Infection, endothelial dysfunction, and atherogenesis.

and Atherogenesis To the Editor: Khairy et al1 reported a lack of association between chronic infection and endothelial function in healthy young men. The study population was highly selective and, excluded women, individuals aged 45 years, and subjects with any conventional risk factors of coronary artery disease (CAD). The authors assumed that serum antibodies against the various infectious agents investigated represented evidence of chronic infection. The results of Khairy et al1 are indirectly supported by findings of other authors,2,3 who reported that seropositivity to infectious agents was not associated with increased atherothrombotic risk. However, they contrast with data by Prasad et al,4 who found a significant correlation between total infectious burden to five infectious agents and decreased intracoronary endothelial function. Khairy et al1 suggest that the discrepancies between studies are due to different patient populations, different infectious agents, and different methods of assessing outcome. Moreover, they point out that interactive effects between conventional risk factors and infectious agents could have played a role in the Prasad et al4 study. The findings of Khairy et al1 contrast also with the results of a recent study by Parchure et al,5 which showed that antibiotic treatment with azithromycin had a favorable effect on endothelial function in patients with CAD and seropositivity to Chlamydia pneumoniae. This randomized, prospective, double-blind, placebo-controlled trial showed that endothelial function was significantly improved by azithromycin treatment compared with placebo.5 Unfortunately, Khairy et al1 omitted any mention of this article, probably because the patients had CAD. Khairy et al1 selected a “pure study population,” in which factors potentially able to affect endothelial function were absent. This stringent selection represents one of the major limitations of the study. Conceivably, this population constitutes a group in which protective factors, genetic or otherwise, operate, making these subjects less susceptible to developing vascular disease. Individuals in this study are unlikely to be a sample representative of the general population. Therefore, extrapolation of these results to other individuals may not be straightforward. Also of concern is that seroprevalence was taken as evidence for chronic infection. IgG antibodies do not necessarily indicate duration or activity of infection. Although I concur that infectious agents may not be entirely responsible for initial endothelial injury, I do not believe that the Khairy et al1 results categorically indicate that chronic, low-grade infection is unlikely to be responsible for the initiation of CAD. A more appropriate conclusion should perhaps be that in selected healthy individuals without CAD risk factors, seropositivity is not associated with systemic endothelial dysfunction. The suggestion that infectious agents are not implicated as early etiologic triggers of CAD is purely speculative.