Disturbance of anabolic hormones such as ghrelin and leptin could be the cause of developing cardiovascular diseases. In addition, imbalance between ghrelin/GH/IGF-1 axis and leptin may be the reason for reduction of ejection fraction among cardiovascular patients. Background: Following detection of receptors for ghrelin and growth hormone (GH) in the cardiovascular system, different clinical trials have used ghrelin or GH for the treatment of cardiac patients. While some of these trials reported improvements in the patients' situation, others reported deterioration. Objectives: To clarify the contradictory outcomes, we designed this study to evaluate the circadian rhythms of acylated ghrelin, GH, and the related factors [Insulin-like Growth Factor-1 (IGF-1), Insulin-like Growth Factor Binding Proteins 1 and 3 (IGFBP-1 and IGFBP-3)], and leptin in patients with reduced ejection fraction (rEF). Patients and Methods: Ten patients with rEF and an equal number of healthy control subjects matched for age and gender participated in this study according to inclusion criteria. All participants were hospitalized in the cardiac care unit (CCU), under identical conditions during collection of blood (every 2 hours). Primary processing of samples was carried out immediately and the plasma was stored at-20ºC until evaluation of the aforementioned parameters using ELISA methods. Results: Evaluation of the collected data showed that among aged participants only circulating leptin is gender-dependent, while the patients had significantly (P < 0.001) lower ghrelin, GH, IGF-1, and IGFBP-1, but a higher level of IGFBP-3 compared to the control group. In addition, except for GH that showed a mild circadian rhythm, the parameters we examined did not have a significant circadian rhythm. Correlation analysis of the data showed a positive correlation between ghrelin and GH or IGF-1, and significant negative or positive correlations between leptin and IGFBP-1, or IGFBP-3, respectively, in both groups. Conclusions: Here, for the first time, we show that circulating ghrelin, GH, and IGF-1 levels are reduced in the patients with rEF, and the condition of patients is deteriorated not only due to reduced IGF-1 but also due to reduction of IGFBP-1 or increase of IGFBP-3, which may be influenced by circulating leptin. Finally, disturbance of the balance between ghrelin/GH/IGF-1 and leptin may be the cause of rEF, and thus evaluation of these parameters could provide diagnostic as well as prognostic tools for the treatment of these patients.