Barthélémy O, Escaut L, Vayre F, Gallet B, Pulik M, Heloire F, Vittecoq D
Service de Cardiologie, Hôpital Cochin, 27 rue du Fg Saint-Jacques, F75679 Paris.
Presse Med. 2002 Mar 2;31(8):343-8.
Cardiovascular complications occurring in patients infected by the human immunodeficient virus (HIV) have considerably changed since the appearance, in April 1996, of highly active antiretroviral tri-therapy (HAART), associating reverse transcriptase and protease HIV-1 inhibitors. The spectacular efficacy of anti-proteases has led to the almost complete disappearance of these opportunistic complications. However, in May 1998, acute coronary accidents were reported in the literature, thus questioning the possible responsibility of antiprotease treatment in the occurrence of accelerated atheroma.
We report a series of 8 seropositive patients in whom an acute coronary event had occurred between February 1997 and February 1999.
The patients were young and all exhibited cardiovascular risk factors (smoking, dyslipidemia) and were treated with HIV-1 protease inhibitors. Six patients presented myocardial infarction, one patient unstable angina and one patient effort angina.
A rise in triglycerides was observed principally on ingestion of ritonavir and a rise in cholesterol and LDL-cholesterol with all the antiprotease agents. Glucose intolerance was observed with indinavir. The occurrence of acute coronary events appeared to be related to antiprotease treatment (at the origin of metabolic disorders, endothelial dysfunction...), although it was impossible to say whether the antiprotease agents were responsible for the early atheroma or whether they simply contributed to the event. The coronary lesions were characterized by their number (single artery) and their topography (proximal or median). Nelfinavir may carry less cardiovascular risks than the other antiproteases. Mean term prognosis was relatively good, after therapeutic adjustment (change in antiprotease, strategic measures against cardiovascular risk factors, introduction of anti-anginal treatment...).
Larger and longer studies would help to specify the role of antiproteases in the occurrence of early coronary events. Rigorous monitoring (lipid and glucose measurements, tests to search for myocardial infarction,..) together with the development of new antiretroviral molecules would reduce the number of coronary events in this type of patient.
自1996年4月高效抗逆转录病毒三联疗法（HAART）问世以来，联合使用HIV-1逆转录酶抑制剂和蛋白酶抑制剂，感染人类免疫缺陷病毒（HIV）患者发生的心血管并发症已发生了相当大的变化。抗蛋白酶药物的显著疗效已使这些机会性并发症几乎完全消失。然而，1998年5月，文献报道了急性冠状动脉事件，从而质疑抗蛋白酶治疗在加速动脉粥样硬化发生中的可能责任。
我们报告了一系列8例血清学阳性患者，他们在1997年2月至1999年2月期间发生了急性冠状动脉事件。
这些患者均较年轻，都表现出心血管危险因素（吸烟、血脂异常），并接受了HIV-1蛋白酶抑制剂治疗。6例患者发生心肌梗死，1例患者发生不稳定型心绞痛，1例患者发生劳力性心绞痛。
主要在服用利托那韦时观察到甘油三酯升高，使用所有抗蛋白酶药物时胆固醇和低密度脂蛋白胆固醇均升高。使用茚地那韦时观察到葡萄糖耐量异常。急性冠状动脉事件的发生似乎与抗蛋白酶治疗有关（代谢紊乱、内皮功能障碍的起因……），尽管无法确定抗蛋白酶药物是导致早期动脉粥样硬化的原因，还是仅仅促成了该事件。冠状动脉病变的特征在于其数量（单支动脉）和部位（近端或中段）。奈非那韦可能比其他抗蛋白酶药物具有更低的心血管风险。经过治疗调整（更换抗蛋白酶药物、针对心血管危险因素的策略性措施、引入抗心绞痛治疗……）后，中期预后相对较好。
规模更大、时间更长的研究将有助于明确抗蛋白酶药物在早期冠状动脉事件发生中的作用。严格的监测（血脂和血糖测量、心肌梗死筛查试验等）以及新型抗逆转录病毒分子的研发将减少这类患者冠状动脉事件的发生数量。
