Cicoira M, Zanolla L, Rossi A, Golia G, Franceschini L, Cabrini G, Bonizzato A, Graziani M, Anker S D, Coats A J, Zardini P
Divisione di Cardiologia, Università degli Studi di Verona, Italy.
J Am Coll Cardiol. 2001 Jun 1;37(7):1808-12. doi: 10.1016/s0735-1097(01)01237-2.
The objective of this study was to assess whether the angiotensin-converting enzyme (ACE) gene insertion/deletion (I/D) polymorphism influences the adequacy of the neurohormonal response to ACE inhibitors in patients with chronic heart failure (CHF).
The renin-angiotensin-aldosterone system (RAAS) plays an important role in the pathophysiology of CHF, and aldosterone levels closely relate to outcome in patients with CHF. Angiotensin-converting enzyme inhibitors suppress the RAAS, but a significant proportion of patients exhibit elevated serum levels of aldosterone despite long-term administration of apparently adequate doses of these agents.
We prospectively studied 132 patients with CHF (ejection fraction <45%) receiving long-term therapy with ACE inhibitors for over six months. Patients taking aldosterone antagonists were excluded from the study. "Aldosterone escape" was defined as being present when plasma aldosterone levels were above the normal range in our laboratory (>42 nmol/L). Patients were then divided into two subgroups according to the presence (group 1) or absence (group 2) of aldosterone escape. Genotype analysis for the ACE I/D polymorphism was performed by polymerase chain reaction.
The prevalence of aldosterone escape in our patients was 10% (13/132). The two groups of patients did not differ regarding the dose of ACE inhibitor, diuretics and their renal function. There was a statistically significant different distribution of genotypes between the two groups, with a higher proportion of DD genotype in group 1 compared with group 2 (62% vs. 24%, p = 0.005).
Patients with CHF with aldosterone escape have a higher prevalence of DD genotype compared with patients with aldosterone within the normal limits. Angiotensin-converting enzyme gene polymorphism contributes to the modulation and adequacy of the neurohormonal response to long-term ACE-inhibitor administration in CHF.
本研究旨在评估血管紧张素转换酶（ACE）基因插入/缺失（I/D）多态性是否会影响慢性心力衰竭（CHF）患者对ACE抑制剂的神经激素反应的充分性。
肾素-血管紧张素-醛固酮系统（RAAS）在CHF的病理生理学中起重要作用，醛固酮水平与CHF患者的预后密切相关。ACE抑制剂可抑制RAAS，但相当一部分患者尽管长期使用明显足够剂量的这些药物，其血清醛固酮水平仍会升高。
我们前瞻性地研究了132例CHF患者（射血分数<45%），这些患者接受了超过六个月的ACE抑制剂长期治疗。服用醛固酮拮抗剂的患者被排除在研究之外。“醛固酮逃逸”定义为血浆醛固酮水平高于我们实验室的正常范围（>42 nmol/L）。然后根据是否存在醛固酮逃逸将患者分为两个亚组（1组存在，2组不存在）。通过聚合酶链反应对ACE I/D多态性进行基因型分析。
我们患者中醛固酮逃逸的发生率为10%（13/132）。两组患者在ACE抑制剂剂量、利尿剂及其肾功能方面没有差异。两组之间的基因型分布存在统计学显著差异，1组的DD基因型比例高于2组（62%对24%，p = 0.005）。
与醛固酮水平在正常范围内的患者相比，CHF合并醛固酮逃逸的患者DD基因型的患病率更高。血管紧张素转换酶基因多态性有助于调节CHF患者对长期ACE抑制剂治疗产生的神经激素反应并使其充分。
