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

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Item Type:	Article
Title:	Effects of ACE gene insertion/deletion polymorphism on response to spironolactone in patients with chronic heart failure
Creators Name:	Cicoira, M., Rossi, A., Bonapace, S., Zanolla, L., Perrot, A., Francis, D.P., Golia, G., Franceschini, L., Osterziel, K.J. and Zardini, P.
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.
Keywords:	Diuretics, Echocardiography, Genetic Polymorphism, Genotype, Heart Failure, Multivariate Analysis, Peptidyl-Dipeptidase A, Regression Analysis, Spironolactone, Stroke Volume
Source:	American Journal of Medicine
ISSN:	0002-9343
Publisher:	Excerpta Medica
Volume:	116
Number:	10
Page Range:	657-661
Date:	15 May 2004
Official Publication:	https://doi.org/10.1016/j.amjmed.2003.12.033
PubMed:	View item in PubMed

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