Low-level plasticizer exposure and all-cause and cardiovascular disease mortality in the general population

Abstract

Background Plasticizers, also called phthalates, are a group of chemicals widely used in daily life. A previous report showed no significant association between phthalate metabolite concentrations and mortality. We investigated the association of urinary phthalate levels and individual phthalate metabolite levels with all-cause and cardiovascular disease (CVD) mortality after standardizing the phthalate concentration. Methods A total of 6,625 participants were recruited from a nationally representative sample of adults aged 40 years or older who were enrolled in the National Health and Nutrition Examination Survey (NHANES) between 2003 and 2014 and were followed up through December 31, 2015. Data were analyzed from January 2021 to June 2021. NHANES-linked updated National Death Index public access files were used to acquire information on mortality status and cause of death. The present study conducted extended follow-up of an earlier analysis. Cox proportional hazard models were performed to calculate the hazard ratios (HRs) and 95% confidence intervals (CIs) of covariate-adjusted creatinine standardization urinary phthalate concentrations with all-cause and CVD mortality after adjusting for demographics, lifestyle factors and comorbidity variables. Results The mean ± standard deviation age of all participants in the final study was 59.9±12.6 years old, and 49.6% of the participants were male. The median follow-up time was 73 months (range 1-157 months). At the censoring date of December 31, 2015, 3,023 participants were identified as deceased (13.4%). A fully adjusted Cox model showed that a urinary di(2-ethylhexyl) phthalate (DEHP) concentration >= 83.4 ng/mL was associated with a slight increase in all-cause mortality (HR 1.27, 95% CI 1.03, 1.57, P for trend= 0.014) and CVD mortality (HR 2.19, 95% CI 1.35, 3.54, P for trend= 0.002). Similarly, urinary mono-2-ethyl-5-carboxypentyl phthalate (MECPP) levels >= 39.2 ng/mL were associated with increased CVD mortality (HR 2.33, 95% CI 1.45, 3.73, P for trend < 0.001). Restricted cubic spline analyses suggested linear associations of DEHP and MECPP levels with all-cause and CVD mortality. Conclusion In this large nationally representative sample of American adults, high urinary DEHP and MECPP were significantly associated with all-cause and CVD mortality after adjusting for demographics, lifestyle factors and comorbidity variables.

Urinary Phthalate Concentrations and Mortality Risk: A Population-Based Study

“…In a recent study by Trasande et al from 2022, a positive association between MEP and cardiovascular mortality was observed, but no further significant associations between individual phthalate metabolites and mortality risks (Trasande et al, 2021). In a similar study by Zeng et al from 2022(Zeng et al, 2022, the strongest association was between MBzP and all-cause mortality risk, which is in line with our study. Zeng et al further reported a significant positive association between MECPP levels and CVD mortality, while cancer mortality was not investigated.…”

“…NHANES is an open resource that is available to researchers worldwide, and three previous analyses on phthalates and mortality risks have been carried out based on data from the study (Sturgeon et al, 2016;Trasande et al, 2021;Zeng et al, 2022). An earlier analysis by Sturgeon et al from 2016 did not provide evidence for associations between urinary phthalate levels and cardiovascular mortality risk (Sturgeon et al, 2016), while all-cause and cancer mortality were not investigated.…”

Sex-Specific Deflection of Age-Related DNA Methylation and Gene Expression in Mouse Heart by Perinatal Toxicant Exposures

“…Although the US government and some states have set guidelines regulating DEHP levels in air, water, and consumer products, human exposure to this chemical is still widespread [25]. Both Pb and DEHP exposure are associated with numerous adverse cardiovascular outcomes in human population studies, including congenital heart defects, heart failure, hypertension, cardiac arrhythmias, myocardial infarction, and stroke in Pb exposed individuals [26][27][28][29][30], and hypertension, atherosclerosis, coronary artery disease, decreased heart rate variability, and increased all-cause CVD mortality in individuals exposed to DEHP and its metabolites [31][32][33][34][35][36].…”

Evidence for the cardiodepressive effects of the plasticizer di-2-ethylhexylphthalate (DEHP)

“…Epidemiological studies have reported associations between phthalate exposure and an increased risk of all-cause and cardiovascular mortality, which has prompted a renewed interest in understanding the direct effect of DEHP on the heart(Trasande et al ., 2022; Zeng et al ., 2022). Identifying the consequences of clinical phthalate exposure on patient outcomes is inherently difficult, given the complexity of clinical care and the heterogenous nature of patient populations.…”