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

• Published in: Clinical biochemistry Vol. 45; no. 7-8; pp. 519 - 524
• Main Authors: Postnikov, A.B., Smolyanova, T.I., Kharitonov, A.V., Serebryanaya, D.V., Kozlovsky, S.V., Tryshina, Y.A., Malanicev, R.V., Arutyunov, A.G., Murakami, M.M., Apple, F.S., Katrukha, A.G.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.05.2012
• Subjects: Acute coronary syndrome; Aged; Aged, 80 and over; Amino Acid Sequence; Animals; Area Under Curve; Biomarkers; Biomarkers - blood; Cardiovascular risk; Coronary Artery Bypass; Cross Reactions; Female; HEK293 Cells; Humans; IGFBP-4 fragments; Immunoassay; Insulin-Like Growth Factor Binding Protein 4 - blood; Ischemia; Major adverse cardiac events (MACE); Male; Mice; Mice, Inbred BALB C; Middle Aged; Molecular Sequence Data; Myocardial infarction; Myocardial Ischemia - diagnosis; Myocardial Ischemia - pathology; Peptide Fragments - blood; Plaque, Atherosclerotic - metabolism; Pregnancy Associated Plasma Protein A (PAPP-A); Pregnancy-Associated Plasma Protein-A - analysis; Prognosis; Proportional Hazards Models; Prospective Studies; Proteolysis; Risk Assessment; Risk Factors; ROC Curve; Sensitivity and Specificity; Time Factors; Myocardial infarction; Immunoassay; Prognosis; Ischemia; Cardiovascular risk; Biomarkers; IGFBP-4 fragments; Major adverse cardiac events (MACE); Acute coronary syndrome; Pregnancy Associated Plasma Protein A (PAPP-A)
• ISSN: 0009-9120; 1873-2933
• DOI: 10.1016/j.clinbiochem.2011.12.030

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. 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. 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≥214μg/L and CT-IGFBP-4 concentrations≥124μg/L were associated with increased risk of future MACE: adjusted hazard ratio 13.79 and 7.93, respectively. IGFBP-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.