Dinitroaniline herbicide exposure, mitochondrial DNA copy number, and 10-year risk of atherosclerotic cardiovascular disease: A community-based cohort study.

Dinitroaniline herbicides are widely used to control weed resistance, but their effects on atherosclerotic cardiovascular disease (ASCVD) are unknown. Serum trifluralin and pendimethalin, mitochondrial DNA copy number (mtDNAcn), and predictors of 10-year ASCVD risk were measured in participants from the Wuhan-Zhuhai cohort. Linear mixed model, restricted cubic spline (RCS) model, Bayesian kernel machine regression (BKMR) model, and weighted quantile sum (WQS) regression model were used for association analyses. Mediation models were used to estimate the potential role of mtDNAcn in the above associations. Cross-sectionally, each 1-unit increase in ln-transformed serum trifluralin and pendimethalin levels were associated with an increase in 10-year ASCVD risk of 0.272 % and 0.178 %, respectively (all P < 0.05). The BKMR and WQS models showed that trifluralin and pendimethalin co-exposure was associated with the increased 10-year ASCVD risk, with trifluralin being the primary contributor. Longitudinally, each 1-unit increase in ln-transformed serum trifluralin and pendimethalin levels were associated with the annual increase in 10-year ASCVD risk of 0.192 % and 0.156 %, respectively (all P < 0.05). Mediation analysis showed that mtDNAcn mediated 3.8 % of the trifluralin-associated increase in 10-year ASCVD risk. In conclusion, trifluralin and pendimethalin were cross-sectionally and longitudinally associated with the increased 10-year ASCVD risk, and mtDNAcn partially mediated the association.