Urinary levels of phthalate metabolites and cardiovascular disease mortality (NHANES, 1999-2008)

Background: Mechanistic data and results from a limited number of cross-sectional epidemiologic studies have suggested a possible link between phthalates and adverse cardiovascular outcomes. Objective: To evaluate the association between urinary levels of eight phthalate metabolites and subsequent risk of cardiovascular death in a prospective cohort analysis. Methods: We identified 5080 individuals 40 years or older who participated in the continuous National Health and Nutrition Examination Survey (NHANES) from 1999 to 2008 and who had measured phthalate levels available. We a priori excluded individuals in later cycles of NHANES with measured phthalates so as to have the potential of at least three years of follow-up time on all members of the cohort. Questionnaire, exam and laboratory data were merged with a public access NHANES mortality file updated through December 31, 2011. The associations between cardiovascular death and quartile levels of the phthalate metabolites were investigated using Cox proportional hazard models. Results: There were 175 deaths due to cardiovascular disease deaths over a mean of 7.0 years of follow-up. No association between cardiovascular disease mortality and individual urinary phthalate metabolites was observed. After adjustments, hazard ratios comparing the highest to lowest quartile ranged from 0.73 (95%CI: 0.5-1.2) for mono-ethyl phthalate [MEP] to 1.4 (95%CI:0.8-2.5) for mono-(2-ethyl-5-hydroxyhexyl) phthalate [MEHHP]. Conclusions: Urinary levels of phthalate metabolites were not associated with increased cardiovascular disease mortality. Additional larger cohort studies with longer follow-up focused on cardiovascular disease incidence are needed. (C)2016 Elsevier GmbH. All rights reserved.