Background

While growing evidence suggests a link between periodontal disease (PD) and cardiovascular disease (CVD), the independence of this association and the pathway remain unclear. Herein, we tested the hypotheses that: (1) inflammation of the periodontium (PD_inflammation ) predicts future CVD independently of disease risk factors shared between CVD and PD, and (2) the mechanism linking the two diseases involves heightened arterial inflammation.

Methods

¹⁸ F-fluorodeoxyglucose positron emission tomography/computed tomography (¹⁸ F-FDG-PET/CT) imaging was performed in 304 individuals (median age 54 years; 42.4% male) largely for cancer screening; individuals without active cancer were included. PD_inflammation and arterial inflammation were quantified using validated ¹⁸ F-FDG-PET/CT methods. Additionally, we evaluated the relationship between PD_inflammation and subsequent major adverse cardiovascular events (MACE) using Cox models and log-rank tests.

Results

Thirteen individuals developed MACE during follow-up (median 4.1 years). PD_inflammation associated with arterial inflammation, remaining significant after adjusting for PD and CVD risk factors (standardized β [95% CI]: 0.30 [0.20-0.40], P < 0.001). PD_inflammation predicted subsequent MACE (standardized HR [95% CI]: 2.25 [1.47 to 3.44], P <0.001, remaining significant in multivariable models), while periodontal bone loss did not. Furthermore, mediation analysis suggested that arterial inflammation accounts for 80% of the relationship between PD_inflammation and MACE (standardized log odds ratio [95% CI]: 0.438 [0.019-0.880], P = 0.022).

Conclusion

PD_inflammation is independently associated with MACE via a mechanism that may involve increased arterial inflammation. These findings provide important support for an independent relationship between PD_inflammation and CVD.