Cardiovascular Biomarkers in Periodontitis: A Systematic Review and Meta‐Analysis

This review aimed to synthesize evidence on cardiovascular biomarkers associated with periodontitis, identified in biofluids such as blood, saliva, and gingival crevicular fluid (GCF). A comprehensive search of five databases was conducted to identify studies comparing cardiovascular biomarker levels in periodontitis and healthy individuals, up to 31 December 2024. Meta-analysis included biomarkers from ≥ 2 studies per biofluid, with sensitivity analysis performed and evidence certainty assessed using the GRADE tool. Thirty-six studies were included in the systematic review, with 31 eligible for meta-analysis. Overall, 39 biomarkers were identified: 33 in blood, 14 in saliva, and 6 in GCF. A meta-analysis was conducted for 12 blood biomarkers, of which high-density lipoprotein (HDL) was significantly reduced, low-density lipoprotein (LDL) was higher in periodontitis (though LDL lost significance on sensitivity analysis), and the oxidative stress index (OSI) was significantly associated with periodontitis. No significant differences were observed for C-reactive protein (CRP), interleukin-1beta (IL-1ß), interleukin (IL)-6, N-terminal pro-B-type natriuretic peptide (NT-proBNP), monocyte chemoattractant protein-1 (MCP-1), and asymmetric dimethylarginine (ADMA). CRP was the only biomarker pooled for saliva and GCF, with no significant findings. Reduced blood HDL and elevated OSI represent potential cardiovascular biomarkers for periodontitis, although the certainty of evidence remains low.