Journal article
Pharmacogenetic interactions between β-blocker therapy and the angiotensin-converting enzyme deletion polymorphism in patients with congestive heart failure
Circulation (New York, N.Y.), Vol.103(12), pp.1644-1648
2001
DOI: 10.1161/01.CIR.103.12.1644
PMID: 11273991
Abstract
Background—Activation of the renin-angiotensin and sympathetic nervous systems adversely affect heart failure progression. The ACE deletion allele (ACE D) is associated with increased renin-angiotensin activation; however, its influence on patient outcomes remains uncertain, and the pharmacogenetic interactions with β-blocker therapy have not been previously evaluated.
Methods and Results—We prospectively followed 328 patients (age, 56.1±11.9 years) with systolic dysfunction (left ventricular ejection fraction, 0.24±0.08) to assess the impact of the ACE D allele on transplant-free survival (median follow-up, 21 months). Transplant-free survival was compared by genotype for the whole cohort and separately in patients with (n=120) and those without β-blocker therapy (n=208) at the time of entry. Transplant-free survival was significantly poorer for patients with the D allele (1-year percent survival II/ID/DD=94/77/75; 2-year=78/65/60; ordered log-rank test, P=0.044). In patients not treated with β-blockers, the adverse impact of ACE D allele was dramatically increased (1-year percent survival II/ID/DD=95/75/67; 2-year=81/61/48; P=0.005). In contrast, in patients receiving β-blocker therapy, no influence of ACE genotype on transplant-free survival was evident (1-year percent survival II/ID/DD=91/80/86; 2-year=70/71/77; P=0.73).
Conclusions—In a cohort of patients with systolic dysfunction, the ACE D allele was associated with a significantly poorer transplant-free survival. This effect was primarily evident in patients not treated with β-blockers and was not seen in patients receiving therapy. These findings suggest a potential pharmacogenetic interaction between the ACE D/I polymorphism and therapy with β-blockers in the determination of heart failure survival.
Details
- Title: Subtitle
- Pharmacogenetic interactions between β-blocker therapy and the angiotensin-converting enzyme deletion polymorphism in patients with congestive heart failure
- Creators
- Dennis M MCNAMARA - Cardiovascular Institute, University of Pittsburgh Medical Center, Pittsburgh, Pa, United StatesRichard HOLUBKOV - Cardiovascular Institute, University of Pittsburgh Medical Center, Pittsburgh, Pa, United StatesKaren JANOSKO - Cardiovascular Institute, University of Pittsburgh Medical Center, Pittsburgh, Pa, United StatesAmy PALMER - Cardiovascular Institute, University of Pittsburgh Medical Center, Pittsburgh, Pa, United StatesJue J WANG - Cardiovascular Institute, University of Pittsburgh Medical Center, Pittsburgh, Pa, United StatesGuy A MACGOWAN - Cardiovascular Institute, University of Pittsburgh Medical Center, Pittsburgh, Pa, United StatesSrinivas MURALI - Cardiovascular Institute, University of Pittsburgh Medical Center, Pittsburgh, Pa, United StatesWarren D ROSENBLUM - Cardiovascular Institute, University of Pittsburgh Medical Center, Pittsburgh, Pa, United StatesBarry LONDON - Cardiovascular Institute, University of Pittsburgh Medical Center, Pittsburgh, Pa, United StatesArthur M FELDMAN - Cardiovascular Institute, University of Pittsburgh Medical Center, Pittsburgh, Pa, United States
- Resource Type
- Journal article
- Publication Details
- Circulation (New York, N.Y.), Vol.103(12), pp.1644-1648
- DOI
- 10.1161/01.CIR.103.12.1644
- PMID
- 11273991
- NLM abbreviation
- Circulation
- ISSN
- 0009-7322
- eISSN
- 1524-4539
- Publisher
- Lippincott Williams & Wilkins; Hagerstown, MD
- Language
- English
- Date published
- 2001
- Academic Unit
- Molecular Physiology and Biophysics; Cardiovascular Medicine; Internal Medicine
- Record Identifier
- 9984025692002771
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