Hypertension induced by chemotherapeutic and immunosuppresive agents: A new challenge
Introduction
Hypertension in cancer patients is a common phenomenon. Factors that cause hypertension in the general population also afflict those with cancer; however, the incidence of hypertension in cancer patients is influenced heavily by the type of chemotherapy used. High blood pressure has often led to treatment limitation and even life-threatening events [1], [2], [3], [4], thus demonstrating the importance of blood pressure (BP) control in this cohort of patients. In cancer patients, the etiology of hypertension is influenced by the type of chemotherapy, radiation therapy, and by the malignancy itself. Not only must the physician choose an antihypertensive medication, but he or she must also take into consideration the drug interactions that may accompany the treatment. The aim of this review is to evaluate the literature on hypertension in cancer patients and to survey the various chemotherapy treatments causing hypertension.
Section snippets
Epidemiology
The prevalence of hypertension in cancer patients is approximately 28% [4], [5], which is similar to the general population. However, the incidence of de novo hypertension is less defined in this cohort. It is accepted that the most common cause of new onset hypertension in those being treated for cancer is the chemotherapy itself. The incidence of de novo hypertension induced by VEGF is between 17% and 80% [6], [7]. Alkylating agents are associated with a 36% incidence of hypertension, while
Pathophysiology
Complex and poorly understood mechanisms are implicated in the origin and pathophysiology of hypertension [10], [11]. These processes include increased sympathetic nervous system activity, psychosocial stress, overproduction of sodium-retaining hormones and vasoconstrictors, chronic excess sodium intake, increased or inappropriate renin secretion inducing increased production of angiotensin II and aldosterone [11], [12], alterations in expression of the kallikrein-kinin system, endothelial
Diagnosis
The diagnosis of hypertension should follow the Joint National Commission (JNC) recommendations and is generally based on documenting BP readings of 140/90 mmHg or more on three separate occasions at least 1 week apart in patients less than 60 years of age (150/90 for patients above 60 years old) [13]. The pretreatment assessment entails repeated BP measurements, a history and physical examination to assess certain risk factors, and laboratory tests to detect end organ damage [14]. Patients
Management
The primary goal in managing hypertension is to reduce morbidity and minimize risks of end organ damage [16], [17]. More importantly, appropriate management of blood pressure will allow continuation of a necessary cancer therapy that might otherwise be discontinued. In the absence of specific data to guide therapy, management should focus on appropriate and timely diagnosis of hypertension, identifying potential secondary/reversible causes, and adequately treating elevated BP to achieve the
Angiogenesis inhibitors
The use of angiogenesis inhibitors over the past few years has risen dramatically, given their proven efficacy in decreasing mortality in cancer patients [1], [2], [3], [4]. Several agents have been approved for marketing worldwide and are divided into two separate classes based on the mechanisms of action leading to a similar effect on angiogenesis: Bevacizumab, a VEGF monoclonal antibody, and the small-molecule tyrosine kinase inhibitors such as Sorafenib, Sunitinib, and Pazopanib. HTN is one
Conclusion
With the development of new chemotherapy agents and subsequent improvement in mortality in those with cancer, the incidence of hypertension has increased in this patient population. Hypertension is a common side effect of many of these new therapies such as VEGF inhibitors. Because more than 30% of patients with cancer will have hypertension and often crucial chemotherapy is stopped solely for that reason, we advise that a protocol be established to assess high-risk patients’ prophylactic
Funding
No source of funding.
Conflicts of interest
No conflicts of interest to disclose.
Reviewers
Felipe Nonato Albuquerque, 3210 Riverdale Ave Apt-5j, Bronx, NY, United States.
Michael S. Ewer, M.D., J.D., Professor of Medicine, UT MD Anderson Cancer Center, Cardiology, 1515 Holcombe Blvd, Houston, TX 77030, United States.
Dr. Simon Abi Aad completed his medical degree at the Holy Spirit University in Kaslik, Lebanon. His postgraduate training included a research internship at the MD Anderson Cancer Center, Department of Cardiology, internal medicine residency at the Mount Sinai – St. Luke's Roosevelt Hospital Center. His clinical and research activities cover anti neoplastic therapy side effects and toxicities. He has a special interest in leukemia and potential targets for treatment associated with it.
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Dr. Simon Abi Aad completed his medical degree at the Holy Spirit University in Kaslik, Lebanon. His postgraduate training included a research internship at the MD Anderson Cancer Center, Department of Cardiology, internal medicine residency at the Mount Sinai – St. Luke's Roosevelt Hospital Center. His clinical and research activities cover anti neoplastic therapy side effects and toxicities. He has a special interest in leukemia and potential targets for treatment associated with it.
Dr. Elie Mouhayar, Associate Professor of Medicine, Department of Cardiology at the UT/MD Anderson Cancer Center in Houston, Texas. He completed his medical degree at the Lebanese University in Beirut, Lebanon. His postgraduate training included a clinical fellowship in cardiology at Geisinger Medical Center. He is board certified in internal medicine, cardiology and vascular medicine. He is the Associate Medical Director of the Cardiopulmonary Center and the Medical Director of the Non-Invasive Vascular Laboratory at the university of Texas/MD Anderson Cancer Center. He serves as a collaborator on several ongoing clinical trials. He has a special interest in pericardial and peripheral arterial diseases and in the early detection and management of cardio-toxicity as a result of conventional or targeted chemotherapy.