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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
Bouabdallaoui, Nadia Claggett, Brian Zile, Michael R. McMurray, John J. V. O'Meara, Eileen Packer, Milton Prescott, Margarett F. Swedberg, Karl Solomon, Scott D. Rouleau, Jean L.
Bouabdallaoui, Nadia
Claggett, Brian
Zile, Michael R.
McMurray, John J. V.
O'Meara, Eileen
Packer, Milton
Prescott, Margarett F.
Swedberg, Karl
Solomon, Scott D.
Rouleau, Jean L.
Abstract
Aims: 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. Methods and results: 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). Conclusion: 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.
Keywords
heart failure with reduced ejection fraction, GDF-15, biomarkers, sacubitril/valsartan, global risk assessment, cardiovascular mortality
Date
2018
Type
Journal article
Journal
European Journal of Heart Failure
Book
Volume
20
Issue
12
Page Range
1701-1709
Article Number
ACU Department
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Relation URI
Source URL
Event URL
Open Access Status
License
File Access
Controlled