Susanna Paju

Dental infections and cardiovascular diseases : A review

Accumulating evidence suggests that chronic infections, such as periodontitis, are associated with increased risk for cardiovascular diseases (CVD). The mechanisms behind the association are not known. Like herpes viruses and Chlamydia pneumoniae, periodontal pathogens cause atherosclerosis in experimental animals and have been found in human atherosclerotic lesions. Higher concentrations of total and low density lipoprotein (LDL) cholesterol and triglycerides and lower concentrations of high density lipoprotein (HDL) cholesterol have been observed in individuals with periodontitis before periodontal treatment. Periodontitis also induces a peripheral inflammatory and immune response, reflected in elevated concentrations of C-reactive protein (CRP) and IgA-class antibodies to periodontal pathogens. The prevalence of CVD seems to be highest in those individuals in whom periodontitis coexists with elevated CRP levels. This may indicate that periodontitis is a CVD risk factor in individuals who react to the infection with a systemic inflammatory and immune response. This may be due to genetic reasons and may also apply to other chronic low-grade infections.

Detection and quantification of five major periodontal pathogens by single copy gene-based real-time PCR

Periodontitis is a common chronic multibacterial infection in the tooth-supporting tissues. It has been shown that periodontitis patients carry higher number of disease-associated bacteria than healthy ones. The aim of this study was to generate a novel, single copy gene-based quantitative real-time PCR (qPCR) assay for five major periodontal pathogens — Aggregatibacter actinomycetemcomitans, Porphyromonas gingivalis, Prevotella intermedia, Treponema denticola, and Tannerella forsythia. The primer/probe sets were designed for conservative lipopolysaccharide-coding gene regions. They proved to be sensitive and able to detect strains representing different serotypes of the target bacteria. The specificity of designed primers was tested using 49 selected bacterial species and no false positive or negative results were observed. We validated the assay with a case-control population, including 165 saliva samples, and proved the diagnostic accuracy by Receiver Operating Characteristic (ROC) curves. All quantified pathogens alone were able to distinguish significantly between the subjects with and without periodontitis, and provided areas under the ROC curve larger than 0.5. The total pathogen burden comprising all five species associated with periodontitis with an area of 0.821 (95% CI, 0.758—0.885, P50.001). Our prominently sensitive and specific assay may have major importance in the diagnosis, prevention, and treatment of periodontitis.

Periodontal pathogen carriage, rather than periodontitis, determines the serum antibody levels

AIMnWe investigated in a nationally representative sample, how periodontitis modifies the association between the carriage of periodontal pathogens and serology.nnnMATERIALS AND METHODSnThe population comprised 1586 dentate subjects who participated in an interview, clinical and radiological oral health examination, and saliva collection. Serum immunoglobulin A (IgA)- and IgG-class antibody levels against Aggregatibacter actinomycetemcomitans and Porphyromonas gingivalis and their salivary occurrence were determined in the whole population. The quantity of the pathogens was measured in a subpopulation.nnnRESULTSnIn the univariate analyses, the corresponding antibody levels were higher in the pathogen carriers compared with the non-carriers, and clearly higher in the carriers with periodontal pockets compared with the carriers without. In the multi-variate analyses, however, all antibody levels associated strongly with age (p<0.001) and the carriage of the corresponding pathogen (p<0.001), but only weakly with the presence or number of teeth with periodontal pockets. In the subpopulation, the antibody levels and the numbers of corresponding bacteria in saliva had a positive association, which was not affected by the disease.nnnCONCLUSIONSnThe carriage of A. actinomycetemcomitans and P. gingivalis is the strongest determinant of the systemic antibody response to these pathogens, and the extent of periodontitis has at most a modest modifying effect.

The Association of Serum Neutrophil Markers and Acute Coronary Syndrome

An association exists between chronic infection‐induced inflammation, such as periodontitis, and acute coronary syndrome (ACS). We studied the association of serum neutrophil markers, myeloperoxidase (MPO), matrix metalloproteinase (MMP)‐8, tissue inhibitor of metalloproteinase (TIMP)‐1 concentrations and MMP‐8/TIMP‐1 ratio, with the risk of recurrent ACS. Radiographic periodontal status was recorded from 141 patients with acute non‐Q‐wave infarction or unstable angina pectoris, who participated in a double‐blind, placebo‐controlled study with clarithromycin for 3u2003months. Serum samples were collected within arrival to the hospital, at 1u2003week, 3u2003months and 1u2003year. Recurrent ACS events were registered during the 1‐year follow‐up. In the whole population, high serum MPO concentrations at 1u2003week (fourth quartile versus quartiles 1–3) were associated with the risk of recurrent ACS with a relative risk (RR) of 2.52 (95% CI, 1.277–4.980; Pu2003=u20030.008). In patients without periodontal disease, high MPO concentration at 1u2003week and 1u2003year predicted recurrent ACS with RRs of 3.54 (1.600–7.831; Pu2003=u20030.002) and 2.87 (1.171–7.038; Pu2003=u20030.021), respectively. In the placebo group, but not in the clarithromycin group, high serum MMP‐8/TIMP‐1 ratio at 1u2003week predicted recurrent ACS with an RR of 3.23 (1.295–8.063; Pu2003=u20030.012). Our results suggest that high serum neutrophil markers reflect increased risk of recurrent ACS, especially in patients without periodontal disease and not receiving antimicrobial medication.

Tracking of plasma antibodies against Aggregatibacter actinomycetemcomitans and Porphyromonas gingivalis during 15 years

Abstract Background: Plasma antibody measurements of antibody levels to periodontal pathogens may be used to support diagnosis, disease activity, classification, and prognosis of periodontitis. Objective: The aim of this study was to investigate the long-term stability of plasma antibody levels against Aggregatibacter actinomycetemcomitans and Porphyromonas gingivalis. Design: Plasma immunoglobulin G (IgG) antibody levels against the pathogens were analyzed annually during 15 years from 21 voluntary subjects, whose periodontal status was not known at the point of selection. The total number of plasma samples was 315. In connection of the last sampling, the clinical and radiographic periodontal status was examined. Pooled bacterial samples from periodontal pockets, as well as salivary samples were collected for A. actinomycetemcomitans and P. gingivalis detection, and antibody determinations, respectively. According to the clinical status, six subjects had periodontitis, whereas 15 did not. Results: Plasma IgG-class antibody levels to periodontal pathogens remained extremely stable during the 15-year period and no significant (p>0.05) intra-individual variations were observed. Retrospectively, the average plasma IgG antibody levels against A. actinomycetemcomitans and P. gingivalis were 1.6–2.3 (p<0.05) and 1.4–1.7 (p<0.05) fold higher in the subjects with periodontitis than those without, respectively, during the whole 15-year tracking. As expected, at the time of the periodontal examination the plasma and salivary IgG antibody levels were associated both with periodontitis and bacterium-positivity. Conclusions: Plasma IgG levels against A. actinomycetemcomitans and P. gingivalis are extremely stable during 15 years both in subjects with and without periodontitis.

Periodontopathogen- and Host-Derived Immune Response in Acute Coronary Syndrome

Owing to molecular mimicry, periodontal pathogen carriage may result in a systemic cross‐reactive immune response with the host. The analyses were performed to investigate if serum antibody levels to human heat shock protein 60 (HSP60) are associated with the antibody levels and salivary carriage of two periodontal pathogens, Aggregatibacter actinomycetemcomitans and Porphyromonas gingivalis, as well as with the dental status in patients with acute coronary syndrome (ACS). ACS patients (nu2003=u2003141) were monitored at baseline when entering to hospital, and after 1u2003week, 3u2003months and 1u2003year. Periodontal status was recorded by dental radiographs, and A. actinomycetemcomitans and P. gingivalis were detected by PCR from saliva at baseline. Serum IgG and IgA antibody levels were determined at all time points. All antibody levels remained quite stable during the follow‐up. Serum IgG‐class antibody levels to A. actinomycetemcomitans and HSP60 had a strong positive correlation with each other at all time points (r∼0.4, Pu2003<u20030.05). Mean serum IgG antibody levels to HSP60 were significantly higher in the A. actinomycetemcomitans IgG‐ and IgA‐seropositive than in the seronegative patients, but did not differ between the pathogen carriers compared to the non‐carriers. HSP60 antibody levels did not differ significantly between the edentulous, non‐periodontitis and periodontitis patients. Despite the observed cross‐reactivity in the systemic IgG‐class antibody response to HSP60 and A. actinomycetemcomitans, the pathogen carriage in saliva or the periodontal status did not affect the HSP60 antibody levels in ACS patients.