INTRODUCTION

Cardiovascular disease is one of the most common diseases in Western countries. Chronic infections and chronic inflammation are two important risk factors in the development of cardiovascular diseases.

Chronic microbial infection and chronic inflammation caused by the dental plaque in periodontal disease may predispose to atherosclerosis. Microbial dental plaque is the cause of inflammatory oral diseases such as gingivitis and periodontitis. Severe periodontal disease is associated with cardiovascular disease because of low-grade chronic inflammation and periodic systemic bacteremia with migration of bacteria in general circulation responsible for the damage to vascular cells. High prevalence of periodontitis is associated with cardiovascular diseases such as atherosclerosis, myocardial infarction, and stroke. Severe periodontitis is also associated with peripheral arterial disease, and subclinical atherosclerosis defined by the measure of carotid artery intima-media thickness.

Two main mechanisms are responsible for the association between atherosclerosis and periodontitis: the general systemic inflammatory response and the specific effects of periodontal bacteria on vascular host tissues.

Cofactors for periodontitis and cardiovascular disease are the following:

• Hypertension
• Diabetes
• Smoking
• Altered lipid metabolism with high low-density lipoprotein cholesterol, low high-density lipoprotein cholesterol, and high triglycerides
• High body mass index
• Low physical activity
• Genetics
• Stress
• Chronic alcohol abuse

There are many risk factors for the development of atherosclerosis in periodontal disease:

• Chronic inflammatory conditions
• Infections with direct microbial effect or systemic bacteremia and indirect cross-reactivity with microbial antigens
• Oxidative damage of plasmatic lipoproteins or lipid peroxidation
• Vascular endothelium dysfunction
• Platelet activation

Chronic Inflammation

Periodontal inflammation is associated with an elevated systemic inflammatory state and an increased risk of cardiovascular diseases such as atherosclerosis, myocardial infarction, and stroke (Mealey and Rose 2008). Systemic inflammation may contribute in the pathogenesis of atherosclerosis, with accumulation of lipids on the vascular walls.

Periodontitis is responsible for a local progressive inflammation leading to the destruction of the supporting tissues and alveolar bone loss. Periodontitis induces systemic inflammation with increased production of serum cytokines and inflammatory mediators. Most patients present elevated levels of systemic inflammation markers such as C-reactive protein, IL-6, and fibrinogen (Amabile et al. 2008; Amar et al. 2003; Bizzarro et al. 2007; Chen et al. 2008; D’Aiuto 2004; Karnoutsos et al. 2008; Linden et al. 2008; Meurman et al. 2003; Smith et al. 2009).

Infection

Chronic infection is a risk factor in the development of cardiovascular diseases. There are two important pathogenic mechanisms.

Periodontal infection, or the response of the host against the infection, may play a role in the pathogenesis of coronary heart disease. Serum antibodies to periodontal pathogens are associated with coronary heart disease. All antibody levels against periodontal pathogens correlate positively with the measure of carotid intima-media thickness. Serum antibody levels to periodontal pathogens are associated with subclinical atherosclerosis and consequently with future incidence of coronary heart disease. Infections caused by Porphyromonas gingivalis increases the risk for myocardial infarction. High P. gingivalis IgA class antibody levels can predict the risk for myocardial infarction independently from other cardiovascular risk factors (Pussinen et al. 2003, 2004, 2005; Yamazaki et al. 2007).

Dyslipidemia

Periodontal infection is associated with elevated plasma levels of atherogenic lipoproteins. Chronic infection is associated with increased risk of systemic diseases because of metabolic changes. Periodontitis is an independent risk factor of cardiovascular diseases because of the systemic inflammatory reaction and hyperlipidemia. In periodontitis patients, elevated serum levels of lipoprotein associated phospholipase A2, which is a marker of dyslipidemia, is correlated with cardiovascular disease risk (D’Aiuto et al. 2006; Katz et al. 2002; Losche et al 2005; Nibali et al. 2007; Rufail et al. 2005, 2007).

Endothelial Dysfunction

Endothelial dysfunction is one mechanism, which combined with inflammation, is responsible for the development of atherosclerosis. Periodontal disease is associated with endothelial dysfunction because the chronic systemic inflammation may lead to impaired functioning of the vascular endothelium. There is a direct interaction of periodontopathic bacteria with vascular tissues. Endothelial dysfunction present in periodontitis is an important element in the pathogenesis of atherosclerosis. Endothelial dysfunction is tested using flow-mediated dilation of the brachial artery.

Periodontal therapy results in an improvement in endothelial function and a decrease in inflammatory markers. Improvement in endothelial function, as measured by flow-mediated dilation of the brachial artery, is possible through elimination of oral infections by periodontal treatment (Amar et al. 2003; Elter et al. 2006; Seinost et al. 2005; Tonetti et al. 2007).

Platelet Activation

Periodontitis is caused by Gram-negative bacteria. Chronic Gram-negative infections represent a risk factor for thromboembolic events. Bacteria from dental plaque and their products disseminate into circulation and can promote thromboembolic events associated with cardiovascular diseases. Platelets from periodontitis patients are more activated because of regularly occurring bacteremic episodes. This may increase impaired fibrinolysis and be responsible for a prothrombotic state. Plasma levels of markers of a prothrombotic state, such as plasminogen activator inhibitor-1, are elevated in patients with periodontal disease. Platelet-activating factor, an inflammatory phospholipid mediator, is present in elevated levels in inflamed gingival tissues, gingival crevicular fluid, and saliva in periodontitis patients (Antonopoulou et al. 2003; Bizzarro et al. 2007; McManus and Pinckard 2000; Renvert et al. 2006; Sharma et al. 2000).

Patient Management

Oral infections may represent a significant risk factor for systemic diseases. The control of oral diseases is necessary in the prevention of systemic conditions. Health education to encourage better oral hygiene is also an important element in the prevention of cardiovascular diseases. Periodontitis patients may benefit from an intensive therapy in order to reduce coronary artery disease progression.

Dentists and physicians should treat or prevent risk factors for cardiovascular disease. These risk factors include the following:

• Atherosclerosis
• Dyslipidemia
• Hypertension
• Diabetes mellitus
• Cigarette smoking
• High body mass index and high waist-to-hip ratio
• Periodontal disease
• Low physical activity
• Stress

Dentists and physicians should also educate patients about the relationship between cardiovascular disease and periodontitis. They should encourage smoking cessation, low-fat diet, regular exercise, and good oral hygiene. In cases of patients with cardiovascular disease, before oral therapy, dentists should minimize stress and check blood pressure and all of the patients’ medical prescriptions.

CHRONIC INFLAMMATORY CONDITIONS

Inflammation Markers and Cytokines

Inflammation markers are as follows:

• C-reactive protein
• Erythrocyte sedimentation rate
• Leukocyte counts
• Fibrinogen
• Serum amyloid A protein.

Inflammatory cytokines are as follows:

• Thromboxane A2
• IL-1β
• IL-6
• Prostaglandin E2
• TNF-α.

Inflammation Markers

C-reactive Protein

Patients with advanced periodontitis present significantly higher serum levels of high-sensitivity C-reactive protein (Amar et al. 2003). Patients with coronary heart disease also show higher levels of serum C-reactive protein (Meurman et al. 2003). Periodontitis is associated with increased levels of C-reactive protein; patients with levels greater than 3 mg/L have 2.49 times higher risk for advanced periodontitis (Linden et al. 2008). Chronic infections such as periodontitis produce inflammatory conditions, and patients with periodontitis show higher levels of serum C-reactive protein than healthy subjects (Bizzarro et al. 2007). Patients with periodontitis have significantly higher levels of serum C-reactive protein, with a median of 2.19 mg/L, compared to healthy people who have a median level of 1.42 mg/L (Briggs et al. 2006). High serum C-reactive protein is significantly associated with a high level of tooth loss, with an odds ratio of 2.17 (Linden et al. 2008). Systemic inflammatory response is more important in periodontitis patients presenting coronary artery lesions, with mean periodontal pocket depth greater than in subjects without coronary lesions. Mean pocket-depth values also correlate significantly with high-sensitivity C-reactive protein and with angiographic score of coronary lesions (Amabile et al. 2008).

Serum C-reactive protein levels are significantly associated with the outcome of periodontal treatment; nonsurgical periodontal therapy significantly decreases serum markers of systemic inflammation, with significant reduction of C-reactive protein levels (D’Aiuto et al. 2004). Intensive periodontal therapy produces significant reduction of inflammatory markers, with significant serum C-reactive protein decrease at 1 and 2 months after treatment (D’Aiuto et al. 2006).

Erythrocyte Sedimentation Rate

Chronic infections such as periodontitis produce inflammatory conditions, with higher serum erythrocyte sedimentation rates (Bizzarro et al. 2007). Patients with coronary heart disease also show higher levels of blood erythrocyte sedimentation rate (Meurman et al. 2003).

Leukocytes

Periodontitis produces inflammatory conditions with higher levels of leukocyte counts (Bizzarro et al. 2006); patients present a low-grade systemic inflammation with significantly increased blood leukocyte counts (Nibali et al. 2007). In periodontitis, the low-grade chronic inflammatory response is characterized by elevated levels of blood neutrophils and monocytes (Smith et al. 2009).

Serum Amyloid A Protein and Fibrinogen

Periodontitis is associated with increased levels of serum inflammation markers such as fibrinogen (Linden et al. 2008). In patients presenting periodontitis and coronary lesions, mean pocket-depth values correlate significantly with serum amyloid A protein and fibrinogen levels (Amabile et al. 2008). Patients with coronary heart disease also show higher levels of serum fibrinogen concentrations (Meurman et al. 2003).

Inflammatory Cytokines

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