Department of Medicine, University of Debrecen Medical and Health Science Center, 4025 Nagyerdei Krt. 98, Debrecen, Hungary.
Pathol Oncol Res. 2013 Jul;19(3):375-83. doi: 10.1007/s12253-012-9589-6. Epub 2012 Dec 16.
Vascular and endothelial functions were investigated in long term survivors of childhood cancer exposed to anthracycline treatment. We enrolled 96 long-term survivors (57 males and 39 females, mean age 14.9 ± 5.3 year) of different childhood cancers and 72 age-, sex-, bodyweight- and blood pressure matched controls (39 males and 33 females, mean age 13.7 ± 4.9 year). Aortic stiffness was characterized by echocardiography. Brachial artery endothelial function was assessed by flow-mediated dilatation (FMD%) and nitrate-mediated dilatation (NTG%). Results were compared between three subgroups: anthracycline treated, only chemotherapy treated and control subgroups. The cumulative anthracycline dose was less than 350 mg/m². The healthy control subgroup had a significantly greater FMD response (13.13 ± 2.40 %), and lower stiffness index (2.08 ± 0.6) than both the anthracycline (7.12 ± 6.28 % and 6.45 ± 3.25, respectively) and only chemotherapy treated (10.17 ± 4.23 % and 4.12 ± 2.32, respectively) subgroups. In the anthracycline treated subgroup a significantly (p < 0.01) lower FMD% response, and higher stiffness index were detected than in the only chemotherapy treated subgroup. Higher triglyceride level, higher cumulative anthracycline dose and lower age at the start of treatment were found to be associated independently with impairment of FMD% response and aortic stiffness. We found a significant negative correlation between FMD and aortic stiffness (p < 0.001) and a positive correlation between FMD and distensibility (p < 0.0001). Childhood cancer long term survivors exposed to anthracycline treatment exhibit a marked preclinical vasculopathy, characterized by endothelial dysfunction and increased arterial stiffness, contributing to a deteriorated cardiovascular function.
血管和内皮功能在接受蒽环类药物治疗的儿童癌症长期幸存者中进行了研究。我们招募了 96 名患有不同儿童癌症的长期幸存者（57 名男性和 39 名女性，平均年龄 14.9±5.3 岁）和 72 名年龄、性别、体重和血压匹配的对照者（39 名男性和 33 名女性，平均年龄 13.7±4.9 岁）。通过超声心动图来描述主动脉僵硬度。通过血流介导的扩张（FMD%）和硝酸盐介导的扩张（NTG%）来评估肱动脉内皮功能。将结果与三个亚组进行比较：蒽环类药物治疗组、仅化疗治疗组和对照组。累积蒽环类药物剂量小于 350mg/m²。健康对照组的 FMD 反应（13.13±2.40%）显著更大，僵硬度指数（2.08±0.6）也显著低于蒽环类药物（7.12±6.28%和 6.45±3.25）和仅化疗治疗组（10.17±4.23%和 4.12±2.32）。在蒽环类药物治疗组中，FMD 反应明显（p<0.01）较低，僵硬度指数也高于仅化疗治疗组。研究发现，较高的甘油三酯水平、较高的累积蒽环类药物剂量和治疗开始时的年龄较低与 FMD%反应和主动脉僵硬度受损独立相关。我们发现 FMD 与主动脉僵硬度之间存在显著的负相关（p<0.001），并且 FMD 与可扩张性之间存在显著的正相关（p<0.0001）。接受蒽环类药物治疗的儿童癌症长期幸存者表现出明显的临床前血管病变，其特征为内皮功能障碍和动脉僵硬度增加，导致心血管功能恶化。
