DNA Methylation Age Mediates Effect of Metabolic Profile on Cardiovascular and General Aging.

BACKGROUND: Alterations in lipid metabolism and DNA methylation are 2 hallmarks of aging. Connecting metabolomic, epigenomic, and aging outcomes help unravel the complex mechanisms underlying aging. We aimed to assess whether DNA methylation clocks mediate the association of circulating metabolites with incident atherosclerotic cardiovascular disease (ASCVD) and frailty. METHODS: The China Kadoorie Biobank is a prospective cohort study with a baseline survey from 2004 to 2008 and a follow-up period until December 31, 2018. We used the Infinium Methylation EPIC BeadChip to measure the methylation levels of 988 participants' baseline blood leukocyte DNA. Metabolite profiles, including lipoprotein particles, lipid constituents, and various circulating metabolites, were measured using quantitative nuclear magnetic resonance. The pace of DNA methylation age acceleration (AA) was calculated using 5 widely used epigenetic clocks (the first generation: Horvath, Hannum, and Li; the second generation: Grim and Pheno). Incident ASCVD was ascertained through linkage with local death and disease registries and national health insurance databases, supplemented by active follow-up. The frailty index was constructed using medical conditions, symptoms, signs, and physical measurements collected at baseline. RESULTS: A total of 508 incident cases of ASCVD were documented during a median follow-up of 9.5 years. The first generation of epigenetic clocks was associated with the risk of ASCVD (P<0.05). For each SD increment in LiAA, HorvathAA, and HannumAA, the corresponding hazard ratios for ASCVD risk were 1.16 (1.05-1.28), 1.10 (1.00-1.22), and 1.17 (1.04-1.31), respectively. Only LiAA mediated the association of various metabolites (lipids, fatty acids, histidine, and inflammatory biomarkers) with ASCVD, with the mediating proportion reaching up to 15% for the diameter of low-density lipoprotein (P=1.2×10-2). Regarding general aging, a 1-SD increase in GrimAA was associated with an average increase of 0.10 in the frailty index (P=2.0×10-3), and a 33% and 63% increased risk of prefrailty and frailty at baseline (P=1.5×10-2 and 5.8×10-2), respectively; this association was not observed with other clocks. GrimAA mediated the effect of various lipids, fatty acids, glucose, lactate, and inflammatory biomarkers on the frailty index, with the mediating proportion reaching up to 22% for triglycerides in very small-sized very low-density lipoprotein (P=6.0×10-3). CONCLUSIONS: These findings suggest that epigenomic mechanisms may play a role in the associations between circulating metabolites and the aging process. Different mechanisms underlie the first and second generations of DNA methylation age in cardiovascular and general aging.

Associations of diabetes, circulating protein biomarkers, and risk of pancreatic cancer.

BACKGROUND: Type 2 diabetes (T2D) is associated with higher risk of pancreatic cancer (PC), but the underlying mechanisms are not fully understood. METHODS: We conducted a case-subcohort study involving 610 PC cases and 623 subcohort participants with 92 protein biomarkers measured in baseline plasma samples. Genetically-instrumented T2D was derived using 86 single-nucleotide polymorphisms (SNPs), including insulin resistance (IR) SNPs. RESULTS: In observational analyses of 623 subcohort participants (mean age, 52 years; 61% women), T2D was positively associated with 13 proteins (SD difference: IL6: 0.52 [0.23-0.81]; IL10: 0.41 [0.12-0.70]), of which 8 were nominally associated with incident PC. The 8 proteins potentially mediated 36.9% (18.7-75.0%) of the association between T2D and PC. In MR, no associations were observed for genetically-determined T2D with proteins, but there were positive associations of genetically-determined IR with IL6 and IL10 (SD difference: 1.23 [0.05-2.41] and 1.28 [0.31-2.24]). In two-sample MR, fasting insulin was associated with both IL6 and PC, but no association was observed between IL6 and PC. CONCLUSIONS: Proteomics were likely to explain the association between T2D and PC, but were not causal mediators. Elevated fasting insulin driven by insulin resistance might explain the associations of T2D, proteomics, and PC.

Long-Term Exposure to Fine Particulate Matter and Incidence of Esophageal Cancer: A Prospective Study of 0.5 Million Chinese Adults.

BACKGROUND & AIMS: Evidence is sparse and inconclusive on the association between long-term fine (≤2.5 µm) particulate matter (PM2.5) exposure and esophageal cancer. We aimed to assess the association of PM2.5 with esophageal cancer risk and compared the esophageal cancer risk attributable to PM2.5 exposure and other established risk factors. METHODS: This study included 510,125 participants without esophageal cancer at baseline from China Kadoorie Biobank. A high-resolution (1 × 1 km) satellite-based model was used to estimate PM2.5 exposure during the study period. Hazard ratios (HR) and 95% CIs of PM2.5 with esophageal cancer incidence were estimated using Cox proportional hazard model. Population attributable fractions for PM2.5 and other established risk factors were estimated. RESULTS: There was a linear concentration-response relationship between long-term PM2.5 exposure and esophageal cancer. For each 10-µg/m3 increase in PM2.5, the HR was 1.16 (95% CI, 1.04-1.30) for esophageal cancer incidence. Compared with the first quarter of PM2.5 exposure, participants in the highest quarter had a 1.32-fold higher risk for esophageal cancer, with an HR of 1.32 (95% CI, 1.01-1.72). The population attributable risk because of annual average PM2.5 concentration ≥35 µg/m3 was 23.3% (95% CI, 6.6%-40.0%), higher than the risks attributable to lifestyle risk factors. CONCLUSIONS: This large prospective cohort study of Chinese adults found that long-term exposure to PM2.5 was associated with an elevated risk of esophageal cancer. With stringent air pollution mitigation measures in China, a large reduction in the esophageal cancer disease burden can be expected.

Mosaic loss of chromosome Y, tobacco smoking, and risk of age-related lung diseases: insights from two prospective cohorts.

BACKGROUND: Little is known about the underlying relationship between mosaic loss of chromosome Y (mLOY), the most common chromosomal alterations in older men, and the risk of age-related lung diseases. METHODS: We included 217 780 participants from the UK Biobank and 42 859 participants from the China Kadoorie Biobank. The mLOY events were detected using the Mosaic Chromosomal Alterations pipeline. Outcomes included all lung diseases, chronic obstructive pulmonary disease (COPD), lung cancer, and idiopathic pulmonary fibrosis (IPF). Cox proportional hazard models were fitted to estimate the hazard ratios (HRs) and 95% confidence intervals (CIs) of mLOY with lung diseases in both cohorts. The combined HRs were derived from meta-analysis. RESULTS: Results from two cohorts showed that expanded mLOY was associated with increased risks of all lung diseases [HR (95% CI): 1.19 (1.04, 1.37)], COPD [HR (95% CI): 1.20 (1.13, 1.28)], lung cancer [HR (95% CI): 1.34 (1.21, 1.48)], and IPF [HR (95% CI): 1.34 (1.16, 1.56) in UKB]. There was evidence of positive interactions between mLOY and smoking behavior [relative excess risk due to interaction (97.5%CI)>0]. Additionally, we observed that current smokers with expanded mLOY had the highest risk of incident lung diseases in both cohorts. CONCLUSION: mLOY may be a novel predictor for age-related lung diseases. For current smokers carrying mLOY, adopting quitting smoking behavior may contribute to substantially reduce their risk of incident lung diseases.

Effects of Cuisine-Based Chinese Heart-Healthy Diet in Lowering Blood Pressure Among Adults in China: Multicenter, Single-Blind, Randomized, Parallel Controlled Feeding Trial.

BACKGROUND: More than one-fifth of the world's population consumes Chinese cuisines regularly, but no evidence-based healthy diets fitting the Chinese food culture are available for implementation. METHODS: A multicenter, patient- and outcome assessor-blind, randomized feeding trial was conducted among 265 participants with 130 to 159 mm Hg baseline systolic blood pressure (SBP) for 4 major Chinese cuisines (Shangdong, Huaiyang, Cantonese, Szechuan). After a 7-day run-in period on a control diet matching the usual local diets, participants were randomized to continue with the control diet or the cuisine-based Chinese heart-healthy diet for another 28 days. The primary outcome was SBP, and secondary outcomes included diastolic blood pressure and food preference score. Linear regression models were used to estimate the intervention effects and adjustments for the center. The incremental cost per 1 mm Hg reduction in SBP was also calculated. RESULTS: A total of 265 participants were randomized (135 on the Chinese heart-healthy diet and 130 on the control diet), with 52% women, mean age of 56.5±9.8 years, and mean SBP and diastolic blood pressure of 139.4±8.3 and 88.1±8.0 mm Hg, respectively, at baseline. The change in SBP and diastolic blood pressure from baseline to the end of the study in the control group was -5.0 (95% CI, -6.5 to -3.5) mm Hg and -2.8 (95% CI, -3.7 to -1.9) mm Hg, respectively. The net difference of change between the 2 groups in SBP and diastolic blood pressure were -10.0 (95% CI, -12.1 to -7.9) mm Hg and -3.8 (95% CI, -5.0 to -2.5) mm Hg, respectively. The effect size did not differ among cuisines (P for interaction=0.173). The mean food preference score was 9.5 (with 10 the best preferred) at baseline, and the net change during intervention was 0.1 (95% CI, -0.1 to 0.2; P=0.558). The incremental cost-effectiveness ratio per 1 mm Hg SBP reduction was CNY 0.4 (USD 0.06) per day. No difference in the number of adverse events was found between the 2 groups (P=0.259), and none of the adverse events was associated with the intervention. CONCLUSIONS: The Chinese heart-healthy diet is effective, palatable, and cost-effective in reducing blood pressure in Chinese adults with high blood pressure, with a clinically significant effect applicable across major Chinese cuisine cultures. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT03882645.

Duration-dependent impact of cardiometabolic diseases and multimorbidity on all-cause and cause-specific mortality: a prospective cohort study of 0.5 million participants.

BACKGROUND: The association of incident cardiometabolic multimorbidity (CMM) with mortality risk is rarely studied, and neither are the durations of cardiometabolic diseases (CMDs). Whether the association patterns of CMD durations with mortality change as individuals progress from one CMD to CMM is unclear. METHODS: Data from China Kadoorie Biobank of 512,720 participants aged 30-79 was used. CMM was defined as the simultaneous presence of two or more CMDs of interest, including diabetes, ischemic heart disease, and stroke. Cox regression was used to estimate the hazard ratios (HRs) and 95% confidence intervals (CIs) for the duration-dependent associations of CMDs and CMM with all-cause and cause-specific mortality. All information on exposures of interest was updated during follow-up. RESULTS: During a median follow-up of 12.1 years, 99,770 participants experienced at least one incident CMD, and 56,549 deaths were documented. Among 463,178 participants free of three CMDs at baseline, compared with no CMD during follow-up, the adjusted HRs (95% CIs) between CMM and all-cause mortality, mortality from circulatory system diseases, respiratory system diseases, cancer, and other causes were 2.93 (2.80-3.07), 5.05 (4.74-5.37), 2.72 (2.35-3.14), 1.30 (1.16-1.45), and 2.30 (2.02-2.61), respectively. All CMDs exhibited a high mortality risk in the first year of diagnosis. Subsequently, with prolonged disease duration, mortality risk increased for diabetes, decreased for IHD, and sustained at a high level for stroke. With the presence of CMM, the above association estimates inflated, but the pattern of which remained. CONCLUSION: Among Chinese adults, mortality risk increased with the number of the CMDs and changed with prolonged disease duration, the patterns of which varied among the three CMDs.

WHO cardiovascular disease risk prediction model performance in 10 regions, China.

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.

Association between Fish Consumption and Risk of Chronic Obstructive Pulmonary Disease among Chinese Men and Women: an 11-Year Population-Based Cohort Study.

BACKGROUND: Epidemiological evidence on the relation between fish consumption and chronic obstructive pulmonary disease (COPD) is limited, especially among Chinese. OBJECTIVES: The aim was to explore the prospective association between fish consumption and COPD among a large population-based Chinese cohort. METHODS: The China Kadoorie Biobank recruited over 0.5 million participants from 10 geographically diverse regions across China from 2004 to 2008. Consumption frequency of fish at baseline was assessed by a validated food-frequency questionnaire. A total of 169,188 men and 252,238 women who had no prior COPD or other major chronic diseases at baseline were included in our analyses. Cox proportional hazard models were used to estimate HRs and 95% CIs for fish consumption categories in relation to incident COPD. RESULTS: During a median follow-up of 11.1 y, 11,292 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 d/wk compared with nonconsumption (HR: 0.83; 95% CI: 0.70, 0.99; P-trend = 0.017), whereas we did not observe such a dose-response relation among men (HR: 0.89; 95% CI: 0.76, 1.05; P-trend = 0.373). The joint analysis showed that COPD risk was 38% and 48% lower in men and women who consumed fish ≥4 d/wk 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 (kg/m2): 18.5-23.9; normal waist circumference; reasonable diet], compared with participants with fish consumption <4 d/wk and an unhealthy lifestyle (≤1 factors). CONCLUSIONS: Higher fish consumption was associated with lower COPD risk among Chinese women but not men. This association was independent of lifestyle factors. Eating adequate fish with an overall healthy lifestyle might help lower the risk of COPD.

Whole-genome sequencing and gene sharing network analysis powered by machine learning identifies antibiotic resistance sharing between animals, humans and environment in livestock farming.

Anthropogenic environments such as those created by intensive farming of livestock, have been proposed to provide ideal selection pressure for the emergence of antimicrobial-resistant Escherichia coli bacteria and antimicrobial resistance genes (ARGs) and spread to humans. Here, we performed a longitudinal study in a large-scale commercial poultry farm in China, collecting E. coli isolates from both farm and slaughterhouse; targeting animals, carcasses, workers and their households and environment. By using whole-genome phylogenetic analysis and network analysis based on single nucleotide polymorphisms (SNPs), we found highly interrelated non-pathogenic and pathogenic E. coli strains with phylogenetic intermixing, and a high prevalence of shared multidrug resistance profiles amongst livestock, human and environment. Through an original data processing pipeline which combines omics, machine learning, gene sharing network and mobile genetic elements analysis, we investigated the resistance to 26 different antimicrobials and identified 361 genes associated to antimicrobial resistance (AMR) phenotypes; 58 of these were known AMR-associated genes and 35 were associated to multidrug resistance. We uncovered an extensive network of genes, correlated to AMR phenotypes, shared among livestock, humans, farm and slaughterhouse environments. We also found several human, livestock and environmental isolates sharing closely related mobile genetic elements carrying ARGs across host species and environments. In a scenario where no consensus exists on how antibiotic use in the livestock may affect antibiotic resistance in the human population, our findings provide novel insights into the broader epidemiology of antimicrobial resistance in livestock farming. Moreover, our original data analysis method has the potential to uncover AMR transmission pathways when applied to the study of other pathogens active in other anthropogenic environments characterised by complex interconnections between host species.

Device-measured movement behaviours in over 20,000 China Kadoorie Biobank participants.

BACKGROUND: Movement behaviours, including physical activity, sedentary behaviour, and sleep have been shown to be associated with several chronic diseases. However, they have not been objectively measured in large-scale prospective cohort studies in low-and middle-income countries. We aim to describe the patterns of device-measured movement behaviours collected in the China Kadoorie Biobank (CKB) study. METHODS: During 2020 and 2021, a random subset of 25,087 surviving CKB individuals participated in the 3rd resurvey of the CKB. Among them, 22,511 (89.7%) agreed to wear an Axivity AX3 wrist-worn triaxial accelerometer for seven consecutive days to assess their habitual movement behaviours. We developed a machine-learning model to infer time spent in four movement behaviours [i.e. sleep, sedentary behaviour, light intensity physical activity (LIPA), and moderate-to-vigorous physical activity (MVPA)]. Descriptive analyses were performed for wear-time compliance and patterns of movement behaviours by different participant characteristics. RESULTS: Data from 21,897 participants (aged 65.4 ± 9.1 years; 35.4% men) were received for demographic and wear-time analysis, with a median wear-time of 6.9 days (IQR: 6.1-7.0). Among them, 20,370 eligible participants were included in movement behavior analyses. On average, they had 31.1 mg/day (total acceleration) overall activity level, accumulated 7.7 h/day (32.3%) of sleep time, 8.8 h/day (36.6%) sedentary, 5.7 h/day (23.9%) in light physical activity, and 104.4 min/day (7.2%) in moderate-to-vigorous physical activity. There was an inverse relationship between age and overall acceleration with an observed decline of 5.4 mg/day (17.4%) per additional decade. Women showed a higher activity level than men (32.3 vs 28.8 mg/day) and there was a marked geographical disparity in the overall activity level and time allocation. CONCLUSIONS: This is the first large-scale accelerometer data collected among Chinese adults, which provides rich and comprehensive information about device-measured movement behaviour patterns. This resource will enhance our knowledge about the potential relevance of different movement behaviours for chronic disease in Chinese adults.

Sleep duration and risk of stroke and coronary heart disease: a 9-year community-based prospective study of 0.5 million Chinese adults.

BACKGROUND: There is uncertainty about the optimum sleep duration for risk of different subtypes of stroke and ischaemic heart disease. METHODS: The present analyses involved 409,156 adults in the China Kadoorie Biobank study without a prior history of coronary heart disease or stroke or insomnia symptoms. The mean age of study participants was 52 years and 59% were women. Self-reported sleep duration including daytime napping was recorded using a questionnaire. The adjusted hazard ratios (HRs) for disease outcomes associated with sleep duration were estimated by Cox proportional hazards after adjustment for confounding factors. RESULTS: The overall mean (SD) sleep duration was 7.4 (1.4) hours. The associations of sleep duration with CVD types were U-shaped, with individuals reporting 7-8 h of sleep having the lowest risks. Compared with those who typically slept 7-8 h, individuals with very short sleep duration (≤ 5 h) had adjusted HRs of 1.10 (95% CI 1.04-1.16), 1.07 (1.01-1.13), 1.19 (1.06-1.33) and 1.23 (1.10-1.37) for total stroke, ischaemic stroke (IS), Intracerebral haemorrhage (ICH) and major coronary events (MCE), respectively. Likewise, individuals with very long sleep duration (≥ 10 h) had HRs of 1.12 (1.07-1.17), 1.08 (1.03-1.14), 1.23 (1.12-1.35) and 1.22 (1.10-1.34) for the same diseases, respectively, with little differences by sex and age. The patterns were similar for all-cause mortality. CONCLUSIONS: While abnormal sleep duration (≤ 6 h or ≥ 9 h) was associated with higher risks of CVD, the risks were more extreme for those reporting ≤ 5 or ≥ 10 h, respectively and such individuals should be prioritised for more intensive treatment for CVD prevention.

Conventional and genetic associations of adiposity with 1463 proteins in relatively lean Chinese adults.

Adiposity is associated with multiple diseases and traits, but little is known about the causal relevance and mechanisms underlying these associations. Large-scale proteomic profiling, especially when integrated with genetic data, can clarify mechanisms linking adiposity with disease outcomes. We examined the associations of adiposity with plasma levels of 1463 proteins in 3977 Chinese adults, using measured and genetically-instrumented BMI. We further used two-sample bi-directional MR analyses to assess if certain proteins influenced adiposity, along with other (e.g. enrichment) analyses to clarify possible mechanisms underlying the observed associations. Overall, the mean (SD) baseline BMI was 23.9 (3.3) kg/m2, with only 6% being obese (i.e. BMI ≥ 30 kg/m2). Measured and genetically-instrumented BMI was significantly associated at FDR < 0.05 with levels of 1096 (positive/inverse: 826/270) and 307 (positive/inverse: 270/37) proteins, respectively, with FABP4, LEP, IL1RN, LSP1, GOLM2, TNFRSF6B, and ADAMTS15 showing the strongest positive and PON3, NCAN, LEPR, IGFBP2 and MOG showing the strongest inverse genetic associations. These associations were largely linear, in adiposity-to-protein direction, and replicated (> 90%) in Europeans of UKB (mean BMI 27.4 kg/m2). Enrichment analyses of the top > 50 BMI-associated proteins demonstrated their involvement in atherosclerosis, lipid metabolism, tumour progression and inflammation. Two-sample bi-directional MR analyses using cis-pQTLs identified in CKB GWAS found eight proteins (ITIH3, LRP11, SCAMP3, NUDT5, OGN, EFEMP1, TXNDC15, PRDX6) significantly affect levels of BMI, with NUDT5 also showing bi-directional association. The findings among relatively lean Chinese adults identified novel pathways by which adiposity may increase disease risks and novel potential targets for treatment of obesity and obesity-related diseases.

Intakes of major food groups in China and UK: results from 100,000 adults in the China Kadoorie biobank and UK biobank.

PURPOSE: Different populations may exhibit differences in dietary intakes, which may result in heterogeneities in diet-disease associations. We compared intakes of major food groups overall, by sex, and by socio-economic status (SES) (defined as both education and income), between participants in the China Kadoorie Biobank (CKB) and the UK Biobank (UKB). METHODS: Data were from ~ 25,000 CKB participants who completed a validated interviewer-administered computer-based questionnaire (2013-2014) and ~ 74,000 UKB participants who completed ≥ 3 web-based 24-h dietary assessments (2009-2012). Intakes of 12 major food groups and five beverages were harmonized and compared between the cohorts overall, by sex and by SES. Multivariable-adjusted linear regression examined the associations between dietary intakes and body mass index (BMI) in each cohort. RESULTS: CKB participants reported consuming more rice, eggs, vegetables, soya products, and less wheat, other staple foods (other than rice and wheat), fish, poultry, all dairy products, fruit, and beverages compared to UKB participants. Red meat intake was similar in both cohorts. Having a higher SES was generally associated with a higher consumption of foods and beverages in CKB, whereas in UKB dietary intakes differed more by education and income, with a positive association observed for meat and income in both UKB and CKB but an inverse association observed for education in UKB. Associations of dietary intakes with BMI varied between the two cohorts. CONCLUSION: The large differences in dietary intakes and their associations with SES and BMI could provide insight into the interpretation of potentially different diet-disease associations between CKB and UKB.

Long-term ambient air pollution exposure and cardio-respiratory disease in China: findings from a prospective cohort study.

BACKGROUND: Existing evidence on long-term ambient air pollution (AAP) exposure and risk of cardio-respiratory diseases in China is mainly on mortality, and based on area average concentrations from fixed-site monitors for individual exposures. Substantial uncertainty persists, therefore, about the shape and strength of the relationship when assessed using more personalised individual exposure data. We aimed to examine the relationships between AAP exposure and risk of cardio-respiratory diseases using predicted local levels of AAP. METHODS: A prospective study included 50,407 participants aged 30-79 years from Suzhou, China, with concentrations of nitrogen dioxide (NO2), sulphur dioxide (SO2), fine (PM2.5), and inhalable (PM10) particulate matter, ozone (O3) and carbon monoxide (CO) and incident cases of cardiovascular disease (CVD) (n = 2,563) and respiratory disease (n = 1,764) recorded during 2013-2015. Cox regression models with time-dependent covariates were used to estimate adjusted hazard ratios (HRs) for diseases associated with local-level concentrations of AAP exposure, estimated using Bayesian spatio-temporal modelling. RESULTS: The study period of 2013-2015 included a total of 135,199 person-years of follow-up for CVD. There was a positive association of AAP, particularly SO2 and O3, with risk of major cardiovascular and respiratory diseases. Each 10 µg/m3 increase in SO2 was associated with adjusted hazard ratios (HRs) of 1.07 (95% CI: 1.02, 1.12) for CVD, 1.25 (1.08, 1.44) for COPD and 1.12 (1.02, 1.23) for pneumonia. Similarly, each 10 µg/m3 increase in O3 was associated with adjusted HR of 1.02 (1.01, 1.03) for CVD, 1.03 (1.02, 1.05) for all stroke, and 1.04 (1.02, 1.06) for pneumonia. CONCLUSIONS: Among adults in urban China, long-term exposure to ambient air pollution is associated with a higher risk of cardio-respiratory disease.

Tobacco smoking and solid fuels for cooking and risk of liver cancer: A prospective cohort study of 0.5 million Chinese adults.

Previous research found tobacco smoking and solid fuel use for cooking to increase the risk of chronic liver disease mortality, but previous cohort studies have not investigated their independent and joint associations with liver cancer incidence in contemporary China. The China Kadoorie Biobank (CKB) study recruited 0.5 million adults aged 30 to 79 years from 10 areas across China during 2004 to 2008. Participants reported detailed smoking and fuel use information at baseline. After an 11.1-year median follow-up via electronic record linkage, we recorded 2997 liver cancer cases. Overall, 29.4% participants were current smokers. Among those who cooked at least once per month, 48.8% always used solid fuels (ie, coal or wood) for cooking. Tobacco smoking and solid fuel use for cooking were independently associated with increased risks of liver cancer, with hazard ratios (95% confidence intervals [CIs]) of 1.28 (1.15-1.42) and 1.25 (1.03-1.52), respectively. The more cigarettes consumed each day, the earlier the age of starting smoking or the longer duration of solid fuels exposure, the higher the risk (Ptrend < .001, =.001, =.018, respectively). Compared with never smokers who had always used clean fuels (ie, gas or electricity), ever-smokers who had always used solid fuels for cooking had a 67% (95% CIs: 1.29-2.17) higher risk. Among Chinese adults, tobacco smoking and solid fuel use for cooking were independently associated with higher risk of liver cancer incidence. Stronger association was observed with higher number of daily cigarette consumption, the earlier age of starting smoking and longer duration of solid fuel use.

Maintaining healthy sleep patterns and frailty transitions: a prospective Chinese study.

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 < 0.001). 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.

External validation of models for predicting risk of colorectal cancer using the China Kadoorie Biobank.

BACKGROUND: In China, colorectal cancer (CRC) incidence and mortality have been steadily increasing over the last decades. Risk models to predict incident CRC have been developed in various populations, but they have not been systematically externally validated in a Chinese population.  This study aimed to assess the performance of risk scores in predicting CRC using the China Kadoorie Biobank (CKB), one of the largest and geographically diverse prospective cohort studies in China. METHODS: Nine models were externally validated in 512,415 participants in CKB and included 2976 cases of CRC. Model discrimination was assessed, overall and by sex, age, site, and geographic location, using the area under the receiver operating characteristic curve (AUC). Model discrimination of these nine models was compared to a model using age alone. Calibration was assessed for five models, and they were re-calibrated in CKB. RESULTS: The three models with the highest discrimination (Ma (Cox model) AUC 0.70 [95% CI 0.69-0.71]; Aleksandrova 0.70 [0.69-0.71]; Hong 0.69 [0.67-0.71]) included the variables age, smoking, and alcohol. These models performed significantly better than using a model based on age alone (AUC of 0.65 [95% CI 0.64-0.66]). Model discrimination was generally higher in younger participants, males, urban environments, and for colon cancer. The two models (Guo and Chen) developed in Chinese populations did not perform better than the others. Among the 10% of participants with the highest risk, the three best performing models identified 24-26% of participants that went on to develop CRC. CONCLUSIONS: Several risk models based on easily obtainable demographic and modifiable lifestyle factor have good discrimination in a Chinese population. The three best performing models have a higher discrimination than using a model based on age alone.

Dairy consumption and risks of total and site-specific cancers in Chinese adults: an 11-year prospective study of 0.5 million people.

BACKGROUND: Previous studies of primarily Western populations have reported contrasting associations of dairy consumption with certain cancers, including a positive association with prostate cancer and inverse associations with colorectal and premenopausal breast cancers. However, there are limited data from China where cancer rates and levels of dairy consumption differ importantly from those in Western populations. METHODS: The prospective China Kadoorie Biobank study recruited ~0.5 million adults from ten diverse (five urban, five rural) areas across China during 2004-2008. Consumption frequency of major food groups, including dairy products, was collected at baseline and subsequent resurveys, using a validated interviewer-administered laptop-based food frequency questionnaire. To quantify the linear association of dairy intake and cancer risk and to account for regression dilution bias, the mean usual consumption amount for each baseline group was estimated via combining the consumption level at both baseline and the second resurvey. During a mean follow-up of 10.8 (SD 2.0) years, 29,277 incident cancer cases were recorded among the 510,146 participants who were free of cancer at baseline. Cox regression analyses for incident cancers associated with usual dairy intake were stratified by age-at-risk, sex and region and adjusted for cancer family history, education, income, alcohol intake, smoking, physical activity, soy and fresh fruit intake, and body mass index. RESULTS: Overall, 20.4% of participants reported consuming dairy products (mainly milk) regularly (i.e. ≥1 day/week), with the estimated mean consumption of 80.8 g/day among regular consumers and of 37.9 g/day among all participants. There were significant positive associations of dairy consumption with risks of total and certain site-specific cancers, with adjusted HRs per 50 g/day usual consumption being 1.07 (95% CI 1.04-1.10), 1.12 (1.02-1.22), 1.19 (1.01-1.41) and 1.17 (1.07-1.29) for total cancer, liver cancer (n = 3191), female breast cancer (n = 2582) and lymphoma (n=915), respectively. However, the association with lymphoma was not statistically significant after correcting for multiple testing. No significant associations were observed for colorectal cancer (n = 3350, 1.08 [1.00-1.17]) or other site-specific cancers. CONCLUSION: Among Chinese adults who had relatively lower dairy consumption than Western populations, higher dairy intake was associated with higher risks of liver cancer, female breast cancer and, possibly, lymphoma.

Coarse Grain Consumption and Risk of Cardiometabolic Diseases: A Prospective Cohort Study of Chinese Adults.

BACKGROUND: Lower consumption of whole grains is associated with higher risks of diabetes and coronary heart disease in Western populations, but evidence is still limited for stroke. Moreover, little is known in China, where the rates of cardiometabolic diseases are high and the grain types consumed are different from those in Western countries. OBJECTIVES: To examine the associations between coarse-grain (e.g., millet, corn, and sorghum) consumption and incident cardiometabolic diseases among Chinese adults. METHODS: The prospective China Kadoorie Biobank enrolled >0.5 million adults aged 30-79 years from 10 urban and rural areas during 2004-2008. At baseline, consumption frequencies (in 5 categories from "never" to "daily") of 12 major food groups, including coarse grains, were collected using a validated FFQ. After a median of 11 years of follow-up, 17,149 cases of diabetes, 29,876 ischemic strokes, 6097 hemorrhagic strokes, and 6704 major coronary events were recorded among 461,047 participants without a prevalence of major chronic diseases at baseline. Cox regression analyses were used to yield adjusted HRs for each disease associated with coarse-grain consumption. RESULTS: Overall, 13.8% of participants reported regularly consuming (i.e., ≥4 days/week, regular consumers) and 29.4% reported never or rarely consuming coarse grains (i.e., nonconsumers) at baseline. Compared with nonconsumers, regular consumers had lower risks of diabetes (adjusted HR, 0.88; 95% CI, 0.78-0.98) and ischemic stroke (adjusted HR, 0.86; 95% CI, 0.81-0.93), but not hemorrhagic stroke (adjusted HR, 0.96; 95% CI, 0.76-1.20) or major coronary events (adjusted HR, 0.95; 95% CI, 0.81-1.12). For diabetes and ischemic stroke, each 100 g/day increase in the usual intake of coarse grains was associated with 14% (adjusted HR, 0.86; 95% CI, 0.76-0.97) and 13% (adjusted HR, 0.87; 95% CI, 0.81-0.94) lower risks, respectively, with similar results in various subgroups. CONCLUSIONS: In Chinese adults, higher coarse-grain consumption is associated with lower risks of diabetes and ischemic stroke, supporting the promotion of coarse-grain consumption in China.

Associations of erythrocyte polyunsaturated fatty acids with incidence of stroke and stroke types in adult Chinese: a prospective study of over 8000 individuals.

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 < 0.001), but not with ICH. Inverted-U shape curve associations were observed of 20:5n-3 with IS (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.