Cedars-Sinai Heart Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA.
J Cardiovasc Pharmacol Ther. 2012 Mar;17(1):72-8. doi: 10.1177/1074248411402078. Epub 2011 Mar 31.
Heart failure (HF) is an important health concern with almost a quarter million deaths each year despite advances in medical therapy. Improvement of cardiac function has been shown to reduce morbidity and mortality in patients with HF. There has been recent interest in the growth hormone (GH) / insulin-like growth factor (IGF) pathway as a potential therapeutic target for patients with HF. Insulin-like growth factor 1 has been shown to augment cardiac function ex vivo and in animals. It was hypothesized that IGF-1/IGF-binding protein 3 levels might be able to provide prognostic benefits in patients with heart disease. Initial observational studies have shown significant benefits from GH supplementation including improved ejection fraction, increased exercise tolerance, and decreased New York Heart Association functional class. These results, however, were not replicated in randomized, controlled trials. Patients with advanced stages of HF might develop cachexia associated with a state of significant GH resistance. The lack of response to GH supplementation may be secondary to a deficiency in IGF-1, the effector hormone. Hypothetically, this group of patients could benefit from direct IGF-1 supplementation. Combined therapy with GH and IGF-1 is appealing; however, future trials in patients with advanced HF are warranted to prove this concept.
心力衰竭(HF)是一个重要的健康问题,尽管医学治疗取得了进展,但每年仍有近 25 万人死亡。改善心脏功能已被证明可降低心力衰竭患者的发病率和死亡率。最近人们对生长激素(GH)/胰岛素样生长因子(IGF)途径作为心力衰竭患者的潜在治疗靶点产生了兴趣。胰岛素样生长因子 1 已被证明可增强离体和动物的心脏功能。研究假设 IGF-1/IGF 结合蛋白 3 水平可能能够为心脏病患者提供预后益处。初步观察性研究表明,GH 补充具有显著益处,包括射血分数提高、运动耐量增加和纽约心脏协会功能分级降低。然而,这些结果在随机对照试验中并未得到复制。患有心力衰竭晚期的患者可能会出现与 GH 抵抗状态相关的恶病质。对 GH 补充没有反应可能是由于效应激素 IGF-1 缺乏所致。从理论上讲,这组患者可能受益于直接 IGF-1 补充。GH 和 IGF-1 的联合治疗很有吸引力;然而,需要在晚期 HF 患者中进行未来的试验来证明这一概念。