Harrell FEJ

World Health Organization

Journal of the American Heart Association : Cardiovascular and Cerebrovascular Disease


            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
              &lt;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
              &lt;0.001) and 2.07 (95% CI 1.41–3.04;
              P
              &lt;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.
            
          </jats:sec

Rikke Hjortebjerg

Søren Lindberg

Sune Pedersen

Rasmus Mogelvang

Jan S. Jensen

Claus Oxvig

Jan Frystyk

Mette Bjerre

Crossref

Journal of the American Heart Association

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

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

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