Introduction
In the modern world, hypertension and cancer are the most common reasons causing morbidity and mortality rates. Their relationship is complex, as the potential risk factors are shared. They can include high body mass index, diabetes, tobacco consumption, etc. Hypertension is a common comorbidity seen in cancer patients. It also affects the prognosis of the condition.
What Is Onco-Hypertension?
The relationship between hypertension and cancer is so intricate that a new branch of medicine called once-hypertension is initiated to manage the concern. Hypertension can be seen in cancer patients in two forms: it can be a comorbidity in the patient even before the diagnosis of the malignancy, or the cancer treatment can cause it. Hypertension can occur as an adverse effect of anti-cancer drugs on the cardiovascular and renal systems.
How Are Cancer and Hypertension Linked?
Cancer and hypertension overlap in their pathophysiological mechanisms. The most common pathophysiology includes inflammation and oxidative stress (an imbalance of antioxidants and free radicals in the body resulting in cell damage). These are commonly associated with risk factors like diabetes, smoking, obesity, physical inactivity, and obstructive sleep apnoea (a condition where a person is unable to breathe correctly while sleeping).
Hypertension can also be exacerbated by the other after-effects of cancer, like sleep disorders, pain, anxiety, and deconditioning. These can also promote hypertension indirectly. Many anticancer therapies and supportive therapies can increase prohypertensive effects. The drugs used in treating cancer and hypertension can increase the risk of direct toxicities on the heart, vascular system, and kidneys. This, in turn, can worsen hypertension in a vicious cycle.
In addition. Hypertension can increase the risk of certain types of cancer. Some studies have shown a link between hypertension and renal cancer. Two studies, namely The Metabolic Syndrome and Cancer Project (which was an extensive study for 12 years), showed that elevated blood pressure was slightly associated with cancer-related mortality in both men and women. However, more research is required to stabilize the relationship between the two.
What Are the Causes of Hypertension in a Cancer Patient?
One of the most extensively studied parts of onco-hypertension is cancer therapy-related hypertension (CTRH). Many classes of anticancer drugs have an association with increased blood pressure. The vascular endothelial growth factor (VEGF) inhibitors (also known as VEGF signaling pathway inhibitors, or VSPIs) are the most common. All patients under VSPIs have an elevated baseline blood pressure or a worsening of the condition (or uncontrolled hypertension) in about eighty percent of the patients. It has been anticipated that one percent of patients using bevacizumab might develop life-threatening hypertensive episodes.
Through the survival, proliferation, and permeability of endothelial cells, VEGF binds to its receptor (VEGFR), activating downstream intracellular signaling pathways that are essential for vasodilation and the preservation of vascular integrity. It plays a vital role in angiogenesis (formation of new blood cells), the lymphatic system, and the glomerular filtration barrier (barriers that promote glomerular filtration). However, it also promotes metastasis and tumor growth.
They impair tumor angiogenesis (forming new blood vessels that promote tumor growth), causing anticancer effects on the tumor. The combination of abnormal endothelin-1 and prostacyclin signaling, microvessel rarefaction (loss of capillaries and arterioles), increased vascular stiffness, impaired nitric oxide (NO) production, and vasodilation, increased podocyte permeability (and proteinuria), impaired renovascular homeostasis (the ability of the kidney to vary the composition of urine according to the body’s requirements), and eventually glomerular endotheliosis (a condition where the glomeruli become enlarged and solidify) and renal damage is thought to be the cause of the hypertensive effect of VSPIs. Studies show that the early signs of hypertension could be due to dysfunction of vascular tone and natriuresis (excretion of sodium through the urine).
How Is Onco-Hypertension Managed?
Patients should be informed regarding the possibility of developing new, worsening, or uncontrolled hypertension before beginning prohypertensive cancer therapy. This creates an awareness of blood pressure monitoring and the importance of starting or increasing the dose of their anti-hypertensives. It must be routine to record baseline blood pressure in all cancer patients under treatment. This helps to understand the potential worsening of blood pressure following therapy and take precautions for already known patients to avoid complications due to uncontrolled blood pressure. The cancer specialist should conduct a thorough cardiovascular risk assessment before the treatment commencement.
Patients who are known to have cardiovascular conditions should receive hypertensive medications if their blood pressure records increased values. The American College of Cardiology/American Heart Association (ACC/AHA, 2017) Clinical Practice Guidelines and the ESC/European Society of Hypertension (2018) guidelines generally assess hypertension and other cardiovascular conditions in cancer patients. The blood pressure levels should be well controlled before anti-cancer therapy is initiated to avoid cardiotoxicity (damage to the heart muscles due to the cancer drugs used). Existing hypertension and hypertension that fails to be managed can be caused by Anthracycline and Trastuzumab-associated cardiomyopathy (a condition affecting the heart muscles that make it difficult for the heart to pump blood) and heart failure.
Care should be taken that, after commencing treatment, a blood pressure of less than 130/80 mmHg should be maintained. For people with uncontrolled hypertension, it should be at least within 140/90 mmHg. For patients who are asymptomatic and have metastatic cancers (with a life expectancy ranging from one to three years), it can be relaxed to 140–159/90–99 mmHg. Cases where the blood pressure shoots above 160/100 mmHg should be appropriately managed, irrespective of their prognosis. This helps to prevent life-threatening complications, discontinuation of anticancer therapy, and hospitalization.
Anticancer agents known to cause hypertension should be paused if the blood pressure is more than 180/110 mmHg and should not be restarted unless it is under control (less than 160/100 mmHg). A multidisciplinary team should study the drug's effect on the patient, and an alternative drug or the same drug at altered doses might be considered accordingly. The International Cardio-Oncology Society (IC-OS) defines a hypertensive emergency as a very high elevation in blood pressure, along with multi-organ damage due to hypertension. These hypertension symptoms can be considered a sign for immediate hospital admission and appropriate care.
Conclusion
Oncologists must choose hypertensive medications that do not interfere with anticancer therapy. Lifestyle modifications, like reducing sodium intake (or following the hypertensive diet) and exercise, must be advised to all patients. Substances known to elevate blood pressure (or causes of hypertension), like caffeine, smoking, alcohol, and NSAIDs, should be avoided at all costs, especially while on oncology medications.
