Periodontitis, Endothelial Dysfunction, and Systemic Inflammation: A Systematic Review and Meta-Analysis of...

Background/Objectives: Periodontal disease is a chronic inflammatory condition associated with systemic vascular dysfunction and elevated cardiovascular risk. This systematic review and meta-analysis aimed to quantitatively evaluate the association between periodontitis and endothelial dysfunction and to assess the effects of periodontal therapy on endothelial function and inflammatory biomarkers. Methods: Conducted per PRISMA 2020 and registered in PROSPERO (CRD420261309247). Electronic databases (PubMed, Scopus, Cochrane Library) were searched for observational and interventional studies assessing endothelial function in patients with periodontitis. Risk of bias was evaluated using RoB 2, ROBINS-I, and the Newcastle-Ottawa Scale; certainty of evidence was assessed with GRADE. Pooled effects on flow-mediated dilation (FMD) and inflammatory markers were estimated using random-effects meta-analysis (DerSimonian-Laird). Results: Fourteen studies were included in qualitative synthesis; six contributed quantitative FMD data. Observational studies consistently demonstrated impaired endothelial function and elevated inflammatory markers in patients with periodontitis versus controls. Meta-analysis showed that periodontal therapy significantly improved endothelial function (pooled FMD: +3.3 percentage points; 95% CI 1.7-4.9; I² = 77%; p < 0.001), though results should be interpreted cautiously given substantial heterogeneity and the limited number of studies (n = 6). Periodontal treatment reduced CRP levels (mean difference -0.38 mg/L; I² = 41%); IL-6 showed a favorable direction but with very low certainty of evidence. Publication bias could not be reliably assessed given the small number of included studies. Conclusions: Periodontitis is associated with impaired endothelial function and systemic inflammation. Periodontal therapy leads to measurable improvements in both, supporting its role as a potentially modifiable contributor to cardiovascular risk. Larger randomized trials with long-term cardiovascular endpoints are warranted.