The correlation between vascular diseases and periodontal diseases – a literature review
Agnieszka Kręgielczak, Marzena Wyganowska-Świątkowska, Janina Stopa
Department of Conservative Dentistry and Periodontology, Poznań University of Medical
Sciences, Poland
ul. Bukowska 70, Poznań, Poland
Head of the Clinic: Prof. Dr Hab. Janina Stopa, MD, PhD
Corresponding author:
Dr n. med. Agnieszka Kręgielczak, MD, PhD
ul. Szczawiowa 9, 61-680 Poznań
Phone: 501 587 670
Fax: 61 853 70 27
akregiel@ump.edu.pl
Abstract
Introduction
The issues concerning the correlation between periodontal diseases and vascular diseases are
the subject of continuous discussion in literature. Chronic periodontitis has been recognised as
one of the risk factors of cardiovascular diseases such as: atherosclerosis, endocarditis,
myocardial infarction or even aortic aneurysms. A particular role is ascribed to the
inflammatory factors participating in the aetiopathogenesis of both vascular and periodontal
diseases.
Aim of study
An evaluation of periodontal diseases as a risk factor of vascular diseases with special
attention given to the role of periopathogens in the development of atherosclerosis and
aneurysms.
Summary
The mechanisms of correlation between the occurrence of periodontal diseases and
atherosclerosis and aortic aneurysms were described on the basis of available literature. The
analysis of clinical, epidemiological and experimental studies confirmed the correlation
between the diseases in question.
Key words: periodontitis, atherosclerosis, aneurysms, periopathogens
Introduction
Diseases of the cardiovascular system are the most frequent cause of deaths in countries with
well-developed health care. The diseases mainly result from the atherosclerotic reconstruction
of the arterial system. There is a continuous search for other risk factors responsible for the
occurrence of vascular diseases than those that have been well investigated so far. On the
basis of the published results of clinical and epidemiological examinations it has been
observed that chronic inflammatory processes occurring in the oral cavity may be a risk factor
responsible for the occurrence of vascular diseases.1,2 Statistically significant correlations
between the poor state of health of the oral cavity and the occurrence of certain systemic
diseases have been proved, especially endocarditis, coronary artery atherosclerosis, carotid
artery atherosclerosis, abdominal aortic atherosclerosis, myocardial infarction and aortic
aneurysms.1,2,3
Along with caries, chronic periodontitis is considered to be the most frequent
pathological process within the oral cavity. Periodontal pockets, which develop in the course
of those diseases, are a perfect niche for microorganisms, especially for anaerobic bacilli,
which are strongly pathogenic. It has been proved that bacteria, bacterial products and
inflammatory and immunological mediators which are present in the pathologically changed
periodontis may act outside the oral cavity and the pathogens from the periodontis may be an
inflammatory factor participating in the aetiopathogenesis of vascular diseases related with
atherosclerotic processes.4
The problem has been investigated by many authors who published both numerous review
papers and research projects.
Aim
The aim of this study is an evaluation of the correlation between periodontal diseases and
vascular diseases with special attention given to the role of periopathogens in the
aetiopathogenesis of arterial atherosclerosis and aneurysms.
On the basis of numerous studies subgingival plaque bacteria in patients with chronic
periodontitis were found to be the possible cause of bacteraemia. The bacteria may enter the
bloodstream through the epithelium of gingival pockets, whose area is equal to the area of the
human palm.5 Scannapienco6 thinks that bacteraemia in the organism may be caused not only
by chronic periodontitis but also by all types of dental treatment or even by everyday hygienic
procedures. The report by the American Academy of Periodontology of 1999, published in
Journal of Periodontology in 2000, states that periodontal diseases may be related with
diabetes, premature births, cardiovascular diseases, joint diseases and pulmonary diseases.1, 3, 7
It was also found that in comparison with healthy people patients with certain systemic
diseases are more susceptible to the occurrence of periodontal diseases. Those diseases
include: diabetes, AIDS, osteoporosis, Crohn's disease, Papillon-Lefevre syndrome, Down
syndrome or even peptic ulcer disease.
There are several mechanisms accounting for the possible influence of periodontitis on
the general state of health. According to Scannapienco6 they are: (1) spreading of the
infection from the periodontis into deeper located adjacent tissues; (2) the passage of
inflammatory mediators into the bloodstream and their influence on the functions of other
organs; (3) the penetration of bacteria from the oral cavity into the bloodstream and causing
inflammations in distant locations; (4) spreading of bacteria and their products through the
mucosa into distant organs.
The first scientific reports discussing the issue of correlation between periodontitis and
cardiovascular diseases appeared in the 1980s and were based on numerous epidemiological
studies.8, 9, 10 Syrjanen et al11 in their publication of 1989 proved the dependence between the
intensification of the periodontal disease and the frequency of incidence of stroke. The studies
by Matilla et al10 of 1989 and 1999 confirmed the concomitance of periodontal diseases and
infarctions in men. De Stefano7 in an analysis of 9760 people aged 25-74 years proved an
increased risk of occurrence of coronary disease by 25% in people with diagnosed periodontal
disease in comparison with the group with healthy periodontium. He also proved that the risk
of occurrence of coronary disease in men aged over 50 years with diagnosed periodontal
disease increases by 70% in comparison with healthy men.7 Elter9 on the basis of a research
on 6436 people found more frequent occurrences of infarcts and coronary disease in patients
with chronic periodontitis in comparison with a group of people with healthy periodontium.
He observed particularly frequent occurrences of vascular diseases in toothless people,
proving the correlations between the number of lost teeth and the occurrence of vascular
diseases.9 The correlation between the occurrence of advanced periodontal diseases and
carotid artery atherosclerosis was also confirmed by Beck et al.1, 2 On the other hand, the
Finnish scientists noticed that the number of lost teeth is a statistically significant risk factor
for the occurrence of coronary artery disease in smokers. 12 Besides, the authors proved the
correlation between the occurrence of moderate and severe periodontitis and the thickening of
the middle layer of the carotid artery wall. As results from the presented overview of the
literature, most authors investigating the problem confirm the correlation between the
occurrence of vascular diseases and periodontal diseases. However, some authors have the
opposite point of view and find no correlation between the number of teeth in the oral cavity,
the state of the periodontis and coronary artery disease.13 The WHO reports of 1994 and 1999
mention a rather coincidental relation between periodontitis and atherosclerosis. However, it
is necessary to remember that the studies which made the material included in the reports
were made in Scandinavia, where most patients’ periodontis is in good state.13
Atherosclerosis is a process which consists in local widening of an arterial vessel wall
by thickening of the internal lining layer and the middle layer, consisting of smooth muscles,
collagen and elastic fibres.14 According to Ross14 the first stage of formation of atherosclerotic
plaque is adhesion of monocytes to the arterial vessel endothelium. This process is regulated
by adhesins located on the surface of endothelial cells of vessels (ICAM-1, ELAM-1, VCAM1). The function of adhesins is influenced by numerous factors, including:
lipopolysaccharides, prostaglandins and inflammatory cytokines. Lipopolysaccharides are
endotoxins which may come from bacterial cells in the periodontitis, whereas prostaglandins
and inflammatory cytokines develop as a result of the immune response which may also be
initiated by periopathogens. In response to bacterial infection monocytes become activated,
penetrate into the middle layer of the vessel and absorb low density lipoproteins (LDL) and
thus transform them into foam cells, of which atherosclerotic plaque is composed. In the
middle layer of the vessel monocytes may also transform into macrophages and produce
inflammatory cytokines: interleukin IL-1β, TNF-α, prostaglandin 2. This will initiate the
development of damage to the vessel wall. Additionally, the fibroblast growth factor and
plaque growth factor stimulate the proliferation of smooth muscles and collagen within the
middle layer of the vessel causing it to thicken. Thus, the vessel lumen is narrowed and the
arterial bloodstream is reduced. The presence of plaque and damage to the vessel endothelium
intensifies the aggregation of thrombocytes and may contribute to the development of
thrombotic diseases or infarctions in distant organs.1, 7, 15 Figure 1 shows the pathomechanism
of development of atherosclerotic plaque according to Lindhe.
Mø+
A
Mø
Mø
B
C
Foam cells
LDL
Atherosclerotic plaque
D
Fig. 1. The pathogenesis of atherosclerosis (by Lindhe, 2003)16
A. Monocytes adhere to the vessel wall. B. Monocytes penetrate into the vessel wall and
stimulate the production of cytokines and growth factor. C. The absorption of low density
lipoproteins (LDL) causes distension of monocytes and formation of foam cells. D. The wall
of the vessel becomes thickened and narrowed due to the proliferation of smooth muscles and
development of atherosclerotic plaque.
Scannapieco and Genco take several factors into consideration in their explanations of
the correlation between atherosclerosis and periodontal diseases. One of them is the direct
influence of bacterial pathogens on the development of atherosclerotic plaque; another one is
the indirect influence of the inflammatory process on the organism. The genetic predisposition
to periodontal diseases and atherosclerosis and the presence of joint risk factors for both units
also justify the correlation under discussion.6 The direct influence of infective factors on the
vessel wall consists in endotoxins causing damage to the vessel endothelium and initiating a
local inflammation. Numerous scientists confirmed the contribution of periopathogens to the
formation of atherosclerotic plaque. Porphyromonas gingivalis was found in the
atherosclerotic plaque of carotid arteries, aortic and cardiac endothelial cells.15, 17
Furthermore, it was proved that such strains as Porphyromonas gingivalis and Strepptoccocus
sanguis may induce thrombocyte aggregation, thus simultaneously favouring thrombotic
incidents.
The indirect influence of chronic inflammatory processes in the periodontis is also an
important mechanism which may account for the dependence under discussion. In the course
of inflammatory reaction there is leukocytosis, increased level of C-reactive protein (CRP),
fibrinogen and increased concentration of inflammatory mediators: IL-1, TNF-α, sICAM-1,
sVCAM-1.8 Moreover, it is known that some bacteria, e.g. Porphyromonas gingivalis have
HSP60 proteins, which are identical with human heat shock proteins. This may lead to the
initiation of autoimmune reaction. Anti-HSP 65/60 antibodies are produced, which may crossreact with the endothelial antigen and trigger a cascade of atherosclerotic processes.8 Also,
the lipopolysaccharides present in the walls of cells of Gram-negative bacteria, e.g.
Actinomyces actinomycetemcomitans stimulate the secretion of cytokines, which may damage
the vessel endothelium and accelerate cholesterol penetration.
In the discussion on genetic predispositions playing an important role in the correlation
between periodontal diseases and atherosclerosis Beck found that the presence of the
phenotype of Mø (hyperreactive monocytes) is a good reason to include patients into risk
groups of atherosclerosis, ischaemic heart disease and periodontitis.1 Offenbacher researched
the risk factors of vascular and periodontal diseases. He described the interdependence
between atherosclerosis and periodontitis as periodontitis-atherosclerosis syndrome (PAS).18
The author thinks that the highest incidence of the syndrome is in men-smokers, with low
social status and suffering from diabetes. In those patients periodontitis has a generalised
character with numerous deep periodontal pockets, considerable loss of connective tissue
attachment and the presence of a large amount of plaque. He defined the patients qualified for
high-risk groups of occurrence of PAS as ‘3:60’, which means that in more than 60% of
places in the periodontium the loss of connective tissue attachment makes at least 3 mm.
Offenbacher18 also noticed a correlation between the amount of plaque and the diagnosing of
periodontal disease in those patients. The more plaque is present on dental surfaces, the higher
the risk of occurrence of PAS.18 On the other hand, Beck compared different risk factors of
vascular diseases and noticed that periodontitis is a risk factor equivalent to fat consumption,
body weight and blood pressure.1
The issue of particular interest is the aforementioned fact that the capability of
colonisation of atherosclerotic plaque is attributed to bacteria present in periodontal pockets.
In the 1990s molecular biology methods were applied to identify some of the following
species of periopathogens in the atherosclerotic plaque structure: Porphyromonas gingivalis,
Actinomyces actinomycetemcomitans, Prevotella intermedia, Tanarella forsythiensis,
Treponema denticola, Campylobacter rectus, Fusobacterium nucleatum and Eiknella
corrodens.15 Numerous publications also confirm the presence of other microorganisms in
specimens from the vessels, which do not come from periodontal pockets. They include:
Chlamydia pneumoniae, Helicobacter pylori, Mycoplasma pneumoniae or Herpes simplex.18
Periodontal bacteria were found in pathologically changed specimens of vessels in patients
with coronary heart disease, carotid artery atherosclerosis, iliac artery atherosclerosis and
abdominal aortic atherosclerosis.15 Chiu15 proved the presence of DNA of Porphyromonas
gingivalis in 42% and Streptoccocus sanguis in 12% of specimens of the walls of
pathologically changed carotid arteries. Mastragelopulos confirmed the presence of bacterial
DNA in 59% of the atherosclerotic plaque collected from carotid arteries, whereas Okuda
proved the presence of Treponema denticola only in 6 out of 26 specimens collected from the
abdominal aorta.19 Ishihara20 noted the presence of Porphyromonas gingivalis, Actinomyces
actinomycetemcomitans, Tanarella forsythiensis, Treponema denticola and Campylobacter
rectus in the coronary vessels. The bacteria made 21%, 23.3%, 5.9%, 23.5% and 15.0%
respectively. The analysis of literature on the subject indicates that not all studies confirm the
presence of bacteria related with periodontal diseases in atherosclerotic plaque. In 2005
Fiehn21 in his research based on analysis of specimens collected from carotid and iliac arteries
defined the presence of periopathogens as sporadic.
In the last decade there have also been studies confirming the correlation between the
occurrence of periodontitis and abdominal aortic aneurysms. Aortic aneurysms are defined as
a local dilatation of the arterial vessel lumen by 50% as compared with the unchanged
segment of the artery located above. They can chiefly be found in elderly patients and are
usually related with the abdominal aorta.22 Historical reports on aneurysms from the 19th
century associate their occurrence with syphilis. Nowadays it is known that the most
significant factor in the process of aneurysm development is the functional and structural loss
of elastin from the arterial vessel wall. In consequence of the action of mechanical force the
vessel lumen becomes stretched and an aneurysm develops. However, the mechanism that
leads to the decomposition of elastin is not known. It has been proved that proteolytic
enzymes, such as metalloproteases – elastases, collagenases and gelatinases participate in the
process. Furthermore, also other diseases related with connective tissue disorders have been
observed in patients with aneurysms. They are: inguinal hernias, emphysema, Marfan
syndrome, Ehlers-Danlos syndrome.22 However, there is no unequivocal evidence that
atherosclerosis is the direct cause of anuerysms.3 Histopathological examinations of aortic
fragments collected from patients with atherosclerosis and from patients with aneurysms do
not exhibit many similarities. However, on the basis of latest studies it is known that chronic
inflammatory processes participate in the pathogenesis of aneurysms.3 However, the role of
microorganisms has not been fully explained yet. The percentage of patients where bacterial
cultures confirmed the presence of microorganisms in aneurysm walls fluctuates between 8%
and 37%, depending on the research.22 Marques Da Silva 1 proved the presence of such
anaerobes as: Propionibacterium acnes, Propionibacterium granulosum, Actinomyces
viscosus, Actinomyces naeslundii and Eggertella lenta in 20 out of 28 specimens of aneurysm
walls under investigation. Martin et al in their studies based on molecular diagnostics
described the case of presence of Actinomyces actinomyctemcomitans from the oral cavity in
the aneurysm wall of a patient with chronic periodontitis. Okuda3 found the presence of
Treponema denticola only in specimens of abdominal aortic aneurysms. On the basis of a
study on 32 patients with abdominal aortic aneurysms Kurihara described the presence of the
DNA of Porphyromonas gingivalis in 85% of the patients and Treponema denticola in 63%
of the collected specimens. On the other hand, the sporadic occurrence of the DNA of
Porphyromonas gingivalis - in 2 cases was proved in PCR examinations of specimens of the
walls of aortic aneurysms collected from 22 patients (11 patients with concomitant
periodontitis and 11 patients with toothlessness). The presence of four other pathogens under
investigation, i.e. Prevotella intermedia, Treponema denticola, Actinobacillus
actinomycetemcomitans, Tanarella forsythiensis was not observed in the specimens.23
Summary
To sum up the discussion, it is necessary to state that periodontal diseases are one of
the most important risk factors related with the inflammatory process in the course of vascular
diseases. The analysis of numerous epidemiological, clinical and experimental studies
confirms the correlation. However, there still is not full agreement concerning the issue if
periodontal bacteria are a factor contributing to the destabilisation of atherosclerotic plaque. It
is known that bacteria are a primary factor in the aetiology of periodontal diseases and
damaged tissues of the organism are the consequence of immune reactions. Those bacteria
stimulate the host cells to secrete enzymes decomposing tissues and to release cytokines
activating enzymatic reaction routes. Periodontal diseases cause increased inflammatory
response of the organism, which may affect the course of cardiovascular diseases.19 One of
the first disorders which may be caused by periopathogens is the dysfunction of vascular
endothelium. Inflammatory factors from the periodontis may also influence the development
of thrombosis.4 Undoubtedly, both joint risk factors and pathophysiological processes
underlie the destabilisation of atherosclerotic plaque and destruction of periodontal tissues.
Appropriate periodontological care and treatment of periodontal diseases has influence of
reduced risk of occurrence of vascular diseases and patients with vascular diseases should be
subject to continuous dental care.
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