High-dose atorvastatin reduces periodontal inflammation: a novel pleiotropic effect of statins.
OBJECTIVE
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).
Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts.
Sharath
S
Subramanian
Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts.
Hamed
H
Emami
Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts.
Esad
E
Vucic
Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts.
Parmanand
P
Singh
Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts.
Jayanthi
J
Vijayakumar
Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts.
Kenneth M
KM
Fifer
Merck Sharp & Dohme Corp., Whitehouse Station, New Jersey.
Achilles
A
Alon
Merck Sharp & Dohme Corp., Whitehouse Station, New Jersey.
Sudha S
SS
Shankar
Peter Munk Cardiac Centre and the Heart and Stroke Richard Lewar Centre of Excellence, the University of Toronto, Toronto, Ontario, Canada.
Michael
M
Farkouh
Division of Cardiovascular Medicine, University of Cambridge, Cambridge, United Kingdom.
James H F
JHF
Rudd
Translational and Molecular Imaging Institute, Icahn School of Medicine at Mount Sinai, New York, New York.
Zahi A
ZA
Fayad
Forsyth Institute, Cambridge, Massachusetts.
Thomas E
TE
Van Dyke
Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts. Electronic address: atawakol@partners.org.
Ahmed
A
Tawakol
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000069059:Atorvastatin; D004311:Double-Blind Method; D005260:Female; D006538:Heptanoic Acids / Q000008:administration & dosage*; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000008:administration & dosage*; D007249:Inflammation / Q000175:diagnosis / Q000188:drug therapy; D008297:Male; D008875:Middle Aged; D010510:Periodontal Diseases / Q000175:diagnosis* / Q000188:drug therapy*; D011758:Pyrroles / Q000008:administration & dosage*; D016896:Treatment Outcome
D006538:Heptanoic Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D011758:Pyrroles; D000069059:Atorvastatin
(18)F-fluorodeoxyglucose; C-reactive protein; CRP; CT; FDG; HDL; LDL-C; PD; PET; ROI; SUV; TBR; atherosclerosis; computed tomography; high-density lipoprotein; imaging; inflammation; low-density lipoprotein cholesterol; nuclear medicine; periodontal disease; positron emission tomography; region of interest; standardized uptake value; statins; target-to-background ratio