Cytomegalovirus Seropositivity and C-Reactive Protein Have Independent and Combined Predictive Value for Mortality in Patients With Angiographically Demonstrated Coronary Artery Disease

Abstract

Background —The role of inflammation in coronary artery disease (CAD) is being increasingly recognized. Markers of inflammation (eg, C-reactive protein [CRP]) and infection (eg, seropositivity to Chlamydia pneumoniae , cytomegalovirus [CMV], and Helicobacter pylori ) have been proposed as risk factors for CAD, but these associations require further evaluation. Methods and Results —We prospectively tested whether CRP levels and IgG seropositivity to C pneumoniae , CMV, and H pylori are predictors of subsequent mortality in 985 consecutive patients with angiographically demonstrated CAD (stenosis ≥70%). Patients were followed for an average of 2.7 years (range 1.5 to 4.0 years). Patients averaged 65 years of age; 77% were men; and 110 (11.2%) died during follow-up. CRP levels were significantly elevated in nonsurvivors compared with survivors (mean CRP 3.1 mg/dL versus 1.5 mg/dL, P =0.003). After controlling for all known baseline variables, the 2nd and 3rd tertiles of CRP compared with the 1st produced a Cox hazard ratio (HR) for mortality of 2.4 ( P =0.001). Of the 3 infectious markers tested, only seropositivity to CMV (HR=1.9, P <0.05) was predictive of mortality. The majority of mortality risk associated with elevated CRP or CMV seropositivity occurred when both risk factors were present ( P for trend <0.0001). Other independent predictors of increased risk of mortality were age (HR=1.07 per year, P <0.0001), left ventricular ejection fraction (HR=0.97 per percent, P <0.0001), and diabetes mellitus (HR=1.7, P =0.02). Conclusions —CMV seropositivity and elevated CRP, especially when in combination, are strong, independent predictors of mortality in patients with CAD. This suggests an interesting hypothesis that a chronic, smoldering infection (CMV) might have the capacity to accelerate the atherothrombotic process.