A systematic review and meta-analyses on C-reactive protein in relation to periodontitis.

AIM Elevated plasma C-reactive protein (CRP) is regarded as a risk predictor for cardiovascular diseases. This systematic review explored the robustness of observations that CRP is elevated in periodontitis. Similarly, the effect of periodontal therapy on CRP levels was investigated. MATERIAL AND METHODS Selection of publications was based on: (1) cross-sectional (case-control) studies; (2) longitudinal (treatment) studies; (3) high-sensitivity CRP measurement; (4) median and/or mean (+/-SD) values presented; and (5) subjects with no systemic disorders. RESULTS Screening of the initially 448 identified studies and reference checking resulted in 18 suitable papers. The majority of the studies showed that CRP levels are higher in patients than in controls. Often, studies showed that patients had CRP levels >2.1 mg/l. A meta-analysis of 10 cross-sectional studies showed that the weighted mean difference (WMD) of CRP between patients and controls was 1.56 mg/l (p<0.00001). Evidence from available treatment studies (n=6) showed lower levels of CRP after periodontal therapy. Eligible treatment studies in a meta-analysis demonstrated a WMD of reductions of CRP after therapy of 0.50 mg/L (95% CI 0.08-0.93) (p=0.02). CONCLUSIONS There is strong evidence from cross-sectional studies that plasma CRP in periodontitis is elevated compared with controls. There is modest evidence on the effect of periodontal therapy in lowering the levels of CRP.

[1]  H. Löe,et al.  Periodontal status of US employed adults in 1985-86 , 1990 .

[2]  A R Jadad,et al.  What contributions do languages other than English make on the results of meta-analyses? , 2000, Journal of clinical epidemiology.

[3]  V. Salomaa,et al.  Association of markers of systemic inflammation, C reactive protein, serum amyloid A, and fibrinogen, with socioeconomic status , 2003, Journal of epidemiology and community health.

[4]  J. Jones,et al.  Meta-analysis of periodontal disease and risk of coronary heart disease and stroke. , 2003, Oral surgery, oral medicine, oral pathology, oral radiology, and endodontics.

[5]  M. Criqui,et al.  Gender and C-reactive protein: data from the Multiethnic Study of Atherosclerosis (MESA) cohort. , 2006, American heart journal.

[6]  J. Meurman,et al.  Oral health, atherosclerosis, and cardiovascular disease. , 2004, Critical reviews in oral biology and medicine : an official publication of the American Association of Oral Biologists.

[7]  S. Amar,et al.  Periodontal Disease Is Associated With Brachial Artery Endothelial Dysfunction and Systemic Inflammation , 2003, Arteriosclerosis, thrombosis, and vascular biology.

[8]  Y. Ichihara,et al.  Associations of medical status and physical fitness with periodontal disease. , 1999, Journal of clinical periodontology.

[9]  P. Ridker,et al.  Inflammation, aspirin, and the risk of cardiovascular disease in apparently healthy men. , 1997, The New England journal of medicine.

[10]  N. E. Boucher,et al.  Occurrence of C-Reactive Protein in Oral Disease , 1967, Journal of dental research.

[11]  M. Ide,et al.  The Short‐Term Effects of Treatment of Chronic Periodontitis on Circulating Levels of Endotoxin, C‐Reactive Protein, Tumor Necrosis Factor‐α, and Interleukin‐6 , 2004 .

[12]  M. Ide,et al.  Effect of treatment of chronic periodontitis on levels of serum markers of acute-phase inflammatory and vascular responses. , 2003, Journal of clinical periodontology.

[13]  J. Califano,et al.  C-reactive protein levels in patients with aggressive periodontitis. , 2006, Journal of periodontology.

[14]  M. Tonetti,et al.  Short-term Effects of Intensive Periodontal Therapy on Serum Inflammatory Markers and Cholesterol , 2005, Journal of dental research.

[15]  O. Ohlsson,et al.  High-sensitivity serum C-reactive protein levels in subjects with or without myocardial infarction or periodontitis. , 2005, Journal of clinical periodontology.

[16]  S. Takashiba,et al.  Antimicrobial periodontal treatment decreases serum C-reactive protein, tumor necrosis factor-alpha, but not adiponectin levels in patients with chronic periodontitis. , 2003, Journal of periodontology.

[17]  J D Beck,et al.  Oral disease, cardiovascular disease and systemic inflammation. , 2000, Periodontology 2000.

[18]  G. Seymour,et al.  Effect of periodontal treatment on the C-reactive protein and proinflammatory cytokine levels in Japanese periodontitis patients. , 2005, Journal of periodontal research.

[19]  H. Loe,et al.  Evaluating periodontal status of US employed adults. , 1990, Journal of the American Dental Association.

[20]  Gary D Slade,et al.  Relationship between periodontal disease and C-reactive protein among adults in the Atherosclerosis Risk in Communities study. , 2003, Archives of internal medicine.

[21]  C. Stefanadis,et al.  Inflammatory and thrombotic mechanisms in coronary atherosclerosis , 2003, Heart.

[22]  S. Bakker,et al.  A pilot study into measurements of markers of atherosclerosis in periodontitis. , 2005, Journal of periodontology.

[23]  J. Lessem,et al.  Periodontal infections cause changes in traditional and novel cardiovascular risk factors: results from a randomized controlled clinical trial. , 2006, American heart journal.

[24]  M. Tonetti,et al.  Periodontitis and Systemic Inflammation: Control of the Local Infection is Associated with a Reduction in Serum Inflammatory Markers , 2004, Journal of dental research.

[25]  J. Ebersole,et al.  Acute-phase reactants in infections and inflammatory diseases. , 2000, Periodontology 2000.

[26]  A. Algra,et al.  Novel risk factors for peripheral arterial disease in young women. , 2002, The American journal of medicine.

[27]  Nancy R Cook,et al.  Comparison of C-reactive protein and low-density lipoprotein cholesterol levels in the prediction of first cardiovascular events. , 2002, The New England journal of medicine.

[28]  P. Vallance,et al.  Periodontal therapy: a novel non-drug-induced experimental model to study human inflammation. , 2004, Journal of periodontal research.

[29]  A. Gustafsson,et al.  Risk factors for cardiovascular disease in patients with periodontitis. , 2003, European heart journal.

[30]  A. Gustafsson,et al.  Constitutionally hyperreactive neutrophils in periodontitis. , 2003, Journal of periodontology.

[31]  J. Pankow,et al.  Acute-phase Inflammatory Response to Periodontal Disease in the US Population , 2000, Journal of dental research.

[32]  P. Papapanou,et al.  Serum antibodies to periodontal pathogens and markers of systemic inflammation. , 2005, Journal of clinical periodontology.

[33]  J. Beck,et al.  Relationships among clinical measures of periodontal disease and their associations with systemic markers. , 2002, Annals of periodontology.

[34]  Dianxu Ren,et al.  Systemic Inflammatory Markers, Periodontal Diseases, and Periodontal Infections in an Elderly Population , 2005, Journal of the American Geriatrics Society.

[35]  P. Ridker,et al.  High sensitivity C-reactive protein for predicting cardiovascular disease: an inflammatory hypothesis. , 2001, European heart journal.

[36]  Victor M Montori,et al.  Conducting systematic reviews of diagnostic studies: didactic guidelines , 2002, BMC medical research methodology.

[37]  B. Åsman,et al.  IL-8 and TNF-α from peripheral neutrophils and acute-phase proteins in periodontitis: Effect of cigarette smoking: a pilot study , 2002 .

[38]  W. Ketterl [Periodontal diseases]. , 1971, Der Zahnarzt; Colloquium med. dent.

[39]  M. Steffen,et al.  Periodontitis in humans and non-human primates: oral-systemic linkage inducing acute phase proteins. , 2002, Annals of periodontology.

[40]  R Peto,et al.  Association of fibrinogen, C-reactive protein, albumin, or leukocyte count with coronary heart disease: meta-analyses of prospective studies. , 1998, JAMA.

[41]  G. Tofler,et al.  Full-mouth Tooth Extraction Lowers Systemic Inflammatory and Thrombotic Markers of Cardiovascular Risk , 2006, Journal of dental research.

[42]  B. Uretsky,et al.  Covered stent septal ablation for hypertrophic obstruction cardiomyopathy. , 2004, Circulation.

[43]  M. Steffen,et al.  Systemic acute‐phase reactants, C‐reactive protein and haptoglobin, in adult periodontitis , 1997, Clinical and experimental immunology.

[44]  M. Tonetti,et al.  Periodontal disease and C-reactive protein-associated cardiovascular risk. , 2004, Journal of periodontal research.

[45]  G. Taylor,et al.  Prevalence and Trends in Periodontitis in the USA: from the NHANES III to the NHANES, 1988 to 2000 , 2005 .

[46]  M. Ide,et al.  The short-term effects of treatment of chronic periodontitis on circulating levels of endotoxin, C-reactive protein, tumor necrosis factor-alpha, and interleukin-6. , 2004, Journal of periodontology.

[47]  E. Ioannidou,et al.  Elevated serum interleukin-6 (IL-6) in solid-organ transplant recipients is positively associated with tissue destruction and IL-6 gene expression in the periodontium. , 2006, Journal of periodontology.

[48]  G. Taylor,et al.  Prevalence and trends in periodontitis in the USA: the [corrected] NHANES, 1988 to 2000. , 2005, Journal of dental research.

[49]  A. Gustafsson,et al.  Effect of periodontitis and smoking on blood leukocytes and acute-phase proteins. , 1999, Journal of periodontology.

[50]  J. Beck,et al.  The effects of periodontal therapy on vascular endothelial function: a pilot trial. , 2006, American heart journal.

[51]  M. McCarty Interleukin-6 as a central mediator of cardiovascular risk associated with chronic inflammation, smoking, diabetes, and visceral obesity: down-regulation with essential fatty acids, ethanol and pentoxifylline. , 1999, Medical hypotheses.

[52]  R. Genco,et al.  Systemic Inflammation in Cardiovascular and Periodontal Disease: Comparative Study , 2002, Clinical and Vaccine Immunology.

[53]  M. Trevisan,et al.  Examination of the relation between periodontal health status and cardiovascular risk factors: serum total and high density lipoprotein cholesterol, C-reactive protein, and plasma fibrinogen. , 2000, American journal of epidemiology.

[54]  F. Hoek,et al.  Elevation of systemic markers related to cardiovascular diseases in the peripheral blood of periodontitis patients. , 2000, Journal of periodontology.

[55]  W. Borgnakke,et al.  Prospective evaluation of the systemic inflammatory marker C-reactive protein in patients with end-stage periodontitis getting teeth replaced with dental implants: a pilot investigation. , 2004, Clinical oral implants research.

[56]  Ryan T Demmer,et al.  Periodontal Microbiota and Carotid Intima-Media Thickness: The Oral Infections and Vascular Disease Epidemiology Study (INVEST) , 2005, Circulation.

[57]  Y. Izumi,et al.  Associations of periodontal status with general health conditions and serum antibody titers for Porphyromonas gingivalis and Actinobacillus actinomycetemcomitans. , 2003, Journal of periodontology.

[58]  Y. Shimazaki,et al.  Association between alveolar bone loss and elevated serum C-reactive protein in Japanese men. , 2003, The Journal of Periodontology.

[59]  B Littenberg,et al.  A Meta-analytic Method for Summarizing Diagnostic Test Performances , 1993, Medical decision making : an international journal of the Society for Medical Decision Making.

[60]  D. Zeng,et al.  Early-life and adult socioeconomic status and inflammatory risk markers in adulthood , 2007, European Journal of Epidemiology.

[61]  M. Trevisan,et al.  Periodontal infections contribute to elevated systemic C-reactive protein level. , 2001, Journal of periodontology.

[62]  C. Stanford,et al.  Periodontal disease and atherosclerosis: from dental to arterial plaque. , 2003, Arteriosclerosis, thrombosis, and vascular biology.

[63]  Nader Rifai,et al.  Blood Pressure, C-Reactive Protein, and Risk of Future Cardiovascular Events , 2003, Circulation.

[64]  B. Loos Systemic Markers of Inflammation in Periodontitis. , 2005, Journal of periodontology.

[65]  R. Tilvis,et al.  Oral health status, C-reactive protein and mortality--a 10 year follow-up study. , 2003, Gerodontology.

[66]  H. Florez,et al.  C-reactive protein is elevated in obese patients with the metabolic syndrome. , 2006, Diabetes research and clinical practice.

[67]  P. Ridker,et al.  Inflammatory bio‐markers and cardiovascular risk prediction , 2002, Journal of internal medicine.

[68]  B. Åsman,et al.  IL-8 and TNF-alpha from peripheral neutrophils and acute-phase proteins in periodontitis. , 2002, Journal of clinical periodontology.

[69]  K. Stoltze,et al.  Periodontal and hematological characteristics associated with aggressive periodontitis, juvenile idiopathic arthritis, and rheumatoid arthritis. , 2006, Journal of periodontology.

[70]  S. Socransky,et al.  Microbial complexes in subgingival plaque. , 1998, Journal of clinical periodontology.

[71]  S. Thompson,et al.  Quantifying heterogeneity in a meta‐analysis , 2002, Statistics in medicine.

[72]  I. Shklair,et al.  C-Reactive protein and periodontal disease. , 1968, Journal of periodontology.

[73]  Francesco D'Aiuto,et al.  Treatment of periodontitis and endothelial function. , 2007, The New England journal of medicine.

[74]  V. Legrand,et al.  Systemic release of endotoxins induced by gentle mastication: association with periodontitis severity. , 2002, Journal of periodontology.

[75]  D. Kinane,et al.  Bacteraemia following periodontal procedures , 2005, Journal of clinical periodontology.

[76]  Ose,et al.  Comparison of C-reactive protein and low-density lipoprotein cholesterol levels in the prediction of first cardiovascular events* , 2002 .

[77]  H. Greenwell Periodontitis as a risk factor for cardiovascular disease. , 2000, The journal of contemporary dental practice.

[78]  P. Söder,et al.  Early Carotid Atherosclerosis in Subjects With Periodontal Diseases , 2005, Stroke.

[79]  François Mach,et al.  Inflammation and Atherosclerosis , 2004, Herz.

[80]  P. Ridker,et al.  C-reactive protein: a surrogate risk marker or mediator of atherothrombosis? , 2003, American journal of physiology. Regulatory, integrative and comparative physiology.

[81]  M. Tonetti,et al.  Periodontal therapy: a novel acute inflammatory model , 2005, Inflammation Research.

[82]  E. Rimm,et al.  Periodontal Disease and Biomarkers Related to Cardiovascular Disease , 2004, Journal of dental research.

[83]  S. Bakker,et al.  Periodontitis is characterized by elevated PAI-1 activity. , 2007, Journal of clinical periodontology.

[84]  M. Brodmann,et al.  Periodontal treatment improves endothelial dysfunction in patients with severe periodontitis. , 2005, American heart journal.

[85]  S. Socransky,et al.  Relationship of destructive periodontal disease to the acute-phase response. , 2003, Journal of periodontology.

[86]  A. Gustafsson,et al.  Hyper-reactive peripheral neutrophils in adult periodontitis: generation of chemiluminescence and intracellular hydrogen peroxide after in vitro priming and FcgammaR-stimulation. , 1998, Journal of clinical periodontology.

[87]  M. Kilian,et al.  Incidence of bacteremia after chewing, tooth brushing and scaling in individuals with periodontal inflammation. , 2006, Journal of clinical periodontology.

[88]  P. Ridker,et al.  Established and emerging plasma biomarkers in the prediction of first atherothrombotic events. , 2004, Circulation.

[89]  M. Nieminen,et al.  Effect of treating periodontitis on C-reactive protein levels: a pilot study , 2002, BMC infectious diseases.