Polycyclic aromatic hydrocarbons exposure and arterial stiffness-related plasma miRNAs: A panel study.

The underlying mechanisms between polycyclic aromatic hydrocarbons (PAHs) exposure and arterial stiffness are poorly understood. We carried out a panel study involving three repeated surveys to examine the associations of individual and mixture of PAHs exposure with arterial stiffness-related miRNAs among 123 community adults. In linear mixed-effect (LME) models, we found that urinary 9-hydroxyfluorene (9-OHFlu), 2-hydroxyphenanthrene (2-OHPh), 9-hydroxyphenanthrene (9-OHPh) at lag 0 day were positively linked to miR-146a and/or miR-222. The Bayesian kernel machine regression (BKMR) analyses revealed positive overall associations of PAHs mixture at lag 0 day with miR-146a and miR-222, and urinary 9-OHFlu contributed the most. In addition, an inter-quartile range (IQR) increase in urinary 9-OHFlu at lag 0 day was associated with elevated miR-146a and miR-222 by 0.16 (95% CI: 0.02, 0.30) to 0.34 (95% CI: 0.13, 0.54). Accordingly, exposure to PAHs, especially 9-OHFlu at lag 0 day, was related to elevated arterial stiffness-related plasma miRNAs.

Polygenic Risk Score Modifies the Association of HbA1c With Hearing Loss in Middle-Aged and Older Chinese Individuals: The Dongfeng-Tongji Cohort.

OBJECTIVE: Evidence regarding the modifying effect of the polygenic risk score (PRS) on the associations between glycemic traits and hearing loss (HL) was lacking. We aimed to examine whether these associations can be influenced by genetic susceptibility. RESEARCH DESIGN AND METHODS: This cross-sectional study included 13,275 participants aged 64.9 years from the Dongfeng-Tongji cohort. HL was defined according to a pure tone average >25 dB in the better ear and further classified by severity. Prediabetes and type 2 diabetes (T2D) were defined based on the 2013 criteria from the American Diabetes Association. A PRS was derived from 37 single nucleotide polymorphisms associated with HL. Multivariable logistic regression models were fitted to estimate the associations of PRS and glycemic traits with HL and its severity. RESULTS: Elevated fasting plasma glucose (FPG), glycosylated hemoglobin (HbA1c), and T2D were positively associated with higher HL risks and its severity, with odds ratios (ORs) ranging from 1.04 (95% CI 1.00, 1.08) to 1.25 (95% CI 1.06, 1.46). We also found significant interaction between HbA1c and PRS on risks of overall HL and its severity (P for multiplicative interaction <0.05), and the effects of HbA1c on HL risks were significant only in the group with high PRS. Additionally, compared with normoglycemia in the group with low PRS, T2D was associated with an OR of up to 2.00 and 2.40 for overall HL and moderate to severe HL, respectively, in the group with high PRS (P for additive interaction <0.05). CONCLUSIONS: PRS modifies the association of HbA1c with HL prevalence among middle-aged and older Chinese individuals.

Long-term night shift work, genetic predisposition, and risk of incident asthma: a prospective cohort study.

BACKGROUND: Evidence about a potential link between current and lifetime night shift work and risk of incident asthma is insufficient. AIM: To investigate the association of current and lifetime night shift work with risk of incident asthma, and the modified effect of genetic susceptibility on this association. DESIGN AND METHODS: We included 253,773 individuals with complete night shift work information in the UK biobank. We calculated the standard polygenetic risk score (PRS) for asthma. The Cox proportional hazard models were conducted to estimate hazard ratios (HRs) and 95% CIs. RESULTS: After multivariable adjustments, we found that current night shift work was associated with an increased risk of incident asthma in a dose-response fashion (P for trend<0.001). Compared with day workers, those working usual/permanent night shifts had a 17% (95% CI: 1.04-1.33) higher risk of asthma incidence. In addition, we observed significant dose-dependent relationships of longer lifetime duration or frequency of night shift work with elevated risk of asthma incidence (all P for trend<0.05). Compared with never night shift workers, those with a duration (≥5 years) or frequency (≥8 nights/month) of night shift work exhibited a 20% (95% CI: 1.03-1.39) or 22% (95% CI: 1.03-1.44) higher risk of incident asthma, respectively. Moreover, the elevated risk of incident asthma related to current and lifetime night shift work exposure was strengthened by high PRS, although no significant shift work-PRS interactions were detected. CONCLUSION: Both current and lifetime night shift work may increase the risk of incident asthma, regardless of genetic predisposition to asthma.

Physical activity modified association of urinary metals mixture and fasting blood glucose in children: From two panel studies.

There is unclear evidence available on the associations between multiple metals and fasting blood glucose (FBG) in children, and whether they could be beneficial from physical activity. We included 283 children aged 4-12 years from two panel studies with 4-consecutive morning urinary 13 essential metals and 10 non-essential metals repeated across 3 seasons. We employed multiple informant model, linear mixed-effect model, and quantile g-computation to evaluate associations of single metal and their mixture with FBG and interactions with extra-school activity. The results showed that positive relations of multiple essential metals (aluminum, chromium, copper, iron, molybdenum (Mo), nickel, selenium (Se), strontium, zinc) and non-essential metals (arsenic (As), cadmium (Cd), rubidium, titanium (Ti), thallium) with FBG were the strongest at lag 0 (the health examination day), especially in overweight & obesity children (FDR <0.05). The strongest effect presented 1-fold increment in As was related to FBG increased 1.66% (95%CI: 0.84%, 2.48%) in overweight & obesity children. Notably, modification of extra-school activity showed significant, and the effects of multiple metals on FBG were attenuated in children taking total extra-school activity ≥1 h/day, and only one type of which, low or moderate & high intensity extra-school activity reached 20 min/day (Pint <0.05). For instance, each 1-fold increased As was associated with 1.41% increased FBG in overall children taking total extra-school activity <1 h/day, while that of 0.13% in those ≥1 h/day. Meanwhile, mixture of all, essential and non-essential metals were associated with increased FBG, a trend that decreased and became nonsignificant in children having certain extra-school activity, which were dominated by Mo, Se, Ti, Cd. And such relations were substantially beneficial from extra-school activity in overweight & obesity children. Accordingly, multiple essential and non-essential metals, both individual and in mixture, were positively related to FBG in children, which might be attenuated by regular physical activity.

Associations between long-term night shift work and incidence of chronic obstructive pulmonary disease: a prospective cohort study of 277,059 UK Biobank participants.

BACKGROUND: Little is known about the effects of night shifts and their interactions with genetic factors on chronic obstructive pulmonary disease (COPD). In this study, we aim to investigate relationships between long-term night shift work exposure and COPD risk, and assess modification effects of genetic predisposition. METHODS: A total of 277,059 subjects who were in paid employment or self-employed were included in the UK Biobank. Information on current and lifetime employment was obtained, and a weighted COPD-specific genetic risk score (GRS) was constructed. We used Cox proportional hazard models to investigate associations between night shift work and COPD risk, and their interaction with COPD-specific GRS. RESULTS: The cohort study included 277,059 participants (133,063 men [48.03%]; mean [SD] age, 52.71 [7.08] years). During a median follow-up of 12.87 years, we documented 6558 incidents of COPD. From day work, irregular night shifts to regular night shifts, there was an increased trend in COPD incidence (P for trend < 0.001). Compared with day workers, the hazard ratio (HR) and 95% confidence interval (CI) of COPD was 1.28 (1.20, 1.37) for subjects with rarely/sometimes night shifts and 1.49 (1.35, 1.66) for those with permanent night shifts. Besides, the longer durations (especially in subjects with night shifts ≥ 10 years) and increasing monthly frequency of night shifts (in workers with > 8 nights/month) were associated with a higher COPD risk. Additionally, there was an additive interaction between night shifts and genetic susceptibility on the COPD risk. Subjects with permanent night shifts and high genetic risk had the highest risk of COPD (HR: 1.90 [95% CI: 1.63, 2.22]), with day workers with low genetic risk as a reference. CONCLUSIONS: Long-term night shift exposure is associated with a higher risk of COPD. Our findings suggest that decreasing the frequency and duration of night shifts may offer a promising approach to mitigating respiratory disease incidence in night shift workers, particularly in light of individual susceptibility.

Exploring the relationship between urinary phthalate metabolites and Crohn's disease via oxidative stress, and the potential moderating role of gut microbiota: A conditional mediation model.

OBJECTIVE: Interactions between phthalic acid esters (PAEs) exposure and Crohn's disease (CD) were unknown. This study aims to examine the association between exposure to PAEs and CD activity and to explore the roles of oxidative stress and microbiota. METHODS: A cross-sectional study with 127 CD patients was conducted. The disease activity was evaluated based on symptoms (Harvey-Bradshaw index, HBI), endoscopy findings (Simple Endoscopic Score for CD, SES-CD), and computed tomography enterography (CTE-scores). Ten urinary PAEs metabolites (mPAEs), two urinary oxidative stress biomarkers, including 8-hydroxydeoxyguanosine (8-OHdG) and 8-iso-prostaglandin-F2α (8-iso-PGF2α), as well as 16S rRNA sequencing of stool samples were determined. Multiple linear regression models and Hayes's PROCESS macro for SPSS were used to evaluate the interplays between urinary PAEs metabolites, CD activities, oxidative stress, and microbiota diversity. RESULTS: There were positive associations between most mPAEs and HBI. Oxidative stress mediated 20.69-89.29% of the indirect associations between low molecular weight (LMW) mPAEs and HBI, while the majority of the high molecular weight (HMW) mPAEs were directly associated with HBI. In addition, microbiota diversity moderated the indirect associations of LMW mPAEs on HBI. CONCLUSIONS: PAEs exposure was related to CD activity, and the association could be mediated by oxidative stress and reversed or alleviated by rich gut microbiota.

Bedtime, sleep duration, and sleep quality and all-cause mortality in middle-aged and older Chinese adults: The Dongfeng-Tongji cohort study.

OBJECTIVE: This study aims to investigate the associations of bedtime and its combination with sleep duration and sleep quality with all-cause mortality. METHODS: We conducted a prospective cohort study using data collected from 2008 to 2018 in the Dongfeng-Tongji cohort. Among 40,097 participants aged 62.1 on average at baseline, we applied Cox regression models to assess hazard ratios and 95% confidence intervals for mortality risk. RESULTS: During a mean follow-up of 8.2years, 4345 deaths were documented. U-shaped associations of bedtime and sleep duration with all-cause mortality were observed. Compared with bedtime between 10:01 PM and 11:00 PM, the hazard ratio (95% confidence interval) for all-cause mortality was 1.34 (1.20-1.49) for ≤9:00 PM, 1.18 (1.09-1.27) for 9:01-10:00 PM, and 1.50 (1.13-2.00) for >12:00 AM, respectively. Participants with sleep duration of <6, 6-<7, 8-<9, and ≥9 h/night had a respective 39%, 21%, 11%, and 25% higher all-cause mortality risk than those sleeping 7-<8 h/night. Additionally, participants with a healthy sleep score of 3, characterized as proper bedtime (10:01 PM-12:00 AM), moderate sleep duration (7-<8h/night), and good/fair sleep quality, had a significantly 36% (hazard ratio, 0.64; 95% confidence interval, 0.56-0.74) lower all-cause mortality risk than those with a score of 0. CONCLUSIONS: Individuals with early or late bedtimes and short or long sleep duration were at higher all-cause mortality risks. Having healthy sleep habits may significantly reduce death risk.

Short-term exposure to multiple metals mixture and mitochondrial DNA copy number among children: A panel study.

BACKGROUND: Little is known regarding the individual and overall associations of short-term co-exposure to metals mixture with mitochondrial DNA copy number (mtDNAcn) among healthy children. METHODS: We conducted a panel study across three seasons among 144 children aged 4 to 12 years in Guangzhou. For each season, we collected the first-morning urine for four consecutive days and fasting blood on the 4th day to detect 23 urinary metals and blood leukocyte mtDNAcn, respectively. Linear mixed-effect (LME) models and multiple informant models were used to examine the relations of individual metals with mtDNAcn over different lag days, and the least absolute shrinkage and selection operator (LASSO) regression was applied to determine the most important metal. We further employed weighted quantile sum (WQS) regression to investigate the overall association of metals mixture with mtDNAcn. RESULTS: Nickel (Ni), manganese (Mn) and antimony (Sb) were independently associated with mtDNAcn in a linear dose-response manner. Each 1-fold increase in Ni at lag 0 day, Mn and Sb at lag 2 day was associated with respective decrements of 8.74 %, 6.93 % and 3.98 % in mtDNAcn in multi-metal LME models. LASSO regression also selected Ni, Mn and Sb as the most significant metals at the corresponding lag day. WQS regression showed overall inverse associations between metals mixture and mtDNAcn both at lag 0 and lag 2 day, with mtDNAcn decreased by 2.75 % and 3.14 % in response to a quartile increase in the WQS index. Additionally, the associations of Ni and Mn with decreased mtDNAcn were stronger among children younger than 7 years, girls and those having less vegetables and fruit intake. CONCLUSION: We found an overall association between metals mixture and decreased mtDNAcn among healthy children, in which Ni, Mn and Sb were the major contributors. Younger children, girls and those with less vegetables and fruit intake were more susceptible.

Hearing loss increases all-cause and cardiovascular mortality in middle-aged and older Chinese adults: the Dongfeng-Tongji Cohort Study.

We aimed to investigate the association between hearing loss and all-cause and cardiovascular disease (CVD) mortality, and whether the relationship could be modified by chronic conditions in middle-aged and older Chinese adults. We selected 18,625 participants who underwent audiometry in 2013 from the Dongfeng-Tongji Cohort conducted in China, and followed them until December 2018. Hearing loss was grouped as normal, mild, and moderate or severe by pure-tone hearing threshold at speech (0.5, 1, and 2 kHz) and high frequency (4 and 8 kHz). We applied Cox regression models to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for all-cause and CVD mortality. Among the 18,625 participants, the mean age was 64.6 (range: 36.7-93.0) years, and 56.2% were women. A total of 1185 died, with 420 CVD deaths during a mean follow-up period of 5.5 years. The adjusted HR for all-cause and CVD mortality increased gradually with the increasing hearing threshold (All p for trend < 0.05). Compared to participants with normal hearing at speech frequency, the adjusted HRs (95% CIs) of moderate or severe hearing loss were 1.42 (1.21-1.67), 1.44 (1.10-1.89), and 1.92 (1.21-3.04) for all-cause, CVD, and stroke mortality, respectively. While moderate or severe hearing loss at high frequency was only related to an increased risk of all-cause mortality (HR, 1.60; 95% CI, 1.18-2.17). The associations were generally consistent across subgroups (All p for interaction > 0.05). Additionally, individuals with a combination of moderate or severe hearing loss and occupational noise exposure, diabetes, or hypertension had higher risk of all-cause or CVD mortality, ranging from 1.45 to 2.78. In conclusion, hearing loss was independently associated with an increased risk of all-cause and CVD mortality, in a dose-response manner. Meanwhile, hearing loss and diabetes or hypertension could jointly increase the risk of all-cause and CVD mortality.

Urinary phthalate metabolites and heart rate variability: A panel study.

Phthalates exposure is linked with cardiovascular disease. Decreased heart rate variability (HRV) is an early indicator of cardiac autonomic imbalance. We conducted a longitudinal panel study in 127 Chinese adults with 3 repeated visits to explore the associations of individual and mixtures of phthalates exposure with HRV. We quantified 10 urinary phthalate metabolites by gas chromatograph-tandem mass spectrometer (GC-MS/MS) and 6 HRV indices by 3-channel digital Holter monitors. Linear mixed-effect (LME) models and Bayesian kernel machine regression (BKMR) models were separately implemented to evaluate the associations. After multivariate adjustments, we found that urinary mono-ethyl phthalate (MEP), mono-iso-butyl phthalate (MiBP), and mono-n-butyl phthalate (MBP) at lag 0 day were inversely associated with low-frequency power (LF) or total power (TP) (all P-FDR <0.05). In mixture analysis, we observed negative overall associations of phthalate mixtures at lag 0 day with LF or TP, and MiBP was the major contributor. Moreover, stratified analysis suggested that the inverse relationships of MiBP at lag 0 day with LF and TP were more prominent in subjects aged >50 years (all Pinteraction < 0.01). Our findings revealed that exposure to individual and mixtures of phthalates, especially MiBP, were related to decreased HRV.

Associations of Urinary Phthalate Metabolites with Thyroid Function and the Mediated Role of Cytokines: A Panel Study of Healthy Children.

Evidence on joint association of a phthalate mixture with thyroid function among children and its underlying mechanism is largely unknown. We aimed to explore the associations of 10 urinary phthalate metabolites (mPAEs), either as individuals or as a mixture, with thyroid function indicators [free thyroxine, free triiodothyronine (FT3), and thyroid-stimulating hormone (TSH)] in 144 children aged 4-12 years with up to 3 repeated visits across 3 seasons. Significant and positive associations were observed for mono-(2-ethylhexyl) phthalate (MEHP), mono-iso-butyl phthalate (MiBP), and mono-n-butyl phthalate (MnBP) with TSH, as well as monobenzyl phthalate (MBzP) with FT3 in dose-response manners. The relationship between MEHP and TSH remained robust in multiple-phthalate models. Bayesian kernel machine regression (BKMR) models revealed overall linear associations of the 10 mPAE mixture with higher TSH and FT3 levels, and MEHP and MBzP were major contributors. Meanwhile, MEHP, MiBP, and MnBP were linked to the elevation of multiple cytokines including CCL 27, CCL3, CXCL1, and IL-16. Among them, IL-16 mediated the relationships of MEHP and MiBP with TSH, and the mediated proportions were 24.16% and 24.27%, respectively. Our findings suggested that mPAEs dominated by MEHP were dose-responsively associated with elevated TSH among healthy children and mediated by IL-16.

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.

Associations of urinary polycyclic aromatic hydrocarbon metabolites and blood pressure with the mediating role of cytokines: A panel study among children.

Little was known regarding the relations of polycyclic aromatic hydrocarbon (PAH) mixture with children's blood pressure (BP) and its potential mechanism. We conducted a panel study with up to 3 visits across 3 seasons in 2017-2018 among 103 children aged 4-13 years. Urinary PAH metabolites (OH-PAHs) were measured by gas chromatograph-tandem triple quadrupole mass spectrometer, and serum cytokines were detected by Bio-Rad 48-Plex Screening Panel. We employed linear mixed-effects models to assess the relations of each urinary OH-PAH with BP, least absolute shrinkage and selection operator (LASSO), and weighted quantile sum (WQS) regression to evaluate associations of OH-PAHs mixture with BP, and mediation analyses for the role of serum cytokines. We found the consistently positive associations of 1-hydroxynaphthalene and 9-hydroxyphenanthrene (9-OHPh) with systolic BP (SBP), 4-OHPh, and 9-OHPh with diastolic BP (DBP) and mean arterial pressure (MAP) in a dose-responsive manner. For instance, each 1-fold increment of 9-OHPh was related with increase of 0.92% (95% confidence interval (CI): 0.25%, 1.60%) in SBP, 1.32% (95%CI: 0.25%, 2.39%) in DBP, and 1.15% (95%CI: 0.40%, 1.88%) in MAP. Meanwhile, based on LASSO and WQS regression, OH-PAHs mixture was linked with increased DBP and MAP, to which 9-OHPh and 4-OHPh were the major contributors. Such relationships were modified by passive smoking status and 3-4 times stronger in passive smokers than non-passive smokers. A 1-fold increase in 9-OHPh was associated with an elevation of 3.51% in SBP among passive smokers while that of 0.55% in SBP among non-passive smokers. Furthermore, 4-OHPh and 9-OHPh were related to multiple cytokines elevation, of which platelet-derived growth factor (PDGF) mediated 9.99% and 12.57% in 4-OHPh-related DBP and MAP elevation, respectively. Accordingly, urinary OH-PAHs dominated by 9-OHPh and 4-OHPh were dose-responsively associated with elevated BP whereby a mechanism partly involving PDGF among children.

The association of co-exposure to polycyclic aromatic hydrocarbon and phthalates with blood cell-based inflammatory biomarkers in children: A panel study.

The association of co-exposure to polycyclic aromatic hydrocarbons (PAHs) and phthalates (PAEs) with blood cell-based inflammatory biomarkers is largely unknown. We conducted a panel study of 144 children aged 4-12 years, with up to 3 repeated visits across 3 seasons. For each visit, we collected the first-morning urine for 4 consecutive days and fasting blood on the day of physical examination. We developed a gas chromatography/tandem mass spectrometry method to detect the metabolites of 10 PAHs (OH-PAHs) and 10 PAEs (mPAEs) in urine samples. We employed linear mixed-effects models to evaluate the individual associations of each OH-PAH and mPAE with blood cell-based inflammatory biomarkers over different lag times. Bayesian kernel machine regression (BKMR) and quantile g-computation were used to evaluate the overall associations of OH-PAHs and mPAEs mixtures with blood cell-based inflammatory biomarkers. After multiple adjustments, we found positive associations of summed hydroxylphenanthrene (∑OHPHE), summed OH-PAHs, and mono-n-butyl phthalate with inflammatory biomarkers such as neutrophil count, neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, and the systemic immune-inflammation index (SII) at lag 0 (the day of physical examination). Each 1% increase in ∑OHPHE was related to a 0.18% (95% confidence interval: 0.10%, 0.25%) increase in SII, which was the strongest among the above associations. The results of BKMR and quantile g-computation suggested that co-exposure to PAHs and PAEs mixture was associated with an elevated white blood cell count, neutrophil count, neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, and SII, to which ∑OHPHE and 1-hydroxypyrene (1-OHPYR) might be the major contributors. In addition, gender and age modified the associations of ∑OHPHE and 1-OHPYR with inflammatory biomarkers, where girls and younger children were more susceptible. In conclusion, co-exposure to PAHs and PAEs was associated with elevated inflammation in children, in which ∑OHPHE and 1-OHPYR might play important roles.

The mediating role of plasma microRNAs in the association of phthalates exposure with arterial stiffness: A panel study.

Phthalates exposure has been reported to be linked with arterial stiffness. However, the biological mechanisms underlying this association remain unclear. We conducted a panel study using 338 paired urine-blood samples by repeated measurements of 123 adults across 3 seasons to assess the potential mediating role of plasma microRNAs (miRNAs) in the association of phthalates exposure with arterial stiffness. We measured 10 urinary phthalate metabolites by gas chromatography-tandem mass spectrometry (GC-MS/MS) and 5 candidate arterial stiffness-related miRNAs (miR-146a, miR-222, miR-125b, miR-126, and miR-21) in plasma by real-time PCR. Arterial stiffness parameters including brachial-ankle pulse wave velocity (baPWV) and ankle-brachial index (ABI) were determined in health examinations during each visit. Linear mixed-effect (LME) models revealed that mono-methyl phthalate (MMP), mono-iso-butyl phthalate (MiBP), mono-n-butyl phthalate (MBP), mono-n-octyl phthalate (MOP), and mono-(2-ethyl-5-carboxypentyl) phthalate (MECPP) were significantly associated with one or more of the 5 plasma miRNAs (all PFDR < 0.05). Based on weighted quantile sum (WQS) regression, we found positive associations of phthalate metabolites mixture with miR-146a, miR-125b, and miR-222, and individual MMP and MBP were the major contributors. Additionally, miR-146a was inversely related to ABI. Mediation analysis further indicated that miR-146a mediated 31.6% and 21.3% of the relationships of MMP and MiBP with ABI, respectively. Our findings suggested that certain phthalates exposure was related to plasma miRNAs alterations in a dose-response manner and miR-146a might partly mediate phthalate-associated ABI reduction.

Co-exposure to priority-controlled metals mixture and blood pressure in Chinese children from two panel studies.

Metals may affect adversely cardiovascular system, but epidemiological evidence on the associations of priority-controlled metals including antimony (Sb), arsenic (As), cadmium, lead, and thallium with children's blood pressure (BP) was scarce and inconsistent. We conducted two panel studies with 3 surveys across 3 seasons among 144 and 142 children aged 4-12 years in Guangzhou and Weinan, respectively. During each seasonal survey, urine samples were collected for 4 consecutive days and BP was measured on the 4th day. We obtained 786 BP values and urinary metals measurements at least once within 4 days, while 773, 596, 612, and 754 urinary metals measurements were effective on the health examination day (Lag 0), and the 1st, 2nd, and 3rd day preceding BP measurement (Lag 1, lag 2 and lag 3), respectively. We used linear mixed-effect models, generalized estimating equations and multiple informant models to assess the associations of individual metal at each lag day and accumulated lag day (4 days averaged, lag 0-3) with BP and hypertension, and Bayesian Kernel Machine Regression to evaluate the relations of metals mixture at lag 0-3 and BP outcomes. We found Sb was positively and consistently related to systolic BP (SBP), mean arterial pressure (MAP), and odds of having hypertension within 4 days, which were the strongest at lag 0 and declined over time. And such relationships at lag 0-3 showed in a dose-response manner. Meanwhile, Sb was the only contributor to the relations of mixture with SBP, MAP, and odds of having hypertension. Also, synergistic interaction between Sb and As was significant. In addition, modification effect of passive smoking status on the association of Sb and SBP was more evident in passive smokers. Accordingly, urinary Sb was consistently and dose-responsively associated with increased BP and hypertension, of which Sb was the major contributor among children.

Urinary phthalate metabolites and arterial stiffness: A panel study.

The link between phthalates exposure and arterial stiffness in adults remains unclear. We aimed to investigate the associations of urinary phthalate metabolites with arterial stiffness in a longitudinal panel study involving 3 repeated visits among 127 Chinese adults. Urine samples were collected once a day for 4 consecutive days and 10 urinary phthalate metabolites were measured by gas chromatography-tandem mass spectrometry (GC-MS/MS). Brachial ankle pulse wave velocity (baPWV) and ankle-brachial index (ABI) were determined using an oscillometric device (BP-203RPEIII; Omron) in physical examinations during each visit. Linear mixed-effect (LME) models with the adaptive Least Absolute Shrinkage and Selection Operator (LASSO) method were applied to assess the associations between urinary phthalate metabolites and arterial stiffness parameters. The odds ratio (OR) for peripheral arterial disease (PAD) was estimated using generalized estimating equations. For ABI, mono-methyl phthalate (MMP) and mono-n-butyl phthalate (MBP) at lag 0 day were selected by the adaptive LASSO, whereas no phthalates were selected for baPWV. After adjusting for potential covariates and other metabolites, we found ABI reduction was associated with one-unit increase of ln-transformed urinary MBP at lag 0 day [ß = 0.013 (SE = 0.006), P = 0.003)]. Stratified analysis revealed that the inverse association was more evident in males (Pinteraction = 0.025). In addition, we observed a borderline risk of PAD in relation to MBP exposure at lag 0 day (P = 0.06). Our data suggested that environmental exposure to MBP may contribute to arterial stiffness, and the effect seems to be sex-specific.