Corcoran Lecture. Angiotensin-converting enzyme inhibition and the heart.
Corcoran Lecture. Angiotensin-converting enzyme inhibition and the heart.
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科克伦讲座。
DOI：
10.1161/01.hyp.23.6.813
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发表时间：
1994
期刊：
影响因子：
--
通讯作者：
Gavras,H
中科院分区：
文献类型：
--
作者：
Gavras,H
在过去的几十年里，高血压的病理生理学研究和抗高血压治疗的发展取得了长足的进步。随着该领域引入的每一种新的治疗方式，直接目标是安全有效地降低血压。20世纪60年代经典的多中心试验建立了这样的预期，即这种降低将预防未经治疗的高血压的并发症。然而，大多数流行病学研究显示，抗高血压治疗对缺血性心脏病的发病率无显著影响。[1]这导致了这样一种观点，即这种心脏病可能不仅仅是高血压本身引起的并发症，而是高血压过程中某些相同病理生理学改变的平行产物。这种推理的逻辑结果是，成功的治疗应该尽可能多地解决这些构成已知冠状动脉危险因素的改变，以保护心脏。我认为血管紧张素转换酶（ACE）抑制剂是唯一的抗高血压药物，具有最大的心脏保护潜力。2由于其双重作用-抑制血管紧张素II（Ang II）和增强缓激肽3 -4-它直接或间接地有益于受这些血管活性激素之一或两者影响的大量风险因素。除了调节全身血压水平和钠处理外，这些激素优先调节重要器官的血管张力，特别是冠状血管的血管张力;通过其血管收缩、电生理和代谢作用调节交感肾上腺系统;影响心肌细胞和血管平滑肌细胞的生长，内皮细胞产生自分泌-旁分泌因子，对胰岛素的敏感性，和葡萄糖摄取率;并改变整体心脏功能。在这篇简短的综述中，我将提供实验和临床证据来支持这些陈述，参考最近的大型多中心试验，这些试验证明了ACE抑制剂治疗心肌功能障碍和/或冠心病患者的发病率和死亡率有所改善。最后，我将对未来进行一次尝试性的展望--遗传流行病学预测谁可能获得最大的
Research in the pathophysiology of hypertension and the development of antihypertensive treatments has evolved with long strides over the last decades. With every new therapeutic modality introduced in the field, the immediate objective has been the safe and effective lowering of blood pressure. Implicit is the expectation, established by the classic multicenter trials in the 1960s, that such lowering will prevent the complications of untreated hypertension. Yet most epidemiologic studies have shown a surprising lack of significant effect of antihypertensive therapy on the incidence of ischemic heart disease. 1 This has led to the notion that such cardiac disease may not be simply a complication resulting from high blood pressure per se but rather a parallel product of some of the same pathophysiological alterations that characterize the hypertensive process. The logical upshot of this reasoning is that a successful therapy should address as many as possible of these alterations that constitute known coronary risk factors to protect the heart. It is my belief that angiotensin-converting enzyme (ACE) inhibition is unique among antihypertensive modalities in offering the greatest potential for cardioprotection. 2 Because of its dual action—inhibition of angiotensin II (Ang II) and potentiation of bradykinin3-4—it benefits, directly or indirectly, a large number of risk factors influenced by either one or both of these vasoactive hormones. In addition to regulating systemic blood pressure levels and sodium handling, these hormones regulate preferentially the vascular tone of vital organs and especially that of the coronary vasculature; modulate the sympathoadrenal system with its vasoconstrictor, electrophysiological, and metabolic actions; affect the growth of cardiac myocytes and vascular smooth muscle cells, the generation of autocrine-paracrine factors by endothelial cells, the sensitivity to insulin, and the rate of glucose uptake; and alter overall cardiac function. In this brief review I will present experimental and clinical evidence in support of these statements, referring to the recent large multicenter trials that have demonstrated improved morbidity and mortality in patients with myocardial dysfunction and/or coronary disease treated with ACE inhibition. I will close with a tentative look in the future—the potential of genetic epidemiology to predict who might derive the greatest