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High Dose Atorvastatin Reduces Periodontal Inflammation: A Novel Pleiotropic Effect of Statins
Study Questions:
Would high-dose statin treatment result in a reduction in periodontal inflammation, as assessed by fluorodeoxyglucose-positron emission tomography/computed tomography (FDG-PET/CT)?
Methods:
Eighty-three adults with risk factors or with established atherosclerosis, who were not taking high-dose statins, were randomized to atorvastatin 80 mg versus 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, 4 weeks, 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 periodontal disease [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 to areas without severe PD (mean TBR [95% confidence interval] = 3.83 [3.36, 4.30] vs. 3.18 [2.91, 3.44], p = 0.004). After 12 weeks, there was a significant reduction in periodontal inflammation in patients randomized to atorvastatin 80 versus 10 mg (ΔTBR mean [95% confidence interval], 80 mg vs. 10 mg group = -0.43 [-0.83, -0.02], p = 0.04). Between-group differences were greater in patients with higher periodontal inflammation at baseline (-0.74 [-1.29, -0.19], p = 0.01) and in patients with severe bone loss at baseline (-0.61 [-1.16, -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 relates to reductions in extra-arterial inflammation (e.g., periodontitis).
Perspective:
That high-dose but not low-dose statins reduce periodontal inflammation and carotid and aortic FDG uptake as early as 4 weeks, and independent of changes in C-reactive protein and low-density lipoprotein cholesterol, enforces a long-held belief that they have pleiotropic actions beyond lipid altering. The latter comprises systemic anti-inflammation, and plaque modulation/stabilization by delipidation, regression, and reduction of plaque inflammation. The findings support the need for clinical outcome trials comparing new lipid-altering agents to high-dose potent statins no matter how effective the novel agents lower apolipoprotein B containing lipid particles and increase high-density lipoprotein cholesterol.
Keywords: Inflammation, Octamer Transcription Factor-1, Plaque, Atherosclerotic, Periodontal Diseases, Tomography, X-Ray Computed, Hydroxymethylglutaryl-CoA Reductase Inhibitors, Periodontitis, Risk Factors, Heptanoic Acids, Positron-Emission Tomography, Pyrroles, Cholesterol, C-Reactive Protein, Cholesterol, HDL, Alveolar Bone Loss
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