Hypertension and Prohypertensive Antineoplastic Therapies in Cancer Patients

Abstract

The development of a wide range of novel antineoplastic therapies has improved the prognosis for patients with a wide range of malignancies, which has increased the number of cancer survivors substantially. Despite the oncological benefit, cancer survivors are exposed to short- and long-term adverse cardiovascular toxicities associated with anticancer therapies. Systemic hypertension, the most common comorbidity among cancer patients, is a major contributor to the increased risk for developing these adverse cardiovascular events. Cancer and hypertension have common risk factors, have overlapping pathophysiological mechanisms and hypertension may also be a risk factor for some tumor types. Many cancer therapies have prohypertensive effects. Although some of the mechanisms by which these antineoplastic agents lead to hypertension have been characterized, further preclinical and clinical studies are required to investigate the exact pathophysiology and the optimal management of hypertension associated with anticancer therapy. In this way, monitoring and management of hypertension before, during, and after cancer treatment can be improved to minimize cardiovascular risks. This is vital to optimize cardiovascular health in patients with cancer and survivors, and to ensure that advances in terms of cancer survivorship do not come at the expense of increased cardiovascular toxicities.

Incidence and Risk of Hypertension in Cancer Patients Treated With Atezolizumab and Bevacizumab: A Systematic Review and Meta-Analysis

“…In 2019, more than 16.9 million Americans with a history of cancer were alive, and this number is projected to grow to more than 22.1 million by 2030 ( 23 ). The development of novel anticancer drugs has significantly contributed to increased survival rates for patients with cancer over recent decades and comes at the cost of potential short-term and long-term toxicities ( 24 ). Cardiovascular toxicity is nonnegligible and adversely affects outcomes ( 25 ).…”

Risk Factors for the Comorbidity of Hypertension and Renal Cell Carcinoma in the Cardio-Oncologic Era and Treatment for Tumor-Induced Hypertension

“…VSP inhibitors could cause depletion of nitric oxide and prostacyclin which are vasodilators as well as increased vasoconstrictive endothelin-1 ( 89 ). In addition, increased reactive oxygen species, functional decreased microvascular density, increased vascular stiffness, and salt sensitivity are other possible reasons ( 90 ).…”

“…However, HTN that is not induced by targeted therapy could increase the risk of RCC mortality ( OR = 1.75, 95% CI : 1.61–1.90) demonstrated by a review such as 6,964 patients of RCC in 2002 ( 91 ). Severe HTN in patients of RCC could cause HF, leukoencephalopathy, suspend, or cessation of targeted drugs ( 75 , 90 ), which will do harm to the prognosis and well-control of BP during targeted therapy could improve prognosis ( 92 ).…”

Mechanistic science in cardiovascular-oncology: the way forward to maximise anti-cancer drug effects and minimise cardiovascular toxicity

“…However, in contrast with the early situation with trastuzumab, the importance of VEGF in cardiovascular haemostasis and development had been well described for decades prior to therapeutic targeting. It is, therefore, not surprising that anti-VEGF drugs are strongly associated with unwanted cardiovascular effects including hypertension [ 7 , 8 ] and left ventricular dysfunction [ 9 ] which, at least partly, reflects microvascular dysfunction. It is notable that other therapies, including targeted inhibition of rapidly accelerated fibrosarcoma B-type (BRAF) and mitogen-activated extracellular signal-regulated kinase (MEK) for the treatment of cutaneous melanoma are also associated with a broad range of toxicities [ 10 ].…”