It is suggested that PFAS may be linked to inflammation and impaired fibrinolysis in midlife women, and none of these associations remained statistically significant after false discovery rate correction.
Abstract
Background Perfluoroalkyl/polyfluoroalkyl substances (PFAS) are emerging clinical and public health concerns, but their role in cardiovascular disease risk remains unclear. Inflammation and thrombosis may link PFAS and cardiovascular disease. Objective We investigated the association between serum PFAS concentrations and inflammatory and hemostatic markers in midlife women, and whether these markers mediated the association between PFAS and incident hypertension. Methods We analyzed 1,387 participants from the Study of Women’s Health Across the Nation from 1999 to 2000 to 2015 to 2016. Linear mixed-effects models estimated the association of 7 PFAS with high-sensitivity C-reactive protein (hs-CRP), fibrinogen, factor VII activity, plasminogen activator inhibitor-1 (PAI-1), and tissue plasminogen activator antigen. Quantile-g-computation evaluated mixture effects. Causal mediation analyses tested whether these markers mediated the PFAS-hypertension association. Results Individual PFAS were positively associated with hs-CRP and PAI-1. For hs-CRP, per doubling of PFAS ranged from 3.59% (95% CI: 0.01%-7.30%) for branched perfluorooctane sulfonic acid isomers to 5.32% (95% CI: 1.67%-9.10%) for 2-(N-methyl-perfluorooctane sulfonamido) acetic acid. For PAI-1, per doubling of PFAS ranged from 2.41% (95% CI: −0.86% to 5.78%) for the linear perfluorooctane sulfonic acid isomer to 3.04% (95% CI: 0.24%-5.93%) for 2-(N-methyl-perfluorooctane sulfonamido) acetic acid. However, none of these associations remained statistically significant after false discovery rate correction. PFAS mixture effects were 6.15% (95% CI: −0.83% to 13.58%) for hs-CRP and 6.05% (95% CI: 0.29%-12.14%) for PAI-1. No associations were found with other markers, and biomarkers did not mediate the PFAS-hypertension association. Conclusions These findings suggest, but do not establish, that PFAS may be linked to inflammation and impaired fibrinolysis in midlife women.
Per- and polyfluoroalkyl substances (PFAS) are pervasive organic compounds that have garnered significant attention due to their potential impacts on human health, particularly in relation to asthma, though current evidence remains limited. This study aimed to examine the association between PFAS exposure and adult asthma using a sample of 7106 participants aged 20 years and older from the NHANES survey, spanning 2003 to 2018. Survey-weighted multivariable logistic regression models, subgroup analysis, weighted quantile sum and Bayesian kernel machine regression models were employed to probe the relationship between PFAS and asthma. In the multivariable logistic regression analysis, higher log10-transformed perfluorooctane sulfonic acid (PFOS) and PFNA concentrations were significantly associated with lower odds of asthma (PFOS: OR = 0.76, 95% CI: 0.61–0.96; PFNA: OR = 0.77, 95% CI: 0.60–0.99). The inverse link between PFAS co-exposure and asthma incidence persisted across multi-pollutant models, weighted quantile sum regression, and Bayesian kernel machine regression models, with PFOS emerging as the primary negative influencer. In conclusion, this study highlights PFAS exposure is inversely associated with asthma risk in adults.
Tiankai Shan, Kai Wu, Jing-Xian Jiang· Medicine· 0 citations
OBJECTIVE
Epidemiological and toxicological studies have associated perfluoroalkyl and polyfluoroalkyl substances (PFAS) with adverse effects on multiple organ systems. However, the potential link between PFAS exposure and obstructive sleep apnea (OSA) remains limited.
METHODS
2,960 participants were selected from two cycles of National Health and Nutrition Examination Survey. OSA was evaluated by the multivariable apnea prediction index, and serum concentrations of nine PFAS were detected. Weighted logistic regression, RCS, and WQS regression were used to assess individual, nonlinear, and mixture associations.
RESULTS
PFDeA and PFUA showed significant inverse dose-response relationships, with quartile-based analyses showing protective effects for PFDeA, PFHxS, Me-PFOSA-AcOH, PFUA, and n-PFOS. RCS analyses revealed L-shaped nonlinear relationships for PFDeA and PFUA. Sex-stratified analyses identified a female-specific inverse association for Sm-PFOS (P for interaction = 0.025). WQS regression indicated significant protective mixture effects (OR = 0.69, P = 0.007), predominantly driven by PFUA, followed by n-PFOA and PFHxS.
CONCLUSION
The relationships between PFAS exposure and OSA risk are characterized by compound-specific, concentration-dependent, and sex-dimorphic patterns.
Mixture exposure showed a significant positive association with chronic obstructive pulmonary disease risk, and these substances disrupt pulmonary homeostasis through concurrent molecular activation and lipid-metabolic disturbance, evidenced by triglyceride-glucose index mediation.
Yansong Hu, Huanyu Cui, Yakun Wang et al.· BMC Pulmonary Medicine· 0 citations
Exposure to per- and polyfluoroalkyl substances (PFASs) has been associated with hypertension in some populations, but the associations among young men and underlying mechanisms remain unclear. We measured 16 plasma PFAS and assessed obesity and hypertension (blood pressure ≥130/80 mmHg) among 1283 Chinese young men. In total, 449 (35.0%) men had hypertension. Plasma 6:2 fluorotelomer phosphate diester (6:2 diPAP) concentrations were positively associated with hypertension in a linear dose–response manner (OR = 1.09, 95% CI: 1.01–1.16 per 2.7-fold increase), with an OR of 1.43 (1.07–1.90) for the highest versus lowest exposure tertile. Individual obesity indicators (body mass index [BMI], waist circumference, and waist-to-height ratio [WHtR]) explained 8.6%–19.2% of the association between 6:2 diPAP and hypertension. A machine learning-derived three-level obesity severity spectrum integrating WHtR and BMI (normal, elevated central adiposity alone, and elevated central adiposity with overweight) explained 36.9% of the association. In summary, exposure to 6:2 diPAP was associated with higher odds of hypertension among young men, partly mediated by obesity, with an integrated body shape pattern combining central and general adiposity showing the largest mediating effect.
Lili Huang, Na Ji, Huiling Shao et al.· Environment & Health· 0 citations
Per- and polyfluoroalkyl substances (PFAS), particularly perfluorooctanoic acid (PFOA) and perfluorooctanesulfonic acid (PFOS), are persistent environmental pollutants with potential immunotoxic effects. Emerging epidemiological evidence suggests a link between PFAS exposure and autoimmune diseases, including rheumatoid arthritis (RA). However, the causal nature of this relationship remains unclear. Genetic instruments for circulating PFOA and PFOS levels were obtained from genome-wide association studies of European populations, while RA outcome data were sourced from the FinnGen consortium and United Kingdom Biobank. Associations were evaluated using multiple Mendelian randomization (MR) methods to assess the robustness of the findings. The inverse variance weighted method served as the primary approach. Additional methods, including MR-Egger, weighted median, simple mode, weighted mode, maximum likelihood estimation, and robust adjusted profile score, were applied to address potential pleiotropy and weak instrument bias. Sensitivity analyses, including Cochran Q-test for heterogeneity, MR-pleiotropy residual sum and outlier (MR-PRESSO) for pleiotropy detection, and leave-one-out analysis, were performed to validate the robustness of the findings. MR analysis identified a significant association between genetically predicted PFOA levels and increased RA risk (odds ratio = 1.87, 95% confidence interval [1.13–3.11], P = .015). Similarly, genetically predicted PFOS levels were positively associated with seropositive RA risk (odds ratio = 1.14, 95% confidence interval [1.00–1.29], P = .049). Sensitivity analyses confirmed the robustness of these findings, and reverse MR analysis did not indicate bidirectional causality. Our findings provide genetic evidence suggesting a potential association between PFAS exposure and RA risk. Given the widespread environmental persistence of PFAS, further investigation into potential health impacts and strategies to reduce exposure may be warranted. Further mechanistic studies are warranted to elucidate the biological pathways underlying the potential relationship between PFAS exposure and RA.
It is suggested that higher plasma PFAS concentrations, particularly HFPO-DA, may be associated with more advanced TNM stage in colorectal cancer and warrant confirmation in larger prospective studies.
Ning Kang, Yang Zhao, Zhi Huang et al.· Frontiers in Toxicology· 1 citation