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

Objectives Pregnancy 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 methods NT- 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. Results Sixteen 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. Conclusions IGFBP-4 fragments can be utilized as biomarkers for MACE prediction in patients with suspected myocardial ischemia.