Environmental Pollution · Mar 10, 2026

The synergistic association of environmental stressors with abdominal aortic calcification: An observational and integrated genetic analysis

By Wang Y, Xiao Y, Tai Y et al.

Abdominal aortic calcification (AAC) serves as a potent independent predictor of cardiovascular disease (CVD). While individual environmental stressors (ESs) have been implicated in cardiovascular risk, their collective influence on AAC and the mechanistic pathways involved remain inadequately characterized. This study aimed to investigate the combined effects of ESs on AAC risk and explore the potential biological mediators. Data from the 2013-2014 National Health and Nutrition Examination Survey were analyzed. Logistic regression and Bayesian kernel machine regression (BKMR) were employed to evaluate the associations of individual and multiple ESs with severe AAC (SAAC, AAC score ≥5). Dose-response relationships were characterized using restricted cubic splines. To investigate the potential causal relevance and pathways, an integrated genetic framework was applied, incorporating network toxicology and summary-data-based Mendelian randomization (SMR) to prioritize molecular targets linking ESs to AAC. Among 608 participants included in the observational analysis, SAAC was identified in 48 individuals. From a panel of 101 ESs, blood selenium (Se; OR: 1.343, 95% CI: 1.034-1.739), urinary barium (Ba; OR: 1.444, 95% CI: 1.056-1.979), and urinary phenylglyoxylic acid (PGA; OR: 1.794, 95% CI: 1.153-2.819) showed positive associations with SAAC. BKMR analysis suggested a synergistic effect of the Se-Ba-PGA mixture on AAC risk. Further analyses revealed 39 genes with genetically supported associations with ESs-related AAC, 13 of which emerged as central nodes within the interaction network, representing potential mechanistic drivers. These findings provide evidence of a synergistic and potential causal relevance between specific ESs and AAC risk. This integrated approach advances the understanding of gene-environment interactions in the pathogenesis of CVD.

doi.org/10.1016/j.envpol.2026.127936PubMed 41819212Populations