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Gut microbiota plays an important role in coronary heart disease, but its compositional and functional changes in unstable angina (UA) remain unexplored. We performed metagenomic sequencing of 133 newly diagnosed UA patients and 133 sex- and age-matched controls, and profiled the fecal and plasma metabolomes in 30 case-control pairs. The alpha diversity of gut microbiota was increased in UA patients: the adjusted odds ratios (ORs) per standard deviation increase in Shannon and Simpson indices were 1.30 (95% confidence interval, 1.01-1.70) and 1.36 (1.05-1.81), respectively. Two common species (depleted Klebsiella pneumoniae and enriched Streptococcus parasanguinis; P ≤ 0.002) and three rare species (depleted Weissella confusa, enriched Granulicatella adiacens and Erysipelotrichaceae bacterium 6_1_45; P ≤ 0.005) were associated with UA. The UA-associated gut microbiota was depleted in the pathway of L-phenylalanine degradation (P = 0.001), primarily contributed by Klebsiella pneumoniae. Consistently, we found increased circulating phenylalanine in UA patients (OR = 2.76 [1.17-8.16]). Moreover, Streptococcusparasanguinis was negatively correlated with fecal citrulline (Spearman's r

Objective: The aim of this study was to evaluate the independent relationship between Serum uric acid (SUA) and blood pressure. Methods: A cross-sectional study was conducted based on a sample of 6035 employees (3605 males and 2430 females). Multivariable regression analysis was performed to identify the association between risk factors for metabolic disorders and hypertension. Results: The SUA levels were closely and independently related to hypertension even after adjusting for age, sex, lipids and glucose. Conclusions: We verified that uric acid was associated with hypertension independent of other metabolic risk factors and that the presence of other risk factors with uric acid had an additive effect on blood pressure.

The joint association of antihypertensive medication use and healthy lifestyle with mortality among individuals with hypertension is unclear.To examine the association of lifestyle factors combined with antihypertensive medication use, as well as changes in lifestyle, with all-cause and cause-specific mortality among individuals with hypertension.This cohort study used data from the Dongfeng-Tongji cohort, a long-term, prospective cohort including employees at a manufacturer in China, with baseline from 2008 to 2010. Participants with hypertension were followed up for a median (IQR) of 7.3 (5.7-10.3) years, ending in 2018. Data were analyzed from February to April 2021.Lifestyle factors, including body mass index, smoking status, diet, physical activity, and sleep duration, were coded on a 3-point scale (range, 0-2, with higher score indicating a healthier lifestyle). Lifestyle was evaluated according to the total score of all 5 factors, and categorized into 3 groups: unfavorable (scores 0-4), intermediate (scores 5-7), and favorable (scores 8-10). Antihypertensive medication use was defined as use within the last 2 weeks.All-cause, cardiovascular, and cancer mortality were identified by linking the cohort database with the health care system through December 31, 2018.A total of 14 392 participants (mean [SD] age, 65.6 [7.4] years; 7277 [50.6%] men and 7115 [49.4%] women) with hypertension were included, and 2015 deaths were documented, including 761 cardiovascular deaths and 525 cancer deaths. Compared with individuals not using antihypertensive medication and with a lifestyle score of 0 to 4, the combination of using antihypertensive medication and having a lifestyle score of 8 to 10 was associated with the lowest risk of all-cause mortality (hazard ratio [HR], 0.32; 95% CI, 0.25-0.42), cardiovascular mortality (HR, 0.33; 95% CI, 0.21-0.53), and cancer mortality (HR, 0.30; 95% CI, 0.19-0.47). In addition, improvement in lifestyle score after hypertension diagnosis was associated with lower risk of all-cause mortality (HR, 0.52; 95% CI, 0.36-0.76) and cardiovascular mortality (HR, 0.53; 95% CI, 0.30-0.94).These findings suggest that adherence to healthy lifestyle and antihypertensive medication treatment were associated with lower risk of mortality among adults with hypertension. These findings further support that, in addition to antihypertensive medication use, adopting a healthy lifestyle is associated with benefits in the prevention of premature death among individuals with hypertension.

Background and aims Cohort studies found blood lipid traits were associated with the risk of chronic kidney disease (CKD). We aimed to investigate whether blood lipid traits were causally associated with the risk of CKD in the Chinese. Methods 15,244 participants without kidney disease and cancer from the Dongfeng-Tongji cohort were recruited in 2008–2010 in Shiyan City, China. Blood total cholesterol (TC), high-density lipoprotein cholesterol (HDL-c), low-density lipoprotein cholesterol (LDL-c), and triglyceride (TG) levels were measured. 5251 participants had genotype data and were included in the Mendelian randomization analysis. Incident CKD was defined as estimated glomerular filtration rate Results Various blood lipid traits were associated with CKD risk, and the odds ratios (95% confidence intervals) for incident CKD comparing the extreme quartiles were 1.45 (1.24–1.70) for TG, 1.26 (1.08–1.46) for nonHDL-c, 2.21 (1.91–2.57) for TC:HDL-c ratio, 2.14 (1.83–2.51) for TG:HDL-c ratio, and 0.47 (0.40–0.55) for HDL-c. The Mendelian randomization analysis indicated that 1 mmol/l increase in the genetic predicted blood TG level was associated with a 5% (95% confidence interval, 0–10%) higher risk of CKD. Conclusions Although blood levels of HDL-c, TG, nonHDL-c, TC:HDL-c ratio, and TG:HDL-c ratio were observed to be associated with incident CKD, the Mendelian randomization analysis provided genetic evidence to support causal relation for blood TG level only.

Although numerous studies have separately investigated the associations of changes in weight or waist circumference with mortality risk, few studies have examined the associations of concurrent changes in these 2 anthropometric parameters with all-cause mortality.To assess the associations of changes in body weight, waist circumference, or both, combined with all-cause mortality.This cohort study used data from 2 longitudinal cohort studies in Dongfeng-Tongji and Kailuan, China. Participants included 58 132 adults (aged 40 years and older) with measures of weight and waist circumference at baseline and follow-up visit. Statistical analysis was performed from June 2020 to September 2021.Changes in weight and waist circumference between 2 visits (2008-2010 to 2013 in the Dongfeng-Tongji cohort, and 2006-2007 to 2010-2011 in the Kailuan study). Stable weight was defined as change in weight within 2.5 kg between the 2 visits and stable waist circumference was defined as changes within 3.0 cm. Changes were categorized as loss, stable, or gain for weight and waist circumference separately, and created a 9-category variable to represent the joint changes.All-cause mortality from follow-up visit (2013 in Dongfeng-Tongji cohort and 2010-2011 in Kailuan study) until December 31, 2018. Cox proportional hazard regression models were used to estimate the associations with adjustment for potential confounders. Results were obtained in the 2 cohorts separately and pooled via fixed-effect meta-analysis.A total of 10 951 participants in the Dongfeng-Tongji cohort (median [IQR] age, 62 [56-66] years; 4203 [38.4%] men) and 47 181 participants in the Kailuan study (median [IQR] age, 51 [46-58] years; 36 663 [77.7%] men) were included in the analysis. During 426 072 person-years of follow-up, 4028 deaths (523 in the Dongfeng-Tongji cohort and 3505 in the Kailuan study) were documented. When changes in weight and waist circumference were examined separately, U-shape associations were found: both gain and loss in weight (weight loss: pooled hazard ratio [HR], 1.33; 95% CI, 1.23-1.43; weight gain: HR, 1.10; 95% CI, 1.02-1.19) or waist circumference (waist circumference loss: HR, 1.14; 95% CI, 1.05-1.24; waist circumference gain: HR, 1.11; 95% CI, 1.03-1.21) were associated with higher mortality risk compared with stable weight or waist group. When changes in weight and waist circumference were jointly assessed, compared with participants with stable weight and waist circumference (16.9% of the total population [9828 of 58 132] with 508 deaths), participants with different combinations of weight and waist circumference change all had higher mortality risks except for those with stable weight but significant loss in waist. Notably, those who lost weight but gained waist circumference (6.4% of the total population [3698 of 58 132] with 308 deaths) had the highest risk of all-cause mortality (HR, 1.69; 95% CI, 1.46-1.96; absolute rate difference per 100 000 person-years in the Dongfeng-Tongji cohort: 414; 95% CI, 116-819; and in the Kailuan study: 333; 95% CI, 195-492) among the joint subgroups.In this cohort study, weight loss with concurrent waist circumference gain was associated with a higher mortality risk in middle-aged and older Chinese adults. This study's findings suggest the importance of evaluating the changes in both body weight and waist circumference when assessing their associations with mortality.

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.

Aims. To investigate the effect of GLP-1/GLP-1R on the polarization of macrophages in the occurrence and development of atherosclerosis. Methods. Totally, 49 patients with coronary heart disease (CHD) and 52 cases of health control (HC) were recruited, all subjects accept coronary angiography gold standard inspection. One or more major coronary arteries (LM, LAD, LCx, and RCA) stenosis degree in 50% of patients as CHD group; the rest of the stenosis less than 50% or not seen obvious stenosis are assigned to the HC group. Flow cytometry were used to detect the percentage of (CD14+) M macrophages, (CD14+CD80+) M1 macrophages, (CD14+CD206+) M2 macrophages, and their surface GLP-1R expression differences in the two groups, using BD cytokine kit to detect the levels of IL-8, IL-1β, IL-6, IL-10, TNF, and IL-12p70. Results. GLP-1R expression on the surface of total macrophages and M2 macrophages was different between the CHD group and the HC group ( P < 0.05 ). There was no difference in the percentage of total, M1 or M2 macrophages ( P > 0.05 ). Concentration of IL-8 in the HC group was higher than that in the CHD group ( P < 0.05 ). There is no significant difference in the cytokine IL-1β, IL-6, IL-10, TNF, and IL-12p70 in the two groups ( P > 0.05 ). After controlling for potential confounders including age, gender, smoking status (S.S.), drinking status (D.S.), HR, SBP, DBP, PP, TC, TG, HDL-C, LDL-C, GHbA1c, M, M1, M2, GLP-1R_M, GLP-1R_M1, GLP-1R_M2, IL-8, IL-1β, IL-6, IL-10, TNF, and IL-12p70 by multiple linear regression, decreasing Gensini Score was significantly associated with increased percentage of M1 macrophage. Conclusion. GLP-1R agonist is independent of the hypoglycemic effect of T2DM and has protective effect on cardiovascular system. GLP-1R may regulate the polarization of macrophages toward M2, thus playing a protective role in the progression of coronary atherosclerosis.

Epicardial movement during diastole is inversely proportional to myocardial stiffness but systolic regional thickening cannot precisely identify ischemic territories. The aim of the present study was to test the hypothesis that a correlation may be present between M-mode echocardiography parameters and poor outcomes in patients with heart failure and preserved ejection fraction. Patients with known cardiovascular disease were included in the test group (n=1,244) and patients without known cardiovascular disease were included in the control group (n=1,952). Patient records of routine measurements, M-mode echocardiography and mortality were collected. The control population and test population had the same left ventricular end-diastolic dimension (P=0.062) and left ventricular end-diastolic volume (P=0.053). A lower mitral flow velocity (P

Background Red cell distribution width (RDW) is associated with a poor prognosis and adverse events in cardiovascular diseases. The aims of this study were to investigate the relationship between serum RDW levels and outcomes after percutaneous coronary intervention and to identify potential novel laboratory markers for evaluating the risk of in-stent restenosis (ISR) with stable angina pectoris. Methods A total of 261 patients with coronary heart disease from Dongfeng General Hospital implanted with a coronary drug-eluting stent (DES) were enrolled in the study. We retrospectively analysed the role and prognosis values of serum parameters that were measured before angiography at the first admission. According to the results of the second angiogram, the patients were divided into two groups as follows: the non-ISR group (n=143) and the ISR group (n=118). The clinical characteristics and all laboratory data were considered for univariate and multivariate logistic regression analyses. Results The white cell count, RDW, neutrophil count, C-reactive protein (CRP), total cholesterol, low-density lipoprotein cholesterol (LDL-C), blood urea nitrogen and uric acid levels were higher in the ISR group than in the non-ISR group. There were no differences in the rates of hypertension, fasting plasma glucose, red cell count, neutrophil to lymphocyte ratio, platelet count, triglyceride, high-density lipoprotein cholesterol and creatinine levels. In the univariate regression analysis, age, diabetes, white cell count, neutrophil count, RDW, CRP, total cholesterol, LDL-C, blood urea nitrogen, Gensini score and number of stents were predictors of ISR. According to the multiple logistic regression analysis, age, RDW and number of stents were independent predictors of ISR. Conclusions Preprocedural blood parameters can independently predict ISR. Our study results demonstrated that a high preprocedural RDW is an independent predictor of DES restenosis.

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.

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.

Estimated glomerular filtration rate (eGFR) has been reported to be associated with risk of incident coronary heart disease (CHD), and blood urea nitrogen (BUN) has been shown to be a strong predictor of mortality in patients with heart failure (HF). However, such epidemiological evidence from Chinese population was still limited. We used Cox proportional-hazards regression models to investigate the associations of eGFR and BUN with risk of incident CHD in the prospective Dongfeng-Tongji (DFTJ) cohort. After fully adjusted for potential confounders, a 10-unit decline in eGFR was associated with higher risk for CHD (hazard ratio [HR] 1.05, 95% confidence interval [CI] 1.01–1.09); compared with individuals with normal eGFR levels (eGFR ≥ 90 ml/min per 1.73 m2), individuals with a mild-to-severe eGFR decline (15 to 60 ml/min per 1.73 m2) were at significantly greater risk for CHD (HR 1.25, 95% CI 1.05–1.48; P = 0.011). Compared with individuals in the lowest tertile of BUN, those in the highest tertile were at significantly greater risk for CHD (HR 1.17, 95% CI 1.03–1.33; P = 0.014). In conclusion, a mild-to-severe decline in eGFR or a raised level of BUN might be associated with increased risk of incident CHD in middle-aged and elderly Chinese populations.

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: 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.

Background Coronary artery disease (CAD) is the most frequent multifactorial disease worldwide and is characterised by endothelial injury, lipid deposition and coronary artery calcification. The purpose of this study was to determine the allelic and genotypic frequencies of two loci (rs2026458 and rs9349379) of phosphatase and actin regulator 1 (PHACTR1) to the risk of developing CAD in the Chinese Han population. Methods A case–control study was conducted including 332 patients with CAD and 119 controls. Genotype analysis was performed by PCR and Sanger sequencing. Genetic model analysis was performed to evaluate the association between single nucleotide polymorphisms and CAD susceptibility using Pearson’s χ2 test and logistic regression analysis. Results The GG genotype of rs9349379 represented 50% and 29% of patients with CAD and controls, respectively (p Conclusions Our study indicate that the PHACTR1 rs9349379 polymorphism is associated with the increased risk for CAD in the female Chinese Han population.

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.

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: 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.

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.

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.

To explore the effects of related environment, occupational, lifestyle, genetic factors as well as their interactions on the etiology of major chronic diseases in an occupational population.Dongfeng-Tongji cohort (DFTJ cohort), one of the large prospective cohort studies with biobank. Baseline study was conducted in Shiyan city, Hubei province from 2008 to 2009. This cohort study included questionnaire, physical examination and tests on blood samples. Dongfeng-Tongji cohort was followed up every 5 years and the first follow-up program was completed, from April to October in 2013. During the first follow-up period in 2013, questionnaire, physical examination, clinical and blood sample tests were conducted again.27 009 retired participants with mean age of 63.6 years including 44.6% males, were recruited in this study. In the first follow-up program in 2013, among 38 295 subjects (44.7% males), 40.5% of them received diploma from high school or above. Prevalence rates of current regular smokers were 33.6% in men and 2.0% in women and the rates on current alcohol drinkers were 39.9% in men and 10.6% in women. The prevalence rates on self-reported hypertension, hypercholesterolemia, diabetes mellitus, coronary heart disease, stroke, chronic bronchitis, and asthma were 41.1%, 24.3%, 13.9%, 16.7%, 5.1%, 12.7% and 4.0%, respectively. The self-reported prevalence of hypertension and stroke in males was higher than that in females. 25 978 individuals who were involved in the baseline database successfully completed the followed up program in 2013, with the follow-up rate as 96.2%.The DFTJ cohort study offered us an opportunity to explore the effects of environmental, genetic, as well as their interactions with major chronic diseases in a Chinese occupational population.

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.

Pim-3 is a member of proto-oncogene Pim family that encodes serine/threonine kinases. Pim proteins regulate both apoptosis and cellular metabolism by phosphorylating their substrates. Here, we report for the first time that Pim-3 is highly expressed at mRNA and protein levels in endothelial cells (ECs). We found that Pim-3 is concentrated at the cellular lamellipodia and co-localized with focal adhesion kinase (FAK). Pim-3 was dispersed from lamellipodia when ECs were treated with cytochalasin D, an inhibitor of actin polymerization. In addition, small-interfering RNA (siRNA)-mediated gene knockdown of Pim-3 significantly impaired EC spreading, migration, and proliferation, leading to a reduction in tube-like structure formation in a Matrigel assay. These results provide the novel evidence that Pim-3 plays an essential role in EC spreading and migration, suggesting that Pim-3 may be an important molecular target for the development of small-molecule inhibitors of angiogenesis.

Camptothecin (CPT) and its derivative have been revealed to possess special anti-cancer activity, extraction methods are necessary for trace determination of CPTs in complex samples. In this work, we prepared a high efficient boronic acid-based polymer monolithic layer for microextraction of CPTs. A disposable membrane filter-based extraction device was developed, and boronic acid groups were co-polymerized into a polyporous polymer skeleton and served as the monolithic sorbent. The prepared poly(4-VB-MA-TRIM) showed good stability and great extraction efficiency toward four CPTs. After optimization of extraction conditions, poly(4-VB-MA-TRIM)-based solid-phase microextraction was coupled HPLC for determination of CPTs in biological samples. The method exhibited low limits of detection of 0.05–0.2 ng mL −1 , which is significantly more sensitive than reported HPLC methods. The method also showed wide linear range (0.1–100 and 0.5–200 ng mL −1 ), good linearity ( R 2 ≥ 0.9981) and good reproducibility (RSD ≤3.76%). The method has been applied in plasma samples, with good selectivity and good recoveries ranging from 85.1 to 104.7%.

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.

Background Uric acid (UA) is a complex phenotype influenced by both genetic and environmental factors as well as their interactions. Current genome-wide association studies (GWASs) have identified a variety of genetic determinants of UA in Europeans; however, such studies in Asians, especially in Chinese populations remain limited. Methods A two-stage GWAS was performed to identify single nucleotide polymorphisms (SNPs) that were associated with serum uric acid (UA) in a Chinese population of 12,281 participants (GWAS discovery stage included 1452 participants from the Dongfeng-Tongji cohort (DFTJ-cohort) and 1999 participants from the Fangchenggang Area Male Health and Examination Survey (FAMHES). The validation stage included another independent 8830 individuals from the DFTJ-cohort). Affymetrix Genome-Wide Human SNP Array 6.0 chips and Illumina Omni-Express platform were used for genotyping for DFTJ-cohort and FAMHES, respectively. Gene-environment interactions on serum UA levels were further explored in 10,282 participants from the DFTJ-cohort. Results Briefly, we identified two previously reported UA loci of SLC2A9 (rs11722228, combined P = 8.98 × 10-31) and ABCG2 (rs2231142, combined P = 3.34 × 10-42). The two independent SNPs rs11722228 and rs2231142 explained 1.03% and 1.09% of the total variation of UA levels, respectively. Heterogeneity was observed across different populations. More importantly, both independent SNPs rs11722228 and rs2231142 were nominally significantly interacted with gender on serum UA levels (P for interaction = 4.0 × 10-2 and 2.0 × 10-2, respectively). The minor allele (T) for rs11722228 in SLC2A9 has greater influence in elevating serum UA levels in females compared to males and the minor allele (T) of rs2231142 in ABCG2 had stronger effects on serum UA levels in males than that in females. Conclusions Two genetic loci (SLC2A9 and ABCG2) were confirmed to be associated with serum UA concentration. These findings strongly support the evidence that SLC2A9 and ABCG2 function in UA metabolism across human populations. Furthermore, we observed these associations are modified by gender.

Objective Tumour biomarkers are used as indicators for cancer screening and as predictors for therapeutic responses and prognoses in cancer patients. We aimed to identify genetic loci that influence concentrations of cancer antigen 19-9 (CA19-9), carcinoembryonic antigen (CEA) and α fetoprotein (AFP), and investigated the associations between the significant single nucleotide polymorphisms (SNPs) with risks of oesophageal squamous cell (OSCC), pancreatic and hepatocellular cancers. Design We carried out a genome wide association study on plasma CA19-9, CEA and AFP concentrations in 3451 healthy Han Chinese and validated the results in 10 326 individuals. Significant SNPs were further investigated in three case control studies (2031 OSCC cases and 2044 controls; 981 pancreatic cancer cases and 1991 controls; and 348 hepatocellular cancer cases and 359 controls). Results The analyses showed association peaks on three genetic loci for CA19-9 ( FUT6-FUT3 at 19p13.3, FUT2 - CA11 at 19q13.3 and B3GNT3 at 19p13.1; p=1.16×10 −13 –3.30×10 −290 ); four for CEA ( ABO at 9q34.2, FUT6 at 19p13.3, FUT2 at 19q13.3 and FAM3B at 21q22.3; p=3.33×10 −22 –5.81×10 −209 ); and two for AFP ( AFP at 4q11-q13 and HISPPD2A at 15q15.3; p=3.27×10 −18 and 1.28×10 −14 ). These explained 17.14% of the variations in CA19-9, 8.95% in CEA and 0.57% in AFP concentrations. Significant ABO variants were also associated with risk of OSCC and pancreatic cancers, and AFP variants with risk of hepatocellular cancer (p Conclusions This study identified several loci associated with CA19-9, CEA and AFP concentrations. The ABO variants were associated with risk of OSCC and pancreatic cancers and AFP variants with risk of hepatocellular cancer.

Plasma lipid levels are important risk factors for cardiovascular disease and are influenced by genetic and environmental factors. Recent genome wide association studies (GWAS) have identified several lipid-associated loci, but these loci have been identified primarily in European populations. In order to identify genetic markers for lipid levels in a Chinese population and analyze the heterogeneity between Europeans and Asians, especially Chinese, we performed a meta-analysis of two genome wide association studies on four common lipid traits including total cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL) and high-density lipoprotein cholesterol (HDL) in a Han Chinese population totaling 3,451 healthy subjects. Replication was performed in an additional 8,830 subjects of Han Chinese ethnicity. We replicated eight loci associated with lipid levels previously reported in a European population. The loci genome wide significantly associated with TC were near DOCK7, HMGCR and ABO; those genome wide significantly associated with TG were near APOA1/C3/A4/A5 and LPL; those genome wide significantly associated with LDL were near HMGCR, ABO and TOMM40; and those genome wide significantly associated with HDL were near LPL, LIPC and CETP. In addition, an additive genotype score of eight SNPs representing the eight loci that were found to be associated with lipid levels was associated with higher TC, TG and LDL levels (P = 5.52 × 10(-16), 1.38 × 10(-6) and 5.59 × 10(-9), respectively). These findings suggest the cumulative effects of multiple genetic loci on plasma lipid levels. Comparisons with previous GWAS of lipids highlight heterogeneity in allele frequency and in effect size for some loci between Chinese and European populations. The results from our GWAS provided comprehensive and convincing evidence of the genetic determinants of plasma lipid levels in a Chinese population.

Bilirubin is an effective antioxidant and is influenced by both genetic and environmental factors. Recent genome-wide association studies (GWAS) have identified multiple loci affecting serum total bilirubin levels. However, most of the studies were conducted in European populations and little attention has been devoted either to genetic variants associated with direct and indirect bilirubin levels or to the gene-environment interactions on bilirubin levels. In this study, a two-stage GWAS was performed to identify genetic variants associated with all types of bilirubin levels in 10,282 Han Chinese individuals. Gene-environment interactions were further examined. Briefly, two previously reported loci, UGT1A1 on 2q37 (rs6742078 and rs4148323, combined P = 1.44 × 10(-89) and P = 5.05 × 10(-69) , respectively) and SLCO1B3 on 12p12 (rs2417940, combined P = 6.93 × 10(-19) ) were successfully replicated. The two loci explained 9.2% and 0.9% of the total variations of total bilirubin levels, respectively. Ethnic genetic differences were observed between Chinese and European populations. More importantly, a significant interaction was found between rs2417940 in SLCO1B3 gene and smoking on total bilirubin levels (P = 1.99 × 10(-3) ). Single nucleotide polymorphism (SNP) rs2417940 had stronger effects on total bilirubin levels in nonsmokers than in smokers, suggesting that the effects of SLCO1B3 genotype on bilirubin levels were partly dependent on smoking status. Consistent associations and interactions were observed for serum direct and indirect bilirubin levels.