Metabolic syndrome and abdominal aortic calcification: evidence from NHANES and network pharmacology analysis

To investigate the association between metabolic syndrome (MetS) and abdominal aortic calcification (AAC) in U.S. adults and to explore potential shared molecular mechanisms using network pharmacology. This cross-sectional study included 1841 adults aged ≥ 40 years from National Health and Nutrition Examination Survey (NHANES) 2013–2014. AAC was assessed using lateral spine dual-energy X-ray absorptiometry and scored by the Kauppila AAC-24 system. AAC presence was defined as AAC score > 0 and severe AAC as AAC score ≥ 6. MetS was defined according to the 2009 Joint Interim Statement criteria (≥ 3 of 5 components). MetS severity score (MSS) was defined as the number of MetS components and categorized as MSS0–MSS4 (≥ 4 components). Linear regression was used for AAC score (continuous outcome), and logistic regression was used for AAC presence and severe AAC (binary outcomes), with multivariable adjustment for demographic and clinical covariates. Prespecified subgroup and interaction analyses were conducted. For network pharmacology, MetS- and AAC-related genes were retrieved from GeneCards, overlapping targets were identified, and PPI/network and enrichment analyses (GO/KEGG) were performed. MetS was independently associated with higher AAC score (β = 0.74; 95% CI 0.37–1.12) and increased odds of AAC (OR = 1.51; 95% CI 1.19–1.92) and severe AAC (OR = 1.77; 95% CI 1.24–2.53) in fully adjusted models. Increasing MSS showed a graded association with AAC outcomes, with progressively higher AAC scores and higher odds of AAC and severe AAC. Associations were generally consistent across subgroups, with evidence of effect modification by BMI. Network pharmacology identified 69 overlapping targets between MetS and AAC; hub genes were enriched in inflammatory and TGF-β–related pathways. MetS and increasing metabolic burden are independently associated with both the presence and severity of AAC in U.S. adults. Network pharmacology findings provide mechanistic support implicating inflammatory signaling and extracellular matrix remodeling in the MetS–AAC link.