CVD & Stroke

In general, approximately 50% of deaths in the United States are attributed to complications of atherosclerosis and consequential cardiovascular diseases (CVDs). The annual incidence of new strokes is 2 per 1,000 persons. Studies on the pathology of stroke indicate that 80 to 85% of these lesions are due to cerebral infarction; 15 to 20% are caused by hemorrhage.

Recent studies have provided statistical associations between periodontitis and CVDs, and have suggested that periodontitis may be a risk factor for CVDs. If so, periodontal disease, because it is both preventable and treatable, may be a modifiable risk factor for CVD. Associations of varying strengths between CVD and periodontitis (Risk Ratios of 1.2-2.8) have been reported from different populations. Persons with minimally severe periodontitis have a 25% greater risk of subsequent coronary artery disease than those without periodontitis. Acknowledged risk factors for these CVDs (i.e., obesity, diabetes, smoking, hypertension and elevated serum lipid and cholesterol concentrations) are also risk factors for periodontal disease.

Epidemiological studies have found an association between periodontal disease and coronary artery disease, however have not proven causality. Periodontitis has been shown to increase the systemic inflammatory response which has been implicated in cerebrovascular events, such as strokes and carotid calcifications. The inflamed periodontium releases inflammatory cytokines, lipopolysaccharides (LPS), and bacteria into the systemic circulation, and they may promote atherosclerosis and affect blood coagulation, the function of platelets, and prostoglandin (PG) synthesis, thereby contributing to the onset of stroke. Studies have found that poor oral health was more common in the patients with cerebral infarction than in individuals without cerebral infarction, and that poor dental and oral conditions were significantly associated with the diagnosis of a cerebral vascular accident. In a different study, gingivitis and edentulism, but not dental caries, have been shown to be associated with the incidence of stroke.

Environmental risk factors consist of socioeconomic status, exercise, stress, diet, nonsteroidal anti-inflammatory drugs (NSAIDS), smoking, and chronic infection. CVDs, for example, atherosclerosis and myocardial infarction (MI) arise on account of a complex set of genetic and environmental factors. Genetic risk factors consist of age, lipid metabolism, obesity, hypertension, diabetes, increased fibrinogen levels, and platelet-specific antigen Zwb (P1) polymorphism. However, classical risk factors of CVD, for example hypertension, hypercholesterolemia, cigarette smoking, and genetics can only explain one-half to two-thirds of the disparity in CVD prevalence.

There are several scientifically proposed mechanisms by which periodontitis may bring forth pathways leading to CVDs. Evidence indicates that certain oral bacteria, such as Streptococcus sanguis andPorphyromonas gingivalis, can induce platelet aggregation leading to thrombus formation. These organisms have a collagen-like molecule on their surfaces, called the platelet aggregation-associated protein. WhenS. sanguis was injected intravenously into rabbits, a heart attack-like series of events occurred, and it was suggested that antibodies reactive to periodontal organisms localize in the heart and trigger complement activation, that is, a series of events leading to T cell sensitization and heart disease. A recent study demonstrated that P. gingivalis can actively adhere to and invade fetal bovine heart endothelial cells, bovine aortic endothelial cells, and human umbilical vein endothelial cells. Researchers studied proteolytic enzymes referred to as gingipains R, which are released in large quantities from P. gingivalis. After entering the circulation, gingipains R can activate factor X, prothrombin, and protein C, and as a result can promote a thrombotic trend through the eventual release of thrombin, subsequent platelet aggregation, conversion of fibrinogen to fibrin, and intravascular clot formation, which in turn can cause thrombosis, coronary heart disease, and stroke.

Another mechanism of action could be an exaggerated host response to a given periodontal bacteria or LPS challenge, as reflected in the release of high levels of proinflammatory mediators such as PGE, TNF-alpha, and IL-1ß, which have been related to inter-individual differences in T-cell range and secretory capacity of monocytic cells. Typically, peripheral blood monocytes from individuals with the hyperinflammatory monocyte phenotype secrete 3- to 10-fold-greater amounts of these mediators in response to LPS compared to those from normal monocyte phenotype individuals, which can directly trigger and modulate the inflammatory response. Patients with certain forms of periodontal disease, such as early-onset periodontitis (aggressive periodontitis) and refractory periodontitis, possess a hyperinflammatory monocyte phenotype.

A third mechanism of action possibly involves the relationship between bacterial and inflammatory products of periodontitis and CVD. LPS from periodontal organisms being transferred to the serum as a result of bacteremias, or bacterial invasion, could have a direct effect on the vascular endothelia and promote atherosclerosis. LPS may also elicit recruitment of inflammatory cells into major blood vessels and stimulate vascular smooth muscle proliferation, vascular fatty degeneration, intravascular coagulation, and blood platelet function. These changes are the result of the action of various biologic mediators, such as PGs, ILs, and TNF-alpha on vascular endothelium and smooth muscle. Fibrinogen and WBC count increases noted in periodontitis patients may be a secondary effect of the above mechanisms or a constitutive feature of those at risk for both CVD and periodontitis.

A fourth mechanism of action is that periodontitis as an infection may stimulate the liver to produce the inflammatory biomarker C-reactive protein (CRP), which can form deposits on injured blood vessels. CRP binds to cells that are damaged and fixes complement, which activates phagocytes, including neutrophils. These cells release nitric oxide, thereby contributing to atheroma formation. Researchers have reported that CRP levels were significantly higher in untreated periodontitis subjects when compared to healthy subjects. Also, subjects with severe periodontitis had significantly higher CRP levels than mild-periodontitis subjects, and both had significantly higher CRP levels when compared to subjects with no periodontitis. Scientists studied the plasma concentrations of 1,043 apparently healthy men, and demonstrated that CRP could predict the risk of future myocardial infarction and stroke. Others have found that patients with adult periodontitis have higher levels of CRP and haptoglobin than subjects without periodontitis. Also, following periodontal therapy, both CRP and haptoglobin levels significantly declined. Researchers have also evaluated the association between CVD and CRP levels. Subjects with both heart disease and periodontal disease had significantly higher mean CRP levels (8.7 g/ml) when compared to subjects with neither disease mean CRP levels of (1.14 g/ml). It was also shown that periodontal disease therapy reduced CRP levels by 65% in three months; which remained reduced for 6 months.

Periopathogenic bacteria, including A. actinomycetemcomitans and P. gingivalis have also been recovered from 42% of atherosclerotic plaques in individuals with severe periodontitis, and DNA probes demonstrated their presence in the right coronary artery of post-mortem subjects. The bacteria may directly effect blood platelet activation and aggregation, causing the initiation and progression of atherosclerosis. A direct relationship between periodontitis and thickening of the inner wall of the carotid artery has also been reported from the Atherosclerosis Risk in Communities (ARIC) study.

Oral infections, especially periodontitis may cause tooth loss, and there is evidence that impaired dentition can affect an individual’s health by causing dietary restrictions due to difficulty in chewing, possibly compromising their nutritional status and well-being. It has also been shown that edentulous persons, with and without dentures, as well as dentate individuals with missing teeth, change their eating habits. This may happen because people who cannot chew or bite comfortably are less likely to consume high-fiber and nutritient-rich foods such as breads, fruits, and vegetables; and tend to select high-calorie, high-fat foods, thereby reducing their intake of essential nutrients. When the foods cannot be chewed well, adverse effects on the internal absorption of nutrients can also occur.

Dysphagia (Difficulty in Swallowing)

Dysphagia is most commonly associated with stroke, however numerous other factors may also cause this problem, including poor oral health. Sequentially, dysphagia can result in decreased fiber and caloric intake. These changes in dietary preference could predispose such individuals to the type of high-fat foods that are acknowledged risk factors for CVD, obesity, diabetes, and dyslipidemia.

Also dysphagia, which commonly follows stroke, can result from insufficient food intake, in terms of lowered food volume intake. Malnutrition, secondary to insufficient protein intake can then occur, resulting in decreased consumption of overall calories and dietary micronutrients. This malnutrition can delay the course of recuperation. It has been reported that individuals with dysphagia improve after one month of adequate dietary intake and speech therapy. Dietary recommendations for individuals suffering from dysphagia range from pureed food to regular food, depending on the individual.

Individuals that have experienced a stroke, especially if this occurred on their predominant side, may not be able to adequately maintain their oral hygiene. They will have difficulty holding a toothbrush, floss and other oral hygiene aids. It is very important for the care-giver a help these individuals maintain optimal oral hygiene. The use of oral health care products has been shown to be very beneficial in reducing dental plaque and their related oral diseases.

Missing Teeth

In individuals with teeth that are missing many teeth, diet-induced elevation of serum low-density lipoprotein has been shown to upregulate monocytic responses to LPS. In these subjects, one would have both the diet-induced sensitization of monocytes and teeth loaded with plaque that could provide the LPS challenge to these cells. Instead of having hyper-responsive monocytes reacting to any LPS introduced from the plaque, there would be elevated secretion of inflammatory cytokines by monocytes stimulated by elevated low-density lipoprotein levels. This interaction between LPS and monocytes may also explain the severity of Gram-negative infections in certain diabetic patients, but it could also be operating in individuals who change to a high-fat diet because of missing teeth. Therefore, all of the mechanisms by which poor oral hygiene and periodontal disease may contribute to CVD described above could also come into play as a result of certain dietary changes secondary to missing teeth. Subsequently, periodontitis and tooth loss can affect nutritional status and food selection, which can have very harmful effects on the body’s general health.

Infective Endocarditis

Infective endocarditis, a bacterial infection of the heart valves or the heart endothelium, occurs when bacteria in the bloodstream embed on abnormal heart valves or damaged heart tissue. Individuals who have certain preexisting heart defects are at greater risk for developing endocarditis when a bacteremia occurs. Infective endocarditis seldomly occurs in people with normal hearts.

Infective endocarditis, a serious problem that can lead to fatality, has been associated with dental diseases, as well as dental treatment. Numerous scientific reports exist regarding the association of dental procedures and/or diseases with the onset of endocarditis in humans and experimental animals. Certain dental procedures, particularly tooth extractions and probably scaling, meet presently established epidemiological standards for causation of endocarditis.

Studies have shown that:

  1. the incidence of infective endocarditis varied between 0.70 and 6.8 per 100,000 person-years;
  2. over 50% of all infective endocarditis cases were not associated with either an obvious procedural or infectious event 3 months prior to the development of symptoms;
  3. 8% of all infective endocarditis cases were associated with periodontal or dental disease without a dental procedure;
  4. the risk of infective endocarditis after a dental procedure was probably in the range of 1 per 3,000 to 5,000 procedures; and
  5. over 80% of all infective endocarditis cases were acquired in the community, with the associated bacteria being part of the host’s endogenous flora.

A mechanism of action recently proposed is that dental disease- and procedure-associated endocarditis involves both early and late bacteremias. The early bacteremia may “prime” the endothelial surface of the heart valves over many years and promote early valve thickening. This, in turn would render the heart valves more susceptible to late adherence and colonization with bacteria, which may work over days to weeks allowing bacterial adherence and colonization of the valve, resulting in a sudden and severe infection.