Cytomegalovirus seropositivity and C-reactive protein have independent and combined predictive value for mortality in patients with angiographically demonstrated coronary artery disease

Circulation. 2000 Oct 17;102(16):1917-23. doi: 10.1161/01.cir.102.16.1917.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Antibodies, Bacterial / blood
  • Antibodies, Viral / blood
  • C-Reactive Protein / metabolism*
  • Chlamydophila Infections / blood
  • Chlamydophila Infections / epidemiology
  • Chlamydophila pneumoniae / isolation & purification
  • Comorbidity
  • Coronary Angiography
  • Coronary Disease / blood*
  • Coronary Disease / diagnostic imaging
  • Coronary Disease / mortality*
  • Cytomegalovirus / isolation & purification
  • Cytomegalovirus Infections / blood*
  • Cytomegalovirus Infections / diagnosis
  • Cytomegalovirus Infections / mortality*
  • Female
  • Follow-Up Studies
  • Helicobacter Infections / blood
  • Helicobacter Infections / diagnosis
  • Helicobacter Infections / epidemiology
  • Helicobacter pylori / isolation & purification
  • Humans
  • Immunoglobulin G / blood
  • Male
  • Predictive Value of Tests
  • Proportional Hazards Models
  • Prospective Studies
  • Risk Assessment
  • Risk Factors
  • Serologic Tests


  • Antibodies, Bacterial
  • Antibodies, Viral
  • Immunoglobulin G
  • C-Reactive Protein