Muhammad Hammadah1, Yiying Fan2, Yuping Wu2, Stanley L Hazen3, W H Wilson Tang4. 1. Department of Cardiovascular Medicine, Heart and Vascular Institute, Cleveland Clinic, Cleveland, Ohio. 2. Department of Mathematics, Cleveland State University, Cleveland, Ohio. 3. 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. 4. 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.
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. METHODS AND 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.
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. METHODS AND 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: W H Wilson Tang; Yuping Wu; Jaana Hartiala; Yiying Fan; Alexandre F R Stewart; Robert Roberts; Ruth McPherson; Paul L Fox; Hooman Allayee; Stanley L Hazen Journal: Arterioscler Thromb Vasc Biol Date: 2011-11-10 Impact factor: 8.311
Authors: Anna L P Chapman; Tessa J Mocatta; Sruti Shiva; Antonia Seidel; Brian Chen; Irada Khalilova; Martina E Paumann-Page; Guy N L Jameson; Christine C Winterbourn; Anthony J Kettle Journal: J Biol Chem Date: 2013-01-10 Impact factor: 5.157
Authors: Muhammad Hammadah; Marie-Luise Brennan; Yuping Wu; Stanley L Hazen; W H Wilson Tang Journal: Am J Cardiol Date: 2016-01-28 Impact factor: 2.778
Authors: Muhammad Hammadah; Andreas P Kalogeropoulos; Vasiliki V Georgiopoulou; Malory Weber; Yuping Wu; Stanley L Hazen; Javed Butler; W H Wilson Tang Journal: Eur J Heart Fail Date: 2017-02-07 Impact factor: 15.534
Authors: Megan C Bakeberg; Maddeson Riley; Michelle Byrnes; Alexa Jefferson; Souyma Ghosh; Malcom K Horne; Sarah McGregor; Rick Stell; Sue Walters; Tess Evans; Katherine Roberts; Frank L Mastaglia; Ryan S Anderton Journal: Parkinsons Dis Date: 2020-09-30
Authors: Tamara Tomin; Matthias Schittmayer; Simon Sedej; Heiko Bugger; Johannes Gollmer; Sophie Honeder; Barbara Darnhofer; Laura Liesinger; Andreas Zuckermann; Peter P Rainer; Ruth Birner-Gruenberger Journal: Int J Mol Sci Date: 2021-02-11 Impact factor: 6.208
Authors: Táňa Andreasová; Jana Vránová; Dagmar Vondráková; Lenka Sedláčková; Zuzana Jirásková Zákostelská; Petr Neužil; Filip Málek Journal: J Int Med Res Date: 2020-08 Impact factor: 1.671