Publications by authors named "Zhengming Chen"

351 Publications

Solid fuel use, socioeconomic indicators and risk of cardiovascular diseases and all-cause mortality: a prospective cohort study in a rural area of Sichuan, China.

Int J Epidemiol 2021 Sep 18. Epub 2021 Sep 18.

Vanke School of Public Health, Tsinghua University, Beijing, China.

Background: Estimates indicate that household air pollution caused by solid fuel burning accounted for about 1.03 million premature mortalities in China in 2016. In the country's rural areas, more than half the population still relies on biomass fuels and coals for cooking and heating. Understanding the health impact of indoor air pollution and socioeconomic indicators is essential for the country to improve its developmental targets. We aimed to describe demographic and socioeconomic characteristics associated with solid fuel users in a rural area in China. We also estimated the risk of cardiovascular disease and all-cause mortality in association with solid fuel use and described the relationship between solid fuel use, socioeconomic status and mortality. We also measured the risk of long-term use, and the effect of ameliorative action, on mortality caused by cardiovascular disease and other causes.

Methods: We used the China Kadoorie Biobank (CKB) site in Pengzhou, Sichuan, China. We followed a cohort of 55 687 people over 2004-13. We calculated the mean and standard deviation among subgroups classified by fuel use types: gas, coal, wood and electricity (central heating additionally for heating). We tested the mediation effect using the stepwise method and Sobel test. We used Cox proportional models to estimate the risk of incidences of cardiovascular disease and mortality with survival days as the time scale, adjusted for age, gender, socioeconomic status, physical measurements, lifestyle, stove ventilation and fuel type used for other purposes. The survival days were defined as the follow-up days from the baseline survey till the date of death or 31 December 2013 if right-censored. We also calculated the absolute mortality rate difference (ARD) between the exposure group and the reference group.

Results: The study population had an average age of 51.0, and 61.9% of the individuals were female; 64.8% participants (n = 35 543) cooked regularly and 25.4% participants (n = 13 921) needed winter heating. With clean fuel users as the reference group, participant households that used solid fuel for cooking or heating both had a higher risk of all-cause mortality: hazard ratio (HR) for: cooking, 1.11 [95% confidence interval (CI) 1.02, 1.26]; heating, 1.34 (95% CI 1.16, 1.54). Solid fuel used for winter heating was associated with a higher risk of mortality caused by cerebrovascular disease: HR 1.64 (95% CI 1.12, 2.40); stroke: HR 1.70 (95% CI 1.13, 2.56); and cardiovascular disease: HR 1.49 (95% CI 1.10, 2.02). Low income and poor education level had a significant correlation with solid fuel used for cooking: odds ratio (OR) for income: 2.27 (95% CI 2.14, 2.41); education: 2.34 (95% CI 2.18, 2.53); and for heating: income: 2.69 (95% CI 2.46, 2.97); education: 2.05 (95% CI 1.88, 2.26), which may be potential mediators bridging the effects of socioeconomic status factors on cardiovascular disease and all-cause mortality. Solid fuel used for cooking and heating accounted for 42.4% and 81.1% of the effect of poor education and 55.2% and 76.0% of the effect of low income on all-cause mortality, respectively. The risk of all-cause mortality could be ameliorated by stopping regularly cooking and heating using solid fuel or switching from solid fuel to clean fuels: HR for cooking: 0.90 (95% CI 0.84, 0.96); heating: 0.76 (95% CI 0.64, 0.92).

Conclusions: Our study reinforces the evidence of an association between solid fuel use and risk of cardiovascular disease and all-cause mortality. We also assessed the effect of socioeconomic status as the potential mediator on mortality. As solid fuel use was a major contributor in the effect of socioeconomic status on cardiovascular disease and all-cause mortality, policies to improve access to clean fuels could reduce morbidity and mortality related to poor education and low income.
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http://dx.doi.org/10.1093/ije/dyab191DOI Listing
September 2021

Alcohol drinking and risks of liver cancer and non-neoplastic chronic liver diseases in China: a 10-year prospective study of 0.5 million adults.

BMC Med 2021 09 17;19(1):216. Epub 2021 Sep 17.

Clinical Trial Service Unit and Epidemiological Studies Unit (CTSU), Nuffield Department of Population Health, University of Oxford, Oxford, UK.

Background: Alcohol consumption is an important risk factor for hepatic neoplastic and non-neoplastic diseases. Questions remain, however, about the relevance to disease risk of drinking patterns and alcohol tolerability, which differ appreciably between Chinese and Western populations.

Methods: The prospective China Kadoorie Biobank included 512,715 adults (41% men) aged 30-79 years recruited from ten areas during 2004-2008, recording alcohol intake, drinking patterns, and other characteristics. After median 10 years' follow-up, 2531 incident liver cancer, 2040 liver cirrhosis, 260 alcoholic liver disease (ALD), and 1262 non-alcoholic fatty liver disease (NAFLD) cases were recorded among 492,643 participants without prior cancer or chronic liver disease at baseline. Cox regression was used to estimate adjusted hazard ratios (HR) relating alcohol intake and drinking patterns to each disease.

Results: Overall, 33% of men and 2% of women drank alcohol regularly (i.e. at least weekly) at baseline. Among male current regular drinkers, alcohol consumption showed positive dose-response associations with risks of several major chronic liver diseases, with HRs per 280 g/week (i.e. around four drinks/day) higher usual alcohol intake of 1.44 (95% CI 1.23-1.69) for liver cancer (n = 547), 1.83 (1.60-2.09) for liver cirrhosis (n = 388), 2.01 (1.77-2.28) for ALD (n = 200), 1.71 (1.35-2.16) for NAFLD (n = 198), and 1.52 (1.40-1.64) for total liver disease (n = 1775). The association with ALD appeared stronger among men reporting flushing (i.e., with low alcohol tolerance). After adjustment for the total amount of weekly alcohol consumption, daily drinkers had significantly increased risk of ALD (2.15, 1.40-3.31) compared with non-daily drinkers, and drinking without meals was associated with significantly greater risks of liver cancer (1.32, 1.01-1.72), liver cirrhosis (1.37, 1.02-1.85), and ALD (1.60, 1.09-2.33) compared with drinking with meals. Female current regular drinkers had significantly higher risk of ALD, but not other liver diseases, than female abstainers.

Conclusions: In Chinese men, alcohol intake was associated with significantly increased risks of several major chronic liver diseases, and certain drinking patterns (e.g. drinking daily, drinking without meals) may further exacerbate the disease risks.
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http://dx.doi.org/10.1186/s12916-021-02079-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8447782PMC
September 2021

Epigenome-wide analysis of DNA methylation and coronary heart disease: a nested case-control study.

Elife 2021 Sep 13;10. Epub 2021 Sep 13.

Epidemiology and Biostatistics, Peking University, Beijing, China.

Identifying environmentally responsive genetic loci where DNA methylation is associated with coronary heart disease (CHD) may reveal novel pathways or therapeutic targets for CHD. We conducted the first prospective epigenome-wide analysis of DNA methylation in relation to incident CHD in the Asian population.

We did a nested case-control study comprising incident CHD cases and 1:1 matched controls who were identified from the 10-year follow-up of the China Kadoorie Biobank. Methylation level of baseline blood leukocyte DNA was measured by Infinium Methylation EPIC BeadChip. We performed the single cytosine-phosphate-guanine (CpG) site association analysis and network approach to identify CHD-associated CpG sites and co-methylation gene module.

After quality control, 982 participants (mean age 50.1 years) were retained. Methylation level at 25 CpG sites across the genome was associated with incident CHD (genome-wide false discovery rate [FDR] < 0.05 or module-specific FDR <0.01). One SD increase in methylation level of identified CpGs was associated with differences in CHD risk, ranging from a 47% decrease to a 118% increase. Mediation analyses revealed 28.5% of the excessed CHD risk associated with smoking was mediated by methylation level at the promoter region of gene (P for mediation effect = 0.036). Methylation level at the promoter region of was associated with blood pressure and subsequent risk of CHD, with the mediating proportion to be 7.7% (P = 0.003) via systolic blood pressure and 6.4% (P = 0.006) via diastolic blood pressure. Network analysis revealed a co-methylation module associated with CHD.

We identified novel blood methylation alterations associated with incident CHD in the Asian population and provided evidence of the possible role of epigenetic regulations in the smoking- and BP-related pathways to CHD risk.

This work was supported by National Natural Science Foundation of China (81390544 and 91846303). The CKB baseline survey and the first re-survey were supported by a grant from the Kadoorie Charitable Foundation in Hong Kong. The long-term follow-up is supported by grants from the UK Wellcome Trust (202922/Z/16/Z, 088158/Z/09/Z, 104085/Z/14/Z), grant (2016YFC0900500, 2016YFC0900501, 2016YFC0900504, 2016YFC1303904) from the National Key and Program of China, and Chinese Ministry of Science and Technology (2011BAI09B01).
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http://dx.doi.org/10.7554/eLife.68671DOI Listing
September 2021

Worsening Quality of Life in Indolent Non-Hodgkin Lymphoma and Chronic Lymphocytic Leukemia Patients in Active Surveillance: A 12-Month Longitudinal Study.

Clin Lymphoma Myeloma Leuk 2021 Aug 12. Epub 2021 Aug 12.

Weill Cornell Medicine; New York Presbyterian Hospital.

Introduction: Newly diagnosed indolent non-Hodgkin lymphoma and chronic lymphocytic leukemia (NHL/CLL) patients are often monitored for disease progression to delay the impact of cancer-directed therapy on patients' quality of life. However, research on quality of life in patients under active surveillance versus in cancer-directed treatment has yielded mixed results. This study examined distress and quality of life in indolent NHL/CLL patients in active surveillance or cancer-directed treatment over the first-year post-diagnosis.

Patients And Methods: Adult patients (≥21 years) with newly diagnosed indolent NHL/CLL completed electronic self-report measure of distress and quality of life every 4 months over the course of a year for a total of 4 surveys. Fisher's exact test and t-tests were used to examine demographic and disease differences between patients receiving different treatments. Mixed-effect models were also used to compare overall differences between treatment status over time, accounting for missing values.

Results: The sample consisted of 64 patients with known baseline treatment status who did not change treatments over the course of the study. Total quality of life and physical, social and functional quality of life improved over time in patients receiving cancer-directed treatment and decreased over time in patients under active surveillance. Relative to patients in active treatment, overall, social, and functional quality of life in patients under surveillance changed more slowly over time.

Discussion: Active surveillance may have negative implications for patient quality of life, despite that a common goal of active surveillance is to delay the impact of treatment (e.g., appointments, toxicities) on quality of life.
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http://dx.doi.org/10.1016/j.clml.2021.08.001DOI Listing
August 2021

Dietary patterns and cardiometabolic diseases in 0.5 million Chinese adults: a 10-year cohort study.

Nutr J 2021 09 3;20(1):74. Epub 2021 Sep 3.

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

Background: The effect of the overall diet quality on cardiometabolic diseases has been well studied in the Western population. However, evidence is still in need regarding dietary patterns depicting unique Chinese dietary habits and their associations with cardiometabolic diseases.

Methods: A prospective cohort recruited around 0.5 million Chinese residents aged 30-79 years from 10 diverse survey sites during 2004-08. Dietary patterns were obtained using factor analysis based on the habitual consumption of 12 food groups collected at baseline. Among 477,465 eligible participants free of prior heart disease, stroke and cancer, linkages to multiple registries and health insurance database recorded 137,715 cardiovascular diseases (CVD) and 17,412 diabetes cases (among 451,846 non-diabetic participants) until 31 December 2017. Adjusted hazard ratios (HRs) were estimated to compare the risks of cardiometabolic diseases across quintiles of dietary pattern scores using the Cox regression.

Results: Two dietary patterns were derived: the traditional northern pattern, characterised by wheat, other staples, egg and dairy products; and the modern pattern, featured with fresh fruit, meat, poultry, fish, dairy products and soybean. Adherence to either dietary pattern was associated with lower risks of major cardiometabolic diseases in a dose-response relationship way. After multivariate adjustment, participants adhering to the traditional northern pattern the most had an 8% (95%CI: 5-11%) lower risk of CVD in comparison with those adhering the least. Corresponding risk reductions were 12% (11-32%) for haemorrhagic stroke (HS), 14% (8-19%) for ischaemic stroke (IS), and 15% (6-24%) for diabetes, respectively. When comparing extreme quintiles of the modern pattern, the adjusted HR of HS was 0.67 (95%CI: 0.59-0.77). Corresponding HRs were 0.89 (0.86-0.92) for CVD, 0.88 (0.77-0.99) for MCE, 0.85 (0.80-0.89) for IS, and 0.89 (0.81, 0.97) for diabetes.

Conclusion: Among Chinese adults, both traditional northern and modern dietary patterns were associated with lower risks of cardiovascular disease and diabetes beyond other risk factors.
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http://dx.doi.org/10.1186/s12937-021-00730-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8418004PMC
September 2021

Utility of single versus sequential measurements of risk factors for prediction of stroke in Chinese adults.

Sci Rep 2021 Sep 2;11(1):17575. Epub 2021 Sep 2.

Clinical Trial Service Unit and Epidemiological Studies, Nuffield Department of Population Health, University of Oxford, Big Data Institute, Old Road Campus, Oxford, OX 7LF, UK.

Absolute risks of stroke are typically estimated using measurements of cardiovascular disease risk factors recorded at a single visit. However, the comparative utility of single versus sequential risk factor measurements for stroke prediction is unclear. Risk factors were recorded on three separate visits on 13,753 individuals in the prospective China Kadoorie Biobank. All participants were stroke-free at baseline (2004-2008), first resurvey (2008), and second resurvey (2013-2014), and were followed-up for incident cases of first stroke in the 3 years following the second resurvey. To reflect the models currently used in clinical practice, sex-specific Cox models were developed to estimate 3-year risks of stroke using single measurements recorded at second resurvey and were retrospectively applied to risk factor data from previous visits. Temporal trends in the Cox-generated risk estimates from 2004 to 2014 were analyzed using linear mixed effects models. To assess the value of more flexible machine learning approaches and the incorporation of longitudinal data, we developed gradient boosted tree (GBT) models for 3-year prediction of stroke using both single measurements and sequential measurements of risk factor inputs. Overall, Cox-generated estimates for 3-year stroke risk increased by 0.3% per annum in men and 0.2% per annum in women, but varied substantially between individuals. The risk estimates at second resurvey were highly correlated with the annual increase of risk for each individual (men: r = 0.91, women: r = 0.89), and performance of the longitudinal GBT models was comparable with both Cox and GBT models that considered measurements from only a single visit (AUCs: 0.779-0.811 in men, 0.724-0.756 in women). These results provide support for current clinical guidelines, which recommend using risk factor measurements recorded at a single visit for stroke prediction.
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http://dx.doi.org/10.1038/s41598-021-95244-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8413314PMC
September 2021

Genetic insights into biological mechanisms governing human ovarian ageing.

Nature 2021 08 4;596(7872):393-397. Epub 2021 Aug 4.

Genome Integrity and Instability Group, Institut de Biotecnologia i Biomedicina, Universitat Autònoma de Barcelona, Cerdanyola del Vallès, Spain.

Reproductive longevity is essential for fertility and influences healthy ageing in women, but insights into its underlying biological mechanisms and treatments to preserve it are limited. Here we identify 290 genetic determinants of ovarian ageing, assessed using normal variation in age at natural menopause (ANM) in about 200,000 women of European ancestry. These common alleles were associated with clinical extremes of ANM; women in the top 1% of genetic susceptibility have an equivalent risk of premature ovarian insufficiency to those carrying monogenic FMR1 premutations. The identified loci implicate a broad range of DNA damage response (DDR) processes and include loss-of-function variants in key DDR-associated genes. Integration with experimental models demonstrates that these DDR processes act across the life-course to shape the ovarian reserve and its rate of depletion. Furthermore, we demonstrate that experimental manipulation of DDR pathways highlighted by human genetics increases fertility and extends reproductive life in mice. Causal inference analyses using the identified genetic variants indicate that extending reproductive life in women improves bone health and reduces risk of type 2 diabetes, but increases the risk of hormone-sensitive cancers. These findings provide insight into the mechanisms that govern ovarian ageing, when they act, and how they might be targeted by therapeutic approaches to extend fertility and prevent disease.
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http://dx.doi.org/10.1038/s41586-021-03779-7DOI Listing
August 2021

Lifestyle, cardiometabolic disease, and multimorbidity in a prospective Chinese study.

Eur Heart J 2021 Sep;42(34):3374-3384

Department of Epidemiology & Biostatistics, School of Public Health, Peking University, Xueyuan Road, Haidian District, Beijing 100191, China.

Aims : The potential difference in the impacts of lifestyle factors (LFs) on progression from healthy to first cardiometabolic disease (FCMD), subsequently to cardiometabolic multimorbidity (CMM), and further to death is unclear.

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

Conclusion : Assuming causality exists, our findings emphasize the significance of integrating comprehensive lifestyle interventions into both health management and CMD management.
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http://dx.doi.org/10.1093/eurheartj/ehab413DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8423468PMC
September 2021

Adherence to healthy lifestyle and attenuation of biological aging in middle-aged and older Chinese adults.

J Gerontol A Biol Sci Med Sci 2021 Jul 30. Epub 2021 Jul 30.

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

Background: Little is known about the effects of lifestyle modification on biological aging in population-based studies of middle-aged and older adults.

Methods: We examined the individual and joint associations of multiple lifestyle factors with accelerated biological aging measured by change in frailty index (FI) over 8 years in a prospective study of Chinese adults. Data were obtained on 24,813 participants in the China Kadoorie Biobank (CKB) on lifestyle factors and frailty status at baseline and at 8 years after baseline. Adherence to healthy lifestyle factors included non-smoking or quitting smoking for reasons other than illness, avoidance of heavy alcohol consumption, daily intake of fruit and vegetables, being physically active, body mass index (BMI) of 18.5-23.9 kg/m 2, and waist-to-hip ratio (WHR) <0.90 (men)/0.85 (women). FI was constructed separately at baseline and resurvey using 25 age- and health-related items.

Results: Overall, 8,760 (35.3%) individuals had a worsening frailty status. In multivariable-adjusted logistic regression analyses, adherence to healthy lifestyle was associated with a lower risk of worsening frailty status. Compared with robust participants maintaining 0-1 healthy lifestyle factors, the corresponding OR (95% CI) was 0.93 (0.83-1.03), 0.75 (0.67-0.84), 0.68 (0.60-0.77), and 0.55 (0.46-0.65) for robust participants with 2, 3, 4, and 5-6 healthy lifestyle factors. The decreased risk of frailty status worsening by adherence to healthy lifestyle factors was similar in both middle-aged and older adults, and in both robust and prefrail participants at baseline.

Conclusions: Adherence to a healthy lifestyle may attenuate the rate of change in biological aging in middle-aged and older Chinese adults.
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http://dx.doi.org/10.1093/gerona/glab213DOI Listing
July 2021

Association between blood pressure categories and cardiovascular disease mortality in China.

PLoS One 2021 30;16(7):e0255373. Epub 2021 Jul 30.

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

Background: Blood pressure (BP) categories are useful to simplify preventions in public health, and diagnostic and treatment approaches in clinical practice. Updated evidence about the associations of BP categories with cardiovascular diseases (CVDs) and its subtypes is warranted.

Methods And Findings: About 0.5 million adults aged 30 to 79 years were recruited from 10 areas in China during 2004-2008. The present study included 430 977 participants without antihypertension treatment, cancer, or CVD at baseline. BP was measured at least twice in a single visit at baseline and CVD deaths during follow-up were collected via registries and the national health insurance databases. Multivariable Cox regression was used to estimate the associations between BP categories and CVD mortality. Overall, 16.3% had prehypertension-low, 25.1% had prehypertension-high, 14.1% had isolated systolic hypertension (ISH), 1.9% had isolated diastolic hypertension (IDH), and 9.1% had systolic-diastolic hypertension (SDH). During a median 10-year follow-up, 9660 CVD deaths were documented. Compared with normal, the hazard ratios (95% CI) of prehypertension-low, prehypertension-high, ISH, IDH, SDH for CVD were 1.10 (1.01-1.19), 1.32 (1.23-1.42), 2.04 (1.91-2.19), 2.20 (1.85-2.61), and 3.81 (3.54-4.09), respectively. All hypertension subtypes were related to the increased risk of CVD subtypes, with a stronger association for hemorrhagic stroke than for ischemic heart disease. The associations were stronger in younger than older adults.

Conclusions: Prehypertension-high should be considered in CVD primary prevention given its high prevalence and increased CVD risk. All hypertension subtypes were independently associated with CVD and its subtypes mortality, though the strength of associations varied substantially.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0255373PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8323908PMC
July 2021

Blood pressure and cardiovascular diseases in Chinese adults with type 2 diabetes: A prospective cohort study.

Lancet Reg Health West Pac 2021 Feb 23;7:100085. Epub 2021 Jan 23.

Clinical Trial Service Unit & Epidemiological Studies Unit (CTSU), Nuffield Department of Population Health, University of Oxford, Old Road Campus, Oxford OX3 7LF, UK.

Background: Controversy persists about the relationship of blood pressure with cardiovascular diseases (CVD) in diabetes and associated disease burden. We assessed these associations among Chinese adults with type 2 diabetes (T2D).

Methods: In 2004-08, the China Kadoorie Biobank recruited >512,000 adults aged 30-79 years from 10 localities across China, including 26,315 with T2D (based on self-report or plasma glucose measurement) but no prior CVD, followed-up for ~9 years. Cox regression yielded adjusted HR for major CVD and all-cause mortality associated with 10 mmHg higher usual (longer-term average) SBP. Attributable fractions were estimated to assess cardiovascular mortality burden due to uncontrolled hypertension (SBP ≥130 mmHg or DBP ≥80 mmHg).

Findings: Overall, 75.7% of participants had self-reported (24.8%) or screen-detected (50.9%) (SBP ≥130 mmHg or DBP ≥80 mmHg) hypertension. Among individuals with self-reported hypertension, 82.3% were treated, of whom 9.3% achieved control. There were positive log-linear associations of blood pressure with CVD, with no evidence of a threshold down to ~120 mmHg for usual SBP. Each 10 mmHg higher usual SBP was associated with HR of 1.28 (95% CI 1.25-1.30), 1.18 (1.15-1.21), 1.17 (1.15-1.19) and 1.45 (1.38-1.52) for cardiovascular death (=1807), major coronary event (=1190), ischaemic stroke (=4362) and intracerebral haemorrhage (=469), respectively. There was an apparent J-shaped association with all-cause mortality (=4503). In this diabetes population, uncontrolled hypertension accounted for 39% of cardiovascular deaths.

Interpretation: Uncontrolled hypertension is common in Chinese adults with T2D, resulting in substantial excess risks of CVD. Improved hypertension management could avoid a large number of cardiovascular-related deaths.

Funding: Kadoorie Foundation, Wellcome Trust, MRC, BHF, CR-UK, MoST, NNSF.
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http://dx.doi.org/10.1016/j.lanwpc.2020.100085DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8315364PMC
February 2021

Long-term solid fuel use and risks of major eye diseases in China: A population-based cohort study of 486,532 adults.

PLoS Med 2021 Jul 29;18(7):e1003716. Epub 2021 Jul 29.

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

Background: Over 3.5 billion individuals worldwide are exposed to household air pollution from solid fuel use. There is limited evidence from cohort studies on associations of solid fuel use with risks of major eye diseases, which cause substantial disease and economic burden globally.

Methods And Findings: The China Kadoorie Biobank recruited 512,715 adults aged 30 to 79 years from 10 areas across China during 2004 to 2008. Cooking frequency and primary fuel types in the 3 most recent residences were assessed by a questionnaire. During median (IQR) 10.1 (9.2 to 11.1) years of follow-up, electronic linkages to national health insurance databases identified 4,877 incident conjunctiva disorders, 13,408 cataracts, 1,583 disorders of sclera, cornea, iris, and ciliary body (DSCIC), and 1,534 cases of glaucoma. Logistic regression yielded odds ratios (ORs) for each disease associated with long-term use of solid fuels (i.e., coal or wood) compared to clean fuels (i.e., gas or electricity) for cooking, with adjustment for age at baseline, birth cohort, sex, study area, education, occupation, alcohol intake, smoking, environmental tobacco smoke, cookstove ventilation, heating fuel exposure, body mass index, prevalent diabetes, self-reported general health, and length of recall period. After excluding participants with missing or unreliable exposure data, 486,532 participants (mean baseline age 52.0 [SD 10.7] years; 59.1% women) were analysed. Overall, 71% of participants cooked regularly throughout the recall period, of whom 48% used solid fuels consistently. Compared with clean fuel users, solid fuel users had adjusted ORs of 1.32 (1.07 to 1.37, p < 0.001) for conjunctiva disorders, 1.17 (1.08 to 1.26, p < 0.001) for cataracts, 1.35 (1.10 to 1.66, p = 0.0046) for DSCIC, and 0.95 (0.76 to 1.18, p = 0.62) for glaucoma. Switching from solid to clean fuels was associated with smaller elevated risks (over long-term clean fuel users) than nonswitching, with adjusted ORs of 1.21 (1.07 to 1.37, p < 0.001), 1.05 (0.98 to 1.12, p = 0.17), and 1.21 (0.97 to 1.50, p = 0.088) for conjunctiva disorders, cataracts, and DSCIC, respectively. The adjusted ORs for the eye diseases were broadly similar in solid fuel users regardless of ventilation status. The main limitations of this study include the lack of baseline eye disease assessment, the use of self-reported cooking frequency and fuel types for exposure assessment, the risk of bias from delayed diagnosis (particularly for cataracts), and potential residual confounding from unmeasured factors (e.g., sunlight exposure).

Conclusions: Among Chinese adults, long-term solid fuel use for cooking was associated with higher risks of not only conjunctiva disorders but also cataracts and other more severe eye diseases. Switching to clean fuels appeared to mitigate the risks, underscoring the global health importance of promoting universal access to clean fuels.
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http://dx.doi.org/10.1371/journal.pmed.1003716DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8321372PMC
July 2021

Functional impact of cancer patient-associated Bcl-xL mutations.

MedComm (Beijing) 2020 Dec 29;1(3):328-337. Epub 2020 Oct 29.

Department of Pathology and Laboratory Medicine, Weill Cornell Medicine, New York, New York.

Bcl-xL, an antiapoptotic protein, is frequently overexpressed in cancer to promote survival of tumor cells. However, we have previously shown that Bcl-xL promotes migration, invasion, and metastasis independent of its antiapoptotic function in mitochondria. The pro-metastatic function of Bcl-xL may require its translocation into the nucleus. Besides overexpression, patient-associated mutations of Bcl-xL have been identified in large-scale cancer genomics projects. Understanding the functions of these mutations will guide the development of precision medicine. Here, we selected four patient-associated Bcl-xL mutations, R132W, N136K, R165W, and A201T, to investigate their impacts on antiapoptosis, migration, and nuclear translocation. We found that all four mutation proteins could be detected in both the nucleus and cytosol. Although all four mutations disrupted the antiapoptosis function, one of these mutants, N136K, significantly improved the ability to promote cell migration. These data suggest the importance of developing novel Bcl-xL inhibitors to ablate both antiapoptotic and pro-metastatic functions of Bcl-xL in cancer.
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http://dx.doi.org/10.1002/mco2.36DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8302207PMC
December 2020

Association between frequency of spicy food consumption and hypertension: a cross-sectional study in Zhejiang Province, China.

Nutr Metab (Lond) 2021 Jul 6;18(1):70. Epub 2021 Jul 6.

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

Background: Hypertension is a known risk factor for multiple chronic diseases. Existing literature on the association between frequency of spicy food consumption and hypertension shows mixed findings.

Methods: The analyses are based on the Tongxiang baseline dataset of the China Kadoorie Biobank prospective study, including data from electronic questionnaires, physical measurements and blood sample collection. A total of 53,916 participants aged 30-79 years were included in the final analysis. Multivariable logistic regression was used to estimate the association of spicy food consumption with hypertension, and multiple linear regression was performed to explore the association of spicy food consumption with systolic and diastolic blood pressure.

Results: Of the 53,916 participants, 23,921 had prevalent hypertension. 12.3% of participants reported consuming spicy food weekly. Among female participants, after adjusting for socio-demographic status, lifestyle factors, BMI, waist circumference, sleep duration and snoring, when compared with females who never consumed spicy food, the odds ratios (95% CI) for hypertension were 1.02 (0.96-1.08), 0.90 (0.79-1.01), and 0.88 (0.78-0.99), respectively, for females who consumed spicy food less than once weekly, 1-2 times weekly, and ≥ 3 times weekly (P = 0.04). The corresponding odds ratios for males were 1.02 (0.95-1.09), 1.07 (0.95-1.20), and 0.91 (0.81-1.01), respectively (P = 0.39). Among current alcohol drinkers, compared to participants who never consumed spicy food, the odds ratio (95% CI) for hypertension among participants consuming spicy food daily was 0.98 (0.80-1.20). The corresponding figure for non-current drinkers was 0.72 (0.62-0.84). The association was stronger among non-current alcohol drinkers than among current drinkers (P = 0.02).

Conclusions: Frequency of spicy food consumption is inversely associated with hypertension in females, but not in males.
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http://dx.doi.org/10.1186/s12986-021-00588-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8259443PMC
July 2021

Body-mass index and obesity in urban and rural China: findings from consecutive nationally representative surveys during 2004-18.

Lancet 2021 07;398(10294):53-63

National Center for Chronic and Non-Communicable Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, China; People's Medical Publishing House, Beijing, China. Electronic address:

Background: In China, mean body-mass index (BMI) and obesity in adults have increased steadily since the early 1980s. However, to our knowledge, there has been no reliable assessment of recent trends, nationally, regionally, or in certain population subgroups. To address this evidence gap, we present detailed analyses of relevant data from six consecutive nationally representative health surveys done between 2004 and 2018. We aimed to examine the long-term and recent trends in mean BMI and prevalence of obesity among Chinese adults, with specific emphasis on changes before and after 2010 (when various national non-communicable disease prevention programmes were initiated), assess how these trends might vary by sex, age, urban-rural locality, and socioeconomic status, and estimate the number of people who were obese in 2018 compared with 2004.

Methods: We used data from the China Chronic Disease and Risk Factors Surveillance programme, which was established in 2004 with the aim to provide periodic nationwide data on the prevalence of major chronic diseases and the associated behavioural and metabolic risk factors in the general population. Between 2004 and 2018 six nationally representative surveys were done. 776 571 individuals were invited and 746 020 (96·1%) participated, including 33 051 in 2004, 51 050 in 2007, 98 174 in 2010, 189 115 in 2013, 189 754 in 2015, and 184 876 in 2018. After exclusions, 645 223 participants aged 18-69 years remained for the present analyses. The mean BMI and prevalence of obesity (BMI ≥30 kg/m) were calculated and time trends compared by sex, age, urban-rural locality, geographical region, and socioeconomic status.

Findings: Standardised mean BMI levels rose from 22·7 kg/m (95% CI 22·5-22·9) in 2004 to 24·4 kg/m (24·3-24·6) in 2018 and obesity prevalence from 3·1% (2·5-3·7) to 8·1% (7·6-8·7). Between 2010 and 2018, mean BMI rose by 0·09 kg/m annually (0·06-0·11), which was half of that reported during 2004-10 (0·17 kg/m, 95% CI 0·12-0·22). Similarly, the annual increase in obesity prevalence was somewhat smaller after 2010 than before 2010 (6·0% annual relative increase, 95% CI 4·4-7·6 vs 8·7% annual relative increase, 4·9-12·8; p=0·13). Since 2010, the rise in mean BMI and obesity prevalence has slowed down substantially in urban men and women, and moderately in rural men, but continued steadily in rural women. By 2018, mean BMI was higher in rural than urban women (24·3 kg/mvs 23·9 kg/m; p=0·0045), but remained lower in rural than urban men (24·5 kg/mvs 25·1 kg/m; p=0·0007). Across all six surveys, mean BMI was persistently lower in women with higher levels of education compared with women with lower levels of education, but the inverse was true among men. Overall, an estimated 85 million adults (95% CI 70 million-100 million; 48 million men [95% CI 39 million-57 million] and 37 million women [31 million-43 million]) aged 18-69 years in China were obese in 2018, which was three times as many as in 2004.

Interpretation: In China, the rise in mean BMI among the adult population appears to have slowed down over the past decade. However, we found divergent trends by sex, geographical area, and socioeconomic status, highlighting the need for a more targeted approach to prevent further increases in obesity in the Chinese general population.

Funding: China National Key Research and Development Program, China National Key Project of Public Health Program, and Youth Scientific Research Foundation of the National Center for Chronic and Noncommunicable Disease Control and Prevention, Chinese Center for Disease Control and Prevention.
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http://dx.doi.org/10.1016/S0140-6736(21)00798-4DOI Listing
July 2021

Associations of toothbrushing behaviour with risks of vascular and nonvascular diseases in Chinese adults.

Eur J Clin Invest 2021 Jun 21:e13634. Epub 2021 Jun 21.

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

Accumulating evidence has shown that poor oral hygiene is associated with increased risk of cardiometabolic diseases in Western populations. However, its relevance about the relationships in Chinese adults remains unclear. The China Kadoorie Biobank enrolled 512 715 adults aged 30-79 years in China during 2004-2008. Cox regression was used to estimate adjusted hazard ratios (HRs) for each disease associated with measures of oral hygiene. Overall 9.3% of the participants reported rarely or never brushing teeth at baseline. Participants who rarely or never brushed teeth had adjusted HR of 1.12 (95% CI: 1.09, 1.15) for MVE, with similar HRs for stroke (1.08, 1.05-1.12), intracerebral haemorrhage (1.18, 1.11-1.26) and pulmonary heart disease (1.22, 1.13-1.32) compared with those who brushed teeth regularly. Those who did not brush teeth also had increased risk of cancer (1.09, 1.04-1.14), chronic obstructive pulmonary disease (COPD) (1.12, 1.05-1.20), liver cirrhosis (1.25, 1.09-1.44) and all-cause death (1.25, 1.21-1.28) but not type 2 diabetes (0.94, 0.86-1.03) and chronic kidney disease (0.98, 0.81-1.18). Among Chinese adults, we found that poor oral hygiene is associated with higher risks of major vascular disease, cancer, COPD, liver cirrhosis and all-cause deaths, but not type 2 diabetes and chronic kidney disease.
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http://dx.doi.org/10.1111/eci.13634DOI Listing
June 2021

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 07 27;31(8):2328-2337. 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
July 2021

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

Breast Cancer Res 2021 05 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

Gender differences in use of invasive diagnostic and therapeutic procedures for acute ischaemic heart disease in Chinese adults.

Heart 2021 May 27. Epub 2021 May 27.

Health Economics Research Centre, Nuffield Department of Population Health, University of Oxford, Oxford, UK

Objective: To investigate gender differences in the use of diagnostic and therapeutic procedures for acute ischaemic heart disease (IHD) in Chinese adults and assess whether socioeconomic or health system factors contribute to such differences.

Methods: In 2004-2008, the China Kadoorie Biobank recruited 512 726 adults from 10 diverse areas in China. Data for 38 928 first hospitalisations with IHD (2911 acute myocardial infarction (AMI), 9817 angina and 26 200 other IHD) were obtained by electronic linkage to health insurance records until 31 December 2016. Multivariate Poisson regression models were used to estimate women-to-men rate ratios (RRs) of having cardiac enzyme tests, coronary angiography and coronary revascularisation.

Results: Among the 38 928 individuals (61% women) with IHD admissions, women were less likely to have AMI (5% vs 12%), but more likely to have angina (26% vs 24%) or other IHD (69% vs 64%). For admissions with AMI, there were no differences in the use of cardiac enzymes between women and men (RR=1.00; 95% CI, 0.97 to 1.03), but women had lower use of coronary angiography (0.80, 0.68 to 0.93) and coronary revascularisation (0.85, 0.74 to 0.99). For angina, the corresponding RRs were: 0.97 (0.94 to 1.00), 0.66 (0.59 to 0.74) and 0.56 (0.47 to 0.67), respectively; while for other IHD, they were 0.97 (0.94 to 1.00), 0.87 (0.76 to 0.99) and 0.61 (0.51 to 0.73), respectively. Adjusting for socioeconomic and health system factors did not significantly alter the women-to-men RRs.

Conclusions: Among Chinese adults hospitalised with acute IHD, women were less likely than men to have coronary angiography and revascularisation, but socioeconomic and health system factors did not contribute to these differences.
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http://dx.doi.org/10.1136/heartjnl-2021-318988DOI Listing
May 2021

Estimating ambient air pollutant levels in Suzhou through the SPDE approach with R-INLA.

Int J Hyg Environ Health 2021 06 24;235:113766. Epub 2021 May 24.

Clinical Trial Service Unit and Epidemiological Studies Unit, Nuffield Department of Population Health, University of Oxford, Oxford, United Kingdom; MRC Population Health Research Unit, University of Oxford, Oxford, United Kingdom.

Spatio-temporal models of ambient air pollution can be used to predict pollutant levels across a geographical region. These predictions may then be used as estimates of exposure for individuals in analyses of the health effects of air pollution. Integrated nested Laplace approximations is a method for Bayesian inference, and a fast alternative to Markov chain Monte Carlo methods. It also facilitates the SPDE approach to spatial modelling, which has been used for modelling of air pollutant levels, and is available in the R-INLA package for the R statistics software. Covariates such as meteorological variables may be useful predictors in such models, but covariate misalignment must be dealt with. This paper describes a flexible method used to estimate pollutant levels for six pollutants in Suzhou, a city in China with dispersed air pollutant monitors and weather stations. A two-stage approach is used to address misalignment of weather covariate data.
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http://dx.doi.org/10.1016/j.ijheh.2021.113766DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8223501PMC
June 2021

High levels of truncated RHAMM cooperate with dysfunctional p53 to accelerate the progression of pancreatic cancer.

Cancer Lett 2021 Aug 24;514:79-89. Epub 2021 May 24.

Department of Pathology and Laboratory Medicine, Weill Cornell Medicine, New York, NY, 10065, USA. Electronic address:

Pancreatic cancer has the lowest survival rate out of all types of cancer. Pancreatic cancer patients are often diagnosed at advanced stages, hence an urgent need for a better therapeutic development of this devastating disease. Receptor for hyaluronan-mediated motility (RHAMM), not expressed in adult normal pancreas, has been suggested as a prognostic factor and a potential therapeutic target for pancreatic ductal adenocarcinoma (PDAC) and pancreatic neuroendocrine tumor (PNET). In this study, we initially sought to determine whether genetic deletion of RHAMM would slow down pancreatic cancer progression using Rhamm mice. However, we found that Rhamm mice expressed a truncated HMMR protein at higher abundance levels than wild-type RHAMM. While HMMR did not enable malignant progression of pancreatic intraepithelial neoplasia in p48-Cre; LSL-KRAS mice, it accelerated the formation of invasive PDAC and shortened the survival of p48-Cre; LSL-KRAS mice with heterozygous p53 knockout. Kras PDAC mice with homozygous p53 knockout mice died around 10 weeks, and the effect of HMMR was not apparent in these short lifespan mice. In addition, HMMR shortened the survival of PNET-bearing RIP-Tag mice, which had inactivated p53. In our analysis of TCGA dataset, pancreatic cancer patients with mutant TP53 or loss of one copy of TP53 had higher RHAMM expression, which, combined, predicted worse outcomes. Taken together, by collaborating with dysfunctional p53, high levels of HMMR , which lacks the centrosome targeting domain and degrons for interaction with the Anaphase-Promoting Complex (APC), accelerated pancreatic cancer progression.
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http://dx.doi.org/10.1016/j.canlet.2021.05.011DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8235875PMC
August 2021

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

Chest 2021 Sep 21;160(3):1053-1063. 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
September 2021

Snoring frequency and risk of type 2 diabetes mellitus: a prospective cohort study.

BMJ Open 2021 05 13;11(5):e042469. Epub 2021 May 13.

Suzhou Center for Disease Control and Prevention, Suzhou, China

Objective: To evaluate the association between snoring frequency and type 2 diabetes mellitus (T2DM) according to age and gender in Chinese population.

Design: A cohort study was performed in Suzhou site of the China Kadoorie Biobank. Residents who didn't suffer from T2DM at baseline survey (2004-2008) and in half a year after baseline were enrolled in this study and followed cause-specific morbidity until 31 December 2013. All participants were requested to complete a detailed questionnaire and undergo anthropometric measurements. Cox regression models were used to estimate HRs and 95% CIs for the snoring and T2DM association.

Setting: Wuzhong district, Suzhou, China.

Participants: A total of 49 453 participants (men: 41.8%; mean age: 51.14±10.28 years) were enrolled in this study.

Outcome Measures: T2DM cases were defined as International Classification of Diseases 10th Revision code of E11 and were identified through disease registries and health insurance databases.

Results: During a media of 7.18 years follow-up, 1120 T2DM cases were identified. Higher T2DM incidence was observed in participants with frequent and occasional snoring compared with those without (4.80 and 2.87 vs 2.39 per 1000 person-years). The multivariable-adjusted model found snoring was independently associated with T2DM (HR 1.28, 95% CI 1.20 to 1.38), both in men (HR 1.25, 95% CI 1.10 to 1.41) and women (HR 1.28, 95% CI 1.17 to 1.39). Moreover, a significant multiplicative interaction effect between snoring and age was detected on T2DM risk (p=0.015).

Conclusions: Snoring was independently associated with an increased risk of T2DM in Chinese population, both in men and women. Meanwhile, there was an interaction effect between snoring and age on T2DM risk.
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http://dx.doi.org/10.1136/bmjopen-2020-042469DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8126309PMC
May 2021

Stroke risk prediction using machine learning: a prospective cohort study of 0.5 million Chinese adults.

J Am Med Inform Assoc 2021 07;28(8):1719-1727

Department of Engineering Science, University of Oxford, Oxford, UK.

Objective: To compare Cox models, machine learning (ML), and ensemble models combining both approaches, for prediction of stroke risk in a prospective study of Chinese adults.

Materials And Methods: We evaluated models for stroke risk at varying intervals of follow-up (<9 years, 0-3 years, 3-6 years, 6-9 years) in 503 842 adults without prior history of stroke recruited from 10 areas in China in 2004-2008. Inputs included sociodemographic factors, diet, medical history, physical activity, and physical measurements. We compared discrimination and calibration of Cox regression, logistic regression, support vector machines, random survival forests, gradient boosted trees (GBT), and multilayer perceptrons, benchmarking performance against the 2017 Framingham Stroke Risk Profile. We then developed an ensemble approach to identify individuals at high risk of stroke (>10% predicted 9-yr stroke risk) by selectively applying either a GBT or Cox model based on individual-level characteristics.

Results: For 9-yr stroke risk prediction, GBT provided the best discrimination (AUROC: 0.833 in men, 0.836 in women) and calibration, with consistent results in each interval of follow-up. The ensemble approach yielded incrementally higher accuracy (men: 76%, women: 80%), specificity (men: 76%, women: 81%), and positive predictive value (men: 26%, women: 24%) compared to any of the single-model approaches.

Discussion And Conclusion: Among several approaches, an ensemble model combining both GBT and Cox models achieved the best performance for identifying individuals at high risk of stroke in a contemporary study of Chinese adults. The results highlight the potential value of expanding the use of ML in clinical practice.
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http://dx.doi.org/10.1093/jamia/ocab068DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8324240PMC
July 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 08;114(2):496-504

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
August 2021

Heterogeneity of Associations between Total and Types of Fish Intake and the Incidence of Type 2 Diabetes: Federated Meta-Analysis of 28 Prospective Studies Including 956,122 Participants.

Nutrients 2021 Apr 7;13(4). Epub 2021 Apr 7.

Postgraduate Program in Epidemiology Faculdade de Medicina, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre 90040-060, Brazil.

The association between fish consumption and new-onset type 2 diabetes is inconsistent and differs according to geographical location. We examined the association between the total and types of fish consumption and type 2 diabetes using individual participant data from 28 prospective cohort studies from the Americas (6), Europe (15), the Western Pacific (6), and the Eastern Mediterranean (1) comprising 956,122 participants and 48,084 cases of incident type 2 diabetes. Incidence rate ratios (IRRs) for associations of total fish, shellfish, fatty, lean, fried, freshwater, and saltwater fish intake and type 2 diabetes were derived for each study, adjusting for a consistent set of confounders and combined across studies using random-effects meta-analysis. We stratified all analyses by sex due to observed interaction ( = 0.002) on the association between fish and type 2 diabetes. In women, for each 100 g/week higher intake the IRRs (95% CIs) of type 2 diabetes were 1.02 (1.01-1.03, = 61%) for total fish, 1.04 (1.01-1.07, = 46%) for fatty fish, and 1.02 (1.00-1.04, = 33%) for lean fish. In men, all associations were null. In women, we observed variation by geographical location: IRRs for total fish were 1.03 (1.02-1.04, = 0%) in the Americas and null in other regions. In conclusion, we found evidence of a neutral association between total fish intake and type 2 diabetes in men, but there was a modest positive association among women with heterogeneity across studies, which was partly explained by geographical location and types of fish intake. Future research should investigate the role of cooking methods, accompanying foods and environmental pollutants, but meanwhile, existing dietary regional, national, or international guidelines should continue to guide fish consumption within overall healthy dietary patterns.
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http://dx.doi.org/10.3390/nu13041223DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8068031PMC
April 2021

SSCA-Net: Simultaneous Self- and Channel-Attention Neural Network for Multiscale Structure-Preserving Vessel Segmentation.

Biomed Res Int 2021 30;2021:6622253. Epub 2021 Mar 30.

College of Internet of Things Engineering, Hohai University Changzhou, China.

Vessel segmentation is a fundamental, yet not well-solved problem in medical image analysis, due to the complicated geometrical and topological structures of human vessels. Unlike existing rule- and conventional learning-based techniques, which hardly capture the location of tiny vessel structures and perceive their global spatial structures, we propose (termed SSCA-Net) to solve the (MSVS) problem. SSCA-Net differs from the conventional neural networks in modeling image global contexts, showing more power to understand the global semantic information by both (SCA) mechanism and offering high performance on segmenting vessels with multiscale structures (e.g., DSC: 96.21% and MIoU: 92.70% on the intracranial vessel dataset). Specifically, the SCA module is designed and embedded in the feature decoding stage to learn SCA features at different layers, in which the self-attention is used to obtain the position information of the feature itself, and the channel attention is designed to guide the shallow features to obtain global feature information. To evaluate the effectiveness of our SSCA-Net, we compare it with several state-of-the-art methods on three well-known vessel segmentation benchmark datasets. Qualitative and quantitative results demonstrate clear improvements of our method over the state-of-the-art in terms of preserving vessel details and global spatial structures.
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http://dx.doi.org/10.1155/2021/6622253DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8026298PMC
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
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