Decreases in serum PFAS are associated with decreases in serum lipids: A longitudinal study on a highly exposed population

Introduction: Perfluoroalkyl substances (PFAS) are widely used, ubiquitous and highly persistent man-made chemicals. Previous cross-sectional studies have consistently linked PFAS exposure to alterations in lipid profiles. However, longitudinal investigations are preferred to mitigate issues related to reverse causation and confounding. Hence, we aimed to investigate the association between changes in serum PFAS and changes in serum lipids, while shedding light on potential modifiers of the examined relationships. Methods: We used data from a health surveillance program offered to residents of a vast area of the Veneto Region (North-Eastern Italy), who had been exposed to PFAS via contaminated drinking water until 2013. We included subjects aged ≥20 years who provided two blood samples over an average 4-year interval (n = 8101). We examined the relationships between changes in PFOA, PFOS and PFHxS and changes in total cholesterol (TC), high-density lipoprotein cholesterol (HDLC) and low-density lipoprotein cholesterol (LDL-C). Linear models were fitted for change in the natural logarithm (ln) of each lipid in relation to the change in the ln of PFAS. From the estimated regression coefficients, we calculated the predicted percentage change in the response for a ln-decrease in PFAS serum concentrations. Results: Overall concentrations of PFOA, PFOS, PFHxS fell by 62.1 %, 24.4 % and 35.4 % from baseline, while small increases in lipids were observed. Declines in PFAS concentrations were associated with decreases in all lipids. For a ln-decrease in PFOA HDL-C decreased by 1.99 % (95 % CI: 1.28, 2.70), TC by 1.49 % (95 % CI: 0.88, 2.10), and LDL-C by 1.40 % (95 % CI: 0.45, 2.37). Conclusions: We found a positive association between changes in PFAS concentrations and changes in cholesterol levels, observing the most marked contrasts across sexes and age groups. Our findings support the reversibility of the associations identified in cross-sectional analyses, emphasizing the importance of water treatment measures in mitigating adverse health effects.