尽管使用了血管紧张素转换酶抑制剂，但严重慢性心力衰竭患者血管紧张素II水平升高的决定因素。

Determinants of increased angiotensin II levels in severe chronic heart failure patients despite ACE inhibition.

作者信息

van de Wal R M A, Plokker H W M, Lok D J A, Boomsma F, van der Horst F A L, van Veldhuisen D J, van Gilst W H, Voors A A

机构信息

Department of Cardiology, St. Antonius Hospital, Koekoekslaan 1, PO Box 2500, 3435 CM Nieuwegein, The Netherlands.

出版信息

Int J Cardiol. 2006 Jan 26;106(3):367-72. doi: 10.1016/j.ijcard.2005.02.016.

DOI:10.1016/j.ijcard.2005.02.016

PMID:16337046

Abstract

INTRODUCTION

The beneficial effects of ACE inhibitors are generally ascribed to blockade of neurohormonal activation. However, especially in chronic heart failure (CHF) patients plasma angiotensin II and aldosterone levels can be elevated despite ACE inhibition, the so-called ACE escape. In the present study, we aimed to identify the frequency and determinants of ACE escape in CHF patients.

METHODS

We studied 99 stable chronic heart failure patients (NYHA class III and IV, 66% ischemic etiology) receiving long-term therapy with ACE inhibitors. In all patients, cardiac, renal, and neurohormonal parameters were measured. ACE escape was defined as plasma angiotensin level > or = 16 pmol/L.

RESULTS

Mean (+/- SD) left ventricular ejection fraction of our 99 patients (79 men and 20 women, age 69 +/- 12 years) was 28 +/- 10%. In addition to an ACE inhibitor, 93% of patients received diuretics, 71% a beta-blocker, and 49% spironolactone. None of the patients used an angiotensin receptor blocker. In our population, 45% of the patients had an angiotensin II plasma concentration higher than 16 pmol/L (median concentration was 14.1 pmol/L). Spironolactone use was an independent predictor of elevated plasma angiotensin II levels. Furthermore, spironolactone users had significantly higher plasma active renin protein and aldosterone levels. Plasma angiotensin II concentration was positively correlated to active renin, plasma angiotensin I and plasma aldosterone. No correlation was found between plasma angiotensin II levels and serum ACE activity, dose of ACE inhibitor, or duration of use.

CONCLUSION

In a group of severe chronic heart failure patients, 45% had elevated plasma angiotensin II levels independent of serum ACE activity despite long-term ACE inhibitor use. Although a causal link could not be proven, an association was found between spironolactone use and active renin protein, angiotensin II and aldosterone levels, suggesting that escape from ACE is mainly caused by a feedback mechanism.

摘要

引言

血管紧张素转换酶（ACE）抑制剂的有益作用通常归因于对神经激素激活的阻断。然而，尤其是在慢性心力衰竭（CHF）患者中，尽管使用了ACE抑制剂，血浆血管紧张素II和醛固酮水平仍可能升高，即所谓的ACE逃逸现象。在本研究中，我们旨在确定CHF患者中ACE逃逸的发生率及其决定因素。

方法

我们研究了99例接受ACE抑制剂长期治疗的稳定慢性心力衰竭患者（纽约心脏协会III级和IV级，66%为缺血性病因）。对所有患者测量心脏、肾脏和神经激素参数。ACE逃逸定义为血浆血管紧张素水平≥16 pmol/L。

结果

我们的99例患者（79例男性和20例女性，年龄69±12岁）的平均（±标准差）左心室射血分数为28±10%。除ACE抑制剂外，93%的患者使用利尿剂，71%使用β受体阻滞剂，49%使用螺内酯。无一例患者使用血管紧张素受体阻滞剂。在我们的研究人群中，45%的患者血浆血管紧张素II浓度高于16 pmol/L（中位浓度为14.1 pmol/L）。使用螺内酯是血浆血管紧张素II水平升高的独立预测因素。此外，使用螺内酯的患者血浆活性肾素蛋白和醛固酮水平显著更高。血浆血管紧张素II浓度与活性肾素、血浆血管紧张素I和血浆醛固酮呈正相关。未发现血浆血管紧张素II水平与血清ACE活性、ACE抑制剂剂量或使用时间之间存在相关性。