Urban Fine Particulate Matter and Elements Associated with Subclinical Atherosclerosis in Adolescents and Young Adults.

The relationships between the elemental constituents of PM2.5 and atherosclerosis remain limited, especially in young populations. This study included 755 subjects aged 12-30 years in the Taipei metropolis. A land use regression model was used to estimate residential annual mean concentrations of PM2.5 and eight elemental constituents. We evaluated the percent differences in carotid intima-media thickness (CIMT) with PM2.5 and elemental constituent exposures by linear regressions. Interquartile range increments for PM2.5 (4.5 µg/m3), sulfur (108.6 ng/m3), manganese (2.0 ng/m3), iron (34.5 ng/m3), copper (3.6 ng/m3), and zinc (20.7 ng/m3) were found to associate with 0.92% (95% confidence interval (CI): 0.17-1.66), 0.51% (0.02-1.00), 0.36% (0.05-0.67), 0.98% (0.15-1.82), 0.74% (0.01-1.48), and 1.20% (0.33-2.08) higher CIMTs, respectively. Factor analysis identified four air pollution source-related factors, and the factors interpreted as traffic and industry sources were associated with higher CIMTs. Stratified analyses showed the estimates were more evident in subjects who were ≥18 years old, females, or who had lower household income. Our study results provide new insight into the impacts of source-specific air pollution, and future research on source-specific air pollution effects in young populations, especially in vulnerable subpopulations, is warranted.

Open space and adult's chronic kidney disease, overweight and diabetes in the metropolitan area of New Taipei City.

BACKGROUND: The beneficial effects of urban open green space on residential health had few investigations in Taiwan. METHODS: A total of 40,375 participants older than 30-year-old attended the health screening program during 2007-2009 in the Metropolitan area in the New Taipei City. We defined urban open green spaces (UOGS) if land use belongs to parks, green, plaza, public schools and sport venues. Small public urban open space (SPUOS) is defined as UOGS with area less than 1 hector and with at least three of the followings: vegetations, sport facilities and benches. Greenness is defined as the mean Normalized Difference Vegetation Index (NDVI). Air quality was accessed by land use regression model. Logistic regression model was used to calculate odds ratios of diseases for proximity to UOGS or greenness. RESULTS: We found that CKD was significantly associated with proximity to SPUOS. No relationship was found between proximity to UOGS or NDVI and overweight or diabetes. The adjusted odds ratio of CKD comparing distance to SPUOS >200 m and ≤200 m was 1.144 (95% CI, 1.059-1.237). The effect of open space on CKD was similar if we incorporated public schools to SPUOS. Greenness was not associated with CKD. Subgroups analyses revealed the effect of SPUOS on CKD was more prominent in health residents, including in those who never smoke, no hypertension, no diabetes and no hypertriglyceridemia. CONCLUSION: Proximity to SPUOS or schools is associated with lower risk of CKD for adults living in the Metropolitan area in New Taipei City.

Urinary heavy metals, DNA methylation, and subclinical atherosclerosis.

PURPOSE: Lead (Pb) or cadmium (Cd) exposure has been linked to atherosclerosis. Co-exposure of these two heavy metals often occurs in humans. Recent evidence has indicated a crucial role of DNA methylation in atherosclerosis, while Pb or Cd exposure has also been shown to alter DNA methylation. However, it is still unknown whether DNA methylation plays a role in the pathological mechanism of these two heavy metals in atherosclerosis. APPROACH AND RESULTS: We enrolled 738 participants (12-30 years) to investigate the association among concentrations of urine Pb or Cd, the 5mdC/dG value (a global DNA methylation marker) and the carotid intima-media thickness (CIMT). When each heavy metal was modeled separately, the results showed urine Pb and Cd concentrations were positively associated with the 5mdC/dG value and CIMT, respectively. When the two heavy metals were analyzed in the same model, urinary Pb concentrations were positively associated with the 5mdC/dG value and CIMT, while urinary Cd concentrations were only positively associated with the CIMT. When Pb and Cd are simultaneously considered in the same logistic regression model, the odds ratios (OR) of thicker CIMT (greater than 75th percentile) with one unit increase in ln-Pb level was 1.67 (95% C.I. = 1.17-2.46, P = 0.005) when levels of 5mdC/dG were above 50th percentile, which is higher than 5mdC/dG bellow the 50th percentile (OR = 1.50 (95% C.I. = 0.96-2.35), P = 0.076). In structural equation model (SEM), Pb or Cd levels are directly associated with CIMT. Moreover, Pb or Cd had an indirect association with CIMT through the 5mdC/dG. When we considered Pb and Cd together, Pb levels had a direct association with CIMT and an indirect association with CIMT through the 5mdC/dG value, while Cd only had a direct association with CIMT. CONCLUSIONS: Our findings imply that Pb and Cd exposure might be associated with subclinical atherosclerosis, and global DNA methylation might mediate Pb-associated subclinical atherosclerosis in this young population. Future effort is necessary to elucidate the causal relationship.

Individual differences in skewed financial risk-taking across the adult life span.

Older adults are disproportionately targeted by fraud schemes that advertise unlikely but large returns (positively skewed risks). We examined adult age differences in choice and neural activity as individuals considered risky gambles. Gambles were symmetric (50% chance of modest win or loss), positively skewed (25% chance of large gain), or negatively skewed (25% chance of large loss). The willingness to accept positively skewed relative to symmetric gambles increased with age, and this effect replicated in an independent behavioral study. Whole-brain functional magnetic resonance imaging analyses comparing positively (vs. negatively) skewed trials revealed that relative to younger adults, older adults showed increased anticipatory activity for negatively skewed gambles but reduced activity for positively skewed gambles in the anterior cingulate and lateral prefrontal regions. Individuals who were more biased toward positively skewed gambles showed increased activity in a network of regions including the nucleus accumbens. These results reveal age biases toward positively skewed gambles and age differences in corticostriatal regions during skewed risk-taking, and have implications for identifying financial decision biases across adulthood.

Nuclear magnetic resonance- and mass spectrometry-based metabolomics to study maleic acid toxicity from repeated dose exposure in rats.

Maleic acid (MA), a chemical intermediate used in many consumer and industrial products, was intentionally adulterated in a variety of starch-based foods and instigated food safety incidents in Asia. We aim to elucidate possible mechanisms of MA toxicity after repeated exposure by (1) determining the changes of metabolic profile using 1 H nuclear magnetic resonance spectroscopy and multivariate analysis, and (2) investigating the occurrence of oxidative stress using liquid chromatography tandem mass spectrometry by using Sprague-Dawley rat urine samples. Adult male rats were subjected to a 28 day subchronic study (0, 6, 20 and 60 mg kg-1 ) via oral gavage. Urine was collected twice a day on days 0, 7, 14, 21 and 28; organs underwent histopathological examination. Changes in body weight and relative kidney weights in medium- and high-dose groups were significantly different compared to controls. Morphological alterations were evident in the kidneys and liver. Metabolomic results demonstrated that MA exposure increases the urinary concentrations of 8-hydroxy-2'-deoxyguanosine, 8-nitroguanine and 8-iso-prostaglandin F2α ; levels of acetoacetate, hippurate, alanine and acetate demonstrated time- and dose-dependent variations in the treatment groups. Findings suggest that MA consumption escalates oxidative damage, membrane lipid destruction and disrupt energy metabolism. These aforementioned changes in biomarkers and endogenous metabolites elucidate and assist in characterizing the possible mechanisms by which MA induces nephro- and hepatotoxicity.

Concurrent quantification of multiple biomarkers indicative of oxidative stress status using liquid chromatography-tandem mass spectrometry.

8-Hydroxy-2-deoxyguanosine (8-OHdG), 8-nitroguanine (8-NO2Gua), 8-iso-prostaglandin F2α (8-IsoPGF2α), and N-acetyl-S-(tetrahydro-5-hydroxy-2-pentyl-3-furanyl)-L-cysteine (HNE-MA) are well-studied and representative biomarkers for oxidative DNA damage, inflammation, and lipid peroxidation; all of which have been associated with increases in risks of various diseases and cancers. A rapid and highly sensitive isotope-dilution liquid-chromatography tandem mass spectrometry (LC-MS/MS) method was developed to simultaneously quantify the aforementioned biomarkers in urine. Upon validation, this method shows excellent feasibility, sensitivity (0.008-0.03 ng/mL) and satisfactory recoveries (88.7-95.4%); the calibration curves displayed excellent linearity with coefficients of determination (R(2)) greater than 0.998. Additionally, low variations were observed in the relative standard deviation for intra- and inter-day measurements for the four analytes. The relative matrix effects for all four analytes ranged from 2.04 to 3.27%, which signaled that interferences from endogenous levels of the analytes were deemed statistically insignificant. This study successfully developed an analytical method capable to simultaneously quantify urinary 8-OHdG, 8-NO2Gua, 8-IsoPGF2α, and HNE-MA. This analytical protocol can be applied towards conducting epidemiological studies to reveal the mechanisms related to disease development, and thus evaluate the associated risks of diseases.

Affective traits link to reliable neural markers of incentive anticipation.

While theorists have speculated that different affective traits are linked to reliable brain activity during anticipation of gains and losses, few have directly tested this prediction. We examined these associations in a community sample of healthy human adults (n=52) as they played a Monetary Incentive Delay task while undergoing functional magnetic resonance imaging (FMRI). Factor analysis of personality measures revealed that subjects independently varied in trait Positive Arousal and trait Negative Arousal. In a subsample (n=14) retested over 2.5years later, left nucleus accumbens (NAcc) activity during anticipation of large gains (+$5.00) and right anterior insula activity during anticipation of large losses (-$5.00) showed significant test-retest reliability (intraclass correlations>0.50, p's<0.01). In the full sample (n=52), trait Positive Arousal correlated with individual differences in left NAcc activity during anticipation of large gains, while trait Negative Arousal correlated with individual differences in right anterior insula activity during anticipation of large losses. Associations of affective traits with neural activity were not attributable to the influence of other potential confounds (including sex, age, wealth, and motion). Together, these results demonstrate selective links between distinct affective traits and reliably-elicited activity in neural circuits associated with anticipation of gain versus loss. The findings thus reveal neural markers for affective dimensions of healthy personality, and potentially for related psychiatric symptoms.

The association of hypertension and prehypertension with greenness and PM2.5 in urban environment.

BACKGROUND: The interplay of air pollution and urban greenness on hypertension (HTN) is not fully understood. METHODS: We conducted a cross-sectional study to explore the role of greenness and PM2.5 on HTN for 40,375 adult residents in the New Taipei City, Taiwan. Normalized Difference Vegetation Index (NDVI) defined greenness and land use regression derived exposures of PM2.5 were used to calculate odds ratios (ORs) of HTN in logistic regression models and common OR of normal to stage 3 HTN in ordinal logistic regression models. Linear regression model was used to evaluate the association between NDVI and blood pressures, including systolic (SBP), diastolic (DBP) and mean (MBP) pressures. The mediation and moderation analysis were used to assess the mediation and moderation effect of PM2.5 on the association between greenness and SBP. RESULTS: We found 37.3%, 21.4%, 8.2% and 2.7% of prehypertension and stage 1-3 hypertensions, respectively, for our study participants with annual PM2.5 exposures of 10.96-43.59 µg/m3 living in an urban environment with NDVI within 500 m buffer ranging from -0.22 to 0.26. The ORs of HTN were 0.744 (95% CI: 0.698-0.793) for NDVI (quartile 4 vs. quartile 1) and 1.048 (1.012-1.085) for each IQR (8.69 µg/m3) increase in PM2.5, respectively. The common OR of the higher level of 5 categories of BP was 1.1310 (1.241-1.383). With each IQR increase of NDVI (0.03), we found SBP, DBP and MBP were decreased by 0.78 mm Hg (-0.93-0.64), 0.52 mm Hg (-0.62-0.43) and 0.61 mm Hg (-0.71-0.51), respectively, in linear regression models. Stratified analysis found greenness effect was more prominent for people who are younger, female, never smoking, and without chronic diseases. PM2.5 is moderated rather than mediated the association between greenness and SBP. CONCLUSIONS: Greenness was associated with lower prevalence of prehypertension and all stages of HTN and this relationship was moderated by PM2.5.

Synergistic Effects of Inflammation and Atherogenic Dyslipidemia on Subclinical Carotid Atherosclerosis Assessed by Ultrasound in Patients with Familial Hypercholesterolemia and Their Family Members.

Low-density lipoprotein cholesterol (LDL-C) and total to high-density lipoprotein cholesterol (TC/HDL-C) ratio are both common risk factors for atherosclerotic cardiovascular diseases (ASCVDs). However, whether high-sensitivity C-reactive protein (hsCRP) has synergistic or attenuated effects on atherogenic dyslipidemia remains unclear. We investigated subclinical carotid atherosclerosis in patients with familial hypercholesterolemia (FH) and their family members. A total of 100 families with 761 participants were prospectively studied. Participants were categorized into four groups according to atherogenic dyslipidemia and inflammatory biomarkers. The group with LDL-C ≥ 160 mg/dL (or TC/HDL-C ratio ≥ 5) combined with hsCRP ≥ 2 mg/L have a thicker carotid intima-media thickness (CIMT) in different common carotid artery (CCA) areas and a higher percentage of high plaque scores compared with other subgroups. Multivariate logistic regression analysis revealed a significantly higher adjusted odds ratio (aOR) for thicker CIMT of 3.56 (95% CI: 1.56-8.16) was noted in those with concurrent LDL-C ≥ 160 mg/dL and hsCRP ≥ 2 mg/L compared with the group with concurrent LDL-C < 160 mg/dL and hsCRP < 2 mg/L. Our results demonstrated that systemic inflammation, in terms of higher hsCRP levels ≥ 2 mg/L, synergistically contributed to atherogenic dyslipidemia of higher LDL-C or a higher TC/HDL-C ratio on subclinical atherosclerosis.

Urban Air Pollution and Subclinical Atherosclerosis in Adolescents and Young Adults.

PURPOSE: The contribution of air pollution to subclinical atherosclerosis in a young population remains limited. This study aimed to assess whether long-term exposure to urban air pollutants increases carotid intima-media thickness (CIMT) in adolescents and young adults. METHODS: This study included 789 subjects between the ages of 12 and 30 years who lived in the Taipei metropolis from a cohort of young Taiwanese individuals. Residential addresses were geocoded, and annual average concentrations of particulate matter (PM) of different diameters, e.g., PM10, PM2.5-10, PM2.5, and nitrogen oxides (NOX), were assessed using land use regression models. The generalized least squares strategy with error term to consider the cluster effect of living addresses between individuals was used to examine the associations between urban air pollution and CIMTs. RESULTS: After adjusting for potential confounders, we found that interquartile range increases in PM2.5 (8.2 µg/m3) and NOX (17.5 µg/m3) were associated with 0.46% (95% CI: 0.02-0.90) and 1.00% (95% CI: 0.10-1.91) higher CIMTs, respectively. Stratified analyses showed that the relationships between CIMT and PM2.5 and NOX were more evident in subjects who were 18 years or older, female, nonsmoking, nonhypertensive, and nonhyperglycemic than in their respective counterparts. DISCUSSION: Long-term exposure to PM2.5 and NOX is associated with subclinical atherosclerosis in a young population. Age, sex, and health status may influence the vulnerability of air pollution-associated subclinical atherosclerosis.

Global DNA methylation mediates the association between urine mono-2-ethylhexyl phthalate and serum apoptotic microparticles in a young Taiwanese population.

Di-(2-ethylhexyl) phthalate (DEHP) has been used as a plasticizer for decades. Recent research evidence has revealed that environmental factors can alter vascular endothelial cell function through DNA methylation. However, no previous in vitro/vivo study has explored the role of DNA methylation in DEHP exposure and vascular endothelial cell function. In the present study, we enrolled 793 subjects aged 12 to 30 years from a young Taiwanese cohort to investigate the association between mono-2-ethylhexyl phthalate (MEHP) (urine DEHP metabolite), 5mdC/dG (global DNA methylation marker), CD31+/CD42a-, CD31+/CD42a+, and CD14 (apoptotic microparticles of vascular cells). In multiple regression analyses, the levels of mono-2-ethylhexyl phthalate (MEHP) were positively associated with 5mdC/dG and all three apoptotic microparticles. In addition, the regression coefficients between MEHP and the three types of apoptotic microparticles were higher when the 5mdC/dG levels were higher than the 50th percentile. In the structural equation model (SEM), we found that MEHP had a direct correlation with CD31+/CD42a- and an indirect association with CD31+/CD42a- through the effect of 5mdC/dG. Moreover, MEHP only had a direct association with CD31+/CD42a+ and an indirect association with CD14. In conclusion, the results show that global DNA methylation mediates the relationship between MEHP and apoptotic microparticles. These findings indicate that DNA methylation may play a role in the pathogenesis of DEHP-induced endothelial cell apoptosis in humans. Further studies are needed to clarify the causal inference.

Forest Bathing Is Better than Walking in Urban Park: Comparison of Cardiac and Vascular Function between Urban and Forest Parks.

Forest bathing is beneficial for human health. To investigate whether walking in forest or urban parks affects cardiovascular functions (CVFs), the present study was conducted in five forest trails in the Xitou Experimental Forest and in five urban parks in Taipei city. We recruited 25 adult volunteers for an observational pilot study in forest parks (n = 14) and urban parks (n = 11). CVFs were assessed by measuring the arterial pressure waveform using an oscillometric blood pressure (BP) device. The baseline and paired differences of systolic BP (SBP), central end SBP, heart rate, left ventricle (LV) dP/dt max and cardiac output in participants were lower before and after walking in a forest park than those in an urban park. In addition, the systemic vascular compliance and brachial artery compliance of those who walked in a forest park were significantly higher compared with those in an urban park. Linear mixed models demonstrated lower levels of SBP by 5.22 mmHg, heart rate by 2.46 beats/min, and cardiac output by 0.52 L/min, and LV dP/dt max by 146.91 mmHg/s among those who walked in forest compared to those in an urban park after controlling covariates. This study provides evidence of the potential beneficial effects of walking exercise in forest parks on CVFs.

Positive Association between Indoor Gaseous Air Pollution and Obesity: An Observational Study in 60 Households.

This study aims to analyze whether exposure to indoor air pollution affects obesity. In our research, we recruited 127 participants, with an average age of 43.30 ± 15.38 years old, residing in 60 households. We monitored indoor air quality for 24 h, and conducted both questionnaire surveys and collected serum samples for analysis, to assess the relationship between indoor air pollutant exposure and obesity. After adjusting for demographic characteristics, the results showed that CO2 exposure is positively associated with being overweight and with a higher risk of being abdominally obese. Exposures to CO and formaldehyde were also positively associated with being overweight. IQR increase in TVOC was positively associated with increases in the risk of a high BMI, being abdominally obese and having a high body fat percentage. Two-pollutant models demonstrate that TVOCs presented the strongest risks associated with overweightness. We concluded that persistent exposure to indoor gaseous pollutants increases the risk of overweightness and obesity, as indicated by the positive association with BMI, abdominal obesity, and percentage body fat. TVOCs display the strongest contribution to obesity.

Association between Urinary Phthalate Metabolites and Markers of Endothelial Dysfunction in Adolescents and Young Adults.

Endothelial function is crucial in the pathogenesis of circulatory and cardiovascular toxicity; epidemiologic research investigating the association between phthalate exposure and endothelial dysfunction remains limited. We examined the associations between exposures to specific phthalates (di-2-ethylhexyl phthalate, DEHP; di-n-butyl phthalate, DnBP) and circulating endothelial and platelet microparticles (EMPs and PMPs) in adolescents and young adults. Of the 697 participants recruited, anthropometric measurements and health-related behaviors relevant to cardiovascular risks were collected and assessed. Urine and serum were collected and analyzed with liquid chromatography-tandem mass spectrometry (LC-MS/MS) and flow cytometry. Multiple linear regression indicated that increases in urinary concentrations of ΣDEHP and MnBP (mono-n-butyl phthalate), across quartiles, were positively associated with serum EMPs level (p for trend <0.001 and <0.001; ß = 0.798 and 0.007; standard error = 0.189 and 0.001, respectively). Moreover, female and overweight subjects had higher MnBP, and males were more vulnerable to DnBP exposure compared to females. In conclusion, our results demonstrate a dose-response relationship between exposures to phthalates (ΣDEHP and MnBP) and microparticle formation (EMPs and PMPs) in adolescents and young adults. The findings indicate that exposures to phthalates of both low and high-molecular weight are positively associated with microparticle production, and might contribute to endothelial dysfunction; such damage might manifest in the form of atherosclerotic-related vascular diseases. Future in vivo and in vitro studies are warranted to elucidate whether a causal relationship exists between phthalate exposure and EMPs and PMPs.

Seasonal Effects of High-Altitude Forest Travel on Cardiovascular Function: An Overlooked Cardiovascular Risk of Forest Activity.

Cardiovascular physiological responses involving hypoxemia in low temperature environments at high altitude have yet to be adequately investigated. This study aims to demonstrate the health effects of hypoxemia and temperature changes in cardiovascular functions (CVFs) by comparing intra-individual differences as participants ascend from low (298 m, 21.9 °C) to high altitude (2729 m, 9.5 °C). CVFs were assessed by measuring the arterial pressure waveform according to cuff sphygmomanometer of an oscillometric blood pressure (BP) device. The mean ages of participants in winter and summer were 43.6 and 41.2 years, respectively. The intra-individual brachial systolic, diastolic BP, heart rate, and cardiac output of participants significantly increased, as participants climbed uphill from low to high altitude forest. Following the altitude increase from 298 m to 2729 m, with the atmosphere gradually reducing by 0.24 atm, the measured average SpO2 of participants showed a significant reduction from 98.1% to 81.2%. Using mixed effects model, it is evident that in winter, the differences in altitude affects CVFs by significantly increases the systolic BP, heart rate, left ventricular dP/dt max and cardiac output. This study provides evidence that cardiovascular workload increased significantly among acute high-altitude travelers as they ascend from low to high altitude, particularly in winter.

Positive Association between Endothelium-Platelet Microparticles and Urinary Concentration of Lead and Cadmium in Adolescents and Young Adults.

(1) Background: In previous research, higher levels of urine heavy metals, especially lead and cadmium, have been associated with increased cardiovascular risk. However, there is no information linking exposure to heavy metal to endothelial and platelet microparticles (EMPs and PMPs), particularly in the younger population, which are novel biomarkers of endothelial dysfunction. (2) Methods: From a nationwide database, which was incepted in 1992-2000, screening for renal health among Taiwanese school children, a total of 789 subjects were recruited. Cross-sectional analysis was performed to evaluate the association between serum EMPs/PMPs and urine iron, nickel, copper, cadmium, lead, chromium, manganese, and zinc levels in the adolescent and young adult population. (3) Results: After we adjusted the conventional cardiovascular risk factors, CD31+/CD42a- and CD31+/CD42a+ counts, in subjects' serum, respective markers of EMP and PMP displayed a significant positive dose-response relationship with urinary lead and cadmium levels. Higher quartiles of urine lead and cadmium levels were associated with an increased risk of higher EMPs/PMPs (≥75th percentile) in a multivariate logistic regression model. (4) Conclusion: Higher urinary lead and cadmium concentrations are strongly associated with endothelium-platelet microparticles in this adolescent and young adult population, which could help explain, in part, the mechanism through which heavy metal exposure results in cardiotoxicity.

3-Urea-1-(phenylmethyl)-pyridones as novel, potent, and selective EP3 receptor antagonists.

A series of 3-urea-1-(phenylmethyl)-pyridones was discovered as novel EP(3) antagonists via high-throughput screening and subsequent optimization. The synthesis, structure-activity relationships, and optimization of the initial hit that resulted in potent and selective EP(3) receptor antagonists such as 11g are described.

Association between urine lead levels and cardiovascular disease risk factors, carotid intima-media thickness and metabolic syndrome in adolescents and young adults.

BACKGROUND: Environmental lead exposure is a known risk factor of cardiovascular disease (CVD) in animal and human epidemiological studies of adults, but limited research has been conducted in young populations. Moreover, the association between lead level and common carotid artery intima-media thickness (CIMT) has never been documented. DESIGN: and Participants: In this study, 738 subjects were recruited from a cohort of Taiwanese adolescents and young adults to study the relationship between lead levels in urine and CVD risk factors, metabolic syndrome (MS) and CIMT. RESULTS: The geometric mean of the urine lead level was 1.50 µg/g creatinine. We found a significant positive association between urine lead levels and CVD risk factors, including diastolic blood pressure (DBP), mean arterial pressure (MAP), as well as markers of glucose homeostasis, such as serum glucose, serum insulin, homeostasis model assessment of insulin resistance (HOMA-IR), homeostasis model assessment of ß-cell function (HOMA-ß), body mass index (BMI) z score, and CIMT. Overall, increased urine lead concentrations were positively correlated with the prevalence of MS, specifically the criteria of waist/BMI and serum HDL-C. The relationship between urine lead levels and CIMT remained unchanged in all subgroups. CONCLUSION: In this study, we found that increased urinary levels of lead were positively associated with CVD risk factors, CIMT, and MS in this cohort. Future research to explore the pathogenic basis of exposure to lead and risk of CVDs and their risk factors are warranted.

The association between urine di-(2-ethylhexyl) phthalate metabolites, global DNA methylation, and subclinical atherosclerosis in a young Taiwanese population.

Di-(2-ethylhexyl) phthalate (DEHP) has been utilized in many products for years. DEHP exposure has been linked to cardiovascular diseases (CVD) and its risk factors. Recent evidence has found a crucial role for epigenetics, including DNA methylation, in CVD. Moreover, DEHP exposure has proved to alter DNA methylation in epidemiological studies. However, the interplay between DEHP exposure, global DNA methylation, and atherosclerosis has never been reported. In this current study, we enrolled 793 participants (12-30 years) from a Taiwanese population to investigate the association between concentrations of DEHP metabolites, 5mdC/dG (global DNA methylation marker) and the carotid intima-media thickness (CIMT). The results showed urine mono-2-ethylhexyl phthalate (MEHP) level was positively correlated with 5mdC/dG and CIMT, respectively. In logistic regression models, the odds ratios (OR) of thicker CIMT (greater than 75th percentile) with one unit increase in ln-MEHP level was higher when levels of 5mdC/dG were above 50%. In structural equation model, the result showed urine MEHP levels are directly associated with CIMT. Moreover, MEHP had an indirect association with CIMT through the 5mdC/dG after adjusting other confounding effects. In the current study, urine DEHP metabolite levels were positively correlated with 5mdC/dG, and CIMT. Our results showed DEHP had a direct and indirect association with CIMT through the 5mdC/dG. The finding implies that DNA methylation may mediate the association between DEHP exposures and subclinical atherosclerosis in this young population. Future effort is needed to elucidate the causal relationship between DEHP exposure, DNA methylation and CVD.