© 2004 European Society of Cardiology
Beta-adrenergic receptor blockade and the angiotensin-converting enzyme deletion polymorphism in patients with chronic heart failure
a Service de Cardiologie C, Hôpital Cardiologique Centre Hospitalier Universitaire de Lille, Boul Prof J Leclercq, 59037 Lille Cedex, France
b INSERM U508, Institut Pasteur de Lille 1 rue Calmette, 59010 Lille Cedex, France
* Corresponding author. Tel.: +33-3-20-44-50-45; fax: +33-3-20-44-48-81. E-mail address: cbauters{at}chru-lille.fr
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Abstract |
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Background: Beta-adrenergic receptor blockade is an established treatment of chronic heart failure (HF). Previous studies have suggested a potential pharmacogenetic interaction between beta-blocker therapy and the angiotensin-converting enzyme (ACE) I/D polymorphism in patients with HF.
Aims: We designed this study to analyze changes in myocardial function of HF patients in response to beta-blocker therapy as a function of the ACE I/D polymorphism.
Methods and results: We studied 199 consecutive patients with chronic HF not treated with beta-blockers. Before initiation of beta-blockers and 3 months after the maximal tolerated dose was reached, patients underwent echocardiography, radionuclide angiography, and a cardiopulmonary exercise test. We extracted genomic DNA from white blood cells and determined the ACE I/D polymorphism. Thirty-five (18%) patients had the II genotype, 86 (43%) the ID genotype and 78 (39%) the DD genotype. A significant and similar improvement in left ventricular ejection fraction (LVEF) was observed in II (from 0.30±0.10 to 0.41±0.13; P<0.0001), ID (from 0.29±0.11 to 0.39±0.13; P<0.0001) and DD patients (from 0.31±0.11 to 0.40±0.13; P<0.0001). Peak Vo2 before and after beta-blockade was similar among the three groups. The proportion of responders to beta-blockers (patients without cardiac events during titration who had an increase in LVEF >5% after beta-blockers) was similar among the three groups (II: 65.9%%, ID: 60.6%%, DD: 65.9%; P=NS). During a median follow-up of 933 days, there was no evidence for any effect of ACE I/D polymorphism on cardiac survival.
Conclusions: We observed no evidence of pharmacogenetic interaction between the ACE I/D polymorphism and the effects of beta-blockade on LVEF and other prognostic parameters in patients with chronic HF. Our results support the initiation of beta-blockers in HF patients with the II or the ID genotype as well as in those with the DD genotype.
Key Words: Congestive heart failure • Beta-blockers • Angiotensin converting enzyme • Polymorphism
Received May 7, 2003; Revised July 14, 2003; Accepted September 15, 2003
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