Per- and polyfluoroalkyl substances and calcifications of the coronary and aortic arteries in adults with prediabetes: Results from the diabetes prevention program outcomes study,Environment International

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Per- and polyfluoroalkyl substances and calcifications of the coronary and aortic arteries in adults with prediabetes: Results from the diabetes prevention program outcomes study
Environment International ( IF 10.3 ) Pub Date : 2021-02-22 , DOI: 10.1016/j.envint.2021.106446
Citlalli Osorio-Yáñez ₁ , Marco Sanchez-Guerra ₂ , Andres Cardenas ₃ , Pi-I D Lin ₄ , Russ Hauser ₅ , Diane R Gold ₆ , Ken P Kleinman ₇ , Marie-France Hivert ₄ , Abby F Fleisch ₈ , Antonia M Calafat ₉ , Thomas F Webster ₁₀ , Edward S Horton ₁₁ , Emily Oken ₄

Affiliation

Instituto de Investigaciones Biomédicas, Universidad Nacional Autonoma de Mexico, Ciudad de Mexico, Mexico.
Department of Developmental Neurobiology, National Institute of Perinatology, Mexico City, Mexico.
Division of Environmental Health Sciences, School of Public Health, University of California, Berkeley, Berkeley, CA, USA.
Division of Chronic Disease Research Across the Lifecourse, Department of Population Medicine, Harvard Medical School and Harvard Pilgrim Health Care Institute, Boston, MA, USA.
Department of Environmental Health, Harvard T.H. Chan School of Public Health, Boston, MA, USA.
Department of Environmental Health, Harvard T.H. Chan School of Public Health, Boston, MA, USA; Channing Division of Network Medicine, Brigham and Women's Hospital, Boston, MA, USA.
Department of Biostatistics, School of Public Health and Human Sciences, University of Massachusetts Amherst, Amherst, MA, USA.
Pediatric Endocrinology and Diabetes, Maine Medical Center, Portland, ME, USA; Center for Outcomes Research and Evaluation, Maine Medical Center Research Institute, Portland, ME, USA.
Division of Laboratory Sciences, National Center for Environmental Health, Centers for Disease Control and Prevention, Atlanta, GA, USA.
Department of Environmental Health, Boston University School of Public Health, Boston, MA, USA.
Joslin Diabetes Center, Harvard Medical School, Boston, MA, USA.

Background

Per- and polyfluoroalkyl substances (PFAS) are endocrine disrupting chemicals that have been associated with cardiovascular risk factors including elevated body weight and hypercholesterolemia. Therefore, PFAS may contribute to the development of atherosclerosis and cardiovascular disease (CVD). However, no previous study has evaluated associations between PFAS exposure and arterial calcification.

Methods and results

This study used data from 666 prediabetic adults enrolled in the Diabetes Prevention Program trial who had six PFAS quantified in plasma at baseline and two years after randomization, as well as measurements of coronary artery calcium (CAC) and ascending (AsAC) and descending (DAC) thoracic aortic calcification 13–14 years after baseline. We performed multinomial regression to test associations between PFAS and CAC categorized according to Agatston score [low (<10), moderate (11–400) and severe (>400)]. We used logistic regression to assess associations between PFAS and presence of AsAC and DAC. We adjusted models for baseline sex, age, BMI, race/ethnicity, cigarette smoking, education, treatment assignment (placebo or lifestyle intervention), and statin use. PFAS concentrations were similar to national means; 53.9% of participants had CAC > 11, 7.7% had AsAC, and 42.6% had DAC. Each doubling of the mean sum of plasma concentrations of linear and branched isomers of perfluorooctane sulfonic acid (PFOS) was associated with 1.49-fold greater odds (95% CI: 1.01, 2.21) of severe versus low CAC. This association was driven mainly by the linear (n-PFOS) isomer [1.54 (95% CI: 1.05, 2.25) greater odds of severe versus low CAC]. Each doubling of mean plasma N-ethyl-perfluorooctane sulfonamido acetic acid concentration was associated with greater odds of CAC in a dose-dependent manner [OR = 1.26 (95% CI:1.08, 1.47) for moderate CAC and OR = 1.37 (95% CI:1.07, 1.74) for severe CAC, compared to low CAC)]. Mean plasma PFOS and n-PFOS were also associated with greater odds of AsAC [OR = 1.67 (95% CI:1.10, 2.54) and OR = 1.70 (95% CI:1.13, 2.56), respectively], but not DAC. Other PFAS were not associated with outcomes.

Conclusions

Prediabetic adults with higher plasma concentrations of select PFAS had higher risk of coronary and thoracic aorta calcification. PFAS exposure may be a risk factor for adverse cardiovascular health among high-risk populations.

中文翻译：

成人糖尿病前期的全氟和多氟烷基物质以及冠状动脉和主动脉钙化：糖尿病预防计划结果研究的结果

背景

全氟和多氟烷基物质 (PFAS) 是干扰内分泌的化学物质，与心血管危险因素有关，包括体重增加和高胆固醇血症。因此，PFAS 可能导致动脉粥样硬化和心血管疾病 (CVD) 的发展。然而，之前没有研究评估 PFAS 暴露与动脉钙化之间的关联。

方法和结果

该研究使用了 666 名参加糖尿病预防计划试验的糖尿病前期成人的数据，这些成人在基线和随机化两年后在血浆中量化了 6 种 PFAS，以及冠状动脉钙化 (CAC) 和上升 (AsAC) 和下降 (DAC) 的测量值) 基线后 13-14 年胸主动脉钙化。我们进行了多项回归以测试根据 Agatston 评分 [低 (<10)、中 (11–400) 和重度 (>400)] 分类的 PFAS 和 CAC 之间的关联。我们使用逻辑回归来评估 PFAS 与 AsAC 和 DAC 的存在之间的关联。我们调整了基线性别、年龄、BMI、种族/民族、吸烟、教育、治疗分配（安慰剂或生活方式干预）和他汀类药物使用的模型。PFAS 浓度与国家平均值相似；53. 9% 的参与者有 CAC > 11，7.7% 有 AsAC，42.6% 有 DAC。全氟辛烷磺酸 (PFOS) 的线性和支化异构体血浆浓度平均总和每增加一倍，严重与低 CAC 的几率（95% CI：1.01、2.21）就增加 1.49 倍。这种关联主要由线性 (n-PFOS) 异构体驱动 [1.54 (95% CI: 1.05, 2.25) 严重与低 CAC 的几率]。平均血浆 N-乙基-全氟辛烷磺酰氨基乙酸浓度每增加一倍，以剂量依赖性方式与更大的 CAC 几率相关 [OR = 1.26 (95% CI:1.08, 1.47) 中度 CAC 和 OR = 1.37 (95% CI：1.07, 1.74）对于严重的 CAC，与低 CAC 相比）]。平均血浆 PFOS 和 n-PFOS 也与更高的 AsAC 几率相关 [OR = 1.67 (95% CI:1.10, 2.54) 和 OR = 1.70 (95% CI:1.13, 2.56)]，但不是 DAC。其他 PFAS 与结果无关。