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

*Corresponding author for this work

Research output: Contribution to journalJournal 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
Issue number3
ISSN2047-9980
DOIs
Publication statusPublished - 17. Mar 2017

Keywords

  • Biomarker
  • Cardiovascular disease
  • Insulin-like growth factor binding protein 4
  • Pregnancy-associated plasma protein A
  • ST-segment elevation myocardial infarction
  • Heart Failure/epidemiology
  • Myocardial Infarction/epidemiology
  • ST Elevation Myocardial Infarction/blood
  • Cardiovascular Diseases/mortality
  • Prognosis
  • Patient Readmission
  • Humans
  • Middle Aged
  • Mortality
  • Proportional Hazards Models
  • Male
  • Cause of Death
  • Insulin-Like Growth Factor Binding Protein 4/blood
  • Aged, 80 and over
  • Female
  • Stroke/epidemiology
  • Aged
  • Peptide Fragments/blood
  • Percutaneous Coronary Intervention

Fingerprint

Dive into the research topics of 'Insulin-Like Growth Factor Binding Protein 4 Fragments Provide Incremental Prognostic Information on Cardiovascular Events in Patients With ST-Segment Elevation Myocardial Infarction'. Together they form a unique fingerprint.

Cite this