Inflammation of the periodontium associates with risk of future cardiovascular events

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.

Keywords: atherosclerosis; cardiovascular disease; positron emission tomography; periodontal disease.

FIGURE 1

Flowchart of study participant selection. CVD, cardiovascular disease; CT, computed tomography; FDG, fluorodeoxyglucose; MGH, Massachusetts General Hospital; PET, positron emission tomography

FIGURE 2

Periodontal and arterial ¹⁸F-FDG uptake. A) shows axial images at the level of periodontium from CT and ¹⁸F-FDG-PET-CT. B) shows coronal images of the ascending aorta. C and D) demonstrate box plots of periodontal inflammation and of atherosclerotic inflammation among individuals with versus without subsequent MACE. CT, computed tomography; ¹⁸F-FDG, ¹⁸F-fluorodeoxyglucose; PET, positron emission tomography

FIGURE 3

Kaplan-Meier survival curves showing MACE-free survival by periodontal activity. Survival curves relating PD_inflammation and MACE are shown. PD_inflammation was dichotomously characterized as “high” or “low” based on two distinct approaches: A) The first approach dichotomized PD_inflammation values by identifying which PD_inflammation threshold most accurately predicted future MACE events using receiver-operator curve (ROC) analyses. B) The second approach dichotomized PD_inflammation based on data distribution with a defined threshold SUV value ≥1 SD above the mean periodontal SUV. MACE, major adverse cardiovascular event; PD_inflammatlon, periodontal disease inflammation; ROC, receiver operating curve; SUV, standardized uptake value

FIGURE 4

Hypothesized pathway linking periodontal disease to CVD