Hypertention:肿瘤与高血压的“恩怨情仇”

2021-01-08 MedSci原创 MedSci原创

了解癌症患者血压变化的机制将有助于确定高血压患者的新治疗靶点。

随着人口老龄化,高血压越来越成为一个严重的全球问题。流行病学数据显示,高血压的发病率在过去40年中翻了一番。同时,高血压和相关血管事件的发病率在全世界范围内不断增加,目前全世界每年有760万人死亡。

另一方面,老龄化人口也在很大程度上促进了癌症成为一个世界性的公共卫生问题。癌症是全球死亡的首要原因,2017年全球新发病例2450万,死亡960万。其中,一些小分子抑制剂用于癌症治疗明显改善了癌症患者的预后,延长了患者的生存期。因此心血管疾病是癌症幸存者晚期发病和死亡的主要原因。

因此, “肿瘤心脏病学”这一概念被提出,只在强调癌症治疗相关心脏功能障碍的预防诊断、治疗和随访的重要性。近期,来自心血管领域的专家最近在《高血压》(Hypertention)杂志引入了一个全新的亚专科——肿瘤高血压,后者着重于高血压和肿瘤的复杂病理生理学研究。

该文章主要从“高血压的发生是否先于肿瘤;抗癌治疗是如何影响患者血压水平的;对于这类患者何谓适宜控制血压”等几个方面进行了探讨。

高血压是癌症的一个潜在危险因素

在一项覆盖577799名成年人的队列中,发现男性的中血压(定义为收缩压和舒张压的平均值)与较高的癌症发生风险相关(每10 mmHg增量,HR=1.07),但上述关系在女性中并不存在。最近的流行病学研究表明,高血压与肾细胞癌(RCC)、结肠癌、食管鳞状细胞癌(SCC)、头颈部癌症、皮肤SCC、绝经后乳腺癌和子宫腺癌的风险较高有关。

高血压与癌症有着共同的风险因素,包括肥胖、糖尿病、钠摄入过多和低体力活动等,因此可能掩盖了高血压和癌症之间存在的因果关系。此外,关于高血压与癌症之间关系的研究结果因癌肿的类型和位置不同而不同。

降压药与癌症的发生

对27项观察性研究的系统性回顾发现,利尿剂的使用与肾癌风险增加相关(RR=1.34),且风险随着治疗时间的增加而增加。此外,在调整高血压和吸烟后,该关联仍然显著。另一项包括9项观察性研究的荟萃分析发现,皮肤癌的风险与噻嗪类药物的使用有关。

此外,ACE抑制剂的使用与ARB的使用相比,肺癌风险高14%。然而,ARB或ACE抑制剂的使用与癌症风险之间的关联并不一致,其原因可能是缺乏对混杂因素的控制,如吸烟和环境暴露,缺乏长期数据,以及研究人群之间的显著异质性。

某些癌症引起的高血压

有研究显示,人肾细胞癌细胞系中过度表达一些血管活性肽,包括尿毒症素Ⅱ、肾上腺髓质素和内皮素等都可能导致RCC患者血压升高。同时,副肿瘤综合征和肝细胞癌的患者高血压发生也较明显,提示某些类型的癌症本身也可引起高血压。

抗癌治疗引起的高血压

高血压是癌症患者最常见的合并症(38%),而且在已有高血压、年龄较大、体重指数较高的患者中比例较高。例如,VEGF信号通路(VSP)抑制剂具有抑制肿瘤进展和转移的作用。但由于VEGF信号通路抑制剂具有升压效应,因此不可避免的引发了高血压的发生。此类患者在停药后症状都能迅速改善。

同样,抗微管类药物、烷基样药和烷化剂等均被报道具有升高癌症患者血压的作用。但目前尚无研究证实,联用≥2种抗癌药物对血压升高具有协同作用。

癌症患者的血压控制策略

有专家意见建议,在服用VSP抑制剂的患者中,收缩压/舒张压应维持在<140/90 mm Hg。同时,在第一个治疗周期应每周测量一次血压,随后至少每2~3周测量一次。在美国心脏病学院(AHA)最近的一篇综述中,建议在收缩压/舒张压≥130/80 mm Hg的癌症患者中使用抗高血压药物。同样,欧洲心脏病学会/欧洲高血压学会(EHA)的高血压指南也建议在化疗第一周期内每周测量一次血压,此后至少每2~3周测量一次。

而就降压治疗,目前尚无针对使用VEGF信号通路抑制剂相关高血压的特定降压药物推荐,二氢吡啶类钙拮抗剂或可为癌症患者降压治疗一线药物,有研究显示有助于降低贝伐单抗相关高血压。

综上,该文章系统性地阐述了高血压与癌症之间的密切关系。了解癌症患者血压变化的机制将有助于确定高血压患者的新治疗靶点。

 

参考文献:

Kidoguchi S, Sugano N, Tokudome G, Yokoo T, Yano Y, Hatake K, Nishiyama A. New Concept of Onco-Hypertension and Future Perspectives. Hypertension. 2021 Jan;77(1):16-27. doi: 10.1161/HYPERTENSIONAHA.120.16044.

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    2021-10-10 feather89
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    2021-02-07 1615858451

    高校博士科研团队,提供SCI论文科研服务,文章提供原始数据,作者审核文章内容及结果后投稿,可指定拟投杂志,文章接受后付款,前期不收任何费用。术业有专攻,期待与您的合作1615858451

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    2021-01-27 Jessica

    如果一个人有高血压并且又吸烟,那患心血管疾病的风险就太大了,患其他癌症的风险也大。

    0

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    2021-01-27 Jessica

    高血压值得重视!#高血压# #肿瘤#

    0

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