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Periodontics

Authors : Dr. M. Siddharth, Dr. Jyoti Kasana, Dr. Anshuman Dwivedi.

ABSTRACT:

Periodontitis is a destructive inflammatory disease of the supporting tissues of the teeth. This condition is caused by a chronic, mixed infection of gram-negative bacteria. Periodontal pathogens affect local and systemic immune and inflammatory responses. Numerous studies have shown that individuals with periodontitis have a significantly increased risk of developing coronary heart disease. In addition to conventional risk factors, chronic infection and subsequent production of systemic inflammatory markers, such as C reactive protein (CRP) may be associated with this increased risk. This review appraises the available evidence to determine the influence of chronic periodontitis on the serum levels of C-reactive protein (CRP) and its effects on systemic health of an individual.

INTRODUCTION:

Periodontitis is a chronic inflammatory, progressive and destructive disease of the supporting tissues of the teeth that is predominantly induced by gram-negative bacteria that colonize the gingival crevice.

In recent years, periodontal disease has been implicated in the onset and development of cardiovascular diseases, including atherosclerosis, cerebrovascular and coronary artery diseases, rheumatoid arthritis, diabetes mellitus, occlusive respiratory diseases, and preterm low birth weight1.

                Periodontal diseases involve chronic inflammatory processes resulting from interaction of selected gram negative bacterial species with the host response in disease susceptible individuals. The ulcerated gingival tissues provide a portal of entry for these sub gingival organisms like Porphyromonas gingivalis and their by products into the systemic circulation. The host responds to the microbial challenge, with a high inflammatory response with increased levels of cytokines like IL-1, IL-6, TNF-α. These mediators promote activation of the acute phase reactants resulting in elevated serum levels of C-reactive protein, α1-acid glycoprotein, ceruloplasmin, serum amyloid A 2  Capsule reactive protein (CRP) is an acute phase reactant synthesized by the liver in response to the inflammatory cytokines interleukin (IL)-6, IL-1, and tumor necrosis factor-alpha 1 . According to Joint National Committee 7 guidelines and American Heart Association, patients with elevated basal levels of CRP are at an increased risk of, hypertension and cardiovascular disease. The objective of this traditional review is to summarize the information of CRP with periodontal disease.

Capsule Reactive Protein (CRP)  The existence of CRP was first reported in 1930 by Tillet and Frances 3Capsule reactive protein (CRP) is an acute phase reactant.C-reactive protein was identified because of its ability to precipitate with the C polysaccharide extract of Streptococcus pneumoniae.

STRUCTURE 4

CRP belongs to the pentraxin family of calcium-dependent ligand-binding plasma proteins.The human CRP molecule is composed of five identical nonglycosylated polypeptide subunits each containing 206 amino acid residues.

Properties and Functions 5

  1. C –reactive protein when binds to bacteria, causes activation of complement to enhance opsonisation and clearance of the bacteria prior to the production of IgM or IgG.
  2. C reactive protein binds to bacteria or cells and interacts with the natural killer cells and with the monocytes and may increase the tumoricidal activity of these cells.
  3. Modulates macrophage function, since macrophages possess C reactive protein receptors and CRP potently increases proinflammatory cytokine production.
  4. C-reactive protein has been shown to induce the synthesis of IL-1α, IL-1β, tumor necrosis factor α and IL-6 in human peripheral blood mononuclear cells, suggesting that one of its physiological roles may be the amplification of inflammatory responses.

Regulation of C-reactive protein synthesis 6

C-reactive protein (CRP) is strong acute phase protein. In healthy subjects the serum concentration is <1.5 mg/l. In acute phase situations, however, the concentration can increase up to a thousand fold. CRP is synthesized mainly in hepatocytes, but mRNA and CRP have been shown to be present in monocytes derived macrophages in atherosclerotic plaques, lymphocytes and alveolar macrophages. Synthesis is regulated mainly by inteleukin (IL)-6, IL-1 and tumor necrosis factor (TNF)-α. Peak values of CRP usually disappear within a few days of the inflammatory stimulus.The concentration of IL-6 is usually strongly correlated with the concentration of CRP. It has been suggested that IL-6 alone is not sufficient to induce an increase in CRP concentrations, and additional factors, such as IL-1, oncostatin M or leukemia inhibition factor, are also required.

Factors affecting C-reactive protein concentration 7:

Many studies have reported a positive association between age and CRP concentration. The extremes are clear when CRP concentrations in newborns (~0.1mg/L) are compared to those in subjects older than 85 years (CRP levels > 10 mg/L in 50% of cases). The CRP concentration is known to be higher in individuals who smoke. Obesity is associated with an increased CRP concentration, presumably because adipose tissue is an important site of synthesis of IL-6 which is the main determinant of CRP gene expression. A relationship between blood pressure and the concentration of CRP has been reported. The concentration of CRP has also been correlated to that of lipids (e.g. triglycerides). Indeed, in the VERA study 9, vitamin C and β -carotene lowered CRP levels but vitamin E had no effect. α -tocopherol was administered to healthy volunteers and to patients with type II diabetes after which CRP levels were decreased in both the groups. It is expected that anti-inflammatory drugs have an effect on the concentration of CRP. It has indeed been shown that non-steroidal anti-inflammatory drugs (NSAID), such as aspirin and ibuprofen, reduce oxidative stress 6.

C-reactive protein and chronic disease 6: The CRP concentration is associated with cardiovascular disease and with other inflammatory diseases, such as rheumatoid arthritis. Also, several components of the insulin-resistance syndrome, such as obesity and increased blood pressure, are associated with altered CRP values. Also, patients with insulin-dependent diabetes mellitus have increased CRP levels. Higher CRP concentrations have been observed in patients with periodontitis versus healthy controls. 

C reactive protein and cardiovascular disease:

Cholesterol has long been known to play a crucial part of predicting risk for heart attack in seemingly healthy people. But half of all heart attacks occur in people who don’t have high cholesterol. Also, the classical risk factors of CVD cannot account for all the variation in the incidence of CVD cases. As a result there is a growing interest to identify additional markers of coronary risk. One likely candidate is C-reactive protein (CRP).

A recent joint consensus conference of the American Heart Association (AHA) and the Centre for Diseases Control (CDC) from a pooled epidemiological data from 40,000 subjects have shown that different levels of serum CRP predict future cardiovascular events in other-wise healthy individuals 8CRP has been shown to be not only a prognostic indicator of acute coronary syndromes, but also, a predictor of future coronary events. Perhaps of greater importance is the demonstration that CRP concentrations predict first MI (Myocardial Infarction) and stroke.

CRP and Periodontitis Several pathophysiological pathways have been proposed as potential links between Periodontitis, Atherosclerotic Vascular Disease and CRP. These pathways involve both direct and indirect interactions between periodontal pathogens and the endothelium or other mechanisms that impact the atherosclerotic process. Systemic inflammation can be measured with several inflammatory markers. A well-studied inflammatory marker is C-reactive protein (CRP). Additional inflammatory markers associated with cardiovascular disease include lipoprotein-associated phospholipase A2, matrix metalloproteinases and tissue inhibitors of matrix metalloproteinase, myeloperoxidase and fibrinogen. Other inflammatory markers (eg, interleukin 6 [IL-6], soluble intercellular adhesion molecule-1, macrophage inhibitory cytokine-1, and soluble CD40 ligand) have been shown to be elevated among those at increased vascular risk, albeit to a lesser magnitude than CRP.

Periodontal inflammation is similarly associated with increased systemic inflammatory markers, including CRP, tumor necrosis factor- , IL-1, IL-6, and IL-8 .Systemic inflammation is associated with cellular activation that involves cellular adhesion molecules, toll-like receptors, matrix metalloproteinase, and nuclear factor- B activation. The resulting interplay between endothelium, monocytes, and platelets might be proatherogenic contributing indirectly to atherogenesis or to adverse cardiovascular outcomes related to atheromatous plaque rupture in subjects with periodontitis The pathogenic role of the subgingival microbiota in the initiation and progression of periodontitis is widely accepted. Periodontal pathogens affect local and systemic immune and inflammatory responses. The local inflammatory response to these bacteria or bacterial products is characterized by infiltration of the periodontal tissues by inflammatory cells including polymorphonuclear neutrophils (PMNs), macrophages, lymphocytes and plasma cells. Activated macrophages release cytokines and some individuals respond to microbial challenge with an abnormally high delivery of such inflammatory mediators as PGE2, IL-1 and TNF-α. These cytokines are involved in the destruction of both the periodontal connective tissue and alveolar bone.They can also initiate a systemic acute phase response. Several studies have examined periodontal disease or other oral health parameters in relation to intermediate variables or biomarkers of CVD such as C-reactive protein.

AUTHORS CONCLUSION
Norman ME (1979)9 Subtle degrees of systemic complement activation occur in experimental gingivitis, but are only detected by sensitive functional assays.
Bruno G.Loos (2000)10 Patients with periodontitis had higher median CRP levels than controls (1.45versus 0.90 mg/L ,respectively, P=0.030).
Slade GD (2000) 11 Dentate people with extensive periodontal disease had an increase of approximately 1/3 in mean CRP and a doubling in prevalence of elevated CRP compared with periodontally healthy people.
Noack B (2001) 12 Extent of increase in CRP levels in periodontitis patients depends on the severity of the disease after adjusting for age, smoking, body mass-index, triglycerides and cholesterol.
D’Aiuto (2002) 13 Non surgical periodontal therapy with ultrasonic instruments led to a significant improvement in clinical parameters but did not decrease serum CRP in severe periodontitis at 2 months.
D’Aiuto, Ready D, Tonetti MS (2004) 14 Periodontitis may add to the inflammatory burden of the individual and may result in increased levels of cardiovascular risk based on serum CRP concentrations.
Paraskevas S, Huizinga JD, Loos BG (2008) 15 In a meta-analysis of 10 cross-sectional studies showed that the weighted mean difference (WMD) of CRP between periodontitis patients and controls was 1.56mg/l (p<0.00001).
Andrea M. Marcaccini, Ce´sar A. Meschiari et al (2009) 1 In apparently otherwise healthy patients, periodontal disease is associated with increased circulating concentrations of IL-6 and highsensitivity CRP, which decreased 3 months after non-surgical periodontal therapy.
Annie Kity george, Prasnthila Janam(2013) 16 Periodontal disease significantly affects the serum levels of hs-CRP and non surgical periodontal therapy could bring about a decrease in its level.
Cauala AL (2014) 17 Median values of C-reactive protein, ESR, total cholesterol, and triglycerides were reduced after 6 month of periodontal treatment in the test group.
CONCLUSION

In conclusion, this review provides evidence that periodontitis elicits a mild acute-phase response with elevation of CRP levels compared with healthy controls.

Periodontal treatment results in lowered CRP levels; however, the treatment studies available are scarce. Elevated plasma CRP is a risk predictor for Cardio Vascular Disease.

Periodontitis is another condition to be considered when evaluating CRP levels in relation to cardiovascular diseases.

Given the relatively high prevalence of periodontitis in the population, health care professionals should be aware that this condition results in an increased systemic inflammatory burden. Periodontal treatment may seem to be an effective way to lower plasma CRP.More studies are required to prove the effectiveness of non surgical periodontal therapy in decreasing the CRP levels, thereby reducing the risk for Cardio vascular diseases.

REFERENCES:

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More references are availabe on request.