ACE Insertion/Deletion,but Not −240A>T Polymorphism,Modulates the Severity in Heart Failure

Objective

ACE gene is reported to be a candidate gene in heart failure. The insertion/deletion (I/D) polymorphism has been observed to be a predictor of mortality in this disease, but no data are available concerning the role of ACE −240A>T polymorphism. In this study, we investigated the role of ACE I/D and −240A>T polymorphisms in influencing both severity and clinical outcomes in patients with heart failure, according to New York Heart Association (NYHA) class.

Patients

We studied 323 patients with heart failure (258 men/65 women; age, 70.8 ± 11.5 years) followed-up for 11.9 ± 6.6 months.

Results

The ACE D and −240T allele frequency significantly increased according to the NYHA functional class (P = 0.0002 and P < 0.0001, respectively).

No significant difference in ACE polymorphism genotype distribution and allele frequency according to N-terminal pro-brain natriuretic peptide tertiles was observed. At multinomial regression analysis, ACE D but not −240T allele has been evidenced to be a significant and independent predictor of severity for both NYHA III and IV classes (P = 0.01 and P = 0.004, respectively). The ACE D allele prevalence was higher, even if not significantly in both death and rehospitalization groups in comparison with survivors and nonrehospitalized (P = 0.6 and P = 0.9, respectively). No difference in −240T allele frequency has been observed for the ACE −240A>T polymorphism, in relation to both death and rehospitalization (P = 0.1 and P = 0.6, respectively).

Conclusions

This study suggests that ACE I/D polymorphism might represent a predisposing factor to severe heart failure, independently of well-known prognostic markers.