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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

^* 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.

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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