Published Online
on December 16, 2002

A more recent version of this article appeared on January 21, 2003

This Article Full Text (PDF) All Versions of this Article: 107/2/258    most recent 01.CIR.0000045668.71683.92v1 Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Horne, B. D. Search for Related Content PubMed PubMed Citation Articles by Horne, B. D. Pubmed/NCBI databases Substance via MeSH Related Collections Cardiovascular Pharmacology Secondary prevention Other etiology Chronic ischemic heart disease Epidemiology

Submitted on July 18, 2002
Revised on October 3, 2002
Accepted on October 7, 2002

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, and 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, Utah.

^* To whom correspondence should be addressed. 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

This article has been cited by other articles:

				M. E. Falagas, G. C. Makris, D. K. Matthaiou, and P. I. Rafailidis Statins for infection and sepsis: a systematic review of the clinical evidence J. Antimicrob. Chemother., April 1, 2008; 61(4): 774 - 785. [Abstract] [Full Text] [PDF]

				C. D. Collard, S. C. Body, S. K. Shernan, S. Wang, D. T. Mangano, and Multicenter Study of Perioperative Ischemia (MCSPI Preoperative statin therapy is associated with reduced cardiac mortality after coronary artery bypass graft surgery. J. Thorac. Cardiovasc. Surg., August 1, 2006; 132(2): 392 - 400. [Abstract] [Full Text] [PDF]

				K. Hindler, C. S. Cleeland, E. Rivera, and C. D. Collard The Role of Statins in Cancer Therapy. Oncologist, January 1, 2006; 11(3): 306 - 315. [Abstract] [Full Text] [PDF]

				A. Rahbar and C. Soderberg-Naucler Human Cytomegalovirus Infection of Endothelial Cells Triggers Platelet Adhesion and Aggregation J. Virol., February 15, 2005; 79(4): 2211 - 2220. [Abstract] [Full Text] [PDF]

				T. J. DeGraba Immunogenetic Susceptibility of Atherosclerotic Stroke: Implications on Current and Future Treatment of Vascular Inflammation Stroke, November 1, 2004; 35(11_suppl_1): 2712 - 2719. [Abstract] [Full Text] [PDF]

				H.-B. Leu, C.-P. Lin, W.-T. Lin, T.-C. Wu, and J.-W. Chen Risk Stratification and Prognostic Implication of Plasma Biomarkers in Nondiabetic Patients With Stable Coronary Artery Disease: The Role of High-Sensitivity C-Reactive Protein Chest, October 1, 2004; 126(4): 1032 - 1039. [Abstract] [Full Text] [PDF]

				W. Pan, T. Pintar, J. Anton, V.-V. Lee, W. K. Vaughn, and C. D. Collard Statins Are Associated With a Reduced Incidence of Perioperative Mortality After Coronary Artery Bypass Graft Surgery Circulation, September 14, 2004; 110(11_suppl_1): II-45 - II-49. [Abstract] [Full Text] [PDF]

				L. Potena, G. Frascaroli, F. Grigioni, T. Lazzarotto, G. Magnani, L. Tomasi, F. Coccolo, L. Gabrielli, C. Magelli, M. P. Landini, et al. Hydroxymethyl-Glutaryl Coenzyme A Reductase Inhibition Limits Cytomegalovirus Infection in Human Endothelial Cells Circulation, February 3, 2004; 109(4): 532 - 536. [Abstract] [Full Text] [PDF]