Can Two Blood Biomarkers Together Better Predict Heart Failure Outcomes? | Research

The takeaway

Combining GDF15 with NT-proBNP significantly improved prediction of heart failure events in patients with HFpEF over nearly 6 years of follow-up.

1.72
Hazard ratio for GDF15 predicting heart failure events, independent of other risk factors

What the researchers found

GDF15 independently predicted heart failure events and improved prediction accuracy when combined with NT-proBNP (C-index improvement: 0.7190 to 0.7405).

Why it matters

Better risk prediction in HFpEF could help doctors identify which patients need more aggressive treatment and closer monitoring.

The numbers in context

- 643 patients studied; mean age 73, 42% female

- Median follow-up: about 5.5 years (1,998 days)

- 132 heart failure events and 88 deaths during follow-up

- GDF15 hazard ratio: 1.72 (95% CI 1.35-2.19, p<0.0001)

- NT-proBNP hazard ratio: 1.63 (95% CI 1.25-2.13, p=0.0003)

- Combined C-index improved from 0.719 to 0.741 (p=0.042)

How the study worked

Prospective observational study of 643 HFpEF patients with median follow-up of 1,998 days (~5.5 years).

Who was studied

N=643 patients with HFpEF. Mean age 73, 42% female. Prospective observational study with median follow-up of 1,998 days.

What this study cannot tell us

Single-center observational study. Results need validation in diverse populations. GDF15 is not specific to heart failure.

How to read the evidence

Prospective observational study with long follow-up. Moderate evidence quality; confirmatory studies needed.

When this study was published

Published in 2025 with long-term follow-up data.

The bigger picture

Multi-biomarker approaches may help address the challenge of risk-stratifying HFpEF, a condition with limited treatment options where identifying high-risk patients matters greatly.

Questions still open

Should GDF15 be routinely measured alongside NT-proBNP in HFpEF patients?
Would GDF15-guided treatment strategies improve outcomes?

Common questions

What is GDF15?

Growth differentiation factor-15 is a protein released during cellular stress and inflammation. Elevated levels are associated with poor outcomes in many cardiovascular diseases.

Should doctors test for GDF15 in heart failure patients?

This study suggests it adds value beyond NT-proBNP alone, but routine clinical use would need further validation and guideline endorsement.

Read the original research

Growth differentiation factor-15 and N-terminal pro-BNP in acute heart failure with preserved ejection fraction.

ESC heart failure, 12(2), 888-899

View on PubMed ↗Publisher’s paper ↗

Citation

Otaki, Yoichiro; Watanabe, Tetsu; Shimizu, Mari; Tachibana, Shingo; Sato, Junya; Kobayashi, Yuta; Tamura, Harutoshi; Kato, Shigehiko; Nishiyama, Satoshi; Takahashi, Hiroki; Arimoto, Takanori; Watanabe, Masafumi. (2025). Growth differentiation factor-15 and N-terminal pro-BNP in acute heart failure with preserved ejection fraction.. ESC heart failure, 12(2), 888-899. https://doi.org/10.1002/ehf2.15068