Salivary Angiotensin-Converting Enzyme and Periodontal Disease in Cardiovascular Disease

Periodontal disease is a chronic inflammatory condition characterized by progressive destruction of the tooth-supporting tissues and has been associated with several systemic disorders, particularly cardiovascular disease (CVD). Although epidemiological evidence consistently supports this association, the biological mechanisms linking periodontal inflammation and cardiovascular disease remain incompletely understood.

The renin-angiotensin system (RAS) has emerged as one potential biological pathway underlying this relationship. In addition to its established role in regulating blood pressure and cardiovascular homeostasis, the RAS contributes to inflammatory responses, oxidative stress, immune regulation, and tissue remodeling. The balance between angiotensin-converting enzyme (ACE) and angiotensin-converting enzyme 2 (ACE2) is considered an important regulator of these processes, and disturbances in the ACE/ACE2 axis have been implicated in both cardiovascular disease and chronic inflammatory conditions.

Experimental studies have demonstrated that components of the RAS are expressed within periodontal tissues, including gingival fibroblasts, periodontal ligament cells, osteoblasts, and inflammatory cells. However, clinical investigations have primarily focused on circulating biomarkers or gingival tissue expression. Saliva represents a readily accessible and non-invasive biological fluid that may provide information about local biological processes within the oral cavity, yet clinical evidence regarding salivary RAS biomarkers remains limited, particularly among individuals with cardiovascular disease.

This completed cross-sectional observational study was conducted at the Departments of Periodontology and Cardiology of Süleyman Demirel University. Adults undergoing coronary angiography as part of their cardiovascular evaluation were enrolled and subsequently underwent comprehensive periodontal examination and biological sample collection during the study visit. Periodontal status was determined according to the 2017 World Workshop Classification of Periodontal and Peri-Implant Diseases and Conditions, providing a standardized classification of periodontal disease severity across the study population. Standardized unstimulated whole saliva and peripheral venous blood samples were collected to evaluate local and systemic components of the ACE/ACE2 axis. Serum and salivary ACE and ACE2 concentrations, together with serum and salivary ACE/ACE2 ratios, were evaluated to characterize the relationship between RAS biomarkers and periodontal disease severity. Demographic characteristics, anthropometric measurements, cardiovascular history, smoking status, and medication use were also recorded to support the interpretation of the observed relationships. By evaluating systemic and salivary RAS biomarkers within the same study population, the study aimed to explore whether salivary measurements could provide information complementary to circulating biomarkers regarding periodontal disease severity.

Inclusion criteria

• Adults aged 18 years or older.

• Having at least 20 natural teeth.
• Diagnosis of cardiovascular disease confirmed by coronary angiography.
• Ability and willingness to provide written informed consent.

Exclusion criteria

• Fewer than 20 natural teeth.

• Pregnancy or lactation.
• Periodontal treatment within the previous 6 months.
• Antibiotic or anti-inflammatory drug use within the previous 3 months.
• Presence of systemic inflammatory, autoimmune, or infectious diseases that could affect periodontal inflammation.
• History of malignancy.
• Requirement for antibiotic prophylaxis before periodontal examination.
• Refusal or inability to provide saliva or blood samples.
• Having a history of COVID-19 infection where less than 2 months had elapsed since the last positive RT-PCR test result