Pinto Y M, van Gilst W H, Kingma J H, Schunkert H
Department of Clinical Pharmacology, University of Groningen, The Netherlands.
J Am Coll Cardiol. 1995 Jun;25(7):1622-6. doi: 10.1016/0735-1097(95)00090-q.
This study sought to determine whether patients who are homozygous for the deletion (D)-type allele of the angiotensin-converting enzyme gene display augmented ventricular dilation after myocardial infarction.
Recent evidence suggests that the deletion-type allele of the angiotensin-converting enzyme gene (DD genotype) is associated with an increased prevalence of myocardial infarction and myocardial hypertrophy. However, it is unknown whether the DD genotype is associated with adverse cardiac remodeling. To address this question we determined the genotype in patients enrolled in the Captopril and Thrombolysis Study (CATS), a prospective trial in which patients received either captopril or placebo during and after thrombolysis for a first anterior myocardial infarction.
Cardiac volume was determined by echocardiography immediately after thrombolysis and at 1-year follow-up. The genotype for the angiotensin-converting enzyme was determined in 96 patients. Norepinephrine levels were assessed during and immediately after thrombolysis.
Immediately after thrombolysis, cardiac volume did not differ between genotype groups. However, at 1-year follow-up, both end-systolic and end-diastolic left ventricular volumes were significantly greater in the DD-genotype group. Norepinephrine increased to higher levels in the DD-genotype group that received placebo therapy. Captopril treatment effectively blunted both the norepinephrine increase and cardiac dilation in the DD-genotype group.
This exploratory study suggests that homozygosity for the angiotensin-converting enzyme deletion-type allele is associated with augmented neurohumoral activation as well as augmented cardiac dilation after an acute anterior myocardial infarction, an effect that may be susceptible to angiotensin-converting enzyme inhibition.
本研究旨在确定血管紧张素转换酶基因缺失（D）型等位基因纯合子患者在心肌梗死后是否表现出更明显的心室扩张。
最近的证据表明，血管紧张素转换酶基因的缺失型等位基因（DD基因型）与心肌梗死和心肌肥大的患病率增加有关。然而，尚不清楚DD基因型是否与不良心脏重塑有关。为了解决这个问题，我们在卡托普利与溶栓研究（CATS）中确定了患者的基因型，这是一项前瞻性试验，患者在首次前壁心肌梗死溶栓期间及之后接受卡托普利或安慰剂治疗。
溶栓后即刻及1年随访时通过超声心动图测定心脏容积。对96例患者测定血管紧张素转换酶的基因型。在溶栓期间及溶栓后即刻评估去甲肾上腺素水平。
溶栓后即刻，各基因型组之间心脏容积无差异。然而，在1年随访时，DD基因型组的收缩末期和舒张末期左心室容积均显著更大。接受安慰剂治疗的DD基因型组去甲肾上腺素升高至更高水平。卡托普利治疗有效抑制了DD基因型组去甲肾上腺素的升高和心脏扩张。
这项探索性研究表明，血管紧张素转换酶缺失型等位基因纯合子与急性前壁心肌梗死后神经体液激活增强以及心脏扩张增强有关，这种效应可能对血管紧张素转换酶抑制敏感。
