Phthalate exposure, oxidative stress and hypertension risk: Exploring associations and mediation effects in a Chinese general population

Phthalates, the most widely used plasticizers, have been reported to be correlated with metabolic disorders. Recent experimental studies found that phthalates may be correlated to cardiovascular diseases; however, the epidemiological evidence, particularly regarding hypertension, remains limited. Therefore, this study aimed to investigate the associations between phthalate exposure and hypertension risk and blood pressure levels, and to determine the mediating role of oxidative stress (OS). Urinary concentrations of 6 phthalate metabolites and 2 OS biomarkers were measured in 1199 general adults in Wuhan, China. The results showed that multiple phthalate metabolites (MEP, MBP, MiBP and MBzP) and the sum of 6 phthalate metabolites (ΣPAEs) were positively associated with hypertension risk and elevated blood pressure levels. In the weighted quantile sum (WQS) models, MEP was identified as the dominant contributor of phthalate mixture-induced hypertension risk. Meanwhile, all urinary phthalate metabolite concentrations were associated with elevated levels of 8-hydroxy-2-deoxyguanosine (8-OHdG) and malondialdehyde (MDA), which in turn were positively related to hypertension and blood pressure. Furthermore, the mediation analysis revealed that 8-OHdG and MDA partially mediated the effects of phthalate exposure on the increase in hypertension risk and blood pressure levels, with mediated proportions ranging from 14.0 % to 59.7 %. These results indicate that phthalate exposure may increase the risk of hypertension, and OS-related oxidative DNA damage and lipid peroxidation damage may be potential mediating mechanisms.