The Evidence Linking Periodontal And Cardiovascular Disease Literature Review Samples
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In adults above the age of 45, cardiovascular diseases are common. There are several risks factors associated with cardiovascular disease such as hypertension, low density lipoprotein (LDL), gender (male), smoking, and low socioeconomic status. Few studies have suggested the link between atherosclerotic diseases and infection. Many researchers have suggested the link between several viruses and bacteria and the etiology of cardiovascular diseases. In transient bacteremia, dental procedures and periodontitis are considered as potential factors. In such cases, full mouth debridement resulted in Schwatzman reactions. In patient with periodontitis, gentle mastication can release bacterial endotoxins in the blood stream. During and after endodontic therapy, oral microorganisms can spread from an infected root canal to the blood stream. (Ahmed U, Tanwir F. 2014 and Carin Starkhammar Johansson. 2013).
Periodontal disease features inflammation in the periodontal tissues and chronic infection that eventually leads to the destruction of the bone surrounding the teeth. This finally leads to tooth loss. Many researchers have predicted that inflammation and chronic infection are considered as key risk factors in the development of cardiovascular diseases. (Dhadse, et al. 2010). In periodontal disease, the proatheroenic role of chronic infection and its association with increased rate of periodontitis is not well established. However, pathogens (periodontal) such as Bacteroidsforshythus (Tannerellaforsythensis), Porphyromonasgingivalis and Prevotellaintermedia, have been observed in aortic and coronary endothelium. Some studies have also found these pathogens in atherosclerotic plaques. (Joshipura, K. et al. 2010)
Many clinical studies and data have suggested the possible link between infection factors, inflammation, and the increased risk of atherosclerotic vascular disease. There is significant improvement in the systemic and hemostatic condition of patients with coronary heart disease after the treatment of poor oral health, especially periodontal disease. Juliana Rico Pires, et al. 2014). Thus, the effect of oral health among heart patients has been of great importance in recent times due to a string evidence showing their relation. (Lockhart et al. 2012). The paper briefly highlights the association of periodontal disease and cardiovascular health by a strong evidence of research and clinical trials.
Search strategy and selection criteria
The search strategy involved article review from searchers of PubMed, MEDLINE, and the Cochrane library. Relevant articles were referred using the key words, periodontitis, periodontal, cardiovascular disease, systemic disease, and coronary heart disease. Only articles that were published after 2010 were referred. Abstracts and reports were only included if the data presented were associated with the topic.
In the pathogenesis of many human diseases, inflammation associated to protective tissue and response to injury are highly implicated. These factors and indications play a critical role in complex multifactorial chronic inflammatory diseases including cardiovascular disease (CVD) and periodontitis. (Sumit Malhotra, and Hari Parkash. 2013).
The word periodontium means the structures that are around the teeth (peri-around) and (odontos-teeth). The periodontium consists of four tissues, the periodontal ligament, the investing tissue (commonly known as the gingiva), the alveolar bone, and the cementum. The alveolar bone is considered as the attachment apparatus. Periodontitis is a disease of multifactorial etiology and is considered as infectious and inflammatory. Most of the periodontal cases are initiated by dental plaque related microorganisms. However, the process of inflammation is sustained by the host organism (humans).
The concept of oral sepsis developed by William Hunter, a British physician led to the probable link between systemic disease and oral health. The association dates back to the year 1900 and was of significant importance. In 1912, Frank Billings superseded ‘focal infection’ which was equally important. Two distinct mechanisms of infection were suggested. One included the metastasis of organisms while the other consisted the spread of toxic products or toxins from a distant focus to other tissues. The metastasis consisted of a near and single focus. Although, the theory received appreciation, it was considered as unfit or unreliable due to various reasons from researchers. The concept of focal infection has changed over the past two decades due to the work done by researchers in 1989 who provided evidence on the association of acute myocardial infarction and poor dental health. Researchers have investigated and confirmed the association of periodontitis and atherosclerotic cardiovascular disease with respect to various oral health conditions. Moreover, researchers have highlighted the biologic plausibility of these two factors.
The purpose of the literature review is to understand and highlight the probable association of periodontal disease (poor oral health) and cardiovascular disease. Most of the clinical data published in the last five years have focused on the different aspects of periodontal disease and cardiovascular disease. Moreover, most of the studies have indicated periodontitis as one of the major risk factors. The only reason for periodontitis \being implicated in such cases is due to the continuous presence of bacteremia which often relates to a constant microbial challenge for an extended time. In developing countries, there is significant global variation observed in periodontal disease. In most populations, the generalized form of the disease is commonly observed. Recent survey and reports suggest that the prevalence of periodontitis is around 20 to 50% of the global population.
PATHOBIOLOGY OF PERIODONTITIS
The initial stage of inflammation is starts in the gingiva and is initially confined to it. The inflammatory process is generally reversible but at an early stage. However, with the progress of the inflammation there is gradual destruction of the tissues over time. Periodontitis is considered as a grave health disorder since advanced stages of the disease is associated with irreversible loss of tissues that surround the teeth. (Ricardo Teles and Cun-Yu Wang. 2012).
It is a known fact that periodontitis is initiated by microorganisms associated with poor oral health. The progression and destruction of tissue is often due to the host response known as the microbial attack or the stander damage. A few researchers have proposed the central role of inflammation in the progression and pathogenesis of the disease. Gram negative bacteria are observed on the teeth if bacterial biofilms are not physically disrupted. The biofilms are considered as factors for periodontitis and gingivitis. Inflammation is initiated to such a level that a series of conditions occur such as gingivitis and periodontitis. This is mainly due to the chronic bacterial challenge observed during the progress of the disease. Many mediators of inflammation and various cytokines are released due to the stimulation of localized tissue response from bacteria and their toxins, namely endotoxin. Periodontal pockets are caused due to chronic damage of epithelial cells. This is also due to damage of connective tissues from periodontitis. (Shad, B et al. 2013)
Toxins that enter the systemic circulation can disrupt the homeostasis. In periodontitis, high tissue concentrations of pro-inflammatory cytokines TNF-á (tumour necrosis factoralpha), IL-1â (interleukin-1 beta), and gamma interferon and PGE2 (prostaglandin E2) are observed. The systemic effects are induced and perpetuated due to the periodontium that served as the reservoir for renewing such mediators that are passed into the systemic circulation. Coagulation and thrombosis are favored by IL-1a but it retards fibrinolysis. Platelet aggregation and adhesion are mainly observed by chemical mediators such as IL-1, TNF-á, and thromboxane. This eventually leads to the deposition of cholesterol in the arteries and formation of lipid-laden foam cells. However, a few researchers may debate that an individual may suffer from other infections and it may not necessarily co-relate coronary heart disease and periodontitis. (Tomoko Kurita-Ochiai and Masafumi Yamamoto 2014).Two main justifications can be provided for this phenomenon, one is the enormous load of bacteria in diseased periodontium while the other is the source of infection that maybe released into the systemic circulation. The size of the pocket epithelium in a patient with sub-gingival bacteria and suffering from generalized moderate periodontitis is estimated to be the size of an adult palm. In more advanced cases, especially in periodontal destruction, the affected area is even larger. (Yu YH et al. 2014).These pockets generally contain a reservoir of renewing lipopolysacchride (LPS) and other gram-negative bacteria. These pass through the periodontal tissues and enter the systemic circulation. The surface of the affected area (inflamed portion) is found to be approximately 8 to 20 square centimeter when this area (dento-gingival epithelium) is exposed to bacterial invasion and infiltration of microbial antigenic components. Major vascular response is observed in case where the systemic challenge is dominant with gram-negative bacteria. Some of the major vascular responses include vascular smooth muscle proliferation, inflammatory cell infiltrate into the vessel walls, and vascular fatty degeneration and intravascular coagulation. Endothelia cell adhesion molecule expression is upregulated by LPS. (Rakshit, K., U. et al. 2014).
Unique features of periodontal infection: For various reasons, periodontal infection is considered unique
1. Periodontitis is a poly-microbial infection.
2. It is asymptomatic for most times and is a longstanding chronic infection.
3. Transient bacteria is caused even while performing daily activities such as brushing, chewing, and flossing. (In the process, cytokines and mediators are also pumped out into systemic circulation).
4. Abnormal anatomic structure: The tooth is partially embedded within the periodontal connective tissue while the remainder is exposed to the environment.
5. The teeth provide an uninterrupted microbial colonization and are non-shedding surfaces (unlike the skin) and comes in contact with the surrounding tissues that support the teeth.
6. A protective environment also known as the biofilm is where the microorganisms associated with periodontal disease are present.
7. Host-parasite relationship is enhanced by the presence of teeth. (R. Anjanaa, & R. Suresh. 201- )
Evidence on the association of periodontal and cardiovascular disease
A clinic-biochemical study provided evidence on the association between periodontal and cardiovascular disease. The study included a total of 50 individuals between the 30 to 65 years. The participants were divided in five distinct groups based on the diagnosed cardiovascular disease. The five groups were Congestive cardiac failure, Ischemic heart disease, valvular heart disease, and cardiomyopathies. The dental investigations consisted of Ramjford’s periodontal disease severity index. For lipid profile analysis, clinical attachment level Laboratory investigations were conducted. There was significant difference between valvular heart disease and bacterial endocarditis as per Ramjford’s periodontal disease severity index. Negative correlation between HDL and positive correlation between total cholesterol, triglycerides and VLDL was observed. Lipid profile showed association between ischemic heart Disease and dyslipidemia. The researchers concluded that ischemic heart disease and bacterial endocarditis were liked to severe periodontitis in comparison to valvular heart disease. (Rakshit, UK. et al. 2014).
A review on periodontal and cardiovascular disease suggests a strong correlation between the two and further recommendations on oral health for such conditions. The evolution of focal infection theory was based on the pathophysiology of periodontal disease and was confirmed upon a systemic review by the researchers. Further on, chronic periodontitis was linked to various systemic diseases such as preterm delivery of low-birth-weight fetuses, respiratory infections, cardiovascular diseases, and diabetes mellitus. (Igari, K. et al. 2014).
A study was conducted to provide strong evidence on the association of periodontal treatment and its link in lowering lipid levels in patients with cardiovascular disease. The study was conducted after a 1 year follow-up. A total of 80 patients were selected for the study and each of them were divided into 4 groups. (20 patients in each group). One group consisted of two sub-groups of patients with cardiovascular disease and conventional periodontal treatment or full-mouth scaling and root planning. The second group consisted of two sub groups that consisted of patients without systemic involvement and conventional periodontal treatment or full-mouth scaling and root planing. For the first 12 months, patients in both groups were evaluated by laboratory examinations. In patients with cardiovascular disease, there was a significant improvement in the clinical and lipid variables. The researchers concluded that the treatment of periodontal disease is associated with controlled lipid levels, especially in patients with cardiovascular disease. (Nassar, AC, et al. 2013).
There are numerous studies that have proven the association between cardiovascular and periodontal disease. In animal models, accelerated atheroma deposition is observed due to causative agents of destructive chronic inflammation (Porphyromonas gingivalis and Aggregatibacter actinomycetemcomitans). Disease resistance is often increased if vaccination against the virulent factors of such pathogens is carried out. Moreover, anti-inflammatory therapy increases disease resistance against periodontal disease. A systemic review was conducted to evaluate the role of inflammatory mechanisms and oxidative modification in the activation and formation of plaques (atherosclerotic) due to P. gingivalis or A. actinomycetemcomitans in high-fat-diet-fed mice an ApoE-deficient mouse model. Mucosal vaccination with a periodontal pathogen or the anti-inflammatory activity of catechins is associated with reduced periodontal accelerated atherosclerosis. (Kurita-Ochiai, et al 2014).
It is well known that oral sepsis is associated with the release of inflammatory cytokines that eventually pass into the systemic circulation. They further exhibit the pro-inflammatory effects. A systemic review revealed the relationship between periodontal infection and coronary artery disease. However, various biologic plausibility and epidemiological studies were reviewed before making a strong conclusion between the association of periodontal and cardiovascular disease. (R. Anjanaa, and R. Suresha. 2010).
The European federation of periodontology provided evidence on the strong association between periodontitis and atherosclerotic disease. The risk of atherosclerotic disease increases by the presence or progression of periodontal disease. Moreover, atherosclerotic disease increases in the presence of coronary heart disease, males and young individuals, Microorganisms that cause periodontitis release endotoxins that eventually enter the systemic circulation and cause inflammation. There is sufficient data to prove that atherosclerotic disease is associated with the prevalence of bacteraemia and plaque indices, viable periodontal bacteria living within atheroma, and presence of periodontal pathogens in atherothrombotic lesions. (EFP, 2013).
A clinical study was conducted in an out-patient department on patients at ITSCDSR in India. The main objectives of the researchers was to evaluate the association between periodontal and coronary heart disease. A total of 60 patients were evaluated for the study. Two groups of patients were segregated, one group that consisted of periodontally healthy patients while the other group consisted of periodontally diseased patients. In both groups, the hs-CRP levels and periodontal parameters were compared. High levels of hs-CRP was observed in the periodontally diseased group of patients. Moreover, it was observed that patients with advanced periodontal diseases has high CRP levels and also had a high risk for coronary heart disease. (Malhotra, S and Parkash, H. 2013).
There has been a deep understanding on the pathophysiology of CVD and its increased prevalence over the past few decades. Moreover, researchers suggest that the rate of CVD risk increases if there is improper oral hygiene. The presence of oral bacteria is directly linked to CVD. The mechanism of CVD and periodontal disease remains unclear but many studies have shown a strong relation between CVD and periodontal disease. A systemic review confirmed the interactions of host bacteria and periodontal disease. Moreover, there is a direct association of periodontal and increased CVD risk by taking account a few underlying factors such as biological plausibility. (Leishman, J. S et al. 2010).
In the past 5 years, research suggests that oral hygiene and oral diseases such as periodontal disease is linked to CVD, especially coronary heart disease. In order to understand the relationship, researchers conducted a longitudinal study in order to evaluate the etiology of periodontal disease and its treatment. Two groups were formed, one consisting of health subjects while the other with coronary heart disease. It was observed that the evolution of periodontal disease was higher in patients with coronary heart disease compared to healthy subjects. The researchers concluded that periodontal indices such as bleeding, plaque index, and probing depth were associated with coronary heart disease. (Machuca, G, et al.2012). Thus, there is sufficient evidence that supports the association of periodontal and cardiovascular disease.
For over more than 100 years, there is a strong evidence on the link between oral health and cardiovascular disease. However, in the past decade, there has been concern regarding the relation between atherosclerotic vascular disease and periodontal disease. Moreover, this relationship has increased to a significant extent that there is a strong and active field that is involved in the investigation of the causality and association of both the diseases. The diseases have common risk factors such as age, smoking, and diabetes mellitus. There is an ever-increasing claims from industrial stakeholders and professionals about the treatment strategies of periodontal disease that leads to atherosclerotic disease prevention or management. The American Heart Association conducted a review to evaluate the current data that highlight the association of periodontal disease treatment and its reduction in atherosclerotic vascular disease prevention or reduction. The AHA member panel also provided a mechanistic approach to periodontal and atherosclerotic vascular disease. The AHA scientific statement also provided the surrogate markers that are associated with periodontal disease. The member panel also suggested the relation between periodontal therapy and atherosclerotic vascular disease event rates. The AHA statement reviewed many methodological studies that provided evidence on bad oral health and increased risk of CVD. Observation studies were also reviewed by the AHA member panel and emphasized on periodontal and atherosclerotic vascular disease. Lastly, periodontal therapy was associated with a reduced risk of cardiovascular risk, especially atherosclerotic disease. (Lockhart, B et al. 2012).
Many investigations have confirmed the association of periodontitis and cardiovascular disease in clinical trials, reports, and scientific meetings. This review further confirmed the clinical studies and several systemic reviews to associate periodontal and cardiovascular disease. The objective of this review and research paper was to assess and evaluate the relation between periodontal and cardiovascular disease. Over 20 articles were reviewed including the scientific statement by the American Heart Association on Periodontal Disease and Atherosclerotic Vascular Disease. The primary focus was based on periodontitis and CVD, oral health and CVD, oral hygiene, periodontitis and increased risk of CVD and ASVD. Only top 20 articles were reviewed and each article primarily focused on periodontal and CVD. The research paper covers all important evidence made after 2010 on atherosclerotic vascular diseases, cardiovascular disease, and periodontal disease.
Thus, there is a significant amount of evidence on the association of periodontal and cardiovascular disease. Oral health is directly associated with cardiovascular risk and thus proper oral health is mandatory.
Key Words. Periodontitis; cardiovascular disease; coronary heart disease; atherosclerotic vascular disease; systematic review; evidence-based practice; evidence-based dentistry.
Ahmed U, Tanwir F. Association of Periodontal Pathogenesis and Cardiovascular Diseases: A Literature Review. Oral Health Prev Dent. 2014 Oct 2.
Carin Starkhammar Johansson. Periodontitis and coronary artery disease. Studies on the association between periodontitis and coronary artery disease. Linköping University Medical Dissertations No. 1343. 2013.
Dhadse, et al. The link between periodontal disease and cardiovascular disease: How far we have come in last two decades? J Indian Soc Periodontol. 2010 Jul-Sep; 14(3): 148–154.
Igari, K. et al. Association between periodontitis and the development of systemic diseases. Oral Biology and Dentistry 2014.
Joshipura, K. et al. Strength of Evidence Relating Periodontal Disease and Atherosclerotic Disease. Compend Contin Educ Dent. 2010 September; 30(7): 430–439.
Joseph T. Kelly. et al. The association between periodontitis and coronary heart disease. A quality assessment of systematic reviews. JADA 144(4).
Juliana Rico Pires, et al. Framingham cardiovascular risk in patients with obesity and periodontitis. J Indian Soc Periodontol. 2014 Jan-Feb; 18(1): 14–18.
Lockhart et al. Periodontal Disease and Atherosclerotic Vascular Disease: Does the Evidence Support an Independent Association? A Scientific Statement from the American Heart Association. 2012.
Machuca, G. et al. Clinical indicators of periodontal disease in patients with coronary heart disease: A 10 years longitudinal study. Med Oral Patol Oral Cir Bucal. 2012 Jul 1;17 (4):e569-74.
Maurizio Trevisan and Joan Dorn. The Relationship between Periodontal Disease (Pd) cardiovascular disease (Cvd). Medit J Hemat Infect Dis 2010; 2(3).
Nassar, AC, et al. Assessment of periodontal treatment on lipid control in patients with cardiovascular disease. Journal of Dentistry & Oral Hygiene. Vol. 5(5), May 2013 pp. 45-50.
Rakshit, K., U. et al. Association between Periodontitis and Cardiovascular Diseases: A Clinicobiochemical Study. International Journal of Recent Trends in Science And Technology, Volume 11, Issue 1, 2014 pp 73-77.
Periodontitis and Atherosclerotic Cardiovascular Disease. European Federation of Periodontology. May 2013.
R. Anjanaa, and R. Suresh. Periodontal infection – a risk for coronary artery disease. Sri Ramachandra Journal of Medicine, July - Dec. 2010, Vol. 3, Issue 2.
Ricardo Teles and Cun-Yu Wang. Mechanisms involved in the association between periodontal diseases and cardiovascular disease. Oral Dis. 2011 July; 17(5): 450–461
Sumit Malhotra, and Hari Parkash. Coronary Artery Disease and Periodontitis: A Prospective Study. JIMSA April - June 2013 Vol. 26 No. 2.
Shaneen J. Leishman et al. Cardiovascular disease and the role of oral bacteria. Journal of Oral Microbiology 2010. .
Shad, B et al. A multi-center study on the relationship of Periodontal Disease to the Presence and Severity of Coronary Artery Disease. American Journal of Research Communication. 2013.
Tomoko Kurita-Ochiai and Masafumi Yamamoto. Periodontal Pathogens and Atherosclerosis: Implications of Inflammation and Oxidative Modification of LDL. BioMed Research International. Volume 2014.
Yu YH et al. Cardiovascular risks associated with incident and prevalent periodontal disease. J Clin Periodontol. 2015 Jan;42(1):21-8.
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