Insulin-Like Growth Factor Axis (Insulin-Like Growth Factor-I/Insulin-Like Growth Factor-Binding Protein-3) as a Prognostic Predictor of Heart Failure: Association with Adiponectin

AIMS: Insulin-like growth factor (IGF)-I is a regulator of glucose/fatty acid metabolism and may be involved in the pathophysiology of cardiovascular disease, but it remains unclear whether endogenous IGF-I is associated with the prognosis of heart failure (HF). We investigated whether the IGF axis, the ratio of IGF-I to IGF-binding protein-3 (IGFBP-3), was a predictor of clinical outcomes in HF. The association of IGF axis with serum adiponectin level, a prognostic marker of HF as well as a regulator of glucose/fatty acid metabolism, was also analysed. METHODS AND RESULTS: We measured serum IGF-I and IGFBP-3 in 142 HF patients with left ventricular systolic dysfunction and 63 control subjects. Patients with HF underwent clinical assessment and measurement of adiponectin and B-type natriuretic peptide (BNP). Compared with controls, HF patients showed significantly decreased serum IGF axis values [median (inter-quartile ranges), 0.114 (0.063-0.150) vs. 0.099 (0.052-0.158), P = 0.042]. In HF patients, the log-transformed IGF axis values were inversely correlated with the log-transformed serum adiponectin levels (r = -0.35, P < 0.0001) and plasma BNP levels (r = -0.25, P = 0.0028). The IGF axis was lower in patients with New York Heart Association (NYHA) functional class III/IV than those with class I/II [0.071 (0.044-0.145) vs. 0.107 (0.068-0.161), P = 0.022]. Furthermore, a decrease in IGF axis was associated with increased rates of all-cause mortality (P = 0.013), cardiac death (P = 0.035), and a composite of cardiac death and re-hospitalization (P = 0.0085). CONCLUSION: Insulin-like growth factor axis is a significant predictor of clinical outcomes in HF and is significantly associated with serum adiponectin levels.