Growth differentiation factor 15 (GDF-15) in patients admitted for acute heart failure: results from the RELAX-AHF study

• Published in: European journal of heart failure Vol. 17; no. 11; pp. 1133 - 1143
• Main Authors: Cotter, Gad, Voors, Adriaan A., Prescott, Margaret F., Felker, G. Michael, Filippatos, Gerasimos, Greenberg, Barry H., Pang, Peter S., Ponikowski, Piotr, Milo, Olga, Hua, Tsushung A., Qian, Min, Severin, Thomas M., Teerlink, John R., Metra, Marco, Davison, Beth A.
• Format: Journal Article
• Language: English
• Published: Oxford, UK John Wiley & Sons, Ltd 01-11-2015
• Subjects: Acute Disease; Acute heart failure; Aged; Aged, 80 and over; Cardiovascular Agents - administration & dosage; Double-Blind Method; Female; GDF-15; Growth Differentiation Factor 15 - blood; Heart Failure - blood; Heart Failure - diagnosis; Heart Failure - drug therapy; Heart Failure - mortality; Heart Failure - physiopathology; Hospitalization; Humans; Male; Middle Aged; Mortality; Natriuretic Peptide, Brain - blood; Peptide Fragments - blood; Recombinant Proteins - administration & dosage; RELAX-AHF study; Relaxin - administration & dosage; Severity of Illness Index; Statistics as Topic; Symptom Flare Up; Treatment Outcome; GDF-15; RELAX-AHF study; Acute heart failure
• ISSN: 1388-9842; 1879-0844
• DOI: 10.1002/ejhf.331

Background
Growth differentiation factor 15 (GDF‐15) was found to be upregulated in patients with chronic heart failure (HF) and associated with disease severity, however, data on patients with acute heart failure (AHF) is lacking.
Methods and results
Levels of GDF‐15 were measured at pre‐specified time‐points (baseline and at days 2, 5, 14, and 60) in patients enrolled in the placebo‐controlled RELAXin in Acute Heart Failure (RELAX‐AHF) study, which examined the effect of serelaxin in 1161 patients with AHF, systolic blood pressure >125 mmHg, and mild to moderate renal impairment. Neither baseline nor changes in GDF‐15 were associated with the degree of dyspnoea or dyspnoea relief. After adjustment for baseline characteristics, baseline GDF‐15 was not associated with the composite endpoint of heart failure or renal failure (HF/RF) readmission at 60 days/cardiovascular (CV) death or CV death at 180 days. In contrast, larger increases in GDF‐15 levels at days 2 and 14 were associated with a greater risk of 60‐day HF/RF rehospitalizations/CV death and CV death at 180 days. Serelaxin treatment was associated with significantly larger decreases of GDF‐15 at days 2 and 5 than placebo.
Conclusions
In AHF patients enrolled in the RELAX‐AHF study, increases in GDF‐15 levels, but not baseline measurements, were associated with a greater likelihood of adverse outcomes. Serelaxin administration was associated with greater decreases in GDF‐15 compared with placebo.