Candidate Biomarkers Linking Periodontitis with Atherosclerotic and Related Cardiovascular Phenotypes: A Systematic Review Focused on Sex-Specific Evidence

Periodontitis and cardiovascular disease share inflammatory, immune, endothelial, oxidative, and lipid-related pathways. Although sex-related differences are well established for many cardiovascular biomarkers, it remains unclear whether sex modifies biomarker patterns at the intersection of periodontal and cardiovascular disease. PubMed, Scopus, and Web of Science were searched in accordance with PRISMA 2020. Eligible adult human studies evaluated periodontitis or periodontal inflammation together with atherosclerotic or related cardiovascular phenotypes and reported candidate biomarkers in blood or, as supportive evidence, oral fluids. High-throughput omics studies were eligible when available. Data on study design, periodontal and cardiovascular assessment, biological matrix, biomarker findings, sex-stratified analyses, and menopausal status were extracted. Twelve studies were included. Most assessed single biomarkers or small predefined panels rather than discovery-scale omics. Reported markers involved inflammation and immunity (CRP, hs-CRP, IL-6, LPS, and periodontal antibodies), endothelial or vascular injury, lipid and autoimmune pathways (PCSK9 and anti-ApoA-1 IgG), innate-immune and metabolic regulation (MBL and SIRT1), cardiac stress, and oxidative stress. Findings were heterogeneous across cardiovascular phenotypes, and several key associations were null or imprecise. Only two studies performed direct male-female comparisons: one enrolled women only, and none stratified women by menopausal status. No study derived and validated a sex-specific omics signature. The literature identifies overlapping candidate-biomarker pathways but does not establish a causal, clinically validated, sex-specific, or menopause-specific signature of periodontitis-associated cardiovascular disease. The current evidence should be considered hypothesis-generating.