Prospective findings from the Dongfeng-Tongji cohort: Exposure to various metals, the expression of microRNA-4286, and the incidence of acute coronary syndrome.

Mounting evidence suggests that metal/metalloid exposure is related to the adverse health effects. Our prior investigation revealed a positive relation between the plasma level of microRNA-4286 (miR-4286) and an increased risk of developing acute coronary syndrome (ACS). However, it is a lack of studies evaluating the connection between metal/metalloid exposure and miRNA expression on ACS. In the prospective Dongfeng-Tongji cohort, we performed a nested case-control study. A total of 480 ACS and 480 controls were carefully selected based on similar age, sex, and blood collection time. Using inductively coupled plasma mass spectrometry, we assessed the plasma concentrations of 24 different metals. Quantitative real-time polymerase chain reaction was used to analyze the plasma miR-4286. We examined the relations of plasma metals with miR-4286 levels, the incidence of ACS, and the potential interactions. Using the multivariate conditional logistic regression models, we observed that the adjusted odds ratios (95% confidence intervals [CI]) for incident ACS were 1.79 (1.03, 3.12; P-trend = 0.03), 0.60 (0.41, 0.87; P-trend = 0.008), and 0.66 (0.46, 0.93; P-trend = 0.02), when comparing the extreme tertiles of aluminum, rubidium, and selenium, respectively. There was a relation between the concentration of rubidium in plasma and a decrease in the level of plasma miR-4286 (percent difference [95% CI]: -13.36% [-22.74%, -2.83%]; P-trend = 0.01). Both multiplicative (P interaction = 0.009) and additive interactions (relative excess risk due to interaction [95% CI]: 0.82 [0.59, 1.06]) were noted in our observation regarding the relationship between plasma aluminum and miR-4286 in incident ACS. The findings indicated that plasma aluminum was positively while plasma rubidium and selenium were negatively linked to an increased risk of developing ACS. Plasma aluminum exposure and plasma miR-4286 expression might synergistically affect the incident ACS risk. Controlling aluminum exposure was important for ACS prevention, especially for individuals with high expression of plasma miR-4286.

Individual and combined associations of estimated pulse wave velocity and systemic inflammation response index with risk of stroke in middle-aged and older Chinese adults: a prospective cohort study.

Background and aims: Estimated pulse wave velocity (ePWV) and systemic inflammatory response index (SIRI) have been recently investigated as a marker of arterial stiffness and a novel systemic inflammatory indicator. This study aims to examine the independent and combined association of ePWV and SIRI with incident stroke and its subtypes. Methods: Data of the Dongfeng-Tongji cohort study was analyzed for 9,154 middle-aged and older adults, who were free of cardiovascular disease and cancer and were followed up to document incident stroke. But their association with incident stroke events and its subtypes have not been well studied. Multivariable adjusted Cox regression models were used to determine the independent and combined association of ePWV and SIRI with incident stroke events. Results: Over a 7.22-year follow-up, the cohort documented 491 stroke cases (387 ischemic stroke and 104 hemorrhagic stroke). The multivariate adjusted model showed that with each one-unit increase in the level of ePWV, the corresponding hazard ratios (HRs) (95% CI) for total stroke, ischemic stroke, and hemorrhagic stroke were 1.53 (95% CI, 1.23-1.90), 1.42 (95% CI, 1.11-1.83), and 1.92 (95% CI, 1.21-3.03), respectively. Similarly, with each one-unit increase in log-transformed levels of SIRI, the corresponding HRs (95% CI) for total stroke, ischemic stroke, and hemorrhagic stroke were 1.23 (95% CI,1.04-1.47), 1.16 (95% CI, 0.96-1.41), and 1.52 (95% CI, 1.05-2.20), respectively. There appeared to be a combined effect of ePWV and SIRI on stroke; Participants with high levels of both ePWV and SIRI had a higher risk of total stroke and hemorrhagic stroke, with multiple adjusted HR of 2.43 (95% CI, 1.09-5.42). Additionally, the incorporation of ePWV in addition to traditional cardiovascular risk factors significantly improved the predictive accuracy for total stroke with C statistic increased from 0.684 (95% CI, 0.661-0.707) to 0.687 (95% CI, 0.664-0.710; x2 = 6.65; p for difference = 0.010), and (suggestively) for ischemic stroke with C statistic increased from 0.684 (95% CI, 0.659-0.71) to 0.691(95% CI, 0.666-0.717; x2 = 3.13, p for difference = 0.077), respectively. Conclusions: The presence of both high ePWV and SIRI individually, as well as together, was found to be associated with an increased incidence of stroke. The combined stroke risk assessment using these two indicators could potentially improve non-invasive assessment and treatment strategies for high-risk patients, as these indicators are easily accessible in clinical practice.

Analysis of Changes in Weight, Waist Circumference, or Both, and All-Cause Mortality in Chinese Adults.

Importance: 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. Objective: To assess the associations of changes in body weight, waist circumference, or both, combined with all-cause mortality. Design, Setting, and Participants: 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. Exposures: 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. Main Outcomes and Measures: 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. Results: 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. Conclusions and Relevance: 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.

Plasma metal concentrations and their interactions with genetic susceptibility on homocysteine levels.

Limited studies have evaluated the associations of multiple metal exposures with homocysteine (Hcy) levels, which were independent risk factor for cardiovascular disease (CVD). Furthermore, the interactions between genetic variants and plasma metals in relation to Hcy levels were largely unknown. We aimed to explore the associations of multiple plasma metals (including metalloids arsenic [As] and selenium [Se]) with Hcy levels and whether their associations were modified by genetic susceptibility. We included 2989 participants from the baseline of the Dongfeng-Tongji cohort (DFTJ cohort) and conducted a cross-sectional study to explore the associations of 17 plasma metals with serum Hcy levels. Both multi-variable linear regression model (single-metal model) and LASSO penalized regression model (multiple-metal model) were used to identify the Hcy-associated metals. The weighted genetic risk score (GRS) was calculated based on 18 established Hcy-associated genetic variants. For metals that were associated with Hcy, we further assessed the gene-metal interactions on Hcy levels. Among 17 metals, plasma molybdenum (Mo), strontium (Sr), and Zinc (Zn) were positively associated with Hcy levels, whereas Se was inversely associated with Hcy levels in both single- and multiple-metal models. We also observed that the genetic predisposition to Hcy significantly modified the association between plasma Se and serum Hcy levels (P for interaction = 0.003), while no significant gene-metal interactions were found for Mo, Sr, and Zn (all P for interactions > 0.05). These findings provide novel insight into the associations of the plasma concentrations of Mo, Se, Sr and Zn with Hcy levels and address the importance of Se as a potential upstream modifiable factor for the personalized prevention of elevated Hcy levels and CVD.

Analysis of the Temporal Distribution Characteristics of PM2.5 Concentration and Risk Evaluation of Its Inhalation Exposure.

PM2.5 poses a threat to human health. It is important to evaluate the potential risk of PM2.5 inhalation exposure when people are located in different spatiotemporal activity locations. In this study, the PM2.5 concentration was detected by the atmospheric cruise monitoring system (ACMS), a new detection technology used for city-wide PM2.5 concentration monitoring. People were divided into eight categories of five typical activity patterns, including rest (R), sedentary behavior (SB), light physical activity (LPA), moderate physical activity (MPA), and vigorous physical activity (VPA). The PM2.5 inhalation exposure risk was then estimated for these typical activities. The research results showed that the time sequence data of the ACMS had a similar tendency to change as those of the traditional air quality monitoring stations (AQMS). Although both passed the stationarity test, the relative error (RE) of the monthly average PM2.5 concentration between the ACMS and AQMS was 7.5-14%. RE was usually lower when the individual air quality index (IAQI) of PM2.5 was higher. Otherwise, RE was higher. The research results also showed that PM2.5 exposure was positively correlated with PM2.5 concentration, respiration rate, and human activity patterns. Because adults had a higher monthly average potential exposure (MAPE) than minors and that males had a higher MAPE than females. The potential exposure generated by LPA and MPA reached 50.76% of the total potential exposure (TPE). VPA brought about a 14.7% increase in the TPE. The research findings are helpful to understand the temporal distribution characteristics of PM2.5 concentrations and guide the potential risk evaluation of PM2.5 inhalation exposure.

DeNO x performance enhancement of Cu-based oxides via employing a TiO2 phase to modify LDH precursors.

CuAl-LDO, CuAl-LDO/TiO2 and CuAl-LDO/TiO2NTs catalysts were obtained from TiO2 modified LDHs precursor which were prepared by in situ assembly method. Then catalysts were evaluated in the selective catalytic reduction of NO x with NH3(NH3-SCR), and the results showed that the CuAl-LDO/TiO2NTs catalyst exhibited preferable deNO x performance (more than 80% NO x conversion and higher than 90% N2 selectivity at a temperature range of 210-330 °C) as well as good SO2 resistance. With the aid of series of characterizations such as XRD, N2 adsorption/desorption, XPS, NH3-TPD, H2-TPR, and in situ DRIFTS, it could be concluded that, doping TiO2NTs afforded the catalyst larger specific surface area, more abundant surface chemisorption oxygen species and more excellent redox performance. Meanwhile, In situ DRIFTS evidenced that CuAl-LDO/TiO2NTs catalyst has a strong adsorption capacity for the reaction gas, which is more conducive to the progress of the SCR reaction.

Alternations in the gut microbiota and metabolome with newly diagnosed unstable angina.

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 rs = -0.470, P = 0.009), a metabolite depleted in UA patients (OR = 0.26 [0.08-0.63]). These findings are informative to help understand the metabolic connection between gut microbiota and UA.

Exposure to polycyclic aromatic hydrocarbons, DNA methylation and heart rate variability among non-current smokers.

Polycyclic aromatic hydrocarbons (PAHs) exposure is associated with heart rate variability (HRV) reduction, a widely used marker of cardiovascular autonomic dysfunction. The role of DNA methylation in the relationship between PAHs exposure and decreased HRV is largely unknown. This study aims to explore epigenome-wide DNA methylation changes associated with PAHs exposure and further evaluate their associations with HRV alternations among non-current smokers. We measured 10 mono-hydroxylated PAHs (OH-PAHs) in urine and DNA methylation levels in blood leukocytes among participants from three panels of Chinese non-current smokers (152 in WHZH, 99 in SY, and 53 in COW). We conducted linear regression analyses between DNA methylation and OH-PAHs metabolites with adjustment for age, gender, body mass index, drinking, blood cell counts, and surrogate variables in each panel separately, and combined the results by using inverse-variance weighted fixed-effect meta-analysis to obtain estimates of effect size. The median value of total OH-PAHs ranged from 0.92 × 10-2 in SY panel (62.6% men) to 13.82 × 10-2 µmol/mmol creatinine in COW panel (43.4% men). The results showed that methylation levels of cg18223625 (COL20A1) and cg07805771 (SLC16A1) were significantly or marginally significantly associated with urinary 2-hydroxynaphthalene [ß(SE) = 0.431(0.074) and 0.354(0.068), FDR = 0.016 and 0.056, respectively], while methylation level of cg09235308 (PLEC1) was positively associated with urinary total OH-PAHs [ß(SE) = 0.478(0.079), FDR = 0.004]. Hypermethylations of cg18223625, cg07805771, and cg09235308 were inversely associated with HRV indices among the WHZH and COW non-current smokers. However, we did not observe significant epigenome-wide associations for the other 9 urinary OH-PAHs. These findings provide new evidence that PAHs exposure is linked to differential DNA methylation, which may help better understand the influences of PAHs exposure on HRV alternations.

Effects of Aricept on intestinal flora diversity in patients with mild Alzheimer's disease explored through high-throughput sequencing technology.

OBJECTIVE: To research the effects of Aricept on the intestinal flora in patients with mild Alzheimer's disease (AD) and explore the relationship between the improvement from Aricept on AD and the changes in intestinal flora. METHODS: One month after Aricept treatment, DNA was extracted from stool samples of patients and the quality of DNA was detected. Then, the library was constructed, quantified, pooled and the quality of the library was checked. Sequencing was conducted using the Miseq sequencer and the related results were analyzed by bioinformatics. RESULTS: The overall structure of intestinal flora in AD patients was largely changed after Aricept treatment (P<0.05), which was mainly shown as decreased abundance of Firmicutes, Proteobacteria, actinobacteria and fusobacteria, and increased abundance of Bacteroidetes. The average abundance of intestinal flora in lipid metabolism pathwa was also different before and after treatment (P<0.05). The function of target receptor molecules in the Aricept drug target network mainly targets G-protein coupled receptors; biological processes in energy metabolism; and biological pathways mostly target proteoglycans. CONCLUSION: The occurrence and progression of AD are closely related to abnormal changes in intestinal flora structure. Bile acids may improve the symptoms of mild AD by changing the intestinal flora through lipid energy metabolism. In other words, Bile acids regulate the activity of the host nervous system through intestinal flora regulation. Intestinal flora maintains the homeostasis of bile acid and further affects the physiological and pathological processes of the host. The analysis of AD related flora structure pattern helps to understand the molecular pathological basis of AD and provides theoretical basis for the development and design of innovative drugs for AD.

Prospective Study on Plasma MicroRNA-4286 and Incident Acute Coronary Syndrome.

Background Mounting evidence suggests that circulating microRNAs (miRNAs) are critical indicators of cardiovascular disease. However, prospective studies linking circulating miRNAs to incident acute coronary syndrome (ACS) are limited, and the underlying effect of associated miRNA on incident ACS remains unknown. Methods and Results Based on a 2-stage prospective nested case-control design within the Dongfeng-Tongji cohort, we profiled plasma miRNAs from 23 pairs of incident ACS cases and controls by microarray and validated the candidate miRNAs in 572 incident ACS case-control pairs using quantitative real-time polymerase chain reaction. We observed that plasma miR-4286 was associated with higher risk of ACS (adjusted odds ratio according to an interquartile range increase, 1.26 [95% CI, 1.07-1.48]). Further association analysis revealed that triglyceride was positively associated with plasma miR-4286, and an interquartile range increase in triglyceride was associated with an 11.04% (95% CI, 3.77%-18.83%) increase in plasma miR-4286. In addition, the Mendelian randomization analysis suggested a potential causal effect of triglyceride on plasma miR-4286 (ß coefficients: 0.27 [95% CI, 0.01-0.53] and 0.27 [95% CI, 0.07-0.47] separately by inverse variance-weighted and Mendelian randomization-pleiotropy residual sum and outlier tests). Moreover, the causal mediation analysis indicated that plasma miR-4286 explained 5.5% (95% CI, 0.7%-17.0%) of the association of triglyceride with incident ACS. Conclusions Higher level of plasma miR-4286 was associated with an increased risk of ACS. The upregulated miR-4286 in plasma can be attributed to higher triglyceride level and may mediate the effect of triglyceride on incident ACS.

Systemic immune-inflammation index and incident cardiovascular diseases among middle-aged and elderly Chinese adults: The Dongfeng-Tongji cohort study.

BACKGROUND AND AIMS: Systemic immune-inflammation index (SII) has been recently investigated as a novel inflammatory and prognostic marker. SII may be used as an indicator reflecting the progressive inflammatory process in atherosclerosis, although its link to incident cardiovascular disease (CVD) has not been examined in previous studies. This study aims to prospectively assess the association of SII with incident CVD and its main subtypes in Chinese adults. METHODS: Using data from the Dongfeng-Tongji cohort study, 13,929 middle-aged and older adults with a mean age of 62.56 years (range 35-91 years), who were free of CVD and cancer, were included for analysis. The baseline study was conducted in Shiyan city, Hubei province from 2008 to 2009. The SII was calculated as platelet count (/L) × neutrophil count (/L)/lymphocyte count (/L). Cox regression models were used to examine the associations of SII with incident CVD, including stroke and coronary heart disease (CHD). RESULTS: Over a median 8.28 years (maximum 8.98 years) of follow-up, 3386 total CVD cases, including 801 stroke cases and 2585 total CHD cases, were identified. In multivariable Cox regression analyses, higher levels of log-transformed SII were significantly associated with total stroke (HR 1.224, 95% CI 1.065-1.407) and ischemic stroke (HR 1.234, 95% CI 1.055-1.442). For those participants with the highest quartiles of SII versus the lowest quartiles of SII, the HRs were 1.358 (95% CI 1.112-1.658) for total stroke, 1.302 (95% CI 1.041-1.629) for ischemic stroke, and 1.600 (95% CI 1.029-2.490) for hemorrhagic stroke. CONCLUSIONS: SII may serve as a useful marker to elucidate the role of the interaction of thrombocytosis, inflammation, and immunity in the development of cerebrovascular diseases in the middle-aged and elderly population.

Profile of copper-associated DNA methylation and its association with incident acute coronary syndrome.

BACKGROUND: Acute coronary syndrome (ACS) is a cardiac emergency with high mortality. Exposure to high copper (Cu) concentration has been linked to ACS. However, whether DNA methylation contributes to the association between Cu and ACS is unclear. METHODS: We measured methylation level at > 485,000 cytosine-phosphoguanine sites (CpGs) of blood leukocytes using Human Methylation 450 Bead Chip and conducted a genome-wide meta-analysis of plasma Cu in a total of 1243 Chinese individuals. For plasma Cu-related CpGs, we evaluated their associations with the expression of nearby genes as well as major cardiovascular risk factors. Furthermore, we examined their longitudinal associations with incident ACS in the nested case-control study. RESULTS: We identified four novel Cu-associated CpGs (cg20995564, cg18608055, cg26470501 and cg05825244) within a 5% false discovery rate (FDR). DNA methylation level of cg18608055, cg26470501, and cg05825244 also showed significant correlations with expressions of SBNO2, BCL3, and EBF4 gene, respectively. Higher DNA methylation level at cg05825244 locus was associated with lower high-density lipoprotein cholesterol level and higher C-reactive protein level. Furthermore, we demonstrated that higher cg05825244 methylation level was associated with increased risk of ACS (odds ratio [OR], 1.23; 95% CI 1.02-1.48; P = 0.03). CONCLUSIONS: We identified novel DNA methylation alterations associated with plasma Cu in Chinese populations and linked these loci to risk of ACS, providing new insights into the regulation of gene expression by Cu-related DNA methylation and suggesting a role for DNA methylation in the association between copper and ACS.

Circulating folate concentrations and risk of coronary artery disease: a prospective cohort study in Chinese adults and a Mendelian randomization analysis.

BACKGROUND: The association between circulating folate concentrations and risk of coronary artery disease (CAD) has been evaluated in Western populations with inconsistent results; however, the observational and causal associations in Chinese populations with relatively low folate concentrations remain unclear. OBJECTIVES: We aimed to examine the association of circulating folate concentrations with incident CAD in Chinese adults, and further evaluated the causal relation using Mendelian randomization (MR) analysis. METHODS: We measured baseline serum folate in 1605 incident CAD cases and 1605 age- and sex-matched controls nested within the Dongfeng-Tongji (DFTJ) cohort, which recruited 27,009 individuals with a mean age of 63.6 y in 2008-2010 and followed up until the end of 2013 (mean: 4.4 y). We quantified the observational association between folate and incident CAD using conditional logistic regression models. A 2-sample MR analysis was performed using summary statistics obtained for genetic variants identified from a genome-wide association study (GWAS) of circulating folate concentrations in participants of European ancestry (n = 37,341) and from the CardiogramplusC4D 1000 genomes-based GWAS meta-analysis (n = 184,305). We also conducted 1-sample MR among 1545 incident CAD cases and 1444 controls with genotyping data in the DFTJ cohort. RESULTS: In the DFTJ cohort, higher serum folate concentrations were associated with a lower risk of CAD: the OR (95% CI) across sex-specific quartiles of folate (from lowest to highest concentrations) was 1.00 (reference), 0.78 (0.63, 0.97), 0.77 (0.61, 0.97), and 0.75 (0.60, 0.95), respectively (P-trend = 0.01). In the MR analysis, the OR of CAD per SD increase in genetically predicted serum folate was 0.99 (0.82, 1.20) and 0.88 (0.59, 1.32) for European and Chinese populations, respectively. CONCLUSIONS: We found an inverse association between circulating folate concentrations and incident CAD among Chinese populations. However, we confirmed that there was no genetic evidence to support the causal relation in both European and Chinese populations.

Multiple plasma metals, genetic risk and serum C-reactive protein: A metal-metal and gene-metal interaction study.

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 < 0.001), whereas selenium was negatively associated with serum CRP (FDR = 0.01). Moreover, selenium and zinc attenuated the positive association between high plasma copper and CRP (P for interaction < 0.001). Participants with a higher GRS had a higher CRP level, with the increase in ln-transformed CRP per increment of 5 risk alleles were 0.64 for weighted GRS, and 0.54 for unweighted GRS (both P < 0.001). Furthermore, the genetic association with CRP was modified by copper concentration (P for interaction < 0.001). CONCLUSIONS: Our results suggest that serum CRP is positively associated with plasma concentration of copper, and inversely associated with selenium. Plasma zinc, selenium and CRP genetic predisposition would modify the associations between plasma copper and serum CRP.

Sleep duration, midday napping, and sleep quality and incident stroke: The Dongfeng-Tongji cohort.

OBJECTIVE: To investigate the associations of sleep duration, midday napping, sleep quality, and change in sleep duration with risk of incident stroke and stroke subtypes. METHODS: Among 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. RESULTS: Compared with sleeping 7 to <8 hours/night, those reporting longer sleep duration (≥9 hours/night) had a greater risk of total stroke (hazard ratio [HR] 1.23; 95% confidence interval [CI] 1.07-1.41), while shorter sleep (<6 hours/night) had no significant effect on stroke risk. The HR (95% CI) of total stroke was 1.25 (1.03-1.53) for midday napping >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. CONCLUSIONS: Long 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.

Maternal Body Mass Index and Risk of Congenital Heart Defects in Infants: A Dose-Response Meta-Analysis.

OBJECTIVE: The exact shape of the dose-response relationship between maternal body mass index (BMI) and the risk of congenital heart defects (CHDs) in infants has not been clearly defined yet. This study aims to further clarify the relationship between maternal obesity and the risk of CHDs in infants by an overall and dose-response meta-analysis. METHODS: PubMed, Embase, and Web of Science databases were searched to identify all related studies. The studies were limited to human cohort or case-control studies in English language. Random-effect models and dose-response meta-analysis were used to synthesize the results. Heterogeneity, subgroup analysis, sensitivity analysis, and publication bias were also assessed. RESULTS: Nineteen studies with 2,416,546 participants were included in our meta-analysis. Compared with the mothers with normal weight, the pooled relative risks (RRs) of infants with CHDs were 1.08 (95% CI=1.03-1.13) in overweight and 1.23 (95% CI=1.17-1.29) in obese mothers. According to the findings from the linear meta-analysis, we observed an increased risk of infants with CHDs (RR=1.07, 95% CI=1.06-1.08) for each 5 kg/m2 increase in maternal BMI. A nonlinear relationship between maternal BMI and risk of infants with CHDs was also found (p=0.012). CONCLUSION: The results from our meta-analysis indicate that increased maternal BMI is related to increased risk of CHDs in infants.

Body Mass Index and the Risk of Rheumatoid Arthritis: An Updated Dose-Response Meta-Analysis.

BACKGROUND: Extensive studies have been carried out to investigate the association between obesity and the risk of rheumatoid arthritis (RA); however, the results of the current reported original studies remain inconsistent. This study aimed to clarify the relationship between body mass index and rheumatoid arthritis by conducting an updated overall and dose-response meta-analysis. METHODS: The relevant literature was searched using the PubMed and Embase databases (through 20 September 2018) to identify all eligible published studies. Random-effect models and dose-response meta-analyses were used to estimate the pooled risk ratio (RR) with a 95% confidence interval (CI). Subgroup analyses were also conducted based on the characteristics of the participants. Sensitivity analyses and publication bias tests were also performed to explore potential heterogeneity and bias in the meta-analysis. RESULTS: Sixteen studies that included a total of 406,584 participants were included in the meta-analysis. Compared to participants with normal weight, the pooled RRs of rheumatoid arthritis were 1.12 (95% CI, 1.04-1.20) in overweight and 1.23 (95% CI, 1.09-1.39) in obese participants. There was evidence of a nonlinear relationship between body mass index (BMI) and RA (P for nonlinearity less than 0.001 in the overall meta-analysis, P for nonlinearity=0.025 in the case-control studies, P for nonlinearity=0.0029 in the cohort studies). No significant heterogeneity was found among studies (I 2=10.9% for overweight and I 2=45.5% for obesity). CONCLUSION: The overall and dose-response meta-analysis showed that increased BMI was associated with an increased risk for rheumatoid arthritis, which might present a prevention strategy for the prevention or control of rheumatoid arthritis. The nonlinear relationship between BMI and RA might present a personal prevention strategy for RA.

Determination of the energy contents and nutrient digestibility of corn, waxy corn and steam-flaked corn fed to growing pigs.

Objective: The research was conducted to determine the DE and ME contents as well as the apparent total tract digestibility (ATTD) of nutrients in corn, waxy corn and steam-flaked corn fed to growing pigs. Methods: Eighteen growing pigs with initial body weight of 15.42 ± 1.41 kg were randomly allotted to three diets including a corn diet, a waxy corn diet and a steam-flaked corn diet in a completely randomized design. Each treatment contained six replicates. The experiment lasted for 12 days, which comprised 7-d adaptation to diets followed by a 5-d total collection of feces and urine. The energy contents and the nutrient digestibility in three ingredients were calculated using direct method. Results: Compared to normal corn, both the amylose and dietary fiber contents in waxy corn were numerically lower, but the starch gelatinization degree was numerically greater. Moreover, the DE and ME contents as well as the ATTD of NDF and ADF in waxy corn were significantly greater (p < 0.05) than those in normal corn when fed to growing pigs. Furthermore, the steam-flaked corn had greater (p < 0.05) DE and ME contents, and ATTD of ether extract (EE) and ADF compared to normal corn. Conclusion: Both variety and processing procedure have influence on chemical compositions, energy contents and nutrient digestibility of corn. The waxy corn and steam-flaked corn had greater starch gelatinization degree and DE and ME contents compared to normal corn when fed to growing pigs.

A multi-stage association study of plasma cytokines identifies osteopontin as a biomarker for acute coronary syndrome risk and severity.

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.

Ideal cardiovascular health metrics and the risk of non-alcoholic fatty liver disease: A cross-sectional study in northern China.

BACKGROUND AND PURPOSE: The components of ideal cardiovascular health (CVH) metrics have been shown to be associated with non-alcoholic fatty liver disease (NAFLD). The present study aimed to determine the association between ideal CVH metrics and NAFLD. METHODS: A total of 10,511 participants (47.26% men) aged 18 to 92 years were selected from the Jidong and Kailuan communities. Ideal CVH was based on 7 ideal CVH metrics: smoking, body mass index (BMI), physical activity, diet, total cholesterol, blood pressure and fasting blood glucose. NAFLD was determined by abdominal ultrasonography. All participants underwent questionnaire assessments and clinical and laboratory examinations. Logistic regression models were used to analyse the relationship of CVH metrics and the number of ideal CVH metrics with NAFLD. RESULTS: The prevalence rates of NAFLD by CVH summary score quartiles were 64.38% (2,015/3,130), 50.16% (786/1,567), 33.28% (1,194/3,588) and 20.89% (465/2,226). Participants in the highest quartile showed a lower odds ratio (OR) than those in the lowest quartile (fully adjusted OR: 0.17, 95% CI: 0.17-0.20, P < 0.001). Similar results were observed in subjects stratified by sex and age (45 years). The ORs were progressively decreased with an increased number of ideal CVH metrics (all P < 0.001). CONCLUSIONS: NAFLD was significantly associated with both the summary score of CVH metrics and the number of ideal CVH metrics. The combined evaluation of ideal CVH may contribute to the prevention of NAFLD.