Total Pathogen Burden As An Aggregate Serological Risk Factor

Given the modest and variable predictive value of most tested pathogen candidates, Epstein et al. (94) proposed the sum of relevant infectious exposures, expressed as a total pathogen burden, as an improved prognostic seromarker of risk. Exposure to a panel of five pathogens was tested and found to improve prediction of angiographic CAD in a cross-sectional study (95) and incident events among patients with CAD in a separate prospective study (Fig. 7) (96). Subsequently, European investigators found an association between the number of exposures to a panel of eight pathogens and cardiovascular mortality in patients with CAD in the Autogene Study (97). In another study of 572 patients, IgG or IgA antibodies to HSV-1 and HSV-2, CMV, Epstein-Barr virus, Hemophilus influenzae, C. pneumoniae, M. pneumoniae, and H. pylori were measured (98). The extent of atherosclerosis was determined by coronary angiography, carotid duplex sonography, and evaluation of the ankle-arm index. Pathogen burden, divided into zero to three, four to five, and six

Number of seropositive pathogens

Fig. 7. Graph of adjusted death/MI HRs based on baseline IgG seropositivity to number of pathogens ("pathogen burden"), including CMV, hepatitis A virus, HSV-1, HSV-2, C.pneumoniae, and H. pylori among 890 patients with significant CAD on angiography who were followed for 3 yr(96).

Number of seropositive pathogens

Fig. 7. Graph of adjusted death/MI HRs based on baseline IgG seropositivity to number of pathogens ("pathogen burden"), including CMV, hepatitis A virus, HSV-1, HSV-2, C.pneumoniae, and H. pylori among 890 patients with significant CAD on angiography who were followed for 3 yr(96).

to eight agents for which seropositivity was evident, was significantly associated with advanced atherosclerosis, with an OR (95% CI) of1.8 (1.2-2.6) for four to five (p < 0.01) and 2.5 (1.2-5.1) for six to eight seropositivities (p < 0.02) (adjusted). After a mean follow-up of 3.2 yr, the cardiovascular mortality rate was 7.0% in patients with advanced atherosclerosis and seropositive for zero to three pathogens compared with 20.0% in those seropositive for six to eight pathogens. Although the full implications of such analyses of multiple infectious seropositivity remain to be discovered, these initial findings do provide further evidence that a variety of infectious processes may play a role in the development and progression of atherosclerosis (99).

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