The DD genotype of the angiotensin-converting enzyme gene is associated with increased mortality in idiopathic heart failure.
OBJECTIVE
The aim of the present study was to investigate the association between the homozygous DD (deletion) genotype of the angiotensin-converting enzyme gene and survival and cardiac function in patients with idiopathic congestive heart failure.


BACKGROUND
The DD genotype gene is a linkage marker for an etiologic mutation at or near the angiotensin-converting enzyme gene and has been associated with increased risk for the development of coronary artery disease, left ventricular hypertrophy and left ventricular dilation after myocardial infarction. We investigated the association between this angiotensin-converting enzyme genotype and mortality in a population-based cohort of patients with idiopathic congestive heart failure.


METHODS
The genotype was determined in 193 patients recruited from a large unselected population of patients with congestive heart failure (n = 2,711). The patients were studied with echocardiography, and survival data were obtained after 5 years of follow-up. A control group from the general population (n = 77) was studied by a similar procedure.


RESULTS
The frequency of the D allele was not significantly different in the study and control groups (0.57 vs 0.56, p = NS). Long-term survival was significantly worse in the patients with the DD genotype than in the remaining patients (5-year survival rate 49% vs. 72%, p = 0.0011 as assessed by log rank test). The independent importance of the DD genotype for prognosis was verified by a multivariate Cox proportional hazards analysis, by which the odds ratio for mortality and the DD genotype was 1.69 (95% confidence interval 1.01 to 2.82). The only significant difference in cardiac function data between the two groups was an increase in left ventricular mass index in the DD group (153 +/- 57 vs 134 +/- 44 g/m2, p = 0.019).


CONCLUSIONS
Angiotensin-converting enzyme gene DD polymorphism was associated with poorer survival and an increase in left ventricular mass in patients with idiopathic heart failure. The results suggest a possible pathophysiologic pathway between angiotensin-converting enzyme gene polymorphism, angiotensin-converting enzyme activity, myocardial hypertrophy and survival. Therefore, the DD genotype may be a marker of poor prognosis in patients with congestive heart failure.
Andersson
B
B
Division of Cardiology, the Wallenberg Laboratory for Cardiovascular Research, University Hospital, Göteborg, Sweden.
Sylvén
C
C
D016022:Case-Control Studies; D015331:Cohort Studies; D004452:Echocardiography; D005260:Female; D005500:Follow-Up Studies; D017353:Gene Deletion; D005787:Gene Frequency; D006333:Heart Failure / Q000000981:diagnostic imaging / Q000235:genetics* / Q000401:mortality*; D006720:Homozygote; D006801:Humans; D017379:Hypertrophy, Left Ventricular / Q000000981:diagnostic imaging / Q000235:genetics / Q000401:mortality; D008297:Male; D008875:Middle Aged; D007703:Peptidyl-Dipeptidase A / Q000235:genetics*; D011110:Polymorphism, Genetic; D011379:Prognosis; D016016:Proportional Hazards Models; D012307:Risk Factors; D015996:Survival Rate; D013548:Sweden / Q000453:epidemiology; D013997:Time Factors
D007703:Peptidyl-Dipeptidase A