High dose atorvastatin also beneficial for gum diseaseLiterature - Subramanian S, Emami H, et al. - J Am Coll Cardiol. 2013 Sep 23
High Dose Atorvastatin Reduces Periodontal Inflammation: A Novel Pleiotropic Effect of Statins.
Subramanian S, Emami H, Vucic E et al.
J Am Coll Cardiol. 2013 Sep 23. doi: 10.1016/j.jacc.2013.08.1627. [Epub ahead of print]
BackgroundPeriodontal disease (PD) is a common, independent risk factor for atherosclerotic disease [1,2]. Local periodontal inflammation, through pro-inflammatory cytokine release, has been proposed to lead to systemic inflammation, as measured by CRP, TNA-α, IL-6 and other biomarkers. This is one of the postulated pathogenic mechanisms linkin PD and cardiovascular (CV) disease [3-5]. Increased levels of circulating inflammatory mediators can then promote inflammatory activity within atherosclerotic plaques [6,7].
Local treatment of PD has been shown to reduce systemic inflammation in patients with a history of CV events . No definitive evidence exists, however, that treatment of periodontal disease decreases CV disease progression or CV events.
18F-Flurodeoxyglucose positron emission tomography (FDG-PET) imaging provides a non-invasive measure of inflammation, also of inflammatory activity within atherosclerotic plaques. The authors have previously shown that periodontal inflammation correlates with carotid artery inflammation . Others have recently demonstrated that periodontal FDG uptake correlates with PD severity as measured by alveolar bone loss .
Retrospective epidemiologic studies have shown that statin therapy is associated with reduced severity of periodontitis [11-14]. Furthermore, it was shown recently that a combination of statins and standard local periodontal treatment was more effective than the local treatment alone .
This double-blind, randomised, active-comparator study aimed to study the direct anti-inflammatory actions of statins in periodontal tissue, by using FDG-PET/CT imaging to test if high-dose atorvastatin treatment lowers periodontal disease activity, similar to its action on atherosclerotic plaque activity. 71 subjects completed the study, and for 59 of those periodontal tissue images were available.
- Mean periodontal FDG uptake was significantly reduced in the entire cohort after 12 weeks of treatment with high (80 mg) vs. low (10 mg) dose atorvastatin (mean Target-to-background ratio (TBR): -0.29 + 0.85 (SD) vs. 0.13 + 0.68, P0.04). The effect of high dose atorvastatin on PD activity remained statistically significant after correction for several possible confounders.
- The effect of high-dose statin treatment was more pronounced in subjects with imaging evidence of periodontal disease at baseline; in individuals with active periodontitis there were clear differences between the two statin doses (change TBR= -0.52 + 0.94 vs. 0.22 + 0.79, P=0.01). The difference between groups was already evident after 4 weeks.
- Baseline FDG uptake (TBR) in periodontal tissue correlated with baseline carotid plaque TBR. Also, after 12 weeks of statin treatment, changes in periodontal inflammation correlated with changes in carotid inflammation.
- Baseline PD activity (periodontal TBR) was inversely correlated with baseline HDL concentration (r= -0.35, P=0.007), but did not correlate with baseline CRP or LDL levels. Changes in PD activity did not correlate with changes in CRP, LDL or HDL.
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ConclusionTwelve weeks of high-dose statin therapy significantly reduces periodontal inflammation. The reduction in PD activity was already seen after 4 weeks of atorvastatin treatment and correlated with changes in FDG uptake in the carotid wall.
It has previously been suggested that statins have effects beyond their lipid-lowering actions. This study provides evidence for a cholesterol-independent, or ‘pleiotropic’ effect of statins, namely reduction in non-arterial inflammation. The authors further postulate that a reduction in local periodontal inflammation may also exert beneficial effects on the systemic arterial milieu, through a reduced release of pro-inflammatory mediators from the periodontal tissue, into the systemic circulation.
1. Genco R, Offenbacher S, Beck J. Periodontal disease and cardiovascular disease: epidemiology and possible mechanisms. J Am Dent Assoc 2002;133 Suppl:14S-22S.
2. Beck J, Garcia R, Heiss G, et al. Periodontal disease and cardiovascular disease. J Periodontol 1996;67:1123-37.
3. Linden GJ, McClean K, Young I, et al. Persistently raised C-reactive protein levels are associated with advanced periodontal disease. J Clin Periodontol 2008;35:741-7.
4. Noack B, Genco RJ, Trevisan M, et al. Periodontal infections contribute to elevated systemic C-reactive protein level. J Periodontol 2001;72:1221-7.
5. Paraskevas S, Huizinga JD, Loos BG. A systematic review and meta-analyses on C reactive protein in relation to periodontitis. J Clin Periodontol 2008;35:277-90.
6. Tonetti MS, D'Aiuto F, Nibali L, et al. Treatment of periodontitis and endothelial function. N Engl J Med 2007;356:911-20.
7. Figuero E, Sanchez-Beltran M, Cuesta-Frechoso S, et al. Detection of periodontal bacteria in atheromatous plaque by nested polymerase chain reaction. J Periodontol 2011;82:1469-77.
8. Offenbacher S, Beck JD, Moss K, et al. Results from the Periodontitis and Vascular Events (PAVE) Study: a pilot multicentered, randomized, controlled trial to study effects of periodontal therapy in a secondary prevention model of cardiovascular disease. Journal of periodontology 2009;80:190-201.
9. Fifer KM, Qadir S, Subramanian S, et al. Positron emission tomography measurement of periodontal (18)f-fluorodeoxyglucose uptake is associated with histologically determined carotid plaque inflammation. J Am Coll Cardiol 2011;57:971-6.
10. Kito S, Koga H, Kodama M, et al. Reflection of (18)F-FDG accumulation in the evaluation of the extent of periapical or periodontal inflammation. Oral Surg Oral Med Oral Pathol Oral Radiol 2012;114:e62-9.
11.Cunha-Cruz J, Saver B, Maupome G, Hujoel PP. Statin use and tooth loss in chronic periodontitis patients. J Periodontol 2006;77:1061-6.
12. Saver BG, Hujoel PP, Cunha-Cruz J, Maupome G. Are statins associated with decreased tooth loss in chronic periodontitis? J Clin Periodontol 2007;34:214-9.
13. Meisel P, Kohlmann T, Wallaschofski H, et al. Cholesterol, CReactive Protein, and Periodontitis: HMG-CoA-Reductase Inhibitors (Statins) as Effect Modifiers. ISRN Dent 2011;2011:125168.
14. Lindy O, Suomalainen K, Makela M, Lindy S. Statin use is associated with fewer periodontal lesions: A retrospective study. BMC Oral Health 2008;8:16.
15. Fajardo ME, Rocha ML, Sanchez-Marin FJ, et al. Effect of atorvastatin on chronic periodontitis: a randomized pilot study. J Clin Periodontol 2010;37:1016-22.