Wei Zhengqi, Wei Keke, Yang Ming, Ying Ming, Yin Ziyue, Wang Na, Zhang Lei
School of Public Health, Guilin Medical University, Guilin, Guangxi 541199, China.
Institute of Women, Children and Reproductive Health, Shandong University, Jinan, Shandong, China; Reproductive Hospital Affiliated to Shandong University, Jinan, Shandong, PR China.
Ecotoxicol Environ Saf. 2024 Dec;288:117395. doi: 10.1016/j.ecoenv.2024.117395. Epub 2024 Nov 27.
PFAS pose a significant threat to cardiovascular health and increase the risk of atherosclerotic cardiovascular disease (ASCVD). However, there is limited research evidence regarding the mechanisms by which PFAS affect the risk of ASCVD and the exposure-risk (E-R) relationship. The effect of kidney function in the relationship between PFAS and ASCVD risk has not been adequately validated.
This study aims to explore the mechanisms by which four PFAS (Perfluorooctanoic acid (PFOA), Perfluorooctanesulfonic acid (PFOS), Perfluorohexanesulfonic acid (PFHS), and Perfluorononanoic acid (PFNA)) affect the risk of ASCVD and to verify and discuss the mediating effect of kidney function in this impact.
This study utilizes data from 14,607 participants in the NHANES 2005-2018 to conduct a cross-sectional study. Initially, Generalized Linear Model (GLM) and Restricted Cubic Splines models are used to assess the impact of four PFAS on ASCVD risk and the E-R relationship. Subsequently, the Weighted Quantile Sum regression (WQS) model is used to evaluate the relationship between mixed four PFAS exposure and ASCVD risk. Finally, Directed Acyclic Graphs (DAG) and causal mediation models are used to confirm and analyze whether the decline in kidney function mediates the impact of four PFAS on ASCVD risk.
The results from GLM and WQS models indicate that both singular and mixed four PFAS exposures are associated with an increased risk of ASCVD. The E-R curves between four PFAS singular and mixed exposures and ASCVD risk are all characterized by nonlinearity. The results from DAG and causal mediation models clearly indicate that the decline in kidney function plays a significant mediating role in the relationship between four PFAS and ASCVD risk.
Exposure levels of four PFAS do not significantly increase the risk of ASCVD unless they reach a certain threshold, and the decline in kidney function exerts a significant mediating effect in the relationship between four PFAS exposure and ASCVD risk.
全氟和多氟烷基物质（PFAS）对心血管健康构成重大威胁，并增加动脉粥样硬化性心血管疾病（ASCVD）的风险。然而，关于PFAS影响ASCVD风险的机制以及暴露-风险（E-R）关系的研究证据有限。肾功能在PFAS与ASCVD风险关系中的作用尚未得到充分验证。
本研究旨在探讨四种PFAS（全氟辛酸（PFOA）、全氟辛烷磺酸（PFOS）、全氟己烷磺酸（PFHS）和全氟壬酸（PFNA））影响ASCVD风险的机制，并验证和讨论肾功能在这一影响中的中介作用。
本研究利用2005 - 2018年美国国家健康与营养检查调查（NHANES）中14,607名参与者的数据进行横断面研究。首先，使用广义线性模型（GLM）和受限立方样条模型评估四种PFAS对ASCVD风险的影响以及E-R关系。随后，使用加权分位数和回归（WQS）模型评估四种PFAS混合暴露与ASCVD风险之间的关系。最后，使用有向无环图（DAG）和因果中介模型来确认和分析肾功能下降是否介导了四种PFAS对ASCVD风险的影响。
GLM和WQS模型的结果表明，四种PFAS的单一暴露和混合暴露均与ASCVD风险增加相关。四种PFAS单一暴露和混合暴露与ASCVD风险之间的E-R曲线均具有非线性特征。DAG和因果中介模型的结果清楚地表明，肾功能下降在四种PFAS与ASCVD风险的关系中起显著的中介作用。
四种PFAS的暴露水平除非达到一定阈值，否则不会显著增加ASCVD风险，并且肾功能下降在四种PFAS暴露与ASCVD风险的关系中发挥显著的中介作用。
