Statin therapy interacts with cytomegalovirus seropositivity and high C-reactive protein in reducing mortality among patients with angiographically significant coronary disease.
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.


RESULTS
We monitored 2315 patients with angiographically significant CAD (stenosis > or =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.
Horne
Benjamin D
BD
Cardiovascular Department, LDS Hospital, Salt Lake City, UT 84143, USA.
Muhlestein
Joseph B
JB
Carlquist
John F
JF
Bair
Tami L
TL
Madsen
Troy E
TE
Hart
Noal I
NI
Anderson
Jeffrey L
JL
D000368:Aged; D002097:C-Reactive Protein / Q000032:analysis*; D015331:Cohort Studies; D015897:Comorbidity; D017023:Coronary Angiography; D003327:Coronary Disease / Q000188:drug therapy* / Q000401:mortality / Q000821:virology*; D003587:Cytomegalovirus / Q000276:immunology*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D016017:Odds Ratio; D016016:Proportional Hazards Models; D011446:Prospective Studies; D012307:Risk Factors; D012698:Serologic Tests; D016019:Survival Analysis; D014589:Utah / Q000453:epidemiology
D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D002097:C-Reactive Protein