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

Rikke Hjortebjerg, Søren Lindberg, Sune Pedersen, Rasmus Mogelvang, Jan S Jensen, Claus Oxvig, Jan Frystyk, Mette Bjerre

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaperJournal articleResearchpeer-review

Abstract

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.

Original languageEnglish
Article numbere005358
JournalJournal of the American Heart Association
Volume6
Issue3
Pages (from-to)1-16
Number of pages17
ISSN2047-9980
DOIs
Publication statusPublished - 17 Mar 2017

Keywords

  • Journal Article

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