Angiotensin-converting enzyme and angiotensin II receptor 1 polymorphism in coronary disease and malignant ventricular arrhythmias

Objectives: It has been reported that patients carrying the angiotensin-converting enzyme (ACE) deletion DD genotype with the angiotensin II type I (AT1) C allele are at increased risk for myocardial infarction. The frequency distribution of the ACE and AT1 receptor gene polymorphism and their possible relation regarding malignant ventricular arrhythmias in patients with coronary artery disease (CAD) and left ventricular dysfunction was determined. Methods: The ACE I/D and AT1 A/C polymorphisms (using polymerase chain reaction) in 100 Caucasian patients suffering from CAD with a history of malignant ventricular arrhythmias treated with an implantable cardioverter defibrillator (ICD group) was compared to 127 age-matched Caucasian patients with CAD and no history of malignant ventricular arrhythmias (control group). All patients had reduced left ventricular ejection fraction of <40% and were comparable regarding sex distribution, body mass index, ACE-inhibitor treatment, lipid status and duration of CAD. Results: The prevalence of DD/CC in the ICD group was significantly higher (19% versus 10%, p<0.0001). The risk for malignant Ventricular arrhythmias was associated with the combination of ACE D and AT1 C alleles (odds-ratio: 2.4, 95% confidence interval 1.41 to 3.94, p<0.001), The distribution of ACE and AT1 genotypes was not different between the two group. Conclusions: Patients with coronary artery disease and left ventricular dysfunction carrying ACE D and ATI C alleles are at increased risk for development of malignant ventricular arrhythmias. Because of available pharmacological inhibitors, these results may have clinical implications for the prevention of sudden cardiac death. (C) 1999 Elsevier Science B.V. All rights reserved.