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Journal of Cardiac Failure


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.


This research was supported by grants R01HL103931, P01HL076491, and P01HL098055 from the National Institutes of Health. Clinical samples used in this study were from Genebank, a study supported by National Institutes of Health grants R01HL103866 and P20HL113452 (with the Office of Dietary Supplements) and the Cleveland Clinic Clinical Research Unit of the Case Western Reserve University Clinical and Translational Science Award (UL1TR 000439).









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