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


CONCLUSIONS
The effects of spironolactone treatment on left ventricular systolic function and remodeling may in part depend on ACE genotype.
Cicoira
Mariantonietta
M
Dipartimento di Scienze Biomediche e Chirurgiche, Sezione di Cardiologia, Università degli Studi di Verona, Verona, Italy. mariantonietta.cicoira@univr.it
Rossi
Andrea
A
Bonapace
Stefano
S
Zanolla
Luisa
L
Perrot
Andreas
A
Francis
Darrel P
DP
Golia
Giorgio
G
Franceschini
Lorenzo
L
Osterziel
Karl J
KJ
Zardini
Piero
P
D004232:Diuretics / Q000494:pharmacology*; D004452:Echocardiography; D005260:Female; D005838:Genotype; D006333:Heart Failure / Q000188:drug therapy* / Q000201:enzymology / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D007703:Peptidyl-Dipeptidase A / Q000235:genetics*; D011110:Polymorphism, Genetic; D012044:Regression Analysis; D013148:Spironolactone / Q000494:pharmacology*; D013318:Stroke Volume / Q000187:drug effects
D004232:Diuretics; D013148:Spironolactone; D007703:Peptidyl-Dipeptidase A