Insulin-like growth factor binding protein-3 (IGFBP-3): a biomarker of coronary artery disease induced myocardial ischaemia.

AIMS

Among individuals presenting to the emergency department (ED) with chest pain, clinical uncertainty surrounds the appropriate identification of non-myocardial infarction (MI) individuals who would most benefit from objective functional/anatomical testing (e.g. imaging). We applied a proteomic biomarker discovery approach to identify novel candidates reflecting coronary artery disease (CAD) induced ischaemia that could translate to measurement in clinical samples.

METHODS AND RESULTS

Mass spectroscopy (MS) of perfusate from an isolated rat heart model of cardiac ischaemia identified >100 novel protein biomarkers. A prominent candidate, insulin-like growth factor binding protein (IGFBP-3), was then interrogated for its ability to identify CAD-related ischaemia (e.g. positive cardiac stress test; unstable angina pectoris, UAP; arterial stenosis >70% on angiography) in multiple patient sample sets [cardiac stress testing, = 12; septal alcohol ablation (SAA), = 12; ED chest pain, = 2977]. In cardiac stress testing, a significant delta IGFBP-3 (ΔIGFBP-3) between 0 and 150 min was seen in positive, but not negative, tests ( = 0.03). In SAA, peripheral IGFBP-3 levels did not change over 24 h ( = 0.57). In ED patients, ΔIGFBP-3 between 0 and 2 h (i) identified more 365-day low-risk major adverse cardiac event cases (27-30%), (ii) provided 7% improvement in positive predictive value over a clinical model for the identification of unstable angina ( = 0.01), and (iii) was a significant, independent predictor of >70% stenosis on angiography, improving indeterminate risk prediction by 9% (95% CI 3-15%).

CONCLUSION

Our discovery approach has translated IGFBP-3 as a potential biomarker to identify significant CAD/ischaemia in patients who do not meet diagnostic thresholds for MI.