Coronary Artery Disease Common oral mucosal diseases, systemic inflammation, and cardiovascular diseases in a large cross-sectional US survey Stefano Fedele, DDS, PhD, a Wael Sabbah, BDS, MSc, b Nikos Donos, DDS, MS, PhD, a Stephen Porter, BSc, MD, PhD, a and Francesco D'Aiuto, DMD, PhD a London, United Kingdom 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. (Am Heart J 2011;161:344-50.) Cardiovascular disease (CVD) remains a leading cause of death in the United States and worldwide. 1 Primary prevention of CVD currently involves targeting inter- ventions 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, dyslipid- emia, smoking, and diabetes. 2 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, 4 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 contri- butes 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 im- provement in risk stratification or reclassification from addition of CRP to current models. 3 From the a UCL Eastman Dental Institute, Oral Medicine, University College London, London, United Kingdom, and b UCL Department of Epidemiology and Public Health, University College London, London, United Kingdom. Submitted January 25, 2010; accepted November 7, 2010. Reprint requests: Stefano Fedele, DDS, PhD, Eastman Dental Institute, University College London, 256 Gray's Inn Rd, London WC1X 8LD, United Kingdom. E-mail: s.fedele@eastman.ucl.ac.uk 0002-8703/$ - see front matter © 2011, Mosby, Inc. All rights reserved. doi:10.1016/j.ahj.2010.11.009