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

• Published in: Arteriosclerosis, thrombosis, and vascular biology Vol. 27; no. 6; pp. 1433 - 1439
• Main Authors: Pussinen, Pirkko J., Tuomisto, Karolina, Jousilahti, Pekka, Havulinna, Aki S., Sundvall, Jouko, Salomaa, Veikko
• Format: Journal Article
• Language: English
• Published: Philadelphia, PA American Heart Association, Inc 01.06.2007; Hagerstown, MD Lippincott
• Subjects: Adult; Aggregatibacter actinomycetemcomitans - immunology; Antibodies, Bacterial - blood; Atherosclerosis (general aspects, experimental research); Biological and medical sciences; Biomarkers - blood; Blood and lymphatic vessels; C-Reactive Protein - metabolism; Cardiology. Vascular system; Cardiovascular Diseases - blood; Cardiovascular Diseases - epidemiology; Cardiovascular Diseases - immunology; Cardiovascular Diseases - microbiology; Case-Control Studies; Diseases of the peripheral vessels. Diseases of the vena cava. Miscellaneous; Endotoxemia - blood; Endotoxemia - complications; Endotoxemia - epidemiology; Endotoxemia - immunology; Endotoxemia - microbiology; Endotoxins - blood; Female; Finland - epidemiology; Follow-Up Studies; General and cellular metabolism. Vitamins; Gram-Negative Bacteria - immunology; Gram-Negative Bacteria - pathogenicity; Humans; Incidence; Interleukin-6 - blood; Male; Medical sciences; Middle Aged; Neuropharmacology; Periodontitis - blood; Periodontitis - complications; Periodontitis - epidemiology; Periodontitis - immunology; Periodontitis - microbiology; Pharmacology. Drug treatments; Porphyromonas gingivalis - immunology; Predictive Value of Tests; Proportional Hazards Models; Prospective Studies; Psychoanaleptics: cns stimulant, antidepressant agent, nootropic agent, mood stabilizer..., (alzheimer disease); Psychology. Psychoanalysis. Psychiatry; Psychopharmacology; Registries; Risk Assessment; Risk Factors; Sepsis - blood; Sepsis - complications; Sepsis - epidemiology; Sepsis - immunology; Sepsis - microbiology; Time Factors; Tumor Necrosis Factor-alpha - blood; Finland; Vascular disease; Infection; Immune response; Atherosclerosis; Lipopolysaccharide; Cardiovascular disease; lipopolysaccharide (LPS), serology; Inflammation; Serology; Endotoxemia
• ISSN: 1079-5642; 1524-4636; 1524-4636
• DOI: 10.1161/ATVBAHA.106.138743

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)-α) 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.