Decoding the periodontitis–coronary artery disease axis through biomarker profiling: a systematic review and meta-analysis

This systematic review and meta-analysis aimed to explore the biomarker profiles in adults diagnosed with periodontitis (PD) and coronary artery disease (CAD). Identifying shared biomarkers is crucial for clarifying the biological link between these two common inflammatory diseases, improving early risk detection, and supporting more integrated approaches to managing oral and cardiovascular health. A comprehensive literature search was conducted in Scopus, PubMed, and Web of Science, covering studies published up to December 2024, in accordance with Cochrane handbook guidelines. The study population consisted of adults diagnosed with PD and either confirmed CAD or cardiovascular risk indicators. The eligibility criteria required original full articles in English that assessed quantitative biomarker levels in individuals with both conditions compared to controls. The study design included observational (n = 14) and randomized controlled trials (n = 6). A random-effects meta-analysis was performed, and heterogeneity was assessed using the I² statistic. A total of 3,245 records were identified from three databases: PubMed (n = 737), Scopus (n = 1241), and Web of Science (n = 1267). The most frequently reported biomarkers among individuals with both PD and CAD were C-reactive protein (CRP/hs-CRP) and interleukin-6 (IL-6), followed by interleukin-1β, interleukin-8, and tumour necrosis factor-alpha. Five studies were included in the primary pooled meta-analysis for CRP analyses, that showed a significant pooled effect (SMD = 0.501; p = 0.001), while three studies stated that IL-6 showed no significant association (SMD = 0.166; p = 0.240). Overall, studies demonstrated elevated systemic inflammatory biomarkers in individuals with both conditions. The findings suggest a potential association between chronic PD and elevated systemic inflammatory biomarkers in individuals with CAD. In particular, CRP was consistently reported across several studies, although the strength and significance of biomarker associations varied. These results indicate that periodontal inflammation may contribute to systemic inflammatory responses relevant to cardiovascular pathology; however, current evidence remains insufficient to establish causality. Further well-designed longitudinal and interventional studies are required to clarify the clinical significance of this relationship.