Alivon Maureen, Giroux Julie, Briet Marie, Goldwasser François, Laurent Stéphane, Boutouyrie Pierre
aUniversité Paris-Descartes bINSERM U970 cAssistance Publique-Hôpitaux de Paris dDepartment of Pharmacology eClinical Investigation Center, Hôpital Européen Georges Pompidou fDepartment of Oncology, CERIA, Hôpital Cochin, Paris, France *Maureen Alivon and Julie Giroux contributed equally to the writing of this article.
J Hypertens. 2015 Jun;33(6):1310-7. doi: 10.1097/HJH.0000000000000550.
Systemic hypertension is a frequent side effect of antiangiogenic drugs (AADs) and may represent a marker of efficacy on cancer. We hypothesized that large artery properties are affected by AADs, and contribute to the rise of blood pressure and may be better related to cancer progression and mortality than hypertension.
Participants were studied before AADs (V0), 10 days later (V1) and then every 2 weeks for 6 weeks (V1-V4). We included 57 consecutive patients in whom treatment with sorafenib (400 mg twice daily) or sunitinib (37.5-50 mg once daily) was indicated. The target dose could be adjusted according to tolerance and response. Aortic and carotid stiffness, brachial and central blood pressure and augmentation index were measured noninvasively at each visit. Data regarding cancer progression and mortality were collected at 6 months. Twenty-eight patients (49%) developed hypertension. Brachial SBP significantly increased during follow-up (V0-V1: +9.6 ± 15.2 mmHg, P < 0.001; V0-V4: +6.0 ± 17.8 mmHg, P = 0.04). Central BP, and aortic and carotid stiffness increased independently of brachial BP changes. Aortic and carotid stiffening were associated with cancer progression independently of BP changes [hazard risk 1.24 (1.01-1.51) and 1.34 (1.03-1.73), respectively; P < 0.05], but not with cancer mortality. Brachial SBP had no predictive value.
Large arteries stiffen during AAD treatment partly independently of BP changes. Arterial mechanical properties are associated with BP rise. Arterial stiffening is related with the effects of AAD on cancer progression independently of BP changes. Large artery properties might help monitor AAD therapy in cancer patients.
系统性高血压是抗血管生成药物（AADs）常见的副作用，可能是癌症疗效的一个标志物。我们推测大动脉特性受AADs影响，促成血压升高，并且与癌症进展和死亡率的关联可能比高血压更好。
在使用AADs之前（V0）、10天后（V1）以及之后每2周共6周（V1-V4）对参与者进行研究。我们纳入了57例连续的患者，这些患者被指示使用索拉非尼（每日两次，每次400mg）或舒尼替尼（每日一次，37.5-50mg）进行治疗。目标剂量可根据耐受性和反应进行调整。每次就诊时采用非侵入性方法测量主动脉和颈动脉僵硬度、肱动脉和中心血压以及增强指数。在6个月时收集有关癌症进展和死亡率的数据。28例患者（49%）发生了高血压。随访期间肱动脉收缩压显著升高（V0-V1：+9.6±15.2mmHg，P<0.001；V0-V4：+6.0±17.8mmHg，P=0.04）。中心血压以及主动脉和颈动脉僵硬度的升高与肱动脉血压变化无关。主动脉和颈动脉僵硬度增加与癌症进展独立相关，与血压变化无关[风险比分别为1.24（1.01-1.51）和1.34（1.03-1.73）；P<0.05]，但与癌症死亡率无关。肱动脉收缩压无预测价值。
在AAD治疗期间，大动脉僵硬度增加部分独立于血压变化。动脉力学特性与血压升高有关。动脉僵硬度增加与AAD对癌症进展的影响独立相关，与血压变化无关。大动脉特性可能有助于监测癌症患者的AAD治疗。
