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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2007;27:1433.)
© 2007 American Heart Association, Inc.

Atherosclerosis and Lipoproteins

Endotoxemia, Immune Response to Periodontal Pathogens, and Systemic Inflammation Associate With Incident Cardiovascular Disease Events

Pirkko J. Pussinen; Karolina Tuomisto; Pekka Jousilahti; Aki S. Havulinna; Jouko Sundvall; Veikko Salomaa

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 Capacity (J.S.), National Public Health Institute, Helsinki, Finland.

Correspondence to Pirkko Pussinen, Institute of Dentistry, University of Helsinki, Haartmaninkatu 8, PO Box 63, FI-00014 Helsinki, Finland. 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.

We investigated the connection between serum inflammation markers, antibody levels to major periodontal pathogens, endotoxin concentration, and CVD events in a prospective case–cohort study. Our results suggest that endotoxemia or systemic immune response to periodontal pathogens together with high concentrations of inflammation markers indicate a high risk of incident CVD.

Key Words: infection • inflammation • lipopolysaccharide (LPS), serology • atherosclerosis

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