CLINICAL STUDY: ACUTE CORONARY SYNDROME
Angiotensin-converting enzyme gene polymorphism interacts with left ventricular ejection fraction and brain natriuretic peptide levels to predict mortality after myocardial infarction
Barry R. Palmer, PhD*,
Anna P. Pilbrow, BSc (Hons)*,
Tim G. Yandle, PhD*,
Chris M. Frampton, PhD*,
A. Mark Richards, MD*,
M. Gary Nicholls, MD, FACC* and
Vicky A. Cameron, PhD*,*
* Christchurch Cardioendocrine Research Group, Department of Medicine, Christchurch School of Medicine and Health Sciences, Christchurch, New Zealand
Manuscript received July 31, 2002;
revised manuscript received October 28, 2002,
accepted November 19, 2002.
* Reprint requests and correspondence: Dr. Vicky A. Cameron, Department of Medicine, Christchurch School of Medicine and Health Sciences, P.O. Box 4345, Christchurch, New Zealand. vicky.cameron{at}chmeds.ac.nz
OBJECTIVES: 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.
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Abbreviations and Acronyms
| | ACE | | angiotensin-converting enzyme | | AII | | angiotensin II | | ANP | | atrial natriuretic peptide | | ApoE | | apolipoprotein E | | BMI | | body mass index | | BNP | | brain natriuretic peptide | | DNA | | deoxyribonucleic acid | | I/D | | insertion/deletion | | LV | | left ventricle/ventricular | | LVEF | | left ventricular ejection fraction | | MI | | myocardial infarction | | N-BNP | | N-terminal brain natriuretic peptide | | PCR | | polymerase chain reaction | | PMI | | Christchurch Post-Myocardial Infarction study | | RAAS | | renin-angiotensin-aldosterone system |
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