Periodontitis and cardiovascular disease: periodontal treatment lowers plasma cholesterol.

In this issue of the Southern Medical Journal, Dr. Oz and colleagues (1) report on the beneficial effect of periodontal treatment in hypercholesterolemic patients suffering from periodontitis.

Periodontitis is an infectious disease caused by a small group of predominantly anaerobic Gram negative bacteria present on the tooth surface as microbial biofilms. Lipopolysaccharides and other microbial substances gain access to the gingival tissue and initiate and perpetuate an inflammatory reaction, which leads to the destruction of the periodontal ligament and alveolar bone and, finally, to tooth loss. Numerous case control and cohort studies have indicated that patients with periodontitis have an increased risk of cardiovascular disease (CVD), ie, myocardial infarction, stroke and peripheral arterial disease, when compared with subjects with a healthy periodontium. (2-4)

The association between periodontitis and CVD may be because of common risk factors such as smoking, diabetes mellitus, aging, male gender and socioeconomic factors, but there is also good evidence of periodontitis being an independent risk factor of CVD. (2-5) Periodontitis is believed to cause a low, but long-lasting, systemic inflammatory reaction, which in turn contributes to the development of atherosclerosis. (5) Furthermore, periodontal pathogens have been identified in early as well as advanced atherosclerotic lesions. (6) There is also some evidence that periodontitis is associated with increased plasma concentrations of pro-atherogenic lipoproteins, in particular, cholesterol-rich low-density lipoproteins (LDL) and triglycerides. (7,8)

Although numerous prospective studies with thousands of patients have shown the association between periodontitis and cardiovascular disease, (2-4,9) no studies have been done so far demonstrating that treatment of periodontitis decreases the risk of CVD as measured by the frequency of hard endpoints such as death or hospitalization due to myocardial infarction or stroke. Due to the large number of patients to be enrolled, the long follow-up periods, and the ethical problems that would arise from a control group of periodontitis patients without appropriate treatment, such studies will probably not be done in the future. However, short-term studies monitoring surrogate markers of CVD, ie, biochemical risk factors, have appeared to be very helpful in obtaining further evidence for periodontitis as an independent CVD risk factor. In these studies, established risk factors of CVD, such as increased plasma levels of C-reactive protein, fibrinogen, pro-inflammatory cytokines or other acute-phase reactants, were measured before and after (up to 6 months) local therapy of periodontitis. Some, but not all, of these studies have shown that the periodontal treatment significantly decreases plasma concentrations of the biochemical CVD risk markers. (10-12)

Hypercholesterolemia was the first biochemical risk factor of atherosclerosis and is still considered one of its most important risk factors. (13,14) Hypercholesterolemia is frequently found in patients with moderate and severe periodontitis. (7,8) Dr. Oz and colleagues (1) demonstrate that periodontal treatment can reduce cholesterol level. Fifty subjects (mean age 50 [+ or -] 7 yr) with more than 3 dental pockets with a probing depth [greater than or equal to]4 mm were included in this study. Three months after therapy, the authors not only observed a significant reduction in the clinical signs of local inflammation and periodontal destruction, but they also measured a significant reduction of total cholesterol by about 12% (from 245 [+ or -] 21-214 [+ or -] 33 mg/dL) and a reduction of LDL cholesterol by 25% (from 155 [+ or -] 19-116 [+ or -] 37 mg/dL). If there are no other risk factors, an LDL cholesterol level of 155 mg/dL is considered to be within the tolerable limits. Nevertheless, a reduction by 25% would result in a substantial reduction in the risk for myocardial infarction within 10 years. Dependent on age, gender and the prevalence of further risk factors (smoking, previous cardiovascular event, family history of CVD, etc.), a statistical risk reduction by 30 to 50% could be expected. (15)

Recently, another study demonstrating a significant reduction of mean LDL cholesterol level in 40 patients (from 132 [+ or -] 23-116 [+ or -] 19 mg/dL) six months after periodontal therapy was published by D'Aiuto et al. (12) In an earlier study on 32 periodontitis patients with comparatively low basal LDL cholesterol levels (median 121 mg/dL), we did not see a significant reduction when the measurements were repeated 3 months after therapy (median 114 mg/dL). (10) The results of the three studies taken together appear to reveal that the effect of periodontal therapy on LDL cholesterol level seems to be more obvious at higher basal levels, compared with lower basal levels.

A simple and practical conclusion that can be drawn from the studies, providing evidence that periodontitis may be an independent risk factor of CVD and that periodontal therapy may reduce other metabolic CVD risk factors, could be that patients with known risk factors or a diagnosis of CVD should be examined for periodontitis and should eventually receive periodontal therapy and vice versa--patients with periodontitis should not only receive periodontal treatment, but should be also checked for other risk factors of CVD. Following such a conclusion could provide an easy and inexpensive benefit to both periodontal or/and cardiovascular health, independent of the strength of association between periodontitis and CVD.

References

1. Oz SG, Fentoglu O, Kilicarslan A, et al. Beneficial effects of periodontal treatment on metabolic control of hypercholesterolemia. South Med J 2007;100:686-691.

2. Hujoel PP. Does chronic periodontitis cause coronary heart disease? A review of the literature. J Am Dent Assoc 2002;133(Suppl):31S-36S.

3. Holmlund A, Holm G, Lind L. Severity of periodontal disease and number of remaining teeth are related to the prevalence of myocardial infarction and hypertension in a study based on 4,254 subjects. J Periodontol 2006;77:1173-1178.

4. Desvarieux M, Demmer RT, Rundek T, et al. Relationship between periodontal disease, tooth loss, and carotid artery plaque: the Oral Infections and Vascular Disease Epidemiology Study (INVEST). Stroke 2003;34:2120-2125.

5. D'Aiuto F, Graziani F, Tete' S, et al. Periodontitis: from local infection to systemic diseases. Int J Immunopathol Pharmacol 2005;18(3 Suppl): 1-12.

6. Padilla C, Lobos O, Hubert E, et al. Periodontal pathogens in atheromatous plaques isolated from patients with chronic periodontitis. J Periodontal Res 2006;41:350-353.

7. Losche W, Karapetow F, Pohl A, et al. Plasma lipids and blood glucose levels in patients with destructive periodontal disease. J Clin Periodontol 2000;27:537-541.

8. Mattila KJ, Pussinen PJ, Paju S. Dental infections and cardiovascular diseases: a review. J Periodontol 2005;76(11 Suppl):2085-2088.

9. Beck JD, Offenbacher S. Systemic effects of periodontitis: epidemiology of periodontal disease and cardiovascular disease. J Periodontol 2005; 76(11 Suppl):2089-2100.

10. Losche W, Marshal GJ, Apatzidou DA, et al. Lipoprotein-associated phospholipase [A.sub.2] and plasma lipids in patients with destructive periodontal disease. J Clin Periodontol 2005;32:640-644.

11. Seinost G, Wimmer G, Skerget M, et al. Periodontal treatment improves endothelial dysfunction in patients with severe periodontitis. Am Heart J 2005;149:1050-1054.

12. D'Aiuto F, Parkar M, Nibali L, et al. Periodontal infections cause changes in traditional and novel cardiovascular risk factors: results from a randomized controlled clinical trial. Am Heart J 2006;151:977-984.

13. Thomas HE Jr, Kannel WB, Dawber TR, et al. Cholesterol-phospholipid ratio in the prediction of coronary heart disease: the Framingham study. N Engl J Med 1966;274:701-705.

14. Assmann G, Cullen P, Schulte H. Simple scoring scheme for calculating the risk of acute coronary events based on the 10-year follow-up of the prospective cardiovascular Munster (PROCAM) study. Circulation 2002;105:310-315.

15. International Task Force for Prevention of Coronary Artery Disease. Available at: http://www.chd-taskforce.com/index.htm. Accessed March 30, 2007.

If I couldn't laugh, I would go insane.
--Jimmy Buffett

Wolfgang Losche, MD, PhD

From the Department of Anesthesiology and Intensive Care Medicine, Experimental Anesthesiology and Hemostasis, University Hospital Jena, Jena, Germany.

Reprint requests to Dr. Wolfgang Losche, University Hospital Jena, Department of Anesthesiology and Intensive Care Medicine, Experimental Anesthesiology and Hemostasis, Erlanger Allee 101, D-07747 Jena, Germany. Email: [e-mail]

There is no commercial or proprietary interest in any drug, device, or equipment mentioned in the Editorial.

Accepted December 14, 2006.