Thohan Vinay, Torre-Amione Guillermo, Koerner Micheal M
DeBakey Heart Center, Winters Center for Heart Failure Research, Houston, Texas, USA.
Curr Opin Cardiol. 2004 Jul;19(4):301-8. doi: 10.1097/01.hco.0000129667.34622.14.
More than 5 million people in the United States alone have congestive heart failure, and an estimated 40 million have established risks and warrant therapy. Mineralocorticoid antagonists have emerged as a new paradigm for the treatment of congestive heart failure. They have established benefits among patients with chronic symptomatic systolic dysfunction, and recent studies have demonstrated substantial effect on the morbidity and mortality among patients with heart failure after myocardial infarction. The exact biologic mechanism is thus far unknown.
Within the last 5 years, efforts have intensified to help define better the biologic mechanisms by which mineralocorticoid receptor antagonisms exert the observed clinical benefit. Elegant human studies have demonstrated some important observations. First, under conditions of increased plasma aldosterone concentrations, the heart will extract aldosterone. Second, aldosterone extraction in the heart stimulates increased collagen turnover culminating in ventricular remodeling. Third, among people with chronic systolic or diastolic heart failure, aldosterone is actually produced and secreted by the heart. Finally, antagonism of the mineralocorticoid receptor will attenuate or abrogate many of these deleterious effects.
Combined clinical and detailed mechanistic investigations have established mineralocorticoid receptor antagonism as the new treatment paradigm for congestive heart failure. Recent clinical data have demonstrated that treatment of patients with a combination of mineralocorticoid receptor antagonism (eplerenone) and angiotensin converting enzyme-inhibitor (ACE-I) results in substantial reduction in left ventricular mass. Furthermore, a federally funded initiative to treat more than 6000 patients with diastolic heart failure with spironolactone is in its final phases of planning. It is foreseeable that, along with ACE-I and beta-blockers, mineralocorticoid receptor antagonism will become part of the treatment paradigm for people across the entire spectrum of cardiovascular disease.
仅在美国就有超过500万人患有充血性心力衰竭，估计有4000万人存在既定风险且需要治疗。盐皮质激素拮抗剂已成为治疗充血性心力衰竭的一种新范例。它们在慢性症状性收缩功能障碍患者中已证实具有益处，并且最近的研究表明对心肌梗死后心力衰竭患者的发病率和死亡率有显著影响。确切的生物学机制目前尚不清楚。
在过去5年中，人们加大了努力以更好地确定盐皮质激素受体拮抗作用发挥观察到的临床益处的生物学机制。精细的人体研究已经得出了一些重要发现。首先，在血浆醛固酮浓度升高的情况下，心脏会摄取醛固酮。其次，心脏摄取醛固酮会刺激胶原蛋白更新增加，最终导致心室重塑。第三，在慢性收缩性或舒张性心力衰竭患者中，醛固酮实际上是由心脏产生和分泌的。最后，盐皮质激素受体拮抗作用将减弱或消除许多这些有害影响。
临床和详细机制研究相结合已确立盐皮质激素受体拮抗作用为充血性心力衰竭的新治疗范例。最近的临床数据表明，联合使用盐皮质激素受体拮抗剂（依普利酮）和血管紧张素转换酶抑制剂（ACE-I）治疗患者可使左心室质量大幅降低。此外，一项由联邦政府资助、用螺内酯治疗6000多名舒张性心力衰竭患者的计划正处于最后规划阶段。可以预见，与ACE-I和β受体阻滞剂一起，盐皮质激素受体拮抗作用将成为整个心血管疾病范围内患者治疗范例的一部分。
