Coschignano Maria Antonietta, De Ciuceis Carolina, Agabiti-Rosei Claudia, Brami Valeria, Rossini Claudia, Chiarini Giulia, Malerba Paolo, Famà Francesca, Cosentini Deborah, Muiesan Maria Lorenza, Salvetti Massimo, Petelca Alina, Capellini Sara, Arnoldi Chiara, Nardin Matteo, Grisanti Salvatore, Rizzoni Damiano, Berruti Alfredo, Paini Anna
Department of Clinical and Experimental Sciences, University of Brescia, Brescia, Italy.
Spedali Civili di Brescia, Clinica Medica University of Brescia and 2nd Division of Medicine, Brescia, Italy.
Front Cardiovasc Med. 2021 Mar 10;8:651594. doi: 10.3389/fcvm.2021.651594. eCollection 2021.
Antiangiogenic therapies (tyrosine kinase inhibitors-TKI and direct anti-VEGF monoclonal antibodies) are being increasingly used in the treatment of solid tumors; hypertension represents a common side effect of these agents. Several mechanisms are involved in the development of hypertension, including microvascular rarefaction and other microvascular alterations. Therefore, the aim of our study was to evaluate whether TKI and direct anti-VEGF agents may affect the structure of retinal arterioles or capillary density. We investigated 20 patients with a diagnosis of cancer who underwent a treatment with either a TKI or an anti-VEGF antibody. Patients were submitted to ambulatory monitoring blood pressure for blood pressure evaluation. Basal and total capillary density were assessed by capillaroscopy whereas, retinal arteriole morphology was measured by Adaptive Optics. Patients were evaluated before starting the antiangiogenic therapy (T0) and re-evaluated after 3 (T3) and 6 (T6) months after treatment. Fourteen patients completed the study. Systolic and diastolic blood pressure values were similar in all patients at T3 and T6 compared to T0. However, during the study antihypertensive treatment was optimized (increased dose and/or addition of drugs) in 57% of patients ( = 8). No differences were observed in retinal arteriole structural parameters and in large artery stiffness. Basal capillary density was reduced by antiangiogenic drugs after 3 or 6 months. Our data suggest that an increase of antihypertensive treatment is necessary in patients treated with a TKI or a direct VEGF inhibitor, confirming pro-hypertensive effects of these drugs. However, under adequate blood pressure control, microvascular structure seem to be partially preserved, since a worsening of basal capillary density but no changes in retinal arteriole morphology were observed.
抗血管生成疗法(酪氨酸激酶抑制剂-TKI和直接抗VEGF单克隆抗体)在实体瘤治疗中的应用越来越广泛;高血压是这些药物常见的副作用。高血压的发生涉及多种机制,包括微血管稀疏和其他微血管改变。因此,我们研究的目的是评估TKI和直接抗VEGF药物是否会影响视网膜小动脉结构或毛细血管密度。我们调查了20例诊断为癌症且接受TKI或抗VEGF抗体治疗的患者。患者接受动态血压监测以评估血压。通过毛细血管显微镜评估基础和总毛细血管密度,而通过自适应光学测量视网膜小动脉形态。在开始抗血管生成治疗前(T0)对患者进行评估,并在治疗后3个月(T3)和6个月(T6)重新评估。14例患者完成了研究。与T0相比,所有患者在T3和T6时的收缩压和舒张压值相似。然而,在研究期间,57%(n = 8)的患者优化了降压治疗(增加剂量和/或添加药物)。视网膜小动脉结构参数和大动脉僵硬度未观察到差异。抗血管生成药物在3或6个月后可降低基础毛细血管密度。我们的数据表明,接受TKI或直接VEGF抑制剂治疗的患者有必要增加降压治疗,证实了这些药物的促高血压作用。然而,在血压得到充分控制的情况下,微血管结构似乎得到了部分保留,因为观察到基础毛细血管密度恶化,但视网膜小动脉形态没有变化。