Abstract

Background:

Per- and polyfluoroalkyl substances (PFAS) are widespread environmental contaminants associated with diseases such as cancer and dyslipidemia. However, few studies have investigated the association between PFAS mixture exposure and mortality in general populations.

Objectives:

This study aimed to explore the association between PFAS mixture, perfluorooctanoic acid (PFOA), and perfluorooctane sulfonic acid (PFOS) and mortality in U.S. adults by a nationally representative cohort.

Methods:

Adults $\ge 18\text{\hspace{0.17em}years}$ of age who were enrolled in the National Health and Nutrition Examination Survey (NHANES) (1999–2014) were included in our study. Baseline serum concentrations of seven PFAS were measured and individuals were followed up to 31 December 2015. Hazard ratios (HRs) and confidence intervals (CIs) were estimated using Cox proportional hazards models. Association between PFAS mixture exposure and mortality was analyzed using the k-means method by clustering PFAS mixtures into subgroups. Association between PFOA/PFOS exposure and mortality was subsequently analyzed in both continuous and categorical models.

Results:

During the follow-up period, 1,251 participants died. In the mixture analysis, the k-means algorithm clustered participants into low-, medium-, and high-exposure groups. Compared with the low-exposure group, participants in the high-exposure group showed significantly higher risks for all-cause mortality ($\text{HR}=1.38$; 95% CI: 1.07, 1.80), heart disease mortality ($\text{HR}=1.58$; 95% CI: 1.05, 2.51), and cancer mortality ($\text{HR}=1.70$; 95% CI: 1.08, 2.84). In single PFAS analysis, PFOS was found to be positively associated with all-cause mortality (third vs. first tertile $\text{HR}=1.57$; 95% CI: 1.22, 2.07), heart disease mortality (third vs. first tertile $\text{HR}=1.65$; 95% CI: 1.09, 2.57), and cancer mortality (third vs. first tertile $\text{HR}=1.75$; 95% CI: 1.10, 2.83), whereas PFOA exposure had no significant association with mortality. Assuming the observed association is causal, the number of deaths associated with PFOS exposure ($\ge 17.1$ vs. $<7.9\text{\hspace{0.17em}ng}/\mathrm{mL}$) was $\sim \mathrm{382,000}$ (95% CI: 176,000, 588,000) annually between 1999 and 2015, and it decreased to 69,000 (95% CI: 28,000, 119,000) annually between 2015 and 2018. The association between PFOS and mortality was stronger among women and people without diabetes.

Discussion:

We observed a positive association between PFAS mixture exposure and mortality among U.S. adults. Limitations of this study include the potential for unmeasured confounding, selection bias, a relatively small number of deaths, and only measuring PFAS at one point in time. Further studies with serial measures of PFAS concentrations and longer follow-ups are necessary to elucidate the association between PFAS and mortality from specific causes. https://doi.org/10.1289/EHP10393

中文翻译：

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美国成年人暴露于全氟和多氟烷基物质和死亡率：基于人群的队列研究

摘要

背景：

全氟和多氟烷基物质 (PFAS) 是与癌症和血脂异常等疾病相关的广泛环境污染物。然而，很少有研究调查 PFAS 混合物暴露与一般人群死亡率之间的关系。

目标：

本研究旨在通过具有全国代表性的队列研究 PFAS 混合物、全氟辛酸 (PFOA) 和全氟辛烷磺酸 (PFOS) 与美国成年人死亡率之间的关系。

方法：

成年人$\ge 18\text{\hspace{0.17em}年}$我们的研究包括参加全国健康和营养检查调查 (NHANES) (1999-2014) 的年龄。测量了七种 PFAS 的基线血清浓度，并对个体进行了随访至 2015 年 12 月 31 日。使用 Cox 比例风险模型估计了风险比 (HR) 和置信区间 (CI)。PFAS 混合物暴露与死亡率之间的关联使用k均值法通过将 PFAS 混合物聚类为亚组进行分析。随后在连续模型和分类模型中分析了全氟辛酸/全氟辛烷磺酸暴露与死亡率之间的关联。

结果：

在随访期间，有 1,251 名参与者死亡。在混合分析中，k -means 算法将参与者分为低、中、高暴露组。与低暴露组相比，高暴露组参与者的全因死亡风险显着更高。$\text{人力资源}=1.38$; 95% CI: 1.07, 1.80), 心脏病死亡率 ($\text{人力资源}=1.58$; 95% CI：1.05, 2.51）和癌症死亡率（$\text{人力资源}=1.70$; 95% CI：1.08、2.84）。在单一 PFAS 分析中，发现 PFOS 与全因死亡率呈正相关（第三与第一三分位数）$\text{人力资源}=1.57$; 95% CI: 1.22, 2.07)，心脏病死亡率（第三与第一三分位数）$\text{人力资源}=1.65$; 95% CI: 1.09, 2.57) 和癌症死亡率（第三与第一三分位数$\text{人力资源}=1.75$; 95% CI：1.10、2.83），而 PFOA 暴露与死亡率没有显着相关性。假设观察到的关联是因果关系，则与 PFOS 暴露相关的死亡人数（$\ge 17.1$对比$<7.9\text{\hspace{0.17em}吴}/\mathrm{毫升}$） 曾是$～\mathrm{382,000}$(95% CI: 176,000, 588,000) 在 1999 年至 2015 年间每年下降至 69,000 (95% CI: 28,000, 119,000)。在女性和非糖尿病患者中，PFOS 与死亡率之间的关联更强。

讨论：

我们观察到美国成年人的 PFAS 混合物暴露与死亡率之间存在正相关关系。本研究的局限性包括可能存在无法测量的混杂、选择偏倚、相对较少的死亡人数以及仅在一个时间点测量 PFAS。需要进一步研究对 PFAS 浓度进行系列测量和更长的随访时间，以阐明 PFAS 与特定原因死亡率之间的关联。https://doi.org/10.1289/EHP10393