Angiotensin-converting enzyme gene polymorphism interacts with left ventricular ejection fraction and brain natriuretic peptide levels to predict mortality after myocardial infarction.
OBJECTIVE
The goal of this study was the exploration of the associations between the angiotensin-converting enzyme (ACE) gene insertion/deletion (I/D) polymorphism and post-myocardial infarction (MI) outcomes, especially any interaction with the accepted clinical prognostic markers brain natriuretic peptide (BNP) and left ventricular ejection fraction (LVEF).


BACKGROUND
The ACE gene I/D polymorphism has been implicated in the development of MI, hypertension, and left ventricular hypertrophy. We examined the association of ACE I/D and prognosis after acute MI.


METHODS
Patients incurring acute MI were genotyped for the ACE I/D polymorphism. Clinical data included assays of neurohormones, radionuclide ventriculography, and mortality over a mean 2.6 years of follow-up.


RESULTS
Patients (n = 978) had a mean age of 62.1 years, and 78% were male. Overall genotype frequencies were II 23.2%, ID 49.5%, and DD 27.3%. Chi-square analysis revealed an association between the ACE D allele and death after MI (88 of 103 who died were DD or ID; p < 0.05), with an odds ratio for mortality of 8.03 (95% confidence interval, 2.16 to 29.88). Patients with the DD genotype had higher (p < 0.05) plasma BNP, N-terminal BNP (N-BNP), and endothelin-1 levels within 96 h after MI than grouped ID/II patients. Multivariate analysis indicated ACE genotype, age, and previous MI were independent predictors of death (p < 0.05). Patients with an ACE D allele in combination with either a lower than median LVEF or greater than median BNP had a higher mortality (p < 0.001 and p < 0.025, respectively) than the risk associated with the D allele itself.


CONCLUSIONS
Angiotensin-converting enzyme genotyping may provide additional prognostic information in patients after MI in combination with the proven utility of LVEF, plasma BNP, and N-BNP measurements.
Palmer
Barry R
BR
Christchurch Cardioendocrine Research Group, Department of Medicine, Christchurch School of Medicine and Health Sciences, Christchurch, New Zealand.
Pilbrow
Anna P
AP
Yandle
Tim G
TG
Frampton
Chris M
CM
Richards
A Mark
AM
Nicholls
M Gary
MG
Cameron
Vicky A
VA
D000368:Aged; D015415:Biomarkers / Q000032:analysis; D015331:Cohort Studies; D004562:Electrocardiography; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000175:diagnosis / Q000235:genetics* / Q000378:metabolism / Q000401:mortality*; D020097:Natriuretic Peptide, Brain / Q000032:analysis*; D007703:Peptidyl-Dipeptidase A / Q000032:analysis / Q000235:genetics*; D011110:Polymorphism, Genetic; D011237:Predictive Value of Tests; D011336:Probability; D011379:Prognosis; D012680:Sensitivity and Specificity; D012720:Severity of Illness Index; D013318:Stroke Volume; D016019:Survival Analysis; D018487:Ventricular Dysfunction, Left / Q000235:genetics* / Q000503:physiopathology
D015415:Biomarkers; D020097:Natriuretic Peptide, Brain; D007703:Peptidyl-Dipeptidase A