Cross-sectional and longitudinal relationships between exposure to polychlorinated biphenyls and predicted 10-year atherosclerotic cardiovascular disease risk: Integrated epidemiological and bioinformatics analysis.

Polychlorinated biphenyls (PCBs) are persistent organic pollutants of global concern, yet their associations with predicted cardiovascular risk remain unclear. In this prospective Wuhan-Zhuhai cohort study, concentrations of seven serum PCBs (PCB-28, 52, 101, 118, 138, 153, and 180) were measured using GC-MS/MS. The validated China-PAR equation was used to calculate predicted 10-year atherosclerotic cardiovascular disease (ASCVD) risk, and urinary 8-iso-prostaglandin F2α (8-iso-PGF2α) served as a marker of oxidative stress. Multivariable linear and logistic regression models were fitted to evaluate PCB-related differences in continuous predicted risk and predicted high-risk status. Cross-sectionally, each one-unit increase in ln-transformed PCB-118, PCB-138, PCB-153, and ΣPCB was associated with 1.249-, 1.253-, 1.457-, and 1.829-percentage-point higher predicted 10-year ASCVD risk, respectively (all P < 0.05). The associations for PCB-118, PCB-138, and PCB-153 remained significant after FDR correction. Longitudinally, persistent high PCB-118 exposure was associated with a 0.510 percentage-point greater increase in predicted 10-year ASCVD risk (95 % confidence interval [CI]: 0.023-0.996, P < 0.05) and a higher risk of transitioning to predicted high-risk status (RR = 1.432, 95 % CI: 1.012-2.027, P < 0.05) compared with persistent low exposure, although neither association remained significant after FDR correction. Exploratory mediation analysis suggested that urinary 8-iso-PGF2α was statistically consistent with partial indirect pathways for the associations, with estimated indirect proportions ranging from 3.29 % to 11.62 %. Database-derived bioinformatics analyses highlighted TNF/NF-κB/IL-17 pathways and identified IL-6, TNF, IL-1β, and ICAM1 as candidate hub genes. Overall, several PCB measures were cross-sectionally associated with higher predicted ASCVD risk, whereas longitudinal evidence was limited and was strongest for persistent high PCB-118 exposure. Exploratory mediation and bioinformatics findings highlighted possible oxidative-stress and inflammation-related pathways that require further validation.