Correlation of Periodontitis with Mortality of US Adults with Cardiovascular- Kidney-Metabolic (CKM) Syndrome: The Mediating Role of Accelerated Biological Aging

Background Periodontitis is a chronic inflammatory disorder whose prognostic implication for CKM syndrome remains unclear. This study investigated the association between periodontitis and mortality among patients with CKM syndrome, and explored the mediating role of accelerated biological aging (ABA). Methods Data on 6,687 stage 1–4 CKM syndrome patients were obtained from NHANES 1999–2004 and 2009–2014. Periodontitis severity was classified using CDC/AAP criteria, and biological aging was quantified via PhenoAge and KDMAge acceleration. Weighted Cox models, subgroup, mediation, and joint association analyses were performed. Ultimately, ten distinct machine learning algorithms were utilized to construct the predictive models. Results Over a median 121-month follow-up, 931 all-cause and 225 CVD deaths were documented. Periodontitis was independently associated with elevated risks of all-cause mortality (HR = 1.21) and CVD mortality (HR = 1.41). PhenoAge acceleration mediated 15.21% and 16.45% of these associations respectively, while KDMAge only mediated 6.23% of the effect on all-cause mortality. Joint analysis indicated that the coexistence of periodontitis and accelerated aging conferred the highest risk of mortality. Patients with both conditions faced significantly elevated hazards for all-cause (HR = 1.57) and CVD mortality (HR = 2.96). Comparative analysis revealed that the Neural Network exhibited superior discriminatory ability for all-cause mortality (AUC = 0.841) compared to the other machine learning approaches. Conclusion Periodontitis is an independent predictor of all-cause and CVD mortality in CKM syndrome patients, and the association is partly mediated by ABA, particularly PhenoAge. Incorporating periodontal health into CKM management may attenuate biological aging and improve survival.