SuPAR predicts postoperative complications and mortality in patients with asymptomatic aortic stenosis

Gethin W Hodges, Casper N Bang, Jesper Eugen-Olsen, Michael H Olsen, Kurt Boman, Simon Ray, Antero Y Kesäniemi, Jørgen L Jeppesen, Kristian Wachtell, Gethin W Hodges, Casper N Bang, Jesper Eugen-Olsen, Michael H Olsen, Kurt Boman, Simon Ray, Antero Y Kesäniemi, Jørgen L Jeppesen, Kristian Wachtell

Abstract

Background: We evaluated whether early measurement of soluble urokinase plasminogen activator receptor (suPAR) could predict future risk of postoperative complications in initially asymptomatic patients with mild-moderate aortic stenosis (AS) undergoing aortic valve replacement (AVR) surgery.

Methods: Baseline plasma suPAR levels were available in 411 patients who underwent AVR surgery during follow-up in the Simvastatin and Ezetimibe in Aortic Stenosis (SEAS) study. Cox analyses were used to evaluate suPAR in relation to all-cause mortality and the composite endpoint of postoperative complications (all-cause mortality, congestive heart failure, stroke and renal impairment) occurring in the 30-day postoperative period.

Results: Patients with initially higher levels of suPAR were at increased risk of postoperative mortality with a HR of 3.5 (95% CI 1.4 to 9.0, P=0.008) and postoperative complications with a HR of 2.7 (95% CI 1.5 to 5.1, P=0.002), per doubling in suPAR. After adjusting for the European System for Cardiac Operative Risk Evaluation or Society of Thoracic Surgeons risk score, suPAR remained associated with postoperative mortality with a HR 3.2 (95% CI 1.2 to 8.6, P=0.025) and 2.7 (95% CI 1.0 to 7.8, P=0.061); and postoperative complications with a HR of 2.5 (95% CI 1.3 to 5.0, P=0.007) and 2.4 (95% CI 1.2 to 4.8, P=0.011), respectively.

Conclusion: Higher baseline suPAR levels are associated with an increased risk for postoperative complications and mortality in patients with mild-moderate, asymptomatic AS undergoing later AVR surgery. Further validation in other subsets of AS individuals are warranted.

Trial registration number: NCT00092677; Post-results.

Keywords: aortic valve disease; inflammation; surgery-valve.

Conflict of interest statement

Competing interests: JEO is a co-founder and shareholder of ViroGates A⁄S, Denmark, the company that produces the suPARnostic assay. He is a co-inventor on patents on suPAR and risk. Copenhagen University Hospital Hvidovre, Denmark, owns the patents, which are licensed to ViroGates A⁄S. KB, SR, AYK and KW served on the SEAS Steering Committee were investigators and members of the steering committees of the SEAS study and have received honoraria from Merck & Co, the sponsor of the SEAS study. KB, SR and KW have received grant support from Merck & Co, the sponsor of the SEAS study. AYK reported Speaker’s fee from Abbott, MSD and Novo Nordisk, Consult for MSD, research funding from MSD and ownership of Orion Pharma stock.

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