Plasma Proteome Analysis Identifies Vascular Endothelial Growth Factor Receptor 1 as a Prognostic Biomarker in Cardiogenic Shock.

Background: Cardiogenic shock (CS) is a severe complication of acute myocardial infarction (AMI) leading to poor outcomes. Specific biomarkers, with subsequent validation of their prognostic relevance in CS, are urgently needed to improve therapies and outcomes. Accordingly, the present study investigated the plasma proteome using proximity extension assay technology to identify novel specific biomarkers with subsequent validation of their prognostic relevance in CS.

Methods: Using proximity extension assay (Olink Explore, 2942 proteins), the proteomic signature in the plasma of 9 AMI patients without shock and 8 AMI patients with CS (AMICS; exploration cohort) at admission was analyzed. Candidate biomarkers were measured in the plasma of 421 patients with AMICS from the CULPRIT-SHOCK cohort (REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT01927549, validation cohort). Their prognostic relevance was assessed for 180-day survival as the primary end point.

Results: Proteome profiling was successful for 2925 proteins and identified VEGFR1 (vascular endothelial growth factor receptor 1, also known as Flt1) as elevated in AMICS compared with nonshock AMI in the exploration cohort (P<0.001). In patients from the independent validation cohort, nonsurvivors had markedly higher VEGFR1 levels (6.8 versus 3.8 ng/L; P<0.001). In Cox regression, VEGFR1 levels were independently associated with a higher 180-day mortality risk even after adjusting for the Simplified Acute Physiology Score II (per ng/L; adjusted hazard ratio, 1.06 [95% CI, 1.03-1.09]; P<0.001) and yielded incremental prognostic information in addition to serum lactate levels (P<0.001). The levels of VEGFR1 in surviving (30 days; n=29) and nonsurviving (n=21) patients with AMICS were determined at different time points (days 0, 1, and 5) in a third cohort, showing continuously higher levels in nonsurvivors.

Conclusions: Plasma proteomic screening identified VEGFR1 as an early biomarker in patients with AMICS that provided independent prognostic information in a large cohort of well-defined patients with AMICS.