Effects of multiple metals exposure on abnormal liver function: The mediating role of low-density lipoprotein cholesterol.

Equilibration of metal metabolism is critical for normal liver function. Most epidemiological studies have only concentrated on the influence of limited metals. However, the single and synergistic impact of multiple-metal exposures on abnormal liver function (ALF) are still unknown. A cross-sectional study involving 1493 Chinese adults residing in Shenzhen was conducted. Plasma concentrations of 13 metals, including essential metals (calcium, copper, cobalt, iron, magnesium, manganese, molybdenum, zinc, and selenium) and toxic metals (aluminum, cadmium, arsenic, and thallium) were detected by the inductively coupled plasma spectrometry (ICP-MS). ALF was ascertained as any observed abnormality from albumin, alanine transaminase, aspartate transaminase, γ-glutamyl transpeptidase, and direct bilirubin. Diverse statistical methods were used to evaluate the single and mixture effect of metals, as well as the dose-response relationships with ALF risk, respectively. Mediation analysis was conducted to evaluate the role of blood lipids in the relation of metal exposure with ALF. The average age of subjects was 59.7 years, and 56.7 % were females. Logistic regression and the least absolute shrinkage and selection operator (LASSO) penalized regression model consistently suggested that increased levels of arsenic, aluminum, manganese, and cadmium were related to elevated risk of ALF; while magnesium and zinc showed protective effects on ALF (all p-trend < 0.05). The grouped weighted quantile sum (GWQS) regression revealed that the WQS index of essential metals and toxic metals showed significantly negative or positive relationship with ALF, respectively. Aluminum, arsenic, cadmium, and manganese showed linear whilst magnesium and zinc showed non-linear dose-response relationships with ALF risk. Mediation analysis showed that LDL-c mediated 4.41 % and 14.74 % of the relationship of plasma cadmium and manganese with ALF, respectively. In summary, plasma aluminum, arsenic, manganese, cadmium, magnesium, and zinc related with ALF, and LDL-c might underlie the pathogenesis of ALF associated with cadmium and manganese exposure. This study may provide critical public health significances in liver injury prevention and scientific evidence for the establishment of environmental standard.

Associations of combined healthy lifestyles with cancer morbidity and mortality among individuals with diabetes: results from five cohort studies in the USA, the UK and China.

AIMS/HYPOTHESIS: Cancer has contributed to an increasing proportion of diabetes-related deaths, while lifestyle management is the cornerstone of both diabetes care and cancer prevention. We aimed to evaluate the associations of combined healthy lifestyles with total and site-specific cancer risks among individuals with diabetes. METHODS: We included 92,239 individuals with diabetes but without cancer at baseline from five population-based cohorts in the USA (National Health and Nutrition Examination Survey and National Institutes of Health [NIH]-AARP Diet and Health Study), the UK (UK Biobank study) and China (Dongfeng-Tongji cohort and Kailuan study). Healthy lifestyle scores (range 0-5) were constructed based on current nonsmoking, low-to-moderate alcohol drinking, adequate physical activity, healthy diet and optimal bodyweight. Cox regressions were used to calculate HRs for cancer morbidity and mortality, adjusting for sociodemographic, medical and diabetes-related factors. RESULTS: During 376,354 person-years of follow-up from UK Biobank and the two Chinese cohorts, 3229 incident cancer cases were documented, and 6682 cancer deaths were documented during 1,089,987 person-years of follow-up in the five cohorts. The pooled multivariable-adjusted HRs (95% CIs) comparing participants with 4-5 vs 0-1 healthy lifestyle factors were 0.73 (0.61, 0.88) for incident cancer and 0.55 (0.46, 0.67) for cancer mortality, and ranged between 0.41 and 0.63 for oesophagus, lung, liver, colorectum, breast and kidney cancers. Findings remained consistent across different cohorts and subgroups. CONCLUSIONS/INTERPRETATION: This international cohort study found that adherence to combined healthy lifestyles was associated with lower risks of total cancer morbidity and mortality as well as several subtypes (oesophagus, lung, liver, colorectum, breast and kidney cancers) among individuals with diabetes.

Individual and joint associations of co-exposure to multiple plasma metals with telomere length among middle-aged and older Chinese in the Dongfeng-Tongji cohort.

Studies on associations of metals with leucocyte telomere length (LTL) were mainly limited to several most common toxic metals and single-metal effect, but the impact of other common metals and especially the overall joint associations and interactions of metal mixture with LTL are largely unknown. We included 15 plasma metals and LTL among 4906 participants from Dongfeng-Tongji cohort. Multivariable linear regression was used to estimate associations of individual metals with LTL. We also applied Bayesian kernel machine regression (BKMR) and quantile g-computation regression (Q-g) to evaluate the overall association and interactions, and identified the major contributors as well as the potential modifications by major characteristics. Multivariable linear regression found vanadium, copper, arsenic, aluminum and nickel were negatively associated with LTL, and a 2-fold change was related to 1.9%-5.1% shorter LTL; while manganese and zinc showed 3.7% and 4.0% longer LTL (all P < 0.05) in multiple-metal models. BKMR confirmed above metals and revealed a linearly inverse joint association between 15 metals and LTL. Q-g regression further indicated each quantile increase in mixture was associated with 5.2% shorter LTL (95% CI: -8.1%, -2.3%). Furthermore, manganese counteracted against aluminum and vanadium respectively (Pint<0.05). In addition, associations of vanadium, aluminum and metal mixture with LTL were more prominent in overweight participants. Our results are among the first to provide a new comprehensive view of metal mixture exposure on LTL attrition in the general population, including identifying the major components, metals interactions and the overall effects.

Regulatory T cells protect fine particulate matter-induced inflammatory responses in human umbilical vein endothelial cells.

OBJECTIVE: To investigate the role of CD4(+)CD25(+) T cells (Tregs) in protecting fine particulate matter (PM-) induced inflammatory responses, and its potential mechanisms. METHODS: Human umbilical vein endothelial cells (HUVECs) were treated with graded concentrations (2, 5, 10, 20, and 40 µg/cm(2)) of suspension of fine particles for 24h. For coculture experiment, HUVECs were incubated alone, with CD4(+)CD25(-) T cells (Teff), or with Tregs in the presence of anti-CD3 monoclonal antibodies for 48 hours, and then were stimulated with or without suspension of fine particles for 24 hours. The expression of adhesion molecules and inflammatory cytokines was examined. RESULTS: Adhesion molecules, including vascular cell adhesion molecule-1 (VCAM-1) and intercellular adhesion molecule-1 (ICAM-1), and inflammatory cytokines, such as interleukin (IL-) 6 and IL-8, were increased in a concentration-dependent manner. Moreover, the adhesion of human acute monocytic leukemia cells (THP-1) to endothelial cells was increased and NF- κ B activity was upregulated in HUVECs after treatment with fine particles. However, after Tregs treatment, fine particles-induced inflammatory responses and NF- κ B activation were significantly alleviated. Transwell experiments showed that Treg-mediated suppression of HUVECs inflammatory responses impaired by fine particles required cell contact and soluble factors. CONCLUSIONS: Tregs could attenuate fine particles-induced inflammatory responses and NF- κ B activation in HUVECs.

Associations between variants in IL-33/ST2 signaling pathway genes and coronary heart disease risk.

The IL-33/ST2 signaling pathway plays an important role in coronary artery disease (CHD); however, few studies have explored how variants in IL-33/ST2 genes influence CHD risk. Here, we examined the association between genetic variants in IL-33, ST2, and IL-1RAcP of the IL-33/ST2 axis and the risk of CHD. We conducted a case-controlled study with 1146 CHD cases and 1146 age- and sex-frequency-matched controls. Twenty-eight single nucleotide polymorphisms (SNPs) in IL-33, ST2, and IL-1RAcP were genotyped by Sequenom MassArray and TaqMan assay. Logistic regression was used to analyze these associations. The SNP rs4624606 in IL-1RAcP was nominally associated with CHD risk. The AA genotype was associated with a 1.85-fold increased risk of CHD (95% confidence interval (CI) = 1.01-3.36; p = 0.045) compared to the TT genotype. Further analysis showed that AA carriers also had a higher risk of CHD than TT + TA carriers (odds ratio (OR) = 1.85; 95% CI = 1.85-3.35; p = 0.043). However, no significant association was observed between variants in IL-33/ST2 genes and CHD risk. Further studies are needed to replicate our results in other ethnic groups with larger sample size.

Association of Combined Healthy Lifestyles With Cardiovascular Disease and Mortality of Patients With Diabetes: An International Multicohort Study.

OBJECTIVE: To prospectively examine the associations of combined lifestyle factors with incident cardiovascular disease (CVD) and mortality in patients with diabetes. PATIENTS AND METHODS: Patients with prevalent diabetes were included from 5 prospective, population-based cohorts in China (Dongfeng-Tongji cohort and Kailuan study), the United Kingdom (UK Biobank study), and the United States (National Health and Nutrition Examination Survey and National Institutes of Health-AARP Diet and Health Study). Healthy lifestyle scores were constructed according to non-current smoking, low to moderate alcohol drinking, regular physical activity, healthy diet, and optimal body weight; the healthy level of each lifestyle factor was assigned 1 point, or 0 for otherwise, and the range of the score was 0 to 5. Cox proportional hazards models were used to estimate hazard ratios for incident CVD, CVD mortality, and all-cause mortality adjusting for sociodemographic, medical, and diabetes-related factors, and outcomes were obtained by linkage to medical records and death registries. Data were collected from October 18, 1988, to September 30, 2020. RESULTS: A total of 6945 incident CVD cases were documented in 41,350 participants without CVD at baseline from the 2 Chinese cohorts and the UK Biobank during 389,330 person-years of follow-up, and 40,353 deaths were documented in 101,219 participants from all 5 cohorts during 1,238,391 person-years of follow-up. Adjusted hazard ratios (95% CIs) comparing patients with 4 or 5 vs 0 or 1 healthy lifestyle factors were 0.67 (0.60 to 0.74) for incident CVD, 0.58 (0.50 to 0.68) for CVD mortality, and 0.60 (0.53 to 0.68) for all-cause mortality. Findings remained consistent across different cohorts, subgroups, and sensitivity analyses. CONCLUSION: The international analyses document that adherence to multicomponent healthy lifestyles is associated with lower risk of CVD and premature death of patients with diabetes.

[Using the stable HSPA1A promoter-driven luciferase reporter HepG2 cells to assess the overall toxicity of coke oven emissions].

OBJECTIVE: Using the stable HSPA1A (HSP70-1) promoter-driven luciferase reporter HepG2 cells (HepG2/HSPA1A cells) to assess the overall toxicity of coke oven emissions. METHODS: The stable HepG2/HSPA1A cells were treated with different concentrations of coke oven emissions (COEs) collected from the top, side, and bottom of a coke oven battery for 24 h. After the treatments, luciferase activity, cell viability, malondialdehyde (MDA) concentration, Olive tail moment, and micronuclei frequency were determined, respectively. RESULTS: The bottom COEs induced significant increases (P < 0.01) in relative luciferase activity up to 1.4 times the control level at 0.15 µg/L. The low dose of side COEs (0.02 µg/L) led to a significant increase (P < 0.01) in relative luciferase activity that progressively increased to 2.1 times the control level at 65.4 µg/L. The top COEs produced a strong dose-dependent induction of relative luciferase activity up to over 5 times the control level at the highest concentration tested (202 µg/L). In HepG2/HSPA1A cells treated with the bottom COEs, relative luciferase activity was positively correlated with MDA concentration (r = 0.404, P < 0.05). For the three COEs samples, positive correlations were observed between relative luciferase activity and Olive tail moment and micronuclei frequency. CONCLUSION: The relative luciferase activity in HepG2/HSPA1A cells can sensitively reflect the overall toxicity of COEs. The stable HepG2/HSPA1A cells can be used for rapid screening of the overall toxicity of complex air pollutants in the workplace.

Anti-SARS-CoV-2 IgG responses are powerful predicting signatures for the outcome of COVID-19 patients.

Introduction: The COVID-19 global pandemic is far from ending. There is an urgent need to identify applicable biomarkers for early predicting the outcome of COVID-19. Growing evidences have revealed that SARS-CoV-2 specific antibodies evolved with disease progression and severity in COIVD-19 patients. Objectives: We assumed that antibodies may serve as biomarkers for predicting the clinical outcome of hospitalized COVID-19 patients on admission. Methods: By taking advantage of a newly developed SARS-CoV-2 proteome microarray, we surveyed IgG responses against 20 proteins of SARS-CoV-2 in 1034 hospitalized COVID-19 patients on admission and followed till 66 days. The microarray results were further correlated with clinical information, laboratory test results and patient outcomes. Cox proportional hazards model was used to explore the association between SARS-CoV-2 specific antibodies and COVID-19 mortality. Results: Nonsurvivors (n = 955) induced higher levels of IgG responses against most of non-structural proteins than survivors (n = 79) on admission. In particular, the magnitude of IgG antibodies against 8 non-structural proteins (NSP1, NSP4, NSP7, NSP8, NSP9, NSP10, RdRp, and NSP14) and 2 accessory proteins (ORF3b and ORF9b) possessed significant predictive power for patient death, even after further adjustments for demographics, comorbidities, and common laboratory biomarkers for disease severity (all with p trend < 0.05). Additionally, IgG responses to all of these 10 non-structural/accessory proteins were also associated with the severity of disease, and differential kinetics and serum positive rate of these IgG responses were confirmed in COVID-19 patients of varying severities within 20 days after symptoms onset. The area under curves (AUCs) for these IgG responses, determined by computational cross-validations, were between 0.62 and 0.71. Conclusions: Our findings might have important implications for improving clinical management of COVID-19 patients.

Variants of HSPA1A in combination with plasma Hsp70 and anti-Hsp70 antibody levels associated with higher risk of acute coronary syndrome.

OBJECTIVES: It was the aim of our study to investigate whether polymorphisms of HSP70 have an affect on antigen and antibody levels in acute coronary syndrome (ACS) patients and normal controls, and the possible joint effect of variants and antigen and antibody levels on the risk of ACS. METHODS: Three single nucleotide polymorphisms of HSPA1A and HSPA1L were evaluated in 520 ACS patients and 520 age- and sex-matched controls. Plasma extracellular Hsp70 (eHsp70) and anti-Hsp70 antibody levels were determined using ELISA. RESULTS: Individuals with +190G/C (rs1043618) CC genotype in HSPA1A had higher levels of eHsp70 in controls and lower levels of anti-Hsp70 body in ACS, compared with +190G/C GG carriers. Significantly increased ACS risks of 2.93 and 3.53 fold were found in subjects with the +190G/C CC genotype and high eHsp70 levels or low anti-Hsp70 antibody levels, respectively. The highest risk of ACS was found in subjects with +190G/C CC genotypes, high eHsp70 and low anti-Hsp70 antibody levels compared with those in the reference group (OR = 7.57, 95% CI 3.04-18.87). CONCLUSIONS: The +190G/C polymorphism of HSPA1A may contribute to influence eHsp70 levels in controls and anti-Hsp70 antibody levels in ACS, and the +190G/C genotypes, eHsp70 and anti-Hsp70 antibody levels may have a joint effect on the risk of ACS.

Leisure-time physical activity and risk of incident cardiovascular disease in Chinese retired adults.

The optimum amounts and types of leisure-time physical activity (LTPA) for cardiovascular disease (CVD) prevention among Chinese retired adults are unclear. The prospective study enrolled 26,584 participants (mean age [SD]: 63.3 [8.4]) without baseline disease from the Dongfeng-Tongji cohort in 2013. Cox-proportional hazard models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). During a mean 5.0 (1.5) years of follow-up, 5704 incident CVD cases were documented. Compared with less than 7.5 metabolic equivalent of task-hours per week (MET-hours/week) of LTPA, participating LTPA for 22.5-37.5 MET-hours/week, which was equivalent to 3 to 5 times the world health organization (WHO) recommended minimum, was associated with a 18% (95% CI 9 to 25%) lower CVD risk; however, no significant additional benefit was gained when exceeding 37.5 MET-hours/week. Each log10 increment of MET-hours/week in square dancing and cycling was associated with 11% (95% CI 2 to 20%) and 32% (95% CI 21 to 41%), respectively, lower risk of incident CVD. In Chinese retired adults, higher LTPA levels were associated with lower CVD risk, with a benefit threshold at 3 to 5 times the recommended physical activity minimum. Encouraging participation in square dancing and cycling might gain favourable cardiovascular benefits.

Elevated heat shock protein 60 levels are associated with higher risk of coronary heart disease in Chinese.

BACKGROUND: Although heat shock protein 60 (Hsp60) is implicated in the pathogenesis of atherosclerosis, its role in coronary heart disease (CHD) is uncertain. This study explored the influence of circulating Hsp60 on CHD in a large case-control study, as well as the impact of acute myocardial infarction on Hsp60 levels in a prospective study. METHODS AND RESULTS: Plasma Hsp60 and anti-Hsp60 antibody levels were determined by immunoassay. In the case-control study (1003 patients with CHD, 1003 matched control subjects), Hsp60 levels were higher in patients with CHD and were related to CHD (OR comparing extreme quartiles=4.14, P<0.0001). This association remained after adjustment for traditional risk factors (P for trend <0.0001). Individuals having high levels of Hsp60 (greater than the median of 160.24 ng/mL) and anti-Hsp60 antibody (greater than the median of 38.42 U/mL) were at a greater risk of CHD than those with low levels (OR 2.30, P<0.0001). Stronger additive effects (OR 14.04, P<0.0001) were apparent at higher Hsp60 and anti-Hsp60 antibody levels (>1000 ng/mL and greater than the median of 38.42 U/mL, respectively). The simultaneous presence of high Hsp60 and anti-Hsp60 antibody levels, current smoking, hypertension, and diabetes were cumulatively associated with CHD. Individuals who had any 4 or more of these 5 factors had an OR of 38.61 for CHD (P<0.0001) compared with individuals who had none of these factors. For the prospective study, blood was drawn from 20 patients immediately after admission for acute myocardial infarction and 2, 3, and 7 days thereafter. Hsp60 levels were significantly higher on the day of and the day after arrival than 7 days after an acute myocardial infarction (P=0.011 and P=0.026, respectively). CONCLUSIONS: Elevated Hsp60 levels are associated with an increased risk for CHD, and Hsp60 and anti-Hsp60 antibody levels combine to increase this risk. In addition, acute myocardial infarction induces Hsp60 release.

Associations between single nucleotide polymorphisms on chromosome 9p21 and risk of coronary heart disease in Chinese Han population.

OBJECTIVE: We aimed to determine whether the single nucleotide polymorphisms (SNPs) on chromosome 9p21 were associated with coronary heart disease (CHD) in a Chinese Han population. METHODS AND RESULTS: We determined the genotypes of rs2383206 and rs2383207 on chromosome 9p21 in 1360 CHD patients and 1360 age- and sex-frequency-matched controls from an unrelated Chinese Han population. GG genotypes in rs2383207 occurred more frequently in CHD patients compared to controls, and the odds ratio (OR) was 1.52 (95% CI 1.13 to 2.04), after adjusting for conventional risk factors. In stratified analysis, the risk associated with the GG genotype of the two SNPs was stronger in subjects who were males, less than 60 years old, overweight, and smokers. The SNP rs2383207 had significant interactions with gender and smoking (P=0.018 and 0.037, respectively). The risk allele G of rs2383207 plus family history of CHD had a cumulative association with CHD (P for trend, 1.0x10(-6)); the OR for CHD was 4.59 (95% CI 2.52 to 8.37) for those with all the risk factors as compared with subjects without any of the factors. CONCLUSIONS: The SNP rs2383207 on chromosome 9p21 is significantly associated with CHD in Chinese. This SNP combined with family history has a cumulative association with CHD.

Hearing loss is associated with increased stroke risk in the Dongfeng-Tongji Cohort.

BACKGROUND AND AIMS: The evidence concerning the association between hearing loss and stroke is limited. We aimed to investigate the association of hearing loss with risk of stroke and its subtypes among the middle-aged and older Chinese population. METHODS: We included 19,238 participants aged 64.6 years from the Dongfeng-Tongji Cohort in 2013. Hearing loss was classified into normal, mild, moderate, severe or greater levels by the pure tone average at speech frequency and high frequency, respectively. We calculated the odds ratios of hearing loss and stroke by logistic regression models. RESULTS: With the increase of hearing loss level, the prevalence risk of stroke has gradually increased. Compared with normal hearing, participants having severe or greater hearing loss had a higher stroke risk of 76% and 39% at speech frequency and at high frequency, respectively. Similarly, individuals with severe or greater hearing loss had an increased risk of ischemic stroke of 69% and 52% at speech frequency and high frequency, respectively; while severe or greater hearing loss was associated with about a 2-fold risk of hemorrhagic stroke than normal hearing only at speech frequency. Stratified analysis suggested that some high cardiovascular risk participants such as male, age ≥65, exposed to occupational noise, smoker and with diabetes, hypertension or hyperlipidemia had higher risk of stroke. Furthermore, severe or greater hearing loss combined with age, diabetes, hypertension and hyperlipidemia had joint effects on stroke. CONCLUSIONS: The results have suggested a dose-response relationship between hearing loss and stroke risk in middle-aged and older adults.

Effect of Physical Activity on Hospital Service Use and Expenditures of Patients with Coronary Heart Disease: Results from Dongfeng-Tongji Cohort Study in China.

The intervention of behaviors, including physical activity (PA), has become a strategy for many hospitals dealing with patients with chronic diseases. Given the limited evidence available about PA and healthcare use with chronic diseases, this study explored the association between different levels of PA and annual hospital service use and expenditure for inpatients with coronary heart disease (CHD) in China. We analyzed PA information from the first follow-up survey (2013) of the Dongfeng-Tongji cohort study of 1460 CHD inpatients. We examined factors such as PA exercise volume and years of PA and their associations with the number of inpatient visits, number of hospital days, and inpatient costs and total medical costs. We found that the number of hospital days and the number of inpatient visits were negatively associated with intensity of PA level. Similarly, total inpatient and outpatient costs declined when the PA exercise volume levels increased. Furthermore, there were also significant associations between the number of hospital days, inpatient costs or total medical costs and levels of PA years. This study provides the first empirical evidence about the effects of the intensity and years of PA on hospital service use and expenditure of CHD in China. It suggests that the patients' PA, especially the vigorous PA, should be promoted widely to the public and patients in order to relieve the financial burden of CHD.

[Study on the association of -689C/T polymorphism in the PPARgamma2 promoter with myocardial infarction].

OBJECTIVE: To investigate the association of -689C/T polymorphism in the peroxisome proliferator-activated receptor-gamma2 (PPARgamma2) promoter with myocardial infarction (MI). METHODS: This is a case-control study, which included 194 subjects with MI and 693 subjects without MI in nondiabetic Han population in Wuhan. Polymerase chain reaction-restriction fragment length polymorphism was used to determine the -689C-->T substitution. RESULTS: The CC,CT, and TT genotype frequencies of -689C/T polymorphism were 88.1%,11.9%,and 0.0 in MI patients and 93.1%,6.6%,and 0.3% in controls, respectively (CC vs. CT+TT, P=0.025). The -689T allele was an independent risk factor for MI (OR=2.125, 95%CI: 1.206-3.744, P=0.009) after adjusting for age,sex,waist circumference,body mass index, smoking, alcohol drinking, physical activities, systolic blood pressure, diastolic blood pressure, fasting blood glucose, total cholesterol, triglyceride, level. The -689T allele carriers had significantly higher TC levels than noncarriers [(5.05+/-1.16) mmol/L vs. (4.78+/-1.05) mmol/L, P=0.004] in the total population. CONCLUSION: The PPARgamma2 promoter -689C/T polymorphism is associated with an increased risk of MI.

Direct, indirect and total bilirubin and risk of incident coronary heart disease in the Dongfeng-Tongji cohort.

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 messages 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.

Hearing loss is associated with increased CHD risk and unfavorable CHD-related biomarkers in the Dongfeng-Tongji cohort.

BACKGROUND AND AIMS: The association between hearing loss and coronary heart disease (CHD) is inconsistent. We aimed to investigate the association of hearing loss with prevalent CHD and CHD-related biomarkers among a middle aged and elderly Chinese population. METHODS: We included 14,755 Chinese aged 64.6 years from the Dongfeng-Tongji Cohort in 2013. Hearing loss was classified into normal, mild, moderate or greater levels by the pure tone average (PTA) at low frequency and high frequency, respectively. Logistic regression models were used to estimate the odds ratios (ORs) of CHD risk in relation to hearing loss. Linear regression models were used to evaluate the effect of hearing loss on CHD-related biomarkers. RESULTS: The adjusted ORs for prevalent CHD increased gradually with the increasing hearing loss levels. Compared with normal hearing, individuals having mild- and moderate or greater-hearing loss had a higher CHD risk of 19% and 20% at low frequency, and 33% and 41% at high frequency, respectively (all p for trend < 0.05). The associations were more evident among subjects who were females, overweight, exposed to occupational noise and with hyperglycemia, hypertension or dyslipidemia at low frequency, and those with hyperglycemia at high frequency. Meanwhile, moderate or greater hearing loss combined with overweight, hyperglycemia, hypertension or dyslipidemia had joint effects on CHD. In addition, the majority of CHD-related biomarkers worsened with increasing hearing loss levels. CONCLUSIONS: There may be a dose-response relationship between hearing loss and CHD prevalence, and the association could partially be explained by intermediate CHD-related biomarkers.

Associations of polymorphism of P22(phox) C242T, plasma levels of vitamin E, and smoking with coronary heart disease in China.

BACKGROUND: The C242T polymorphisms of P22(phox) and plasma vitamin E have been associated with the risk of coronary heart disease (CHD) in several studies, but the results have been inconsistent. In this study, we sought to examine potential interactions between P22(phox) genotypes, plasma vitamin E concentrations, and smoking in relation to CHD risk. METHODS: We determined C242T genotype frequency in the P22(phox) gene and plasma levels of vitamin E in 565 Chinese patients with CHD and 609 control subjects. Logistic regression was used to control for potential confounders in multivariate analyses. RESULTS: Compared with subjects with a CC genotype, subjects with a CT or TT genotype had a lower risk of CHD (multivariate-adjusted odds ratio [OR] 0.45, 95% CI 0.28-0.74, P = .001). Plasma concentrations of vitamin E were lower in case patients than in control subjects (multivariate-adjusted OR 0.65, 95% CI 0.50-0.86, P = .025). Compared with nonsmokers with a CC genotype, nonsmokers with a CT or TT genotype had a decreased risk of CHD (OR 0.25, 95% CI 0.12-0.53), but smokers with a CT or TT genotype had an increased risk (OR 2.04, 95% CI 0.74-5.61, P for interaction = .039). Smokers with a lower vitamin E concentration had a >3.0-fold greater risk of CHD than did nonsmokers with a higher vitamin E concentration (OR 3.52, 95% CI 2.36-5.24, P for interaction = .041). CONCLUSIONS: These data provide evidence that P22(phox) genotypes are significantly associated with CHD risk in a Chinese population and suggest potential interactions among smoking, P22(phox) genotypes, and vitamin E in relation to CHD risk.

Corrigendum: Green tea consumption is associated with reduced incident CHD and improved CHD-related biomarkers in the Dongfeng-Tongji cohort.

This corrects the article DOI: 10.1038/srep24353.