Free IGF-1, Intact IGFBP-4, and PicoPAPP-A are Altered in Acute Myocardial Infarction Compared to Stable Coronary Artery Disease and Healthy Controls.

Insulin-like growth factor-1 (IGF-1) and its binding proteins have been implicated in the pathophysiology of coronary artery disease (CAD) and myocardial infarction (MI). We investigated components of the IGF-1 system in circulation at the time of acute MI and following reperfusion in relation to levels of stable CAD patients and controls. Patients with MI (MI Group, n=31) treated with percutaneous coronary intervention (PCI) were compared to patients with stable CAD subjected to scheduled PCI (CAD Group, n=40) and controls with symptoms mimicking CAD without stenosis in angiography (Control Group, n=43). The number and extent of stenosis were recorded. Total and free IGF-1, total and intact IGF binding protein (IGFBP)-3 and -4, pico-Pregnancy Associated Plasma Protein-A (PAPP-A), and the known markers ALT, AST, CK and CK-MB were measured at baseline and 6 or 24 h after the intervention. Patients with MI had higher free IGF-1 (p=0.003) and PAPP-A (p=0.011), but lower intact IGFBP-4 (p=0.006) compared with patients with stable CAD or healthy controls. None of the investigated molecules changed following reperfusion or correlated with the extent of stenosis. AST (p<0.001), CK (p<0.001) and CK-MB (p<0.001), were also higher. Free IGF-1, intact IGFBP-4 and PAPP-A could predict MI, but with lower accuracy than CK-MB. In conclusion, free IGF-1 levels are higher in MI compared to CAD patients and controls and this could result from increased cleavage of its binding protein IGFBP-4 by the higher PAPP-A levels. Free IGF-1, intact IGFBP-4, and/or PAPP-A are inferior to CK-MB as predictors or markers of myocardial damage.

Circulating irisin levels are lower in patients with either stable coronary artery disease (CAD) or myocardial infarction (MI) versus healthy controls, whereas follistatin and activin A levels are higher and can discriminate MI from CAD with similar to CK-MB accuracy.

BACKGROUND: Several myokines are produced by cardiac muscle. We investigated changes in myokine levels at the time of acute myocardial infarction (MI) and following reperfusion in relation to controls. METHODS: Patients with MI (MI Group, n=31) treated with percutaneous coronary intervention (PCI) were compared to patients with stable coronary artery disease (CAD) subjected to scheduled PCI (CAD Group, n=40) and controls with symptoms mimicking CAD without stenosis in angiography (Control Group, n=43). The number and degree of stenosis were recorded. Irisin, follistatin, follistatin-like 3, activin A and B, ALT, AST, CK and CK-MB were measured at baseline and 6 or 24h after the intervention. RESULTS: MI and CAD patients had lower irisin than controls (p<0.001). MI patients had higher follistatin, activin A, CK, CK-MB and AST than CAD patients and controls (all p≤0.001). None of the myokines changed following reperfusion. Circulating irisin was associated with the degree of stenosis in all patients (p=0.05). Irisin was not inferior to CK-MB in predicting MI while folistatin and activin A could discriminate MI from CAD patients with similar to CK-MB accuracy. None of these myokines was altered following PCI in contrast to CK-MB. CONCLUSIONS: Irisin levels are lower in MI and CAD implying that their production may depend on myocadial blood supply. Follistatin and activin A are higher in MI than in CAD suggesting increased release due to myocardial necrosis. They can predict MI with accuracy similar to CK-MB and their role in the diagnosis of MI remains to be confirmed by prospective large clinical studies.