Urinary metals and phenols mixtures, oxidative stress, and heart rate variability: Association and mediation analyses

Few studies have examined the effects of co-exposure to metals and phenols on heart rate variability (HRV), and the underlying mechanisms are unknown. We aim to investigate individual and joint associations of metals and phenols with HRV and the mediating role of oxidative stress among 118 adults in Wuhan with 3 repeated visits. Urine samples of 23 metals, 6 phenols and 3 oxidative stress biomarkers were measured. The associations were estimated using linear mixed-effect models (LMEs), weighted quantile sum (WQS) regression, adaptive Least Absolute Shrinkage and Selection Operator (LASSO) and mediation analyses. WQS regression revealed that the mixture of metals and phenols had an overall inverse association with standard deviation of normal-to-normal intervals (SDNN) and a positive relationship with low-frequency/high-frequency ratio (LF/HF). For SDNN, urinary thallium (Tl) and propyl paraben (PrP) were selected by adaptive LASSO, and urinary Tl was selected for LF/HF. After multivariate adjustments, we found that per doubling of urinary Tl and PrP was associated with a 3.54 % (95 % CI: -6.01 %, -1.01 %) and 1.20 % (95 % CI: -2.05 %, -0.33 %) decrease in SDNN, respectively. Additionally, the inverse relationships of urinary Tl and PrP with SDNN were mediated by urinary 8-iso-prostaglandin-F2α (8-isoPGF2ɑ) and 8-hydroxy-2'-deoxyguanosine (8-OHdG), with the mediated proportions of 15.83 % and 8.36 %, respectively. Our findings suggest that environmental exposure to Tl and PrP was associated with decreased HRV, and the association was partly mediated by oxidative stress.