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.
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.
Authors: Christina Christersson; Tomasz Baron; Frank Flachskampf; Lars Lindhagen; Bertil Lindahl; Agneta Siegbahn Journal: J Cardiovasc Transl Res Date: 2022-06-21 Impact factor: 4.132
Authors: Nels C Olson; Laura M Raffield; Anne H Moxley; Tyne W Miller-Fleming; Paul L Auer; Nora Franceschini; Debby Ngo; Timothy A Thornton; Ethan M Lange; Yun Li; Deborah A Nickerson; Neil A Zakai; Robert E Gerszten; Nancy J Cox; Adolfo Correa; Karen L Mohlke; Alexander P Reiner Journal: Circ Genom Precis Med Date: 2021-10-28
Authors: Angela S Koh; Bhaarathy Velmurugan; Fei Gao; Ru San Tan; Jia-Ing Wong; Louis L Y Teo; Bryan M H Keng; Serene J M Chua; Jian-Min Yuan; Woon-Puay Koh; Christine Cheung Journal: BMC Geriatr Date: 2017-11-28 Impact factor: 3.921
Authors: Nina S Godtfredsen; Ditte V Jørgensen; Kristoffer Marsaa; Charlotte S Ulrik; Ove Andersen; Jesper Eugen-Olsen; Line J H Rasmussen Journal: Respir Res Date: 2018-05-21