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

Abstract

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 Ն70%) 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 (ϩ) with high CRP (hazard ratio [HR], 2.0) and lower for statins (HR, 0.50). Compared with CMV(Ϫ)/low CRP (mortality rate, 5% with statin versus 4% without statin), the protective effect of statin therapy was markedly greater for CMV(ϩ)/low CRP (mortality rate, 2% versus 7%; HR, 0.44; 95% CI, 0.16 to 1.3), CMV negative (Ϫ)/high CRP (mortality rate, 1% versus 8%; HR, 0.16), and CMV(ϩ)/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(ϩ)/low CRP (P for interactionϭ0.065), CMV(Ϫ)/high CRP (P for interactionϭ0.051), and CMV(ϩ)/high CRP (P for interactionϭ0.024). 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.

Infection with Cytomegalovirus is not Associated with Premature Mortality

“…5,8 Nor did we include exclusively elderly patients or only those with coronary artery disease, as in other studies. 3,4,5,13,18 Our observations appear to support previous studies and contradict others. Three recent studies did observe an association between those with high antibody titers to CMV and reduced longevity.…”

Hydroxymethyl-Glutaryl Coenzyme A Reductase Inhibition Limits Cytomegalovirus Infection in Human Endothelial Cells

“…These results, while confirming the anti-inflammatory properties of statins, identify novel pharmacological targets potentially relevant in improving the therapeutic profile of statins in the treatment of atherosclerosis progression and, possibly, CMV infection development. 26 …”

Statins Are Associated With a Reduced Incidence of Perioperative Mortality After Coronary Artery Bypass Graft Surgery

“…Long-term statin administration in ambulatory patient populations has been previously associated with a reduced risk of adverse cardiovascular events, including death, MI, stroke, and renal dysfunction. [1][2][3][4][5][6][7][8][9][10] Furthermore, the beneficial effects of statin therapy are not limited to patients with hypercholesterolemia. Multiple randomized clinical trials have shown that even in patients with normal total and low-density lipoprotein cholesterol levels, long-term statin administration is associated with reduced incidence of adverse cardiovascular outcomes and a decreased need for coronary angioplasty or CABG surgery.…”

“…[1][2][3][4][5][6][7][8][9][10] However, the beneficial effects of statin therapy on adverse cardiovascular events in the acute perioperative period are largely unknown. [11][12][13] Recently, statins were shown to be associated with a reduced incidence of perioperative mortality in patients undergoing major noncardiac vascular surgery.…”