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Background and aims Obesity often initiates or coexists with certain metabolic abnormalities. This study sought to examine the independent and joint relations of weight and metabolic syndrome (MetS) with incident chronic kidney disease (CKD) among Chinese elderly people. Methods and Results A total of 15 229 participants (mean age: 62.8 years) from the Dongfeng-Tongji Cohort with complete baseline questionnaire and medical examination data were followed from 2008-2010 to 2013. All participants were categorized into four phenotypes: metabolically healthy non-overweight/obesity (MHNO), metabolically healthy overweight/obesity (MHO), metabolically unhealthy non-overweight/obesity (MUNO), metabolically unhealthy overweight/obesity (MUO). Multivariable-adjusted logistic regression models were applied to estimate the odds ratios (ORs) and confidence intervals (CIs) of four phenotypes with the risk of incident CKD, which was defined as estimated glomerular filtration rate (eGFR) 60 years or with baseline diabetes. Conclusion Both overweight/obesity and MetS were associated with an increased risk of CKD. It's worth noting that MHO and MUNO also have an elevated risk. Maintaining both normal weight and healthy metabolic profile is recommended.

ObjectiveTo investigate the associations of sleep duration, midday napping, sleep quality, and change in sleep duration with risk of incident stroke and stroke subtypes.MethodsAmong 31,750 participants aged 61.7 years on average at baseline from the Dongfeng-Tongji cohort, we used Cox regression models to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for incident stroke.ResultsCompared with sleeping 7 to 90 minutes vs 1–30 minutes. The results were similar for ischemic stroke. Compared with good sleep quality, those with poor sleep quality showed a 29%, 28%, and 56% higher risk of total, ischemic, and hemorrhagic stroke, respectively. Moreover, we observed significant joint effects of sleeping ≥9 hours/night and midday napping >90 minutes (HR 1.85; 95% CI 1.28–2.66), and sleeping ≥9 hours/night and poor sleep quality (HR 1.82; 95% CI 1.33–2.48) on risk of total stroke. Furthermore, compared with persistently sleeping 7–9 hours/night, those who persistently slept ≥9 hours/night or switched from 7 to 9 hours to ≥9 hours/night had a higher risk of total stroke.ConclusionsLong sleep duration, long midday napping, and poor sleep quality were independently and jointly associated with higher risks of incident stroke. Persistently long sleep duration or switch from average to long sleep duration increased the risk of stroke.

Cytokines play a critical role in the pathogenesis and development of cardiovascular diseases. However, data linking cytokines to risk and severity of acute coronary syndrome (ACS) are still limited. We measured plasma profile of 280 cytokines using a quantitative protein microarray in 12 ACS patients and 16 healthy controls, and identified 15 differentially expressed cytokines for ACS. Osteopontin, chemokine ligand 23, brain derived neurotrophic factor and C-reactive protein (CRP) were further validated using immunoassay in two independent case-control studies with a total of 210 ACS patients and 210 controls. We further examined their relations with incident ACS among 318 case-control pairs nested within the Dongfeng-Tongji cohort, and found plasma osteopontin and CRP concentrations were associated with incident ACS, and the multivariable-adjusted odds ratio (95% confidence interval) was 1.29 (1.06–1.57) per 1-SD increase for osteopontin and 1.30 (1.02–1.66) for CRP, respectively. Higher levels of circulating osteopontin were also correlated with higher severity of ACS, and earlier ACS onset time. Adding osteopontin alone or in combination with CRP modestly improved the predictive ability of ACS beyond the Framingham risk scores. Our findings suggested that osteopontin might be a biomarker for incident ACS, using osteopontin adds moderately to traditional cardiovascular risk factors.

Introduction and aim It is indicated that high levels of serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) are associated with increased incident type 2 diabetes risk. However, whether serum ALT levels could improve the discrimination of type 2 diabetes remains unclear. Methods The data was derived from the Dongfeng-Tongji cohort study, which was established in 2008 and followed until October 2013. A total of 17,173 participants free of type 2 diabetes at baseline were included and 1159 participants developed diabetes after 4.51 (0.61) years of follow-up. Cox proportional hazard regression model was used to calculate the hazard ratios (HRs) for the association between ALT and AST levels with incident diabetes risk. Receiver-operating characteristic (ROC) curves analysis was used to evaluate the predictive accuracy of models incorporating traditional risk factors with and without ALT. Results Compared with the lowest quartile of ALT and AST levels, the highest quartile had a significantly higher risk of developing type 2 diabetes (HR: 2.17 [95% CI: 1.78–2.65] and 1.29 [1.08–1.54], respectively) after adjustment for potential confounders. The addition of ALT levels into the traditional risk factors did not improve the predictive ability of type 2 diabetes, with AUC increase from 0.772 to 0.774; P = 0.86. Conclusions Although elevated ALT or AST levels increased incident type 2diabetes risk, addition of ALT levels into the prediction model did not improve the discrimination of type 2 diabetes.

Metal exposures are ubiquitous around the world, while it is lack of prospective studies to evaluate the associations of exposure to multiple metal/metalloids with incident dyslipidemia. A total of 2947 participants without dyslipidemia at baseline were included in the analyses. We utilized inductively coupled plasma mass spectrometry to measure the baseline plasma metal concentrations. Unconditional logistic regression models were applied to estimate the relations between plasma metals and risk of incident dyslipidemia, and principal component analysis was performed to extract principal components of metals. During 5.01 ± 0.31 years of follow-up, 521 subjects were diagnosed with incident dyslipidemia. After multivariable adjustment, the odds ratios (ORs) of dyslipidemia comparing the highest quartiles to the lowest were 1.58 (95% CI: 1.20, 2.08; P trend = 0.001) for aluminum, 1.34 (95% CI: 1.03, 1.75; P trend = 0.03) for arsenic, 1.44 (1.09, 1.91; P trend = 0.03) for strontium, and 1.47 (95% CI: 1.09, 2.00; P trend = 0.005) for vanadium. The four metals also showed significant associations with the subtypes of dyslipidemia, including low HDL-C and high LDL-C. The first principal component, which mainly represented aluminum, arsenic, barium, lead, vanadium, and zinc, was associated with increased risk of incident dyslipidemia, and the adjusted OR was 1.40 (95% CI: 1.07, 1.84; P trend = 0.02) comparing extreme quartiles. The study indicated that elevated plasma aluminum, arsenic, strontium, and vanadium concentrations were associated with a higher incidence of dyslipidemia. These findings highlight the importance of controlling metal exposures for dyslipidemia prevention.

Background: Exposure to metals/metalloids from both the natural environment and anthropogenic sources have a complex influence on human health. However, relatively few studies have explored the relations of exposure to multiple metals/metalloids with mortality. Therefore, this prospective study aims to examine the relations of multiple metal/metalloids exposures with all-cause and cardiovascular disease (CVD) mortality. Methods: A total of 6155 participants within the Dongfeng-Tongji (DF-TJ) cohort were involved in this analysis, which were followed for mortality until December 31, 2018. We applied inductively coupled plasma mass spectrometry (ICP-MS) to measure baseline plasma concentrations of 23 metals. We utilized Cox regression models to calculate the hazard ratios (HRs) for all-cause and CVD mortality associated with metal concentrations. We proposed plasma metal score to assess the simultaneous exposure to multiple metals through summing each metal concentration weighted by the regression coefficients with all-cause mortality. Results: During the follow-up (mean duration, 9.8 years), we ascertained 876 deaths, including 416 deaths of CVD (157 deaths of coronary heart disease and 259 deaths of stroke). In the multiple-metals model, after adjusting for potential confounders, plasma copper, molybdenum, and vanadium were positively associated with all-cause mortality, whereas manganese, selenium, and thallium were negatively associated with the risk of all-cause mortality, with adjusted HRs (95% Confidence Interval, CI) of the fourth quartiles were 1.73 (1.42–2.11, P-trend

The long-term associations between multiple metals and incident diabetes are uncertain. We aimed to examine the relationship between plasma concentrations of 23 metals and the incidence of type 2 diabetes among Chinese senior adults. We quantified fasting plasma concentrations of 23 metals by inductively coupled plasma mass spectrometry among 1039 incident diabetes cases and 1039 controls (age and sex matched) nested in a prospective study, the Dongfeng-Tongji cohort. Both cases and controls were free of diabetes at baseline (2008–2010), incident diabetes were identified using the following criteria: fasting glucose ≥ 7.0 mmoL/l; or hemoglobin A1c (HbA1c) ≥ 6.5%; or self-reported physician diagnosis of diabetes or use of anti-diabetic medication during the follow-up visits in 2013. In the conditional logistic regression models, the multivariable adjusted ORs (95% CIs) of diabetes across quartiles (Q1–Q4) of metal concentrations were as follows: titanium, 1.00, 0.92, 1.31, 1.38 (1.00–1.91, Ptrend = 0.011); selenium, 1.00, 1.08, 1.45, 1.27 (0.93–1.74, Ptrend = 0.05); and antimony, 1.00, 0.79, 0.77, 0.60 (0.44–0.83, Ptrend = 0.002). Arsenic was significantly associated with diabetes in the crude model (ORs comparing extreme quartiles 1.30; 1.02–1.65; Ptrend = 0.006), but was not significant after adjustment for socio-demographic factors. No significant associations were found for other metals. In conclusion, titanium and selenium were positively while antimony was negatively associated with incident diabetes.

Background: Total bilirubin (TBIL) is known to be inversely associated with coronary heart disease (CHD) risk, however, whether this association is dose-response remains inconsistent and it is unclear which subtype of bilirubin is responsible for the potential protective effect. Methods: We included 12,097 participants who were free of CHD, stroke, cancer and potential liver, biliary and renal diseases at baseline from September 2008 to June 2010 and were followed-up until October 2013. Cox proportional hazards models were used to assess the hazard ratios (HR) and 95% confidence interval (95% CI) of bilirubin with incident CHD risk. Results: The adjusted HRs for incident CHD increased with increasing direct bilirubin (DBIL) (p for trend = .013). Participants within the highest quintile of DBIL had 30% higher risk of incident CHD compared to those in the lowest quintile (95% CI: 1.07, 1.58). In contrast, compared with subjects in the lowest quintile of TBIL, those in the third quintile had the lowest of 24% risk for CHD incidence (95% CI: 0.63, 0.92), which showed a U-shaped association (p for quadratic trend = .040). Conclusions: DBIL was associated with a dose-response increased risk for CHD incidence. However, a U-shaped association existed between TBIL, indirect bilirubin and incident CHD risk.Key messagesDirect bilirubin is independently associated with incident coronary heart disease (CHD) in a dose-response manner.A similarly consistent U-shaped association was found between total bilirubin, indirect bilirubin and incident CHD.The potential protective effect of total bilirubin within the normal range on incident CHD should be mainly attributed to mild-to moderate elevated levels of indirect bilirubin. Direct bilirubin is independently associated with incident coronary heart disease (CHD) in a dose-response manner. A similarly consistent U-shaped association was found between total bilirubin, indirect bilirubin and incident CHD. The potential protective effect of total bilirubin within the normal range on incident CHD should be mainly attributed to mild-to moderate elevated levels of indirect bilirubin.

The aim of this study was to develop a new risk score system to predict 5-year incident diabetes risk among middle-aged and older Chinese population. This prospective study included 17,690 individuals derived from the Dongfeng–Tongji cohort. Participants were recruited in 2008 and were followed until October 2013. Incident diabetes was defined as self-reported clinician diagnosed diabetes, fasting glucose ≥7.0 mmol/l, or the use of insulin or oral hypoglycemic agent. A total of 1390 incident diabetic cases were diagnosed during the follow-up period. β-Coefficients were derived from Cox proportional hazard regression model and were used to calculate the risk score. The diabetes risk score includes BMI, fasting glucose, hypertension, hyperlipidemia, current smoking status, and family history of diabetes. The β-coefficients of these variables ranged from 0.139 to 1.914, and the optimal cutoff value was 1.5. The diabetes risk score was calculated by multiplying the β-coefficients of the significant variables by 10 and rounding to the nearest integer. The score ranges from 0 to 36. The area under the receiver operating curve of the score was 0.751. At the optimal cutoff value of 15, the sensitivity and specificity were 65.6 and 72.9%, respectively. Based upon these risk factors, this model had the highest discrimination compared with several commonly used diabetes prediction models. The newly established diabetes risk score with six parameters appears to be a reliable screening tool to predict 5-year risk of incident diabetes in a middle-aged and older Chinese population.

Educational achievement was related to cardiovascular disease in some western populations, but prospective evidence on the relationship between education and the risk of incident coronary heart disease (CHD) in Asians is scarce. We aimed to explore this association and the potential modifying effect of major CHD risk factors related to education in middle-aged and older Chinese adults. We included 18,551 participants with mean age 62.8 years at baseline between September 2008 and June 2010, and followed the population until October 2013. Cox proportional hazard models and log-binomial regression models were used for multivariate analyses. Compared with participants with low education, the adjusted hazard ratio (HR) and 95% confidence interval (95% CI) for incident CHD in those with high education was 0.89 (95% CI: 0.80, 0.98). In addition, such inverse association between education and the risk of incident CHD was more evident among individuals who were more than 60 years, physically active, overweight, and hypertension. Besides, decreases in the relative index of inequality with high education versus low education were from 0.83 to 0.76 for hypertension, from 0.85 to 0.82 for diabetes. In conclusion, education was inversely associated with the risk of incident CHD among middle-aged and older Chinese adults.

Background C-reactive protein (CRP) is a well-recognized biomarker of inflammation, which can be used as a predictor of cardiovascular disease. Evidence have suggested exposure to multiple metals/metalloids may affect immune system and give rise to cardiovascular disease. However, it is lack of study to comprehensively evaluate the association of multiple metals and CRP, the interactions between metals, and the gene-metal interaction in relation to CRP levels. Aims To explore the associations of multiple plasma metals with serum CRP, and to test the interactions between metals, and gene-metal interactions on the levels of serum CRP. Methods We included 2882 participants from the Dongfeng-Tongji cohort, China, and measured 23 plasma metals and serum CRP concentrations. The genetic risk score (GRS) was calculated based on 7 established CRP-associated variants. For metals which were associated with the levels of CRP, we further tested the interactions between metals on CRP, and analyzed the gene-metal interactions on CRP. Results The median level for CRP in the total population was 1.17 mg/L. After multivariable adjustment, plasma copper was positively associated with serum CRP (FDR, Highlights • We found that serum CRP was positively associated with plasma copper, and inversely associated with selenium. • The positive association of plasma copper with serum CRP appeared to be attenuated with high plasma zinc and selenium. • This is the first study that explored the potential gene-metal interactions in relation to CRP levels. • These novel findings may provide new insights to personalized prevention and interventions for inflammation.

Lung cancer is the leading cause of cancer-related death in the world. Several genome-wide association studies (GWAS) have identified TERT-CLPTM1L as plausible causative locus for lung cancer development. This study aimed to investigate the associations of genetic variations in TERT-CLPTM1L and the expression level of TERT with the survival of early stage non-small cell lung cancer (NSCLC) patients. We selected three single-nucleotide polymorphisms of TERT-CLPTM1L (rs2853669, rs2736108 and rs31490) and genotyped in 140 early stage NSCLC patients by TaqMan assay. Associations between these variations and survival outcome of early stage NSCLC patients were further investigated. We also used TCGA data to evaluate the associations of TERT messenger RNA (mRNA) expression and survival outcome of early stage NSCLC patients. Survival analysis showed that, compared with early NSCLC patients carrying TERT rs2853669 TT+TC genotypes, patients with rs2853669 CC genotype had significantly longer median survival time (MST=102.2 vs 52.4 months; log-rank P=0.028) and lower death risk [hazard ratio (HR) with 95% confidence interval (CI))=0.38(0.17-0.82), P=0.014]. Early NSCLC patients carrying TERT rs2736108 AA genotype had significantly shorter MST (MST=29.0 vs 63.3 months; log-rank P=0.020) and increased death risk [HR (95% CI)=2.22(1.01-5.80), P=0.046], when compared with patients carrying rs2736108 GG genotypes. TCGA data revealed that early NSCLC patients with higher expression level of TERT mRNA in lung tumor tissues had a longer MST and decreased death risk than those with low expression level of TERT mRNA [MST=54.4 vs 49.0 months; log-rank P=0.041; adjusted HR (95% CI)=0.68(0.50-0.94)]. These findings may add potential evidence to understand the prognostic value of TERT and provide a new prospect of individualized prevention and treatment for early stage NSCLC.

Elevated serum bilirubin levels are associated with decreased coronary heart disease (CHD) risk in cross-sectional studies among diabetic patients, but prospective evidence is limited. We investigated the relationship of serum bilirubin levels with incident CHD risk among type 2 diabetes patients. In a prospective study of 2918 type 2 diabetes embedded in the Dongfeng–Tongji cohort, serum total bilirubin (TBil), direct bilirubin (DBil), and indirect bilirubin (IBil) were measured at baseline. Cox proportional hazards models were used to examine the association between serum bilirubin levels and CHD risk. A total of 440 CHD cases were identified during 12,017 person-years of follow-up. Compared with extreme quartiles, the adjusted hazard ratio and 95% confidence interval of incident CHD were 0.74 (0.56–0.99) with P trend = 0.08 in IBil, while in TBil and DBil, the bilirubin–CHD associations were not significant. Moreover, serum TBil and IBil levels were interacted with drinking status on the risk of incident CHD (P interaction = 0.021 and 0.037, respectively), and the associations were evident in ever drinkers. In drinkers, when serum TBil or IBil concentrations increased 1 μmol/L, the CHD risk both decreased 6% (95% CIs 0.89–0.99 and 0.87–1.00, respectively). Serum IBil levels were marginally related to decreased incident CHD risk among type 2 diabetes. Drinking could potentially enhance the associations of serum TBil and DBil levels with incident CHD risk.

Background In prospective studies, relationship of serum uric acid (SUA) with risk of coronary heart disease (CHD) incidence is inconsistent. We evaluated the association of SUA with incident CHD and the potential modifying effect of major CHD risk factors related to SUA among a middle aged and elderly Chinese population. Methods We included 16, 063 participants who were free of CHD, stroke, cancer and renal diseases at baseline from Sep. 2008 to June 2010, and were followed until Oct. 2013. Cox proportional hazard model was used to estimate the hazard ratios (HR) and 95% confidence interval (95% CI) of CHD incidence in relation to SUA. Results The adjusted HR for incident CHD increased gradually with the increasing SUA levels ( P for linear trend=0.005), and the HR across sex-specific SUA quartile was 1.26 (95% CI: 1.09, 1.47), 1.13 (95% CI: 0.97, 1.31), 1.23 (95% CI: 1.06, 1.43) and 1.00 (reference; P for trend=0.014), respectively. In particular, the association was more evident in individuals with normal-weight and those without hypertension or metabolic syndrome (all P for interactions Conclusions These findings suggested that higher SUA levels were independently associated with a dose-response increased risk of CHD incidence.

Background Evidence shows that exposure to poor conditions in early life is associated with an increased risk of chronic diseases in adults. Objective We investigated whether exposure to the Chinese famine (1959-1961) in the fetal stage or in childhood (0-9 y) was associated with type 2 diabetes (T2D) and hyperglycemia in adulthood. Methods We included 7801 subjects aged 56.4 ± 3.3 y from the Dongfeng-Tongji cohort. Subjects were classified into late-, middle-, and early-childhood-exposed, fetal-exposed, and unexposed groups. Excess mortality rate was used to evaluate the severity of famine. Logistic regression models were used to analyze the famine-dysglycemia associations. Generalized linear models were used to assess the famine effects on dysglycemia risk during the 5-y follow-up period among 3100 subjects. Results In descriptive analyses, the risk of T2D was significantly greater in the middle-childhood-exposed group (OR: 1.44; 95% CI: 1.10, 1.87; P = 0.007), and the risk of hyperglycemia was higher in the middle- and late-childhood-exposed groups than in the unexposed group (OR: 1.54; 95% CI: 1.26, 1.88 and OR: 1.51; 95% CI: 1.23, 1.85, respectively). In sex-specific analyses, women exposed in middle childhood (OR: 1.55; 95% CI: 1.16, 2.06) and late childhood (OR: 1.40; 95% CI: 1.05, 1.87) had a higher risk of T2D than unexposed women. This association was not found in men. Similar associations were found for hyperglycemia risk. Moreover, subjects who experienced severe famine in childhood had a 38% higher T2D risk (95% CI: 1.05, 1.81) than those exposed to less severe famine. In retrospective cohort analyses, participants who experienced famine in middle childhood had a higher hyperglycemia risk relative to the unexposed group (RR: 2.06; 95% CI: 1.08, 3.90). Conclusion Exposure to the Chinese famine in childhood was related to an increased risk of adulthood T2D and hyperglycemia, particularly in women.

Background Metabolomics studies in Caucasians have identified a number of novel metabolites in association with the risk of type 2 diabetes (T2D). However, few prospective metabolomic studies are available in Chinese populations. In the present study, we sought to identify novel metabolites consistently associated with incident T2D in two independent cohorts of Chinese adults. Methods We performed targeted metabolomics (52 metabolites) of fasting plasma samples by liquid chromatography-mass spectrometry in two prospective case-control studies nested within the Dongfeng-Tongji (DFTJ) cohort and Jiangsu Non-communicable Disease (JSNCD) cohort. After following for 4.61 ± 0.15 and 7.57 ± 1.13 years, respectively, 1039 and 520 eligible participants developed incident T2D in these two cohorts, and controls were 1:1 matched with cases by age (± 5 years) and sex. Multivariate conditional logistic regression models were constructed to identify metabolites associated with future T2D risk in both cohorts. Results We identified four metabolites consistently associated with an increased risk of developing T2D in the two cohorts, including alanine, phenylalanine, tyrosine and palmitoylcarnitine. In the meta-analysis of two cohorts, the odds ratios (95% confidence intervals, CIs) comparing extreme quartiles were 1.79 (1.32-2.42) for alanine, 1.91 (1.41-2.60) for phenylalanine, 1.85 (1.37-2.48) for tyrosine and 1.63 (1.21-2.20) for palmitoylcarnitine (all Ptrend ≤ 0.01). Conclusions We confirmed the association of alanine, phenylalanine and tyrosine with future T2D risk and further identified palmitoylcarnitine as a novel metabolic marker of incident T2D in two prospective cohorts of Chinese adults. Our findings might provide new aetiological insight into the development of T2D.

In this study, we investigated the independent and combined effects of sleep duration and afternoon napping on the risk of incident diabetes among a cohort of middle-aged and older Chinese adults.Information of sleep and napping was obtained by questionnaires during face-to-face interviews. We categorized sleep duration into 7 h, 7∼8 h (reference), 8∼9 h, 9∼10 h, and ≥ 10 h. Afternoon napping was divided into no napping (0 min) (reference), 1-30 min, 31-60 min, 61-90 min, and 90 min. Cox proportional hazard regression models were used.Compared with referential sleeping group, subjects sleeping ≥10 h had a 42% higher risk of developing diabetes. The HR was 1.28 for napping 90 min when compared with no napping. These associations were more pronounced in individuals without hypertension. Combined effects of long sleep duration and afternoon napping were further identified. Individuals with both sleep duration ≥ 10 h and napping 60 min had a 72% higher risk of incident diabetes than those with sleeping 7∼8 h and napping 0 min (all above p 0.05).Both long sleep duration and afternoon napping were independently and jointly associated with higher risk of incident diabetes. Key messages Sleep duration was associated with diabetes, but whether it is a real cause of incident diabetes especially in Chinese still remains to be elucidated. The association of afternoon napping and diabetes was not consistent and definite, we clarified this association in a large prospective study. Long sleep duration and afternoon napping were independently and jointly associated with higher risk of incident diabetes.

To analyze the independent and combined relations of sleep duration and midday napping with coronary heart diseases (CHD) incidence along with the underlying changes of cardiovascular disease (CVD) risk factors among Chinese adults.We included 19,370 individuals aged 62.8 years at baseline from September 2008 to June 2010, and they were followed until October 2013. Cox proportional hazards models and general linear models were used for multivariate longitudinal analyses.Compared with sleeping 7-8 h/night, the hazard ratio (HR) of CHD incidence was 1.33 (95% CI = 1.10 to 1.62) for sleeping ≥ 10 h/night. The association was particularly evident among individuals who were normal weight and without diabetes. Similarly, the HR of incident CHD was 1.25 (95% CI = 1.05 to 1.49) for midday napping90 min compared with 1-30 min. When sleep duration and midday napping were combined, individuals having sleep duration ≥ 10 h and midday napping90 min were at a greater risk of CHD than those with sleeping 7-8 h and napping 1-30 min: the HR was 1.67 (95% CI = 1.04 to 2.66; P for trend = 0.017). In addition, longer sleep duration ≥ 10 h was significantly associated with increases in triglycerides and waist circumference, and a reduction in HDL-cholesterol; while longer midday napping90 min was related to increased waist circumference.Both longer sleep duration and midday napping were independently and jointly associated with a higher risk of CHD incidence, and altered lipid profile and waist circumference may partially explain the relationships.

Background: The associations of age-related changes in body weight and waist circumferences with cardiovascular disease (CVD) and mortality remain unclear. Methods: We assessed changes in weight and waist circumference from baseline survey and resurvey among 27 964 participants in the China Kadoorie Biobank (CKB, 2004-2008) and Dongfeng-Tongji Cohort (DF-TJ, 2008-2013). We used Cox proportional hazards models to evaluate the associations between adiposity changes and the subsequent risks of incident CVD, CVD mortality and all-cause mortality. Findings: On average, during a median of 3·4 years from baseline to resurvey, participants experienced a weight loss of 0·6 kg, accompanied by a 2·1 cm increase in waist circumference. We identified 3589 incident CVD cases, 485 CVD deaths, and 1283 all-cause deaths during the follow-up in the CKB (2008-2016) and DF-TJ (2013-2016). Weight loss and waist gain were associated with increased risks of those outcomes in the two cohorts. In particular, compared with participants who had stable waist (waist change -2·0 to 7·0 cm) and weight (weight change -2·5 to 2·5 kg), those who gained waist but lost weight (waist circumference change >7·0 cm, weight change ≤ -2·5 kg) had the highest risk of incident CVD, CVD mortality and all-cause mortality, with the pooled multivariate hazard ratios (HRs) of 1·41 (95% CI, 1·13 to 1·75), 2·48 (1·40 to 4·37), and 1·71 (1·16 to 2·51), respectively. Among the weight-stable participants, waist circumference was linearly associated with CVD risk, with 17% higher risk (HR 1·17, 1·04 to 1·32) for those gained waist while 13% lower risk (HR 0·87, 0·77 to 0·99) for those lost waist compared to waist-stable participants. Interpretation: Increased waist circumference with concurrent weight loss is significantly associated with increased risks of CVD morbidity, CVD mortality, and all-cause mortality among Chinese middle-aged and elderly adults. Funding Statement: This work was partly supported by grants from the Foundation of National Key Programs of Research and Development of China (2016YFC0900800, 2016YFC0900500, 2017YFC0907501 and 2017YFC0907504), the National Natural Science Foundation of China (91643202 and 81390540), the 111 Project and the Program for Changjiang Scholars and Innovative Research Team in University. The China Kadoorie Biobank baseline survey and the first resurvey were supported by the Kadoorie Charitable Foundation in Hong Kong. The long-term follow-up has been supported by the UK Wellcome Trust (grants 088158/Z/09/Z, 104085/Z/14/Z), and the Chinese Ministry of Science and Technology (2011BAI09B01). The British Heart Foundation, UK Medical Research Council, and Cancer Research provide core funding to the Clinical Trial Service Unit and Epidemiological Studies Unit at Oxford University for the project. Declaration of Interests: The authors declare no competing interests. Ethics Approval Statement: The CKB study was approved by the ethics committees or institutional review boards at the University of Oxford, the Chinese Center for Disease Control and Prevention (China CDC), the Chinese Academy of Medical Sciences. The DF-TJ cohort was approved by the ethics committees of Tongji Medical College and the Sinopharm Dongfeng General Hospital. All participants provided written informed consents.

Introduction Suboptimal sleep is associated with weight gain and related chronic diseases in adults, adolescents, and older children. However, little is known regarding the associations between sleep and physical growth in infants. We investigated prospectively the associations between objectively-measured sleep patterns at 1 month and physical growth in the first 6 months of life. Methods We studied 344 full term infants in the ongoing longitudinal Rise & SHINE (Sleep Health in Infancy & Early Childhood) birth cohort study. At 1 month, infants underwent 7-day ankle actigraphy, estimating average sleep duration (24-hour, nighttime, and daytime) and sleep fragmentation (number of nighttime awakenings). Weight and length were measured at birth and 6 months and used to calculate weight-for-length z (WFL-z) scores. We used linear and logistic regression analyses to examine the associations between sleep patterns at 1 month with WLF-z at 6 months and rapid weight gain from birth to 6 months, defined as an increase in WFL-z greater than or equal to 0.67, controlling for covariates. Results Each 1-hour increase in 24-hour sleep duration was associated with a 0.07-unit (95% CI [0.01, 0.12]) increase in WFL-z at 6 months. Daytime, but not nighttime, sleep duration was positively associated with WFL-z. Greater number of nighttime awakenings was associated with higher WFL-z (beta = 0.28; 95% CI [0.08, 0.49]). 24-hour and nighttime sleep duration were positively associated with a 18.5% (95% CI [1.04, 1.35]) and a 23.4% (95% CI [1.02, 1.49]) higher odds of rapid weight gain from birth to 6 months, respectively. Conclusion Longer 24-hour sleep duration was associated with higher 6-month WFL-z and more rapid increases in WFL-z from birth to 6 months. Greater nighttime sleep fragmentation was associated with higher 6-month WFL-z. Sleep at 1 month might provide modifiable targets to help avoid lifetime complications of excess weight. Support R01DK107972.

Background Although the association of Helicobacter pylori (H. pylori) infection with diabetes mellitus has been evaluated, findings are controversial. This study investigated the association in a Chinese population. Methods A cross-sectional study, including a total of 30 810 subjects from the Dongfeng-Tongji Cohort study, was conducted. H. pylori status was measured via 14C urea breath test. Association analysis was performed by logistic regression, with multivariable adjustment for sex, age, body mass index, smoking, alcohol consumption, family history of diabetes, physical activity and the use of antibiotics. Results Among a middle-age and old-age Chinese population, individuals with H. pylori infection also had a higher prevalence of type 2 diabetes (21.3% versus 20.2%, p = 0.026). H. pylori infection was associated with higher risk of type 2 diabetes [odds ratio, 1.08 (95% confidence interval: 1.02–1.14); p = 0.008] after adjustment for other confounders. The association was significant among women, those who were above 65 years old, not overweight or obese, and those who did not smoke, did not consume alcohol and without family history of diabetes. However, there was no interaction between H. pylori infection and other traditional risk factors on type 2 diabetes risk. Subjects with H. pylori infection had a lower level of high-density lipoprotein cholesterol (p

Background: Circulating metals from both the natural environment and pollution have been linked to cardiovascular disease. However, few prospective studies have investigated the associations between exposure to multiple metals and incident coronary heart disease (CHD). Objectives: We conducted a nested case–control study in the prospective Dongfeng-Tongji cohort, to investigate the prospective association between plasma metal concentrations and incident CHD. Methods: A total of 1,621 incident CHD cases and 1,621 controls free of major cardiovascular disease at baseline and follow-up visits were matched on age (±5 years) and sex. We measured baseline fasting plasma concentrations of 23 metals and used conditional logistic regression models to estimate odds ratios (ORs) of CHD for metal concentrations categorized according to quartiles in controls. Results: Five metals (titanium, arsenic, selenium, aluminum, and barium) were significantly associated with CHD based on trend tests from single-metal multivariable models adjusted for established cardiovascular risk factors. When all five were included in the same model, adjusted ORs for barium and aluminum were close to the null, whereas associations with titanium, arsenic, and selenium were similar to estimates from single-metal models, and ORs comparing extreme quartiles were 1.32 (95% CI: 1.03, 1.69; p-trend=0.04), 1.78 (95% CI: 1.29, 2.46; p-trend=0.001), and 0.67 (95% CI: 0.52, 0.85; p-trend=0.001), respectively. Conclusions: Our study suggested that incident CHD was positively associated with plasma levels of titanium and arsenic, and inversely associated with selenium. Additional research is needed to confirm these findings in other populations. https://doi.org/10.1289/EHP1521

Background Epidemiologic studies have found that moderate alcohol consumption was associated with a decreased risk of coronary heart disease (CHD) incidence. Nevertheless, whether the drinking pattern is associated with CHD incidence still remains inconclusive. Methods We included 8,469 Chinese men aged 45–81 years, who were free of CHD, stroke, or cancer at baseline from Dongfeng-Tongji cohort. A semi-structured questionnaire was used to collect information on alcohol consumption and other covariates. Cox proportional hazard regression model was applied to estimate the multivariable-adjusted hazard rations (HRs) and 95% confidence intervals (95% CIs). Results During an average of 4.36 years of follow-up, we identified 959 incident CHD events. Compared with non-drinkers, the multivariable-adjusted HR (95% CI) of CHD incidence was 0.84 (0.71–0.98) in current drinkers. With respect to drinking pattern, men who consumed 20.01–40 grams ethanol once a time had a 24% lower risk of incident CHD (HR = 0.76, 95% CI = 0.62, 0.94) compared with non-drinkers. The adjusted HRs (95% CI) of CHD incidence were 0.80 (0.65, 0.99), 1.02 (0.84, 1.22), and 0.75 (0.59–0.96) in subjects who consumed 0.01–10, 10.01–30, and > 30 grams ethanol per day, respectively. Participants who consumed 20.01–40 grams ethanol per time with less than 5 times per week had the lowest risk of CHD incidence (HR = 0.73, 95% CI = 0.52, 0.96). No significant associations were observed between type or frequency of alcohol consumption and CHD incidence. Conclusions Drinking was associated with a lower risk of CHD incidence in middle-aged and older Chinese men and moderate quantity of ethanol amounts once a time with lower frequency could been considered as a healthy drinking pattern, which might modify the relationship between alcohol consumption and incident CHD.

Prospective studies on the association of green tea with risk of coronary heart disease (CHD) incidence were scarce. This study examined whether green tea can reduce CHD incidence and have a beneficial effect on CHD-related risk markers in middle-aged and older Chinese population. We included 19,471 participants who were free of CHD, stroke or cancer at baseline from September 2008 to June 2010, and were followed until October 2013. Cox proportional hazard models were used to examine the hazard ratios (HR) of CHD incidence in relation to green tea consumption. Linear regression models were used to evaluate the effect of green tea on 5-year changes of CHD-related biomarkers. Compared with non-green tea consumers, the multivariable-adjusted HR for CHD was 0.89 (95% CI, 0.81-0.98) in green tea consumers. Particularly, the reduced risk of CHD incidence with green tea consumption was more evident among participants who were male, more than 60 years old, overweight, or with diabetes mellitus. In addition, green tea consumption improved multiple CHD-related risk markers including total cholesterol, HDL-cholesterol, triglycerides, mean platelet volume, and uric acid. In conclusion, green tea consumption was associated with a reduced risk of CHD incidence in the middle-aged and older Chinese populations, and the association might be partly due to altered CHD-related biomarkers.

Metals are widespread pollutants in the environment which have been reported to be associated with kidney dysfunction in many existing epidemiological studies. However, most of the studies are cross-sectional design and mainly focus on several toxic metals including arsenic, lead and cadmium. Therefore, we conducted this prospective study within the Dongfeng-Tongji cohort to evaluate the associations of plasma multiple metals with the decline in kidney function among Chinese middle-aged and elderly. In total, 1434 participants free of chronic diseases at baseline were included in analysis. We measured baseline plasma concentrations of 23 metals and calculated estimated glomerular filtration rate (eGFR) using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation based on serum creatinine, age, sex and ethnicity. Bonferroni correction was used for multiple testing to reduce the probability of a type I error. Principal component analysis was conducted to evaluate the combined effect of multiple metal co-exposure. Most of the plasma metal concentrations were within the literature reported reference values, whereas the concentration of lead and nickel exceeded the guideline value. We found that plasma concentrations of aluminum, arsenic, barium, lead, molybdenum, rubidium, strontium, vanadium and zinc were significantly associated with the decline in kidney function measured by annual eGFR decline, rapid renal function decline (defined as an annual decline in eGFR ≥ 5 mL/min/1.73 m2) or incident eGFR

Objective To investigate the effect of passive smoking on the changes in mean platelet volume (MPV) in healthy adults. Methods Participants (N = 17,825) were drawn from the Dongfeng-Tongji cohort. Multiple logistic regression analysis was used to examine relationships between MPV and selected variables among subgroups of MPV clarified by the MPV reference range for Chinese adults. Results Female never smokers exposed to passive smoke ≥ 60 minutes every day (OR: 1.471, 95%CI: 1.147-1.886) or ≥ 30 years had a higher risk of having low MPV (OR: 1.260, 95%CI: 1.004-1.583). Conclusions Certain duration of passive smoke exposure (≥ 60 minutes/day or ≥ 30 years) was associated with higher risk of having low MPV in female never smokers.

Our aim was to study whether there is causal association between serum uric acid and metabolic syndrome (MetS). A cross-sectional study was performed, including a total of 27,009 subjects (23,345 subjects having uric acid data) from the Dongfeng-Tongji Cohort study. The MetS was defined by the International Diabetes Foundation criteria of 2005. Association analysis was performed by logistic regression. A genetic risk score was calculated by adding the uric acid increasing alleles in two SNPs (rs11722228 in SLC2A9 and rs2231142 in ABCG2) which were identified from our genome-wide association study on uric acid levels. The causal association was examined by mendelian randomization analysis. Among a middle- and old-age Chinese population, serum uric acid concentrations were strongly associated with the risk of MetS and its several components (P < 0.0001). The effects were stronger in women than in men. Despite the lack of statistical significance, both SNPs exhibited a trend with increased MetS risk (rs11722228, OR = 1.06, 95 % CI 0.99–1.14; rs2231142, OR = 1.02, 95 % CI 0.95–1.10), consistent with their increasing uric acid effects. Each additional uric acid increasing allele in the genetic risk score was associated with 3 % increased MetS risk (OR = 1.03, 95 % CI 0.98–1.09; P = 0.23). Further adjustment for serum uric acid attenuated the trend of individual SNP and genetic risk score with increased MetS risk (all OR < 1.0). These findings suggested that serum uric acid was associated with MetS risk in a middle- and old-age Chinese population. Whether this association was causal remained to be investigated in the future studies.

Serum bilirubin is a potent endogenous antioxidant and has been identified as cardiovascular risk in cohort studies, while the relation to type 2 diabetes (T2D) in the elderly remains unclear. We investigated both cross-sectional and prospective associations between serum bilirubin levels and T2D risk in the Dongfeng-Tongji (DFTJ) cohort, and replicated the prospective findings in a nested case-control study (509 cases and 509 controls) within the Singapore Chinese Health Study (SCHS). In the cross-sectional analysis of DFTJ cohort (15,575 participants with 2,532 diabetes cases), serum bilirubin levels (total, direct and indirect) increased in new on-set diabetes and decreased with the diabetic duration. In the longitudinal analysis of DFTJ cohort (772 incident diabetes cases during 4.5 years of follow-up among 12,530 diabetes-free participants at baseline), positive association was found between direct bilirubin and T2D risk comparing extreme quartiles, similar results were observed in the nested case-control study within SCHS. Total and indirect bilirubin levels were not significantly associated with T2D in either cohort. In conclusion, our findings do not support the protective association between serum bilirubin levels and incident T2D in the middle-aged and elderly adults; instead, direct bilirubin levels were associated with increased risk of T2D.

STUDY OBJECTIVES Prospective evidence on the association of sleep duration and midday napping with metabolic syndrome (MetS) is limited. We aimed to examine the associations of sleep duration and midday napping with risk of incidence and reversion of MetS and its components among a middle-aged and older Chinese population. METHODS We included 14,399 subjects from the Dongfeng-Tongji (DFTJ) Cohort Study (2008-2013) who were free of coronary heart disease, stroke, and cancer at baseline. Baseline data were obtained by questionnaires and health examinations. Odds ratios (ORs) and 95% confidence interval (CI) were derived from multivariate logistic regression models. RESULTS After controlling for potential covariates, longer sleep duration (≥ 9 h) was associated with a higher risk of MetS incidence (OR, 1.29; 95% CI, 1.08-1.55) and lower reversion of MetS (OR, 0.80; 95% CI, 0.66-0.96) compared with sleep duration of 7 to < 8 h; whereas shorter sleep duration (< 6 h) was not related to incidence or reversion of MetS. For midday napping, subjects with longer napping (≥ 90 min) was also associated with a higher risk of MetS incidence and a lower risk of MetS reversion compared with those with napping of 1 to < 30 min (OR, 1.48; 95% CI, 1.05-2.10 and OR, 0.70; 95% CI, 0.52-0.94, respectively). Significance for incidence or reversion of certain MetS components remained in shorter and longer sleepers but disappeared across napping categories. CONCLUSIONS Both longer sleep duration and longer midday napping were potential risk factors for MetS incidence, and concurrently exert adverse effects on MetS reversion.

Prospective studies on the association of green tea with risk of coronary heart disease (CHD) incidence were scarce. This study examined whether green tea can reduce CHD incidence and have a beneficial effect on CHD-related risk markers in middle-aged and older Chinese population. We included 19 471 participants who were free of CHD, stroke or cancer at baseline from September 2008 to June 2010, and were followed until October 2013. Cox proportional hazard models were used to examine the hazard ratios (HR) of CHD incidence in relation to green tea consumption. Linear regression models were used to evaluate the effect of green tea on 5-year changes of CHD-related biomarkers. Compared with non-green tea consumers, the multivariable-adjusted HR for CHD was 0.89 (95% CI, 0.81-0.98) in green tea consumers. Particularly, the reduced risk of CHD incidence with green tea consumption was more evident among participants who were male, more than 60 years old, overweight, or with diabetes mellitus. In addition, green tea consumption improved multiple CHD-related risk markers including total cholesterol, HDL-cholesterol, triglycerides, mean platelet volume, and uric acid. In conclusion, green tea consumption was associated with a reduced risk of CHD incidence in the middle-aged and older Chinese populations, and the association might be partly due to altered CHD-related biomarkers.

BACKGROUND Epidemiological studies suggest that elevated serum uric acid (SUA) is associated with heightened incident kidney disease in both the general population and the type 2 diabetes (T2D) cases, although the results were not entirely consistent. METHODS We investigated prospective association between SUA levels and estimated glomerular filtration (eGFR) decline risk (eGFR

Aims Studies indicate that elevated serum total bilirubin (TBil) levels are associated with lower risk of diabetic kidney disease (DKD). Few studies examined the associations of direct bilirubin (DBil) and indirect bilirubin (IBil) with the development of DKD. Methods Type 2 diabetes patients (n=2,958) with estimated glomerular filtration (eGFR)≥60mlmin −1 1.73m −2 from the Dongfeng–Tongji cohort were selected and followed up for 5years. Development of DKD was defined as decline in eGFR≥30% during follow-up. Generalize linear model was used to assess the associations of bilirubin levels with DKD development. Results Compared with those in the first tertile of serum TBil, the relative risks (RRs) and 95% confidence intervals (CIs) of incident eGFR decline for tertile 2 to 3 were 0.83 (0.64–1.09) and 0.74 (0.56–0.98), P trend =0.04. The counterpart RRs (95% CIs) in IBil were 0.74 (0.57–0.97) and 0.75 (0.57–0.98), P trend =0.04. No significant associations were observed in DBil. Moreover, TBil and IBil interacted with smoking, the bilirubin-DKD associations were evident in ever smokers. Conclusions Our findings suggest that elevation of serum TBil or IBil levels are independent protective factors for development of DKD, particularly in smokers.

Hypoxia is a prominent characteristic of inflammatory tissue lesions. It can affect platelet function. While mean platelet volume (MPV) and platelet distribution width (PDW) are sample platelet indices, they may reflect subcinical platelet activation. To investigated associations between adiposity indices and platelet indices, 17327 eligible individuals (7677 males and 9650 females) from the Dongfeng-Tongji Cohort Study (DFTJ-Cohort Study, n=27009) were included in this study, except for 9682 individuals with missing data on demographical, lifestyle, physical indicators and diseases relative to PDW and MPV. Associations between adiposity indices including waist circumstance (WC), waist-to-height ratio (WHtR), body mass index (BMI), and MPV or PDW in the participants were analyzed using multiple logistic regressions. There were significantly negative associations between abnormal PDW and WC or WHtR for both sexes (p trend

The prevalence of metabolic syndrome (MetS) persistently increased. Several studies have found serum creatinine (SCr) concentrations related to cardiovascular disease and type 2 diabetes. The relationship between SCr concentrations and MetS is unknown.We measured SCr concentrations and MetS in 22363 individuals (10,151 males, 12,212 females) from the Dongfeng-Tongji Cohort in Shiyan, China from 2008 to 2009.The prevalence of MetS was 30.6% in the study population. In the multivariable-adjusted logistic regression analyses, higher SCr concentrations were associated with a higher risk of MetS (P trend0.0001). Compared with the lowest extreme quintiles, subjects with the highest quintiles had 1.34 fold risk of MetS (95% confidence interval (CI): 1.22-1.47). The SCr concentrations were also associated with the individual component of MetS. In addition, higher SCr concentrations were associated with higher risk of MetS with more components.There is a graded positive association between the SCr concentrations and MetS risk in a middle aged and older Chinese population. Higher SCr concentrations, even within normal ranges, were associated with higher risk of MetS. The SCr might be a useful indicator of MetS and its related diseases.

Purpose: To compare size-specific dose estimate (SSDE) in abdominal fat quantitative CT with another dose estimate Dsize,L that also takes into account scan length. Methods: This study complied with the requirements of the Health Insurance Portability and Accountability Act. At our institution, abdominal fat CT is performed with scan length = 1 cm and CTDI vol = 4.66 mGy (referenced to body CTDI phantom). A previously developed CT simulation program was used to simulate single rotation axial scans of 6–55 cm diameter water cylinders, and dose integral of the longitudinal dose profile over the central 1 cm length was used to predict the dose at the center of one-cm scan range. SSDE and Dsize,L were assessed for 182 consecutive abdominal fat CT examinations with mean water-equivalent diameter (WED) of 27.8 cm ± 6.0 (range, 17.9 - 42.2 cm). Patient age ranged from 18 to 75 years, and weight ranged from 39 to 163 kg. Results: Mean SSDE was 6.37 mGy ± 1.33 (range, 3.67–8.95 mGy); mean Dsize,L was 2.99 mGy ± 0.85 (range, 1.48 - 4.88 mGy); and mean Dsize,L/SSDE ratio was 0.46 ± 0.04 (range, 0.40 - 0.55). Conclusion: The conversion factors for size-specific dose estimate in AAPM Report No. 204 were generated using 15 - 30 cm scan lengths. One needs to be cautious in applying SSDE to small length CT scans. For abdominal fat CT, SSDE was 80–150% higher than the dose of 1 cm scan length.

China has seen rapid socio-economic and epidemiolo-gical changes over the past several decades. Economicgrowth plus shifts in environment, lifestyles and diethave increased life expectancy, but they have also ledto a higher burden of chronic, non-communicablediseases. Stroke, coronary heart disease (CHD), cancerand diabetes account for 80% of the deaths and 70%of the disability-adjusted life-years lost in China.