N-terminal and C-terminal fragments of IGFBP-4 as novel biomarkers for short-term risk assessment of major adverse cardiac events in patients presenting with ischemia

ObjectivesPregnancy Associated Plasma Protein A (PAPP-A)-derived N- and C-terminal fragments of IGF-binding protein-4 (NT- and CT-IGFBP-4) released from vulnerable atherosclerotic plaques are proposed to be used for cardiovascular risk assessment.Design and methodsNT- and CT-IGFBP-4 were measured by novel immunoassays in EDTA-plasma of 180 patients admitted to the emergency department with symptoms of myocardial ischemia but without ST-segment elevation. Six-month incidence of major adverse cardiac events (MACE), including myocardial infarction, cardiac death, percutaneous coronary interventions, and coronary artery bypass grafting was recorded.ResultsSixteen patients met the endpoint. NT- and CT-IGFBP-4 were strong predictors of MACE: area under ROC curve (AUC) 0.856 and 0.809, respectively. NT-IGFBP-4 concentrations ≥ 214 μg/L and CT-IGFBP-4 concentrations ≥ 124 μg/L were associated with increased risk of future MACE: adjusted hazard ratio 13.79 and 7.93, respectively.ConclusionsIGFBP-4 fragments can be utilized as biomarkers for MACE prediction in patients with suspected myocardial ischemia.

► N- and C-terminal fragments of IGFBP-4 for cardiovascular risk assessment. ► We examine patients with symptoms of myocardial ischemia but without ST-elevation. ► We examine 6-month incidence of major adverse cardiac events (MACE). ► Elevated NT- or CT-IGFBP-4 is associated with increased risk of future MACE.