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Growth differentiation factor-15 is not modified by sacubitril/valsartan and is an independent marker of risk in patients with heart failure and reduced ejection fraction: the PARADIGM-HF trial.
- Source :
- European Journal of Heart Failure; Dec2018, Vol. 20 Issue 12, p1701-1709, 9p, 3 Charts, 3 Graphs
- Publication Year :
- 2018
-
Abstract
- <bold>Aims: </bold>Growth differentiation factor-15 (GDF-15) is associated with adverse prognosis in cardiovascular (CV) and non-CV diseases. We evaluated the association of GDF-15 with CV and non-CV outcomes in the PARADIGM-HF trial.<bold>Methods and Results: </bold>In 1935 patients with heart failure and reduced ejection fraction (HFrEF) in PARADIGM-HF, median GDF-15 values were elevated and similar in sacubitril/valsartan and enalapril patients (1626 ng/L and 1690 ng/L, respectively). Diabetes, age, creatinine, high-sensitive troponin T, N-terminal pro-B-type natriuretic peptide, and New York Heart Association class III/IV were most strongly associated with elevated GDF-15 values (all P < 0.001) (adjusted R2 = 0.3857). Baseline GDF-15 and changes in GDF-15 at both 1 month and 8 months (log-transformed) were associated with subsequent mortality and CV events. Each 20% increment in baseline GDF-15 value was associated with a higher risk of mortality [adjusted hazard ratio (HR) 1.13, 95% confidence interval (CI) 1.08-1.18, P < 0.001], the combined endpoint of CV death or hospitalization for heart failure (adjusted HR 1.09, 95% CI 1.05-1.14, P < 0.001) and heart failure death (adjusted HR 1.16, 95% CI 1.05-1.28, P < 0.001). Changes in GDF-15 were not influenced by assigned therapy (all P-values ≥ 0.1).<bold>Conclusion: </bold>In patients with ambulatory HFrEF, GDF-15 is not modified by sacubitril/valsartan and is strongly associated with mortality and CV outcomes, suggesting that GDF-15 is a marker of poor outcomes in these patients.<bold>Clinical Trial Registration: </bold>ClinicalTrials.gov Identifier NCT01035255. [ABSTRACT FROM AUTHOR]
- Subjects :
- AMINOBUTYRIC acid
HETEROCYCLIC compounds
ANGIOTENSIN receptors
CLINICAL trials
COMPARATIVE studies
CYTOKINES
ENZYME-linked immunosorbent assay
HEART failure
LONGITUDINAL method
RESEARCH methodology
MEDICAL cooperation
RESEARCH
RESEARCH funding
TIME
EVALUATION research
TREATMENT effectiveness
DISEASE progression
STROKE volume (Cardiac output)
THERAPEUTICS
Subjects
Details
- Language :
- English
- ISSN :
- 13889842
- Volume :
- 20
- Issue :
- 12
- Database :
- Complementary Index
- Journal :
- European Journal of Heart Failure
- Publication Type :
- Academic Journal
- Accession number :
- 133603810
- Full Text :
- https://doi.org/10.1002/ejhf.1301