Sirkka Asikainen

Role of Infection as a Risk Factor for Atherosclerosis, Myocardial Infarction, and Stroke

An increasing body of evidence has linked infections to atherosclerosis and thrombosis. Herpesviruses cause atherosclerosis in experimental animals. Herpesviruses can also be detected in atherosclerotic lesions in humans. Cytomegalovirus may play a role in arteriosclerosis in transplanted hearts, and this virus, together with tumor suppressor protein p53, can be found in restenosis lesions following angioplasty. Chlamydia pneumoniae and dental infections are associated with coronary heart disease in cross-sectional and longitudinal studies, and preceding respiratory infections are associated with ischemic stroke. Infections may favor formation of atherosclerosis and thrombosis by elevation of blood levels of fibrinogen, leukocytes, clotting factor, and cytokines and by alteration of the metabolism and functions of endothelial cells and monocyte macrophages. Low-grade infections may also be one of the causes of the inflammatory reaction observed in atherosclerotic lesions and acute ischemic symptoms, reflected in elevated levels of C-reactive protein. These observations warrant further studies in this field.

Antibodies to Periodontal Pathogens Are Associated With Coronary Heart Disease

Objective—We analyzed the association of coronary heart disease (CHD) and serology of periodontitis in a random sample (n=1163) of men (aged 45 to 74 years) by determining serum IgG-antibodies to Actinobacillus actinomycetemcomitans and Porphyromonas gingivalis. Methods and Results—CHD (n=159) was more prevalent among edentulous than dentate subjects (19.8% and 12.1%, P =0.003). In the dentate population, CHD was more common among subjects seropositive for P. gingivalis compared with those seronegative (14.0% and 9.7%, P =0.029). Accordingly, CHD was more prevalent in subjects with a high combined antibody response than those with a low response (17.4% and 11.1%, P =0.026). When adjusted for age and several CHD risk factors, the subjects with a high combined antibody response had an odds ratio of 1.5 (95% CI, 0.95 to 2.50, P =0.077) for prevalent CHD. In a linear regression model, the combined antibody response was directly associated with prevalent CHD (P =0.046) and inversely with serum HDL cholesterol concentration (P =0.050). Conclusions—In conclusion, edentulousness and serum antibodies to major periodontal pathogens were associated with CHD. This suggests that periodontal infection or response of the host against the infection may play a role in the pathogenesis of CHD.

Antibodies to periodontal pathogens and stroke risk.

Background and Purpose— The association between cerebrovascular events and periodontitis has been found in few studies based on clinical periodontal examinations. However, evidence on the association between periodontal pathogens and stroke is lacking. Therefore, the aim of the study was to investigate whether elevated levels of serum antibodies to major periodontal pathogens predict stroke in a case–control study. Methods— The study population comprised 6950 subjects (aged 45 to 64 years) who participated in the Mobile Clinic Health Survey in 1973 to 1976 in Finland. During a follow-up of 13 years, a total of 173 subjects had a stroke. From these, 64 subjects had already experienced a stroke or had signs of coronary heart disease (CHD) at baseline, whereas 109 subjects were apparently healthy. Two controls per case were matched for age, gender, municipality, and disease status. Serum IgG and IgA class antibody levels to the periodontal pathogens, Actinobacillus actinomycetemcomitans and Porphyromonas gingivalis, were determined by multiserotype enzyme-linked immunosorbent assay. Results— The cases identified during the follow-up that were free of stroke or CHD at baseline were more often IgA-seropositive for A. actinomycetemcomitans than were their controls, 41.3% versus 29.3%. Compared with the seronegative, the seropositive subjects had a multivariate odds ratio of 1.6 (95% CI, 1.0 to 2.6) for stroke. The patients with a history of stroke or CHD at baseline were more often IgA-seropositive for P. gingivalis than were their controls, 79.7% versus 70.2%. When compared with the seronegative, the seropositive subjects had an odds ratio of 2.6 (1.0 to 7.0) for secondary stroke. Conclusions— The present prospective study provides serological evidence that an infection caused by major periodontal pathogens is associated with future stroke.

Effect of treating periodontitis on C-reactive protein levels: a pilot study

BackgroundPeriodontitis is associated with elevated levels of C-reactive protein and fibrinogen and it may be a coronary heart disease risk factor. We wanted to study if treatment of periodontitis can decrease the levels of these inflammatory markers.MethodsC-reactive protein and fibrinogen levels were measured in 35 patients (21 M, 14 F, mean age 50 years) with adult periodontitis, before and after treatment.ResultsThe median baseline C-reactive protein level in the patients was 1.05 mg/l and it decreased to 0.7 mg/l (p = 0.05) after periodontal treatment. Of the 30 patients who could be included in the analyses, 24 patients had a baseline level below 2 mg/l (the 95th percentile limit in Finland); 6 patients had levels higher than this. Elevation of the baseline C-reactive protein level or the magnitude of its decrease were not associated with severe form of periodontitis. The decrease in C-reactive protein levels was at least 50 % in 4/6 of those with elevated baseline levels, as compared with 3/24 of the rest of the patients (p = 0.016). No corresponding effect was observed in fibrinogen levels.ConclusionsPeriodontitis seems to increase C-reactive protein only in some individuals, presumably the ones reacting to it with a systemic inflammatory reaction. Periodontal treatment decreases C-reactive protein levels in these individuals and it may thus decrease their risk of coronary heart disease.

Oral colonization by more than one clonal type of mutans streptococcus in children with nursing-bottle dental caries

By ribotyping the genetic diversity of mutans streptococci in six 1.5-3-yr-old children with nursing-bottle caries and in six caries-free, age-matched children and in their mothers was examined. The proportion of mutans streptococci in the dental plaque of the children and their levels in the saliva of the mothers were also examined. For ribotyping, chromosomal DNA of isolates obtained from the plaque of the children (3-12 isolates per child) and from the saliva of the mothers (4-13 isolates per mother) was digested with restriction endonuclease HindIII. The DNA fragments were hybridized to the plasmid pKK3535 which contains the rRNA operon of the Escherichia coli chromosome. The results showed that children with nursing-bottle caries exposed to frequent consumption of sucrose had a high proportion of mutans streptococci in plaque and four of them were colonized with more than one ribotype, whereas caries-free children had a low proportion of mutans streptococci in plaque and only one of them harboured more than one ribotype. Mothers of children with nursing bottle caries had similar levels and numbers of ribotypes of mutans streptococci in saliva as the mothers of the caries-free children. In both child groups, mothers were probably the main source of infection with mutans streptococci. Thus, children with nursing-bottle caries were not only heavily infected with mutans streptococci but also often colonized with more than one clonal type. In the childs acquisition of such clones, frequent sugar consumption may have an important role.

High serum antibody levels to Porphyromonas gingivalis predict myocardial infarction

Background An association between coronary heart disease (CHD) and clinically diagnosed periodontitis has been found in several epidemiological studies. However, seroepidemiologic evidence based on prospective data on this association is totally lacking. Design The aim of the study was to investigate serum antibodies to major periodontal pathogens for their prediction of myocardial infarction (MI) in men free of CHD at baseline. Methods Cases and controls were ascertained from a random population sample of 4255 men aged 30 to 59 years at baseline. The study cases included 63 men with nonfatal MI or coronary death within the follow-up time of 10 years. Age-matched control subjects (n = 63) were randomly chosen from the same cohort. Serum antibody levels to two major periodontopathogenic bacteria, Actinobacillus actinomycetemcomitans and Porphyromonas gingivalis, were determined. Results There was no significant association between the risk for MI and IgG- or IgA-class antibody levels to A. actinomycetemcomitans or IgG-class antibody levels to P. gingivalis. However, a high P. gingivalis IgA-class antibody level predicted MI independently of classical cardiovascular risk factors. The risk for MI increased by increasing quartiles of antibody levels (P for the trend 0.021). Compared with the first quartile, the multivariate odds ratios of MI in the second, third and fourth quartiles were 2.47 (95% CI 0.75-8.11), 3.30 (1.03-10.58) and 3.99 (1.22-13.10), respectively. Conclusion The study provides serological evidence that an infection caused by the periodontal pathogen, P. gingivalis, increases the risk for MI.

Severe Periodontitis Enhances Macrophage Activation via Increased Serum Lipopolysaccharide

Objective—In periodontitis, overgrowth of Gram-negative bacteria and access of lipopolysaccharide (LPS) to circulation may activate macrophages leading to foam cell formation. We investigated whether periodontal treatment affects proatherogenic properties of low-density lipoprotein (LDL) and, thus, macrophage activation. Methods and Results—LDL was isolated and characterized before and after treatment from 30 systemically healthy patients with periodontitis. Production of cytokines and LDL cholesteryl ester (LDL-CE) uptake by macrophages (RAW 264.7) was determined. Baseline periodontal variables correlated positively with serum LPS and C-reactive protein concentrations, as well as macrophage cytokine production and LDL-CE uptake. LPS concentration correlated positively with serum concentration of oxidized LDL and cytokine production. Higher cytokine production and LDL-CE uptake were induced by LDL isolated from patients with elevated number of affected teeth before treatment. Patients with serum LPS concentrations above the median (0.87 ng/mL) at baseline had higher serum high-density lipoprotein (HDL) cholesterol (baseline versus after treatment, 1.30±0.19 versus 1.48±0.28 mmol/L; P=0.002) and HDL/LDL ratio (0.31±0.01 versus 0.34±0.10; P=0.048), but lower serum LPS concentration (1.70±0.49 versus 0.98±0.50 ng/mL; P=0.004) and autoantibodies to &bgr;2-glycoprotein I (0.11±0.06 versus 0.09±0.04 ELISA units; P=0.022) after treatment. Conclusions—Our results suggest that in systemically healthy patients, the infected/inflamed area in periodontitis is associated with macrophage activation via increased serum LPS concentration.

Establishment of Oral Anaerobes during the First Year of Life

Anaerobic species constitute a significant part of the bacterial community of the mouth. Although the time and species involved in the primary colonization of infants are of great importance by forming the basis for further colonization, the development of the oral anaerobic microflora with age is still inadequately understood. In the present study, time and succession of colonization of oral anaerobes were longitudinally examined in 44 healthy Caucasian infants at 2, 6, and 12 months of age. Unstimulated saliva samples were quantitatively cultured on non-selective Brucella blood agar and several selective media for the isolation of anaerobic micro-organisms. The most frequent anaerobic finding in two-month-old infants was Veillonella spp. The Prevotella melaninogenica group also represented early colonizing species, and the frequency increased remarkably during the first year of life, whereas the Prevotella intermedia group organisms seemed to be late colonizers. Fusobacterium nucleatum, non-pigmented Pr...

Multiserotype Enzyme-Linked Immunosorbent Assay as a Diagnostic Aid for Periodontitis in Large-Scale Studies

ABSTRACT Periodontitis is a common chronic oral infection caused by gram-negative bacteria, including Actinobacillus actinomycetemcomitans and Porphyromonas gingivalis. Periodontitis evokes inflammatory host response locally in the periodontium but also systemically. The systemic humoral antibody response against oral pathogens can conveniently be measured by an immunoassay. The aim of the study was to measure serum immunoglobulin G class antibodies against A. actinomycetemcomitans and P. gingivalis by an enzyme-linked immunosorbent assay (ELISA) in which mixtures of several serotypes of the pathogens were used as antigens to avoid biasing of the results in favor of a particular strain. For A. actinomycetemcomitans the antigen consisted of six strains representing serotypes a, b, c, d, and e and one nonserotypeable strain. In the P. gingivalis ELISA, antigens representing serotypes a, b, and c were used. Serum samples from 90 subjects, including 35 samples from patients with diagnosed periodontitis, 10 samples from periodontally healthy controls, and 45 samples from randomly selected apparently healthy volunteers (referred to as “healthy subjects”), were tested. For both pathogens the antibody levels (means ± standard deviations) of the patients—expressed as area under the dilution curve—were significantly higher than those for healthy controls or healthy subjects, with values for A. actinomycetemcomitans and P. gingivalis, respectively, as follows: patients, 22.60 ± 9.94 mm2 and 26.72 ± 11.13 mm2; healthy controls, 9.99 ± 3.92 mm2 and 6.90 ± 3.38 mm2; and healthy subjects, 16.85 ± 6.67 mm2 and 8.51 ± 4.23 mm2. The serotype mixture ELISA is suitable for measuring antibodies against periodontal pathogens in large epidemiological studies in order to evaluate the role of periodontitis as a risk factor for other diseases.

Salivary Levels of Suspected Periodontal Pathogens in Relation to Periodontal Status and Treatment

The primary ecological niche for suspected periodontal pathogens seems to be the subgingival area, even though periodontal pathogens are also frequently recovered from saliva. The interrelationship of different periodontal conditions and the salivary levels of suspected periodontal pathogens is not known. In the present study, salivary levels of Actinobacillus actinomycetemcomitans, Porphyromonas gingivalis, Prevotella intermedia, Campylobacter rectus, and Peptostreptococcus micros were determined by bacterial culture and related to clinical periodontal status in 40 subjects with either advanced, moderate, or initial/no periodontitis. Culture-positive subjects harbored the 5 bacterial species in mean numbers ranging from 2 x 105 to 6 x 107 colony-forming units (CFU)/mL saliva. A. actinomycetemcomitans was found in none and P. gingivalis in one of the subjects with initial periodontitis, whereas both species were found in 33% and 44%, respectively, of the subjects with moderate periodontitis and in 60% and 40%, respectively, of the subjects with advanced periodontitis. The mean numbers of CFU/mL of P. intermedia, C. rectus and P. micros were significantly higher in subjects with advanced periodontitis than in subjects with initial/no periodontitis. Ten patients with advanced periodontitis were treated mechanically and with adjunctive systemic metronidazole, and were re-examined 1 and 6 months after treatment. Periodontal treatment eradicated or significantly reduced the levels of salivary periodontal pathogens for half a year, whereas in untreated subjects, the levels and the detection frequencies generally remained fairly stable. In conclusion, the results showed that the salivary levels of periodontal pathogens reflect the periodontal status of the patient.