Infections, inflammation, and the risk of coronary heart disease.
BACKGROUND
The role of infections and inflammation in the pathophysiology of coronary heart disease is emerging. We studied the independent and joint effects of these 2 components on coronary risk.


METHODS AND RESULTS
We measured baseline levels of C-reactive protein (CRP) and antibodies to adenovirus, enterovirus, cytomegalovirus, and herpes simplex virus as well as to Chlamydia pneumoniae (Cpn) and Helicobacter pylori in 241 subjects who suffered either myocardial infarction or coronary death during the 8.5-year trial in the Helsinki Heart Study, a coronary primary prevention trial. The 241 controls in this nested case-control study were subjects who completed the study without coronary events. Antibody levels to herpes simplex type I (HSV-1) and to Cpn were higher in cases than in controls, whereas the distributions of antibodies to other infectious agents were similar. Mean CRP was higher in cases (4.4 versus 2.0 mg/L; P<0.001), and high CRP increased the risks associated with smoking and with high antimicrobial antibody levels. The odds ratios in subjects with high antibody and high CRP levels were 25.4 (95% CI 2.9-220.3) for HSV-1 and 5.4 (95% CI 2.4-12.4) for Cpn compared with subjects with low antibody levels and low CRP. High antibody levels to either HSV-1 or to Cpn increased the risk independently of the other, and their joint effect was close to additive.


CONCLUSIONS
Two chronic infections, HSV-1 and Cpn, increase the risk of coronary heart disease. The effect is emphasized in subjects with ongoing inflammation, denoted by increased CRP levels.