Prospective study of pathogen burden and risk of myocardial infarction or death

Background-We previously demonstrated that the risk of coronary artery dise ase (CAD) increased in relation to the number of pathogens (the "pathogen b urden") in a cross-sectional study. In the present prospective study with a different patient cohort, we evaluated the effect of pathogen burden on th e risk of myocardial infarction (MI) or death among CAD patients. Methods and Results-IgG antibodies to cytomegalovirus (CMV), hepatitis A vi rus (HAV), herpes simplex virus type 1 (HSVI), HSV type 2 (HSV2), Chlamydia pneumoniae and Helicobacter pylori, and C-reactive protein (CRP) levels we re tested in baseline blood samples from 890 patients who had significant C AD on angiography. The mean follow-up period was 3 years. The baseline prev alence of antibodies directed against CMV, HAV, HSV1, or HSV2, but not C pn eumoniae and H pylori, was significantly higher among patients who subseque ntly developed MI or death than among control subjects. After adjustment fo r traditional risk factors, number of diseased vessels, and clinical presen tation, relative hazards (95% confidence limits) for MI or death were 2.0 ( 1.4 to 3.2) for CMV, 1.6 (1.1 to 2.3) for HAV, and 1.5 (1.0 to 2.2) for HSV 2. Increasing pathogen burden was significantly associated with increasing risk of MI or death in a dose-response fashion. Adjusted relative hazards o f MI or death associated with pathogen burden were significant among indivi duals with low or high CRP levels. Conclusions-The results suggest that infection plays an important role in i ncident MI or death and that the risk posed by infection is independently r elated to the pathogen burden.