Impact of Volatile Organic Compound Mixtures on Cardiovascular Health in Adults With Metabolic Dysfunction–Associated Fatty Liver Disease: A US Population Study

Background Metabolic dysfunction–associated fatty liver disease (MAFLD) is among the most prevalent chronic liver diseases worldwide, whereas cardiovascular disease remains the primary cause of mortality in this population. Volatile organic compounds (VOCs), ubiquitous in the environment, have been linked to adverse cardiovascular outcomes; however, their impact on cardiovascular health (CVH) in MAFLD remains underexplored. Methods We performed an analysis of nationally representative National Health and Nutrition Examination Survey (NHANES) data from 2011 to 2020. Urinary 15 VOC metabolites were obtained from laboratory measurements using standardized ultraperformance liquid chromatography–electrospray tandem mass spectrometry. CVH was assessed using the Life′s Essential 8 (LE8) and Life′s Crucial 9 (LC9). Mixed‐exposure effects and individual contributions were examined using survey‐weighted linear regression, weighted quantile sum (WQS), quantile g‐computation (q‐gcomp), and Bayesian kernel machine regression (BKMR). Results Among 1280 adults with MAFLD, higher VOCs exposure was associated with lower CVH (LE8: β = −5.51, p < 0.001; LC9: β = −4.90, p < 0.001), WQS (LE8: β = −2.30, p < 0.001; LC9: β = −2.05, p < 0.001) and q‐gcomp (LE8: β = −1.09, p = 0.04; LC9: β = −0.97, p = 0.04) supported inverse mixture associations, whereas BKMR showed pronounced decrements at higher mixture percentiles among nicotine‐exposed participants (75th percentile LE8: β = −6.18, p < 0.001; LC9: β = −4.90, p < 0.001). Across methods, the metabolites CYMA (acrylonitrile), MHBMA3 (1,3‐butadiene), and HPMMA (crotonaldehyde) emerged as the dominant contributors. Conclusion In US adults with MAFLD, mixed VOCs exposure was consistently linked to poorer CVH and had a stronger association in those with nicotine exposure.