[Association between perfluoroalkyl substance exposure and adverse cardiovascular outcomes in adults]

Objective: To explore the correlation between exposure to perfluoroalkyl substances (PFAS) and the risk of cardiovascular disease, and investigate the mediating role of uric acid and the protective effects of vitamin C and vitamin E intake on cardiovascular health (CVH), providing a basis for the prevention of cardiovascular disease. Methods: Based on survey data from the National Health and Nutrition Examination Survey database in the United States from 2005 to 2020, we used a weighted generalized linear model (GLM) to analyze the association between each PFAS compound and CVH impairment in adults. Using quantile g estimation, weighted quantile summation, and regression analysis. We examined the combined effects of exposure to four perfluoroalkyl substances on cardiovascular and cerebrovascular health impairments in adults. Results: Recruited a total of 7 482 participants aged 20 and above who were included for analysis. According to the CVH score, patients were divided into high, medium, and low groups, with 775 (10.3%), 4 987 (66.7%), and 1 720 (23.0%), respectively. After adjusting for covariates, weighted GLM analysis revealed that compared with the high CVH group, exposure to perfluoroalkyl substances (PFAS), perfluorooctanoic acid (PFOA), perfluorooctanesulfonic acid (PFOS), and perfluorononanoic acid (PFNA) was significantly positively associated with CVH impairment in both the low and moderate CVH groups. [PFAS (low CVH group: OR=1.209, 95%CI: 1.037-1.410; medium CVH group: OR=1.192, 95%CI: 1.085-1.309, P<0.001); PFOA (low CVH group: OR=1.226, 95%CI: 1.031-1.457; medium CVH group: OR=1.178, 95%CI: 1.068-1.299, P=0.003); PFOS (low CVH group: OR=1.155, 95%CI: 1.010-1.321; medium CVH group: OR=1.151, 95%CI: 1.061-1.249, P=0.002); PFNA (low CVH group: OR=1.239, 95%CI: 1.076-1.427; medium CVH group: OR=1.133, 95%CI: 1.024-1.252, P<0.001)]. Uric acid served as a mediating variable in the association between PFAS exposure and CVH impairment. The mediation analysis revealed that the effects of PFAS, PFOS, and PFNA exposure on CVH were 0.331, 0.208, and 0.423. The association between PFAS exposure and CVH impairment was modified by vitamin C and E intake, with the association being attenuated in individuals with sufficient intake and strengthened in those with a deficiency. Conclusions: PFAS exposure is closely associated with impaired CVH, primarily through uric acid as an intermediary that further affects CVH. Additionally, adequate intake of vitamins C and E can effectively mitigate CVH impairment caused by PFAS exposure.