Elsevier

JACC: Heart Failure

Volume 5, Issue 4, April 2017, Pages 268-277
JACC: Heart Failure

Focus Issue: Biomarkers and Risk Prediction
Soluble Urokinase-Type Plasminogen Activator Receptor Improves Risk Prediction in Patients With Chronic Heart Failure

https://doi.org/10.1016/j.jchf.2016.12.008Get rights and content
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Abstract

Objectives

This study investigated the predictive value of soluble urokinase-type plasminogen activator receptor (suPAR) in patients with chronic heart failure (CHF).

Background

SuPAR originates from proteolytic cleavage of the membrane-bound receptor from activated immune and endothelial cells and reflects the level of immune activation. As inflammation plays a crucial role in the complex pathophysiology of CHF, we hypothesized that suPAR might be a suitable prognostic biomarker in patients with CHF.

Methods

SuPAR levels were determined in 319 patients with CHF admitted to our outpatient department for heart failure and in a second cohort consisting of 346 patients with CHF, for validation.

Results

During a median follow-up time of 3.2 years, 119 patients (37.3%) died. SuPAR was a strong predictor of mortality with a crude hazard ratio (HR) per increase of 1 SD (HR per 1 SD) of 1.96 (95% confidence interval [CI]: 1.63 to 2.35; p < 0.001) in univariate analysis and remained significant after comprehensive multivariate adjustment with an adjusted HR per 1 SD of 1.38 (95% CI: 1.04 to 1.83; p = 0.026). SuPAR added prognostic value beyond the multivariate model indicated by improvements in C-statistics (area under the curve: 0.72 vs 0.74, respectively; p = 0.02), the category-free net reclassification index (24.9%; p = 0.032), and the integrated discrimination improvement (0.011; p = 0.05). Validation in the second cohort yielded consistent results.

Conclusions

SuPAR is a strong and independent predictor of mortality in patients with CHF, potentially suitable to refine risk assessment in this vulnerable group of patients. Our results emphasize the impact of immune activation on survival in patients with CHF.

Key Words

heart failure
prognosis
soluble urokinase-type plasminogen activator receptor
suPAR

Abbreviations and Acronyms

AF
atrial fibrillation
CART
classification and regression tree analysis
CHF
chronic heart failure
CRP
C-reactive protein
eGFR
estimated glomerular filtration rate
IDI
integrated discrimination increment
NRI
net reclassification index
NT-proBNP
N-terminal pro B-type natriuretic peptide
NYHA
New York Heart Association
suPAR
soluble urokinase-type plasminogen activator receptor

Cited by (0)

This work was supported by the Association for the Promotion of Research on Arteriosclerosis, Thrombosis, and Vascular Biology and the Ludwig Boltzmann Cluster for Cardiovascular Research. Dr. Koller is recipient of a DOC fellowship of the Austrian Academy of Sciences (24346).

The authors have reported that they have no relationships relevant to the contents of this paper to declare.