Urinary Polycyclic Aromatic Hydrocarbons and Advanced Cardiovascular‐Kidney‐Metabolic Syndrome: Inflammatory‐Nutritional Pathways as Mediators

BACKGROUND: Polycyclic aromatic hydrocarbons (PAHs) are widespread environmental pollutants linked to adverse health outcomes. Their role in the different statuses of Cardiovascular-Kidney-Metabolic (CKM) syndrome remains poorly understood. METHODS: A cross-sectional analysis of 11,043 participants was conducted using data from NHANES. Urinary PAH levels were measured, and advanced CKM status was assessed using established diagnostic criteria. Mediation analysis was performed to evaluate the role of the red blood cell distribution width-to-albumin ratio (RAR). RESULTS: Higher urinary levels of PAHs, particularly 2-NAP and 2-FLU, were significantly associated with advanced CKM syndrome (p < 0.05). Exposure-response relationships and threshold effects were observed for these key PAHs. Mediation analysis identified RAR as a novel biomarker, explaining 6.13%-37.81% of the association depending on the specific metabolite. CONCLUSIONS: This study reveals that PAHs are independently and jointly associated with advanced CKM status, with RAR serving as a critical mediator. These findings underscore the importance of reducing environmental PAH exposure and highlight RAR as a potential biomarker for early detection and risk stratification.