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Background: Perfluoroalkyl substances (PFAS) are highly persistent synthetic chemicals with high global demand. Although PFAS may affect different components of cardiometabolic risk through the peroxisome proliferator-activated receptor (a master regulator of lipid and glucose metabolism), evidence remains scarce and inconsistent.Objective: Our aim was to evaluate plasma levels of six PFAS in association with cardiometabolic risk factors in a longitudinal setting among 40-50 year old women and men.Methods: Participants in the Västerbotten Intervention Programme visited their health center twice, 10 years apart: during 1990 to 2003 (baseline) and during 2001 to 2013 (follow-up). Participant underwent a medical examination, and measurements of systolic and diastolic blood pressure, total cholesterol and triglycerides were performed twice 10 years apart. PFAS were measured in 374 participants. The PFAS analysed were perfluorooctanoic acid (PFOA), perfluorooctanesulfonic acid (PFOS), perfluorononanoic acid (PFNA), perfluorohexanesulfonic acid (PFHxS), perfluorodecanoic acid (PFDA), and perfluoroundecanoic acid (PFUnA). A generalized estimated equations method was used to assess repeated measurements and to provide beta coefficients (β) with their 95% confidence intervals (CI).Results: Overall, we observed little or no evidence of associations between PFAS and cardiometabolic risk factors. Exceptions were statistically significant inverse associations between PFOS and PFHxS with total cholesterol (β~-0.30; mmol/L, comparing 3rd tertile vs 1st) and PFOS, PFOA and PFDA with triglycerides (β from -0.17 to -0.26 mmol/L, comparing 3rd tertile vs 1st), when analysis were restricted to those who did not develop diabetes during the follow-up.Conclusions: Our findings did not support the emerging premise that PFAS might increase cardiovascular risk through disrupting lipid metabolism and/or vascular system.