Insulin-Like Growth Factor Binding Protein 4 Fragments Provide Incremental Prognostic Information on Cardiovascular Events in Patients With St-Segment Elevation Myocardial Infarction

Background--fragments of insulin-like growth factor binding protein 4 (igfbp-4) are potential new biomarkers for cardiac risk assessment. the fragments are generated on specific cleavage by pregnancy-associated plasma protein-a,which exerts proatherogenic activity. this study investigated the prognostic value of igfbp-4 fragments in patients with st-segment elevation myocardial infarction. methods and results--we prospectively included 656 patients with st-segment elevation myocardial infarction treated with percutaneous coronary intervention from september 2006 to december 2008. blood samples were drawn before percutaneous coronary intervention,and levels of intact igfbp-4 and n-terminal and c-terminal igfbp-4 fragments were measured by specific assays. end points were 5-year all-cause and cardiovascular mortality and the combined end point of major adverse cardiac events. prognostic potential was evaluated on top of a clinical model in terms of discrimination,calibration,and reclassification analysis. during follow-up,166 patients experienced a major adverse cardiac event and 136 patients died,of whom 69 died from cardiovascular causes. both igfbp-4 fragments were associated with all end points (p<0.001). after multivariable adjustments,both n-terminal and c-terminal igfbp-4 fragment levels remained associated with all end points,including cardiovascular mortality with hazard ratios per doubling in protein concentration of 2.54 (95% ci 1.59-4.07; p<0.001) and 2.07 (95% ci 1.41-3.04; p<0.001),respectively. incorporation of igfbp-4 fragments into a clinical model with 15 risk factors improved c-statistics and model calibration and provided incremental prognostic contribution,as assessed by net reclassification improvement and integrated discrimination improvement. conclusions--igfbp-4 fragments are associated with increased risk of all-cause mortality,cardiovascular mortality,and major adverse cardiac events in patients with st-segment elevation myocardial infarction.