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

Study Questions:

What is the prognostic power of novel biomarkers, incremental to the N-terminal portion of the B-type natriuretic peptide (NT-proBNP), in chronic heart failure (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. In consecutive multivariate models, GDF-15, hs-CRP, Gal-3, and hs-TnT were adjusted for age and gender, renal function, HF etiology, NT-proBNP concentrations, and all other univariate significant biomarkers.


Of 209 patients (ages 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 was 0.78, hs-CRP was 0.66, Gal-3 was 0.68, and hs-TnT was 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], 1.1-178; p = 0.005), hs-CRP (HR, 1.38; CI, 1.15-1.67; p = 0.001), and hs-TnT (HR, 1.27; CI, 1.06-1.53; p = 0.008) were independently related to mortality. All novel markers had an incremental value to NT-proBNP, using the integrated discrimination improvement.


The authors concluded that in chronic HF, GDF-15, hs-CRP, and hs-TnT are independent prognostic markers, incremental to NT-proBNP, in predicting long-term mortality.


This study reported that GDF-15, hs-CRP, and hs-TnT have independent predictive power for long-term mortality, incremental to established clinical and biochemical risk factors. Furthermore, GDF-15 showed to be the strongest prognosticator. Also, the presence of each individual marker significantly enhanced integrated discrimination improvement. Given the small sample size, these findings on the additive value of novel markers in chronic HF need to be confirmed prospectively in a larger cohort of patients.

Clinical Topics: Anticoagulation Management, Heart Failure and Cardiomyopathies, Acute Heart Failure, Heart Failure and Cardiac Biomarkers

Keywords: Follow-Up Studies, Multivariate Analysis, Troponin T, Transcription Factors, Risk Factors, Galectin 3, New York, Natriuretic Peptides, Prognosis, C-Reactive Protein, Biological Markers, Heart Failure, Growth Differentiation Factor 15, Peptide Fragments, Confidence Intervals

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