Brunner-La Rocca H P, Schneider J, Künzli A, Turina M, Kiowski W
Division of Cardiology, University Hospital Zurich, Switzerland.
Transplantation. 1998 Feb 27;65(4):538-43. doi: 10.1097/00007890-199802270-00015.
Graft coronary artery disease (CAD) is an increasingly important problem during long-term survival after heart transplantation, but the importance of cellular rejection, in particular late after transplantation, remains undetermined.
We analyzed 492 coronary angiographies (967+/-705 days after transplantation; range, 49 days to 9.4 years) and 5201 endomyocardial biopsies (518+/-648 days after transplantation) from 156 patients (age, 47+/-11 years). Patients with angiographically detectable graft CAD had significantly more episodes of rejection requiring augmentation of immunosuppressive therapy (i.e., International Society of Heart and Lung Transplantation score > or = 3A) than those without graft CAD during the first (3.7+/-2.6 vs. 2.2+/-2.0, P<0.001) as well as subsequent years after transplantation (1.2+/-1.9 vs. 0.4+/-0.9, P<0.01). Multivariate logistic regression analysis including established risk factors for CAD, ischemic time, gender and age of donors and recipients, number of mismatches, cytomegalovirus infection, and drug therapy showed that the number of rejections during the first [odds ratio (OR)=1.39, P<0.005] as well as subsequent years (OR=1.49, P<0.05), previous cytomegalovirus infection (OR=3.21, P<0.05), donor age >40 years (OR=2.97, P<0.05), and current or former smoker status (OR=2.76, P<0.05) were independent predictors of graft CAD. In patients without angiographically detectable graft CAD 1 year after transplantation, the number of rejections after the first year was even more strongly related to graft coronary artery disease than in the total patient population, underlining the importance of late cellular rejection (OR=1.74, P<0.005).
Rejection requiring augmentation of immunosuppression early and late after transplantation is an independent risk factor for the development of angiographically detectable graft CAD. Hence, the search for and treatment of moderate or severe rejection seems to be prudent even late after transplantation.
移植冠状动脉疾病（CAD）是心脏移植后长期存活期间日益重要的问题，但细胞排斥反应的重要性，尤其是移植后期的重要性，仍未确定。
我们分析了156例患者（年龄47±11岁）的492次冠状动脉造影（移植后967±705天；范围49天至9.4年）和5201次心内膜心肌活检（移植后518±648天）。与无移植CAD的患者相比，血管造影可检测到移植CAD的患者在移植后的第一年（3.7±2.6对2.2±2.0，P<0.001）以及随后几年（1.2±1.9对0.4±0.9，P<0.01）需要增加免疫抑制治疗的排斥反应发作明显更多。多因素逻辑回归分析包括CAD的既定危险因素、缺血时间、供体和受体的性别与年龄、错配数量、巨细胞病毒感染和药物治疗，结果显示移植后第一年（比值比[OR]=1.39，P<0.005）以及随后几年（OR=1.49，P<0.05）的排斥反应次数、既往巨细胞病毒感染（OR=3.21，P<0.05）、供体年龄>40岁（OR=2.97，P<0.05）以及当前或既往吸烟状态（OR=2.76，P<0.05）是移植CAD的独立预测因素。在移植后1年血管造影未检测到移植CAD的患者中，第一年之后的排斥反应次数与移植冠状动脉疾病的相关性甚至比总体患者人群更强，这突出了晚期细胞排斥反应的重要性（OR=1.74，P<0.005）。
移植后早期和晚期需要增加免疫抑制的排斥反应是血管造影可检测到的移植CAD发生的独立危险因素。因此，即使在移植后期，寻找并治疗中度或重度排斥反应似乎也是明智的。
