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

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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 P for trend P P 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.