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(Circulation. 2000;102:2491.)
© 2000 American Heart Association, Inc.

Clinical Investigation and Reports

Host Response to Cytomegalovirus Infection as a Determinant of Susceptibility to Coronary Artery Disease

Sex-Based Differences in Inflammation and Type of Immune Response

Jianhui Zhu, MD, PhD; Gene M. Shearer, PhD; James E. Norman, PhD; Ligia A. Pinto, PhD; Francesco M. Marincola, MD; Abhiram Prasad, MD; Myron A. Waclawiw, PhD; Gyorgy Csako, MD; Arshed A. Quyyumi, MD; Stephen E. Epstein, MD

From the Cardiovascular Research Institute and MedStar Research Institute, Washington Hospital Center, Washington, DC (J.Z., S.E.E.); and the Cardiology Branch (A.A.Q., A.P.) and Division of Epidemiology and Clinical Applications (J.E.N., M.A.W.), National Heart, Lung, and Blood Institute; the National Cancer Institute (G.M.S., L.A.P., F.M.M.); and the Clinical Center (G.C.), National Institutes of Health, Bethesda, Md.

Correspondence to Dr Stephen E. Epstein, CRI, Washington Hospital Center, 110 Irving St, NW, Suite 4B-1, Washington, DC 20010.

Background—Positive and negative associations between cytomegalovirus (CMV) infection and coronary artery disease (CAD) have been reported. We postulated that the susceptibility to CMV-induced CAD might relate to patterns of inflammatory and immune responses to CMV infection and that sex might have an effect on these responses.

Methods and Results—In 151 men and 87 women being evaluated for CAD, blood samples were tested for humoral (Ab+) and cellular (Tc+) responses to CMV and for C-reactive protein (CRP). In men, an elevated CRP level was a significant determinant of CAD even after adjustment for CAD risk factors (OR, 3.1; 95% CI, 1.21 to 7.97). CMV seropositivity was associated with elevated CRP levels on multivariate analysis (P=0.006). In contrast, in women, CMV seropositivity was independently predictive of CAD (OR, 41.8; 95% CI, 4.12 to 423.74). CRP level in women with CAD was >25% higher than those without CAD, but the difference did not reach statistical significance. Importantly, compared with CMV Ab-/Tc- women, CAD prevalence was higher in Ab+/Tc- and Ab+/Tc+ (13% versus 68% and 64%, both P<0.005) but not in Ab-/Tc+ women (25%). There were no differences in age, smoking, diabetes, hypertension, and hypercholesterolemia among women with different types of immune responses to CMV infection.

Conclusions—The mechanisms by which CMV predisposes to CAD in men and women may be different. In men, CMV appears to contribute to CAD risk, insofar as it predisposes to inflammation. In women, other mechanisms, possibly related to the type of immune response generated by the host, appear to be responsible for the proatherogenic effects of CMV.

Key Words: immunology • infection • inflammation • sex • risk factors

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