抗血管生成靶向药致药物性高血压发生风险的影响因素和预测模型

Influencing factors and predictive model for the risk of drug-induced hypertension caused by anti-angiogenic targeting drugs

    摘要
  • 摘要:
    目的  分析抗血管生成靶向药物（ATD）引发药物性高血压的风险因素，为临床实践中能够有效监测与管理该类药物副作用提供参考。
    方法  本研究为前瞻性研究，对在复旦大学附属肿瘤医院就诊使用ATD的非高血压患者开展血压随访。收集患者的性别、年龄、ATD类别、饮食情况、活动情况、焦虑抑郁水平、行为类型等。采用Cox回归模型进行多因素分析，探讨药物性高血压发生的风险因素；采用R统计软件及rms程序包建立使用ATD的患者发生药物性高血压的列线图预测模型。
    结果  本研究共纳入964例使用ATD的非高血压患者，通过为期6个月的随访，有291例患者在随访过程中发生了药物性高血压。Kaplan-Meier分析显示，性别、体重指数（BMI）、靶向药类型、饮食习惯、行为类型等5个变量可影响药物性高血压的发生（均P＜0.05）。多因素Cox回归分析结果显示，BMI、靶向药类型、行为类型是ATD所致药物性高血压的风险因素，使用酪氨酸激酶抑制剂（TKIs）的患者发生药物性高血压的风险较使用贝伐珠单抗的患者高85.0%（HR = 1.850, 95%CI：1.469～2.331, P＜0.001）；BMI在18.5～＜24.0、24.0～＜28.0、 ≥ 28.0 kg/m2的患者发生药物性高血压的发生风险分别比BMI＜18.5 kg/m2的患者高1.262倍（HR = 2.262, 95%CI：1.229～4.162, P = 0.009）、1.309倍（HR = 2.309, 95%CI：1.232～4.328, P = 0.009）、2.508倍（HR = 3.508, 95%CI：1.710～7.196, P＜0.001）；行为类型为偏B型和典型B型的患者，其药物性高血压发生风险是典型A型的51.6%（HR = 0.516, 95%CI：0.355～0.749, P＜0.001）和44.5%（HR = 0.445, 95%CI：0.301～0.659, P＜0.001）。
    结论  肿瘤患者使用ATD后发生药物性高血压的风险较高。BMI、靶向药类型、行为类型等因素是ATD所致药物性高血压的风险因素。

     

    Abstract:
    Objective  To analyze the risk factors for drug-induced hypertension caused by anti-angiogenesis targeted drug (ATD), and to provide insights and references for effective monitoring and management of this adverse drug reaction in clinical practice.
    Methods Non-hypertensive patients treated with ATD at Fudan University Shanghai Cancer Center were enrolled. Data on gender, age, ATD category, dietary habits, physical activity, anxiety and depression levels, and behavior type were collected. A Cox regression model was employed for multivariate analysis to investigate the influencing factors of drug-induced hypertension; a logistic regression model predicting the occurrence of drug-induced hypertension in patients using ATD was established using R statistical software and the rms package.
    Results  A total of 964 participants completed the blood pressure monitoring, 291 patients developed drug-induced hypertension during follow-up. Kaplan-Meier analysis revealed that five variables—gender, body mass index (BMI), type of targeted drug, dietary habits, and behavior type—significantly influenced the incidence of drug-induced hypertension (P ＜ 0.05). Cox regression analysis indicated that BMI, type of targeted drug, and behavior type were independent risk factors for ATD-induced hypertension. Patients receiving tyrosine kinase inhibitors (TKIs) had an 85.0% higher risk of drug-induced hypertension compared to those using bevacizumab (HR = 1.850,95%CI: 1.469 to 2.331, P＜0.001). Patients with BMI 18.5 to ＜24.0, 24.0 to ＜28.0 and ≥ 28.0 kg/m2 showed 1.262 times (HR = 2.262, 95%CI 1.229 to 4.162, P = 0.009),1.309 times (HR = 2.309, 95%CI 1.232 to 4.328, P = 0.009), and 2.508 times (HR = 3.508, 95%CI 1.710 to 7.196, P＜0.001) higher risks than patients with BMI＜18.5 kg/m2 , respectively. The risk of developing drug-induced hypertension in patients with behavioral type B and typical B type was 51.6% (HR = 0.516, 95%CI: 0.355 to 0.749, P＜0.001) and 44.5% times (HR = 0.445, 95%CI: 0.301 to 0.659, P＜0.001) of that in typical A type patients.
    Conclusion  Patients with tumors have a relatively high risk of drug-induced hypertension after using ATD. BMI, type of targeted drugs, and behavioral patterns were independent risk factors for ATD-induced hypertension.

     

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