The II genotype of the angiotensin-converting enzyme gene delays the onset of acute coronary syndromes.

Abstract

The DD genotype of the angiotensin-converting enzyme (ACE) gene has been reported to be a risk factor for myocardial infarction. However, this association has not been confirmed in some populations. We hypothesized that the discrepancies between these studies may be due to their definition of ischemic heart diseases. According to the genotype of the ACE gene, we analyzed the profiles of 320 patients who underwent coronary angiography for possible ischemic heart diseases. Of these, 23 patients had no significantly diseased vessels and no acetylcholine-induced vasospasm (normal acetylcholine responder [NAR]) (II, 7; ID, 14; DD, 2), 34 patients had no significantly diseased vessels and acetylcholine-induced vasospasm (paradoxical acetylcholine responder: [PAR]) (II, 15; ID, 18; DD, 1), 80 angina pectoris (AP) patients had significantly diseased vessels (II, 41; ID, 37; DD, 2), and 183 patients demonstrated myocardial infarction (MI) (II, 67; ID, 91; DD, 25). The frequency of the DD genotype was significantly lower in PAR and AP patients than in those with MI (P = .0344). Next we analyzed the length of time between the first anginal pain and the onset of myocardial infarction in the MI group. We obtained reliable information regarding this period in 149 of the 183 patients. This period was significantly shorter in the ID and DD groups than in the II group (P = .0022). Multiple regression analyses revealed that this period was significantly determined (P = .0003, R = .324) by the genotype of the ACE gene (II = 1, ID + DD = 2, P = .0003) and age (P = .034). The D allele of the ACE gene and lower age were associated with a shorter period. On the other hand, the genotype of the ACE gene had no significant effect on the number of significantly diseased (> 50%) lesions. The frequency of the D allele in subjects with a rapid progression of MI was significantly higher than that in subjects with a prolonged history of stable AP (P < .0001). In summary, the II genotype of the ACE gene was associated with a longer period of time between the first anginal pain and the onset of myocardial infarction than the ID and DD genotypes of the ACE gene.