Growth differentiation factor 15 predicts poor prognosis in patients with heart failure and reduced ejection fraction and anemia: results from RED-HF.

Abstract

AIMS:

We aimed to assess the value of GDF-15, a stress-responsive cytokine, in predicting clinical outcomes in patients with heart failure (HF) with reduced ejection fraction (HFrEF) and anemia METHODS AND RESULTS: Serum GDF-15 was assessed in 1582 HFrEF and mild-to-moderate anemia patients who where followed for 28 months in the Reduction of Events by Darbepoetin alfa in Heart Failure (RED-HF) trial, an overall neutral RCT evaluating the effect darbepoetin alfa on clinical outcomes in patients with systolic heart failure and mild-to-moderate anemia. Association between baseline and change in GDF-15 during 6 months follow-up and the primary composite outcome of all-cause death or HF hospitalization were evaluated in multivariable Cox-models adjusted for conventional clinical and biochemical risk factors. The adjusted risk for the primary outcome increased with (i) successive tertiles of baseline GDF-15 (tertile 3 HR 1.56 [1.23-1.98] p < 0.001) as well as with (ii) a 15% increase in GDF-15 levels over 6 months of follow-up (HR 1.68 [1.38-2.06] p < 0.001). Addition of change in GDF-15 to the fully adjusted model improved the C-statistics (p < 0.001). No interaction between treatment and baseline or change in GDF-15 on outcome was observed. GDF-15 was inversely associated with several indices of anemia and correlated positively with ferritin.

CONCLUSIONS:

In patients with HF and anemia, both higher baseline serum GDF-15 levels and an increase in GDF-15 during follow-up, were associated with worse clinical outcomes. GDF-15 did not identify subgroups of patients who might benefit from correction of anemia but was associated with several indices of anemia and iron status in the HF patients.

• Authors: Thor Ueland, Lars Gullestad, Lei Kou, James B Young, Marc A Pfeffer, Dirk Jan van Veldhuisen, Karl Swedberg, John J V Mcmurray, Akshay S Desai, Inderjit S Anand, Pål Aukrust
• Journal: Clinical research in cardiology : official journal of the German Cardiac Society (Clin Res Cardiol) Vol. 111 Issue 4 Pg. 440-450 (Apr 2022) ISSN: 1861-0692 [Electronic] Germany
• PMID: 34611778 (Publication Type: Clinical Trial, Journal Article)
• Copyright: © 2021. The Author(s).

Chemical References

• Growth Differentiation Factor 15

Topics

• Anemia (diagnosis, drug therapy)
• Growth Differentiation Factor 15
• Heart Failure (diagnosis, drug therapy)
• Heart Failure, Systolic (complications)
• Humans
• Prognosis
• Stroke Volume