An Infectious Etiology of CAD? Cytomegalovirus in the Pathogenesis of Atherosclerosis
abstract & commentary
Synopsis: Susceptibility to the atherogenic effects of CMD depends, at least in part, on the capacity of the host to suppress CMV-induced inflammatory activity.
Source: Zhu J, et al. J Am Coll Cardiol 1999;34:1738-1743.
Zhu and associates have long been interested in the possible infectious etiology of atherosclerosis. In this study, cytomegalovirus (CMV) infection was assessed in 238 subjects undergoing evaluation of chest pain with invasive testing. Any angiographic evidence of atherosclerosis classified a patient into the coronary artery disease (CAD) group. CAD risk factors were carefully assessed. Anti-CMV IgG antibodies and CRP were assayed. Of the entire cohort, two-thirds had evidence of CAD on angiography, ranging from plaquing to angiographic stenoses. Multivariate analysis indicated that CAD was associated with advanced age, male gender, and hypercholesterolemia; Zhu et al believe that their cohort represents typical CAD patients. CMV levels were found to be strongly correlated with CAD, with mean values significantly higher in these individuals compared to those without CAD (0.89 vs 0.68 mg/dL; P = 0.01). Elevated CRP remained a significant predictor of CAD after adjustment for traditional CAD risk factors (OR 2.4; P = 0.02). Furthermore, of the two-thirds of the patients who had positive anti-CMV IgG antibodies, mean CRP was 0.88 vs. 0.69 mg/dL in those who were seronegative (P = 0.02). After adjusting for other risk factors, Zhu et al conclude that "CMV infection is an independent determinant of CRP levels."
Nevertheless, while 70% of the CAD group had antibodies to CMV, 54% of the non-CAD group were also CMV seropositive. Thus, while elevated CRP was associated with CAD, CMV seropositivity did not achieve statistical significance. With increasing seropositivity and/or elevated CRP levels, the prevalence of CAD was greater. Thus, the highest rates (78%) were noted when both were elevated, and only 22% of individuals without CAD were CMV seropositive with an elevated CRP. Zhu et al hypothesize that CMV stimulates an inflammatory response in the host, which induces a variable reaction, and that the magnitude of the inflammatory response will influence the development of or progression of CAD. They conclude that CMV is an independent determinant of elevated CRP and "predisposes to the induction of chronic sub-clinical inflammation." Thus, variation of the inflammatory response may be an important factor in determining whether an individual who has been exposed to CMV progresses to atherogenesis. Zhu et al believe that this helps explain the conflicting observations in the literature regarding the relationship of CMV to CAD. These results are compatible with the hypothesis that susceptibility to the atherogenic effects of CMD depends, at least in part, on the capacity of the host to suppress CMV-induced inflammatory activity. (Dr. Crawford is Robert S. Flinn Professor, Chief of Cardiology, University of New Mexico, Albuquerque.)
Coronary atherosclerosis may be associated with:
a. herpes simplex.
d. All of the above