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(Circulation. 2003;107:258.)
© 2003 American Heart Association, Inc.

Clinical Investigation and Reports

Statin Therapy Interacts With Cytomegalovirus Seropositivity and High C-Reactive Protein in Reducing Mortality Among Patients With Angiographically Significant Coronary Disease

Benjamin D. Horne, MPH; Joseph B. Muhlestein, MD; John F. Carlquist, PhD; Tami L. Bair, BS; Troy E. Madsen, BA; Noal I. Hart, BS; Jeffrey L. Anderson, MD, for the Intermountain Heart Collaborative (IHC) Study Group

From the Cardiovascular Department, LDS Hospital (B.D.H., J.B.M., J.F.C., T.L.B., T.E.M., N.I.H., J.L.A.), and the University of Utah (J.B.M., J.F.C., J.L.A.), Salt Lake City.

Correspondence to Joseph B. Muhlestein, MD, LDS Hospital Cardiovascular Department, 8th Ave and C St, Salt Lake City, UT 84143. E-mail ldbmuhle{at}ihc.com

Background— Seropositivity to cytomegalovirus (CMV) and elevated C-reactive protein (CRP) may jointly predict increased mortality rates in patients with coronary artery disease (CAD). Therapy with statins reduces lipid levels but may also have other beneficial (eg, antiinflammatory) effects. This study prospectively evaluated the effect of statins on CMV-and CRP-associated death among patients with significant, angiographically defined CAD.

Methods and Results— We monitored 2315 patients with angiographically significant CAD (stenosis 70%) for an average of 2.4 years (maximum, 5.8 years). Anti-CMV IgG antibody levels and CRP concentrations were measured at baseline, and statin prescription was recorded. As previously reported, mortality rate was higher for CMV seropositivity (+) with high CRP (hazard ratio [HR], 2.0) and lower for statins (HR, 0.50). Compared with CMV(-)/low CRP (mortality rate, 5% with statin versus 4% without statin), the protective effect of statin therapy was markedly greater for CMV(+)/low CRP (mortality rate, 2% versus 7%; HR, 0.44; 95% CI, 0.16 to 1.3), CMV negative (-)/high CRP (mortality rate, 1% versus 8%; HR, 0.16), and CMV(+)/high CRP (mortality rate, 6% versus 17%; HR, 0.42; 95% CI, 0.25 to 0.70). After adjustment, interactions were found for statin therapy with CMV(+)/low CRP (P for interaction=0.065), CMV(-)/high CRP (P for interaction=0.051), and CMV(+)/high CRP (P for interaction=0.024).

Conclusions— The survival benefit of statins interacted with CMV seropositivity and high CRP to significantly reduce mortality rates among patients with CAD. This finding supports the hypothesis that statins have beneficial, "lipid-independent," antiinflammatory effects. The mechanism of statin benefit associated with CMV seropositivity remains to be determined.

Key Words: infection • inflammation • drugs • survival • risk factors

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