Associations between perfluoroalkyl substances and lipid profile in a highly exposed young adult population in the Veneto Region

Canova, Cristina; Barbieri, Giulia; Jeddi, Maryam Zare; Gion, Massimo; Fabricio, Aline S C; Daprà, Francesca; Russo, Federico; Fletcher, Tony; Pitter, Gisella

doi:10.1016/j.envint.2020.106117

Cited by 67 publications

(54 citation statements)

References 70 publications

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“…This association is consistently evident for altered total and LDL cholesterol but not for HDL-C and TG. Our findings of inverse associations between PFAS, triglycerides (mainly for PFOS) and HDL-C are in the same direction as other studies [17,31,36,37]. As for elevated blood pressure, positive associations are reported for some PFAS in recent studies [11,18,38].…”

Section: Discussionsupporting

confidence: 90%

Associations of Perfluoroalkyl Substances with Prevalence of Metabolic Syndrome in Highly Exposed Young Adult Community Residents—A Cross-Sectional Study in Veneto Region, Italy

Jeddi

Zuanna

Barbieri

et al. 2021

IJERPH

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Background: Studies on the association between perfluoroalkyl substances (PFAS) and metabolic syndrome (MetS) are limited, and results are inconsistent. We aimed to examine the associations between PFAS serum levels and the prevalence of MetS among highly exposed young adults (ages 20–39) residents of a large area of the Veneto Region (North-Eastern Italy) primarily stemming from PFAS water contamination before September 2013. A total of 15,876 eligible young adult residents living in the investigated municipalities were enrolled in the study from January 2017 to July 2019. Methods: MetS was defined by using a modified harmonized definition requiring the presence of 3 of the following: obesity (body mass index ≥30), elevated triglyceride (TG), reduced high-density lipoprotein cholesterol, elevated blood pressure, and hemoglobin A1c ≥ 6.1% or self-reported diabetes mellitus or drug treatment for hyperglycemia. Multivariable generalized additive models were performed to identify the associations between four serum PFAS, including perfluorooctane sulfonic acid (PFOS), perfluorooctanoic acid (PFOA), perfluorohexane sulfonic acid (PFHxS), and perfluorononanoic acid (PFNA), and risk of MetS controlling for potential confounders. Results: A total of 1282 participants (8.1%) met the criteria of MetS with a higher prevalence among men. PFOA, PFHxS, and PFNA were not associated with the risk of MetS, whereas PFOS showed a consistent protective effect against the risk of MetS (OR 0.76, (95% CI: 0.69, 0.85) per ln-PFOS). However, we found statistically significant positive associations between PFAS serum levels and individual components of MetS, mainly elevated blood pressure and elevated TG. Conclusion: Our results did not support a consistent association between PFAS and MetS and conflicting findings were observed for individual components of MetS.

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Section: Discussionsupporting

confidence: 90%

Associations of Perfluoroalkyl Substances with Prevalence of Metabolic Syndrome in Highly Exposed Young Adult Community Residents—A Cross-Sectional Study in Veneto Region, Italy

Jeddi

Zuanna

Barbieri

et al. 2021

IJERPH

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“…These findings are quite similar to those we previously reported in a group of more than 16,000 young adults (age 20-39 years) recruited in the Veneto Region's health surveillance program [13]: also in that sub-population, we found that PFOS had a stronger effect compared to PFOA and PFHxS and that the relationship was log-linear.…”

Section: Serum Lipidssupporting

confidence: 91%

PFAS Concentrations and Cardiometabolic Traits in Highly Exposed Children and Adolescents

Canova¹,

Nisio²,

Barbieri³

et al. 2021

Preprint

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Background: Residents of a large area of North-Eastern Italy were exposed for decades to high concentrations of perfluoroalkyl and polyfluoroalkyl substances (PFAS) via drinking water. Despite the large amount of evidence in adults of a positive association between serum PFAS and metabolic outcomes, studies focusing on children and adolescents are limited. We evaluated the associations between serum PFAS concentrations and lipid profile, blood pressure and body mass index (BMI) in highly exposed adolescents and children. Methods: A cross-sectional analysis was conducted in 6669 adolescents (14-19 years) and 2693 children (8-11 years) enrolled in the health surveillance program of the Veneto Region. Non-fasting blood samples were obtained and analyzed for perfluorooctanoic acid (PFOA) perfluorooctane sulfonate (PFOS), perfluorohexanesulfonic acid (PFHxS), perfluorononanoic acid (PFNA), total cholesterol (TC) high-density lipoprotein cholesterol (HDL-C) and triglycerides. Low-density lipoprotein cholesterol (LDL-C) was calculated. Systolic and diastolic blood pressure (BP) were measured and BMI z-score accounting for age and sex was estimated. The associations between ln-transformed PFAS (and categorized into quartiles) and continuous outcomes were assessed using generalized additive models. Analyses were stratified by gender and adjusted for potential confounders. Results: Among adolescents, significant associations were detected between all investigated PFAS and TC, LDL-C, and to a fewer extent HDL-C. Among children, PFOS and PFNA had significant associations with TC, LDL-C and HDL-C, while PFOA and PFHxS had significant associations with HDL-C only. Increased serum concentrations of PFAS, particularly PFOS, were associated with decreased BMI z-score. No statistically significant associations were observed between PFAS concentrations and BP. Conclusions: Our study supports a consistent association between PFAS concentration and serum lipids, stronger for PFOS and PFNA and with a greater magnitude among children compared to adolescents, and a negative association of PFAS with BMI.

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“…The epidemiological evidence mainly comprises cross-sectional associations between serum PFOS/PFOA and increased levels of cholesterol in blood, with a few examples of longitudinal studies (EFSA CONTAM Panel 2018a). Most studies have used general population samples with the "normal" range of PFOS/PFOA concentrations for that country at that time (Nelson et al 2010;Eriksen et al 2013;Geiger et al 2014;Starling et al 2014) and some have used specific populations with occupational exposure Sakr et al 2007a;Sakr et al 2007b) or contaminated community drinking water supplies (Steenland et al 2009;Frisbee et al 2010;Canova et al 2020;Li et al 2020). Exposure to the chemicals was in general for several decades.…”

Section: Effects Observed In Human Studiesmentioning

confidence: 99%

“…Much of the increase is observed at low PFOS/ PFOA serum levels and seems to level off at higher levels (above about 50 ng/mL), as also shown by the modeling of the data (EFSA CONTAM Panel 2018a). Another large population with PFAS exposure from contaminated drinking water, predominantly PFOA, is in the Veneto region of Italy (Canova et al 2020). A cross sectional analysis of PFASs and lipids was carried out in nearly 16 000 people, between 20 and 39 years.…”

Section: Effects Observed In Human Studiesmentioning

confidence: 99%

Systemic PFOS and PFOA exposure and disturbed lipid homeostasis in humans: what do we know and what not?

Fragki

Dirven

Fletcher

et al. 2021

Critical Reviews in Toxicology

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103

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Associations between per-and polyfluoroalkyl substances (PFASs) and increased blood lipids have been repeatedly observed in humans, but a causal relation has been debated. Rodent studies show reverse effects, i.e. decreased blood cholesterol and triglycerides, occurring however at PFAS serum levels at least 100-fold higher than those in humans. This paper aims to present the main issues regarding the modulation of lipid homeostasis by the two most common PFASs, PFOS and PFOA, with emphasis on the underlying mechanisms relevant for humans. Overall, the apparent contrast between human and animal data may be an artifact of dose, with different molecular pathways coming into play upon exposure to PFASs at very low versus high levels. Altogether, the interpretation of existing rodent data on PFOS/PFOA-induced lipid perturbations with respect to the human situation is complex. From a mechanistic perspective, research on human liver cells shows that PFOS/PFOA activate the PPARa pathway, whereas studies on the involvement of other nuclear receptors, like PXR, are less conclusive. Other data indicate that suppression of the nuclear receptor HNF4a signaling pathway, as well as perturbations of bile acid metabolism and transport might be important cellular events that require further investigation. Future studies with human-relevant test systems would help to obtain more insight into the mechanistic pathways pertinent for humans. These studies shall be designed with a careful consideration of appropriate dosing and toxicokinetics, so as to enable biologically plausible quantitative extrapolations. Such research will increase the understanding of possible perturbed lipid homeostasis related to PFOS/ PFOA exposure and the potential implications for human health.

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Associations between perfluoroalkyl substances and lipid profile in a highly exposed young adult population in the Veneto Region

Cited by 67 publications

References 70 publications

Associations of Perfluoroalkyl Substances with Prevalence of Metabolic Syndrome in Highly Exposed Young Adult Community Residents—A Cross-Sectional Study in Veneto Region, Italy

Associations of Perfluoroalkyl Substances with Prevalence of Metabolic Syndrome in Highly Exposed Young Adult Community Residents—A Cross-Sectional Study in Veneto Region, Italy

PFAS Concentrations and Cardiometabolic Traits in Highly Exposed Children and Adolescents

Systemic PFOS and PFOA exposure and disturbed lipid homeostasis in humans: what do we know and what not?

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