全氟化合物暴露与中老年女性血脂水平的关联

Associations of per-and poly-fluoroalkyl substances exposure with blood lipids in middle-aged and elderly women

[背景]全氟化合物(PFAS)是一类新型持久性有机污染物,其健康危害受到广泛关注。PFAS暴露对血脂稳态的影响尚缺乏流行病学研究。[目的]探究中老年女性中全氟辛基磺酸(PFOS)和全氟辛酸(PFOA)暴露与血脂水平和血脂异常之间的关联性。[方法]以东风-同济队列的女性子队列人群为研究对象,排除基线时未参与血脂水平测试者和使用降脂药物者,使用超高效液相色谱质谱联用仪检测795名中老年女性基线血浆中PFOS和PFOA的质量浓度,使用全自动分析仪检测基线血清中总胆固醇(TC)、甘油三酯(TG)、高密度脂蛋白胆固醇(HDL-C)和低密度脂蛋白胆固醇(LDL-C)的浓度。符合正态分布的资料采用均数±标准差(x±s)表示,偏态分布资料采用中位数M和第25、75百分位数(P25,P75)表示;采用广义线性回归模型、广义加性模型和logistic回归模型评估研究人群PFOS和PFOA暴露与血脂水平和血脂异常发生风险的关联性,并根据研究人群的基线人口学特性、生活方式和绝经状态进行分层分析,探讨PFOS和PFOA暴露与上述因素对血脂影响的交互效应。[结果]基线时研究对象年龄的x±s为(59.4±8.6)岁,体质量指数(BMI)为(24.3±3.4)kg·m^(-2),血浆PFOS和PFOA质量浓度的M(P25,P75)分别为9.96(6.24,15.09)和1.20(0.84,1.80)μg·L^(-1)。广义线性模型分析显示,随着血浆PFOS水平的增加,血清HDL-C浓度逐渐增加[b(95%CI):0.04(0.01~0.07)];随着血浆PFOA水平的增加,血清TC和LDL-C浓度也逐渐增加,b(95%CI)分别为0.05(0.02~0.08)和0.05(0.01~0.09)。未观察到血浆PFOS水平与血清TC、TG和LDL-C浓度的关联,也未观察到血浆PFOA水平与血清TG和HDL-C浓度的关联。分层分析发现,PFOA与LDL-C间的关联性主要体现在<60岁女性人群[b(95%CI):0.06(0.01~0.11),P=0.014];血浆PFOA水平与年龄在影响血清LDL-C浓度上存在交互作用(P交互=0.046)。对PFOS和PFOA暴露与血脂异常发生风险的关联性分析显示,血浆PFOA水平升高与高TC血症发生风险的增加相关联[OR(95%CI):1.69(1.23~2.15)];但未观察到PFOS暴露与血脂异常发生风险的关联性。[结论]以东风-同济队列女性子队列人群为基础的横断面研究发现,常见PFAS暴露可能影响机体的血脂稳态水平,该结果为PFAS的健康危害提供了新的证据。

[Background]Per-and poly-fluoroalkyl substances(PFAS)are a class of emerging persistent organic pollutants,and their negative health impacts have been widely concerned.There is a lack of epidemiological studies on the associations of PFAS exposure with lipid homeostasis.[Objective]To investigate the associations of perfluorooctanesulfonic acid(PFOS)and perfluorooctanoic acid(PFOA)exposure with blood lipid levels and dyslipidemia in middle-aged and elderly women.[Methods]This study was based on 795 middle-aged and elderly women from a female sub-cohort of the Dongfeng-Tongji cohort study,excluding the participants without blood lipid measurements and/or reported use of lipid-lowering drugs at baseline.The concentrations of plasma PFOS and PFOA were measured by ultra-high performance liquid chromatography-tandem mass spectrometry(UPLC-MS/MS).The concentrations of serum total cholesterol(TC),triglyceride(TG),high-density lipoprotein cholesterol(HDL-C),and low-density lipoprotein cholesterol(LDL-C)were measured using an automatic analyzer.The normally distributed continuous variables were presented as mean±standard deviation(x±s), while the skewedly distributed continuous variables were presented as median(M)and the 25^(th) and 75^(th) percentiles(P_(25),P_(75)).Generalized linear models(GLM),generalized additive models(GAM),and logistic regression models were applied to evaluate the associations of PFOS and PFOA exposure with blood lipid levels and the risk of dyslipidemia.Stratified analyses were also implemented to explore potential modification effects of sociodemographic characteristics,lifestyles,and menopause on associations of PFOS and PFOA exposure and blood lipids.[Results]The x±s of baseline age for the study participants was(59.4±8.6)years old,and their baseline body mass index(BMI)was(24.3±3.4)kg·m^(−2).The M(P25,P75)of baseline plasma concentrations for PFOS and PFOA were 9.96(6.24,15.09)μg·L^(−1) and 1.20(0.84,1.80)μg·L^(−1) respectively.The GLM analysis showed that plasma concentration of PFOS was positively associated with serum HDL-C[b(95%CI):0.04(0.01,0.07)].The plasma concentration of PFOA was also positively associated with serum TC[b(95%CI):0.05(0.02,0.08)]and serum LDL-C[b(95%CI):0.05(0.01,0.09)].No significant association was observed between plasma PFOS and serum TC,TG,or LDL-C,nor between plasma PFOA and serum TG or HDL-C.The stratified analyses showed that the association between PFOA and LDL-C was significant among the participants aged<60 years old[b(95%CI):0.06(0.01,0.11),P=0.014].A modification effect was observed for age on the association of plasma PFOA with serum LDL-C,with Pinteraction=0.046.The analysis of the associations between PFOS/PFOA exposure and the risk of dyslipidemia showed that an increased plasma PFOA was significantly associated with an increased risk of hypercholesterolemia,with an OR(95%CI)of 1.69(1.23,2.15).No association was observed between PFOS exposure and the risk of dyslipidemia.[Conclusion]This cross-sectional study reveals that common PFAS exposure could affect the homeostasis of blood lipids based on the female sub-cohort of the Dongfeng-Tongji cohort,which provides new evidence for the negative health impact of PFAS.