Growth differentiation factor 15 as mortality predictor in heart failure patients with non-reduced ejection fraction
Por:
Fernandez, ABM, Ferrero-Gregori, A, Garcia-Osuna, A, Mirabet-Perez, S, Pirla-Buxo, MJ, Cinca-Cuscullola, J, Ordonez-Llanos, J, Minguell, ER
Publicada:
1 oct 2020
Ahead of Print:
1 jun 2020
Resumen:
Aims The prognostic value of biomarkers in patients with heart failure (HF) and mid-range (HFmrEF) or preserved ejection fraction (HFpEF) has not been widely addressed. The aim of this study was to assess whether the prognostic value of growth differentiation factor 15 (GDF-15) is superior to that of N-terminal pro-brain natriuretic peptide (NT-proBNP) in patients with HFmrEF or HFpEF. Methods and results Heart failure patients with either HFpEF or HFmrEF were included in the study. During their first visit to the HF unit, serum samples were obtained and stored for later assessment of GDF-15 and NT-proBNP concentrations. Patients were followed up by the HF unit. The main endpoint was all-cause mortality. A total of 311 patients, 90 (29%) HFmrEF and 221 (71%) HFpEF, were included. Mean age was 72 +/- 13 years, and 136 (44%) were women. No differences were found in GDF-15 or NT-proBNP concentrations between both HF groups. During a median follow-up of 15 months (Q1-Q3: 9-30 months), 98 patients (32%) died, most (71%) of cardiovascular causes. Patients who died had higher median concentrations of GDF-15 (4085 vs. 2270 ng/L,P< 0.0001) and NT-proBNP (1984 vs. 1095 ng/L,P< 0.0001). A Cox multivariable model identified New York Heart Association Functional Class III (P= 0.04), systolic blood pressure (P= 0.01), left atrial diameter (P= 0.03), age >65 years (P< 0.0001), and GDF-15 concentrations (P= 0.01) but not NT-proBNP as independent predictors of all-cause mortality. The area under the curve was 0.797 for the basic model including NT-proBNP, and the area under the curve comparing the overall model was 0.819,P= 0.016 (DeLong's test). Integrated discrimination improvement index after the inclusion of GDF-15 in the model with the mortality risk factors was 0.033; that is, the ability to predict death increased by 3.3% (P= 0.004). Net reclassification improvement was 0.548 (P< 0.001); that is, the capacity to improve the classification of the event (mortality) was 54.8%. GDF-15 concentrations were divided in tertiles (<1625, 1625-4330, and >4330 ng/L), and survival curves were evaluated using the Kaplan-Meier technique. Patients in the highest tertile had the poorest 5 year survival, at 16%, whereas the lowest tertile had the best survival, of 78% (P< 0.001). Conclusions Growth differentiation factor 15 was superior to NT-proBNP for assessing prognosis in patients with HFpEF and HFmrEF. GDF-15 emerges as a strong, independent biomarker for identifying HFmrEF and HFpEF patients with worse prognosis.
Filiaciones:
Fernandez, ABM:
Hosp Santa Creu & Sant Pau, CIBERCV, Dept Cardiol, Carrer St Quinti 89, Barcelona 08041, Spain
Ferrero-Gregori, A:
Hosp Santa Creu & Sant Pau, CIBERCV, Dept Cardiol, Carrer St Quinti 89, Barcelona 08041, Spain
Garcia-Osuna, A:
IIB St Pau, Dept Biochem, Barcelona, Spain
Mirabet-Perez, S:
Hosp Santa Creu & Sant Pau, CIBERCV, Dept Cardiol, Carrer St Quinti 89, Barcelona 08041, Spain
Pirla-Buxo, MJ:
Hosp Santa Creu & Sant Pau, CIBERCV, Dept Cardiol, Carrer St Quinti 89, Barcelona 08041, Spain
Cinca-Cuscullola, J:
Hosp Santa Creu & Sant Pau, CIBERCV, Dept Cardiol, Carrer St Quinti 89, Barcelona 08041, Spain
Ordonez-Llanos, J:
IIB St Pau, Dept Biochem, Barcelona, Spain
Univ Autonoma Barcelona, Dept Biochem & Mol Biol, Barcelona, Spain
Minguell, ER:
Hosp Santa Creu & Sant Pau, CIBERCV, Dept Cardiol, Carrer St Quinti 89, Barcelona 08041, Spain
Gold, Green Published
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