Abstract and Introduction
Background Inflammation of the gingivae (periodontitis) has been associated with raised serum biomarkers of inflammation, sub-clinical markers of atherosclerosis, and increased risk of and/or mortality from cardiovascular disease (CVD). There remain little information regarding the association between other common oral inflammatory disease, systemic inflammation, and CVD. The objective of the study was to assess the association between common oral mucosal diseases, circulating markers of inflammation, and increased prevalence of CVD in a cross-sectional survey of a nationally representative sample of the noninstitutionalized civilians in the United States.
Methods Data for this study are from 17,223 men and women aged ≥17 years who received oral examination as part of the Third National Health and Nutrition Examination Survey. The primary and secondary outcome measures were the association of oral mucosal diseases with raised serum levels of C-reactive protein/fibrinogen and increased prevalence of CVD, respectively. Adjustment for common confounding factors was performed.
Results Having oral mucosal disease was associated with systemic inflammation (serum levels of C-reactive protein ≥10 mg/dL) (odds ratio 1.41, 95% CI 1.02–1.94). Individuals with oral mucosal disease were 1.36 times (95% CI 1.02–1.80) more likely to have history of myocardial infarction and 1.33 times (95% CI 1.03–1.71) more likely to report angina than unaffected individuals. All associations were independent of common confounding factors.
Conclusions This is the first study to suggest that common oral mucosal diseases are independently associated with raised markers of systemic inflammation and history of CVD.
Cardiovascular disease (CVD) remains a leading cause of death in the United States and worldwide. Primary prevention of CVD currently involves targeting interventions to those individuals at high absolute risk, identified using risk-prediction instruments such as the Framingham equation that integrate information on established risk factors such as hypertension, dyslipidemia, smoking, and diabetes. Yet these factors do not explain all of the excess risk because a proportion of cardiovascular events occur among individuals with no or near-average levels of traditional risk factors.[3,4] Approximately 40% of coronary heart disease deaths occur in persons with cholesterol levels that are lower than the population average, and there remains a large part of the population who is classified as intermediate risk via current criteria.[5,6] There is an urgent need for new or emerging factors that could account for some of the unexplained variability in CVD risk and identify those individuals in this group who are actually at high risk and may benefit from more aggressive risk reduction strategies.[5,6]
Inflammation is frequently discussed as a potential major mechanistic contributor to atherothrombosis, and measurement of inflammatory markers could have the potential of improving risk stratification beyond current global risk assessment.[3–8] Indeed, inflammation contributes to all stages in the pathogenesis of atherogenesis from plaque formation, the acute atherothrombotic event, and the myocardial damage following ischemia.[7–9] Low-grade systemic inflammation as assessed by raised serum biomarkers such as C-reactive protein (CRP) has been linked to future risk of coronary events, subclinical measures of atherosclerosis, and stroke,[3–9] although there remains controversy regarding the potential improvement in risk stratification or reclassification from addition of CRP to current models.
Recent evidence supports the notion that extravascular chronic inflammation might also contribute to individuals' CVD risk. Examples include chronic bacteria-induced inflammation of the periodontal tissues (periodontitis)[10–12] and chronic immunomediated inflammation of the skin (psoriasis)[13–16] and joints (arthritis).[17,18,19] These disorders have been associated with systemic inflammation, endothelial dysfunction, and subclinical atherosclerosis, which have all been associated with increased risk/prevalence of and/or mortality from CVD.[9–19] Further acute inflammatory episodes from intercurrent infection in the respiratory (eg, influenza) or urinary tracts have also been associated with increased odds of CVD events.[20,21] Nevertheless, the evidence remains controversial, as these associations may have noncausal explanations but merely be a result of reverse causality or residual confounding.
Periodontitis has received great attention because of its high prevalence worldwide (10%-30% of the adult population) and because it is easier to control (via mechanical cleaning of the diseased dentition) than most other risk factors. Indeed, interventional studies have suggested that treatment of periodontitis improves endothelial function and reduces systemic inflammation.[9,23]
The oral cavity, however, can be affected by a wide range of common disorders other than periodontitis that are characterized by recurrent or chronic local inflammation of the oral mucosa and submucosal stroma. The inflammatory component of these disorders can be primary (autoimmune) or secondary to infections (fungal, viral, or bacterial). Recurrent aphthous stomatitis and recurrent secondary herpes simplex virus–1 infection (herpes labialis), for example, can affect up to 40% of the general population;[24,25] oropharyngeal candidiasis is by far the most common oral fungal infection in men and can affect up to 90% of individuals in certain disease groups (eg, HIV infected); and oral lichen planus has been reported to affect 1% to 2% of the general population, this figure being very similar to psoriasis prevalence. Currently, limited evidence exists on the possible association of these oral mucosal disorders with a state of systemic inflammation and CVD.
The primary aim of the present study was to investigate whether non-periodontal oral mucosal inflammatory diseases are independently associated with increased circulating markers of inflammation in a large representative sample of the US population, based on the 1988–1994 Third National Health and Nutrition Examination Survey (NHANES III). Secondary aims included association of oral mucosal diseases with increased prevalence of history of CVD.
Am Heart J. 2011;161(2):344-350. © 2011 Mosby, Inc.
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