Endotoxemia, immune response to periodontal pathogens, and systemic inflammation associate with incident cardiovascular disease events.
OBJECTIVE
In periodontitis, overgrowth of gram-negative bacteria may cause endotoxemia and systemic inflammation leading to cardiovascular diseases (CVD). We investigated in a prospective study the associations of serum endotoxin, antibodies to periodontal pathogens, and inflammation markers with the risk of incident CVD.


RESULTS
The FINRISK 1992 cohort of 6051 individuals was followed up for 10 years. We examined 185 incident CVD events and a control cohort of 320 individuals using a prospective case-cohort design. High antibody response to periodontal pathogens independently predicted incident CVD events with hazard ratios (HR, quartile 4 versus quartiles 1 to 3, 95% CI) of 1.87 (1.13 to 3.08). The subjects with a high antibody response and high CRP or interleukin (IL)-6 had multivariate-adjusted HRs of 3.01 (1.27 to 7.09) and 3.11 (1.42 to 6.83) compared with low-responders, respectively. The corresponding HRs for high endotoxin concentration were 1.82 (1.22 to 2.73, alone), 3.92 (1.99 to 7.74, with CRP), 3.54 (1.78 to 7.03, with IL-6), and 2.26 (1.13 to 4.52, with tumor necrosis factor (TNF)-alpha) after adjusting for age and gender. These associations were abolished after adjusting for serum lipids. High endotoxin/HDL ratio, however, had a multivariate-adjusted HR of 1.92 (1.19 to 3.08) for CVD events.


CONCLUSIONS
Our results suggest that the exposure to periodontal pathogens or endotoxin induces systemic inflammation leading to increased risk for CVD.
Pussinen
Pirkko J
PJ
Institute of Dentistry, University of Helsinki, Haartmaninkatu 8, PO Box 63, FI-00014 Helsinki, Finland. pirkko.pussinen@helsinki.fi
Tuomisto
Karolina
K
Jousilahti
Pekka
P
Havulinna
Aki S
AS
Sundvall
Jouko
J
Salomaa
Veikko
V
D000328:Adult; D016976:Aggregatibacter actinomycetemcomitans / Q000276:immunology; D000907:Antibodies, Bacterial / Q000097:blood*; D015415:Biomarkers / Q000097:blood*; D002097:C-Reactive Protein / Q000378:metabolism; D002318:Cardiovascular Diseases / Q000097:blood / Q000453:epidemiology / Q000276:immunology / Q000382:microbiology*; D016022:Case-Control Studies; D019446:Endotoxemia / Q000097:blood / Q000150:complications* / Q000453:epidemiology / Q000276:immunology / Q000382:microbiology; D004731:Endotoxins / Q000097:blood*; D005260:Female; D005387:Finland / Q000453:epidemiology; D005500:Follow-Up Studies; D006090:Gram-Negative Bacteria / Q000276:immunology* / Q000472:pathogenicity; D006801:Humans; D015994:Incidence; D015850:Interleukin-6 / Q000097:blood; D008297:Male; D008875:Middle Aged; D010518:Periodontitis / Q000097:blood / Q000150:complications* / Q000453:epidemiology / Q000276:immunology / Q000382:microbiology; D016966:Porphyromonas gingivalis / Q000276:immunology; D011237:Predictive Value of Tests; D016016:Proportional Hazards Models; D011446:Prospective Studies; D012042:Registries; D018570:Risk Assessment; D012307:Risk Factors; D018805:Sepsis / Q000097:blood / Q000150:complications* / Q000453:epidemiology / Q000276:immunology / Q000382:microbiology; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000097:blood
D000907:Antibodies, Bacterial; D015415:Biomarkers; D004731:Endotoxins; C508600:IL6 protein, human; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; D002097:C-Reactive Protein