Phthalate exposure is associated with subclinical coronary atherosclerosis: The Aragon Workers' Health Study (AWHS)

Phthalates are implicated in mechanisms underlying the development of cardiovascular disease, such as oxidative stress, lipid peroxidation, endothelial dysfunction, and activation of procoagulant pathways. This study aimed to evaluate the association between phthalate exposure and subclinical coronary atherosclerosis (SCA). A total of 1119 Spanish male workers from a car assembly plant (mean age: 50.9 years) were included. Urinary metabolites of 11 phthalates and ΣDEHP were analyzed. SCA was defined as coronary artery calcium ≥ 100 Agatston units. Logistic regression models were used to estimate the association between phthalates (natural log-transformed) and SCA, adjusting for sociodemographic, lifestyle, and cardiovascular risk factors. Dose-response relationships were explored using restricted cubic splines. The prevalence of SCA was 10.2 %. Participants with SCA had a median Mono-ethyl phthalate (MEP) concentration of 126.1 µg/g-creatinine compared to 99.3 µg/g-creatinine in those without SCA. A 1-unit increase in the natural logarithm of MEP was associated with a 21 % higher prevalence of SCA (OR: 1.21; 95 % CI: 1.02-1.44), showing a linear relationship. Positive but non-significant associations were observed for MiBP and MnBP. Sensitivity analyses with phthalates in original units (ng/ml) and adjustments for urinary creatinine showed consistent results. Exposure to MEP is associated with an increased prevalence of SCA in male workers, suggesting that the exposure to this phthalate may play a role in the early stages of cardiovascular disease. These findings provide a basis for public health initiatives aimed at reducing phthalate exposure for the primary prevention of cardiovascular disease.