Associations of polycyclic aromatic hydrocarbons mixtures with cardiovascular diseases mortality and all-cause mortality and the mediation role of phenotypic ageing: A time-to-event analysis

The associations of polycyclic aromatic hydrocarbons (PAHs) with cardiovascular diseases (CVDs) and all-cause mortality are unclear, especially the joint effects of PAHs exposure. Meanwhile, no studies have examined the effect of phenotypic ageing on the relationship between PAHs and mortality. Therefore, this study aimed to investigate the independent and joint associations between PAHs and CVDs, all-cause mortality, and assess whether phenotypic age acceleration (PhenoAgeAccel) mediate this relationship. We retrospectively collected data of 11,983 adults from the National Health and Nutrition Examination Survey database. Firstly, Cox proportional hazards regression and restricted cubic splines were applied to evaluate the independent association of single PAH on mortality. Further, time-dependent Probit extension of Bayesian Kernel Machine Regression and quantile-based g-computation models were conducted to test the joint effect of PAHs on mortality. Then, difference method was used to calculate the mediation proportion of PhenoAgeAccel in the association between PAHs and mortality. Our results revealed that joint exposure to PAHs showed positive association with CVDs and all-cause mortality. By controlling potential confounders, 1-Hydroxynapthalene (1-NAP) (HR = 1.24, P = 0.035) and 2-Hydroxyfluorene (2-FLU) (HR = 1.25, P < 0.001) showed positive association with CVDs mortality, and they were the top 2 predictors (weight: 0.82 for 1-NAP, 0.14 for 2-FLU) of CVDs mortality. 1-NAP (HR = 1.15, P < 0.001) and 2-FLU (HR = 1.13, P < 0.001) also showed positive association with all-cause mortality, and they were also the top 2 predictors of all-cause mortality (weight: 0.66 for 1-NAP, 0.34 for 2-FLU). PhenoAgeAccel mediated the relationship between 1-NAP, 2-FLU and CVDs, all-cause mortality, with a mediation proportion of 10.00 % to 24.90 % (P < 0.05). Specifically, the components of PhenoAgeAccel including C-reactive protein, lymphocyte percent, white blood cell count, red cell distribution width, and mean cell volume were the main contributors of mediation effects. Our study highlights the hazards of joint exposure of PAHs and the importance of phenotypic ageing on the relationship between PAHs and mortality.