Thyroid hormones and oxidative stress moderated the association between urinary phthalate metabolites and cardiovascular risk factors

Abstract

While previous studies suggested that phthalate exposure poses a risk to cardiovascular health, the results are mixed and indicated variability based on population characteristics and health outcomes assessed. Research that simultaneously investigates the association between urinary phthalate metabolites and multiple cardiovascular risk factors within a single study is relatively scarce. This study assessed human exposure to phthalates by determining urinary metabolite concentrations, and applied multiple statistical techniques to systematically evaluate the individual dose-response relationships and joint effects of phthalate exposure on blood lipids, blood pressure, and fasting blood glucose. The results revealed significant negative associations between urinary phthalate metabolites and low-density lipoprotein cholesterol, triglycerides, total cholesterol, diastolic blood pressure, systolic blood pressure, and fasting blood glucose. Significant nonlinear associations were obtained between specific individual metabolites and diastolic blood pressure. The oxidative stress biomarker 8-hydroxydeoxyguanosine levels in urine and thyroid hormone levels in paired serum were measured simultaneously. Then, we examined the indirect roles of thyroid hormones and oxidative stress in the association between urinary phthalate metabolites and cardiovascular risk factors by mediation and moderation analysis. While the mediation effect was not statistically significant, the negative associations of urinary phthalate metabolites with fasting blood glucose, triglyceride, and lipoprotein cholesterol were statistically significant at lower levels of thyroid hormones by moderation analysis. The association was also significant under certain levels of oxidative stress. The results demonstrated that phthalate exposure is associated with several cardiovascular risk factors, and maintaining appropriate oxidative stress levels and ensuring sufficient thyroid hormone levels may attenuate these associations.