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Updated: Jun 28, 2025
Lumped-Parameter and Finite Element Modeling of Heart Failure with Preserved Ejection Fraction
Published on: February 13, 2021
Prognostic value of growth differentiation factor-15 in heart failure among whole ejection fraction phenotypes
1Department of Cardiology, The Second Medical Centre, Chinese PLA General Hospital, Beijing, China.
Insights
Growth differentiation factor-15 (GDF-15) predicts adverse outcomes in heart failure (HF) patients with coronary heart disease (CHD). Adding GDF-15 to the MAGGIC risk score improves prediction of mortality and rehospitalization, especially in HF with preserved ejection fraction (HFpEF).
Area of Science:
- Cardiology
- Biomarkers
- Heart Failure Research
Background:
- The prognostic utility of growth differentiation factor-15 (GDF-15) in heart failure (HF) patients, particularly across different ejection fraction (EF) phenotypes in coronary heart disease (CHD), remains incompletely understood.
- Existing risk stratification models for HF may not fully capture long-term adverse event risks.
Purpose of the Study:
- To investigate the association between GDF-15 levels and long-term adverse outcomes (all-cause mortality and HF rehospitalization) in HF patients with varying EF.
- To evaluate the incremental prognostic value of incorporating GDF-15 into the Meta-Analysis Global Group in Chronic Heart Failure (MAGGIC) risk score.
Main Methods:
- A single-center cohort study included 823 HF patients categorized into HF with reduced EF (HFrEF), mid-range EF (HFmrEF), and preserved EF (HFpEF).
- GDF-15 levels and MAGGIC risk scores were assessed.
- Cox regression models and metrics like C-index, integrated discrimination improvement (IDI), and net reclassification improvement (NRI) were used to analyze associations and prognostic value over a 9.4-year follow-up.
Main Results:
- Higher GDF-15 concentrations were observed in the HFpEF group compared to HFrEF and HFmrEF groups.
- Elevated GDF-15 levels were significantly associated with increased risks of all-cause mortality (HR=1.36) and HF rehospitalization (HR=1.75) across all HF phenotypes.
- Integrating GDF-15 into the MAGGIC risk score model significantly improved prognostic capability for adverse outcomes (Δ C-index=0.021 for mortality, 0.034 for rehospitalization), particularly in the HFpEF subgroup.
Conclusions:
- GDF-15 is an independent predictor of adverse outcomes in HF patients across the full spectrum of EF in the context of CHD.
- The addition of GDF-15 to the MAGGIC risk score enhances risk prediction for mortality and HF rehospitalization in the general HF population.
- The incremental prognostic benefit of GDF-15 was most pronounced in the HFpEF subgroup.
Aims:
The utility of growth differentiation factor-15 (GDF-15) in predicting long-term adverse outcomes in heart failure (HF) patients is not well established. This study explored the relationship between GDF-15 levels and adverse outcomes in HF patients across various ejection fraction (EF) phenotypes associated with coronary heart disease (CHD) and evaluated the added prognostic value of incorporating GDF-15 into the Meta-Analysis Global Group in Chronic Heart Failure (MAGGIC) risk score-based model.
Methods And Results:
This single-centre cohort study included 823 HF patients, categorized into 230 (27.9%) reduced EF (HFrEF), 271 (32.9%) mid-range EF (HFmrEF), and 322 (39.1%) preserved EF (HFpEF) groups. The median age was 68.0 years (range: 56.0-77.0), and 245 (29.8%) were females. Compared with the HFrEF and HFmrEF groups, the HFpEF group had a higher GDF-15 concentration (P = 0.002) and a higher MAGGIC risk score (P < 0.001). We examined the associations between GDF-15 levels and the risks of all-cause mortality and HF rehospitalization using Cox regression models. The C-index, integrated discrimination improvement (IDI), and net reclassification improvement (NRI) metrics were employed to assess the incremental prognostic value. During the 9.4 year follow-up period, 425 patients died, and 484 were rehospitalized due to HF. Multivariate Cox regression analysis revealed that elevated GDF-15 levels were significantly associated with an increased risk of all-cause mortality [hazard ratio (HR) = 1.36, 95% confidence interval (CI): 1.20-1.54; P < 0.001] and HF rehospitalization (HR = 1.75, 95% CI: 1.57-1.95; P < 0.001) across all HF phenotypes. This association remained significant when GDF-15 was treated as a categorical variable (high GDF-15 group: all-cause death: HR = 1.73, 95% CI: 1.40-2.14; P < 0.001; HF rehospitalization: HR = 3.37, 95% CI: 2.73-4.15; P < 0.001). Inclusion of GDF-15 in the MAGGIC risk score-based model provided additional prognostic value for all HF patients (Δ C-index = 0.021, 95% CI: 0.002-0.041; IDI = 0.011, 95% CI: 0.001-0.025; continuous NRI = 0.489, 95% CI: 0.174-0.629) and HF rehospitalization (Δ C-index = 0.034, 95% CI: 0.005-0.063; IDI = 0.021, 95% CI: 0.007-0.032; continuous NRI = 0.307, 95% CI: 0.147-0.548), particularly in the HFpEF subgroup.
Conclusions:
GDF-15 is identified as an independent risk factor for adverse outcomes in HF patients across the entire EF spectrum in the context of CHD. Integrating GDF-15 into the MAGGIC risk score-based model enhances its prognostic capability for adverse outcomes in the general HF population. This incremental prognostic effect was observed specifically in the HFpEF subgroup and not in other subgroups.
