpretation Among Chinese adults, smoking was associated with higher risks of morbidity and mortality from a wide range of diseases. Among men, the future smoking-attributed disease burden will increase further, highlighting a pressing need for reducing consumption through widespread cessation and uptake prevention. Funding British Heart Foundation, Cancer Research UK, Chinese Ministry of Science and Technology, Kadoorie Charitable Foundation, UK Medical Research Council, National Natural Science Foundation of China, Wellcome Trust.

The evidence about the association between dietary patterns and the incidence of chronic obstructive pulmonary disease (COPD) among Chinese adults is limited. In the present study, we analyzed the prospective data of 421,426 participants aged 30–79 years from the China Kadoorie Biobank. Factor analysis with a principal component method was employed to identify dietary patterns. Cox proportional hazard regression models were performed to explore the association between dietary patterns and incident COPD. Two dietary patterns were identified: the traditional northern dietary pattern was characterized by a low intake of rice and a high intake of wheat and other staple foods, while the balanced dietary pattern was characterized by a high intake of fresh fruit and protein-rich foods (soybean, meat, poultry, fish, eggs, and dairy products). During a median follow-up of 11.13 years, 5542 men and 5750 women developed COPD. After adjustments for potential confounders, the balanced dietary pattern was associated with a lower risk of COPD (p for trend

Importance: Reliable evidence on modifiable risk factors for hip and major osteoporotic fractures in untreated populations could inform prevention strategies for hip fracture worldwide. Objectives: To estimate the age- and sex-specific incidence of hip, major osteoporotic and any fractures and examine their associated risk factors in Chinese adults. Design, Setting, and Participants: Prospective study of 512,715 adults, aged 30-79 years, recruited for the China Kadoorie Biobank from 10 diverse areas in China in 2004-2008 and followed up for 10 years. Exposures: Sociodemographic factors (e.g. age, sex, and education), medical history (e.g. CVD, diabetes, fracture, and rheumatoid arthritis), anthropometry (e.g. weight, waist-hip ratio) and lifestyle factors (e.g. smoking, alcohol drinking, physical activity, diet). Main Outcomes and Measures: Age- and sex-specific incidence rates of fracture types, and adjusted hazard ratios (HR) and population attributable fractions (PAF) for individual risk factors associated with fracture types. Results: The incidence rates of hip fracture in Chinese adults were 5.1 (95%CI 5.0- 5.3) per 10,000 person-years (2616 cases); and were higher in women than men (5.8 [5.5-6.1] vs 4.2 [3.9-4.5]) and increased by about 2 to 3-fold per 10 years older age. Among men, five risk factors for hip fracture including low education (HR=1.23; 95%CI 1.04-1.45), regular smoker (1.22, 1.03-1.45), lower weight (lowest vs other quintiles: 1.59, 1.34-1.88), alcohol drinker (1.18, 1.02-1.36), and prior fracture (1.62, 1.33-1.98) accounted for 44.3% of hip fractures. Among women, five risk factors including lower weight (lowest vs other quintiles: 1.30, 1.15-1.46), low physical activity (lowest vs other quintiles: 1.22, 1.10-1.35), diabetes (1.62, 1.41-1.86), prior fracture (1.54, 1.33-1.77), and self-rated poor health (1.29, 1.13-1.47), accounted for 24.9% of hip fractures. Associations of these risk factors with major osteoporotic (6857 cases) or any (15762 cases) fractures were weaker than those with hip fracture. Conclusions: The age- and sex-specific incidence rates of hip fracture in Chinese adults were comparable with those in Western populations. Five potentially modifiable factors accounted for half of all hip fractures in men and one quarter in women.

China has made rapid progress in reducing the incidence of HBV infection in the past three decades, along with a rapidly changing lifestyle and aging population. We aimed to develop and validate an up-to-date liver cancer risk prediction model with routinely available predictors and evaluate its applicability for screening guidance. Using data from the China Kadoorie Biobank, we included 486 285 participants in this analysis. Fifteen risk factors were included in the model. Flexible parametric survival models were used to estimate the 10-year absolute risk of liver cancer. Decision curve analysis was performed to evaluate the net benefit of the model to quantify clinical utility. A total of 2706 participants occurred liver cancer over the 4 814 320 person-years of follow-up. Excellent discrimination of the model was observed in both development and validation datasets, with c-statistics (95% CI) of 0.80 (0.79-0.81) and 0.80 (0.78-0.82) respectively, as well as excellent calibration of observed and predicted risks. Decision curve analysis revealed that use of the model in selecting participants for screening improved benefit at a threshold of 2% 10-year risk, compared to current guideline of screening all HBsAg carriers. Our model was more sensitive than current guideline for cancer screening (28.17% vs 25.96%). We developed and validated a CKB-PLR (Prediction for Liver cancer Risk Based on the China Kadoorie Biobank Study) model to predict the absolute risk of liver cancer for both HBsAg seropositive and seronegative populations. Application of the model is beneficial for precisely identifying the high-risk groups among the general population.

Background:Identifying environmentally responsive genetic loci where DNA methylation is associated with coronary heart disease (CHD) may reveal novel pathways or therapeutic targets for CHD. We conducted the first prospective epigenome-wide analysis of DNA methylation in relation to incident CHD in the Asian population.Methods:We did a nested case-control study comprising incident CHD cases and 1:1 matched controls who were identified from the 10 year follow-up of the China Kadoorie Biobank. Methylation level of baseline blood leukocyte DNA was measured by Infinium Methylation EPIC BeadChip. We performed the single cytosine-phosphate-guanine (CpG) site association analysis and network approach to identify CHD-associated CpG sites and co-methylation gene module.Results:After quality control, 982 participants (mean age 50.1 years) were retained. Methylation level at 25 CpG sites across the genome was associated with incident CHD (genome-wide false discovery rate [FDR] < 0.05 or module-specific FDR < 0.01). One SD increase in methylation level of identified CpGs was associated with differences in CHD risk, ranging from a 47 % decrease to a 118 % increase. Mediation analyses revealed 28.5 % of the excessed CHD risk associated with smoking was mediated by methylation level at the promoter region of ANKS1A gene (P for mediation effect = 0.036). Methylation level at the promoter region of SNX30 was associated with blood pressure and subsequent risk of CHD, with the mediating proportion to be 7.7 % (P = 0.003) via systolic blood pressure and 6.4 % (P = 0.006) via diastolic blood pressure. Network analysis revealed a co-methylation module associated with CHD.Conclusions:We identified novel blood methylation alterations associated with incident CHD in the Asian population and provided evidence of the possible role of epigenetic regulations in the smoking- and blood pressure-related pathways to CHD risk.Funding:This work was supported by National Natural Science Foundation of China (81390544 and 91846303). 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 (202922/Z/16/Z, 088158/Z/09/Z, 104085/Z/14/Z), grant (2016YFC0900500, 2016YFC0900501, 2016YFC0900504, 2016YFC1303904) from the National Key R&D Program of China, and Chinese Ministry of Science and Technology (2011BAI09B01).

Purpose There is limited and inconsistent evidence about the relationships of erythrocyte polyunsaturated fatty acids (PUFAs) with stroke and stroke types, particularly in China where the stroke rates are high. We aimed to investigate the associations of different erythrocyte PUFAs with incidence of total stroke, ischemic stroke (IS), and intracerebral hemorrhage (ICH) in Chinese adults. Methods In the prospective China Kadoorie Biobank, erythrocyte PUFAs were measured using gas chromatography in 10,563 participants who attended 2013–14 resurvey. After a mean follow-up of 3.8 years, 412 incident stroke cases (342 IS, 53 ICH) were recorded among 8,159 participants without prior vascular diseases or diabetes. Cox regression yielded adjusted hazard ratios (HRs) for stroke associated with 13 PUFAs. Results Overall, the mean body mass index was 24.0 (3.4) kg/m2 and the mean age was 58.1 (9.9) years. In multivariable analyses, 18:2n–6 was positively associated with ICH (HR = 2.33 [95% CIs 1.41, 3.82] for top versus bottom quintile, Ptrend = 0.007), but inversely associated with IS (0.69 [0.53,0.90], Ptrend = 0.027), while 20:3n-6 was positively associated with risk of IS (1.64 [1.32,2.04], Ptrend Pnonlinear = 0.002) and total stroke (Pnonlinear = 0.008), with a threshold at 0.70%. After further adjustment for conventional CVD risk factors and dietary factors, these associations remained similar. Conclusion Among relatively lean Chinese adults, erythrocyte PUFAs 18:2n–6, 20:3n–6 and 20:5n–3 showed different associations with risks of IS and ICH. These results would improve the understanding of stroke etiology.

Background:Few studies have assessed the role of individual plasma cholesterol levels in the association between egg consumption and the risk of cardiovascular diseases. This research aims to simultaneously explore the associations of self-reported egg consumption with plasma metabolic markers and these markers with the risk of cardiovascular disease (CVD).Methods:Totally 4778 participants (3401 CVD cases subdivided into subtypes and 1377 controls) aged 30–79 were selected based on the China Kadoorie Biobank. Targeted nuclear magnetic resonance was used to quantify 225 metabolites in baseline plasma samples. Linear regression was conducted to assess associations between self-reported egg consumption and metabolic markers, which were further compared with associations between metabolic markers and CVD risk.Results:Egg consumption was associated with 24 out of 225 markers, including positive associations for apolipoprotein A1, acetate, mean HDL diameter, and lipid profiles of very large and large HDL, and inverse associations for total cholesterol and cholesterol esters in small VLDL. Among these 24 markers, 14 were associated with CVD risk. In general, the associations of egg consumption with metabolic markers and of these markers with CVD risk showed opposite patterns.Conclusions:In the Chinese population, egg consumption is associated with several metabolic markers, which may partially explain the protective effect of moderate egg consumption on CVD.Funding:This work was supported by the National Natural Science Foundation of China (81973125, 81941018, 91846303, 91843302). 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 (2016YFC0900500, 2016YFC0900501, 2016YFC0900504, 2016YFC1303904) from the National Key R&D Program of China, National Natural Science Foundation of China (81390540, 81390541, 81390544), and Chinese Ministry of Science and Technology (2011BAI09B01). The funders had no role in the study design, data collection, data analysis and interpretation, writing of the report, or the decision to submit the article for publication.

Background Little is known about the effects of lifestyle modification on biological aging in population-based studies of middle-aged and older adults. Method We examined the individual and joint associations of multiple lifestyle factors with accelerated biological aging measured by change in frailty index (FI) over 8 years in a prospective study of Chinese adults. Data were obtained on 24 813 participants in the China Kadoorie Biobank on lifestyle factors and frailty status at baseline and at 8 years after baseline. Adherence to healthy lifestyle factors included nonsmoking or quitting smoking for reasons other than illness, avoidance of heavy alcohol consumption, daily intake of fruit and vegetables, being physically active, body mass index of 18.5–23.9 kg/m2, and waist-to-hip ratio of Results Overall, 8 760 (35.3%) individuals had a worsening frailty status. In multivariable-adjusted logistic regression analyses, adherence to healthy lifestyle was associated with a lower risk of worsening frailty status. Compared with robust participants maintaining 0–1 healthy lifestyle factors, the corresponding odds ratios (95% CIs) were 0.93 (0.83–1.03), 0.75 (0.67–0.84), 0.68 (0.60–0.77), and 0.55 (0.46–0.65) for robust participants with 2, 3, 4, and 5–6 healthy lifestyle factors. The decreased risk of frailty status worsening by adherence to healthy lifestyle factors was similar in both middle-aged and older adults, and in both robust and prefrail participants at baseline. Conclusions Adherence to a healthy lifestyle may attenuate the rate of change in biological aging in middle-aged and older Chinese adults.

Background Evidence from epidemiological studies remains inconsistent or limited about the associations of tea consumption with incident diabetes and risk of diabetic complications and death among patients with diabetes. Objectives We aimed to investigate the associations of tea consumption with long-term risk of developing type 2 diabetes (T2D) and risks of diabetic complications and death among patients with diabetes. Methods This study included 482,425 diabetes-free participants and 30,300 patients with diabetes aged 30–79 y at study enrollment from the China Kadoorie Biobank. Tea consumption information was collected at baseline by interviewer-administered questionnaires. Incidences of diabetes, diabetic complications, and death were identified by linkages to the National Health Insurance system, disease registries, and death registries. Cox proportional hazard regression models were used to estimate HRs and 95% CIs. Results The mean ± SD age of participants free of diabetes was 51.2 ± 10.5 y and 41% were male. The mean ± SD age of patients with diabetes was 58.2 ± 9.6 y and 39% were male. Of all daily tea consumers, 85.8% preferred green tea. In the diabetes-free population, 17,434 participants developed incident T2D during 11.1 y of follow-up. Compared with participants who never consumed tea in the past year, the HR (95% CI) of T2D for daily consumers was 0.92 (0.88, 0.97). In patients with diabetes, we identified 6572 deaths, 12,677 diabetic macrovascular cases, and 2441 diabetic microvascular cases during follow-up. Compared with patients who never consumed tea in the past year, the HRs (95% CIs) of all-cause mortality and risk of microvascular complications for daily consumers were 0.90 (0.83, 0.97) and 0.88 (0.78, 1.00), respectively. Tea consumption was not associated with risk of macrovascular complications among patients with diabetes. With regard to tea consumed, the inverse associations between daily tea consumption and risks of T2D and all-cause mortality in patients with diabetes were only observed among daily green tea drinkers. Conclusions In Chinese adults, daily green tea consumption was associated with a lower risk of incident T2D and a lower risk of all-cause mortality in patients with diabetes, but the associations for other types of tea were less clear. In addition, daily tea consumption was associated with a lower risk of diabetic microvascular complications, but not macrovascular complications.

Background and ObjectivesContemporary cardiovascular disease (CVD) risk prediction models are rarely applied in routine clinical practice in China due to substantial regional differences in absolute risks of major CVD types within China. Moreover, the inclusion of blood lipids in most risk prediction models also limits their use in the Chinese population. We developed 10-year CVD risk prediction models excluding blood lipids that may be applicable to diverse regions of China.MethodsWe derived sex-specific models separately for ischemic heart disease (IHD), ischemic stroke (IS), and hemorrhagic stroke (HS) in addition to total CVD in the China Kadoorie Biobank. Participants were age 30–79 years without CVD at baseline. Predictors included age, systolic and diastolic blood pressure, use of blood pressure–lowering treatment, current daily smoking, diabetes, and waist circumference. Total CVD risks were combined in terms of conditional probability using the predicted risks of 3 submodels. Risk models were recalibrated in each region by 2 methods (practical and ideal) and risk prediction was estimated before and after recalibration.ResultsModel derivation involved 489,596 individuals, including 45,947 IHD, 43,647 IS, and 11,168 HS cases during 11 years of follow-up. In women, the Harrell C was 0.732 (95% CI 0.706–0.758), 0.759 (0.738–0.779), and 0.803 (0.778–0.827) for IHD, IS, and HS, respectively. The Harrell C for total CVD was 0.734 (0.732–0.736), 0.754 (0.752–0.756), and 0.774 (0.772–0.776) for models before recalibration, after practical recalibration, and after ideal recalibration. The calibration performances improved after recalibration, with models after ideal recalibration showing the best model performances. The results for men were comparable to those for women.DiscussionOur CVD risk prediction models yielded good discrimination of IHD and stroke subtypes in addition to total CVD without including blood lipids. Flexible recalibration of our models for different regions could enable more widespread use using resident health records covering the overall Chinese population.Classification of EvidenceThis study provides Class I evidence that a prediction model incorporating accessible clinical variables predicts 10-year risk of IHD, IS, and HS in the Chinese population age 30–79 years.

BackgroundThe relationship between educational attainment and ischaemic heart disease (IHD) is limited in evidence in middle-income countries like China. Exploring lifestyle-related mediators, which might be not universal between socioeconomic status and health outcomes in diverse regions, can contribute to interventions targeted at the Chinese to narrow the educational gap in IHD.MethodsBased on the China Kadoorie Biobank of 489 594 participants aged 30–79 years who did not have heart disease or stroke at baseline, this study examined the association of educational attainment with IHD. Total IHD cases were further divided into acute myocardial infarction (AMI) cases and non-AMI cases. The Cox proportional hazard model was performed to estimate the HRs and 95% CIs for mortality and incidence of IHD. Logistic regression was used to estimate the ORs and 95% CIs for case fatality.ResultsDuring the median follow-up period of 11.1 years, this study documented 45 946 (6668) incident IHD (AMI) cases and 5948 (3689) deaths altogether. Lower educational attainment was associated with increased risk of incident AMI as well as death and fatality of total IHD including its subtypes (ptrend trend DiscussionInterventions targeting unhealthy lifestyles are ideal ways to narrow the educational gap in IHD while solving ‘upstream’ causes of health behaviours might be the most fundamental ones.

BackgroundsIn contrast to developed countries, breast cancer in China is characterized by a rapidly escalating incidence rate in the past two decades, lower survival rate, and vast geographic variation. However, there is no validated risk prediction model in China to aid early detection yet.MethodsA large nationwide prospective cohort, China Kadoorie Biobank (CKB), was used to evaluate relative and attributable risks of invasive breast cancer. A total of 300,824 women free of any prior cancer were recruited during 2004–2008 and followed up to Dec 31, 2016. Cox models were used to identify breast cancer risk factors and build a relative risk model. Absolute risks were calculated by incorporating national age- and residence-specific breast cancer incidence and non-breast cancer mortality rates. We used an independent large prospective cohort, Shanghai Women’s Health Study (SWHS), with 73,203 women to externally validate the calibration and discriminating accuracy.ResultsDuring a median of 10.2 years of follow-up in the CKB, 2287 cases were observed. The final model included age, residence area, education, BMI, height, family history of overall cancer, parity, and age at menarche. The model was well-calibrated in both the CKB and the SWHS, yielding expected/observed (E/O) ratios of 1.01 (95% confidence interval (CI), 0.94–1.09) and 0.94 (95% CI, 0.89–0.99), respectively. After eliminating the effect of age and residence, the model maintained moderate but comparable discriminating accuracy compared with those of some previous externally validated models. The adjusted areas under the receiver operating curve (AUC) were 0.634 (95% CI, 0.608–0.661) and 0.585 (95% CI, 0.564–0.605) in the CKB and the SWHS, respectively.ConclusionsBased only on non-laboratory predictors, our model has a good calibration and moderate discriminating capacity. The model may serve as a useful tool to raise individuals’ awareness and aid risk-stratified screening and prevention strategies.

Objective To compare Cox models, machine learning (ML), and ensemble models combining both approaches, for prediction of stroke risk in a prospective study of Chinese adults. Materials and Methods We evaluated models for stroke risk at varying intervals of follow-up (10% predicted 9-yr stroke risk) by selectively applying either a GBT or Cox model based on individual-level characteristics. Results For 9-yr stroke risk prediction, GBT provided the best discrimination (AUROC: 0.833 in men, 0.836 in women) and calibration, with consistent results in each interval of follow-up. The ensemble approach yielded incrementally higher accuracy (men: 76%, women: 80%), specificity (men: 76%, women: 81%), and positive predictive value (men: 26%, women: 24%) compared to any of the single-model approaches. Discussion and Conclusion Among several approaches, an ensemble model combining both GBT and Cox models achieved the best performance for identifying individuals at high risk of stroke in a contemporary study of Chinese adults. The results highlight the potential value of expanding the use of ML in clinical practice.

An author correction to this article published in December 2020 is available at https://doi.org/10.1038/s41588-020-00760-4. Rupture of an intracranial aneurysm leads to subarachnoid hemorrhage, a severe type of stroke. To discover new risk loci and the genetic architecture of intracranial aneurysms, we performed a cross-ancestry, genome-wide association study in 10,754 cases and 306,882 controls of European and East Asian ancestry. We discovered 17 risk loci, 11 of which are new. We reveal a polygenic architecture and explain over half of the disease heritability. We show a high genetic correlation between ruptured and unruptured intracranial aneurysms. We also find a suggestive role for endothelial cells by using gene mapping and heritability enrichment. Drug-target enrichment shows pleiotropy between intracranial aneurysms and antiepileptic and sex hormone drugs, providing insights into intracranial aneurysm pathophysiology. Finally, genetic risks for smoking and high blood pressure, the two main clinical risk factors, play important roles in intracranial aneurysm risk, and drive most of the genetic correlation between intracranial aneurysms and other cerebrovascular traits.

Background and aims Observational studies have associated resting heart rate with incident diabetes. Whether the associations are causal remains unclear. We aimed to examine the shape and strength of the associations and assessed the causal relevance of such associations in Chinese adults. Methods and results The China Kadoorie Biobank enrolled 512,891 adults in China. Cox proportional hazard regression models was conducted to estimate hazard ratios (HRs) for the associations of resting heart rate with type 2 diabetes and total diabetes. Among 92,724 participants, 36 single-nucleotide polymorphisms (SNPs) related to resting heart rate were used to construct genetic risk score. We used Mendelian randomization analyses to make the causal inferences. During a median follow-up of 9 years, 7872 incident type 2 diabetes and 13,349 incident total diabetes were documented. After regression dilution bias adjustment, each 10 bpm higher heart rate was associated with about a 26% higher risk of type 2 diabetes (HR, 1.26 [95% CI, 1.23, 1.29]) and 23% higher risk of total diabetes (HR, 1.23 [95% CI, 1.20, 1.26]). Instrumental variable analyses showed participants at top quintile compared with those at bottom quintile had 30% higher risk for type 2 diabetes (HR, 1.30 [95% CI, 1.17, 1.43]), and 10% higher risk for total diabetes (HR, 1.10 [95% CI, 1.02, 1.20]). Conclusions This study provides evidence that resting heart rate is an important risk factor for diabetes risk. The results suggest that novel treatment approaches targeting reduction of high heart rate for incidence of diabetes may be worth further investigation.

Background Blood pressure (BP) categories are useful to simplify preventions in public health, and diagnostic and treatment approaches in clinical practice. Updated evidence about the associations of BP categories with cardiovascular diseases (CVDs) and its subtypes is warranted. Methods and findings About 0.5 million adults aged 30 to 79 years were recruited from 10 areas in China during 2004–2008. The present study included 430 977 participants without antihypertension treatment, cancer, or CVD at baseline. BP was measured at least twice in a single visit at baseline and CVD deaths during follow-up were collected via registries and the national health insurance databases. Multivariable Cox regression was used to estimate the associations between BP categories and CVD mortality. Overall, 16.3% had prehypertension-low, 25.1% had prehypertension-high, 14.1% had isolated systolic hypertension (ISH), 1.9% had isolated diastolic hypertension (IDH), and 9.1% had systolic-diastolic hypertension (SDH). During a median 10-year follow-up, 9660 CVD deaths were documented. Compared with normal, the hazard ratios (95% CI) of prehypertension-low, prehypertension-high, ISH, IDH, SDH for CVD were 1.10 (1.01–1.19), 1.32 (1.23–1.42), 2.04 (1.91–2.19), 2.20 (1.85–2.61), and 3.81 (3.54–4.09), respectively. All hypertension subtypes were related to the increased risk of CVD subtypes, with a stronger association for hemorrhagic stroke than for ischemic heart disease. The associations were stronger in younger than older adults. Conclusions Prehypertension-high should be considered in CVD primary prevention given its high prevalence and increased CVD risk. All hypertension subtypes were independently associated with CVD and its subtypes mortality, though the strength of associations varied substantially.

Objective: Bone loss is accelerated after menopause in women, as is the risk of hip fracture, but little is known about the importance of age at menopause, time since menopause, and total reproductive years for risk of hip fracture. Methods: Between 2004 and 2008, the China Kadoorie Biobank recruited 125,336 postmenopausal women who had a natural menopause and recorded 1,327 incident cases of hip fracture during the first 10 years of follow-up. Multivariable Cox regression was used to estimate hazard ratios and 95% CIs for incident hip fracture for age at menopause, time since menopause, and total reproductive years. Results: The mean (SD) age at menopause was 48.8 (4.0) years. Compared with women who reached menopause before age 53 years, women with a later age at menopause had a 22% (95% CI, 11%-35%) lower risk of hip fracture. Compared with women who were ≺5 years since menopause, those who were 5 to 9, 10 to 14, 15 to 19, and ≥20 years since menopause had hazard ratios of hip fracture of 1.43 (95% CI, 1.01-2.04), 2.10 (95% CI, 1.71-2.57), 2.50 (95% CI, 2.21-2.83), and 2.33 (95% CI, 1.97-2.75), respectively. Women with a longer (≥36 y) versus shorter (≺30 y) duration of total reproductive years had a 19% (95% CI, 9-28) lower risk of hip fracture. Conclusions: Women with younger age at menopause, longer interval since menopause, or shorter duration of total reproductive years had the highest risks of hip fracture.