King V, Constine L S, Clark D, Schwartz R G, Muhs A G, Henzler M, Hutson A, Rubin P
Department of Radiation Oncology, Albany Medical College, NY, USA.
Int J Radiat Oncol Biol Phys. 1996 Nov 1;36(4):881-9. doi: 10.1016/s0360-3016(96)00295-7.
a) To assess the age-related incidence of morbid cardiac events including cardiac death (CD), nonfatal myocardial infarction (MI), and angina pectoris (AP) in all patients treated for Hodgkin's disease at a single institution; b) to examine the prevalence of cardiac risk factors and presence of coronary artery disease (CAD) in affected patients.
475 patients were treated for Hodgkin's disease in our institution between 1954 and 1989. The status of 97% of the cohort was established either by patient visit and examination in 1992-1993, personal telephone contact, or documentation of death. The 326 of these patients who had mantle irradiation (RT) and survived 3 years formed the study population. Patients who experienced AP, MI, or CD secondary to CAD were assessed for the presence of specific cardiac risk factors. Cardiac catheterization and necropsy data were reviewed to determine the presence and degree of coronary artery stenosis.
Eighteen of 326 patients (5.5%) have had a morbid cardiac event directly related to CAD. Seven patients had CD. Seven patients experienced nonfatal MI, and four patients had AP. The mean interval from RT to morbid cardiac event was 13.1 years (range: 4.4-27.0), and the mean age at the time of the event was 39.4 years (range: 24-65). Four of these patients had morbid cardiac events between ages 24-29 years. Based on US statistics of CD secondary to MI, the relative risk of CD for the treated group was 2.8 (3.1 for males and 1.8 for females). Remarkably, no difference was found in the risk of experiencing a morbid cardiac endpoint in patients stratified by either decile of age at which RT was given, or by duration of follow-up. Only one patient experiencing an event (AP) had received an anthracycline. The mean RT dose to the central cardiac volume for the affected patients was 44.3 Gy (range: 35-60.4). Autopsy or catheterization data were available on 15 patients and revealed 90-100% stenosis of at least one major vessel in 11 patients (73%), and no single artery was more commonly stenosed. Specifically, the left anterior descending and right coronary arteries were each greater than or equal to 60% stenosed in 10 out of 15 patients (67%), and either the left main or circumflex arteries were greater than or equal to 50% stenosed in 5 out of 15 patients (33%); triple vessel disease was present in seven patients. Risk factor data were available on all patients experiencing morbid cardiac events: 72% smoked, 72% were male, 78% had hypercholesterolemia, 61% were obese, 28% had a positive family history, 33% had hypertension, and 6% (one) had diabetes. The average number of risk factors per patient was 2.9; seven patients had at least four risk factors, and all patients had at least one risk factor. This frequency of risk factors is elevated when compared to the US population.
In our institution, 5.5% of patients treated for Hodgkin's disease experienced a morbid cardiac event following RT to the central cardiac volume. The doses given were greater than commonly used today. Some patients experienced events at a young age, and the likelihood of experiencing CD was increased compared to the general population. This observation is consistent with RT as an additional risk factor in the induction of morbid cardiac events. Appropriate cardiac shielding and radiation doses, careful follow-up, which includes monitoring of cardiac function, and a preventative program of sensible dietary habits, exercise, and nonsmoking may be beneficial in reducing cardiac morbidity in long-term survivors of Hodgkin's disease.
a）评估在单一机构接受霍奇金病治疗的所有患者中，与年龄相关的病态心脏事件发生率，包括心源性死亡（CD）、非致命性心肌梗死（MI）和心绞痛（AP）；b）检查受影响患者的心脏危险因素患病率及冠状动脉疾病（CAD）的存在情况。
1954年至1989年间，我院对475例患者进行了霍奇金病治疗。通过1992 - 1993年患者就诊及检查（97%队列）、个人电话联系或死亡记录确定了队列状态。其中326例接受斗篷野放疗（RT）且存活3年的患者构成研究人群。对继发于CAD的AP、MI或CD患者评估特定心脏危险因素的存在情况。回顾心脏导管检查和尸检数据以确定冠状动脉狭窄的存在及程度。
326例患者中有18例（5.5%）发生了与CAD直接相关的病态心脏事件。7例患者发生心源性死亡，7例经历非致命性心肌梗死，4例发生心绞痛。从放疗至病态心脏事件的平均间隔为13.1年（范围：4.4 - 27.0年），事件发生时的平均年龄为39.4岁（范围：24 - 65岁）。其中4例患者在24 - 29岁时发生病态心脏事件。根据美国MI继发心源性死亡的统计数据，治疗组心源性死亡的相对风险为2.8（男性为3.1，女性为1.8）。值得注意的是，按放疗时年龄的十分位数或随访时间分层的患者，在发生病态心脏终点事件的风险方面未发现差异。仅1例发生事件（AP）的患者接受过蒽环类药物治疗。受影响患者心脏中心体积的平均放疗剂量为44.3 Gy（范围：35 - 60.4 Gy）。15例患者有尸检或导管检查数据，其中11例（73%）显示至少一支主要血管狭窄90 - 100%，且无单一动脉更常发生狭窄。具体而言，15例患者中有10例（67%）左前降支和右冠状动脉狭窄均≥60%，15例患者中有5例（33%）左主干或回旋支动脉狭窄≥50%；7例患者存在三支血管病变。所有发生病态心脏事件的患者均有危险因素数据：72%吸烟，72%为男性，78%有高胆固醇血症，61%肥胖，28%有家族史阳性，33%有高血压，6%（1例）有糖尿病。每位患者的平均危险因素数量为2.9个；7例患者至少有4个危险因素，且所有患者至少有一个危险因素。与美国人群相比，这些危险因素的频率有所升高。
在我院，接受心脏中心体积放疗的霍奇金病患者中有5.5%发生了病态心脏事件。所给予的剂量高于当今常用剂量。一些患者在年轻时发生事件，且与一般人群相比，发生心源性死亡的可能性增加。这一观察结果与放疗作为诱发病态心脏事件的额外危险因素一致。适当的心脏屏蔽和放疗剂量、仔细的随访（包括监测心脏功能）以及合理饮食习惯、运动和戒烟的预防计划，可能有助于降低霍奇金病长期存活者的心脏发病率。
