Publications by authors named "Junshi Chen"

157 Publications

Association of heart rate and diabetes among 0.5 million adults in the China Kadoorie biobank: Results from observational and Mendelian randomization analyses.

Nutr Metab Cardiovasc Dis 2021 Apr 27. Epub 2021 Apr 27.

Department of Epidemiology and Biostatistics, School of Public Health, Peking University Health Science Center, Beijing, China; Peking University Center for Public Health and Epidemic Preparedness & Response, Beijing, China. Electronic address:

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.
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http://dx.doi.org/10.1016/j.numecd.2021.04.015DOI Listing
April 2021

Development and external validation of a breast cancer absolute risk prediction model in Chinese population.

Breast Cancer Res 2021 May 29;23(1):62. Epub 2021 May 29.

Department of Epidemiology and Biostatistics, School of Public Health, Peking University Health Science Center, 38 Xueyuan Road, Beijing, 100191, China.

Backgrounds: In 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.

Methods: A 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.

Results: During 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.

Conclusions: Based 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.
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http://dx.doi.org/10.1186/s13058-021-01439-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8164768PMC
May 2021

Age-Specific Associations Between Habitual Snoring and Cardiovascular Diseases in China: A 10-Year Cohort Study.

Chest 2021 May 21. Epub 2021 May 21.

Department of Epidemiology and Biostatistics, School of Public Health, Peking University Health Science Center, Beijing, China. Electronic address:

Background: Limited convincing evidence is available of the relationship between habitual snoring and cardiovascular diseases (CVDs).

Research Question: Is habitual snoring associated with total CVD and CVD subtypes in different age groups of Chinese adults?

Study Design And Methods: The China Kadoorie Biobank study enrolled more than 0.5 million adults aged 30 to 79 years from 10 regions in China. Snoring status and other baseline characteristics were collected from 2004 to 2008, using an interviewer-administered laptop-based questionnaire. The current analysis included 489,583 participants without stroke or coronary heart disease at baseline. Cox proportional hazards models were used to calculate the adjusted hazard ratios (HRs) and 95% CIs of cardiovascular diseases (CVDs) for habitual snoring vs nonhabitual snoring.

Results: During a median follow-up of 9.6 years, 130,935 participants developed CVDs. Associations between habitual snoring and CVDs varied with age. Among participants aged younger than 50 years at baseline, habitual snoring was associated with an increased risk of total CVD (HR, 1.11; 95% CI, 1.07-1.14) after adjustment for known CVD risk factors, including systolic BP. The corresponding HRs (95% CIs) for ischemic heart disease, ischemic stroke, and hemorrhagic stroke were 1.18 (1.12-1.24), 1.12 (1.05-1.19), and 1.05 (0.92-1.19), respectively. However, such associations in adults aged 50 to 64 years were much weaker, and no statistically significant association was observed among individuals aged ≥65 years. Age-specific risk estimates were generally similar across sex and obesity subgroups.

Interpretation: Habitual snoring was associated with increased risks of total CVD, ischemic heart disease, ischemic stroke, but not hemorrhagic stroke in Chinese, and these associations were mainly limited to those aged <50 years. Clinicians in China are encouraged to identify snoring, particularly in younger adults.
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http://dx.doi.org/10.1016/j.chest.2021.04.070DOI Listing
May 2021

Metabolic risk factors, genetic predisposition, and risk of severe liver disease in Chinese: a prospective study of 0.5 million people.

Am J Clin Nutr 2021 May 8. Epub 2021 May 8.

Department of Epidemiology & Biostatistics, School of Public Health, Peking University, Beijing, China.

Background: Metabolic risk factors have been shown to be associated with severe liver disease (SLD) in Chinese populations. However, there is limited evidence on the combined impact of these factors, or the genetic variants associated with SLD.

Objectives: We examined the associations of combined metabolic risk factors with risks of SLD, both overall and by genetic predisposition to SLD.

Methods: The study population involved 486,828 participants of the prospective China Kadoorie Biobank aged 30-79 years from 10 diverse areas in China without a history of cancer or liver disease at baseline. Cox regression was used to estimate adjusted HRs for SLD associated with combined metabolic risk factors (central adiposity, physical inactivity, and diabetes) by stratum of genetic risk [assessed separately by a PNPLA3 variant (rs738409) and a BMI genetic risk score].

Results: During ∼10 years of follow-up, 3279 incident cases of SLD were recorded. The overall mean BMI was 23.8 kg/m2 (SD, 3.4 kg/m2), and 5.9% participants had diabetes. Compared with those with 3 metabolic factors, participants with 2, 1, and 0 metabolic factors had 31% (HR, 0.69; 95% CI: 0.65-0.73), 43% (HR, 0.57; 95% CI: 0.53-0.60), and 52% (HR, 0.48; 95% CI: 0.42-0.56) lower risks of SLD, respectively. For both BMI and nonalcoholic fatty liver disease variants, participants with fewer metabolic factors had a lower risk of SLD, lower levels of gamma-glutamyl transferase, and lower fatty liver index scores, in participants with low and high genetic risks (P value for interaction > 0.05).

Conclusions: In relatively lean Chinese adults, individuals with fewer metabolic risk factors had a lower relative risk of SLD and a more favorable profile of liver biomarkers across all strata of genetic risk.
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http://dx.doi.org/10.1093/ajcn/nqab099DOI Listing
May 2021

Pneumonia hospitalizations and the subsequent risk of incident ischaemic cardiovascular disease in Chinese adults.

Int J Epidemiol 2021 Apr 7. Epub 2021 Apr 7.

Department of Epidemiology and Biostatistics, School of Public Health, Peking University Health Science Center, Beijing, China.

Background: Acute respiratory infections have been associated with a transient increase in cardiovascular risk. However, whether such an association persists beyond 1 month and the potential modifying effect of cardiovascular risk factors on such an association are less well established.

Methods: The China Kadoorie Biobank enrolled 512 726 participants aged 30-79 years from 10 areas across China during 2004-2008. By the end of 2017, a total of 5444 participants with new-onset ischaemic heart disease (IHD) and 4846 with ischaemic stroke (IS) who also had at least a record of hospitalization for pneumonia during follow-up were included. We used a self-controlled case-series method and calculated the age- and season-adjusted relative incidences (RIs) and 95% confidence intervals (CIs) for ischaemic cardiovascular disease (CVD) after pneumonia.

Results: The risk of ischaemic CVD increased during days 1-3 after pneumonia hospitalization, with an RI (95% CI) of 4.24 (2.92-6.15) for IHD and 1.85 (1.02-3.35) for IS. The risk gradually reduced with longer duration since pneumonia hospitalization but remained elevated until days 92-365 for IHD (1.23, 1.12-1.35) and days 29-91 for IS (1.25, 1.05-1.48). Pre-existing cardiovascular risk factors amplified the associations between pneumonia and ischaemic CVD risks, such as chronic obstructive pulmonary disease for both IHD and IS, and diabetes and smoking for IHD (all Pinteraction < 0.05). Besides, the risk of ischaemic CVD was also higher among the participants aged ≥70 years (Pinteraction < 0.001 for IHD and 0.033 for IS).

Conclusion: Among middle-aged and older Chinese adults, pneumonia hospitalization was associated with both short- and long-term increases in ischaemic CVD risk for ≤1 year.
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http://dx.doi.org/10.1093/ije/dyab039DOI Listing
April 2021

Consumption of Tea, Alcohol, and Fruits and Risk of Kidney Stones: A Prospective Cohort Study in 0.5 Million Chinese Adults.

Nutrients 2021 Mar 29;13(4). Epub 2021 Mar 29.

Department of Epidemiology and Biostatistics, School of Public Health, Peking University, Beijing 100191, China.

A few prospective studies have suggested that tea, alcohol, and fruit consumption may reduce the risk of kidney stones. However, little is known whether such associations and their combined effect persist in Chinese adults, for whom the popular tea and alcohol drinks are different from those investigated in the aforementioned studies. The present study included 502,621 participants from the China Kadoorie Biobank (CKB). Information about tea, alcohol, and fruit consumption was self-reported at baseline. The first documented cases of kidney stones during follow-up were collected through linkage with the national health insurance system. Cox regression was used to calculate the hazard ratio (HR) and 95% confidence interval (CI). During a median of 11.1 years of follow-up, we collected 12,407 cases of kidney stones. After multivariable adjustment, tea, alcohol, and fruit consumption were found to be negatively associated with kidney stone risk, but the linear trend was only found in tea and fruit consumption. Compared with non-tea consumers, the HR (95% CI) for participants who drank ≥7 cups of tea per day was 0.73 (0.65-0.83). Compared with non-alcohol consumers, the HR (95% CI) was 0.79 (0.72-0.87) for participants who drank pure alcohol of 30.0-59.9 g per day but had no further decrease with a higher intake of alcohol. Compared with less-than-weekly consumers, the HR (95% CI) for daily fruit consumers was 0.81 (0.75-0.87). Even for those who did not drink alcohol excessively, increasing tea and fruit consumption could also independently reduce the stone risk. Among Chinese adults, tea, alcohol, and fruit consumption was associated with a lower risk of kidney stones.
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http://dx.doi.org/10.3390/nu13041119DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8065818PMC
March 2021

Educational disparities in ischaemic heart disease among 0.5 million Chinese adults: a cohort study.

J Epidemiol Community Health 2021 Mar 29. Epub 2021 Mar 29.

Department of Epidemiology and Biostatistics, School of Public Health, Peking University Health Science Centre, Beijing, China.

Background: The 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.

Methods: Based 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.

Results: During 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 (p <0.001). Although the risk of incident non-AMI was greater for participants with higher levels of education in the whole population (p <0.001), an inverse association of education with its incidence was found in participants from <50 years age group and rural areas. Smoking and dietary habits were the two most potent mediating factors in the associations of education with mortality and AMI incidence; whereas, physical activity was the major mediating factor for non-AMI incidence in the whole population.

Discussion: Interventions 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.
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http://dx.doi.org/10.1136/jech-2020-216314DOI Listing
March 2021

Causal effects of gallstone disease on risk of gastrointestinal cancer in Chinese.

Br J Cancer 2021 May 26;124(11):1864-1872. Epub 2021 Mar 26.

Department of Epidemiology and Biostatistics, School of Public Health, Peking University Health Science Centre, Beijing, China.

Background: Gallstone disease (GSD) is associated with a higher risk of gastrointestinal (GI) cancer. However, it is unclear whether the associations are causal.

Methods: The prospective China Kadoorie Biobank (CKB) recorded 17,598 cases of GI cancer among 510,137 participants without cancer at baseline during 10 years of follow-up. Cox regression was used to estimate hazard ratios (HRs) for specific cancer by GSD status and duration. Mendelian randomisation was conducted to assess the genetic associations of GSD with specific cancer.

Results: Overall 6% of participants had symptomatic GSD at baseline. Compared with those without GSD, individuals with symptomatic GSD had adjusted HRs of 1.13 (1.01-1.29) for colorectal, 2.01 (1.78-2.26) for liver, 3.70 (2.88-4.87) for gallbladder, 2.31 (1.78-3.07) for biliary tract, and 1.38 (1.18-1.74) for pancreatic cancer. Compared with participants without GSD, the risks of colorectal, liver, gallbladder, biliary tract, and pancreatic cancer were highest during 0 to <5 years following disease diagnosis. There was evidence of genetic associations of GSD with these cancers, with odds ratios per 1-SD genetic score of 1.08 (1.05-1.11) for colorectal, 1.22 (1.19-1.25) for liver, 1.56 (1.49-1.64) for gallbladder, 1.39 (1.31-1.46) for biliary tract, and 1.16 (1.10-1.22) for pancreatic cancer. When meta-analysing the genetic estimates in CKB and UK Biobank, there was evidence of causal associations of GSD with colon cancer, gallbladder and biliary tract cancer (GBTC), and total GI cancer (RR per 1-SD: 1.05 [0.99-1.11], 2.00 [1.91-2.09], and 1.09 [1.05-1.13]).

Conclusions: GSD was associated with higher risks of several GI cancers, warranting future studies on the underlying mechanisms.
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http://dx.doi.org/10.1038/s41416-021-01325-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8144569PMC
May 2021

A large-scale genome-wide association analysis of lung function in the Chinese population identifies novel loci and highlights shared genetic etiology with obesity.

Eur Respir J 2021 Mar 25. Epub 2021 Mar 25.

Program in Genetic Epidemiology and Statistical Genetics, Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA

Lung function is a heritable complex phenotype with obesity being one of its important risk factors. However, the knowledge of their shared genetic basis is limited. Most genome-wide association studies (GWASs) for lung function have been based on European populations, limiting the generalisability across populations. Large-scale lung function GWAS in other populations are lacking.We included 100 285 subjects from China Kadoorie Biobank (CKB). To identify novel loci for lung function, single-trait GWAS were performed on FEV1, FVC, FEV1/FVC in CKB. We then performed genome-wide cross-trait analysis between the lung function and obesity traits (body mass index [BMI], BMI-adjusted waist-to-hip ratio, and BMI-adjusted waist circumference) to investigate the shared genetic effects in CKB. Finally, polygenic risk scores (PRSs) of lung function were developed in CKB and its interaction with BMI's association on lung function were examined. We also conducted cross-trait analysis in parallel with CKB using 457 756 subjects from UK Biobank (UKB) for replication and investigation of ancestry specific effect.We identified 9 genome-wide significant novel loci for FEV1, 6 for FVC and 3 for FEV1/FVC in CKB. FEV1 and FVC showed significant negative genetic correlation with obesity traits in both CKB and UKB. Genetic loci shared between lung function and obesity traits highlighted important pathways, including cell proliferation, embryo and tissue development. Mendelian randomisation analysis suggested significant negative causal effect of BMI on FEV1 and on FVC in both CKB and UKB. Lung function PRSs significantly modified the effect of change-in-BMI on change-in-lung function during an average follow-up of 8 years.This large-scale GWAS of lung function identified novel loci and shared genetic etiology between lung function and obesity. Change-in-BMI might affect change-in-lung function differently according to a subject's polygenic background. These findings may open new avenue for the development of molecular-targeted therapies for obesity and lung function improvement.
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http://dx.doi.org/10.1183/13993003.00199-2021DOI Listing
March 2021

Tea consumption and long-term risk of type 2 diabetes and diabetic complications: a cohort study of 0.5 million Chinese adults.

Am J Clin Nutr 2021 Mar 11. Epub 2021 Mar 11.

Department of Epidemiology and Biostatistics, School of Public Health, Peking University, Beijing, China.

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.
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http://dx.doi.org/10.1093/ajcn/nqab006DOI Listing
March 2021

Tea consumption and long-term risk of type 2 diabetes and diabetic complications: a cohort study of 0.5 million Chinese adults.

Am J Clin Nutr 2021 Mar 11. Epub 2021 Mar 11.

Department of Epidemiology and Biostatistics, School of Public Health, Peking University, Beijing, China.

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.
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http://dx.doi.org/10.1093/ajcn/nqab006DOI Listing
March 2021

Metabolic signatures of genetically elevated vitamin D among Chinese: observational and Mendelian randomization study.

J Clin Endocrinol Metab 2021 Feb 17. Epub 2021 Feb 17.

Department of Epidemiology and Biostatistics, School of Public Health, Peking University Health Science Center, Beijing, China.

Background: Observational studies have suggested that higher circulating 25-hydroxyvitamin D [25(OH)D] levels were associated with favorable serum lipids and related metabolites. However, if such observations reflect causality remains unclear.

Objective: We aimed to investigate the causal effect of elevated 25(OH)D with the detailed systemic metabolite profile in Chinese adults.

Methods: A total of 225 lipid and other metabolites were quantified in 4,662 individuals in China Kadoorie Biobank. Instrumental variable analyses were performed to test the causal associations of plasma 25(OH)D with the lipids and metabolites.

Results: Higher plasma 25(OH)D was related to favorable lipid profiles in observational analyses. The genetic risk score was robustly correlated with observed 25(OH)D (beta[SE]= 3.54 [0.32]; P<1×10 -5, F-statistic =122.3) and explained 8.4% of the variation in 25(OH)D in the Chinese population. For all individual metabolites, the causal estimates were not significant for at the threshold P<5×10 -4 (multiple testing corrected). However, the MR estimate showed that per 1-SD increase in genetically determined 25(OH)D was suggestive associated with decreased levels of cholesterol, lipoprotein particle, phospholipids within very small very low-density lipoprotein (VLDL) and intermediate-density lipoprotein (IDL) (P≤0.05, nominal significance). For amino acids, fatty acids, ketone bodies, glycoprotein acetyls, fatty acids and other traits, we did not observe any significant causal association.

Conclusions: The MR analysis of metabolic data based a population-based cohort suggested a potential causal association of plasma 25(OH)D with cholesterol, lipoprotein particle, phospholipids concentrations and total lipids within very small VLDL and IDL. Our findings highlight long-term effect of 25(OH)D levels in maintaining healthy lipid metabolism.
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http://dx.doi.org/10.1210/clinem/dgab097DOI Listing
February 2021

Improved lipidomic profile mediates the effects of adherence to healthy lifestyles on coronary heart disease.

Elife 2021 Feb 9;10. Epub 2021 Feb 9.

Department of Epidemiology and Biostatistics, School of Public Health, Peking University Health Science Center, Beijing, China.

Adherence to healthy lifestyles is associated with reduced risk of coronary heart disease (CHD), but uncertainty persists about the underlying lipid pathway. In a case-control study of 4681 participants nested in the prospective China Kadoorie Biobank, 61 lipidomic markers in baseline plasma were measured by targeted nuclear magnetic resonance spectroscopy. Baseline lifestyles included smoking, alcohol consumption, dietary habit, physical activity, and adiposity levels. Genetic instrument was used to mimic the lipid-lowering effect of statins. We found that 35 lipid metabolites showed statistically significant mediation effects in the pathway from healthy lifestyles to CHD reduction, including very low-density lipoprotein (VLDL) particles and their cholesterol, large-sized high-density lipoprotein (HDL) particle and its cholesterol, and triglyceride in almost all lipoprotein subfractions. The statins genetic score was associated with reduced intermediate- and low-density lipoprotein, but weak or no association with VLDL and HDL. Lifestyle interventions and statins may improve different components of the lipid profile.
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http://dx.doi.org/10.7554/eLife.60999DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7872516PMC
February 2021

Frailty index and all-cause and cause-specific mortality in Chinese adults: a prospective cohort study.

Lancet Public Health 2020 12;5(12):e650-e660

Department of Epidemiology and Biostatistics, School of Public Health, Peking University, Beijing, China.

Background: The fraily index is a useful proxy measure of accelerated biological ageing and in estimating all-cause and cause-specific mortality in older individuals in European and US populations. However, the predictive value of the frailty index in other populations outside of Europe and the USA and in adults younger than 50 years is unknown. We aimed to examine the association between the frailty index and mortality in a population of Chinese adults.

Methods: In this prospective cohort study, we used data from the China Kadoorie Biobank. We included adults aged 30-79 years from ten areas (five urban areas and five rural areas) of China who had no missing values for the items that made up the frailty index. We did not exclude participants on the basis of baseline morbidity status. We calculated the follow-up person-years from the baseline date to either the date of death, loss to follow-up, or Dec 31, 2017, whichever came first, through linkage with the registries of China's Disease Surveillance Points system and local residential records. Active follow-up visits to local communities were done annually for participants who were not linked to any established registries. Causes of death from official death certificates were supplemented, if necessary, by reviewing medical records or doing standard verbal autopsy procedures. The frailty index was calculated using 28 baseline variables, all of which were health status deficits measured by use of questionnaires and physical examination. We defined three categories of frailty status: robust (frailty index ≤0·10), prefrail (frailty index >0·10 to <0·25), and frail (frailty index ≥0·25). The primary outcomes were all-cause mortality and cause-specific mortality in Chinese adults aged 30-79 years. We used a Cox proportional hazards model to estimate the associations between the frailty index and all-cause and cause-specific mortality, adjusting for chronological age, education, and lifestyle factors.

Findings: 512 723 participants, recruited between June 25, 2004, and July 15, 2008, were followed up for a median of 10·8 years (IQR 10·2-13·1; total follow-up 5 551 974 person-years). 291 954 (56·9%) people were categorised as robust, 205 075 (40·0%) people were categorised as prefrail, and 15 694 (3·1%) people were categorised as frail. Women aged between 45 years and 79 years had a higher mean frailty index and a higher prevalence of frailty than did men. During follow-up, 49 371 deaths were recorded. After adjustment for established and potential risk factors for death, each 0·1 increment in the frailty index was associated with a higher risk of all-cause mortality (hazard ratio [HR] 1·68, 95% CI 1·66-1·71). Such associations were stronger among younger adults than among older adults (p<0·0001), with HRs per 0·1 increment of the frailty index of 1·95 (95% CI 1·87-2·03) for those younger than 50 years, 1·80 (1·76-1·83) for those aged 50-64 years, and 1·56 (1·53-1·59) for those 65 years and older. After adjustments, there was no difference between the sexes in the association between the frailty index and all-cause mortality (p=0·75). For each 0·1 increment of the frailty index, the corresponding HRs for risk of death were 1·89 (95% CI 1·83-1·94) from ischaemic heart disease, 1·84 (1·79-1·89) from cerebrovascular disease, 1·19 (1·16-1·22) from cancer, 2·54 (2·45-2·63) from respiratory disease, 1·78 (1·59-2·00) from infection, and 1·78 (1·73-1·83) from all other causes.

Interpretation: The frailty index is associated with all-cause and cause-specific mortality independent of chronological age in younger and older Chinese adults. The identification of younger adults with accelerated ageing by use of surrogate measures could be useful for the prevention of premature death and the extension of healthy active life expectancy.

Funding: The National Natural Science Foundation of China, the National Key R&D Program of China, the Chinese Ministry of Science and Technology, the Kadoorie Charitable Foundation, and the Wellcome Trust.
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http://dx.doi.org/10.1016/S2468-2667(20)30113-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7708389PMC
December 2020

Associations of Adiposity, Circulating Protein Biomarkers, and Risk of Major Vascular Diseases.

JAMA Cardiol 2021 Mar;6(3):276-286

Clinical Trial Service Unit & Epidemiological Studies Unit, Nuffield Department of Population Health, University of Oxford, United Kingdom.

Importance: Obesity is associated with a higher risk of cardiovascular disease (CVD), but little is known about the role that circulating protein biomarkers play in this association.

Objective: To examine the observational and genetic associations of adiposity with circulating protein biomarkers and the observational associations of proteins with incident CVD.

Design, Setting, And Participants: This subcohort study included 628 participants from the prospective China Kadoorie Biobank who did not have a history of cancer at baseline. The Olink platform measured 92 protein markers in baseline plasma samples. Data were collected from June 2004 to January 2016 and analyzed from January 2019 to June 2020.

Exposures: Measured body mass index (BMI) obtained during the baseline survey and genetically instrumented BMI derived using 571 externally weighted single-nucleotide variants.

Main Outcomes And Measures: Cross-sectional associations of adiposity with biomarkers were examined using linear regression. Associations of biomarkers with CVD risk were assessed using Cox regression among those without prior cancer or CVD at baseline. Mendelian randomization was conducted to derive genetically estimated associations of BMI with biomarkers.

Findings: In observational analyses of 628 individuals (mean [SD] age, 52.2 [10.5] years; 385 women [61.3%]), BMI (mean [SD], 23.9 [3.6]) was positively associated with 27 proteins (per 1-SD higher BMI; eg, interleukin-6: 0.21 [95% CI, 0.12-0.29] SD; interleukin-18: 0.13 [95% CI, 0.05-0.21] SD; monocyte chemoattractant protein-1: 0.12 [95% CI, 0.04-0.20] SD; hepatocyte growth factor: 0.31 [95% CI, 0.24-0.39] SD), and inversely with 3 proteins (Fas ligand: -0.11 [95% CI, -0.19 to -0.03] SD; TNF-related weak inducer of apoptosis, -0.14 [95% CI, -0.23 to -0.06] SD; and carbonic anhydrase 9: (-0.14 [95% CI, -0.22 to -0.05] SD), with similar associations identified for other adiposity traits (eg, waist circumference [r = 0.96]). In mendelian randomization, the associations of genetically elevated BMI with specific proteins were directionally consistent with the observational associations. In meta-analyses of genetically elevated BMI with 8 proteins, combining present estimates with previous studies, the most robust associations were shown for interleukin-6 (per 1-SD higher BMI; 0.21 [95% CI, 0.13-0.29] SD), interleukin-18 (0.16 [95% CI, 0.06-0.26] SD), monocyte chemoattractant protein-1 (0.21 [95% CI, 0.11-0.30] SD), monocyte chemotactic protein-3 (0.12 [95% CI, 0.03-0.21] SD), TNF-related apoptosis-inducing ligand (0.23 [95% CI, 0.13-0.32] SD), and hepatocyte growth factor (0.14 [95% CI, 0.06-0.22] SD). Of the 30 BMI-associated biomarkers, 10 (including interleukin-6, interleukin-18, and hepatocyte growth factor) were nominally associated with incident CVD.

Conclusions And Relevance: Mendelian randomization shows adiposity to be associated with a range of protein biomarkers, with some biomarkers also showing association with CVD risk. Future studies are warranted to validate these findings and assess whether proteins may be mediators between adiposity and CVD.
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http://dx.doi.org/10.1001/jamacardio.2020.6041DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7711564PMC
March 2021

Characteristics of spicy food consumption and its relation to lifestyle behaviours: results from 0.5 million adults.

Int J Food Sci Nutr 2021 Jun 18;72(4):569-576. Epub 2020 Nov 18.

Department of Epidemiology and Biostatistics, School of Public Health, Peking University Health Science Center, Beijing, China.

This study aimed to describe the characteristics and lifestyle differences of spicy food consumption in 0.5 million adults. Participants were recruited from 2004 to 2008 in the baseline research of the CKB study. Higher frequency and stronger pungency degree in spicy food positively correlated with preference for salty taste, eating snacks/deep-fried foods, tea/alcohol drinking and tobacco smoking. Among weekly tea/alcohol drinkers and current regular smokers, participants with a higher frequency of spicy food consumption or preference for stronger pungency degree were more likely to prefer strong tea, drink alcohol exceed the healthy amount, drink alcohol in the morning every day, smoke ≥ 40 cigarettes per day, consume a larger amount of tea leaves, alcohol and cigarettes each day, and start habitual tea/alcohol drinking or smoking at an earlier age. Differences existed in lifestyle factors related to major chronic diseases according to spicy food consumption frequency and pungency degree among the Chinese population.
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http://dx.doi.org/10.1080/09637486.2020.1849038DOI Listing
June 2021

Metabolically healthy obesity, transition to unhealthy metabolic status, and vascular disease in Chinese adults: A cohort study.

PLoS Med 2020 10 30;17(10):e1003351. Epub 2020 Oct 30.

Department of Epidemiology and Biostatistics, School of Public Health, Peking University Health Science Center, Beijing, China.

Background: Metabolically healthy obesity (MHO) and its transition to unhealthy metabolic status have been associated with risk of cardiovascular disease (CVD) in Western populations. However, it is unclear to what extent metabolic health changes over time and whether such transition affects risks of subtypes of CVD in Chinese adults. We aimed to examine the association of metabolic health status and its transition with risks of subtypes of vascular disease across body mass index (BMI) categories.

Methods And Findings: The China Kadoorie Biobank was conducted during 25 June 2004 to 15 July 2008 in 5 urban (Harbin, Qingdao, Suzhou, Liuzhou, and Haikou) and 5 rural (Henan, Gansu, Sichuan, Zhejiang, and Hunan) regions across China. BMI and metabolic health information were collected. We classified participants into BMI categories: normal weight (BMI 18.5-23.9 kg/m²), overweight (BMI 24.0-27.9 kg/m²), and obese (BMI ≥ 28 kg/m²). Metabolic health was defined as meeting less than 2 of the following 4 criteria (elevated waist circumference, hypertension, elevated plasma glucose level, and dyslipidemia). The changes in obesity and metabolic health status were defined from baseline to the second resurvey with combination of overweight and obesity. Among the 458,246 participants with complete information and no history of CVD and cancer, the mean age at baseline was 50.9 (SD 10.4) years, and 40.8% were men, and 29.0% were current smokers. During a median 10.0 years of follow-up, 52,251 major vascular events (MVEs), including 7,326 major coronary events (MCEs), 37,992 ischemic heart disease (IHD), and 42,951 strokes were recorded. Compared with metabolically healthy normal weight (MHN), baseline MHO was associated with higher hazard ratios (HRs) for all types of CVD; however, almost 40% of those participants transitioned to metabolically unhealthy status. Stable metabolically unhealthy overweight or obesity (MUOO) (HR 2.22, 95% confidence interval [CI] 2.00-2.47, p < 0.001) and transition from metabolically healthy to unhealthy status (HR 1.53, 1.34-1.75, p < 0.001) were associated with higher risk for MVE, compared with stable healthy normal weight. Similar patterns were observed for MCE, IHD, and stroke. Limitations of the analysis included lack of measurement of lipid components, fasting plasma glucose, and visceral fat, and there might be possible misclassification.

Conclusions: Among Chinese adults, MHO individuals have increased risks of MVE. Obesity remains a risk factor for CVD independent of major metabolic factors. Our data further suggest that metabolic health is a transient state for a large proportion of Chinese adults, with the highest vascular risk among those remained MUOO.
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http://dx.doi.org/10.1371/journal.pmed.1003351DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7598496PMC
October 2020

Observational and Genetic Associations of Body Mass Index and Hepatobiliary Diseases in a Relatively Lean Chinese Population.

JAMA Netw Open 2020 10 1;3(10):e2018721. Epub 2020 Oct 1.

Clinical Trial Service Unit and Epidemiological Studies Unit, Nuffield Department of Population Health, Big Data Institute University of Oxford, Oxford, United Kingdom.

Importance: There is some support for the existence of genetic associations between adiposity and certain hepatobiliary diseases in Western populations. However, there is little evidence of such genetic associations in China, where the causes of these diseases may differ from those in Western populations and the mean body mass index (BMI) is much lower.

Objectives: To compare the observational associations of BMI with hepatobiliary diseases and liver biomarkers with the genetic associations between BMI and these factors and to assess whether the genetic associations of BMI with liver diseases differed by hepatitis B virus infection status.

Design, Setting, And Participants: This cohort study used data from the prospective China Kadoorie Biobank, including 473 938 adults aged 30 to 79 years without hepatobiliary diseases at baseline from 10 diverse areas in China from June 25, 2004, to July 15, 2008. A random sample of 75 736 participants with genotyping data was included in the Mendelian randomization analysis. Follow-up was completed January 1, 2017 (median [interquartile range] length of follow-up, 10.2 [9.2-11.1] years). Data were analyzed from January to October 2019.

Exposures: Measured BMI obtained during the baseline survey and genetically instrumented BMI derived using 92 single-nucleotide variations.

Main Outcomes And Measures: Incident cases of hepatobiliary diseases, liver enzymes, fatty liver index, and fibrosis score.

Results: Among 473 938 individuals (276 041 [58.2%] women), the mean (SD) age was 52 (10.9) years and mean (SD) BMI was 23.8 (3.4). Baseline BMI was associated with higher risks of chronic liver disease (adjusted risk ratio per 1-SD increase, 1.14; 95% CI, 1.11 to 1.17) and gallbladder disease (adjusted risk ratio per 1-SD increase, 1.29; 95% CI, 1.27 to 1.31), with heterogeneity by disease subtype (P < .001). Genetically instrumented BMI was associated with higher risks of chronic liver disease (risk ratio per 1-SD increase, 1.55; 95% CI, 1.08 to 2.24) and gallbladder disease (risk ratio per 1-SD increase, 1.40; 95% CI, 1.11 to 1.76), with no heterogeneity between subtypes. A meta-analysis of the genetic associations in China Kadoorie Biobank and those calculated in UK Biobank gave a risk ratio of 1.55 (95% CI, 1.30 to 1.84) for chronic liver disease and 1.42 (95% CI, 1.22 to 1.64) for gallbladder disease. In the China Kadoorie Biobank study, there were positive genetic associations of BMI with liver enzymes, steatosis, and fibrosis scores, consistent with observational associations. The genetic associations of BMI with liver diseases and biomarkers did not differ by hepatitis B virus infection status.

Conclusions And Relevance: In this cohort study of a relatively lean Chinese population, there were positive genetic associations of BMI with hepatobiliary diseases. These results suggest that maintaining a healthy weight through diet and physical activity may help prevent hepatobiliary diseases.
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http://dx.doi.org/10.1001/jamanetworkopen.2020.18721DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7532388PMC
October 2020

The Association Between Age at Initiation of Alcohol Consumption and Type 2 Diabetes Mellitus: A Cohort Study of 0.5 Million Persons in China.

Am J Epidemiol 2020 12;189(12):1478-1491

It is well known that alcohol consumption is associated with type 2 diabetes mellitus. However, the association of age at initiation of alcohol consumption and duration of alcohol drinking with type 2 diabetes mellitus among Chinese adults is not fully understood. This study was based on data from the China Kadoorie Biobank, which included 512,712 participants aged 30-79 years who were living in China in 2004-2008. A Cox proportional hazards model was used to estimate the association of AAI and drinking duration with type 2 diabetes. After adjustment for potential covariates, ages at alcohol initiation (AAIs) of 18.1-29.0 years, 29.1-39.0 years, and >39.0 years were associated with 22% (95% confidence interval (CI): 14, 30), 25% (95% CI: 17, 33), and 32% (95% CI: 24, 39) lower hazards of type 2 diabetes compared with abstaining, respectively. Drinking durations of <10.1 years, 10.1-20.0 years, and 20.1-30.0 years were associated with a lower risk of type 2 diabetes, compared with abstaining. Among current (weekly) drinkers, AAI <18.1 years and drinking duration >30.0 years were associated with 18% (95% CI: 4, 33) and 20% (95% CI: 3, 40) higher hazards of type 2 diabetes, compared with AAI 18.1-29.0 years and drinking duration <10.1 years, respectively. In conclusion, late AAI and a short drinking duration were associated with a lower risk of type 2 diabetes in this large prospective cohort study of Chinese adults, but early AAI and long drinking duration were not.
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http://dx.doi.org/10.1093/aje/kwaa119DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7857693PMC
December 2020

Body-mass index and long-term risk of sepsis-related mortality: a population-based cohort study of 0.5 million Chinese adults.

Crit Care 2020 08 31;24(1):534. Epub 2020 Aug 31.

Department of Epidemiology and Biostatistics, School of Public Health, Peking University Health Science Center, 38 Xueyuan Road, Beijing, 100191, China.

Background: Sepsis represents a major worldwide healthcare burden. However, how body-mass index (BMI) is related to the long-term risk of sepsis-related mortality in low- and middle-income countries remains uncertain.

Methods: We examined the associations of sepsis-related mortality with both baseline BMI and waist circumference (WC) using data from China Kadoorie Biobank, a prospective cohort recruited during 2004-2008 and followed up to December 2016. After excluding participants with chronic obstructive pulmonary disease, tuberculosis, cancer, heart disease, and stroke, and omitting the first 3 years of follow-up, 440,763 participants remained for analysis.

Results: During a median follow-up of 10.0 years, 1957 sepsis-related deaths (3,134,870 person-years) were included for analysis. Compared with reference BMI of 22.5 to < 25.0 kg/m, the multivariable-adjusted hazard ratios (HRs) for sepsis-related mortality were 2.42 (95% CIs 2.07-2.84) for BMI of < 18.5, 1.59 (1.36-1.85) for 18.5 to < 20.0, 1.21 (1.06-1.38) for 20.0 to < 22.5, 0.97 (0.83-1.13) for 25.0 to < 27.5, 0.98 (0.80-1.21) for 27.5 to < 30.0, and 1.22 (0.93-1.60) for ≥ 30.0 kg/m. Further adjustment for WC led to slightly augmentation of the effect size for the lower BMI groups and null association in the obese group. In the association analysis between WC and sepsis-related mortality, compared with the middle quintile group, only the highest quintile group showed an increased risk of sepsis-related mortality after adjusted for BMI (HR = 1.54; 95% CI 1.28-1.84).

Conclusions: Underweight, lower normal weight, and abdominal obesity are associated with increased future risk of sepsis-related mortality over 10 years in the Chinese population. The double burden of underweight and obesity indicates a heavy sepsis burden faced by low- and middle-income countries.
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http://dx.doi.org/10.1186/s13054-020-03229-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7457784PMC
August 2020

Association of physical activity with risk of hepatobiliary diseases in China: a prospective cohort study of 0.5 million people.

Br J Sports Med 2020 Aug 21. Epub 2020 Aug 21.

Department of Epidemiology and Biostatistics, School of Public Health, Peking University Health Science Center, Beijing, China

Objective: There is limited prospective evidence on the association of physical activity with hepatobiliary cancer subtypes and other major hepatobiliary diseases, especially in China. We aimed to quantify the associations with risk of these diseases.

Methods: The study population involved 460 937 participants of the prospective China Kadoorie Biobank aged 30-79 years from 10 diverse areas in China without history of cancer or hepatobiliary disease at baseline. Cox regression was used to estimate adjusted hazard ratios (HRs) for each disease associated with self-reported total and domain-specific physical activity (occupational and non-occupational, ie, leisure time, household and commuting).

Results: During ~10 years of follow-up, 22 012 incident cases of hepatobiliary diseases were recorded. The overall mean (SD) total physical activity was 21.2 (13.9) metabolic equivalent of task (MET)-hours/day, with 62% from occupational activity. Total physical activity was inversely associated with hospitalised non-alcoholic fatty liver disease (HR comparing top vs bottom quintile: 0.62, 95% confidence interval (CI) 0.53 to 0.72), viral hepatitis (0.73, 95% CI 0.62 to 0.87), cirrhosis (0.76, 95% CI 0.66 to 0.88) and liver cancer (0.81, 95% CI 0.71 to 0.93), as well as gallstone disease (0.86, 95% CI 0.81 to 0.90), gallbladder cancer (0.51, 95% CI 0.32 to 0.80) and biliary tract cancer (0.55, 95% CI 0.38 to 0.78). The associations for occupational physical activity were similar to those for total physical activity, but for non-occupational physical activity they differed by disease subtype. For leisure-time physical activity, there was an inverse association with liver cancer and an inverse trend for gallstone disease (HR comparing ≥7.5 MET-hours/day with none: 0.83, 95% CI 0.75 to 0.91 and 0.82, 95% CI 0.66 to 1.01).

Conclusion: Among Chinese adults, high total physical activity, particularly occupational physical activity, was inversely associated with risk of major hepatobiliary cancers and diseases, including non-alcoholic fatty liver disease, cirrhosis and certain types of cancer.
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http://dx.doi.org/10.1136/bjsports-2020-102174DOI Listing
August 2020

Protocol of a multicenter, single-blind, randomised, parallel controlled feeding trial evaluating the effect of a Chinese Healthy Heart (CHH) diet in lowering blood pressure and other cardiovascular risk factors.

BMJ Open 2020 08 20;10(8):e036394. Epub 2020 Aug 20.

Peking University Clinical Research Institute, Peking University First Hospital, Beijing, China.

Introduction: Unhealthy diet has been identified as the number one attributor of total mortality in China, accounting for more than 20% of total deaths. Although the Dietary Approach to Stop Hypertension (DASH) and Mediterranean diets have been proven beneficial in managing cardiovascular risk factors in Western countries, whether healthy diets with similar cardiovascular benefits can be developed that are consistent with Chinese food culture remains unknown.

Methods/design: The Diet, ExerCIse and CarDiovascular hEalth (DECIDE)-Diet trial is a multicentre, single-blind, randomised controlled feeding trial to evaluate the effect of the Chinese Healthy Heart (CHH) diet, in comparison with the Chinese usual diet, in lowering cardiovascular risk factors among community residents with the increased cardiovascular risk. A total of 360 adults aged between 25 and 75 years old and with systolic blood pressure between 130 and 159 mm Hg will be recruited from four centres located in four areas representing four major Chinese cuisines: Beijing, Shanghai, Guangzhou and Chengdu. After 1 week of run-in period with local usual diet, the compliant participants will be randomised to the intervention group with the CHH diet or the control group with the usual local diet, on a 1:1 ratio, for 4 weeks. Body weight of study participants will be maintained during the entire study period. The primary outcome is the change in SBP from the baseline to the end of the study. DECIDE-Diet trial will be the first randomised controlled feeding trial to evaluate the effect of a CHH diet in lowering cardiovascular risk factors. This trial will provide compelling evidence on the CHH diet in effect of improving cardiovascular health among Chinese food consumers all around the world.

Ethics And Dissemination: This trial adheres to the Declaration of Helsinki and guidelines of Good Clinical Practice. Signed informed consent will be obtained from all participants. The trial has been approved by the Peking University Institutional Review Board (approval number: IRB00001052-18094). The results will be disseminated through academic conferences and publications in international peer-reviewed journals.

Trail Registration Number: ClinicalTrials.gov Registry (NCT03882645); Pre-results.
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http://dx.doi.org/10.1136/bmjopen-2019-036394DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7440703PMC
August 2020

Communicating to and engaging with the public in regulatory science.

EFSA J 2019 Jul 8;17(Suppl 1):e170717. Epub 2019 Jul 8.

European Food Safety Authority Italy.

This paper presents selected highlights from the 'Engaging with society' session of EFSA's third Scientific Conference 'Science, Food and Society' (Parma, Italy, 18-21 September 2018). The social dimension for scientific advisory bodies largely concerns science communication and public engagement. The political, economic and technological transformation of contemporary societies is challenging conventional structures and approaches in these areas. The disintermediation of communication and the proliferation of misinformation, it is argued, herald the onset of the post-truth society. A better understanding of the way individuals consume information today has led to the development of tools to guide mediators such as journalists and communication specialists in countering these trends. Public engagement can reinforce confidence in regulatory bodies and potentially contribute to the quality of the scientific process. Scientific advisory bodies in Europe have created strategies and mechanisms to engage the public that are designed to increase transparency and representativeness. To be effective, several engagement mechanisms are needed, although factors such as resource constraints, institutional culture and public/stakeholder attitudes may limit their development. In conclusion, a more vigorous role for social research is needed to place scientific risk assessment within broader socio-economic and political contexts. Social science expertise can help to define more impactful public information strategies and to explore the potential opportunities that engaged stakeholders and citizens can make to sustain and strengthen regulatory science.
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http://dx.doi.org/10.2903/j.efsa.2019.e170717DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7015506PMC
July 2019

Impact of salt substitute and stepwise reduction of salt supply on blood pressure in residents in senior residential facilities: Design and rationale of the DECIDE-Salt trial.

Am Heart J 2020 08 30;226:198-205. Epub 2020 May 30.

Peking University Clinical Research Institute, Peking University First Hospital, Beijing, China; Department of Epidemiology and Biostatistics, Peking University School of Public Health, Beijing, China. Electronic address:

Background: High sodium intake has been considered as the leading dietary risk factor for deaths and disability-adjusted life-years among older adults. High-quality randomized trials to evaluate the effects of practical sodium reduction strategies are needed.

Methods: The study is a cluster randomized trial with a 2 × 2 factorial design conducted in 48 senior residential facilities in northern China. These facilities are randomly assigned (1:1:1:1) to 1 of 4 groups: stepwise salt supply control (SSSC) in which 5%-10% of the study salt supply in the institutional kitchens will be reduced every 3 months, replacing normal salt with salt substitute (SS); SSSC only; SS only; or neither SSSC nor SS. The interventions last for 2 years with follow-up every 6 months. The primary outcome is the change in systolic blood pressure from baseline to 24 months. Secondary outcomes include the incidence of hyperkalemia, hyponatremia, cardiovascular events, and death.

Current Status: The study has recruited and randomized 48 senior residential facilities with 1,606 participants. Mean age at baseline was 71 years, and 76% are male. Both types of salt intervention were initiated in the study facilities between January and April 2018.

Conclusion: The study is well placed to define the effects of 2 practical and scalable sodium reduction strategies for blood pressure reduction and will provide important new data about safety of these strategies among older adults in China.
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http://dx.doi.org/10.1016/j.ahj.2020.05.013DOI Listing
August 2020

Publisher Correction: Systemic inflammation is associated with incident stroke and heart disease in East Asians.

Sci Rep 2020 May 12;10(1):8084. Epub 2020 May 12.

Clinical Trial Service Unit & Epidemiological Studies Unit (CTSU), Nuffield Department of Population Health, University of Oxford, Oxford, United Kingdom.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
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http://dx.doi.org/10.1038/s41598-020-64764-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7217894PMC
May 2020

Weight loss since early adulthood, later life risk of fracture hospitalizations, and bone mineral density: a prospective cohort study of 0.5 million Chinese adults.

Arch Osteoporos 2020 04 19;15(1):60. Epub 2020 Apr 19.

Department of Epidemiology and Biostatistics, School of Public Health, Peking University Health Science Center, Beijing, China.

In a Chinese population from both urban and rural areas, weight loss of ≥ 5 kg from early adulthood to midlife was associated with a higher risk of hip fracture and lower BMD in later life.

Introduction: This study investigates the association of the long-term weight loss from young adulthood through the middle ages with the subsequent 10-year risk of hospitalized fracture and calcaneus bone mineral density (BMD).

Methods: China Kadoorie Biobank (CKB) was established during 2004-2008 in ten areas across China. Weight at age 25 years was self-reported at baseline, and weight at baseline and resurvey was measured by the calibrated equipment. Outcomes were hospitalized fracture during follow-up and calcaneus BMD measured at resurvey. Analysis for fracture risk included 411,812 participants who were free of fracture in the last 5 years before baseline, cancer, or stroke at any time before baseline. Analysis for BMD included 21,453 participants who participated in the resurvey of 2013-2014 with the same exclusion criteria as above.

Results: The mean age was 50.8 at baseline and 58.4 at resurvey. Median weight change from age 25 to baseline was 4.4 kg, with 20.7% losing weight and 58.5% gaining weight. During a median follow-up of 10.1 years, we documented 13,065 cases of first diagnosed fracture hospitalizations, including 1222 hip fracture. Compared with participants whose weight was stable (± 2.4 kg), the adjusted hazard ratios (95% CIs) for those with weight loss of ≥ 5.0 kg from age 25 to baseline was 1.39 (1.17 to 1.66) for hip fracture. Weight loss was not associated with fracture risk at other sites. Those with weight loss from age 25 to resurvey had the lowest BMD measures, with β (95% CIs) of - 4.52 (- 5.08 to - 3.96) for broadband ultrasound attenuation (BUA), - 4.83 (- 6.98, - 2.67) for speed of sound (SOS), and - 4.36 (- 5.22, - 3.49) for stiffness index (SI).

Conclusions: Weight loss from early adulthood to midlife was associated with a higher risk of hip fracture and lower BMD in later life.
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http://dx.doi.org/10.1007/s11657-020-00734-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7167376PMC
April 2020

Systemic inflammation is associated with incident stroke and heart disease in East Asians.

Sci Rep 2020 03 27;10(1):5605. Epub 2020 Mar 27.

Clinical Trial Service Unit & Epidemiological Studies Unit (CTSU), Nuffield Department of Population Health, University of Oxford, Oxford, United Kingdom.

Systemic inflammation, reflected by increased plasma concentrations of C-reactive protein (CRP) and fibrinogen, is associated with increased risk of coronary heart disease, but its relevance for stroke types remains unclear. Moreover, evidence is limited in non-European populations. We investigated associations of CRP and fibrinogen with risks of incident major coronary events (MCE), ischemic stroke (IS) and intracerebral hemorrhage (ICH) in a cohort of Chinese adults. A nested case-control study within the prospective China Kadoorie Biobank included 1,508 incident MCE cases, 5,418 IS cases, 4,476 ICH cases, and 5,285 common controls, aged 30-79 years. High-sensitivity CRP and low-density lipoprotein cholesterol (LDL-C) were measured in baseline plasma samples from all participants, and fibrinogen in a subset (n = 9,380). Logistic regression yielded adjusted odds ratios (ORs) per SD higher usual levels of log-transformed CRP and fibrinogen. The overall mean (SD) baseline LDL-C was 91.6 mg/dL (24.0) and geometric mean (95% CI) CRP and fibrinogen were 0.90 mg/L (0.87-0.93) and 3.01 g/L (2.98-3.03), respectively. There were approximately log-linear positive associations of CRP with each outcome, which persisted after adjustment for LDL-C and other risk factors, with adjusted ORs (95% CI) per SD higher CRP of 1.67 (1.44-1.94) for MCE and 1.22 (1.10-1.36) for both IS and ICH. No associations of fibrinogen with MCE, IS, or ICH were identified. Adding CRP to prediction models based on established risk factors improved model fit for each of MCE, IS, and ICH, with small improvements in C-statistic and correct reclassification of controls to lower risk groups. Among Chinese adults, who have low mean LDL-C, CRP, but not fibrinogen, was independently associated with increased risks of MCE and stroke.
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http://dx.doi.org/10.1038/s41598-020-62391-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7101367PMC
March 2020

Habitual snoring, adiposity measures and risk of type 2 diabetes in 0.5 million Chinese adults: a 10-year cohort.

BMJ Open Diabetes Res Care 2020 02;8(1)

Department of Epidemiology and Biostatistics, School of Public Health, Peking University, Beijing, China

Objectives: The present study aimed to examine whether habitual snoring was independently associated with risk of type 2 diabetes among Chinese adults, and to assess the role that adiposity measures play in the snoring-diabetes association, as well as to evaluate the joint influence of snoring and adiposity measures on diabetes.

Research Design And Methods: The China Kadoorie Biobank study recruited 512 715 adults aged 30-79 years from 10 regions in China during 2004 and 2008. Data from 482 413 participants without baseline diabetes were analyzed in the present study. Autoregressive cross-lagged panel analysis was used to assess the longitudinal relationship between adiposity measures and habitual snoring. Cox proportional hazards models were used to examine the association between habitual snoring and diabetes risk.

Results: Both higher body mass index and waist circumference were associated with higher risks of subsequent habitual snoring, whereas no reverse association was detected. A total of 16 479 type 2 diabetes cases were observed during a 10-year follow-up. Habitual snoring was independently associated with 12% (95% CI 6% to 18%) and 14% (95% CI 9% to 19%) higher risks of diabetes among men and women, respectively. Habitual snorers who had general obesity or central obesity were about twice as likely to develop diabetes as non-snorers at the lowest levels of adiposity measures.

Conclusion: Habitual snoring was independently associated with a higher risk of type 2 diabetes among Chinese adults. It is important to maintain both a healthy weight and a normal waist circumference to prevent or alleviate habitual snoring and ultimately prevent diabetes among Chinese adults.
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http://dx.doi.org/10.1136/bmjdrc-2019-001015DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7050323PMC
February 2020

Socioeconomic Status in Relation to Risks of Major Gastrointestinal Cancers in Chinese Adults: A Prospective Study of 0.5 Million People.

Cancer Epidemiol Biomarkers Prev 2020 04 27;29(4):823-831. Epub 2020 Jan 27.

Clinical Trial Service Unit & Epidemiological Studies Unit (CTSU), Nuffield Department of Population Health, University of Oxford, Oxford, United Kingdom.

Background: Low socioeconomic status (SES) is associated with higher risk of certain gastrointestinal (e.g., colorectal, pancreatic, and liver) cancers in Western populations. Evidence is very limited in China, where correlates and determinants of SES differ from those in the West.

Methods: The prospective China Kadoorie Biobank recruited 512,715 adults (59% women, mean age 51 years) from 10 (5 urban, 5 rural) regions. During 10 years of follow-up, 27,940 incident cancers (including 3,061 colorectal, 805 pancreatic, and 2,904 liver) were recorded among 510,131 participants without prior cancer at baseline. Cox regression was used to estimate adjusted HRs for specific cancers associated with area-level (e.g., per capita gross domestic product, disposable income) and individual-level (e.g., education, household income) SES.

Results: Area-level SES and household income showed positive associations with incident colorectal and pancreatic cancers and inverse associations with liver cancer ( < 0.05). Education showed no association with colorectal cancer but inverse associations with pancreatic and liver cancers, with adjusted HRs comparing university to no formal schooling being 1.05 [95% confidence interval (CI), 0.85-1.29], 0.49 (95% CI, 0.28-0.85), and 0.61 (95% CI, 0.47-0.81), respectively. Potential risk factors (e.g., smoking, alcohol) partly explained the inverse associations of education with pancreatic and liver cancers (17.6% and 60.4%), respectively.

Conclusions: Among Chinese adults, the associations of SES with gastrointestinal cancers differed by cancer type and SES indicator. Potential risk factors partially explained the inverse associations of education with pancreatic and liver cancers.

Impact: The different associations between SES with gastrointestinal cancers may inform cancer prevention strategies.
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http://dx.doi.org/10.1158/1055-9965.EPI-19-0585DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7242093PMC
April 2020

Association between adiposity measures and COPD risk in Chinese adults.

Eur Respir J 2020 04 30;55(4). Epub 2020 Apr 30.

Dept of Epidemiology and Biostatistics, School of Public Health, Peking University Health Science Center, Beijing, China.

Bodyweight and fat distribution may be related to COPD risk. Limited prospective evidence linked COPD to abdominal adiposity. We investigated the association of body mass index (BMI) and measures of abdominal adiposity with COPD risk in a prospective cohort study.The China Kadoorie Biobank recruited participants aged 30-79 years from 10 areas across China. Anthropometric indexes were objectively measured at the baseline survey during 2004-2008. After exclusion of participants with prevalent COPD and major chronic diseases, 452 259 participants were included and followed-up until the end of 2016. We used Cox models to estimate adjusted hazard ratios relating adiposity to risk of COPD hospitalisation or death.Over an average of 10.1 years of follow-up, 10 739 COPD hospitalisation events and deaths were reported. Compared with subjects with normal BMI (18.5-<24.0 kg·m), underweight (BMI <18.5 kg·m) individuals had increased risk of COPD, with adjusted hazard ratio 1.78 (95% CI 1.66-1.89). Overweight (BMI 24.0-<28.0 kg·m) and obesity (BMI ≥28.0 kg·m) were not associated with an increased risk after adjustment for waist circumference. A higher waist circumference (≥85 cm for males and ≥80 cm for females) was positively associated with COPD risk after adjustment for BMI. Additionally, waist-to-hip ratio and waist-to-height ratio were positively related to COPD risk.Abdominal adiposity and underweight were risk factors for COPD in Chinese adults. Both BMI and measures of abdominal adiposity should be considered in the prevention of COPD.
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http://dx.doi.org/10.1183/13993003.01899-2019DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7236866PMC
April 2020