Background

Residents of a large area of the Veneto Region (North-Eastern Italy) were exposed for decades to drinking water contaminated by perfluoroalkyl substances (PFAS). PFAS have been consistently associated with raised serum lipids, mainly in cross-sectional studies and in background exposure contexts, but the shape of the dose-response relationships has been poorly investigated. The objectives of our study were to evaluate the association between serum PFAS and serum lipids and their dose-response patterns in a large exposed population.

Methods

A cross-sectional study was conducted in 16,224 individuals aged 20–39 years recruited in the regional health surveillance program. 15,720 subjects were analysed after excluding pregnant women (n = 327), participants reporting use of cholesterol lowering medications (n = 67) or with missing information on the selected covariates (n = 110). Twelve PFAS were measured by HPLC-MS in serum; three (PFOA, PFOS and PFHxS) were quantifiable in at least 50% of samples. Non-fasting serum total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C) and triglycerides were measured by enzymatic assays in automated analysers and low-density lipoprotein cholesterol (LDL-C), non-HDL cholesterol and total/HDL cholesterol ratio were calculated. The associations between natural log (ln) transformed PFAS and lipids were assessed through generalized additive models using linear regression and smoothing thin plate splines, adjusted for potential confounders.

Results

There were strong positive associations between the ln-transformed PFOA, PFOS, and PFHxS and TC, HDL-C, and LDL-C, and between ln PFOA and PFHxS and triglycerides. Each ln-increase in PFOA was associated with an increase of 1.94 mg/dL (95% CI 1.48–2.41) in TC, with 4.99 mg/dL (CI 4.12–5.86) for PFOS and 2.02 mg/dL (CI 1.45–2.58) for PFHxS.

Conclusions

Investigation of the shape of exposure-response associations using splines showed a positive association with the largest increases per unit of PFAS in cholesterol levels occurring at the lower range of PFAS concentrations for each compound.

中文翻译：

---

威尼托大区高度暴露的年轻成年人群中全氟烷基物质与脂质分布之间的关联

背景

威尼托大区（意大利东北部）的居民几十年来一直暴露于被全氟烷基物质（PFAS）污染的饮用水中。PFAS一直与血脂升高相关联，主要是在横断面研究和背景暴露的背景下，但是剂量反应关系的形状尚未得到充分研究。我们研究的目的是评估大量暴露人群中血清PFAS与血脂之间的关联及其剂量反应模式。

方法

对在区域健康监测计划中招募的16224名20-39岁的个体进行了横断面研究。在排除孕妇（n = 327），参与者报告使用降胆固醇药物（n = 67）或缺少所选协变量信息（n = 110）之后，对15,720名受试者进行了分析。用HPLC-MS法测定血清中的十二种全氟辛烷磺酸。在至少50％的样品中可定量三种（PFOA，PFOS和PFHxS）。非空腹血清总胆固醇（TC），高密度脂蛋白胆固醇（HDL-C）和甘油三酸酯通过自动分析仪中的酶法测定以及低密度脂蛋白胆固醇（LDL-C），非HDL胆固醇和总/ HDL计算胆固醇比率。

结果

ln转化的PFOA，PFOS和PFHxS与TC，HDL-C和LDL-C之间以及ln PFOA和PFHxS与甘油三酸酯之间存在很强的正相关。PFOA的每增加一次，TC的增加1.94 mg / dL（95％CI 1.48–2.41），PFOS的增加4.99 mg / dL（CI 4.12–5.86）和2.02 mg / dL（CI 1.45–2.58） ）用于PFHxS。

结论

使用样条对暴露-反应关联的形状进行的研究显示，与每种化合物中较低的PFAS浓度范围内发生的胆固醇中每单位PFAS的最大增加呈正相关。