Angiotensin-converting enzyme gene polymorphism interacts with left ventricular ejection fraction and brain natriuretic peptide levels to predict mortality after myocardial infarction

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 (...

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Bibliographic Details
Published in:Journal of the American College of Cardiology 2003-03, Vol.41 (5), p.729-736
Main Authors: Palmer, Barry R, Pilbrow, Anna P, Yandle, Tim G, Frampton, Chris M, Richards, A.Mark, Nicholls, M.Gary, Cameron, Vicky A
Format: Article
Language:English
Subjects:
Aged
Biological and medical sciences
Biomarkers - analysis
Blood
Cardiology
Cardiology. Vascular system
Cardiovascular disease
Cohort Studies
Coronary heart disease
Deoxyribonucleic acid
DNA
Electrocardiography
Enzymes
Ethnicity
Female
Fractions
Gene expression
Genotype
Genotype & phenotype
Heart
Heart attacks
Humans
Male
Medical sciences
Middle Aged
Mortality
Myocardial Infarction - diagnosis
Myocardial Infarction - genetics
Myocardial Infarction - metabolism
Myocardial Infarction - mortality
Natriuretic Peptide, Brain - analysis
Peptides
Peptidyl-Dipeptidase A - analysis
Peptidyl-Dipeptidase A - genetics
Polymorphism, Genetic
Predictive Value of Tests
Probability
Prognosis
Rodents
Sensitivity and Specificity
Severity of Illness Index
Stroke Volume
Studies
Survival Analysis
Ventricular Dysfunction, Left - genetics
Ventricular Dysfunction, Left - physiopathology
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Summary: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). 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. 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. 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. 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.
ISSN:0735-1097
1558-3597
DOI:10.1016/S0735-1097(02)02927-3