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. 2022 Nov 2;11(10):731–738.
doi: 10.1093/ehjacc/zuac096. Epub 2022 Aug 11.

Soluble urokinase-type plasminogen activator receptor improves early risk stratification in cardiogenic shock

Mari Hongisto  1 , Johan Lassus  2 , Tuukka Tarvasmäki  2 , Jordi Sans-Roselló  3 , Heli Tolppanen  2 , Anu Kataja  1 , Toni Jäntti  2 , Tuija Sabell  2 , Marek Banaszewski  4 , Jose Silva-Cardoso  5 , John Parissis  6 , Raija Jurkko  2 , Jindrich Spinar  7 , Maaret Castrén  1 , Alexandre Mebazaa  8 , Josep Masip  9 , Veli Pekka Harjola  1 ; CardShock Study Investigators and the GREAT Network
Affiliations

Soluble urokinase-type plasminogen activator receptor improves early risk stratification in cardiogenic shock

Mari Hongisto et al. Eur Heart J Acute Cardiovasc Care. .

Abstract

Aims: Soluble urokinase-type plasminogen activator receptor (suPAR) is a biomarker reflecting the level of immune activation. It has been shown to have prognostic value in acute coronary syndrome and heart failure as well as in critical illness. Considering the complex pathophysiology of cardiogenic shock (CS), we hypothesized suPAR might have prognostic properties in CS as well. The aim of this study was to assess the kinetics and prognostic utility of suPAR in CS.

Methods and results: SuPAR levels were determined in serial plasma samples (0-96 h) from 161 CS patients in the prospective, observational, multicentre CardShock study. Kinetics of suPAR, its association with 90-day mortality, and additional value in risk-stratification were investigated. The median suPAR-level at baseline was 4.4 [interquartile range (IQR) 3.2-6.6)] ng/mL. SuPAR levels above median were associated with underlying comorbidities, biomarkers reflecting renal and cardiac dysfunction, and higher 90-day mortality (49% vs. 31%; P = 0.02). Serial measurements showed that survivors had significantly lower suPAR levels at all time points compared with nonsurvivors. For risk stratification, suPAR at 12 h (suPAR12h) with a cut-off of 4.4 ng/mL was strongly associated with mortality independently of established risk factors in CS: OR 5.6 (95% CI 2.0-15.5); P = 0.001) for death by 90 days. Adding suPAR12h > 4.4 ng/mL to the CardShock risk score improved discrimination identifying high-risk patients originally categorized in the intermediate-risk category.

Conclusion: SuPAR associates with mortality and improves risk stratification independently of other previously known risk factors in CS patients.

Keywords: Biomarker; Cardiogenic shock; Risk stratification; suPAR.

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Conflict of interest statement

Conflict of interest: J.P. received honoraria for lectures from Orion Pharma, Roche Diagnostics, Novartis, Astra and Servier. A.M. reports personal fees from Orion, Servier, Otsuka, Philips, Sanofi, Adrenomed, Epygon and Fire 1 and grants and personal fees from 4TEEN4, Abbott, Roche and Sphyngotec. All other authors have no conflicts to declare.

Figures

Graphical Abstract
Graphical Abstract
Soluble urokinase-type plasminogen activator receptor (suPAR) improves early risk stratification in cardiogenic shock spesifically in patients with intermediate risk.
Figure 1
Figure 1
Soluble urokinase–type plasminogen activator receptor 0–96 h levels in survivors vs. non-survivors. Soluble urokinase–type plasminogen activator receptor levels during 0–96 h in survivors and non-survivors. Soluble urokinase–type plasminogen activator receptor median levels at each time point are presented below the figure.
Figure 2
Figure 2
Receiver operating characteristic curves for predicting 90-day mortality. Receiver operating characteristic curves for 90-day mortality prediction for (i) soluble urokinase–type plasminogen activator receptor at 12 h, (ii) CardShock risk score, and (iii) CardShock risk score + soluble urokinase–type plasminogen activator receptor12h > 4.4 ng/mL.
Figure 3
Figure 3
Kaplan–Meier survival curves for 90-day mortality stratified by the CardShock risk score categories and soluble urokinase–type plasminogen activator receptor above or below the cut-off-value 4.4 ng/mL at 12 h. Panel (A) comparison of survival curves according to the CardShock risk score categories (low/intermediate/high risk), (B) comparison of survival curves according to the CardShock risk score categories (low/intermediate/high risk) divided by the soluble urokinase–type plasminogen activator receptor cut-off 4.4 ng/mL at 12 h into two subgroups.
See this image and copyright information in PMC

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