Abstract
Aim: Elevated levels of inflammatory biomarker soluble urokinase plasminogen activator receptor (suPAR) predict poor cardiovascular outcomes. Although heavily glycosylated, the influence of glycosylation on suPAR measurement is unknown. We assessed glycosylation effects on suPAR measurement and its discriminative ability for myocardial infarction (MI) and separately, for acute decompensated heart failure (ADHF).
Method: EDTA plasma samples were collected from (i) healthy individuals (n=70), (ii) acute chest pain patients with and without MI (n=65), and (iii) acutely breathless patients with and without ADHF (n=103). Paired plasma samples were treated with deglycosylating enzymes or diluent under identical testing conditions. suPAR concentrations were measured using the CE-marked suPARnostic assay (Virogates). Percentage changes between enzyme-treated and non-treated samples were assessed using the Mann-Whitney test. ROC-AUC analysis compared the discriminative performance of enzyme-treated vs. non-treated suPAR for MI and ADHF.
Results: Following deglycosylation, suPAR concentrations increased across all groups. In healthy individuals, suPAR increased by 52.8% (from 1.9 to 3.0 ng/mL, p<0.0001). Similar increases were observed in MI (53.6%) and non-MI (53.3%) patients. In acutely breathless patients, overall percentage increases were smaller (p<0.0001), but were higher in ADHF (38.6%) than in non-HF breathless patients (24.4%, p=0.002). Deglycosylation did not improve suPAR’s discrimination for MI (n=33) (AUC 0.49 vs. 0.50, p=0.51) but significantly enhanced ADHF (n=53) discrimination (AUC 0.85 vs. 0.78, p=0.003), comparable to NT-proBNP (AUC 0.91, p=0.21) (Figure 1).
Conclusion: Glycosylation underestimates suPAR levels. While effects varied across groups, deglycosylation improved ADHF discrimination in acute breathlessness. Novel assays unaffected by glycosylation could enhance suPAR’s measurement accuracy.