Analysis of the association between serum PFAS levels measured in NHANES and subsequent development of stroke or myocardial infarction as assessed through linked Medicare claims data

Abstract

Background/Aim: Per- and polyfluoroalkyl substances (PFAS) are persistent chemicals used in many products and manufacturing processes. Human exposure to some PFAS has been associated with serum cholesterol concentrations, but observed cardiovascular disease (CVD) associations have been inconsistent. Previous cross-sectional analyses of PFAS-CVD associations used U.S. National Health and Nutrition Examination Survey (NHANES) data. We prospectively examined associations between NHANES serum PFAS concentrations and subsequent myocardial infarction (MI), ischemic stroke (IS) or any stroke (AS), using linked National Death Index and Medicare claims data, for participants aged ≥65 years with PFAS measurements and Medicare fee-for-service enrollment (study population).Methods: NHANES (1999-2000, 2003-2012) serum PFAS concentrations [perfluorooctane sulfonate, perfluorooctanoic acid (PFOA), perfluorononanoic acid, perfluorohexane sulfonate] were analyzed using quartile (among cases) indicator variables and the natural log of quartile geometric means (continuous variable, trend test). CVD outcomes occurring after serum collection were identified, among participants reporting no prior history of the outcome, using linked (through 2013) Medicare claims ICD-9-CM codes and underlying cause-of-death ICD-10 codes. Survival analysis models with an age time scale; weighted to account for survey design and Medicare matching; and stratified on body mass index; controlled for survey cycle, age, gender, race/ethnicity, smoking, alcohol consumption, physical activity, education, and income-to-poverty ratio.Results: Among 1248 in the study population, 1078 reported no prior MI (72 developed MI) and 1102 reported no prior stroke (67 developed IS; 78 developed AS). Quartile-specific hazard ratios (HRs) and trends for all PFAS-outcome combinations were not statistically significant, but some elevated HRs were observed [e.g., IS HRs (95% confidence intervals) for PFOA quartiles 2-4 vs. 1: 2.04 (0.79-5.28), 1.98 (0.75-5.19), 1.63 (0.61-4.36)].Conclusions: This analysis did not provide clear evidence of an association between serum PFAS concentrations and MI, IS, or AS. Results should be interpreted considering study limitations (e.g., limited power, single exposure measurement).