Per- and Polyfluoroalkyl Substances and Incident Hypertension in Multi-Racial/Ethnic Women: The Study of Women's Health Across the Nation

Background: Perfluoroalkyl and polyfluoroalkyl substances (PFAS) are ubiquitous synthetic chemicals that may disrupt blood pressure controls; however, human evidence to support this hypothesis is scant. We examined the association between serum concentrations of PFAS and risks of developing hypertension. Methods: This study included 1058 midlife women initially free of hypertension from the multiracial and multiethnic SWAN (Study of Women's Health Across the Nation) with annual follow-up visits between 1999 and 2017. Hypertension was defined as blood pressure >= 140 mm Hg systolic or >= 90 mm Hg diastolic or receiving antihypertensive treatment. Cox proportional hazards models were utilized to calculate hazard ratios and 95% CIs. Quantile g-computation was implemented to evaluate the joint effect of PFAS mixtures. Results: During 11 722 person-years of follow-up, 470 participants developed incident hypertension (40.1 cases per 1000 person-years). Compared with the lowest tertile, women in the highest tertile of baseline serum concentrations had adjusted hazard ratios of 1.42 (95% CI, 1.19-1.68) for perfluorooctane sulfonate (P trend=0.01), 1.47 (95% CI, 1.24-1.75) for linear perfluorooctanoate (P trend=0.01), and 1.42 (95% CI, 1.19-1.70) for 2-(N-ethyl-perfluorooctane sulfonamido) acetate (P trend=0.01). No significant associations were observed for perfluorononanoate and perfluorohexane sulfonate. In the mixture analysis, women in the highest tertile of overall PFAS concentrations had a hazard ratio of 1.71 (95% CI, 1.15-2.54; P trend=0.008), compared with those in the lowest tertile. Conclusions: Several PFAS showed positive associations with incident hypertension. These findings suggest that PFAS might be an underappreciated contributing factor to women's cardiovascular disease risk.