Impact of Endodontic Treatment of Teeth With Apical Periodontitis on Levels of Inflammatory Biomarkers Associated...

Apical periodontitis (AP) is an inflammatory response to microbial infection of the root canal system. The microorganisms that cause AP can modulate the host's immune response by secreting inflammatory biomarkers, which might be associated with cardiovascular diseases.

To evaluate the existing evidence on the relationship between endodontic treatment of teeth with AP and changes in the levels of inflammatory biomarkers associated with cardiovascular risk.

This systematic review was registered in PROSPERO (CRD42024574082) and followed the PRISMA guidelines (2020) and Cochrane Handbook (2023). Searches were performed in April 2025 in Medline/PubMed, Embase, Web of Science, Scopus, Cochrane, LILACS, and gray literature, with no publication year restrictions. The PICO strategy was followed: (1) population: healthy adult patients with AP; (2) intervention: evaluation of the levels of inflammatory biomarkers of cardiovascular disease risk (IL-6, hs-CRP, IL-1β, TNF-α, and others) before and after endodontic procedures; (3) comparison: the same patients before any endodontic intervention; and (4) outcomes: reduction in the levels of cardiovascular disease risk biomarkers.

Twenty clinical studies were included in the qualitative analysis, and 18 reported a reduction in inflammatory biomarkers after endodontic treatment. A meta-analysis evaluated hs-CRP at 1 and 6 months post-treatment, as well as IL-6 and TNF-α at 6 months and 1 year post-treatment and IL-1β at 6 months. There was a significant reduction in hs-CRP 6 months post-treatment. No significant changes were found in the other biomarkers.

A significant reduction in hs-CRP was observed 6 months after endodontic treatment. However, there was no association between endodontic treatment of teeth with AP and the reduction in the other biomarkers evaluated in this systematic review and meta-analysis. Furthermore, the certainty of evidence was classified as low according to the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system, mainly because of the heterogeneity across primary studies and the lack of adequate control for potential confounding factors such as marginal periodontitis and smoking, which are linked to increased systemic inflammatory burden. Well-designed clinical trials using rigorous control of these factors, standardized methodologies, and longer follow-up periods are needed to confirm these findings.