Abstract 3173: The ACE D Allele and Clinical Outcomes in African Americans with Heart Failure
Introduction: The angiotensin-converting enzyme deletion allele (ACE D) has been linked to poorer clinical outcomes in predominantly white cohorts with heart failur e. Renin angiotensin activation may differ in black cohorts, however the impact of the ACE D allele in African Americans with heart failure has not been evaluated. We examined the impact of the ACE D/I polymorphism on the heart failure (HF) phenotype and outcomes for subjects in the African American Heart Failure Trial (A-HeFT).
Method: 347 subjects enrolled in the Genetic Risk Assessment in Heart Failure (GRAHF) sub-study of A-HeFT were genotyped for the ACE D/I polymorphism. Subjects were followed prospectively for the endpoint of death or heart failure hospitalization. Event-free survival (EFS) was assessed overall and by ACE genotype. In a subset of subjects (n=262), the impact of the ACE D/I polymorphisms on LVEF and LV diastolic diameter (LVDD) at baseline and 6 months after entry into AHeFT was assessed by transthoracic echocardiography.
Results: The GRAHF cohort was 60% male, 25% ischemic, 97% class III with a mean age of 57.3 ± 13 years and a qualifying LVEF of 23.9%. Overall 84% were on beta blockers, 76 % ACE inhibitors, 36% aldosterone receptor antagonists and 22%, angiotensin receptor antagonists in addition to either hydralazine and isosorbide (HYD-ISDN, n=162) or placebo(n=185). In terms of ACE D/I genotype, 64 subjects were II (18%), 180 (52%) were ID, and 103 (30%) were DD homozygotes. ACE D/I genotype did not impact on either LVEF or LVDD at baseline evaluation (mean LVEF for genotype subsets ACE II/ID/ DD=0.34/0.34/0.36, p=0.25; LVDD (cm)=6.3/6.4/6.4, p=0.64) or at the six month assessment (mean LVEF II/ID/DD=0.36/0.36/0.38, p=0.36; LVDD=6.3/6.2/6.1, p=0.30). EFS overall was 90% at 180 days and 78% at 360 days, and was similar in ACE D/I genotype subsets (180 and 360 day EFS, II= 88%/78%, ID=91%/81%, DD=92%/82%. P=0.42).
Conclusion: In contrast to its impact in previous predominantly white heart failure cohorts, the ACE D allele did not influence either Left ventricular remodeling or clinical outcomes in the AHeFT genetic substudy. Renin angiotensin activation and the ACE D allele may play a less significant role in disease progression in African Americans with heart failure.