Of toothaches and heart attacks:

Can dentistry put a dent in heart disease?

WRITTEN BY
Sara C. Gordon, BSC, BA, DDS, MSc FRCD(C), Monika M. Safford, BA, MD, and Andrei Barasch, BA, DMD, MDSc

Does poor dental health increase a person’s risk of cardiovascular disease? Or could it simply be that people with good oral health are also diligent in minimizing other risk factors for cardiovascular disease? These questions are at the center of intense research, discussion, and controversy about the relationship between specific mouth diseases and the status of the circulatory system. We will review here the current evidence that fuels this discussion.

Dental disease is present to some degree in most adults,1 and cardiovascular disease is the most common cause of death in the United States.2 It is not surprising then that the suggestion of a link between these two conditions should spark the intense interest of dentists, physicians, and the public at large. If a cause-and-effect relationship between oral disease and cardiovascular disease (CVD) can be proven, it will likely produce major changes in the relationship between dentists and physicians, between dentists and health insurers, and between dentists and their patients. Additionally, food labels of the future may include cariogenic and periodontopathic information; recommendations for high-risk patients may include dietary changes, exercise, and a professional dental cleaning every month; sulcular tooth brushing may become the topic of prime-time television shows. Indeed, this new paradigm could give dentistry a position much closer to the center of the health-care stage. So, are we there yet?

This question may elicit more than one answer. However, regardless of one’s bias, the truth must be rooted in evidence.

Atherosclerosis

CVD is typically related to atherosclerosis, in which an atheroma progressively restricts the flow of blood through an artery. Atheromas are lesions of the inner (intima) and middle (media) arterial layers, and are composed of fibro-fatty plaques. In addition to occluding arteries and directly disturbing the flow, atheromas may also weaken arterial walls, which can result in rupture or development of aneurisms. Atheromatous plaques can also break off, become emboli, and cause ischemia and infarction at distant sites.3

So, what is the link between oral disease and atherosclerosis? Haynes and Stanford4 outlined four main possibilities:

➊ Oral inflammation may stimulate production of antibodies to oral pathogens, which may cross-react with platelets or endothelial cells.

➋ Oral (periodontal) pathogens may enter blood circulation and locate in pre-existing atheromas, triggering an immune response and inflammation.

➌ Certain people may be genetically predisposed to developing inflammatory diseases such as periodontitis and atherosclerosis.

➍ CVD and periodontitis share many risk factors such as smoking and diabetes.

One or more of these mechanisms, or others, may be at work on a direct connection between the mouth and the circulatory system. Since the etiology of atherosclerosis is not fully understood, all possibilities are worthy of consideration.

Inflammation, pathogens, and arteries

For a number of years, atherosclerosis has been suspected of being caused at least in part by inflammation. In this context, it is plausible that common chronic infections (like periodontal disease) could play a role in its development. As early as 1891, Miller proposed that oral disease served as a “focus of infection” that could cause systemic disease.5 More recently, Beck et al.6 postulated a link between periodontitis and atherosclerosis. These authors reasoned that Gram-negative infections, with their accompanying endotoxin (lipopolysaccharide, LPS) and associated inflammatory cytokines, could promote the development of atheromas and/or thromboemboli. Page7 elaborated on the periodontal pathogen hypothesis, pointing out that LPS and Gram-negative oral bacteria can enter the bloodstream. He agreed with Beck that inflammatory cytokines produced in response to chronic periodontal infection may also play a role in platelet aggregation, thrombosis, and atheroma formation.

In support of the bacterial invasion theory, Herzberg and Weyer used an animal model to demonstrate that injected plaque bacteria can induce platelet aggregation.8 Other groups reported that mice deficient in apolipoprotein E developed accelerated atherosclerotic plaque when injected with invasive Porphyromona gingivalis, a common periodontal pathogen.9 Recent studies have found evidence of bacteria in cardiac tissues, including the coronary arteries. 10 11 Other cardiovascular problems have been connected to oral bacteria when researchers have shown that the spirochete Treponema denticola was present in and around foam cells in aneurysmal lesions.12

Other common human pathogens such as Chlamydia pneumoniae and Helicobacter pylori have also been suggested as culprits in atherogenesis. However, evidence linking C. pneumoniae to CVD is inconsistent13,14 and the association between Helicobacter infection and CVD is weak.15

Risk factor studies

Periodontal disease and CVD share a number of known risk factors, and there are probably other risk factors that have not yet been recognized. Chief among acknowledged risks for the two diseases are increasing age, tobacco use, and diabetes mellitus. These risks have been amply discussed and we will not address them in this paper.16,17

Hypercholesterolemia is an all-too-familiar CVD risk factor.18 Katz et al.19 demonstrated that patients with high cholesterol tend to have more severe periodontal disease, although high triglyceride levels and periodontitis do not appear to have the same correlation.

Obesity also appears to be connected to an increased risk of both CVD and periodontitis. Saito et al.20,21 reported an association between prevalence of periodontitis and both large body mass index and upper body obesity. The authors suggested that periodontitis might be exacerbated by conditions like the “metabolic syndrome” (insulin resistance, hypertension, and dyslipidemia). Ritchie22 pointed out that failure to acknowledge this relationship “could potentially distort the true association” between periodontitis and CVD. Consequently, Nishimura et al. proposed recently that “periodontal disease should be considered as part of the insulin resistance syndrome.”23

The relationship of tobacco use and CVD is well-known; Tomar and Asma made the link between smoking and periodontitis clear in 2000.24 Their analysis of the third National Health and Nutrition Examination Survey (NHANES-3) data indicated that more than half of the periodontitis prevalence in the United States was attributable to smoking.

Many studies have examined other markers for increased risk of CVD. For example, Danesh et al. reported that fibrinogen, C-reactive protein (CRP), albumin levels, and leukocyte counts are associated with risk for coronary heart disease.25 Other groups26,27,28 found that CRP levels were higher in patients with periodontal disease, and that this disease can induce hyper-reactivity in neutrophils.

These findings point to the commonality of various risk factors and provide circumstantial evidence that oral disease and CVD may be related. This evidence was strengthened by the results of a study of 94 patients with severe generalized periodontitis: nonsurgical periodontal therapy was associated with improvement of the periodontal condition as well as significant reductions in systemic CRP and other inflammatory proteins.29

Cardiac event studies

Mattila et al. first reported an association between poor dental health and heart attack in a case-control study.30 Other groups also found that periodontitis was associated with a 25 percent increased risk of heart disease, and suggested that the risk of death was associated with the severity of periodontal disease.31 Similarly, Arbes et al. examined NHANES data and found that self-reported heart attack was 3.8 times greater among patients who had periodontal attachment loss greater than 3 mm in 67 percent or more of their oral sites.32 Other researchers found that tooth loss and periodontal disease were jointly associated with coronary heart disease, and speculated that weaker relationships may be seen in aged patients because older people have fewer teeth.33

A recent study described poorer oral health in 256 patients with severe heart disease than in 250 controls without CVD. Levels of inflammatory markers (CRP and fibrinogen) were consistently higher among the oral disease/CVD patients. Serum H. pylori and C. pneumoniae antibodies were also significantly higher in this group. The authors suggested that acute soft-tissue inflammation, such as gingivitis, pericoronitis, or remaining root tips, might contribute more to the levels of inflammatory cytokines than a single chronic pathologic process, such as periodontitis, which often is subclinical. They also noted that CVD patients were more likely to be hypertensive, and that many hypertension medications cause xerostomia, which in turn promotes oral disease. The study did not adjust for the effects of smoking on oral health (in particular on periodontitis).34

Stroke studies

Various studies examined the epidemiologic relationship between stroke and oral disease. Loesche et al. found that the risk of stroke was associated with the dental plaque index, oral neglect, and oral hygiene, and inversely associated with salivary flow.35 Wu et al. also examined NHANES data and found an increased relative risk of 2.11 for stroke among patients with periodontitis and 1.41 among edentulous patients.36

Opposing evidence

A number of other reports challenge the existence of a significant association between oral and cardiovascular health. A very large study found no significant association between periodontal disease and heart disease in 44,119 adult U.S. males.39 Similarly, another analysis of the NHANES data accounting for all possible confounding factors found no relation between CVD and periodontitis or gingivitis.40

Another large, prospective study, which also controlled for important CVD risk factors, found only a modest increase in the relative risk of heart attack when comparing subjects with zero to 10 teeth to subjects with 25 to 32 teeth (1.36 for men, and 1.64 for women). When the authors analyzed CVD death rates, the relative risk was 1.79 for men, and 1.65 for women with zero to 10 teeth.41 Similarly, another study found the adjusted relative risk ratios between heart disease/stroke and periodontal disease/tooth loss, were low, ranging from 1.01 to 1.3742.

A longitudinal 12-year study of 6,500 subjects found that adjustment for well-known risk factors (such as smoking, obesity, hypertension, and age) reduced the association between periodontitis and CVD to statistical insignificance.43 Finally, a rigorous meta-analysis of data on the relationship between periodontal disease and CVD showed only a modest increase in risk ratio.44

Can we draw any firm conclusions?

In the view of the current authors, this debate is not yet closed. Definitive proof of a cause-and-effect relationship between oral disease and CVD is still missing. However, there is a tantalizing body of evidence suggesting that this relationship may be real, and more new studies are being published every month.

Shortcomings in the current literature include the paucity of studies controlling for BMI and metabolic syndrome rather than overt diabetes. Similarly, many cardiovascular medications cause dry mouth, which is associated with increased risk of dental disease; this factor has not been rigorously studied as a potential confounder. Other variables and risk factors may still be waiting to be discovered, and may explain the variability of study results. Most importantly, as yet, there is insufficient evidence that treating periodontal disease improves CVD outcomes. While we wait for this, we must still say “maybe.”

Until the final pin falls, dentists should not make treatment claims that could prove unfounded. Instead, dentists can continue to prevent and treat all oral diseases, including periodontal disease. We can examine panoramic radiographs for signs of carotid calcifications, so that procedures can be considered to prevent stroke. We can teach nutrition to our patients. Finally, we can work much harder to prevent and treat addiction to tobacco, the most destructive lifestyle habit in North America.

References

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Sara C. Gordon, BSC, BA, DDS, MSc FRCD(C)
Dr. Gordon is an associate professor in the Department of Diagnostic Sciences, School of Dentistry, University of Detroit Mercy, and the associate director of oral pathology at St. John Clinical Laboratories. You may contact Dr. Gordon at [email protected].

Monika M. Safford, BA, MD

Dr. Safford is assistant professor of medicine at the Deep South Center on Effectiveness at the Birmingham VA Medical Center and School of Medicine, University of Alabama at Birmingham. You may contact Dr. Safford at [email protected].

Andrei Barasch, BA, DMD, MDSc

Dr. Barasch is an associate professor in the Department of Diagnostic Sciences, School of Dentistry, at the University of Alabama at Birmingham. You may contact Dr. Barasch at [email protected].