Serum insulin-like growth factor binding protein-1 (IGFBP-1) phosphorylation status in subjects with and without ischaemic heart disease

Background: Insulin-like growth factor binding protein-1 (IGFBP-1) modulates the activity of IGF-I. It exists in serum as phosphorylated and less phosphorylated forms. We wished to measure serum levels of both these forms of IGFBP-1, using a novel assay, in subjects with, or without ischaemic heart disease (IHD).

Methods: We measured serum concentrations of the phosphorylated and less phosphorylated forms of IGFBP-1 in 75 subjects (36 with and 39 without IHD). Two immunoassays were used, one which detects non-, and less-phosphorylated forms (LpIGFBP-1), and another which specifically detects the serine phosphorylated form of IGFBP-1 (pIGFBP-1).

Results: LpIGFBP-1 concentrations were significantly higher in subjects without IHD than in those with IHD (5.3+/-0.5 microg/L vs. 2.7+/-0.4 microg/L, p<0.001). pIGFBP-1 levels were also significantly higher in subjects without IHD compared to those with IHD (33.3+/-2.0 microg/L vs. 25.3+/-2.2 microg/L, p<0.01). The correlation between LpIGFBP-1 and pIGFBP-1 for all subjects was (r=0.71, p<0.001). This association was stronger in subjects without IHD (r=0.76, p<0.001) than for those with IHD (r=0.60, p<0.001). A significant negative association was observed between IGF-I and the ratio between the two forms (r=-0.45, p<0.0001). Receiver-Operating Characteristic (ROC) curve showed the highest area under the curve for LpIGFBP-1 (0.75) [95% CI: 0.63-0.86] and optimum cut-off value of 2.83 microg/L with 75% sensitivity and 74% specificity.

Conclusions: We propose that low serum concentrations of IGFBP-1 forms could be a marker of coronary risk, and the LpIGFBP-1:pIGFBP-1 ratio may be an index of biologically active IGF-I.