title: Prognostic value of elevated serum ceruloplasmin levels in patients with heart failure.
abstract: BACKGROUND
  Ceruloplasmin (Cp) is a copper-binding acute-phase protein that is increased in inflammatory states and deficient in Wilson's disease. Recent studies demonstrate that increased levels of Cp are associated with increased risk of developing heart failure. Our objective was to test the hypothesis that serum Cp provides incremental and independent prediction of survival in stable patients with heart failure.
  
  
  RESULTS
  We measured serum Cp levels in 890 patients with stable heart failure undergoing elective cardiac evaluation that included coronary angiography. We examined the role of Cp levels in predicting survival over 5 years of follow-up. Mean Cp level was 26.6 ± 6.9 mg/dL and demonstrated relatively weak correlation with B-type natriuretic peptide (BNP; r = 0.187; P < .001). Increased Cp levels were associated with increased 5-year all-cause mortality (quartile [Q] 4 vs Q1 hazard ratio [HR] 1.9, 95% confidence interval [CI] 1.4-2.8; P < .001). When controlled for coronary disease traditional risk factors, creatinine clearance, dialysis, body mass index, medications, history of myocardial infarction, BNP, left ventricular ejection fraction (LVEF), heart rate, QRS duration, left bundle branch blockage, and implantable cardioverter-defibrillator placement, higher Cp remained an independent predictor of increased mortality (Q4 vs Q1 HR 1.7, 95% CI 1.1-2.6; P < .05). Model quality was improved with addition of Cp to the aforementioned covariables (net reclassification improvement of 9.3%; P < .001).
  
  
  CONCLUSIONS
  Ceruloplasmin is an independent predictor of all-cause mortality in patients with heart failure. Measurement of Cp may help to identify patients at heightened mortality risk.
authors.affiliation: Department of Cardiovascular Medicine, Heart and Vascular Institute, Cleveland Clinic, Cleveland, Ohio.
authors.forename: Muhammad
authors.initials: M
authors.lastname: Hammadah
authors.affiliation: Department of Mathematics, Cleveland State University, Cleveland, Ohio.
authors.forename: Yiying
authors.initials: Y
authors.lastname: Fan
authors.affiliation: Department of Mathematics, Cleveland State University, Cleveland, Ohio.
authors.forename: Yuping
authors.initials: Y
authors.lastname: Wu
authors.affiliation: Department of Cardiovascular Medicine, Heart and Vascular Institute, Cleveland Clinic, Cleveland, Ohio; Department of Cellular and Molecular Medicine, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio.
authors.forename: Stanley L
authors.initials: SL
authors.lastname: Hazen
authors.affiliation: Department of Cardiovascular Medicine, Heart and Vascular Institute, Cleveland Clinic, Cleveland, Ohio; Department of Cellular and Molecular Medicine, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio. Electronic address: tangw@ccf.org.
authors.forename: W H Wilson
authors.initials: WH
authors.lastname: Tang
mesh_terms: D000046:Academic Medical Centers; D000368:Aged; D015415:Biomarkers / Q000097:blood; D006328:Cardiac Catheterization; D002570:Ceruloplasmin / Q000032:analysis / Q000378:metabolism*; D015331:Cohort Studies; D016001:Confidence Intervals; D018450:Disease Progression; D018572:Disease-Free Survival; D005260:Female; D006333:Heart Failure / Q000097:blood* / Q000401:mortality* / Q000503:physiopathology; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D008991:Monitoring, Physiologic / Q000379:methods; D020097:Natriuretic Peptide, Brain / Q000097:blood; D009820:Ohio; D011237:Predictive Value of Tests; D011379:Prognosis; D016016:Proportional Hazards Models; D012372:ROC Curve; D012189:Retrospective Studies; D016019:Survival Analysis
chemical_list: D015415:Biomarkers; D020097:Natriuretic Peptide, Brain; D002570:Ceruloplasmin
keywords: Heart failure; biomarkers; ceruloplasmin; outcomes