血管紧张素转换酶（ACE）基因插入/缺失多态性对慢性心力衰竭患者螺内酯治疗反应的影响。

Effects of ACE gene insertion/deletion polymorphism on response to spironolactone in patients with chronic heart failure.

作者信息

Cicoira Mariantonietta, Rossi Andrea, Bonapace Stefano, Zanolla Luisa, Perrot Andreas, Francis Darrel P, Golia Giorgio, Franceschini Lorenzo, Osterziel Karl J, Zardini Piero

机构信息

Dipartimento di Scienze Biomediche e Chirurgiche, Sezione di Cardiologia, Università degli Studi di Verona, Verona, Italy.

出版信息

Am J Med. 2004 May 15;116(10):657-61. doi: 10.1016/j.amjmed.2003.12.033.

DOI:10.1016/j.amjmed.2003.12.033

PMID:15121491

Abstract

BACKGROUND

Angiotensin-converting enzyme (ACE) is involved in the pathophysiology of chronic heart failure, and its activity is determined in part by a polymorphism of the ACE gene. We hypothesized that the benefits of spironolactone, which inhibits downstream elements of ACE-mediated abnormalities, may depend on ACE genotype.

METHODS

We randomly assigned 93 chronic heart failure patients to treatment with spironolactone (n = 47) or to a control group (n = 46) and followed them for 12 months. Genotype for the insertion/deletion polymorphism of the ACE gene was determined by polymerase chain reaction. An echocardiographic examination was performed at baseline and at the end of the 12 months.

RESULTS

The mean (+/- SD) age of the 93 patients was 62 +/- 9 years, and the mean New York Heart Association class was 2 +/- 1. The genotype was DD in 26 patients (28%). Forty-seven patients were assigned to spironolactone treatment (mean dose, 32 +/- 16 mg). In the treated group, only patients with a non-DD genotype showed significant improvement in left ventricular ejection fraction (3.0%; 95% confidence interval [CI]: 1.2% to 4.8%; P = 0.002), end-systolic volume (-23 mL; 95% CI: -36 to -11; P = 0.0005), and end-diastolic volume (-27 mL; 95% CI: -43 to -12; P = 0.001). In the multivariate analysis, the estimated net effect of treatment was 29 mL better (95% CI: -20 to 78 mL) for end-diastolic volume, 20 mL better (95% CI: -18 to 58 mL) for end-systolic volume, but 1.4% worse (95% CI: -3.4% to 6.2%) for left ventricular ejection fraction in patients with non-DD versus DD genotypes.

CONCLUSION

The effects of spironolactone treatment on left ventricular systolic function and remodeling may in part depend on ACE genotype.

摘要

背景

血管紧张素转换酶（ACE）参与慢性心力衰竭的病理生理过程，其活性部分由ACE基因的多态性决定。我们推测，抑制ACE介导异常的下游元件的螺内酯的益处可能取决于ACE基因型。

方法

我们将93例慢性心力衰竭患者随机分为螺内酯治疗组（n = 47）或对照组（n = 46），并随访12个月。通过聚合酶链反应确定ACE基因插入/缺失多态性的基因型。在基线和12个月末进行超声心动图检查。

结果

93例患者的平均（±标准差）年龄为62±9岁，平均纽约心脏协会心功能分级为2±1级。26例患者（28%）的基因型为DD。47例患者接受螺内酯治疗（平均剂量，32±16 mg）。在治疗组中，只有非DD基因型的患者左心室射血分数有显著改善（3.0%；95%置信区间[CI]：1.2%至4.8%；P = 0.002），收缩末期容积减少（-23 mL；95% CI：-36至-11；P = 0.0005），舒张末期容积减少（-27 mL；95% CI：-43至-12；P = 0.001）。在多变量分析中，非DD基因型患者与DD基因型患者相比，舒张末期容积的估计净治疗效果更好29 mL（95% CI：-20至78 mL），收缩末期容积更好20 mL（95% CI：-18至58 mL），但左心室射血分数差1.4%（95% CI：-3.4%至6.2%）。