LAUSR

INTRODUCTION Perfluoroalkyl substances (PFAs) are ubiquitous, anthropogenic organic compounds that have been linked with cardiovascular disease and cardiovascular risk factors. Older, long-chain PFAs have been phased out due to adverse cardiometabolic health effect and replaced by newer short-chain PFAs. However, emerging research suggests that short-chain PFAs may also have adverse cardiovascular effects. Non-invasive measures of vascular function can detect preclinical cardiovascular disease and serve as a useful surrogate for early CVD risk. We hypothesized that serum concentrations of PFAs would be associated with noninvasive measures of vascular function, carotid-femoral pulse wave velocity (PWV) and brachial artery reactivity testing (BART), in adults with non-occupational exposure to PFAs. METHODS We measured serum concentrations of 14 PFAs with hybrid solid-phase extraction and ultrahigh-performance liquid chromatography-tandem mass spectrometry in 94 adult outpatients with no known cardiovascular disease. We collected clinical and demographic data; and measured vascular function, PWV and BART, using standard protocols. We assessed associations of individual PFAs with log-transformed BART and PWV using linear regression. We used weighted quantile sum regression to assess effects of correlated PFA mixtures on BART and PWV. RESULTS Ten PFAs were measured above the limit of detection in >50% of participants. Each standard deviation increase in concentration of perfluoroheptanoic acid (PFHpA) was associated with 15% decrease in BART (95% CI: -28.5, -0.17). The weighted index of a mixture of PFAs with correlated concentrations was inversely associated with BART: each tertile increase in the weighted PFA mixture was associated with 25% lower BART, with 73% of the effect driven by PFHpA. In contrast, no PFAs or mixtures were associated with PWV. CONCLUSIONS Serum concentration of PFHpA, a new, short-chain PFA, was associated with impaired vascular function among outpatients without CVD. Our findings support a potential adverse cardiovascular effect of newer, short-chain PFAs.