Valantine Hannah
Division of Cardiovascular Medicine, Stanford University Medical School, Stanford, California, USA.
J Heart Lung Transplant. 2004 May;23(5 Suppl):S187-93. doi: 10.1016/j.healun.2004.03.009.
Cardiovascular disease post-transplant, particularly ischemic heart disease, is a significant problem for all transplant recipients. The major risk factors-smoking, obesity, diabetes, dyslipidemia and hypertension-are often more prevalent in heart transplant populations than in the general population. One of the main risk factors influencing graft loss and patient survival is cardiac allograft vasculopathy (CAV). Because CAV affects between 30% and 60% of cardiac transplant recipients within 5 years of surgery, prevention is a key focus for cardiac transplant teams today. CAV is caused by both immunologic mechanisms (e.g., acute rejection and anti-HLA antibodies) and non-immunologic mechanisms relating to the transplant itself or the recipient (e.g., donor age, hypertension, hyperlipidemia and pre-existing diabetes) or to the side effects often associated with immunosuppression with calcineurin inhibitors or corticosteroids (e.g., cytomegalovirus infection, nephrotoxicity and new-onset diabetes after transplantation). The calcineurin inhibitors, cyclosporine and tacrolimus, effectively prevent acute rejection, but do not prevent the development of CAV. CAV prevention will require a combined approach of new adjunct immunosuppressant agents (e.g., the proliferation signal inhibitors) and reduction in cardiovascular risk. Hypertension, hyperlipidemia and diabetes are also associated with the immunosuppression required to prevent organ rejection. Some studies have shown that hypertension is present more frequently in cyclosporine-treated patients than in tacrolimus-treated patients and that tacrolimus may be associated with a more favorable lipid profile. On the other hand, tacrolimus may be more diabetogenic than cyclosporine with current data suggesting a trend but no statistically significant supporting evidence. New-onset diabetes after transplantation is at times difficult to manage and may be an important determinant along with hypertension and hyperlipidemia of ischemic heart disease, cerebrovascular disease and peripheral vascular disease. The choice of calcineurin inhibitor for an immunosuppressive regimen in heart transplantation should consider the associated relative cardiovascular risks.
移植后心血管疾病，尤其是缺血性心脏病，是所有移植受者面临的重大问题。主要危险因素——吸烟、肥胖、糖尿病、血脂异常和高血压——在心脏移植人群中往往比在普通人群中更为普遍。影响移植物丢失和患者生存的主要危险因素之一是心脏移植血管病变（CAV）。由于CAV在手术5年内影响30%至60%的心脏移植受者，因此预防是当今心脏移植团队的关键重点。CAV由免疫机制（如急性排斥反应和抗HLA抗体）以及与移植本身或受者相关的非免疫机制（如供体年龄、高血压、高脂血症和既往糖尿病）或与钙调神经磷酸酶抑制剂或皮质类固醇免疫抑制相关的副作用（如巨细胞病毒感染、肾毒性和移植后新发糖尿病）引起。钙调神经磷酸酶抑制剂环孢素和他克莫司可有效预防急性排斥反应，但不能预防CAV的发生。CAV的预防需要新的辅助免疫抑制剂（如增殖信号抑制剂）和降低心血管风险的联合方法。高血压、高脂血症和糖尿病也与预防器官排斥所需的免疫抑制有关。一些研究表明，环孢素治疗的患者比他克莫司治疗的患者高血压更常见，并且他克莫司可能与更有利的血脂谱相关。另一方面，他克莫司可能比环孢素更易导致糖尿病，目前的数据表明存在一种趋势，但没有统计学上显著的支持证据。移植后新发糖尿病有时难以控制，并可能是缺血性心脏病、脑血管疾病和外周血管疾病的重要决定因素，与高血压和高脂血症一样。心脏移植免疫抑制方案中钙调神经磷酸酶抑制剂的选择应考虑相关的相对心血管风险。
