The Complexity of the Periodontal Disease – Atherosclerotic Vascular Disease Relationship And Opportunities for Interprofessional Collaboration

It is clear that viewing oral health as separate from general health has become obsolete. Challenges to our understanding of oral and systemic disease connections arise in part from the compartmentalization of dental care and medical care that exists in the United States (U.S.). Oral disease assessment has historically not been well-taught to physicians, with most medical schools in the U.S. offering under 5 hours of oral health curriculum.¹ In this AHA Scientific Statement, Lockhart and colleagues² further the physician reader’s understanding of basic periodontal anatomy, pathophysiology, microbiology, and the inflammatory/immune response to periodontal disease (PD) in order to provide a framework for an understanding of the biologic plausibility for its relationship to atherosclerotic vascular disease (ASVD).

Dentistry, as recognized by an Institute of Medicine report in 1995, needs to become more closely integrated with medicine and the health care system on all levels: education, research, and patient care, as science and technology in fields such as molecular biology, immunology, and genetics continue to forge links between dentistry and medicine and our aging population presents with more complex health problems.³ Publication of the U.S. Surgeon General’s report on Oral Health in America in 2000 stimulated renewed interest in determining the strength of the evidence and potential for causality of observed associations between PD and systemic diseases, such as diabetes, ASVD, respiratory disease, and low birth weight/preterm births.⁴

ASVD and PD are among the most prevalent diseases of adults and heart disease is the leading cause of death in the U.S., making ASVD prevention and treatment a national health concern. Providing physicians, dentists and the public with an evidence-based understanding of the nature of the relationship between these diseases that share common risk factors is the purpose of this AHA Scientific Statement.² This rigorous review and assessment of the published literature demonstrates the challenge of sorting and interpreting the body of research available to address the association of PD and ASVD and to explore support for causality.² Heterogeneity in study populations, diverse research designs, definition of periodontal and cardiovascular diseases or events, appropriateness of surrogate markers of disease, and frequent lack of adjustment for socioeconomic status, a profound confounder of chronic diseases, further complicate interpretation of study findings. In addition, like the acute triggering factors of increased inflammation and a cascade of hemostasis and thrombosis that lead to catastrophic cardiac events or stroke, PD can exhibit periods of acute inflammation superimposed on chronic disease progression or can appear stable with evidence of past periodontal tissue destruction, making results of periodontal disease intervention trials in individuals with ASVD challenging to interpret. Nonetheless, the consistency among the results of the large number of observational studies suggests that the observed association is independent of known confounding factors of smoking, age, education, and diabetes. Laboratory studies have supported biologic plausibility with proposed pathogenic mechanisms involving both direct and indirect interactions between periodontal pathogens and the endothelium and other mechanisms that impact the atherosclerotic process.² Since PD results in elevation of local and systemic inflammatory markers such as C-reactive protein (CRP), it is likely the PD can increase the inflammatory burden, possibly impacting cardiovascular disease. Clinical trials have shown that rigorous periodontal treatment may result in improvement in ASVD markers. Although the current body of scientific evidence does not support a relationship of causality between PD and specific ASVD events, this AHA Scientific Statement found that an association between the two conditions is supported by Level A evidence (data derived from multiple randomized clinical trials or meta-analyses), independent of known confounders.²

Given the magnitude of ASVD, cardiologists and primary care physicians and dentists must engage patients in risk reduction efforts inclusive of known risk factors. Although oral diseases do not often lead to death, they create morbidity and add to an individual’s disease burden. While research has to date fallen short of demonstrating PD to be a robust risk factor for ASVD, at minimum PD might be viewed as a warning sign and a potential source of pathology affecting the human vasculature. Unfortunately, oral health continues to elude many Americans who face socioeconomic barriers that impede their ability to get dental care in our existing healthcare system, leading to oral health disparities.⁵ Similar health disparities are seen for cardiovascular diseases, with people of lower socioeconomic status being at higher risk for developing heart disease despite long term improvement in risk factors such as cholesterol, hypertension and smoking.⁶

Behavioral habits including diet, exercise, smoking, and oral hygiene (brushing and flossing) routines that contribute to development of ASVD and PD begin in childhood or adolescence and are strongly affected by family and peer influence and education. Shifting the focus upstream to address both the underlying risk factors and social determinants through health education and prevention rather than focusing on surgical and non-surgical procedures to treat established ASVD and PD may lead to improved personal and population health outcomes.⁷ Physician’s increased interest in and awareness of oral and periodontal disease in their patients and their efforts to educate patients on the importance of maintaining oral health and the emerging connections between oral and general health, may encourage patients to improve their oral hygiene habits and to seek oral healthcare on a regular basis. Improved oral and periodontal health, an admirable goal in and of itself, is dependent on patient education, motivation, behaviors and choices. Physician’s advice will have an impact.

This AHA Scientific Statement² demonstrates that we are just beginning to refine our understanding of the nature of the relationship between PD and ASVD. These multifactorial, co-morbid, chronic diseases are caused by complex gene-environment interactions, intertwined with socio-economic determinants. Genomic and proteomic research has recently shown that several of the multiple susceptibility single nucleotide polymorphisms for aggressive periodontitis revealed on chromosome 9p21.3 non-coding region are shared with coronary heart disease, suggesting that common inflammatory pathogenic mechanisms may contribute to both diseases.^8,9 If the epigenetic theory of existence of an inflammatory phenotype predisposing some individuals to inflammatory clinical conditions including PD and ASVD¹⁰ is correct, are certain individuals doomed to encounter morbidity and possible mortality from inflammatory diseases? Should identification of one inflammatory disease (such as PD or ASVD) be a wake-up call for the need for more intensive prevention, surveillance, and intervention for inflammatory diseases throughout the body? A systems medicine approach may be required to identify other elements contributing to the complexity of these diseases elucidate disease phenotypes and enable a transition to a predictive, preventive, personalized and participatory approach to medicine in the future.¹¹

Where do we go from here?

ASVD and PD are typically silent diseases that develop over time and have shared and independent risk factors, many of which are influenced by education and behavioral patterns. As we await additional research discoveries, a rational basis for promoting oral and general health for those with PD and ASVD is to approach prevention and management of these chronic conditions through their common risk factors¹² and underlying social determinants¹³ where possible, and through common biologic pathways. Increased efforts are needed to promote physician-dentist collaboration to encourage and to support patients in achieving optimal oral and cardiovascular health.

Research

A robust research agenda using systems biology and integrative mathematical modeling including data at genetic and cellular levels, combined with clinical and patient-reported disease markers and outcomes, and behavioral and socioeconomic markers, would further advance our understanding. In the interim, prevention and intervention trials focusing on common risk factors, or addressing endothelial dysfunction or the major biologic theories (bacteriological theory, inflammatory theory, and immune theory)¹⁴ to explain the relationship between PD and ASVD, may be helpful. An example is an ongoing clinical trial to assess the effect of doxycycline and related non-antibiotic chemically modified tetracyclines (known to have inhibitory effects on inflammatory mediators and effector molecules, including cytokines and matrix metalloproteinases) on improving PD and ASVD biomarkers in patients who exhibit both diseases.¹⁵ Further collaborative research between cardiology and oral health researchers could help to determine if the relationship between PD and ASVD is bidirectional as suggested for PD and diabetes.^16,17

Education and Practice

Interprofessional education and practice may enhance management of chronic diseases. Dentistry must adopt a more collaborative approach in relation to other health disciplines and assist individuals in creating the conditions in which they can be healthy.

Healthcare team members should recommend patients engage in behaviors and practices known to prevent both PD and cardiovascular disease. When either disease develops, patients should be encouraged to be monitored by health professionals in order to prevent disease progression resulting in acute events, such as myocardial infarction or tooth loss. While strong evidence is lacking that treatment of PD will reduce risk of ASVD events, the role of PD as a potential risk indicator for ASVD should heighten the oral health worker’s awareness of need for blood pressure screening, observation for carotid atheroma on panoramic dental radiographs,¹⁸ and awareness of other cardiovascular disease signs and symptoms. The affected dental patient should be informed of potential increased ASVD risk so timely medical assessment and intervention can be sought. A study by Greenberg and coworkers¹⁹ utilized oral health care professionals to identify patients in dental practices with an increased coronary heart disease risk who could benefit from primary cardiovascular disease prevention activities. Using a cardiovascular disease risk-screening questionnaire and measurement of blood pressure, cholesterol levels, high-density lipoprotein levels and hemoglobin A1c levels, 17% of dental patients were found to have an increased global risk of experiencing a coronary heart disease event within 10 years (Framingham risk score>10 percent).¹⁹

Although the purpose of this AHA Scientific Statement² was not to provide guidance for clinicians, the evidence-review conclusions are consistent with a recent expert panel literature review conducted in January 2009 convened by the Editors of The American Journal of Cardiology and Journal of Periodontology.²⁰ This interdisciplinary panel made clinical recommendations for an approach to reducing risk for primary and secondary atherosclerotic cardiovascular disease events in patient with PD, and included parameters of patient information/education, medical and dental evaluations, and the importance of risk factor treatment for abnormal lipids, cigarette smoking, hypertension, and metabolic syndrome.²⁰ They also recommended interprofessional collaboration to optimize cardiovascular disease risk reduction and periodontal care for patients with ASVD and PD; and a referral for periodontal evaluation and treatment in patients with ASVD and no prior PD diagnosis if patients have signs and symptoms of gingival disease, significant tooth loss, and unexplained elevations of CRP or other inflammatory markers.²⁰

This AHA Scientific Statement² is a “call to action” for heightening the awareness among health professionals of the complexity of the relationship between PD and ASVD. It is also a “call for research” to strengthen the gaps in our scientific understanding of the interaction of PD and ASVD through further well-designed and controlled studies, using uniform PD case criteria and treatment protocols, to explore the longitudinal effectiveness of different management approaches in recognition of the extended evolution of both diseases and their manifestations. While the much over-used expression ”Floss or Die” may be an overstatement, “Healthy Mouth, Healthy Heart” may bear some truth –but until further research is available, this remains unsupported by current evidence.