BACKGROUND The associations of perfluoroalkyl substance (PFAS) exposure with blood lipids and lipoproteins are inconsistent, and existing studies did not account for metabolic heterogeneity of lipoprotein subspecies. This study aimed to examine the associations between plasma PFAS concentrations and lipoprotein and apolipoprotein subspecies. METHODS The study included 326 men and women from the 2-year Prevention of Obesity Using Novel Dietary Strategies (POUNDS) Lost randomized trial. Five PFASs, including perfluorooctanesulfonic acid (PFOS), perfluorooctanoic acid (PFOA), perfluorohexanesulfonic acid (PFHxS), perfluorononanoic acid (PFNA), and perfluorodecanoic acid (PFDA), were measured in plasma at baseline. For lipoprotein and apolipoprotein subspecies, total plasma was fractionated first by apolipoprotein (apo) C-III content and then by density. Each subfraction was then measured for apoB, apoC-III, and apoE concentrations, as well as triglyceride and cholesterol contents, both at baseline and at 2 years. RESULTS For lipids and apolipoproteins in total plasma at baseline, elevated plasma PFAS concentrations were significantly associated with higher apoB and apoC-III concentrations, but not with total cholesterol or triglycerides. After multivariate adjustment of lifestyle factors, lipid-lowering medication use, and dietary intervention groups, PFAS concentrations were primarily associated with lipids or apolipoprotein concentrations in intermediate-to-low density lipoprotein (IDL + LDL) and high-density lipoprotein (HDL) that contain apoC-III. Comparing the highest and lowest tertiles of PFOA, the least-square means (SE) (mg/dl) were 4.16 (0.4) vs 3.47 (0.4) for apoB (P trend = 0.04), 2.03 (0.2) vs 1.66 (0.2) for apoC-III (P trend = 0.04), and 8.4 (0.8) vs 6.8 (0.8) for triglycerides (P trend = 0.03) in IDL + LDL fraction that contains apoC-III. For HDL that contains apoC-III, comparing the highest and lowest tertiles of PFOA, the least-square means (SE) (mg/dl) of apoC-III were 11.9 (0.7) vs 10.4 (0.7) (P trend = 0.01). In addition, elevated PFNA and PFDA concentrations were also significantly associated with higher concentrations of apoE in HDL that contains apoC-III (P trend< 0.01). Similar patterns of associations were demonstrated between baseline PFAS concentrations and lipoprotein subspecies measured at 2 years. Baseline PFAS levels were not associated with changes in lipoprotein subspecies during the intervention. CONCLUSIONS Our results suggest that plasma PFAS concentrations are primarily associated with blood lipids and apolipoproteins in subspecies of IDL, LDL, and HDL that contain apoC-III, which are associated with elevated cardiovascular risk in epidemiological studies. Future studies of PFAS-associated cardiovascular risk should focus on lipid subfractions.

中文翻译：

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全氟烷基物质与脂蛋白亚种中的血脂和载脂蛋白的关联：POUNDS-loss 研究。


背景 全氟烷基物质（PFAS）暴露与血脂和脂蛋白的关联并不一致，现有研究并未考虑脂蛋白亚种的代谢异质性。本研究旨在探讨血浆 PFAS 浓度与脂蛋白和载脂蛋白亚种之间的关联。方法 该研究纳入了来自为期 2 年的使用新型饮食策略预防肥胖 (POUNDS) Lost 随机试验的 326 名男性和女性。基线时在血浆中测量了五种 PFAS，包括全氟辛烷磺酸 (PFOS)、全氟辛酸 (PFOA)、全氟己烷磺酸 (PFHxS)、全氟壬酸 (PFNA) 和全氟癸酸 (PFDA)。对于脂蛋白和载脂蛋白亚种，总血浆首先按载脂蛋白 (apo) C-III 含量进行分级，然后按密度进行分级。然后在基线和 2 年时测量每个亚组分的 apoB、apoC-III 和 apoE 浓度以及甘油三酯和胆固醇含量。结果 对于基线时总血浆中的脂质和载脂蛋白，血浆 PFAS 浓度升高与较高的 apoB 和 apoC-III 浓度显着相关，但与总胆固醇或甘油三酯无关。在对生活方式因素、降脂药物使用和饮食干预组进行多变量调整后，PFAS浓度主要与中低密度脂蛋白（IDL + LDL）和高密度脂蛋白（HDL）中的脂质或载脂蛋白浓度相关，含有apoC-III。比较 PFOA 的最高和最低三分位数，apoB 的最小二乘平均值 (SE) (mg/dl) 分别为 4.16 (0.4) 与 3.47 (0.4)（P 趋势 = 0.04）、2.03 (0.2) 与 1.66 (0.2)对于 apoC-III（P 趋势 = 0.04），以及 8.4 (0.8) 与 6.8 (0.8) 含有 apoC-III 的 IDL + LDL 级分中的甘油三酯（P 趋势 = 0.03）。对于含有 apoC-III 的 HDL，比较 PFOA 的最高和最低三分位数，apoC-III 的最小二乘平均值 (SE) (mg/dl) 分别为 11.9 (0.7) 和 10.4 (0.7)（P 趋势 = 0.01） 。此外，PFNA 和 PFDA 浓度升高也与含有 apoC-III 的 HDL 中 apoE 浓度升高显着相关（P 趋势 < 0.01）。基线 PFAS 浓度与 2 年测量的脂蛋白亚种之间存在类似的关联模式。干预期间基线 PFAS 水平与脂蛋白亚种的变化无关。结论 我们的结果表明，血浆 PFAS 浓度主要与含有 apoC-III 的 IDL、LDL 和 HDL 亚种的血脂和载脂蛋白相关，在流行病学研究中，这些亚种与心血管风险升高相关。 PFAS 相关心血管风险的未来研究应集中在脂质亚组分上。