on March 15, 2007
Published online before print March 15, 2007, doi: 10.1161/ATVBAHA.106.138743
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Submitted on July 11, 2006
Accepted on February 15, 2007
Endotoxemia, Immune Response to Periodontal Pathogens, and Systemic Inflammation Associate With Incident Cardiovascular Disease Events
Pirkko J. Pussinen *;
From the Institute of Dentistry (P.J.P.), University of Helsinki, and Department of Oral and Maxillofacial Diseases, Helsinki University Central Hospital; the Department of Epidemiology and Health Promotion (K.T., P.J., A.S.H., V.S.), National Public Health Institute, Helsinki; the School of Public Health (P.J.), University of Tampere; and the Department of Health and Functional Capacit (J.S.), National Public Health Institute, Helsinki, Finland.
* To whom correspondence should be addressed. E-mail: pirkko.pussinen{at}helsinki.fi.
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.
Methods and 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)-
) 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.
Key words: infection • inflammation • lipopolysaccharide (LPS), serology • atherosclerosis
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