Cytomegalovirus infection with interleukin-6 response predicts cardiac mortality in patients with coronary artery disease

Background-Prospective data relating previous exposure to cytomegalovirus ( CMV) to the risk of cardiac mortality are controversial. We investigated th e effect of previous exposure to CMV infection on the risk of future cardia c disease-related death in relation to an underlying inflammatory response. Methods and Results-Coronary angiography was performed in 1134 subjects, an d 989 patients with documented coronary artery disease were studied prospec tively. CMV-IgG titers and interleukin (IL)-6 levels were measured before a ngiography. Increasing titers of CMV correlated with the elevation of IL-6 levels (P<0.001) after adjustment for possible confounders. All patients we re followed up for a median of 3.1 years (maximum 4.3 years). During Follow -up, 96 patients died, 70 of cardiac disease. Overall. CMV seropositivity w as not related to cardiac mortality after adjustment for confounding variab les (P=0.19). In contrast, in patients with elevated IL-6 levels (<greater than or equal to>11.9 pg/mL, median level), CMV seropositivity was independ ently associated with a 3.2-fold (95% CI 1.4 to 7.3, P=0.007) increase in r isk of future cardiac death, whereas in individuals without IL-6 elevation. previous CMV infection had no effect on cardiac mortality. Conclusions-CMV seropositivity in patients with an inflammatory response is independently associated with future cardiac mortality, whereas this assoc iation is lost in patients who do not demonstrate an inflammatory response. These data support the hypothesis that the atherosclerotic effects of CMV are mediated through an underlying inflammatory response.