Can aggressive treatment of periodontal disease decrease chronic systemic inflammation and thereby improve vascular function and slow progression of atherosclerosis? To address this intriguing question, investigators from Connecticut and London performed a randomized, blinded clinical study of a group of otherwise healthy subjects with objectively defined severe periodontitis. One group was treated once with a standard oral hygiene regimen, while the others received an aggressive protocol that included extensive plaque scaling, dental extractions, and topical antibiotics. Subjects were then monitored for six months with serial assessments of endothelial function, oral health, and plasma markers of inflammation, coagulation, and endothelial cell "activation." While the control group showed minimal or no change in these markers, on the day after therapy those subjects treated with the intensive regimen demonstrated a remarkable spike in markers of inflammation, including neutrophil count, CRP, and IL-6, with a more modest increase in markers of coagulation and endothelial activation (vWF, PAI-1, and soluble E-selectin). These data are consistent with the systemic entry of periodontal pathogens that is known to occur after therapy of this type. Within a week, levels of the markers began to drop, and by six months they were back to or below baseline. Of greater interest, beginning at about one month, the intensively treated group showed improvement in endothelial function, assessed by ultrasound measurement of flow-mediated dilation (FMD) of the brachial artery. At the end of the study, these subjects had further improvement in FMD with lower neutrophil counts and soluble E-selectin levels than the controls.
In Brief
An association between chronic inflammation and atherothrombotic disorders is supported by abundant epidemiologic and laboratory evidence. A pathological hallmark of early atherosclerosis is accumulation of inflammatory leukocytes in the vessel wall, and among the best predictors of atherothrombotic risk are circulating levels of "markers" of chronic inflammation (e.g., leukocyte count, CRP, factor VIII, fibrinogen, and myeloperoxidase). Patients with chronic inflammatory diseases such as lupus and rheumatoid arthritis are known to be at increased risk for coronary disease and stroke. Recently, chronic periodontal infection has been hypothesized to represent a potentially reversible source of chronic systemic inflammation, and periodontal pathogens have been associated with activation of inflammatory cells in the atheromatous vessel wall. The potential importance of this hypothesis is supported by the population incidence of severe periodontitis, which is as high as 3 percent in some estimates. Using a simple, non-invasive assessment of endothelial function that tests the integrity of endothelial-dependent vasodilating pathways (mostly nitric oxide), these authors demonstrated that a single intensive treatment of severe periodontal disease was associated with a sustained improvement in dental health, endothelial function, and markers of chronic inflammation. It is important to note that the endpoints of this study were surrogate markers for inflammation and vascular health, and that subjects were monitored for only six months, but nevertheless the data are consistent with known pathophysiological data and support the need for a larger study examining the effects of intensive treatment of periodontal disease on atherosclerosis progression and coronary events.
Competing Interests
Dr. Silverstein indicated no relevant conflicts of interest.
