Potential Association Between Apical Periodontitis and Cardiovascular Disease: A Narrative Review of Evidence and Clinical Implications.

Apical periodontitis (AP) affects 52% of adults globally, yet its systemic cardiovascu-lar implications remain understudied compared to periodontal disease. This narrative review synthesizes current evidence on the potential bidirectional association between apical periodontitis and cardiovascular disease (CVD), examining proposed mechanistic pathways and clinical implications. A comprehensive literature search was conducted using PubMed, Web of Science, and Scopus databases, including clinical studies, animal models, and mechanistic investigations. Epidemiological evidence suggests that patients with apical periodontitis have a 1.38-5.3 times higher risk of cardiovascular disease com-pared to controls. Three major pathways are proposed to explain the potential link from apical periodontitis to cardiovascular disease: bacterial translocation through oral-gut axis disruption, systemic inflammation characterized by elevated interleukin-1β, inter-leukin-6, tumor necrosis factor-α, and C-reactive protein, and oxidative stress-induced endothelial dysfunction. Conversely, emerging evidence indicates that cardiovascular disease accelerates periapical lesion progression through RANKL/RANK/OPG pathway dysregulation, microcirculatory compromise, and enhanced macrophage M1 polariza-tion. Root canal treatment significantly reduces systemic inflammatory markers with parallel improvements in flow-mediated dilation, suggesting a potential cardiovascular benefit. While substantial evidence supports bidirectional associations, definitive causal relationships require prospective validation through large-scale cohort studies and ran-domized controlled trials examining whether endodontic intervention reduces cardiovas-cular event rates.