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阿托伐他汀对儿童期癌症成年幸存者血管功能和结构的影响:一项随机、安慰剂对照的初步临床试验。

The Effect of Atorvastatin on Vascular Function and Structure in Young Adult Survivors of Childhood Cancer: A Randomized, Placebo-Controlled Pilot Clinical Trial.

机构信息

1Pennington Biomedical Research Center, Baton Rouge, Louisiana.

2Department of Pediatrics, University of Minnesota Medical School, Minneapolis, Minnesota.

出版信息

J Adolesc Young Adult Oncol. 2019 Aug;8(4):442-450. doi: 10.1089/jayao.2017.0075. Epub 2017 Aug 30.

Abstract

Many adult survivors of childhood cancer are at high-risk of developing cardiovascular disease. Cancer therapy may cause damage to the vascular endothelium, thereby initiating atherosclerosis. Atorvastatin has been shown to improve endothelial function independent of reducing cholesterol, as well as reduce/slow arterial stiffness and thickening, yet has never been studied in childhood cancer survivors (CCS). Twenty-seven young adult (age 26.8 ± 6.2 years) survivors of childhood acute lymphoblastic leukemia or Non-Hodgkin's lymphoma were randomly assigned (1:1) 40 mg/day of atorvastatin or placebo for 6 months. Brachial artery flow-mediated dilation (FMD), small artery reactive hyperemia index (RHI), arterial stiffness, and carotid artery elasticity/thickness were assessed. Fifteen participants completed the trial. No significant treatment effect for any vascular outcomes was observed at 6 months; however, a significant decrease in peak FMD (-3.0 [95% confidence interval [CI]: -5.3, -0.7]) and a trending significant decrease in RHI (-0.3 [95% CI: -0.62, 0.01]) was observed in the placebo group, resulting in a trend toward a treatment effects ( < 0.10). No effect on arterial stiffness, carotid arterial elasticity, or thickness was observed. Six months of atorvastatin treatment did not improve endothelial function or arterial stiffness in young adult CCS. While a trend toward an improvement in endothelial function was present, findings should be interpreted with caution owing to the small number of evaluable participants and subsequent lack of sufficient power. Further research in a larger sample size is needed to fully elucidate the effects of atorvastatin on vascular function. Trial registered at as NCT01733953.

摘要

许多儿童癌症幸存者成年后存在发生心血管疾病的高危风险。癌症治疗可能会导致血管内皮损伤,从而引发动脉粥样硬化。阿托伐他汀已被证明可改善血管内皮功能,且不依赖于降低胆固醇水平,还可降低/减缓动脉僵硬和增厚,但尚未在儿童癌症幸存者(CCS)中进行研究。27 名年轻成年(年龄 26.8±6.2 岁)急性淋巴细胞白血病或非霍奇金淋巴瘤儿童癌症幸存者被随机分配(1:1)接受阿托伐他汀 40mg/天或安慰剂治疗 6 个月。评估肱动脉血流介导的扩张(FMD)、小动脉反应性充血指数(RHI)、动脉僵硬和颈动脉弹性/厚度。15 名参与者完成了试验。6 个月时,未观察到任何血管结局的显著治疗效果;然而,安慰剂组的峰值 FMD 显著下降(-3.0[95%置信区间:-5.3,-0.7]),RHI 呈下降趋势(-0.3[95%置信区间:-0.62,0.01]),这表明存在治疗效果的趋势( <0.10)。未观察到动脉僵硬、颈动脉弹性或厚度的变化。6 个月的阿托伐他汀治疗并未改善年轻成年 CCS 的内皮功能或动脉僵硬。尽管内皮功能改善的趋势存在,但由于可评估参与者数量较少,随后缺乏足够的效力,因此应谨慎解释研究结果。需要在更大的样本量中进一步研究,以充分阐明阿托伐他汀对血管功能的影响。试验在 注册为 NCT01733953。

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