Interpretation:

Among patients with preexisting or at high risk for CV disease, exposure to CMV but not to C pneumoniae, H pylori, or HAV was associated with a small but significant excess risk of MI, stroke, or CV death by 4.5 years. Likewise, total pathogen score based on these 4 infections predicted an increased risk of CV events.

Previous retrospective and case-control studies have identified an association between coronary and cerebrovascular disease with prior exposure to the bacteria C pneumoniae and helicobacter pylori, and with the viruses CMV, herpes simplex virus types 1 and 2, enteroviruses, and hepatitis A. The HOPE substudy is one of the first prospective studies to examine such relationships and, notably only the virus CMV was associated with increased CV death, MI or stroke. However, the study population in the HOPE trial was comprised of patients with preexisting or at high risk for CV disease. As such, the present study cannot address the association of these pathogens in first CV events.

Additionally, it is unknown if the infection is ongoing or resolved. Several studies have shown a stronger relationship between CV events and the sum of multiple infectious exposures (i.e., a total pathogen score), rather than individual infection exposures. The earlier studies showed that the increased risk was primarily due to seropositivity of the viral pathogens included in the score. Similar results occurred in the HOPE substudy analysis, with a total pathogen score of 4 associated with a higher risk of CV death, MI or stroke compared with a pathogen score of 0 or 1, largely driven by the CMV status. The use of other markers more specifically associated with active infection may prove to be more strongly associated with atherosclerosis progression and CV risk.