title: 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.
  
  
  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.
authors.affiliation: LDS Hospital, University of Utah, Salt Lake City 84143, USA. ldbmuhle@ihc.com
authors.forename: J B
authors.initials: JB
authors.lastname: Muhlestein
authors.forename: B D
authors.initials: BD
authors.lastname: Horne
authors.forename: J F
authors.initials: JF
authors.lastname: Carlquist
authors.forename: T E
authors.initials: TE
authors.lastname: Madsen
authors.forename: T L
authors.initials: TL
authors.lastname: Bair
authors.forename: R R
authors.initials: RR
authors.lastname: Pearson
authors.forename: J L
authors.initials: JL
authors.lastname: Anderson
mesh_terms: D000368:Aged; D000907:Antibodies, Bacterial / Q000097:blood; D000914:Antibodies, Viral / Q000097:blood; D002097:C-Reactive Protein / Q000378:metabolism*; D023521:Chlamydophila Infections / Q000097:blood / Q000453:epidemiology; D016993:Chlamydophila pneumoniae / Q000302:isolation & purification; D015897:Comorbidity; D017023:Coronary Angiography; D003327:Coronary Disease / Q000097:blood* / Q000000981:diagnostic imaging / Q000401:mortality*; D003587:Cytomegalovirus / Q000302:isolation & purification; D003586:Cytomegalovirus Infections / Q000097:blood* / Q000175:diagnosis / Q000401:mortality*; D005260:Female; D005500:Follow-Up Studies; D016481:Helicobacter Infections / Q000097:blood / Q000175:diagnosis / Q000453:epidemiology; D016480:Helicobacter pylori / Q000302:isolation & purification; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood; D008297:Male; D011237:Predictive Value of Tests; D016016:Proportional Hazards Models; D011446:Prospective Studies; D018570:Risk Assessment; D012307:Risk Factors; D012698:Serologic Tests
chemical_list: D000907:Antibodies, Bacterial; D000914:Antibodies, Viral; D007074:Immunoglobulin G; D002097:C-Reactive Protein