|Year : 2015 | Volume
| Issue : 1 | Page : 15-20
Hs-CRP levels in patients with periodontitis- a cross sectional study
MA Shah1, BK Shah2, BB Modi2, EB Shah2, DH Dave3
1 Professor, Department of Periodontics, K M Shah Dental College, Sumandeep Vidyapeeth, Piparia, Vadodara. 391760, India
2 Senior Lecturer, Department of Periodontics, K M Shah Dental College, Sumandeep Vidyapeeth, Piparia, Vadodara. 391760, India
3 Professor & HOD, Department of Periodontics, K M Shah Dental College, Sumandeep Vidyapeeth, Piparia, Vadodara. 391760, India
|Date of Web Publication||3-Aug-2018|
M A Shah
Professor, Department of Periodontics, K M Shah Dental College, Sumandeep Vidyapeeth, Piparia, Vadodara. 391760
Source of Support: None, Conflict of Interest: None
Background: During the last century, cardiovascular disease (CVD) has common occurrence in most of the population and the great attendant mortality, loss of independence, impaired quality life and social and economic costs forming a compelling reason for public health concern. C reactive protein (CRP) in particular has been the focuses of attention as a key marker of atherosclerosis and elevated level constitutes a risk predictor for CVD.
Aim: The present study focuses the association between periodontal inflammatory status as assessed by clinical periodontal sum score (CPSS) and levels of CRP and to co-relate periodontal destruction levels with levels of hs- CRP.
Methodology: Patients with chronic generalized periodontitis were selected. Periodontal destruction of the patient included in the study was recorded by CPSS and blood was tested for hs-CRP levels. Mean, Standard deviation and range of CPSS and hs-CRP were calculated. The correlation between CPSS and hs-CRP that is clinical index and biochemical marker was made by Spearman correlation test for significant.
Results: A total of 20 patients had participated in this study. The CPSS ranged from 31 to 205 and the hs-CRP levels ranged from 0.18 to 16.45. 2 tailed Spearman correlation test showed significant p value (0.05).
Conclusion: Statistical significant co-relation was found between periodontal disease as assessed by CPSS and hs-CRP level. Results of this study point to the importance of diagnosing cases of severe periodontal destruction, and the need for proper health education and prompt periodontal therapy for the cases identified.
Keywords: CRP, CVD, Periodontitis, Risk factor
|How to cite this article:|
Shah M A, Shah B K, Modi B B, Shah E B, Dave D H. Hs-CRP levels in patients with periodontitis- a cross sectional study. J Integr Health Sci 2015;3:15-20
|How to cite this URL:|
Shah M A, Shah B K, Modi B B, Shah E B, Dave D H. Hs-CRP levels in patients with periodontitis- a cross sectional study. J Integr Health Sci [serial online] 2015 [cited 2019 Jan 22];3:15-20. Available from: http://www.jihs.in/text.asp?2015/3/1/15/238514
| Introduction|| |
During the last century, cardiovascular disease (CVD) has burgeoned from a relatively minor disease worldwide to a leading cause of morbidity and mortality. By 2020 it is projected that CVD will surpass infectious disease as the world’s leading cause of death and disability. These changes are most pronounced in the countries comprising the developing world. Smoking, lack of physical activity, obesity, an unhealthy diet and eating too much salt, excess alcohol are the proven risk factors for CVD however research is looking at some other risk factors like stress, C-reactive protein, socioeconomic status, high blood levels of fibrinogen, apolipoprotein B, and homocysteine. Numerous biomarkers involved at various levels of the inflammation cascade have been shown to be associated with adverse cardiovascular outcomes. Among all blood biomarkers, C-reactive protein (CRP), the classical acute phase reactant that can be measured with high-sensitivity (hs) assays seems to be the most promising candidate. Whether the patient has been diagnosed with cardiovascular disease or not minimizing the risk factors should be the first step for prevention. Healthcare providers can work to identify the best choices for the patient among a range of treatment and prevention options.
C-reactive protein (CRP) is an acute phase protein which reflects a measure of the acute phase response. The term “acute phase” refers to local and systemic events that accompany inflammatory local response which includes vasodilatation, platelet aggregation, neutrophil chemotaxis, and release of lysosomal enzymes. Systemic responses include fever, leukocytosis, and a change in the hepatic synthesis of acute phase proteins. CRP production is part of the non-specific acute-phase response to most forms of inflammation, infection and tissue damage. Prospective epidemiological studies have demonstrated that CRP levels independently predict the risk of first coronary events. CRP can increase up to 1000 fold after the onset of a stimulus. Due to its opsonising abilities and its capability to activate human complement, CRP plays an important role in the innate host defence against different microorganisms such as bacteria and fungi. As hs- CRP values related with CHD risk, American Heart Association and U. S. Centers for disease control and prevention have defined risk groups of coronary heart disease as low risk – less than 1.0 mg/l, average risk - 1.0 to 3.0 mg/l, high risk above 3.0 mg/l.
CRP in particular has been the focus of attention as a key marker of atherosclerosis and elevated levels constitute a risk predictor for CVD. CRP is currently regarded as a biomarker of systemic inflammation. Periodontitis has also been linked to elevated CRP levels in adults. CVD and a heightened acute phase response with increased levels of CRP share many common risk factors including smoking, high body- mass index and older age. It is thus postulated that CRP might be a possible mediator of the association between periodontitis and these systemic conditions.
Periodontitis is an inflammatory disorder characterized by the destruction of periodontal tissues with a subsequent attachment loss. The periodontal destruction is host mediated by locally produced pro- inflammatory cytokines in response to the bacterial flora and its products. Subjects affected by periodontal disease develop an intense local production of pro-inflammatory cytokines that may enter the blood stream as shown by the high levels of inflammatory bio-markers in both gingival tissues and serum. However, it is host susceptibility and ability of the host defense to respond appropriately to the bacterial challenge that results in differences in the disease severity from one individual to another.
Evidence suggests that this may trigger a systemic acute-phase inflammatory response, characterized increased levels of acute phase proteins such as C- reactive protein and vascular dysfunction.
Recent evidence also suggests the presence of chronic inflammatory periodontal disease may significantly affect systemic health conditions such as coronary heart disease (CHD), stroke, or adverse pregnancy outcomes. The relationship between periodontal disease and systemic disease (periodontal medicine) is a two-way relation, with systemic host factors acting locally to reduce resistance to periodontal destruction and the local bacterial challenge generating widespread effects with the potential to induce adverse systemic outcomes.
CRP has been shown to predict cardiovascular mortality in recent studies, and elevated CRP levels have been observed in middle-aged patients with periodontitis. Combination of chronic infections like periodontitis with elevated CRP is associated with higher chronic heart diseases., A summary of systematic reviews conducted for the U.S. Preventive Services Task Force shows that Traditional risk factors do not explain all of the risk for incident coronary heart disease (CHD) events. Various new or emerging risk factors have the potential to improve global risk assessment for CHD.
An inter-relationship between periodontal disease and systemic health has been suspected for centuries, but evidence to explain the connection has only been elucidated in the past few decades and to obtain one representative value per patient for describing the periodontal status of each patient. Matilla et al. (2000) formed an index clinical periodontal sum score (CPSS) which describes the proportions of diseased periodontal areas on the sites examined by including the numbers of various recordings that indicate periodontal pathology. As most of the previous studies measured periodontal condition using various indices to measure either destruction or present inflammatory status of periodontium. CPSS is an only index which measure inflammatory burden, infection as well as amount of destruction in single scoring system.
The aim of this study is to establish the association between periodontal inflammatory status as assessed by CPSS and levels of CRP and to co-relate periodontal destruction levels with levels of hs-CRP.
| Methodology|| |
Twenty patients with chronic generalized periodontitis were selected from the OPD of Department of Periodontics. Patients with a medical history, smoking habit, history of antibiotic therapy in the past three months or history of having undergone periodontal treatment were excluded. Exclusions were made to avoid the confounding effects of the diseases/conditions or the medications. All the subjects were informed about the procedure prior to the treatment and a written consent was obtained from them before their inclusion in the study. The approval from the ethical committee was taken from Sumandeep Vidyapeeth University. Periodontal destruction of the patient included in the study was recorded by (CPSS) and blood was withdrawn on the same day. Serum was separated and assessed for hs- CRP levels.
CPSS clinical periodontal sum score includes recording of the following clinical parameters: probing pocket depth, bleeding on probing, suppuration and furcation involvement the scores given to the various clinical parameters are then added giving us a final cumulative score of the periodontal status of the patient.
The clinical periodontal examination was conducted to determine the severity and extent of inflammation in periodontal tissues. The measurements were completed by an experienced specialist in Periodontology. The probing depth measurements were assessed by means of a manual calibrated HuFriedy UNC 15 Probe and the measurements were recorded to the nearest mm. The presence or absence of bleeding was determined within 30 sec after probing; presence or absence of suppuration was determined during the probing. Furcation lesions of grades 2 and 3 were assessed by a HuFriedyNabers probe. Six sites per tooth were examined in all teeth in the dentition (disto-buccal, mid-buccal, mesio- buccal, mesio-lingual, mid-lingual, disto-lingual).
Two additional sites were examined in the middle of the mesio-buccal and disto-buccal roots of the upper molars, and 4 additional sites in the middle of the mesial and distal roots, both buccally and lingually, in the lower molars.
The number of sites per patient with probing pocket depths 4 mm or greater was added to the number of teeth with bleeding on probing, to those with visible suppuration on probing and to the number of furcation lesions exceeding grade 1. This sum is called the CPSS.
Collection of blood samples
Venous blood samples were obtained from the central veins through the skin in the anti-cubital fossa. 3 ml of blood was drawn using a 5c disposable syringe and 23 gauge needles. The blood was allowed to clot and then centrifuged at 3,000 rpm (revolutions per minutes) for 5 minutes and serum was separated. The serum thus obtained was used for testing the CRP levels using the commercially available kits.
Assessment of Hs-CRP levels
hs-CRP levels were assessed from the serum separated from the acquired blood samples by commercially available immune turbidimetric assay. Serum C- reactive protein levels were assessed by means of commercial high sensitive immune turbidimetric assay at baseline.
Mean, Standard deviation and range of CPSS and hs- CRP were calculated. The correlation between CPSS and hs-CRP that is clinical index and biochemical marker was made by Spearman correlation test for significant.
| Results|| |
A total of 20 patients, 12 females and 8 males had participated in this study. The participants included in this study ranged from gingivitis to advanced periodontitis. The periodontal status was recorded using CPSS which ranged from 31 to 205 and the hs- CRP levels ranged from 0.18 to 16.45 [Table 1]. Two tailed Spearman correlation test showed significant p value (0.05).30% of chronic periodontitis patients shows >3mg/L of hs-CRP where 35% were in<1.0 mg/L [Table 2].
| Discussion|| |
Inflammatory processes play a pivotal role in the pathogenesis of atherosclerosis and mediate many of the stages of atheroma development from initial leukocyte recruitment to eventual rupture of the unstable atherosclerotic plaque. C-reactive protein (CRP), an acute phase reactant that reflects different degree of inflammation, has been indicated an independent risk factor in a variety of cardiovascular disease (CVD), especially in unstable coronary syndrome. Increased level of CRP in patients with unstable angina was associated with short-term clinical outcomes, response for conventional therapy and activation of nuclear factor-kappa B (NF-kappaB). CRP also serves as an activator of the complement system, an immunological cascade that assists the innate immune system by marking and destroying nonself antigens. Activation of complement is thought to contribute to the perpetuation of the inflammatory response, and is implicated in neurodegenerative processes.
Monocytes exhibit an enhanced production of interleukin-6 (IL-6) in response to CRP. This may be of important interest in the connection between CVD and CRP. Extensive periodontal disease and BMI are jointly associated with increased CRP levels in otherwise healthy, middle-aged adults, suggesting the need for medical and dental diagnoses when evaluating sources of acute-phase response in some patients.
Traditionally, CRP has been thought of as a bystander marker of vascular inflammation, without playing a direct role in the CVD. More recently, accumulating evidence suggest that CRP may have direct proinflammatory effects, which is associated with all stages of atherosclerosis and treatments that reduce CRP should be benefit for primary and secondary prevention of CVD.
Present study have demonstrated that the extent of increase in CRP levels in periodontitis patient depends on the severity of disease and that the elevation of CRP is associated with the presence of periodontopathic bacteria and has been suggested that inflammation status, as assessed by CRP concentration, modifies the vascular protective effects.,Previous study suggested that patients with CVD with fresh myocardial infarction had poor oral hygiene, more periodontal destruction and need of complex treatment compared to healthy subjects of control group.
A total of 20 participants with periodontal destruction were included in the analysis of CRP periodontal destruction was assessed by CPSS.
Patients with the history antibiotic therapy three months before or during the study period were excluded because history of antibiotic suggests presence of an infectious condition which would have an effect on the CRP levels.
Patients with past history of periodontal therapy were also excluded because it would decrease the inflammatory burden and thus would decrease the CRP levels. Also periodontal therapy would lead to tissue injury which would again lead to an inflammatory response which would increase the CRP levels immediately post treatment.
The index CPSS is taken as it includes clinical parameters bleeding on probing, probing pocket depth, suppuration and furcation involvement. It gives a cumulative sum of the overall periodontal status and the inflammatory burden of an individual instead of individual parameter to which the level of CRP can be directly co-related to CPSS obtains one representative value per patient for describing the periodontal status of each patient. This index, clinical periodontal sum score (CPSS), which describes the proportions of diseased periodontal areas on the sites examined by including the numbers of various recordings that indicate periodontal pathology.
In the present study, 20 patients, 8 males and 12 females, participated in the study. Two values for each patient were obtained CPSS and hs-CRP.
The baseline CPSS ranged from 31 and 205 with the mean being 95 whereas thehs- CRP value ranged from 0.18 to 16.45mg/L with the mean being 3.29mg/ L. In this study all included patients were diagnosed patients of chronic generalized periodontitis and inflammation burden due to disease were measured by CPSS. CPSS score is 95 ± 47.77 with 95% CI 72.64-117.4. hs-CRP values 3.29 ± 4.66 with 1.115.47. As hs-CRP values related with CHD risk, American Heart Association and U. S. Centers for disease control and prevention have defined risk groups of coronary heart disease as low risk – less than 1.0 mg/l, average risk – 1.0 to 3.0 mg/l, high risk above 3.0 mg/l.
In this study all periodontitis patients were at average to high risk of coronary heart disease as measure with hs-CRP. (Mean3.29 ± 4.66, 95% CI 1.11-5.47) periodontal destruction and disease burden shows significant relation (p=0.05) with hs-CRP.There was positive association between the levels of CPSS and hs-CRP (p = 0.05, 2-tailed) by Spearman’s correlation.
Results when categories in Low, Average and High risk of CHD depending on values of hs-CRP, 30% of patients were in high risk group that is >3mg/L of hs- CRP. Only 35% of patients are in Low risk group and remaining 35% were in Average risk group.
The limitation of this study is small sample size. Although we utilized an hs-CRP assay, and excluded smokers, patients with medical history and antibiotics, and, as far as possible, subjects with any other infections or inflammatory conditions. Further better designed case control study can be done.
| Conclusion|| |
Statistical significant co-relation was found between periodontal disease as assessed by CPSS and hs-CRP level. Results of this study point to the importance of diagnosing cases of severe periodontal destruction, and the need for proper health education and prompt periodontal therapy for the cases identified. CRP, the classical marker of acute phase response, is an indicator of a variety of pathological processes including infection, tissue damage, and chronic inflammatory disease. As the goal of modern health care continues to shift from an attitude of treatment to one of prevention, investigations will increasingly be directed toward elucidating predisposing factors that lead to atherosclerosis and developing appropriate early intervention. Periodontal diseases may represent one such factor. It will be incumbent on all dental professionals to take appropriate measures to both counsel patients in the prevention of periodontal diseases and, where necessary, arrange treatment for affected individuals to receive appropriate care in a specialist setting.
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[Table 1], [Table 2]