分子バイオマーカーと診断のジャーナル

Serum Biomarkers that Stimulate the Mitogen-Activated Protein Kinase Cascade in Relation to Recurrent Coronary Events Following an Acute Coronary Syndrome

Abstract

Maxime M Vroegindewey, Nermina Buljubasic, Rohit M Oemrawsingh, Isabella Kardys, Folkert W Asselbergs, Pim van der Harst, Victor A Umans, Bas Kietselaer, Timo Lenderink, Anho Liem, Henk Mouthaan, Eric Boersma and K Martijn Akkerhuis

Background: The intracellular mitogen-activated protein kinase (MAPK) cascade regulates intracellular processes that modulate cardiovascular disease progression. We explored the time-course of serum biomarkers that stimulate the MAPK-cascade in post-acute coronary syndrome (ACS) patients, prior to a recurrent coronary event.

Methods: BIOMArCS is a high-frequent repeated blood sampling study in post-ACS patients. We performed a nested case-control study selecting the 45 patients who experienced a recurrent event (cases) and 2 matched event-free controls per case during 1-year follow-up. Olink Proteomics ’immunoassay was used to measure 25 serum biomarkers. Results are expressed in the arbitrary Normalized Protein eXpression (NPX) unit on the 2log-scale. Linear mixed-effects models were applied to examine time-courses and differences between cases and controls.

Results: Mean age was 66 ± 12 years and 80% were men, with no differences between cases and controls. Early cases had significantly higher levels of ANG-1 (difference 0.95 NPX (95%CI 0.36-1.54), PAR-1 (difference 0.50 NPX (95%CI 0.22-0.77) and BMP-6 (difference 0.55 NPX (95%CI 0.21-0.90) than controls. No differences in biomarker levels were observed between late cases and matching controls. In particular, in cases, no increase was observed prior to the moment of the recurrent event.

Conclusion: Patients with an early recurrent coronary event after an index-ACS had higher levels of ANG-1, PAR-1 and BMP-6 than patients who remained event-free.