Periodontitis, accelerated biological aging, and advanced stages in cardiovascular-kidney-metabolic syndrome in U.S. Adults: A mediation analysis

AIMS: Cardiovascular-Kidney-Metabolic (CKM) syndrome is a five-stage framework integrating cardiovascular, renal, and metabolic health. Periodontitis may contribute to multi-system conditions like CKM syndrome, but its overall impact and mechanisms remain unclear. METHODS: We analyzed 3,102 U.S. adults (30-79 years) from NHANES 2009-2014. Periodontal status was classified as none, mild, moderate, or severe; CKM stage (0-4) was determined by clinical criteria. Biological age was estimated via the Klemera-Doubal Method (KDMAge) and Phenotypic Age (PhenoAge) algorithms. Ordinal and binary logistic regression assessed periodontitis-CKM associations, adjusting for sociodemographic and lifestyle factors. Mediation analysis quantified the proportion of this association explained by biological age acceleration (BAA). RESULTS: Advanced CKM (stage 3-4) affected 17.8 % of participants. Severe periodontitis versus none/mild was associated with 1.50-fold higher odds of a more advanced CKM stage (95 % CI: 1.15-1.96) and 2.05-fold higher odds of advanced CKM in binary models (95 % CI: 1.50-2.80). Severe periodontitis corresponded to + 1.1 years of KDMAge acceleration and + 1.2 years of PhenoAge acceleration (p < 0.001). BAA mediated 20.1 % of the effect via KDMAge and 13.9 % via PhenoAge (p < 0.001). CONCLUSION: These findings underscore the importance of integrating oral health into cardiometabolic care, suggesting that addressing periodontal inflammation and BAA could improve CKM outcomes.