Periodontitis is one of the most prevalent chronic inflammatory diseases of mankind. In 1998, Garcia and colleagues reported on the association between periodontitis, expressed as alveolar bone loss (ABL) and pocket depth, and mortality from any cause. They followed a cohort of 804 men over 25 years; while all were medically healthy at the start of the study, some men had periodontitis and others did not. They found that, over time, men with severe periodontitis at the start were more likely to die younger, even after controlling for smoking status, age, blood pressure, cholesterol, and family history of heart disease. Even in a sub-analysis of never smokers, they found that men with the worst periodontitis had a 2.49 times higher rate of death. Jimenez et al. re-visited the data (2009) some 40+ years from study commencement and present data at this meeting on 516 recorded deaths. In brief, their analyses confirm a 1.46-fold increase in “all cause” rate of death in men with moderate to severe ABL compared to men with no or minor ABL. Interestingly, death rates amongst edentulous men were more than two-fold higher than in men with no/minor periodontal bone loss. Whilst this finding may in part reflect tooth loss resulting from severe periodontitis or other infective oral sequelae, there are also several other potential explanations. The question then is how do we explain such data?
The periodontium is unique in that it is the only site in the body where the internal connective tissues (the tooth root) protrude through an intact ectodermal (skin) barrier, and into an environment colonised by 800+ bacterial species. Unsurprisingly, the junction between the tooth and mucosa (the dento-gingival complex) has developed specialised mechanisms to protect the body’s internal tissues and vital organs from infection. One key feature is that the lining epithelium that separates the plaque-coated tooth surface from the connective tissues beneath is permeable to components of the inflammatory-immune response. The latter pass from blood vessels through the periodontal tissues and emerge as an anti-microbial fluid, which bathes the epithelium. However, when the gingivae become “inflamed” due to a build up of plaque, the lining epithelium ulcerates and exposes an 8-20 cm2 area of connective tissue, and associated vasculature, to biofilm organisms and their virulence factors. Is the reason for the association between periodontitis and all cause mortality due to the adverse effects of low grade chronic infection or inflammation in the vasculature, arising from the periodontium?
Hippocrates was one of the earliest reported advocates of the “focal infection” theory, whereby occult infections arising within sites like the mouth lead to disease at distant unrelated sites. He claimed to have “cured a patient’s rheumatism” by extracting an infected tooth. Anthony van Leeuwenhoek’s 1650’s description of the existence of “strange little animals” in dental plaque he scraped from his teeth and visualised under his “new microscope” fuelled an expansion of the theory. This now largely obsolete paradigm informed substantial changes in surgical practice for centuries. Interestingly, dePablo et al. recently demonstrated that patients with rheumatoid arthritis were about 80 % more likely to have periodontitis. A meta-analysis of the impact of periodontitis upon cardiovascular disease demonstrated an overall increased risk of 19 % in all ages and 44 % in < 65-year olds. The relative risk of stroke was increased 2.85 fold by periodontitis. Another disease whose complications are largely underpinned by inflammation is type 2 diabetes. Diabetes patients with periodontitis are reported to be 6-fold more likely to have poor glycaemic control and type 2 diabetes sufferers appear 3 times more likely to have periodontitis. There is a common theme here, one of inflammation-mediated pathologies, leading to morbidity and/or mortality.
In summary, evidence has emerged over the last decade that periodontitis is associated with an elevated risk of systemic inflammatory diseases that are associated with premature mortality. Whether periodontitis is causally-related to those conditions remains unclear. Whilst there is some evidence for causality from biomarker studies of the impact of periodontal therapy on systemic inflammation, there remains a paucity of periodontal intervention studies which employ robust clinical outcome measures. The existence of a specific patient phenotype, modifiable by environmental exposures and characterised by a predisposition to exaggerated inflammation, has emerged. Thus a co-susceptibility to apparently un-related inflammatory conditions confounds existing disease associations, but remains biologically plausible as an explanation for their cumulative effects upon morbidity and mortality. We propose that periodontitis leads to “focal inflammation” rather than “focal infection”, which aggravates the destructive processes of co-morbid inflammatory diseases, but which if treated may improve clinical as well as biochemical outcomes.
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