(1) Odontóloga. Colaboradora Honoraria de Clínica Odontológica Integrada de Pacientes Especiales
(2) Profesor Titular. Clínica Odontológica Integrada de Pacientes Especiales. Facultad de Odontología de Sevilla

Address:
Prof. Guillermo Machuca Portillo.
Facultad de Odontología. Departamento de Estomatología.
Universidad de Sevilla.
c/ Avicena s/n.
41009-Sevilla.
Teléfono: 954481128. FAX: 954481157
E-mail:gmachuca@us.es

Received: 21-11-2004  Accepted: 9-04-2005

Cardiovascular diseases imply a great health problem in today’s society in industrialized countries and they are the first cause of mortality in men as well as in women (1).

On specifically analyzing deaths due to circulatory apparatus diseases in males, ischemic heart disease is the most frequent cause, closely followed by cerebrovascular pathology and hypertensive illness; in women ischemic heart disease is second in importance after cerebrovascular pathology while hypertensive illness occupies third place (2,3).

Ischemic heart disease is of multifactor origen. The factors which render it liable must fulfill the causality criterion: strength of association (relatively high risk), consistency of association (demonstrated in several studies), temporal relation (the cause precedes the effect), biological acceptability,experimental evidence and above all, evidence from studies in humans.

The risk factors can be non modifiable such as the sex or age and others modifiable such as cholesterol levels. arterial hypertension, a smoking habit, others. In the last few years new ones have appeared such as lipoprotein A, homocistein .. etc, which prevail more in atherosclerotic disease and some allow us to increase prediction capacity in vascular disease. However,in clinical practice, their role in the prevention is limited to weak associations, lack of treatment, difficulty in their determination.. etc (2).

Arterial hypertension (AHT) is, together with a smoking habit and hypercholesteroloemy, one of the main risk factors in the development of ischemic heart disease and the main risk factor for cerebrovascular events (CVA). Moreover, it is a frequent cause of cardiac insufficiency in the adult and other cardiovascular diseases such as aorta disecting aneurysm (3).

The sanitary importance of AHT largely derives from its high prevalence. Diverse epidemiological studies carried out on the Spanish population over the last decade obtain a AHT prevalence that varies between 30 and 40% of the population over 18, which means it affects more than 8 million people in our country. Almost 68% of elderly people are hypertense (4).

Likewise, the risk of cardiovascular disease in hypertense patients is three fold higher than those who are not; a 2.5 fold higher risk exists of suffering ischemic heart disease and 7 fold greater of suffering cardiovascular disease, thus, in this case, a risk factor of a high degree of association can be spoken of (5,6).

RELATION BETWEEN PERIODONTAL DISEASE AND CORONARY DISEASE

It is strange to think that two such different groups of diseases such as the coronary and periodontal,without any apparent connection in their clinical and systemic severity pathogenesis, have been able to be related, although it is only superficially at the moment.Initially, the only thing they seem to have in common is their enormous frequency in advanced societies. However,the progress in the knowledge of mecanisms that trigger both entities has allowed us to establish an unsuspected approximation of both processes and, besides, all the above has been able to be corroborated epidemiologically.

Periodontal diseases are conditioned to their beginning, development and severity by a series of generally well known factors.So then, the possible role of periodontal pathology in the evolution of certain systemic disorders is ourstanding nowadays, basically those derived from ischemic cardiovascular processes (7).

Too much time has had to pass to understand that the mouth is not an isolated structure within the organism, and although the importance of the oral cavity is known in the field of human phisiology and in certain groups of diseases such as oral cancer, little is known about the relation of the characteristic infections of dental and periodontal tissues with other organs or systems in the human body.

The question would be, Is it possible that a harmful effect could occur in an organism as a consequence of a continuous bacterial agression in a healthy patient with a chronic infectious oral disease? This question is certainly important, and the affirmative answer to this could modify the patient, doctor and dentist’s attitude towards this type of diseases.

There is a close relationship between inflammatory processes and atherosclerosis, as is proved by the fact that factors such as hypertension,diabetes,cholesterol or obesity, which increase the inflammatory tone of the body, are closely related to cardiovascular risk. The explanation for this increase in risk in the long term is found in the fact that coronary disease is a multifactor process, in which the inflammatory mecanisms play an important role, since the conventional risk factors, chronic infections and the production of oxygen free radicals raise the levels of cytokines. These pass into the blood, act on other cells and the final result is damage to the vessel (8).

The genetic factors are very important in periodontal disease and must be taken into account not only at the time of diagnosis but also on treatment.While the genes of interleukine -1 (IL1) have been related to coronary diseases and osteoporosis, whereas a specific association of polymorphisms IL-1A and IL-1B are related to a serious periodontal disease in the adult (9).

When the relation that could exist between two such different groups is analyzed, it is logical to discard all that which is related to its clinical,diagnosis, treatment and prognosis , as it is evident how little they have in common. If the relation is of cause and effect, the common mecanism that could unite these two diseases will have to be found in the etiopathogenic ambit.

Analyzing the actual bases of the etiology of periodontal diseases, it is undoubtedly the really important role that gramnegative bacteria play at the start and in the progression of these (8). We also know that these microorganisms or the products derived from them can accede to the vascular system of the subjacent/underlying connective tissue, and from there pass to the general circulation, so providing high possibilities of interchange of bacterial toxic products between the periodontal pocket and the circulatory system. This situation does not go unnoticed for the organism, being able to generate a greater immune response than expected.A sufficiently clear example is (to know) that the leucotoxin of Actinobacillus actinomycetemcomitans provokes an antibody response with serous levels similar to those which can be detected in some disseminated systemic diseases such as tertiary syphilis (10).

On the other hand, high white cell counts and increased levels of fibrinogen have been found in certain individuals with periodontal disease (11). One of the organisms that has aroused a major interest is Streptococcus sanguis, predominant in the initial bacterial plaque. It colonizes the dental surface and exercises a protecting effect in toothed individuals.

Nonetheless, this bacteria can be harmful in certain circumstances. Its influence in the etiology of bacterial endocarditis has been known for years and recently it has been associated with the increase of platelet aggregation.A protein associated to platelet aggregation has been identified in this bacteria, which can act directly by interacting with the plaques or indirectly by provoking an immune response.

On the other hand, the loss of epithelial integrity of periodontal tissues allows the bacteria to pass to the sanguineous torrent, so developing bacteremia that would be proportional in intensity and duration to the severity of the periodontal disease (12). In this way a chronic state of interchange of bacteria and their product is created, which is not appreciable neither by the patient nor by the doctor or dentist, favoring the possibility of generating organic damage at a distance in certain circumstances. Thus, if we bear in mind that the myocardium ischemy is derived from the obstruction of its arteries by the atherosclerosis process, it is possible that it is at this level where the products derived from periodontal pathology can act.

Nowadays it is thought that the most probable common factor between both diseases is the interaction between the products of the bacterial plaque and the host’s inflammatory and immunological responses (12). As has already been said previously, as a consequence of bacterial aggression in periodontal disease, a series of mediators of the inflammation are liberated among which interleucine 1 (IL-1), tumoral necrosis factor (TNF) and thromboxane A2 stand out. These cytokines, apart from the harmful effect that they produce in periodontal tissues, can stimulate adhesion and platelet aggregation, promote the accumulation of lipid-laden foam cells and the deposition of cholesterol in the vascular intimal. Furthermore, these cytokines associated to the plaque derived growth factor action (PDGF) stimulate the proliferation of smooth vascular musculature, favoring the narrowing of vessel lumen and promoting, at the same time, the formation of the atheroma plaque (12).

At pathogenesis level, the monocytes are probably the cells with a fundamental role. There are recent works that implicate the monocyte response opposed to the action of bacteria as the factor that can regulate the expression of periodontal disease. The monocytes reply to the presence of bacterial lipopolysaccharides with the secretion of mediators of PGE2, IL-1 and TNF inflammation.These products are the ones that act harmfully on periodontal tissues since they provoke vasodilation,increase permeability, augment the inflammatory infiltrate in the area, degradation of the connective tissue and bone destruction. There is an important increase in the levels of these mediators depending on the severity of the disease and their periods of activity.

Nowadays it is thought, with regard to atherosclerosis, that monocyte adhesion to epithelial receptors can be one of the initial processes in the development of the atheroma plaque (12,13).This can be produced as a consequence of stimulation of bacterial lipopolysaccharides on the endothelium, or by the direct action of certain monocyte cytokines such as TNF or IL-1. The increase of the expression of this last substance favors coagulation and thrombosis at the same time as it delays the fibrinolisis process. In this way the monocytes are incorporated in the atheroma plaque. Other monocyte derived mediators such as the transformer growth factor (TGF) and the plaque derived growth factor (PDGF) increase the proliferation of smooth muscular fibres in the intimal, so contributing to the narrowing of the vascular lumen.

Of particular interest are the free arakidonic acid metabolytes (ARA) produced by the monocytes ( thrombxane-TXA2, prostaglandines-PGE2 and leucotrienes-LTB4), platelets, erithrocytes (LTC4), neutrophils (LTB4), endothelial cells (PGI2) and smooth muscle cells (PGE2). All these molecules have important effects on the function of smooth muscular fiber, cellular inflammatory phenomenum, cholesterol metabolism, platelet aggegation and cytokine liberation (14).

The response to aggression of periodontopathogenic bacteria is very variable from one person to another (15). These differencies must reside in the host’s defense system in such a way that some people respond to the presence of certain bacterias to their lipopolysaccharides with an exaggerated inflammatory reaction, characterized by the secretion of very high levels of the mediators previously described by means of their monocytes. These people secrete these substances in higher concentrations than normal persons, the mediators having a fundamental role in the pathogenesis of periodontal destruction (16,17). Moreover, the monocytes play an important role in the development of the ateroma plaque, and can justify a biological base which unites periodontal diseases and coronary pathology, so the bacterial lipopolysaccharides action is able to act as a common triggering mecanism (16-18).

Subsequent studies (19,20) expound a coherent and rational biological model (corroborating the previously disclosed) that allows the association between periodontitis and cardiac disease to be biologically possible. Said model is based on those common aspects in the pathogenesis of both diseases, concretely the endotoxina-monocyte Mq+ path. This coincides in the liberation of proinflammatory cyotkines originated by the monocytes that enter in contact with the bacterial endotoxins proceeding from the periodontal bags, which together with the activation of these latter cells are going to favor the development of ateroma plaques.Within the role of the host’s inflammatory response those individuals with a monocyte phenotype Mq+ stand out,who are the most susceptible ones to suffering cardiovascular accidents as they present hyperreactive monocytes which free cytokines with exaggeration in comparison to normal individuals (19-21).

Anyway, inspite of all the previously related data, there does not exist uniformity of criterion about the impact that periodontal pathology could have on cardiovascular diseases. As opposed to cohorts of studies, relatively recent, carried out on a large number of patients that associate periodontal disease and death due to cardiovascular diseases (22), or periodontal disease and the high risk of suffering cerebral vascular events (23), there are other cohorts of studies equally important and numerous that affirm just the opposite (24-26). Despite the relation found in patients with active periodontitis, in which an increase in the intimal of vessels and a higher index of atheromatosis than in patients who do not suffer it has been described (27), and the appearance of periodontopathogenesis in the cultures of atheromas obtained from endarterectomy by carotid pathology (28), the opinion of the authors of this paper is, perhaps it is a little premature to establish this relation as something beyond any doubt, although a supposedly "PAS syndrome" ("periodontitis-atherosclerosis syndrome" ) has already been postulated (22). In this sense, it would really be important to clarify this concept from a therapeutical point of view, inasmuch as to really establish the unmistakable relation, the periodontal treatment could be precociously instituted, possibly complemented with antibiotics (betalactamics,tetraciclines) and antiseptics which would reduce the risk of cardiovascular disease in these patients (29).

Despite all these suggestive theories, we believe that we should wait for the development of a greater number of studies to clarify in which way the numerous and very different discrepancies existing nowadays must be considered.

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