Angiotensin-converting enzyme gene deletion polymorphism modulation of onset of symptoms and survival rate of patients with heart failure

Background: Angiotensin-converting enzyme is involved in the pathophysiology of heart failure. We hypothesized that clinical characteristics as well as survival rate in patients with heart failure of different etiologies may be modulated by functional variants DD, ID and II of the angiotensin-converting enzyme gene. Methods: We studied 333 patients with heart failure, aged 43.3±10.5 years, 262 (78.7%) men and 71 (21.3%) women. Heart failure was ascribed to idiopathic dilated cardiomyopathy in 125 patients. Heart failure was caused by ischemic heart disease in 63 patients, Chagas' disease in 58, hypertensive heart disease in 41, alcoholic cardiomyopathy in 24, and was due to other etiologies in 22 patients. Statistical analysis was performed with the χ2 test, Student's t-test, analysis of variance, Kaplan-Meier and Cox proportional hazards methods. Results: The DD genotype was associated with increased systolic left ventricular diameter (p=0.031). Earlier onset of symptoms was observed in patients with alcoholic cardiomyopathy and DD genotype (p=0.033, codominant D) and in patients with hypertensive cardiomyopathy and DD genotype (p=0.048, codominant D; p=0.024, recessive D). Mortality was higher in patients older than 50 years with DD genotype (p=0.007, codominant D; p=0.002, recessive D). Variables independently associated with higher mortality in patients older than 50 years were age, diabetes mellitus, Chagas' disease etiology and DD genotype. Conclusions: These results add evidence for an association of the DD genotype of the angiotensin-converting enzyme gene with earlier onset of symptoms and decreased survival rate of selected patients with heart failure.