Abstract
We investigated whether the additional determination of ceruloplasmin (Cp) levels could improve the prognostic value of N-terminal pro-B-type natriuretic peptide (NT-proBNP) in heart failure (HF) patients in a 1-year follow-up. Cp and NT-proBNP levels and clinical and laboratory parameters were assessed simultaneously at baseline in 741 HF patients considered as possible heart transplant recipients. The primary endpoint (EP) was a composite of all-cause death (non-transplant patients) or heart transplantation during one year of follow-up. Using a cut-off value of 35.9 mg/dL for Cp and 3155 pg/mL for NT-proBNP (top interquartile range), a univariate Cox regression analysis showed that Cp (hazard ratio (HR) = 2.086; 95% confidence interval (95% CI, 1.462–2.975)), NT-proBNP (HR = 3.221; 95% CI (2.277–4.556)), and the top quartile of both Cp and NT-proBNP (HR = 4.253; 95% CI (2.795–6.471)) were all risk factors of the primary EP. The prognostic value of these biomarkers was demonstrated in a multivariate Cox regression model using the top Cp and NT-proBNP concentration quartiles combined (HR = 2.120; 95% CI (1.233–3.646)). Lower left ventricular ejection fraction, VO2max, lack of angiotensin-converting enzyme inhibitor or angiotensin receptor blocker therapy, and nonimplantation of an implantable cardioverter-defibrillator were also independent risk factors of a poor outcome. The combined evaluation of Cp and NT-proBNP had advantages over separate NT-proBNP and Cp assessment in selecting a group with a high 1-year risk. Thus multi-biomarker assessment can improve risk stratification in HF patients.
Highlights
Systolic heart failure (HF) is a complex disease caused by reduced ejection fraction of the left ventricle, often leading to the worsening of symptoms and poor quality of life, despite proper diagnosis and treatment according to current guidelines
The aim of this study was to examine the prognostic value of clinical factors, with special consideration of Cp, in a large cohort of HF patients and to investigate whether the combination of Cp and NT-proBNP could provide additional prognostic information in HF patients in a 1-year follow-up
We analyzed data in a subgroup of patients included in the Prospective Registry of Heart Failure (PR-HF) and Studies Investigating Co-morbidities Aggravating Heart Failure (SICA-HF) studies described elsewhere [17]
Summary
Systolic heart failure (HF) is a complex disease caused by reduced ejection fraction of the left ventricle, often leading to the worsening of symptoms and poor quality of life, despite proper diagnosis and treatment according to current guidelines. Stratification of risk factors is a great challenge in out-patient clinic cohorts, in which patients still undergo significant mortality and morbidity, despite stable HF. Different clinical and laboratory parameters can be helpful to identify patients at higher risk of adverse outcomes. NT-proBNP is recommended as a marker over BNP, because of its longer plasma half-life and lower levels of biological variation. The usefulness of NT-proBNP for risk stratification varies depending on the stage of HF, time of assessment (onset of hospitalization, pre-discharge, or out-patient clinic evaluation), and duration of follow-up. Ceruloplasmin (Cp) is an acute-phase reactant that is synthesized and secreted by the liver and monocyte/macrophages. It is elevated in conditions of acute inflammation. Several recent reports have indicated that Cp levels are elevated in patients with heart failure, regardless of its etiology [14,15,16]
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