Independent and Joint Associations of Polycyclic Aromatic Hydrocarbons with Cardiovascular Diseases: Mediation by Phenotypic Ageing?

The potential mechanisms via which exposure to polycyclic aromatic hydrocarbons (PAHs) results in cardiovascular diseases (CVDs) remain unclear. This study aimed to investigate the independent and joint associations between PAHs and CVDs, and assess whether phenotypic age acceleration (PhenoAgeAccel) mediates this relationship. This study pooled data from the National Health and Nutrition Examination Survey. Of 11,210 participants included, the number of participants in the CVDs group was 1202 (10.72%). A noteworthy association between elevated levels of the urinary PAHs metabolites mixture and an augmented risk of CVDs was observed. Higher level of 2-Hydroxyfluorene (2-FLU) concentration was significantly associated with increased risk of CVDs in both individual (OR = 1.31; 95% CI, 1.22-1.41; P < 0.001) and joint exposures. Furthermore, our study revealed that the relationship between 2-FLU and CVDs was mediated by PhenoAgeAccel (mediation proportion: 9.21% [95% CI, 5.79%-14.95%]), the mediation effects were also found in the subtypes of each CVDs. Additionally, when considering each of the 9 variables comprising the PhenoAgeAccel as mediators, we identified albumin, lymphocyte percent, white blood cell count, and creatinine as the primary contributors to the mediation effects. In the sensitivity analyses, during a median of 9.16 years of follow-up, 253 CVDs deaths occurred in a population of 10,008. The mediation effects remained robust.