Abstract The oral cavity is a major site of chronic infection and inflammation, particularly periodontal or chronic gum diseases

Humagain M

Nayak Dg

Uppoor As

CiteSeerX

 379
Review Article  
Periodontal infections and cardiovascular disease: Is it a mere 
association? 
Humagain M1, Nayak DG2, Uppoor AS3 
1Post graduate student, 2Professor and HoD, 3Professor, Dept. of Periodontics, MCODS, Mangalore 
 
 
Abstract 
The oral cavity is a major site of chronic infection and inflammation, particularly periodontal or chronic gum 
diseases. In recent years there has been increasing interest in the “periodontal systemic connection” between 
periodontal health parameters and risks of cardiovascular disease. Given that poor oral health and cardiovascular 
disease are major worldwide health problems, their association are potentially important. The article summarizes the 
evidences from epidemiologic studies and studies that focused on potential contributing mechanisms to provide an 
insight of this association    
 
 
 
ardiovascular disease including atherosclerosis 
and myocardial infarction is a major cause of 
premature death and occurs because of complex set 
of genetic and environmental factors. It is interesting 
to note that classical risk factors for CVD 
(hypertension, hypercholesterolemia, cigarette 
smoking) can account for one half to one thirds of the 
variation in the incidence of CVD cases. Thus, it is 
likely that others, as yet unrecognized factors may 
contribute to the pathogenesis of atherosclerosis.  
Many other putative risk factors for atherosclerosis 
have been proposed including traits related to 
obesity, inflammation and infection. Periodontal or 
chronic gum disease, a candidate risk factor shares 
many of these related traits. It is likely that exposure 
to dental microorganisms over a lifetime occurs for 
more frequently than to any other atherosclerosis-
associated microbes. Work to elucidate the 
relationship between oral infections and systemic 
disease is now underway on every continent around 
the globe. 
 
                                      
  
 
 
 
 
 
 
 
 
 
 
 
 
 
The 2005 Nobel Prize in Physiology and Medicine 
was awarded to Baray Marshall and Roben Warren 
who made the remarkable and unexpected discovery 
of the bacterium Helicobacter Pylori and its role in 
gastritis and peptic ulcer disease. Many diseases in 
humans such as Crohn’s disease, ulcerative colitis, 
rheumatoid arthritis and atherosclerosis are due to 
chronic inflammation. The discovery that one of the 
most common diseases of mankind, peptic ulcer 
disease has a microbial cause has stimulated the 
search for microbes as possible causes of other 
chronic inflammatory conditions1. 
 
During the last two decades, there has been an 
increasing interest in the impact of oral health on 
atherosclerosis and subsequent cardiovascular disease 
(CVD). The advent of the inflammation paradigm in 
coronary pathogenesis stimulated research in chronic 
infections caused by a variety of micro-organisms—
such as Chlamydia pneumoniae, Helicobacter pylori, 
and cytomegalovirus—as well as dental pathogens 
 
 
 
 
 
 
 
 
 
 
 
 
Correspondence 
Dr  Manoj Humagain 
Post graduate student 
Depatment of Periodontics 
Manipal College of Dental Sciences 
Light House Hill Road, Mangalore, Karnataka, India. 
Email: mhumagain@yahoo.com 
C 
Kathmandu University Medical Journal (2006), Vol. 4, No. 3, Issue 15, 379-382 
 380
Pathophysiology of inflammation in atherosclerosis 
Inflammatory processes have become an integral part 
of the pathophysiology of atherosclerosis and are 
presumed to be involved from the initiation to the 
progression and final stages of infarction. Normal 
endothelium does not allow for the attachment of 
leukocytes. When initial damage of the endothelium 
occurs, either by infection or by an atherogenic diet, 
the endothelial cells express adhesion molecules that 
allow leukocytes to bind to them. These adhesion 
molecules are called ‘vascular cell adhesion 
molecules’ (VCAM) and ‘intercellular adhesion 
molecules’ (ICAM). Selectins and integrins also 
support leukocyte attachment (Libby et al.)2. 
 
 Once this attachment is established, the atheroma 
accumulates more lipids and promotes the production 
of various chemokines and growth factors that 
stimulate the recruitment of monocytes and 
macrophages. These chemokines also promote the 
migration of smooth-muscle cells. These muscle cells 
respond to the inflammatory stimuli by secreting 
specific enzymes (metalloproteinases) that are able to 
degrade elastin and collagen. Further, these 
metalloproteinases may disintegrate the fibrous 
capsule holding the cholesterol plaque together, and 
cause plaque rupture. Plaque rupture greatly increases 
the risk of myocardial infarction and stroke.  
 
This relationship between chronic inflammation and 
atherogenesis has been recently expanded to include 
other pro-inflammatory processes related to a 
hyperactive immune response (Beck et al.)3 or 
autoimmune reaction to microbial or other metabolic 
stimuli. For example, systemic lupus erythematosus 
patients have been found to be at a higher risk for 
developing cardiovascular disease (Nuttall et al).4 
These generalized hyper-inflammatory states may be 
characterized by elevated CRP concentrations (Libby 
and Ridker,1999; Mendall et al., 2000)5,6 
 
Wu and colleagues7 reported that increased serum 
levels of CRP and fibrinogen, both well-established 
biological markers for CHD, were associated with 
periodontitis. Noack et al.8 observed statistically 
significant increases in CRP levels in 109 subjects 
with moderate to severe periodontitis when compared 
with 65 periodontally healthy controls. After 
adjustment for factors known to be associated with 
elevated CRP, including age, smoking, BMI, 
triglycerides, and cholesterol, subjects with high 
levels of periodontal disease had significantly higher 
mean CRP levels than the controls. The presence of 
periodontal pathogens—including Porphyromonas 
gingivalis, Prevotella intermedia, and Tanerella 
forsythensis—from subgingival plaque samples was 
positively associated with elevated CRP levels. 
 
Joshipura et al9 have recently published cross-
sectional data from the prospective male health 
professionals follow-up study, where self-reported 
periodontal disease was analyzed in a sample of 468 
men with respect to a variety of biomarkers of CVD. 
Their results showed, in part, that periodontal disease 
was associated with higher levels of CRP and LDL, 
thereby supporting the hypothesis that periodontal 
disease might also be causally linked with CVD.  
 
Taylor-Robinson and colleagues10 isolated several 
infectious agents by DNA identification methods 
from all major arteries affected by atherosclerosis. 
Among these were periodontal pathogens A. 
actinomycetemcomitans and P. intermedia, in 
addition to C. pneumoniae. Nearly 40% of specimens 
were positive for C. pneumoniae DNA, and 35.4% 
were positive for a mixture of Chlamydia and oro-
dental pathogen DNA. These findings suggest a 
possible invasion of the major arteries by oro-dental 
pathogens together with Chlamydia. Interestingly, 
Mäntylä et al.11 have recently shown that traces of 
Chlamydia can also be detected in periodontal pocket 
samples. The examination of atherosclerotic plaque 
which had been obtained from diseased part of 
arteries during bypass operation in 50 patients made 
identification of perio-pathogenic bacteria possible 
besides C. pneumonie and H. pylori (Harzasthy et 
al)12. 
 
Further evidence of association between 
Periodontal infection and CVD: 
Several epidemiological studies investigating the 
relation between infections – including dental 
infections – and various clinical manifestations of 
atherosclerotic vessel disease have been published in 
the last decade suggesting periodontal disease as a 
risk factor for CHD. The topic has proved difficult to 
study and this is especially true for dental infections, 
as they share several common etiologic factors with 
CHD. These include smoking, low socio – economic 
class and unfavourable health care practice of the 
individual.  
 
A study conducted by Buhlin et al13, suggests that 
periodontitis, once considered purely a local disease 
can cause systemic inflammation lipid changes 
known to increase risk of CHD. The study of 
Pearsson et al 200314 concluded that patients who 
demonstrate evidence of bone loss around several 
teeth can predictably be identified as being risk for 
future AMI.  
 
 381
A case control study by Mattila et al15 observed that 
the patients with periodontal infections had 
significant elevation of plasma fibrinogen and white 
blood cell count, leading to the hypothesis that 
periodontal disease might increase risk of CHD in 
part by inducing a systemic proinflammatory,  
prothrombotic  state . 
 
Pussinen et al16, report that antibodies to select 
periodontal pathogens are associated with coronary 
heart disease. Importantly, only antibodies to 
Porphyromonas gingivalis were associated with 
CHD. Similarly, DeStefano et al17, found 25% 
increased risk of CHD in individuals with mild to 
moderate periodontitis compared to individuals with 
gingivitis.  
 
A study conducted by D’Aiuto F et al18, showed that 
control of peridontitis achieved with non surgical 
periodontal therapy, significantly decreases serum 
mediators and markers of acute phase response. The 
significance of serum response was associated with 
the half of the population that responded better to non 
– surgical periodontal therapy. The result of this pilot 
study indicates that severe generalized periodontitis 
cause systemic inflammation. This is consistent with 
the causative role of periodontitis in atherosclerosis.  
A meta- analysis of prospective follow up studies by 
Jukkha et al 200419, has shown that periodontal 
disease may increase the risk of cardiovascular 
disease by approximately 2%.  Similarly in a recent 
study conducted by Sabine O et al20, periodontitis 
was revealed to be a significant risk factor for CAD 
after adjusting for other confounding factors, with the 
level of association increasing with the individual 
extent of periodontal lesions.  
 
Choi and colleagues21 isolated P. gingivalis heat-
shock protein-specific T-cells in atherosclerotic 
plaque from subjects with severe atherosclerosis. 
Bacterial heat-shock proteins are believed to be 
involved in regulating autoimmune mechanisms, and 
they also appear to be associated with the 
pathogenesis of periodontitis22.  
 
These important studies shed new light on the role of 
the periodontal disease in causation of atherosclerotic 
events and CHD. However, they are unable to prove 
the causal relation between periodontitis and CHD 
but, definitely they provide valuable new information 
about this controversial topic. 
 
Conclusion  
The accumulation of epidemiologic, in vitro and 
animal evidence presented to date suggests a 
potential role of periodontal infection as a risk factor 
for CVD. These findings from the cross – sectional 
and longitudinal epidemiologic studies are supported 
by in vitro and animal studies describing plausible 
mechanisms linking periodontal infection to 
development of atherosclerotic diseases, to the 
triggering of clinical coronary events or to both. 
 
The cumulative evidence presented in this report 
supports, but does not prove a mere association 
between periodontal infection and atherosclerotic 
cardiovascular disease or its sequelae.  We are aware 
of the fact that research into the relationship between 
the periodontal infection and CVD is still in its early 
stage compared with research on more established 
risk factors for CVD.  
 
More prospective and interventional studies in 
various populations are needed to confirm the 
association and to elucidate its nature. However, the 
current evidence supporting an association raises an 
important question: “If periodontal infection is 
suppressed by anti-infective intervention, will this 
result in a decreased risk of heart disease?” Answers 
to this question would be clinically meaningful and 
may more directly implicate periodontal disease as 
risk factor cardiovascular disease, and possibly as 
one of its causes. 
 
Because periodontal infection is common in 
population, it can be account for a significant portion 
of the proposed infection associated risk factor of 
CVD. If periodontal disease is found to be a 
causative risk factor for CHD, the patients who 
receive treatment for periodontal disease have 
significantly reduced the risk for CHD. If causative 
relationship is not proven, the patient will receive 
benefit of treatment of periodontal infection. 
Periodontal infection obviously merits prevention and 
treatment as a health problem in itself.  
 
Therefore the new knowledge being gained in the 
discipline of periodontal medicine will serve as an 
impetus to further coalesce medicine and dentistry. 
Dentists will need to assume a large responsibility for 
the overall health of the patients and periodontal care 
may become a medical necessity.  
 
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Periodontal infections and cardiovascular disease: Is it a mere association?

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Periodontal infections and cardiovascular disease: Is it a mere association?

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