Periodontal Disease and Overall Health: A Clinician's Guide

CHAPTER 3 Infection and Inflammation 33for the initiation and progression of a varietyof inflammatory diseases, including arthritis,peptic ulcers, and appendicitis. As a result,therapeutic full-mouth extractions became acommon dental practice. However, many teethwere extracted without evidence of infection.When it was finally realized that there wasno therapeutic benefit, the theory was finallydiscredited and the practice abandoned. Duringthe final two decades of the twentiethcentury—as our knowledge concerning theinflammatory component of systemic diseaseswas enriched and our understanding ofthe relationship of periodontal disease tosystemic inflammation increased—the ideathat periodontal infection may affect theprogression of systemic disorders such ascardiovascular disease, adverse pregnancycomplications, diabetes mellitus, and otherdiseases re-emerged.In this possible association, systemicinflammation seems to play a key role.Specifically, on one hand, periodontal diseasemay induce systemic inflammation andon the other, there is increasing evidencesuggesting that elevated levels of the markersof systemic inflammation are associatedwith an increased risk for systemic diseases.Cardiovascular Disease (CVD)There is now abundant clinical evidencedemonstrating that many biomarkers of inflammationare elevated years in advance offirst-ever myocardial infarction (MI) orthrombotic stroke, and that these same biomarkersare highly predictive of recurrentMI, recurrent stroke, and death due to CVD. 2Moreover, studies demonstrate that serumIL-6 levels were significantly elevated insubjects who subsequently experienced anMI compared to age-matched controls. 34Similarly, plasma levels of soluble P-selectin,soluble CD40L, and macrophage-inhibitorycytokine-1 were all significantly increased inhealthy subjects who subsequently developedCVD events compared to matched controls. 35Elevated plasma concentrations of TNF-αhave also been associated with CVD, andspecifically with recurrent nonfatal MI orother CVD events. Moreover, TNF-α levelswere persistently higher among post-MIpatients at increased risk for recurrent coronaryevents.Besides these pro-inflammatory cyto -kines, several acute-phase reactants have alsobeen associated with CVD. One of the factorswith the strongest evidence as a biomarkerfor predicting CVD events is CRP(specifically, high sensitivity CRP, hsCRP).When measured in the blood, hsCRP provedto be a strong, independent predictor of futureMI and stroke among apparently healthyasymptomatic men. Also, the relative riskfor first MI and ischemic stroke increasedsignificantly with each increasing quartileof baseline concentrations of CRP. 36 As describedalready, CRP may contribute to theinitiation and development of atherothromboticlesions not only by up-regulating theexpression of pro-inflammatory cytokines,but also by mediating proliferation and activationof SMCs and by activating the procoagulantsystem. This last property may befurther enhanced by another acute-phase protein,fibrinogen, which is often found to beelevated in CVD patients.Adverse Pregnancy OutcomesSystemic inflammation has also beenimplicated in adverse pregnancy outcomes,since elevated concentrations of CRP in earlypregnancy are associated with an increasedrisk of preterm birth and very-preterm birth.Diabetes MellitusFinally, systemic inflammation hasbeen associated with both Type 1 and Type2 diabetes mellitus. Recent studies suggestthat in Type 1 diabetes, the levels of systemicmarkers of inflammation, such as CRP,do not differ between healthy individualsand subjects for which Type 1 diabetes has