Document Detail


Angiotensin-converting enzyme genotype modulates pulmonary function and exercise capacity in treated patients with congestive stable heart failure.
MedLine Citation:
PMID:  12356632     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
BACKGROUND: The gene encoding ACE exhibits an insertion/deletion polymorphism resulting in 3 genotypes (DD, ID, and II), which affects serum and tissue ACE activity as well as other vasoactive substances. Pulmonary function is frequently abnormal in patients with congestive heart failure (CHF), the mechanism of which has not been completely characterized. ACE inhibition has been shown to improve diffusion across the alveolar-capillary membrane and to improve exercise capacity and gas exchange in CHF. The aim of the current study was to determine if ACE genotype is associated with altered pulmonary function and exercise intolerance in patients with treated CHF. METHODS AND RESULTS: Fifty-seven patients (stratified according to ACE genotype as 17 DD, 28 ID, 12 II) with ischemic and dilated cardiomyopathy, left ventricular ejection fraction (LVEF) <35%, and <10 pack-years of smoking history were studied. All patients were receiving standard therapy for left ventricular systolic dysfunction. Pulmonary function, LVEF, serum ACE, plasma angiotensin II, atrial natriuretic peptide, and brain natriuretic peptide were measured at baseline. Peak VO2 and gas exchange measurements were assessed with graded exercise. Resting LVEF was similar among the genotype groups (25% to 28%), and no differences were observed in diastolic function or pulmonary artery pressures (P>0.05). Mean peak VO2 and forced vital capacity (% Pred) were significantly reduced (P<0.05), whereas mean serum ACE activity and plasma angiotensin II concentration were highest in DD homozygotes. Subjects homozygous for the D-allele also demonstrated higher mean ventilatory equivalents for carbon dioxide (VE/VCO2) during exercise (P<0.05). CONCLUSIONS: ACE DD genotype is associated with decreased exercise tolerance in CHF, possibly mediated by altered pulmonary function. Pharmacological strategies effecting more complete inhibition of serum and tissue ACE and/or potentiation of bradykinin may improve exercise capacity in patients with CHF and ACE DD genotype.
Authors:
M Roselle Abraham; Lyle J Olson; Michael J Joyner; Stephen T Turner; Ken C Beck; Bruce D Johnson
Publication Detail:
Type:  Clinical Trial; Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Circulation     Volume:  106     ISSN:  1524-4539     ISO Abbreviation:  Circulation     Publication Date:  2002 Oct 
Date Detail:
Created Date:  2002-10-01     Completed Date:  2002-10-24     Revised Date:  2007-11-15    
Medline Journal Info:
Nlm Unique ID:  0147763     Medline TA:  Circulation     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1794-9     Citation Subset:  AIM; IM    
Affiliation:
Division of Cardiovascular, Mayo Clinic and Foundation, Rochester, Minn 55905, USA.
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MeSH Terms
Descriptor/Qualifier:
Angiotensin II / blood
Atrial Natriuretic Factor / blood
Echocardiography
Exercise Test
Exercise Tolerance / genetics*
Female
Genotype
Heart Failure / blood,  physiopathology*,  therapy
Humans
Lung / physiopathology*
Male
Middle Aged
Natriuretic Peptide, Brain / blood
Peptidyl-Dipeptidase A / blood,  genetics*
Pulmonary Gas Exchange
Regression Analysis
Respiratory Function Tests
Stroke Volume
Grant Support
ID/Acronym/Agency:
HL71478/HL/NHLBI NIH HHS; M01-RR00585/RR/NCRR NIH HHS
Chemical
Reg. No./Substance:
11128-99-7/Angiotensin II; 114471-18-0/Natriuretic Peptide, Brain; 85637-73-6/Atrial Natriuretic Factor; EC 3.4.15.1/Peptidyl-Dipeptidase A

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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