Periodontitis Beyond ASCVD: Emerging Cardiovascular Phenotypes in Perio-Medicine

Periodontitis is increasingly recognized as a chronic inflammatory disease with systemic implications beyond the oral cavity. Within perio-medicine, its association with cardiovascular disease has been extensively investigated, particularly in relation to atherosclerotic cardiovascular disease (ASCVD). However, the field is now expanding toward a broader and more phenotype-specific cardiovascular framework.

This narrative review critically examines how the periodontitis-cardiovascular field has evolved from a predominantly ASCVD-centered model toward a broader spectrum of cardiovascular phenotypes, with particular emphasis on differences in evidence maturity, contemporary mechanistic concepts, and unresolved translational questions.

A structured literature search was conducted in PubMed/MEDLINE, Scopus, Web of Science, and the Cochrane Library. Evidence from mechanistic, observational, and interventional studies was qualitatively synthesized according to its contribution to established clinical associations, supportive mechanistic evidence, emerging cardiovascular phenotypes, and unresolved questions regarding causality and clinical translation.

The association between periodontitis and coronary atherosclerotic disease represents the most mature component of the literature, with substantial observational and meta-analytic support, while ischemic cerebrovascular disease is also supported by consistent but more heterogeneous evidence. Beyond ASCVD, atrial fibrillation and heart failure currently represent the most developed emerging cardiovascular phenotypes, whereas evidence concerning abdominal aortic aneurysm and venous thromboembolism remains more preliminary and hypothesis-generating. Contemporary mechanistic models extend beyond bacteremia and systemic inflammation to include endothelial dysfunction, thrombo-inflammatory signaling, trained immunity, immune-cell trafficking, functional dysregulation of the oral microbiome, and shared biological vulnerabilities. However, these pathways differ markedly in cardiovascular-specific evidentiary maturity and should not be interpreted as equivalent evidence of human causality. Periodontal therapy can improve inflammatory biomarkers, endothelial function, selected metabolic parameters, and blood pressure in specific populations, but a persistent translational gap remains between surrogate-marker improvement and demonstrated reduction in major adverse cardiovascular events. Periodontitis may also contribute to chronic systemic inflammatory burden in susceptible individuals, although its role within cardiovascular residual inflammatory risk remains an emerging hypothesis.

The periodontal-cardiovascular field is evolving from a predominantly ASCVD-centered model toward a phenotype-specific continuum of evidence maturity. Periodontitis is best interpreted as a potential modifier of cardiovascular vulnerability rather than as an established causal determinant. Future research should prioritize adequately powered cardiovascular-outcome trials, standardized periodontal phenotyping, and prospective validation of emerging phenotypes and mechanistic frameworks before periodontal information can be considered clinically actionable for cardiovascular prevention.