Phthalate exposure is associated with cardiovascular risk. Among the various phthalates, di-(2-ethylhexyl) phthalate (DEHP) is a deleterious plasticizer in our daily lives. This study investigated the association between DEHP exposure and the alteration of heart rate variability (HRV). During 2017–2019, we recruited 974 young adults to investigate the effects of living environments and dietary habits on cardiometabolic disorders in Taiwan. We quantitatively analyzed urinary metabolites of DHEP. A continuous electrocardiogram was recorded to obtain a 5-min ECG. Time-domain and frequency-domain HRV analyses were performed. Multiple linear regression showed that urinary oxidized DEHP metabolites MEHHP and MEOHP were associated with decreased HRV after controlling for associated cardiovascular risk factors. A higher MEHHP level was associated with a lower triangular interpolation of NN interval histogram (TINN), very low frequency (VLF), and low frequency/high frequency (LF/HF) ratio. A higher MEOHP level was associated with a decreased LF/HF ratio. In addition, trend analysis showed that higher MEHHP and MEOHP quantiles were significantly associated with a decreased LF/HF ratio. DEHP is a potentially harmful and invisible chemical. The urinary DEHP metabolites MEHHP and MEOHP are associated with decreased HRV, indicating an adverse effect on autonomic balance in young adults in Taiwan.

Background: Exposure to lead and cadmium has been linked to changes in lipid metabolism and the development of arteriosclerosis, but the role of lipoprotein profiles in this relationship is not well understood, including the potential role of novel lipid biomarkers. Methods: In this study, we enrolled 736 young Taiwanese subjects aged 12 to 30 years to assess the correlation between urine levels of lead and cadmium, lipoprotein profiles, and carotid intima-media thickness (CIMT). Results: Higher levels of lead and cadmium were significantly associated with higher levels of low-density lipoprotein cholesterol (LDL-C), small dense LDL-C (sdLDL-C), LDL-triglyceride (LDL-TG), and CIMT. Participants with higher levels of lead and cadmium had the highest mean values of CIMT, LDL-C, sdLDL-C, and LDL-TG. In a structural equation model, lead had a direct and indirect association with CIMT through LDL-C and sdLDL-C, whereas cadmium had a direct association with CIMT and an indirect association through LDL-C. Conclusion: Our results suggest higher levels of lead and cadmium are associated with abnormal lipid profiles and increased CIMT. These heavy metals could have additive effects on lipids and CIMT, and the relationship between them may be mediated by lipoprotein levels. Further research is needed to determine the causal relationship.

Purpose: This study aimed to investigate the associations between serum per- and polyfluoroalkyl substances (PFAS) and reproductive hormones, including follicle-stimulating hormone (FSH), anti-Müllerian hormone (AMH), estradiol, and progesterone, in U.S. women. Approach and Results: We conducted a cross-sectional study using data from the National Health and Nutrition Examination Survey (NHANES) 2017–2018. The study included 612 women aged ≥18 years with available PFAS and sex hormone measurements. Serum concentrations of four major PFASs (linear perfluorooctanoic acid [n-PFOA], perfluorooctane sulfonic acid [PFOS], perfluorononanoic acid [PFNA], and perfluorohexane sulfonic acid [PFHxS]) were analyzed, along with serum levels of FSH, AMH, estradiol, and progesterone measured by isotope dilution liquid chromatography–tandem mass spectrometry. Higher serum PFAS concentrations were associated with increased FSH and decreased AMH, estradiol, and progesterone. For example, each interquartile range (IQR) increase in ln-PFNA was associated with a 42.0% increase in ln-FSH (p = 0.01) and 32.2% lower ln-AMH (p < 0.001), 33.0% lower ln-estradiol (p = 0.004), and 40.9% lower ln-progesterone (p = 0.02). A PFAS exposure index was related to higher FSH and lower AMH, estradiol, and progesterone, with stronger effects in premenopausal women. Conclusions: PFAS exposure was linked to broad endocrine disruption in women, with consistent alterations across gonadotropins and sex steroids. These findings suggest that PFAS exposure was associated with hormonal patterns consistent with diminished ovarian reserve and potential changes in reproductive function, underscoring the need for longitudinal studies and regulatory actions to mitigate exposure.

Lead and cadmium have been linked to alterations in DNA methylation (DNAm) and increased mortality. However, the role of smoking-related DNAm in the link between these heavy metals and mortality remains unclear. We analyzed data from 2110 participants aged 50 and older from the 1999-2002 National Health and Nutrition Examination Survey (NHANES), linked to mortality data from the National Center for Health Statistics (NCHS) with follow-up through 2019. Our study examined the associations between blood lead and cadmium levels, DNA methylation-predicted pack years of smoking (DNAmPackYrs), and mortality outcomes. Our analysis found that higher natural logarithm (Ln)-transformed lead and cadmium levels were positively associated with ln-DNAmPackYrs, with a percent change of 11.34 % (P = 0.001) for lead and 35.57 % (P < 0.001) for cadmium. Participants with both heavy metals above the 50th percentile had the highest DNAmPackYrs, with P for trend < 0.001. Weighted Cox regression analysis demonstrated both ln-lead and ln-DNAmPackYrs were linked to an elevated risk of all mortality outcomes, while ln-cadmium specifically predicted all-cause mortality. A significant interaction between lead and cadmium in relation to all-cause mortality was observed (P for interaction = 0.036). Additionally, significant interactions between DNAmPackYrs and both heavy metals were found in relation to all-cause mortality (P for interaction = 0.001 for lead; P for interaction = 0.013 for cadmium). Drawing from a nationally representative cohort of older U.S. adults, this study provides robust evidence linking blood lead and cadmium levels to smoking-related DNAm and increased mortality risk. Moreover, the analysis revealed additive effects of these metals on smoking-related DNAm, as well as synergistic impacts on all-cause mortality. Additionally, smoking-induced DNAm may play a role in mediating the connection between heavy metal exposure and mortality risk. Additional research is required to investigate the underlying mechanisms of these associations.

As one of the most common alkylphenols, 4-tertiary-octylphenol (4-tOP) is commonly used in many consumer products. Our previous epidemiological study revealed a negative correlation between serum 4-tOP levels and carotid intima-media thickness (CIMT), which serves as a biomarker of arteriosclerosis. We aimed to explore the role of apoptotic microparticles, markers of vascular endothelial cell function, in the 4-tOP and CIMT connection. To investigate this, we enrolled 886 Taiwanese adolescents and young adults (aged 12–30 years) and examined the relationships among serum 4-tOP levels, apoptotic microparticles (CD31+/CD42a−, CD31+/CD42a+), and CIMT. Our results showed negative associations among serum 4-tOP levels, both apoptotic microparticles, and CIMT in multiple linear regression analysis. The odds ratios for CIMT (≥75th percentile) and the natural logarithm of 4-tOP were highest when both CD31+/CD42a− and CD31+/CD42a+ were greater than the 50th percentile. Conversely, the odds ratios were lowest when both CD31+/CD42a− and CD31+/CD42a+ were less than the 50th percentile. In the structural equation model, we demonstrated that serum 4-tOP levels were negatively correlated with CIMT and indirectly and negatively correlated with CIMT through both apoptotic microparticles. In conclusion, our study reported the inverse association between 4-tOP apoptotic microparticles and CIMT in a young Taiwanese population. Further experimental studies are needed to clarify these associations.

Cadmium exposure has been associated with shortened telomeres, alterations in DNA methylation patterns, and increased mortality. However, the role of DNA methylation in mediating the relationship between cadmium and telomere dynamics is still unclear. Additionally, it is unknow how telomere dynamics and DNA methylation alterations may affect the association between cadmium exposure and mortality outcomes. We utilized data from 8716 National Health and Nutrition Examination Survey (NHANES) participants aged 18 and above, collected between 1999 and 2002, and linked these to mortality outcomes from the National Center for Health Statistics (NCHS) through 2019. In the final model, ln-blood cadmium was significantly and inversely associated with ln-T/S ratio (β = −0.043, 95% CI: −0.059 to −0.027, p < 0.001), while ln-Horvath DNAmTL was strongly and positively associated with ln-T/S ratio (β = 1.782, 95% CI: 1.467 to 2.097, p < 0.001). Moreover, ln-blood cadmium also showed a significant inverse association with ln-Horvath DNAmTL (β = −0.010, 95% CI: −0.014 to −0.006, p < 0.001). Structural equation modeling showed that the association between cadmium and T/S ratio was mediated by Horvath DNAmTL, with a total effect of −0.044, a direct effect of −0.027, and an indirect effect of −0.017. Furthermore, stratified analyses revealed that a 1-unit increase in ln-blood cadmium was associated with higher all-cause mortality, with hazard ratios (HR) of 1.47 for participants with T/S ratio below the median and 1.41 for those above. Similar patterns were observed for cardiovascular (HR = 1.68 vs. 1.30) and cancer mortality (HR = 1.75 vs. 1.42). For Horvath DNAmTL, the association was significant only for all-cause mortality (HR = 1.36 vs. 1.31). However, no significant interactions were detected. In conclusion, our findings suggest that Horvath DNAmTL is associated with the relationship between cadmium and telomere length, suggesting a potential DNA methylation pathway that warrants further longitudinal investigation. Individuals with lower T/S ratios or Horvath DNAmTL appear to be more susceptible to cadmium-related mortality. Further research is necessary to confirm these results.