Instituto de Investigaciones Biomédicas, Universidad Nacional Autonoma de Mexico, Ciudad de Mexico, Mexico.
Department of Developmental Neurobiology, National Institute of Perinatology, Mexico City, Mexico.
Environ Int. 2021 Jun;151:106446. doi: 10.1016/j.envint.2021.106446. Epub 2021 Feb 22.
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.
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.
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.
全氟和多氟烷基物质（PFAS）是内分泌干扰化学物质，与包括体重升高和高胆固醇血症在内的心血管危险因素有关。因此，PFAS 可能导致动脉粥样硬化和心血管疾病（CVD）的发生。然而，以前没有研究评估过 PFAS 暴露与动脉钙化之间的关系。
本研究使用了参加糖尿病预防计划试验的 666 名糖尿病前期成年人的数据，这些人在基线和随机分组后两年内血浆中有 6 种 PFAS 被定量，在基线后 13-14 年时进行了冠状动脉钙（CAC）和升主动脉（AsAC）及降主动脉（DAC）钙化的测量。我们使用多项分类回归来检验根据 Agatston 评分[低（<10）、中（11-400）和高（>400）]分类的 CAC 与 PFAS 之间的关联。我们使用逻辑回归来评估 PFAS 与 AsAC 和 DAC 存在之间的关联。我们调整了模型以纳入基线时的性别、年龄、BMI、种族/民族、吸烟状况、教育程度、治疗分配（安慰剂或生活方式干预）和他汀类药物使用情况。PFAS 浓度与全国平均值相似；53.9%的参与者 CAC>11，7.7%有 AsAC，42.6%有 DAC。血浆中线性和支链全氟辛烷磺酸（PFOS）的平均总和每增加一倍，严重 CAC 与低 CAC 的比值比（OR）就增加 1.49 倍（95%CI：1.01，2.21）。这种关联主要是由线性（n-PFOS）异构体引起的[严重 CAC 与低 CAC 的比值比（OR）为 1.54（95%CI：1.05，2.25）]。血浆中 N-乙基全氟辛烷磺酰胺基乙酸的平均浓度每增加一倍，与 CAC 呈剂量依赖性的更大比值比相关[中度 CAC 的比值比（OR）为 1.26（95%CI：1.08，1.47），严重 CAC 的比值比（OR）为 1.37（95%CI：1.07，1.74），而低 CAC 的比值比（OR）为 1.00]）。血浆中 PFOS 和 n-PFOS 的平均浓度也与 AsAC 的比值比增加有关[OR=1.67（95%CI：1.10，2.54）和 OR=1.70（95%CI：1.13，2.56）]，但与 DAC 无关。其他 PFAS 与结果无关。
具有较高血浆浓度的特定 PFAS 的糖尿病前期成年人患冠状动脉和胸主动脉钙化的风险更高。PFAS 暴露可能是高危人群心血管健康不良的一个风险因素。
