Abstract
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.