Abstract 4069: Endotoxemia, Immune Response to Periodontal Pathogens, and Systemic Inflammation Predict Incident Cardiovascular Disease Events
Background: In periodontitis, overgrowth of Gram-negative bacteria and access of endotoxin to circulation may result in a systemic inflammatory response increasing the risk of cardiovascular diseases (CVD).
Methods and Results: We investigated in a prospective case-cohort study the associations of serum inflammatory markers, antibody levels to major periodontal pathogens, and serum total endotoxin concentration with the risk of incident CVD events. A cohort of 6,051 persons aged 25– 64 years was followed up for ten years, during which 189 incident CVD events (136 coronary and 53 ischemic stroke events) were observed. A stratified random sample (n=320) of the original cohort was used as the comparison group. A weighted Cox proportional hazards regression model, modified to account for the case-cohort sampling design, was used for computing the hazard ratios (HR) and 95% confidence intervals (CI) for the CVD end point. Endotoxin concentration was associated with the risk of incident CVD events when adjusted for age and sex (HR 1.83, 95% CI 1.1–3.1 comparing the fourth quartile with the first quartile), but the association disappeared after adjustment for serum lipids. High IgG-class antibody levels to Actinobacillus actinomycetemcomitans and Porphyromonas gingivalis were associated with CVD events independently of traditional risk factors, whereas the IgA antibodies showed no association. Persons with a high IgG antibody response to periodontal pathogens and a high concentration of C-reactive protein (CRP) had a multivariate adjusted HR of 2.0, (95% CI 1.0–3.8) for an incident CVD event compared to those with a low antibody response and a low CRP.
Conclusions: Our results suggest that endotoxemia and high IgG-class antibody response to periodontal pathogens predict acute CVD events in a prospective setting. In particular, high antibody response combined with high levels of inflammation markers indicated high risk of incident CVD events.