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Possible Linkage between Cardiovascular Disease and Periodontitis : A Survey Abstract: There have been numberious published studies describes between oral conditions and cardiovascular disease. Recent research has yielded conflicting data regarding the relationship between dental disease, particularly periodontitis and cardiovascular disease. There is plausible theoretical basis for such a link, as increased levels of inflammatory mediators may increase the risk of atherosclertic plaque formation. Clinical conformation and other studies of a causative relationship has been difficult in part because cardiovascular disease and periodontal disease share common risk factors. This article review’s possible evidence for relationship between cardiovascular diseases and periodontitis. Keyword: Periodontal disease, Cardiovascular disease, Survey. Possible Linkage between Cardiovascular Disease and Periodontitis : A Survey Introduction: Periodontal disease, a common chronic oral inflammatory disease is characterized by destruction of soft tissue and bone of tooth. Atheroclorosis starts early in life, since disease progression is usually slow, clinical symptoms or hospitalization on are rare before 40 years of age. Epidemiological associations between periodontitis and cardiovascular disease have been reported.1,2 Periodontitis and atherosclerosis have complex aetiologies, genetic and gender predispositions and may share pathogenic mechanisms as well as common risk factors. It is becoming increasingly clear that infections and chronic inflammatory conditions such as periodontitis may influence the atherosclerotic process. The crucial casual relation might be established by prospective treatment studies, which elucidate the connection between treatment of poor health and systemic inflammatory marker3-4. Haemostatic and rheological variable are associated with both prevalent and incident cardiovascular disease, and may be mechanisms through which risk factors such as smoking, hyperlipidemia and infections may promote vascular events. Low grade chronic infections are increasingly being recognized as potential instigators of systemic diseases. Periodontal disease manifests as a prevalent chronic infection impinging throughout the entire adult life in a significant proportion of the population and is probably a significant risk factor for cardiovascular disease in the population as a whole and particularly in certain groups.5 This article review the link between periodontitis and cardiovascular risk. Cross sectional studies Cross sectional studies type of studies are useful tool for generation of hypothesis: Sr. Author Work done Reference No. No. 1 Syrjanen et al. Dental infection was associated with 6 (1989) cerebral infraction in young and middle aged men 2. Paunio (1993) 3. Mattila (1993) et al. Missing teeth were associated with 7 ischemic heart disease KJ Significant association between 8 clinically evident attachment loss and self reported history of myocardial infraction 4. Loesche et al. A positive association between dental 9 (1998) disease and cerebrovascular accident in US Veterans 5. Arbes et (1999) 6. Slade al. Statistical association between severity 10 of coronary artery stresses et (2000) al. Edentulism and periodontal disease 11 associated with increased systemic inflammatory response, even with adjustment for established risk factors 7. Buhlin (2002) et al. CVD was increased is the patient had 12 experienced problems with her/his teeth in absence of dental care. These type of studies are a wonderful tool for hypothesis generation. Usually, they are not adjusted for all major co-existing risk factors, and since the outcome (CHD) and the predictor (periodontal disease) are measured at the same time, a temporal relationship cannot be established. Hence, the strength of evidence for casual association is weak. Interference from Table 1, inadequate prior dental histories and numerous factors such as age, gender, smoking, diabetic, socio-economic and marital status and education for the patients. Studies have shown a significant association between disease and myocardial infarction, cerebrovascular accidents. Case control studies : Case control studies generate the next level of strength of evidence, although they are still laden with biases. These studies generate the increase the level of strength of evidences, although they were still laden with biases. A ideal case-control study requires that the disease (CHD) be ascertained at the beginning of the study, and the past exposure, according to the disease status has been assessed i.e. it must be ascertained that the CHD patients and controls are similar in every aspect expect the CHD status. These studies observed that strong association between periodontal disease and cardiovascular disease (Table 2). Table 2: Summaries of case control studies on relationships between periodontal infections and cardiovascular disease (CVD) Sr. Author No. 1 Mattila Work done et (1989 b) Reference No. al. Total dental index (combined several 13 dental infections was associated with acute significantly myocardial infraction 2. Grau (1997) et al. Stroke victims tended to have more 14 severe periodontitis than controls 3. Emingil et (2000) al. Periodontal disease may have been 15 associated with acute myocardial infraction 4. Maltila et (2000) al. No significant association between 16 chronic (CAD) and severity as dental disease 5. Janket et al. No effects on each other 17 (2001) 6. Reutger person Periodontal disease may have been 18 et al. (2003) associated with CAD was indeed elevated with increasing disease severity of periodontal 7. Maltila (2003) Increased alveolar boneloss associated 19 with severity of cardiovascular disease 8. Janket (2004) et al. Oral health has the potential to affect 20 systemic health via more than just the inflammatory process Periodontal disease has been associated with increased risk of CAD and CHD. Longitudinal studies: This study design establishes the temporal relation between a predictor and an outcome. These studies are equivocal about periodontal disease involvement in development of CAD. Table 3: Summaries of longitudinal studies on the relationship between periodontal infections and coronary artery disease Sr. Author Work done Reference No. No. 1. De Stefano et al. Periodontal disease and tooth loss 21 (1993) weakly associated with CAD development; stronger association for subjects > 50 years old 2. Maltila et (1995) al. Statistical evidence for association 22 between oral infections and development of adverse cardiovascular outcomes in patients at increased for coronary artery disease (CAD) 3. Beck et (1996) al. Result support hypothesis that 23 periodontal disease is involved in development of CAD 4. Genco (1997) et al. Alveolar bone level predictive of 24 cardiovascular disease for persons < 60 years old 5. Danesh et (1997) 6. al. Significant association between the 25 number of teeth myocardial infraction Morrison et al. Significant (1999) correlation between 27 periodontal disease and risk of fatal cardiovascular disease 7. Saito et (1998) 8. Hujoel al. High BMI tend to exhibit poor 26 periodontal status et (2000) al. Elimination of chronic dental infections 28 did not lead to reductions in risk of CAD 9. Howell (2001) et al. Self reported periodontal disease not an 29 independent predictor of cardiovascular disease in middle aged to elderly men when adjusted for major cardiovascular risk factors 10. Tuominen et al. The association between oral health 30 (2003) and fatal CAD might simply be due to behavioral factors 11. Scannapieco al. (2003) et There is insufficient evidence available 31 to justify periodontal intervention to prevent the onset or progression of atherosclerosis induced diseases Systemic markers of inflammation: Most systemic markers of inflammation are regarded as predictive markers for cardiovascular diseases. These markers include leukocytes count (WBC), C-reactive proteins (CRP), fibronogen and lipid profile. Raised WBC counts, CRP and fibrinogen levels correlated with periodontal disease (Table 4-6). On the other hand HDL levels are found to be lowered in this condition. (Table 7), haemotocrit value and thrombocyte counts are lowered in periodontal condition disease (Table 7). From the available literature it is appears that the total number of leukocytes and plasma levels of C-reactive protein are consistently higher in periodontitis patients compared to healthy control. Number of red blood cells and the levels of heamoglobin are lower in periodontitis and those as a trend towards anemia of chronic disease. Most systemic markers of inflammation diseased (Table 4 to 8) regarded as predictive markers for cardiovascular disease. Hence, analogous to other infections inflammatory diseases, it is conceivable that the chronically, slightly elevated or depressed systemic markers in blood exacerbated ongoing inflammatory process in other organ systems and this way perhaps increase the risk for atherosclerosis, leading to cardiovascular and cerebrosvascular events. Table 4: Summaries of leukocytes in periodontitis and healthy controls Sr. No. 1 Authors Gustafsson Leukocytes mean+SD Periodontitis al. 7.7 + 2.1 (x109/l) Reference Controls 7.3 + 2.2 32 5.6 + 1.1 33 6.5 + 1.9 5.8 + 1.4 34 et al. 6.6 + 1.7 5.9 + 1.3 35 et al. 7.3 + 2.3 5.7 + 1.3 36 8.0 + 2.2 7.2 + 2.2 37 et (1996) 2 Frederiksson et al. 7.0 + 1.4 (1998) 3 Loss et al. (2000) 4 Fokhema (2002) 5 Bizzarro (2005) 6 Rai et al. (2006) Table 5: Summaries of c-reactive protein (CRP) plasma level (mg/l) in periodontitis and healthy controls Sr. No. 1 (CRP) Authors Patients Controls Frederiksson et al. 2.62 + 2.90 0.80 + 1.73 Reference 33 (1998) 2 Loss et al. (2000) 2.64 + 3.48 1.21 + 1.34 34 3 Noack et al. (2001) 4.06 + 5.55 1.70 + 1.91 38 4 Glurich et al. (2002) 2.40 + 1.80 1.68 + 1.42 39 5 Craig et al. (2003) 5.78 + 1.07 2.46 + 1.44 40 6 Bizzarro al. 3.12 + 3.81 1.88 + 2.04 36 3.82 + 0.33 1.42 + 0.43 41 et (2005) 7 Rai et al. (2006) Table 6: Summaries of fibrinogen plasma level (g/l) in periodontitis patients and healthy controls Sr. No. 1 Fibrinogen plasma level Authors Patients Controls Shingur et al. (2003) 2.50 + 0.10 2.25 + 0.12 Reference 42 2 Bizzarro 36 (2005) et al. 3.26 + 0.68 2.90 + 0.63 Table 7: Summaries of some other value of periodontitis and normal healthy controls Sr. Authors No. 1 Christan Work done et Reference al. Non-surgical periodontal therapy 43 (2002) among 27 patients with aggressive periodontal resulted in a reduced of numbers of thromocytes in the peripheral circulation : the media value at baseline of 2.6 x 1011/l was reduced after therapy to 2.3 x 1011/l 2 Hutler et al. (2001) Periodontitis is a disease process 44 which can result in a form of anemia periodontitis patients have lower hematocrit 3 Lainson et al.(1968) 58% of female periodontitis patients 45 and 30% of male periodontitis patients had a depressed hematocrit 4 Loos et al. (2000) 11 of 26 control subjects (42%) and 34 47 of 88 periodontitis patients (53%) had mearable IL-6 in plasma. The Il-6 levels, like CRP, showed a positive relation to extent of disease 5 Buhlin et al. (2003) Elevated IL-6 plasma levels in 46 patients with severe periodontitis compared to healthy controls Table 8: Summaries of lipid profile in periodontitis and normal healthy controls Sr. No. Authors 1 Work done Reference Katz et al. (2002) Periodontal disease may influence 47 blood lipid concentrations 2 Buhlin’s (2001) 3 et al. Relation between periodontitis and 48 low concentrations of HDL Joshipura et Periodontal disease was associated 49 al.(2004) with higher levels of LDL as compared to healthy Table 9: Summaries of oral health and stroke relationship Sr. Authors No. 1 Work done Beck et al. (1996) Strong association periodontitis with Reference between 22 incidence of stroke among US veterans 2 Morrison et al. No-significant increase in risk of 50 (2001) 3 4 Joshipura fatal stroke in periodontitis patients et A significant association between 51 al.(2003) stroke and periodontitis Janket et al. (2003) Relationship between periodontal 52 disease and stroke to be much stronger that periodontal disease and CHD Table 10: Summaries the ratio for cardiovascular disease for patients with periodontal disease Sr. Authors No. 1 De stefano et al. 1.46 (1993) Ratio (fatal cardiovascular disease/stroke) Reference 21 2 Beck et al. (1996) 1.9/2.8 23 3 Gran et al. (1997) 2.6 14 Thus poor oral health in term in terms of periodontitis has strong relationship between CHD and stroke in most of the studies reviewed (Table 10). Table 11: Summaries of microbiological aspect of periodontitis and cardiovascular disease Sr. Authors No. 1 Herzberg Work done et (1990) Reference al. Oral bacteria such as streptococous 53 sanguis and gingivalis porphyromanas induce platelet aggression; which lead to thrombus formation 2 Page et al. (1998) Lipopolysacchride and gram 54 negative oral bacteria may enter the blood stream and increase susceptibility to systemic disease 3 Sacransky et (2002) al. P. gingivalis can actively adhere to 55 and invade fotal bovine heart endothelial cells, bovine arotic endothelial cells, and human umbilical vein endothelial cells 4 Wolf et al. (2003) Oral pathogens are not the only 56 bacteria that have a postulated link to the development atherosclerosis of chlamydia pneumoniae anid H. pylori are also suspected infectious agents in atherogenesis Conclusion: The debate about whether periodontal disease is a risk factor for cardiovascular disease is interesting, but still unresolved. Current evidence is insufficient to unequivocally support the premise that dental infections constitute an independent risk factor for cardiovascular disease. However, the deposition of atherematous plaque in the coronary arteries may be associated with many other infections in addition to periodontitis. Although some studies have demonstrated that the relative risk for cardiovascular disease is increased among patients with periodontitis, other analysis have been potentially confounded by the fact that smoking and diabetes seen to have a casual relationship with cardiovascular disease and periodontitis. As long as the mechanism of cardiovascular remains obscure, it will be difficult to determine the real relationship between oral and cardiovascular disease. Therefore, evidence for potential association between oral and systemic disease must be carefully reexamined to distinguish potential confounding factors from other risk factors before treatment with the aim of preventing or treating cardiovascular disease can be justified. References: 1. Beck J, Garcia R, Heiss G. Periodontal disease and cardiovascular disease. 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