THE II-GENOTYPE OF THE ANGIOTENSIN-CONVERTING ENZYME GENE DELAYS THE ONSET OF ACUTE CORONARY SYNDROMES

The DD genotype of the angiotensin-converting enzyme (ACE) gene has be en reported to be a risk factor for myocardial infarction. However, th is association has not been confirmed in some populations. We hypothes ized that the discrepancies between these studies may be due to their definition of ischemic heart diseases. According to the genotype of th e ACE gene, we analyzed the profiles of 320 patients who underwent cor onary angiography for possible ischemic heart diseases. Of these, 23 p atients had no significantly diseased vessels and no acetylcholine-ind uced vasospasm (nor mal acetylcholine responder [NARI]) (II, 7; ID, 14 ; DD, 2), 34 patients had no significantly diseased vessels and acetyl choline-induced vasospasm (paradoxical acetylcholine responder: [PAR]) (II, 15, ID, 18; DD, 1), 80 angina pectoris (AP) patients had signifi cantly diseased vessels (II, 41; ID, 37; DD, 2), and 183 patients demo nstrated myocardial infarction (MI) (II, 67; ID, 91; DD, 25). The freq uency of the DD genotype was significantly lower in PAR and AP patient s 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 peri od in 149 of the 183 patients. This period was significantly shorter i n the ID and DD groups than in the II group (P=.0022). Multiple regres sion 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=.00 03) 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 t he ACE gene had no significant effect on the number of significantly d iseased (>50%) lesions. The frequency of the D allele in subjects with a rapid progression of MI was significantly higher than that in subje cts with a prolonged history of stable AP (P<.0001). In summary, the I I 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.