Heart failure
Incremental Prognostic Power of Novel Biomarkers (Growth-Differentiation Factor-15, High-Sensitivity C-Reactive Protein, Galectin-3, and High-Sensitivity Troponin-T) in Patients With Advanced Chronic Heart Failure

https://doi.org/10.1016/j.amjcard.2013.05.013Get rights and content

Elevated natriuretic peptides provide strong prognostic information in patients with heart failure (HF). The role of novel biomarkers in HF needs to be established. Our objective was to evaluate the prognostic power of novel biomarkers, incremental to the N-terminal portion of the natriuretic peptide (NT-proBNP) in chronic HF. Concentrations of circulating NT-proBNP, growth differentiation factor 15 (GDF-15), high-sensitivity C-reactive protein (hs-CRP), galectin-3 (Gal-3), and high-sensitivity troponin T (hs-TnT) were measured and related to all-cause long-term mortality. Of 209 patients (age 71 ± 10 years, 73% male patients, 97% New York Heart Association class III), 151 (72%) died during a median follow-up of 8.7 ± 1 year. The calculated area under the curve for NT-proBNP was 0.63, GDF-15 0.78, hs-CRP 0.66, Gal-3 0.68, and hs-TnT 0.68 (all p <0.01). Each marker was predictive for mortality in univariate analysis. In multivariate analysis, elevated concentrations of GDF-15 (hazard ratio [HR] 1.41, confidence interval [CI] 1.1 to 178, p = 0.005), hs-CRP (HR 1.38, CI 1.15 to 1.67, p = 0.001), and hs-TnT (HR 1.27, CI 1.06 to 1.53, p = 0.008) were independently related to mortality. All novel markers had an incremental value to NT-proBNP, using the integrated discrimination improvement. In conclusion, in chronic HF, GDF-15, hs-CRP, and hs-TnT are independent prognostic markers, incremental to NT-proBNP, in predicting long-term mortality. In this study, GDF-15 is the most predictive marker, even stronger than NT-proBNP.

Section snippets

Methods

The present study was conducted as a substudy from the Deventer-Alkmaar Heart Failure study (DEAL-HF), which has been described elsewhere.13, 14 In brief, 240 patients with typical signs and symptoms of chronic HF combined with findings of a reduced left ventricular ejection fraction (45%) or diastolic dysfunction, according to the 2001 guidelines for the diagnosis of HF of the European Society of Cardiology, were included.15 Main exclusion criteria were an expected survival of <1 year, kidney

Results

Characteristics of the study population are described in Table 1. Medical care was provided according to the guidelines of the European Society of Cardiology prevailing at the time of inclusion and execution of the study with optimal application of therapy (baseline medication, Table 1). At baseline, beta blockers were prescribed in 60% of the patients. This figure went up to 69% after 1 year of follow-up. Almost all patients used a blocker of the renin-angiotensin system (96%) and diuretic

Discussion

Our study examined the predictive power of GDF-15, hs -CRP, Gal-3, and hs-TnT incremental to NT-proBNP, with respect to long-term outcome in patients with advanced chronic HF. The main findings of the present study are that GDF-15, hs-CRP, and hs-TnT have independent predictive power for long-term mortality, incremental to established clinical and biochemical risk factors. GDF-15 showed to be the strongest prognosticator. Second, the presence of each individual marker significantly enhanced

Disclosures

BG Medicine, Inc., has rights related to Galectin-3 measurements. BG Medicine, Inc., provided an unrestricted research grant to the Department of Cardiology of the University Medical Center Groningen, which employs P.v.d.M., R.A.d.B., and D.J.v.V. D.J.v.V and R.A.d.B. have received consultancy and speakers fees from BG Medicine, Inc. The Deventer Cardiology Research department received an unrestricted research grant from BG Medicine, Inc. Roche Diagnostics performed laboratory assessments for

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    A.A. Voors is funded through Grant 242209 from the European Commission FP7-Health-2009-BIOSTAT-CHF.

    See page 836 for disclosure information.

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