Association Between Environmental Chemicals Phthalates and Stroke Among the US Adults: A Cross-Sectional Study

Clinical Snapshot

Key Findings

• P Value: Significant associations reported (specific p-values not provided in abstract)

• Effect Size: Significant positive associations for MECPP, MCPP, MNBP, and MEOHP with stroke risk

• Primary Outcome: Stroke prevalence associated with urinary phthalate metabolite levels

• Nnt Or Sensitivity: Random Forest model achieved AUC = 0.833 for stroke prediction

• Confidence Interval: Coffee consumption OR = 0.63 (95%CI: 0.51-0.77)

Clinical Application

Urinary phthalate testing not routinely available in clinical practice; coffee consumption easily assessable Relevant to Australian practice given similar phthalate exposure patterns; aligns with RACGP environmental health guidelines and cardiovascular risk prevention strategies Adult population with environmental phthalate exposure, particularly relevant for cardiovascular risk assessment

Abstract

Stroke has a multifactorial etiology, and phthalates, as widely used environmental chemicals, may play an underexplored role in cerebrovascular health. This study aimed to evaluate the association between urinary phthalate metabolites and stroke risk using data from the National Health and Nutrition Examination Survey (NHANES), complemented by network toxicology, molecular docking, and machine learning approaches. We analyzed data from 10,771 adult participants in NHANES (2003-2018) who had complete records of stroke status, urinary phthalates, and clinical covariates. Multivariable logistic regression and restricted cubic spline (RCS) models were used to assess associations. We constructed protein-protein interaction networks and performed molecular docking to identify potential toxicological targets. Five machine learning algorithms were employed to develop predictive models for phthalate-related stroke risk. Higher levels of MECPP, MCPP, MNBP, and MEOHP were significantly associated with increased stroke prevalence. Network toxicology identified SRC as a key target, and molecular docking confirmed strong binding affinity between MBZP and SRC. Among the machine learning methods, Random Forest achieved the highest predictive performance (AUC = 0.833). Notably, moderate coffee consumption (≤ 170 g/day) was significantly associated with a reduced risk of stroke (OR = 0.63, 95%CI: 0.51-0.77), suggesting potential dietary mitigation against phthalate-related stroke risk. Our findings demonstrate that certain phthalates may increase stroke risk via molecular pathways involving SRC. Furthermore, moderate coffee consumption may mitigate the adverse cerebrovascular effects of these environmental pollutants.

References

1. 1.Yang, Q., Wu, P., Li, H., Yang, R., Luo, Y., Li, M., Yin, S., Dang, X., & Liu, Y. (2026). Association Between Environmental Chemicals Phthalates and Stroke Among the US Adults: A Cross-Sectional Study. Cardiovascular Toxicology. https://doi.org/10.3390/ijms130810143