Exposure to Perfluoroalkyl Chemicals and Cardiovascular Disease: Experimental and Epidemiological Evidence

Meneguzzi, Alessandra; Fava, Cristiano; Castelli, Marco; Minuz, Pietro

doi:10.3389/fendo.2021.706352

Cited by 86 publications

(38 citation statements)

References 81 publications

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“…There is also increasing experimental evidence linking PFAS exposure to platelet activation and thrombus formation. 11 Our observed associations with arrhythmias have not been previously examined and may suggest a novel cardiac parameter worthy of further investigation. Outside of these individual chronic diseases, we also observed associations with osteoporosis.…”

Section: Discussionmentioning

confidence: 79%

“…airborne dust, food packaging, and cookware may all remain relevant to this day. 4 PFAS exposure is associated with multiple health outcomes including cancer, 5 lipid metabolism, 6 , 7 thyroid disruption, 8 , 9 cardiovascular disease, 10 , 11 and kidney disease. 12 , 13 In addition, mechanistic studies have probed the molecular actions that lead to such a wide array of health outcomes for PFAS and have shown that PFAS are associated with increases in markers of oxidative stress.…”

Section: Introductionmentioning

confidence: 99%

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Associations between PFAS occurrence and multimorbidity as observed in an electronic health record cohort

Ward‐Caviness¹,

Moyer²,

Weaver³

et al. 2022

Environmental Epidemiology

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Background: Per and polyfluoroalkyl substances (PFAS) are associated with health outcomes ranging from cancer to high cholesterol. However, there has been little examination of how PFAS exposure might impact the development of multiple chronic diseases, known as multimorbidity. Here, we associated the presence of one or more PFAS in water systems serving the zip code of residence with chronic disease and multimorbidity. Methods: We used data from the unregulated contaminant monitoring rule 3 to estimate exposure to PFAS for a random sample of 10,168 patients from the University of North Carolina Healthcare System. The presence of 16 chronic diseases was determined via. their electronic health records. We used a logistic regression model in a cross-sectional study design to associate the presence of one or more PFAS with multimorbidity. Models were adjusted for age, race, sex, smoking status, socioeconomic status, and 20 county-level confounders. Results: There were four PFAS found in water systems that served at least one zip code represented in our patient data: PFOA, PFHpA, PFOS, and PFHxS. Exposure to any PFAS was associated with a odds ratio of 1.25 for multimorbidity (95% confidence interval = 1.09, 1.45). Among the chronic diseases with at least 300 cases, we observed associations with dyslipidemia, hypertension, ischemic heart disease, and osteoporosis. Conclusion: Exposure to PFAS is associated with a range of chronic diseases as well as multimorbidity. Accounting for the joint impacts of PFAS on multiple chronic conditions may give an increasingly clear picture of the public health impacts of PFAS.

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Section: Discussionmentioning

confidence: 79%

Section: Introductionmentioning

confidence: 99%

Associations between PFAS occurrence and multimorbidity as observed in an electronic health record cohort

Ward‐Caviness¹,

Moyer²,

Weaver³

et al. 2022

Environmental Epidemiology

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“…PFAS are exclusively man-made EDCs and environmentally persistent chemicals which are used to manufacture a wide variety of consumer and industrial products, non-stick, stain and water resistant coatings, fire suppression foams, and cleaning products (Liu et al (2018) and Jain and Ducatman (2018)). Both PFAS and metals have been associated with increase in cardiovascular disease (CVD) or death using many cross-sectional and longitudinal observational studies and experimental animal models (Meneguzzi et al (2021)). Hypercholesterolemia is one of the significant risk factors for CVD and it is characterized by the presence of high levels of cholesterol in the blood.…”

Section: Application In Exposure-mixture Association Of Per-and Poly-...mentioning

confidence: 99%

“…4 Application in exposure-mixture association of PFAS and metals with serum lipids among US adults PFAS are exclusively man-made EDCs and environmentally persistent chemicals which are used to manufacture a wide variety of consumer and industrial products, non-stick, stain and water resistant coatings, fire suppression foams, and cleaning products (Liu et al (2018) and Jain and Ducatman (2018)). Both PFAS and metals have been associated with increase in cardiovascular disease (CVD) or death using many crosssectional and longitudinal observational studies and experimental animal models (Meneguzzi et al (2021)).…”

Section: Notion Of Sufficient Sample Sizementioning

confidence: 99%

Quantifying the Effect Size of Exposure-Outcome Association Using δ-score: Application to Environmental Chemical Mixture studies

Midya

Liao

Gennings

et al. 2022

Preprint

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In environmental epidemiology, analysis of environmental mixture in association to health effects is gaining popularity. Such models mostly focus on inferences of hypotheses or summarizing strength of association through regression coefficients and corresponding estimates of precision. Nonetheless, when a decision is made against alternative hypothesis, it becomes increasingly difficult to tease apart whether the decision is influenced by sample size or represents genuine absence of association and whether the result warrants further investigation. Similarly, in case of a decision made in favour of alternative hypothesis, a significant association may indicate influence of large sample and not a strong effect. Moreover, the disparate type 1 and type 2 errors, might render these inferences unreliable. Using Cohen’s f2 to evaluate the strength of explanatory associations in a more fundamental way, we herein propose a new concept, optimal impact, to quantify the maximum explanatory association solely contributed by an environmental-mixture after controlling for confounders and covariates such that the type 2 error remains at its minimum. optimal impact is built upon a novel hypothesis testing procedure in which the rejection region is determined in a way that type 1 and type 2 errors are balanced. Even when an association does not achieve statistical significance, its optimal impact might deem it meaningful and strong enough for further investigation. This idea was naturally extended to estimate sample size in designing studies by striking a balance between explanatory precision and utility. The properties of this framework are carefully studied and detailed results are established. A straightforward application of this procedure is illustrated using an exposure-mixture analysis of per-and-poly-fluoroalkyl substances and metals with serum cholesterols using data from 2017–2018 US National Health and Nutrition Examination Survey.

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“…A common thread linking these diseases is a change in hemodynamics connected to ischemic injury [180][181][182], a factor that independently drives LUTD in mice [174]. Environmental chemical exposures have been linked to cardiovascular disease and diabetes [183][184][185][186], and this is another mechanism by which they may drive LUTD.…”

Section: The Relationship Between Lutd and Comorbiditiesmentioning

confidence: 99%

Male Lower Urinary Tract Dysfunction: An Underrepresented Endpoint in Toxicology Research

Peterson

Vezina

2022

Toxics

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Lower urinary tract dysfunction (LUTD) is nearly ubiquitous in men of advancing age and exerts substantial physical, mental, social, and financial costs to society. While a large body of research is focused on the molecular, genetic, and epigenetic underpinnings of the disease, little research has been dedicated to the influence of environmental chemicals on disease initiation, progression, or severity. Despite a few recent studies indicating a potential developmental origin of male LUTD linked to chemical exposures in the womb, it remains a grossly understudied endpoint in toxicology research. Therefore, we direct this review to toxicologists who are considering male LUTD as a new aspect of chemical toxicity studies. We focus on the LUTD disease process in men, as well as in the male mouse as a leading research model. To introduce the disease process, we describe the physiology of the male lower urinary tract and the cellular composition of lower urinary tract tissues. We discuss known and suspected mechanisms of male LUTD and examples of environmental chemicals acting through these mechanisms to contribute to LUTD. We also describe mouse models of LUTD and endpoints to diagnose, characterize, and quantify LUTD in men and mice.

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Exposure to Perfluoroalkyl Chemicals and Cardiovascular Disease: Experimental and Epidemiological Evidence

Cited by 86 publications

References 81 publications

Associations between PFAS occurrence and multimorbidity as observed in an electronic health record cohort

Associations between PFAS occurrence and multimorbidity as observed in an electronic health record cohort

Quantifying the Effect Size of Exposure-Outcome Association Using δ-score: Application to Environmental Chemical Mixture studies

Male Lower Urinary Tract Dysfunction: An Underrepresented Endpoint in Toxicology Research

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