High-dose atorvastatin reduces periodontal inflammation: a novel pleiotropic effect of statins.

OBJECTIVES: The purpose of this study was to test whether high-dose statin treatment would result in a reduction in periodontal inflammation as assessed by (18)F-fluorodeoxyglucose positron emission tomography (FDG-PET)/computed tomography (CT).

BACKGROUND: Periodontal disease (PD) is an independent risk factor for atherosclerosis.

METHODS: Eighty-three adults with risk factors or with established atherosclerosis and who were not taking high-dose statins were randomized to atorvastatin 80 mg vs. 10 mg in a multicenter, double-blind trial to evaluate the impact of atorvastatin on arterial inflammation. Subjects were evaluated using FDG-PET/CT at baseline and at 4 and 12 weeks. Arterial and periodontal tracer activity was assessed while blinded to treatment allocation, clinical characteristics, and temporal sequence. Periodontal bone loss (an index of PD severity) was evaluated using contrast-enhanced CT images while blinded to clinical and imaging data.

RESULTS: Seventy-one subjects completed the study, and 59 provided periodontal images for analysis. At baseline, areas of severe PD had higher target-to-background ratio (TBR) compared with areas without severe PD (mean TBR: 3.83 [95% confidence interval (CI): 3.36 to 4.30] vs. 3.18 [95% CI: 2.91 to 3.44], p = 0.004). After 12 weeks, there was a significant reduction in periodontal inflammation in patients randomized to atorvastatin 80 mg vs. 10 mg (ΔTBR 80 mg vs. 10 mg group: mean -0.43 [95% CI: -0.83 to -0.02], p = 0.04). Between-group differences were greater in patients with higher periodontal inflammation at baseline (mean -0.74 [95% CI: -1.29 to -0.19], p = 0.01) and in patients with severe bone loss at baseline (-0.61 [95% CI: -1.16 to -0.054], p = 0.03). Furthermore, the changes in periodontal inflammation correlated with changes in carotid inflammation (R = 0.61, p < 0.001).

CONCLUSIONS: High-dose atorvastatin reduces periodontal inflammation, suggesting a newly recognized effect of statins. Given the concomitant changes observed in periodontal and arterial inflammation, these data raise the possibility that a portion of that beneficial impact of statins on atherosclerosis relate to reductions in extra-arterial inflammation, for example, periodontitis. (Evaluate the Utility of 18FDG-PET as a Tool to Quantify Atherosclerotic Plaque; NCT00703261).