Background
Improvements in early diagnosis and novel cancer treatments have increased the survival rate of cancer patients [ 1 ]. Decreased cancer mortality due to novel cancer therapies resulting from novel cancer therapies has led to an increase in short- and long-term cardiovascular complications in these patients [ 2 ]. Cardiovascular disease is one of the most common cause of mortality and morbidity in cancer patients [ 3 ]. Among cancer patients, cardiovascular adverse events such as heart failure, coronary artery disease, valvular heart disease, and hypertension are prevalent [ 4 , 5 ]. Previous studies have shown that hypertension is associated with an increased risk of developing certain malignancies, and hypertensive patient experienced higher rates of cancer-related mortality [ 6 – 8 ]. In the older population of cancer patients, specific cancer treatments such as new tyrosine kinase-targeting and Vascular endothelial growth factor inhibitor (VEGFi) drugs can lead to hypertension in cancer patients [ 9 , 10 ]. Certain pieces of evidence in recent guidelines on managing cardiovascular toxicities in cancer patients may create uncertainty in clinicians' therapeutic and clinical decisions [ 11 , 12 ]. Hypertension management in cardio-oncology presents significant challenges [ 13 ]. Our review aims to provide an updated understanding of the etiology and management of hypertension in cancer patients and offer a practical guide to current treatment approaches. Given the high prevalence of various cancer patients, hypertension management in oncology is applicable not only to cardio-oncologists but would be an essential part of practice among oncologists, general cardiologists, and primary care physicians in the near future. This review has the potential to be a reference guide for clinicians who care for cancer patients with hypertension.
Etiologies of cancer treatment-induced Hypertension
Vascular endothelial growth factor inhibitors
Vascular endothelial growth factor inhibitors (VEGFi) drugs are effective and safe components of the anti-cancer treatment for patients with solid malignancy tumors [ 14 ]. Next, we will discuss the mention most commonly used VEGFi drugs in cancer treatment. Bevacizumab (Avastin) is utilized in the treatment of various cancers, including colorectal, lung, kidney, and ovarian cancer [ 15 ]. Sorafenib (Nexavar) is also commonly used to treat Renal cell carcinoma, hepatocellular carcinoma, and advanced thyroid carcinoma [ 16 ]. Sunitinib (Sutent) is another drug used to treat kidney cancer (renal cell carcinoma) and gastrointestinal stromal tumors (GISTs) [ 17 , 18 ].
Notably, VEGFi increases blood pressure in almost all patients [ 19 ]. VEGFi-induced hypertension is dose-dependent and is associated with these drugs' anti-cancer effects [ 20 ]. VEGFi increases blood pressure by increasing endothelin-1(ET-1), reducing NO bioavailability, and increasing salt sensitivity by activating the renal epithelial sodium channels(ENaC) [ 20 ]. Moreover, some new findings indicate the critical roles of prostacyclin and endothelial microparticles in VEGFi-induced hypertension [ 21 – 25 ].
The primary mechanism of VEGFi-induced hypertension is increased ET-1, leading to vasoconstriction and hypertension [ 26 , 27 ]. VEGFi increases ET-1 with several mechanisms, including the inactivation of ET B receptors, endothelial dysfunction, and producing vasoconstrictor prostanoids [ 14 , 23 , 28 , 29 ]. VEGFi decreases Nitric Oxide(NO) by inactivating the endothelial nitric oxide synthase (eNOS) enzyme and subsequently reduces the bioavailability of NO [ 30 ]. As mentioned above, increased vasoconstrictors, mainly ET-1 and decreased vasodilators, especially NO, are two key mechanisms of VEGFi-induced hypertension.
The incidence of VEGFi-induced hypertension varies based on differences in genetics, dosage, and duration of treatment [ 13 ]. Axitinib and Sorafenib induce hypertension in 40.4% and 29.0% of patients with renal cell carcinoma, respectively [ 31 ]. Recent studies have reported the incidence and relative risk of VEGFi-induced hypertension to be ranging from 4% to 84% and 3 to 9%, respectively [ 13 , 20 ].
Immunotherapeutic agents
Mammalian target rapamycin (mTOR) inhibitors
Mammalian target rapamycin (mTOR) inhibitors are used as an effective anti-cancer treatment in various solid organ neoplasms like pancreatic neuroendocrine tumors, mantle cell lymphoma, and renal cancer [ 32 , 33 ]. mTOR inhibitors may induce hypertension through various mechanisms, including increased oxidative stress and sympathetic activation, leading to afferent arteriolar vasoconstriction and hypertension [ 34 ].
Everolimus (mTOR inhibitor) in combination with lenvatinib causes hypertension in 42% of metastatic renal cell carcinoma patients [ 35 ]. Notably, the incidence of hypertension with everolimus and sirolimus ranges between 17%-30% and 21%-38%, respectively. Hypertension is a common side effect of mTOR inhibitors, whereas some clinical trials demonstrate no significant hypertension increase compared to comparator agents [ 34 , 36 , 37 ].
Proteasome inhibitor
Dysregulation of The ubiquitin-proteasome system by proteasome inhibitors like bortezomib and carfilzomib has been tested in different cancers, such as multiple myeloma [ 38 ]. Proteasome inhibition in cardiomyocytes and smooth muscle endothelium, resulting in dysregulated NO hemostasis and vasoconstriction are possible mechanisms of hypertension induced by these drugs [ 39 , 40 ]. Carfilzomib is strongly associated with increased cardiovascular adverse events, including heart failure, hypertension, cardiac ischemia, arrhythmia, and cardiac arrest [ 41 ]. Carfilzomib, a first-generation proteasome inhibitor, is associated with the risk of hypertension in multiple myeloma patients (HR= 3.33, p < 0.0001) [ 42 ].
Traditional chemotherapeutic agents
Alkylating agents, the earliest drugs used in cancer treatment, work by ultimately creating cross-linkage between two DNA strands, leading to cell death [ 43 ]. These drugs are frequently used in the treatment of leukemia, lymphoma, head and neck cancers, and genitourinary cancers [ 44 ]. The connection between Alkylating agents and hypertension remains unclear because they are usually used in combination with other drugs for cancer treatment [ 45 ]. Cyclophosphamide has a wide range of complications, such as nephrotoxicity, endothelial injury, and abnormalities in the renin-angiotensin system leading to hypertension [ 46 , 47 ]. While the mechanisms mentioned above could potentionally render Cyclophosphamide-associated Hypertension possible, it has not yet been recognized as an independent risk factor for hypertension in cancer patients. Hypertension was reported in pediatric cancer patients who were treated with ifosfamide [ 48 ].
Recent studies do not indicate hypertension as one of the complications in cancer treatment field [ 49 ]. Notably, in the meta-analysis of Zhang et al., Hypertension (OR: 2.95, 95%CI: 1.75-4.97, p < 0.0001) is one of the risk factors of anthracycline-induced cardiotoxicity [ 50 ].
Since the first time cisplatin was used for cancer treatment, platinum-based cancer therapy drugs have been one of the most popular and widespread of their kind for cancer treatment [ 51 ]. Platinum-based drugs are used in the treatment of lymphomas, sarcomas, breast, colorectal, germ cell, ovarian, lung, gastro-oesophageal, and bladder cancers [ 52 ]. In a study by Herradón et al., the administration of cisplatin for five weeks caused a decrease in systolic and diastolic blood pressure in rats [ 53 ]. After ten weeks of treatment, blood pressure decreased significantly after cisplatin- and bleomycin-containing chemotherapy for testicular cancer [ 54 ]. Notably, after a median follow-up time of 11.2 years in patients with testicular cancer, the ones treated with cisplatin had higher systolic and diastolic blood pressure levels than those treated with surgery [ 55 ]. Therefore, it can be concluded that cisplatin treatment may cause a decrease in blood pressure in early stages of treatment, but, in the long run, it will bring about an upsurge in systolic and diastolic blood pressure.
BCR-ABL tyrosine-kinase inhibitors (TKIs)
BCR-ABL tyrosine kinase inhibitors (TKIs) are a type of targeted therapy agents used in cancer treatment, particularly in chronic myeloid leukemia (CML). BCR-ABL TKIs block the function of the BCR-ABL1 protein, causing CML cells to die. The first-line of treatment for CML is BCR-ABL TKI therapy, which includes imatinib mesylate, dasatinib, nilotinib, and bosutinib. BCR-ABL TKIs have been developed as a targeted treatment for BCR-ABL1 kinase activity suppression and are used to treat various malignancies. Second-generation BCR-ABL TKIs have been developed to overcome mutations. Drug resistance is the main challenge in BCR-ABL TKI therapy, and designing treatment strategies targeting epigenetic pathways is a potential solution [ 56 , 57 ].
Limited data available suggests that BCR-ABL tyrosine-kinase inhibitors (TKIs) are associated with multiple cardiovascular and pulmonary adverse events, including pulmonary hypertension, potentially attributable to the fact that the inhibition of the tyrosine kinase BCR-ABL1 is not specific to cancer cells, but rather can affect healthy cells. Renovascular hypertension has been reported as a rare side effect of BCR-ABL TKIs that inhibits vascular endothelial growth factors. However, edema and fluid retention are reported as more common side effects of BCR-ABL TKIs. Recent evidence suggests that tyrosine kinase has a particular role in cardiovascular calcification, specifically the calcification of heart vessels and valves [ 58 , 59 ].
BRAF and MEK inhibitors
BRAF and MEK inhibitors are targeted therapies used in cancer treatment, targeting the MAPK signaling pathway. Trametinib was the first FDA-approved MEK inhibitor for cancer therapy which has the property of BRAF/MEK heterodimer breaker and binds to the interface of MEK and BRAF [ 60 ]. These groups of drugs are effective in the treatment of various types of cancer, particularly those accociated with RAS or BRAF mutations [ 61 ]. BRAF and MEK inhibitors have several side effects, including skin rash, diarrhea, nausea, vomiting, fatigue, and liver toxicity. MEK inhibitors monotherapy or in combination with other targeted drugs harboring the MAPK pathway is becoming a promising strategy for non-small cell lung cancer (NSCLC) patients with BRAF or KRAS mutations [ 62 ]. It is noteworthy to mention that 19.5% of hypertension incidence is observed in patients who have used BRAF and MEK inhibitors [ 63 ]. In a meta-analysis on the incidence of treatment-related adverse events of BRAF and MEK inhibitors, for patients receiving Dabrafenib + Trametinib, the predominant grade 3 or higher adverse events were pyrexia, rash, and hypertension, collectively accounting for 6% of cases. Also individuals undergoing Encorafenib + Binimetinib regimen encountered incidences of rash and hypertension, amounting to 6% [ 64 ].
Vinca alkaloids
Vinca alkaloids are effective microtubule-targeting agents used in treating hematological and lymphatic neoplasms [ 65 ]. Recent studies suggest Vinca Alkaloids are associated with cardiovascular adverse events, such as hypertension [ 66 , 67 ]. The mechanism of Vinca Alkaloids-induced hypertension is unclear, however, mitosis-mediated inhibition of endothelial cell proliferation and endothelial cell caspase-mediated apoptosis are the possible routes [ 44 ]. Considering Vinca Alkaloids are usually used in combination with other chemotherapy agents, the specific effects of these drugs on patients' blood pressure are not well defined.
Endocrine therapy
Recent improvements in understanding how tumors evolve during treatment with endocrine agents have identified changes in gene expression and mutational profiles in the primary cancer cells as well as in circulating tumor cells. Endocrine therapy is a standard treatment for hormone receptor-positive breast cancer [ 68 ].
Anti-androgen therapy, including Cyproterone acetate, Flutamide, Bicalutamide, and Enzalutamide, is adjuvant chemotherapy used to treat different cancer types, such as prostate, breast, kidney, and ovarian cancer [ 69 ]. Abiraterone and enzalutamide are novel anti-cancer agents used in the treatment of prostate cancer. Based on a meta-analysis of 7 articles, Abiraterone has induced hypertension in 20% of patients. It was associated with an increased risk of cardiotoxicity [ 70 ]. Notably, enzalutamide was associated with increased risks of any grade (RR = 2.66, 95% CI = 1.93-3.66) and severe grade hypertension (RR = 2.79, 95% CI = 1.86-4.18) [ 71 ]. Anti-androgen agents cause hypertension by blocking the cytochrome P450 17A1, leading to a decrease in androgen synthesis and an increase in ACTH, resulting in increased mineralocorticoid production. Increased production of mineralocorticoids will lead to hypertension [ 72 ].
Adjuvant therapies
Corticosteroids are used in cancer treatment as adjuvant therapy for pain alleviation or as an antineoplastic agent in treating brain tumors [ 73 , 74 ]. Corticosteroids such as hydrocortisone, methylprednisone, and prednisone cause dose-dependent hypertension because of their mineralocorticoid effect, especially at high doses [ 75 ]. They cause salt and water retention and increase sensitivity to other vasoconstrictive drugs, eventually leading to hypertension [ 13 ].
Calcineurin inhibitors like cyclosporine and tacrolimus are essential immunosuppressive drugs used in oncology, almost as adjuvant therapy [ 76 , 77 ]. They cause salt and water retention and increase sensitivity to other vasoconstrictive drugs, eventually leading to hypertension [ 78 ]. They suppressed the transcription of IL-2 and several other cytokines in T lymphocytes [ 79 ].
Hypertension is a common side effect of erythropoietin-stimulating agents in healthy individuals, especially in patients with chronic kidney disease [ 80 – 82 ]. Based on a meta-analysis of 52 clinical trials, using erythropoietin-stimulating agents to treat cancer-related anemia causes hypertension and increases adverse events such as mortality [ 83 ]. Vasoconstriction of vessels by rising levels of ET-1 and constrictor prostanoids, calcium influx in smooth muscle cells of blood vessels, and anti-natriuresis are underlying mechanisms of erythropoietin-stimulating agents-induced hypertension [ 84 ].
30% to 50% of individuals with cancer will experience moderate to severe pain, and non-steroidal anti-inflammatory drugs (NSAIDs) are widely used for chronic pain control in cancer patients [ 85 , 86 ]. Hypertension is one of the side effects of regular NSAID use because they inhibit the production of prostaglandins; a decrease in prostaglandins I2 and E2 results in vasoconstriction and sodium retention, provoking hypertension [ 87 , 88 ].
Radiotherapy
Head and neck radiotherapy may subsequently cause baroreflex failure, leading to resistant hypertension and hypertension crisis [ 89 , 90 ]. Conversely, in an analysis of 19 patients undergoing head and neck radiation, the systolic and diastolic blood pressure was significantly reduced 90 days after surgery [ 91 ].
The baroreceptors regulate blood pressure by transmitting signals to the central nervous system, altering peripheral vascular resistance and cardiac output. Development of labile or paroxysmal hypertension in some individuals after receiving radiation treatment were observed in some studies [ 92 ]. Labile hypertension is defined as occasional asymptomatic blood pressure variations, usually attributable to emotional distress [ 93 ]. Paroxysmal hypertension is characterized by a sudden rise of blood pressure, passing over 200/110 mmHg, combined with an abrupt onset of physical symptoms, such as headache, chest discomfort, dizziness, nausea, palpitations, flushing, and sweating, taking anywhere between 10 minutes to several hours [ 94 ]. On the other hand, baroreceptors' damage can lead to hypotension. Low blood pressure can occur as a result of peripheral, autonomic nervous, and carotid baroreceptor system damage, leading to orthostatic hypotension, presented by dizziness in an upright position after sitting or lying down for a while [ 95 , 96 ].
Radiation nephropathy is a renal injury caused by ionizing radiation [ 97 ]. Besides hypertension, hypertensive crisis and encephalopathy may happen as a result of renal injury [ 97 ]. Renal artery stenosis is one of the abdominal radiation complications leading to hypertension [ 98 ]. Table 1 summarizes the mechanisms of action responsible for hypertension and other side effects of each anti-cancer agents. Figure 1 illustrates these mechanisms in detail. Table 1 Hypertension induced anticancer drugs; mechanism of action and side effects Medication Group Mechanism of action leading to hypertension Drugs Side effects Vascular endothelial growth factor inhibitors • ET-1and vasoconstriction [ 26 , 27 ]. • through inactivation of ETB receptors, endothelial dysfunction, vasoconstrictor prostanoids • reducing NO bioavailability [ 30 ]. • inactivating endothelial eNOS • increasing salt sensitivity [ 20 ] • ENaC Axitinib [ 31 ] sorafenib [ 31 ] dose-dependent hypertension [ 20 ]. Immune therapeutic agents Immune checkpoint inhibitors [ 39 , 40 , 99 ] • dysregulated NO hemostasis and vasoconstriction Bortezomib [ 38 ] Carfilzomib [ 38 ] Everolimus [ 35 ] Myocarditis [ 100 ] arrhythmias, conduction abnormalities [ 100 ] pericardial diseases [ 100 ] interstitial nephritis glomerulonephritis [ 99 , 101 ] Acute kidney injury [ 101 ] cardiotoxicity [ 102 – 104 ] mTOR inhibitors • increased oxidative stress [ 34 ] sympathetic activation [ 34 ] Rapamycin Hyperglycemia [ 105 ], hypercholesterolemia [ 105 ], hypertriglyceridemia [ 105 ] CAR-T therapy fever, flu-like symptoms, low blood pressure, and organ damage [ 106 ] Ubiquitin-proteasome inhibitors [ 39 , 40 , 99 ] • blocking the β proteolytic subunits of the 20s proteasome bortezomib and carfilzomib muscle weakness and tingling [ 107 ] Traditional chemotherapeutic agents Alkylating agents • creating cross-linkage in DNA strands and cell death [ 43 ] • disturbance in renin-angiotensin system [ 48 ]. Cyclophosphamide [ 46 , 47 ] ifosfamide [ 48 ] Anthracycline [ 49 ] Cisplatin [ 51 ]. Nephrotoxicity endothelial injury abnormalities in the renin-angiotensin system [ 46 , 47 ] BCR-ABL tyrosine-kinase inhibitors (TKIs) • inhibiting the development and maturation of monocytes [ 108 ] Nilotinib [ 109 ], dasatinib [ 110 ], bosutinib [ 111 ] and ponatinib [ 112 ] itching and rash, nausea, diarrhea, and tiredness [ 113 ] RAF and MEK inhibitors vemurafenib and cobimetinib, dabrafenib and trametinib, and encorafenib and binimetinib rash, diarrhea, peripheral edema, fatigue, and dermatitis acneiform [ 114 ] Vinca alkaloids • Mitosis-mediated inhibition of endothelial cell proliferation [ 44 ]. • Endothelial cell caspase-mediated apoptosis [ 44 ]. • Cardiovascular Autonomic neuropathy [ 115 ] Vinblastine [ 116 ] Vincristine [ 117 ] Hypertension Hypotension Endocrine therapy Anti-androgens • Blocking the cytochrome P450 17A1 • Decrease in androgen synthesis Increase in ACTH • Increase mineralocorticoid production Cyproterone acetate, Flutamide, Bicalutamide, Enzalutamide [ 69 ] Abiraterone, Enzalutamide [ 70 ] Cardiotoxicity [ 70 ]. Radiotherapy Baroreflex failure [ 89 , 90 ]. hypertensive encephalopathy renal injury [ 97 ] Renal artery stenosis resulting from abdominal radiation [ 98 ] Adjuvant therapies Corticosteroids Mineralocorticoid Salt and water retention Hydrocortisone, methylprednisolone, prednisone induce dose-dependent hypertension Calcineurin inhibitors Salt and water retention cyclosporine tacrolimus Non-steroidal anti-inflammatory drugs (NSAIDs) Inhibit the production of prostaglandins Decrease in prostaglandins I2 and E2 sodium retention [ 87 , 88 ]. ibuprofen naproxen diclofenac mefenamic acid etoricoxib ENaC epithelial sodium channel, mTOR Mammalian target rapamycin Fig. 1 mechanisms of anti-cancer agents in inducing hypertension. Anti-cancer agents induce hypertension through various mechanisms. A better understanding of these mechanisms can help physicians to choose the proper therapeutic strategies for hypertension treatment in cancer patients. ACTH= Adrenocorticotropic Hormone, CVD=Cardiovascular disease, ET= Endothelin, ET-1 = Endothelin-1, NO=Nitric oxide, RAAS= Renin-angiotensin-aldosterone system VEGFi = Vascular endothelial growth factor inhibitor
Table 1
Hypertension induced anticancer drugs; mechanism of action and side effects
ENaC epithelial sodium channel, mTOR Mammalian target rapamycin
| Medication Group | Mechanism of action leading to hypertension | Drugs | Side effects |
| Vascular endothelial growth factor inhibitors | • ET-1and vasoconstriction [ 26 , 27 ]. • through inactivation of ETB receptors, endothelial dysfunction, vasoconstrictor prostanoids • reducing NO bioavailability [ 30 ]. • inactivating endothelial eNOS • increasing salt sensitivity [ 20 ] • ENaC | Axitinib [ 31 ] sorafenib [ 31 ] | dose-dependent hypertension [ 20 ]. |
| Immune therapeutic agents | Immune checkpoint inhibitors [ 39 , 40 , 99 ] • dysregulated NO hemostasis and vasoconstriction | Bortezomib [ 38 ] Carfilzomib [ 38 ] Everolimus [ 35 ] | Myocarditis [ 100 ] arrhythmias, conduction abnormalities [ 100 ] pericardial diseases [ 100 ] interstitial nephritis glomerulonephritis [ 99 , 101 ] Acute kidney injury [ 101 ] cardiotoxicity [ 102 – 104 ] |
| mTOR inhibitors • increased oxidative stress [ 34 ] sympathetic activation [ 34 ] | Rapamycin | Hyperglycemia [ 105 ], hypercholesterolemia [ 105 ], hypertriglyceridemia [ 105 ] | |
| CAR-T therapy | fever, flu-like symptoms, low blood pressure, and organ damage [ 106 ] | ||
| Ubiquitin-proteasome inhibitors [ 39 , 40 , 99 ] | • blocking the β proteolytic subunits of the 20s proteasome | bortezomib and carfilzomib | muscle weakness and tingling [ 107 ] |
| Traditional chemotherapeutic agents | Alkylating agents • creating cross-linkage in DNA strands and cell death [ 43 ] • disturbance in renin-angiotensin system [ 48 ]. | Cyclophosphamide [ 46 , 47 ] ifosfamide [ 48 ] Anthracycline [ 49 ] Cisplatin [ 51 ]. | Nephrotoxicity endothelial injury abnormalities in the renin-angiotensin system [ 46 , 47 ] |
| BCR-ABL tyrosine-kinase inhibitors (TKIs) | • inhibiting the development and maturation of monocytes [ 108 ] | Nilotinib [ 109 ], dasatinib [ 110 ], bosutinib [ 111 ] and ponatinib [ 112 ] | itching and rash, nausea, diarrhea, and tiredness [ 113 ] |
| RAF and MEK inhibitors | vemurafenib and cobimetinib, dabrafenib and trametinib, and encorafenib and binimetinib | rash, diarrhea, peripheral edema, fatigue, and dermatitis acneiform [ 114 ] | |
| Vinca alkaloids | • Mitosis-mediated inhibition of endothelial cell proliferation [ 44 ]. • Endothelial cell caspase-mediated apoptosis [ 44 ]. • Cardiovascular Autonomic neuropathy [ 115 ] | Vinblastine [ 116 ] Vincristine [ 117 ] | Hypertension Hypotension |
| Endocrine therapy | Anti-androgens • Blocking the cytochrome P450 17A1 • Decrease in androgen synthesis Increase in ACTH • Increase mineralocorticoid production | Cyproterone acetate, Flutamide, Bicalutamide, Enzalutamide [ 69 ] Abiraterone, Enzalutamide [ 70 ] | Cardiotoxicity [ 70 ]. |
| Radiotherapy | Baroreflex failure [ 89 , 90 ]. | hypertensive encephalopathy renal injury [ 97 ] Renal artery stenosis resulting from abdominal radiation [ 98 ] | |
| Adjuvant therapies | |||
| Corticosteroids | Mineralocorticoid Salt and water retention | Hydrocortisone, methylprednisolone, prednisone | induce dose-dependent hypertension |
| Calcineurin inhibitors | Salt and water retention | cyclosporine tacrolimus | |
| Non-steroidal anti-inflammatory drugs (NSAIDs) | Inhibit the production of prostaglandins Decrease in prostaglandins I2 and E2 sodium retention [ 87 , 88 ]. | ibuprofen naproxen diclofenac mefenamic acid etoricoxib |
Assessment, diagnosis, and management of cancer treatment-induced hypertension
Based on recent studies, cancer patients are considered at a higher risk of hypertension compared to the general population [ 6 ]. Hypertension in cancer patients may sometimes occur just after the initiation of chemotherapies and sometimes, years after; hence, both short and long-term management approaches should be considered [ 118 ].
Hypertension is associated with an increased risk of mortality among cancer patients [ 8 ]. Recent studies have demonstrated that untreated hypertension is strongly associated with the risk of heart failure during treatments with anthracyclines, ibrutinib, and VEGFi [ 118 – 121 ]. Hypertension is an independent risk factor for coronary artery disease, heart failure, valvular heart disease, and arrhythmias in cancer patients [ 122 ].
Therefore, Timely diagnosis and proper management of hypertension in cancer patients is a substantial issue for increasing the quality of life and decreasing mortality and morbidity in these patients. Risk assessment for cardiovascular toxicity prior to treatment is essential in cancer patients. Blood pressure should be monitored and assessed before the initiation of chemotherapy [ 123 ].
Assessment and diagnosis
2022 ESC Guidelines on cardio-oncology suggest treatment of hypertension in cancer patients based on 2018 ESC/European Society of Hypertension (ESH) Guidelines [ 12 , 124 ]. Special cofounders for in-office hypertention in cancer patients are pain, anxiety-driven sympathetic overactivity, NSAIDs, or steroids as adjuvant therapies. Also, it has been noted that both white-coat hypertension and masked hypertension are much more prevalent among cancer patients compared to the general population [ 125 ]. Based on 2021 European Society of Hypertension practice guidelines, standard condition, posture, measurement frequency, and interval should be considered to minimizing confounders in in-office hypertention [ 126 ].
The 2013 ESH guideline recommended only in-office BP measurement for hypertention diagnosis, however, the 2018 ESH guideline suggested out-of-office BP measurements such as Ambulatory Blood Pressure Monitoring (ABPM) and home blood pressure monitoring (HBPM) [ 124 ].
After detecting the initial episodes of increased blood pressure, it is suggested to perform ambulatory blood pressure monitoring for twenty-four hours, but it has its limitations, and it is not feasible for the majority of the patients. Situations in which frequent blood pressure measurements are required over longer periods (during treatment initiation or dose changes in patients receiving anti-cancer treatments) makes the patients susceptible to hypertensive crisis. Worsening of hypertension can occur in a matter of days and can progress to a hypertensive emergency. Hence, home blood pressure monitoring (also known as self-monitoring of blood pressure) with a validated device is an appropriate choice to prevent this situation. This type of monitoring can be done by the patient and is quite feasible. It has less accuracy compared to ambulatory blood pressure monitoring but can be cost-effective in preventing neglected hypertension [ 63 , 127 , 128 ]. It is indicated that cancer patients should take their blood pressure twice a day, once before medication use and bedtime [ 129 ]. The threshold for initation of anti-hypertensive agents and how to select the proper anti-hypertensive agents are explained in Figs. 2 and 3 . It is recommended to check the blood pressure for a second time 2 weeks after the initiation of the hypertension treatment. If the goals of the treatment are not met, clinicians should take the next step by changing the anti-hypertensive agents, increasing the dose of dihydropyridine CCB or beta-blocker, and perform a sleep study [ 130 ]. Fig. 2 Thresholds for asymptomatic hypertension treatment in cancer patients. The threshold for initiating the hypertension treatment increases as the patient has a worse prognosis. Starting the hypertension treatment at the proper time is crucial in managing hypertension in cancer patients, especially in patients under treatment of VEGFi, because it has been indicated that the efficacy of these drugs is related to blood pressure increase in these patients Fig. 3 Pharmacological management of hypertension in cancer patients. Choosing the proper anti-hypertensive agent for cancer patients is essential in managing hypertension in these patients. ACE or ARB and CCB are the first-line treatment in hypertension treatment. In patients with resistant hypertention, beta-blockers, diuretics, and nitrates can be added to the therapeutic drugs. Beta-blockers are a good choice if cancer patients have high sympathetic tone, tumors with beta-receptor expression (such as angiosarcoma and multiple myeloma), and other cardiovascular comorbidities
Treatment
Treatment thresholds for asymptomatic hypertension in cancer patients are determined by the prognosis, metastasis, and chemotherapy status of the patients. As the prognosis worsens, treatment thresholds for asymptomatic hypertension increase, as shown in Fig. 2 .
Lifestyle modification as a part of hypertension treatment:
Lifestyle modifications can be an important part of hypertension treatment for cancer patients. The following is an overview of findings that can help manage hypertensive disorders in non-pharmacological treatments.
Various types of anti-cancer medications have been accociated with the developement of hypertension in patients without a prior history of the condition, or with an aggravation of hypertension that was previously under control. Consequently, individuals diagnosed with cancer may be advised to modify their lifestyle in order to assist in managing their hypertension [ 7 ].
Modifications in daily life, such as maintaining a healthy weight and exercising regularly, can contribute to reducing blood pressure levels. One may significantly improve their health by following a diet that is low in salt and abundant in fruits, vegetables, and whole grains. Adhering to a consistent schedule of physical activity, limiting alcohol consumption, and cessasion of smoking also have a considerable impact on the prevention of hypertensive disorders [ 131 ]. Various classes of medications used for the treatment of cancer have been associated with the development of new-onset hypertension or exacerbation of previously well-controlled hypertension. Management of hypertension in patients on anti-cancer therapy is primarily empirical, with no current trial data supporting specific agents or strategies [ 63 ]. Although anti-hypertensive medication use has no consistent evidence of any impact on cancer risk, lifestyle modifications can still be an important part of hypertension treatment in cancer patients [ 132 ] Therefore, these modifications are recommended in order to help manage hypertension in cancer patients [ 133 ].
Pharmacological treatments
Notably, hypertension is an independent risk factor for developing cancer therapy-related cardiac dysfunction; Therefore, Angiotensin-converting enzyme (ACE) inhibitors and Angiotensin receptor blockers (ARBs) are the first choices in the treatment of hypertension in these patients [ 134 ]. It has been indicated that using renin-angiotensin system blockers may improve survival in cancer patients. To put it in more detail, in metastatic renal cell carcinoma, patients treated with sunitinib, the use of ACEIs or ARBs was associated with an improved overall survival rates [ 135 – 138 ]. In cases of proteinuria presence, ACEIs or ARBs are recommended as the first line of treatment [ 139 – 141 ].
Dihydropyridine Calcium channel blockers (CCBs) can be used for patients with uncontrolled hypertention despite the treatment with ACE/ ARBs [ 12 , 122 ]. Notably, hepatotoxicity occurs using some VEGF inhibitors such as Pazopanib, Ponatinib, Regorafenib, Sorafenib, Sunitinib, and Vandetanib. Thus, the use of CCBs should be approached with caution [ 142 ].
Non-dihydropyridine calcium channel blockers use cytochrome p450 3A4, possibly leading to decreased metabolism of chemotherapy agents. Therefore, they are not suggested in the treatment of hypertension in cancer patients [ 143 ].
The blood pressure target for hypertension treatment in cancer patients is 140/90. Blood pressure targets for patients with chronic kidney disease and diabetes should be 130/80 mmHg [ 144 ]. 2022 ESC Guidelines on cardio-oncology suggest a blood pressure target of 140-160/90-100 mmHg for asymptomatic patients suffering from metastatic cancer [ 12 ]. Individualized blood pressure targets based on the prognosis of diabetes or kidney disease should be considered in managing hypertension in the cardio-oncology clinics.
If the patient's blood pressure is above 180/110 mmHg, any associated cancer treatment should be withheld tunill the blood pressure is below 160/100 mmHg [ 3 , 12 ].
Diuretics, nitrates, and beta blockers are suggested for resistant hypertension as first-line Treatments (ACEIs, ARBs, and CCBs ) [ 12 , 145 ]. Proper anti-hypertensive medication selection depends on various factors, as Fig. 3 demonstrates the approach to hypertension therapy in cancer patients.
Patient education
Cancer patients should be educated about the importance of blood pressure control and the potential risks of uncontrolled hypertension, such as target organ damage and cardiovascular adverse events. In this regard, patients should be informed about the causes of hypertension in cancer patients, including various anti-cancer therapies, and the potential side effects of anti-hypertensive drugs. The caregiver must educate them on which anti-cancer therapies have potential risks for developing malignant hypertension [ 7 , 63 , 131 , 133 , 144 ]. Patients should be educated about lifestyle modifications that can help lower blood pressure, such as weight loss, regular exercise, a healthy diet, and stress reduction. They need to be advised to monitor their blood pressure regularly at home and keep a record of their readings to share with their healthcare providers [ 7 , 92 ].
Patient adherence to treatment
Patients should be encouraged to take their anti-hypertensive medications as prescribed and not to skip doses or discontinue them without consulting with their healthcare providers. Patients should be informed about the potential side effects of anti-hypertensive drugs and how to manage them [ 7 , 144 ]. Also, they have to be educated to report any symptoms of uncontrolled hypertension to their healthcare providers, such as headache, chest pain, shortness of breath, or vision changes, immediately [ 131 ] . They need to be reminded to attend regular follow-up appointments with their physicians to monitor their blood pressure and adjust their treatment if necessary [ 7 , 63 , 131 , 133 , 144 ].
Summary and conclusion
Hypertension is a common cardiovascular complication in cancer patients, especially those who are treated with angiogenesis inhibitors. Chemotherapeutic agents, Radiation, Adjuvant therapies, and other causes such as pain, renal dysfunction, alcohol consumption, and even untreated sleep apnea cause hypertension in cancer patients. The burden of hypertention in cancer patients is much higher than the general population. Therefore, blood pressure assessment before chemotherapy initiation, timely diagnosis, and appropriate treatment are critical in these patients. In this review, we focused on the details of the appropriate approach for the treatment of hypertension, including thresholds for initiating the treatment, targets, and meticulous selection of anti-hypertensive agents for hypertension management. Figure 4 demonstrates the summary of the etiology, assessment, and management of hypertension in the cardio-oncology clinic. Fig. 4 Etiology, Assessment, Diagnosis, and Management of Hypertension in Cancer patients. Anti-cancer agents induce hypertension by different mechanisms, including vasoconstriction, salt and water retention, RAAS dysfunction, baroreflex failure and other mechanisms illustrated in the figure. Physicians should initiate the treatment at the right time by choosing the proper anti-hypertension drug
Main message
Hypertension is a common cardiovascular complication with a significant impact on the mortality and morbidity of cancer patients. Blood pressure assessment before chemotherapy initiation, timely diagnosis, and appropriate treatment are critical in these patients. Further studies are needed to clarify the benefits of hypertension control in cancer patients in detail.
Abbreviations
Acute kidney injury
Epithelial sodium channel
Endothelial nitric oxide synthase
Endothelin-1
Mammalian target rapamycin
Nitric oxide
Tyrosine kinase inhibitors
Vascular endothelial growth factor inhibitor
Vascular endothelial growth factor tyrosine kinase inhibitors
Publisher’s Note
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Authors’ contributions
Azin Alizadeh: Conceptualization, and Final Revision, Amir Askari nejad : Data curation, Writing- Original draft preparation. Amir Ghaffari : Visualization, Table Preperation, Validation Sara Adimi : Writing- Reviewing and Editing.
Declarations
Competing interests
The authors declare no competing interests.
References
1. Siegel RL Miller KD Fuchs HE Jemal A Cancer Statistics, 2021 CA Cancer J Clin. 2021 71 1 7 33 10.3322/caac.21654 33433946
2. Ahmed T Marmagkiolis K Ploch M Irizarry-Caro JA Amatullah A Desai S The Year in Cardio-oncology 2022 Curr Probl Cardiol. 2023 48 1 101435 10.1016/j.cpcardiol.2022.101435 36183977
3. Essa H Dobson R Wright D Lip GYH Hypertension management in cardio-oncology J Hum Hypertens. 2020 34 10 673 681 10.1038/s41371-020-0391-8 32747676 PMC7398285
4. Chang HM Moudgil R Scarabelli T Okwuosa TM Yeh ETH Cardiovascular Complications of Cancer Therapy: Best Practices in Diagnosis, Prevention, and Management: Part 1 J Am Coll Cardiol. 2017 70 20 2536 2551 10.1016/j.jacc.2017.09.1096 29145954 PMC5825187
5. Totzeck M Schuler M Stuschke M Heusch G Rassaf T Cardio-oncology - strategies for management of cancer-therapy related cardiovascular disease Int J Cardiol. 2019 280 163 175 10.1016/j.ijcard.2019.01.038 30661849
6. Kibret AA Aragie H Belay DG Molla MD Teferi ET Melese EB Hypertension and Its Associated Factors Among Cancer Patients at University of Gondar Comprehensive Specialized Hospital, Northwest Ethiopia: Hospital-Based Cross-Sectional Study J Multidiscip Healthc. 2022 15 793 803 10.2147/JMDH.S352114 35444426 PMC9015048
7. Mohammed T Singh M Tiu JG Kim AS Etiology and management of hypertension in patients with cancer Cardiooncology. 2021 7 1 14 33823943 10.1186/s40959-021-00101-2 PMC8022405
8. Grossman E Messerli FH Boyko V Goldbourt U Is there an association between hypertension and cancer mortality? Am J Med. 2002 112 6 479 486 10.1016/S0002-9343(02)01049-5 11959059
9. Fraeman KH, Nordstrom BL, Luo W, Landis SH, Shantakumar S. Incidence of new-onset hypertension in cancer patients: a retrospective cohort study. Int J Hypertens. 2013;2013:379252. 10.1155/2013/379252. 10.1155/2013/379252 PMC3876828 24455206
10. Duvillier P Hypertension and cancer : Dangerous Liaisons Ann Cardiol Angeiol. 2022 71 5 317 320 10.1016/j.ancard.2022.08.003 36075765
11. Alexandre J Cautela J Ederhy S Damaj GL Salem JE Barlesi F Cardiovascular Toxicity Related to Cancer Treatment: A Pragmatic Approach to the American and European Cardio-Oncology Guidelines J Am Heart Assoc. 2020 9 18 e018403 10.1161/JAHA.120.018403 32893704 PMC7727003
12. Lyon AR López-Fernández T Couch LS Asteggiano R Aznar MC Bergler-Klein J 2022 ESC Guidelines on cardio-oncology developed in collaboration with the European Hematology Association (EHA), the European Society for Therapeutic Radiology and Oncology (ESTRO) and the International Cardio-Oncology Society (IC-OS) Eur Heart J. 2022 43 41 4229 4361 10.1093/eurheartj/ehac244 36017568
13. Gudsoorkar P Ruf R Adnani H Safdar K Sparks MA Onco-hypertension: An Emerging Specialty Adv Chronic Kidney Dis. 2021 28 5 477 89.e1 10.1053/j.ackd.2021.09.011 35190114
14. Camarda N Travers R Yang VK London C Jaffe IZ VEGF Receptor Inhibitor-Induced Hypertension: Emerging Mechanisms and Clinical Implications Curr Oncol Rep. 2022 24 4 463 474 10.1007/s11912-022-01224-0 35179707 PMC9218917
15. Garcia J Hurwitz HI Sandler AB Miles D Coleman RL Deurloo R Bevacizumab (Avastin®) in cancer treatment: A review of 15 years of clinical experience and future outlook Cancer Treat Rev. 2020 86 102017 10.1016/j.ctrv.2020.102017 32335505
16. Ben MA Sorafenib in the treatment of advanced hepatocellular carcinoma Saudi J Gastroenterol. 2008 14 1 40 42 10.4103/1319-3767.37808 19568496 PMC2702892
17. Kollmannsberger C Soulieres D Wong R Scalera A Gaspo R Bjarnason G Sunitinib therapy for metastatic renal cell carcinoma: recommendations for management of side effects Can Urol Assoc J. 2007 1 2 Suppl S41 S54 18542784 10.5489/cuaj.67 PMC2422945
18. Wang D Xiao F Feng Z Li M Kong L Huang L Sunitinib facilitates metastatic breast cancer spreading by inducing endothelial cell senescence Breast Cancer Res. 2020 22 1 103 10.1186/s13058-020-01346-y 32993785 PMC7526390
19. Abdel-Qadir H Ethier JL Lee DS Thavendiranathan P Amir E Cardiovascular toxicity of angiogenesis inhibitors in treatment of malignancy: A systematic review and meta-analysis Cancer Treat Rev. 2017 53 120 127 10.1016/j.ctrv.2016.12.002 28104567
20. Versmissen J Mirabito Colafella KM Koolen SLW Danser AHJ Vascular Cardio-Oncology: Vascular Endothelial Growth Factor inhibitors and hypertension Cardiovasc Res. 2019 115 5 904 914 10.1093/cvr/cvz022 30726882
21. Lugo-Gavidia LM Burger D Matthews VB Nolde JM Kiuchi MG Carnagarin R Role of Microparticles in Cardiovascular Disease: Implications for Endothelial Dysfunction, Thrombosis, and Inflammation Hypertension. 2021 77 6 1825 1844 10.1161/HYPERTENSIONAHA.121.16975 33979187
22. Sansone R Baaken M Horn P Schuler D Westenfeld R Amabile N Release of endothelial microparticles in patients with arterial hypertension, hypertensive emergencies and catheter-related injury Atherosclerosis. 2018 273 67 74 10.1016/j.atherosclerosis.2018.04.012 29684662
23. Amraoui F Spijkers L Hassani Lahsinoui H Vogt L van der Post J Peters S SFlt-1 elevates blood pressure by augmenting endothelin-1-mediated vasoconstriction in mice PloS One. 2014 9 3 e91897 10.1371/journal.pone.0091897 24632840 PMC3954828
24. Mirabito Colafella KM Neves KB Montezano AC Garrelds IM van Veghel R de Vries R Selective ETA vs. dual ETA/B receptor blockade for the prevention of sunitinib-induced hypertension and albuminuria in WKY rats Cardiovasc Res. 2020 116 10 1779 1790 10.1093/cvr/cvz260 31593221
25. Steeghs N Gelderblom H Roodt JO Christensen O Rajagopalan P Hovens M Hypertension and rarefaction during treatment with telatinib, a small molecule angiogenesis inhibitor Clin Cancer Res. 2008 14 11 3470 3476 10.1158/1078-0432.CCR-07-5050 18519779
26. Kappers MH van Esch JH Sluiter W Sleijfer S Danser AJ van den Meiracker AH Hypertension induced by the tyrosine kinase inhibitor sunitinib is associated with increased circulating endothelin-1 levels Hypertension. 2010 56 4 675 681 10.1161/HYPERTENSIONAHA.109.149690 20733093
27. Banfor PN Franklin PA Segreti JA Widomski DL Davidsen SK Albert DH ETA receptor blockade with atrasentan prevents hypertension with the multitargeted tyrosine kinase inhibitor ABT-869 in telemetry-instrumented rats J Cardiovasc Pharmacol. 2009 53 2 173 178 10.1097/FJC.0b013e3181993493 19188829
28. Saleh L Verdonk K Visser W van den Meiracker AH Danser AJ The emerging role of endothelin-1 in the pathogenesis of pre-eclampsia Ther Adv Cardiovasc Dis. 2016 10 5 282 293 10.1177/1753944715624853 26755746 PMC5933567
29. Lee S Chen TT Barber CL Jordan MC Murdock J Desai S Autocrine VEGF signaling is required for vascular homeostasis Cell. 2007 130 4 691 703 10.1016/j.cell.2007.06.054 17719546 PMC3010851
30. Neves KB Rios FJ van der Mey L Alves-Lopes R Cameron AC Volpe M VEGFR (Vascular Endothelial Growth Factor Receptor) Inhibition Induces Cardiovascular Damage via Redox-Sensitive Processes Hypertension. 2018 71 4 638 647 10.1161/HYPERTENSIONAHA.117.10490 29483228
31. Rini BI Quinn DI Baum M Wood LS Tarazi J Rosbrook B Hypertension among patients with renal cell carcinoma receiving axitinib or sorafenib: analysis from the randomized phase III AXIS trial Target Oncol. 2015 10 1 45 53 10.1007/s11523-014-0307-z 24595903 PMC4363524
32. Gasparri ML Bardhi E Ruscito I Papadia A Farooqi AA Marchetti C PI3K/AKT/mTOR pathway in ovarian cancer treatment: are we on the right track? Geburtshilfe Frauenheilkd. 2017 77 10 1095 1103 10.1055/s-0043-118907 29093603 PMC5658232
33. Chiarini F Evangelisti C McCubrey JA Martelli AM Current treatment strategies for inhibiting mTOR in cancer Trends Pharmacol Sci. 2015 36 2 124 135 10.1016/j.tips.2014.11.004 25497227
34. Kaplan B Qazi Y Wellen JR Strategies for the management of adverse events associated with mTOR inhibitors Transplant Rev. 2014 28 3 126 133 10.1016/j.trre.2014.03.002 24685370
35. Bendtsen MAF, Grimm D, Bauer J, Wehland M, Wise P, Magnusson NE, Infanger M, Krüger M. Hypertension Caused by Lenvatinib and Everolimus in the Treatment of Metastatic Renal Cell Carcinoma. Int J Mol Sci. 2017;18(8). 10.3390/ijms18081736. 10.3390/ijms18081736 PMC5578126 28796163
36. De Simone P Nevens F De Carlis L Metselaar HJ Beckebaum S Saliba F Everolimus With Reduced Tacrolimus Improves Renal Function in De Novo Liver Transplant Recipients: A Randomized Controlled Trial Am J Transplant. 2012 12 11 3008 3020 10.1111/j.1600-6143.2012.04212.x 22882750 PMC3533764
37. Tsai M-K Wu F-LL Lai L-R Lee C-Y Hu R-H Lee P-H Decreased Acute Rejection and Improved Renal Allograft Survival Using Sirolimus and Low-Dose Calcineurin Inhibitors without Induction Therapy Int J Artif Organs. 2009 32 6 371 380 10.1177/039139880903200608 19670189
38. Park J Cho J Song EJ Ubiquitin-proteasome system (UPS) as a target for anticancer treatment Arch Pharm Res. 2020 43 11 1144 1161 10.1007/s12272-020-01281-8 33165832 PMC7651821
39. Wu P Oren O Gertz MA Yang EH Proteasome Inhibitor-Related Cardiotoxicity: Mechanisms, Diagnosis, and Management Curr Oncol Rep. 2020 22 7 66 10.1007/s11912-020-00931-w 32514632
40. Chari A Hajje D Case series discussion of cardiac and vascular events following carfilzomib treatment: possible mechanism, screening, and monitoring BMC Cancer. 2014 14 1 1 9 10.1186/1471-2407-14-915 25471129 PMC4289164
41. Waxman AJ, Clasen S, Hwang WT, Garfall A, Vogl DT, Carver J, O'Quinn R, Cohen AD, Stadtmauer EA, Ky B, Weiss BM. Carfilzomib-associated cardiovascular adverse events: A systematic review and meta-analysis. JAMA Oncol. 2018;4(3):e174519. 10.1001/jamaoncol.2017.4519/. 10.1001/jamaoncol.2017.4519 PMC5885859 29285538
42. Bishnoi R Xie Z Shah C Bian J Murthy HS Wingard JR Real-world experience of carfilzomib-associated cardiovascular adverse events: SEER-Medicare data set analysis Cancer Med. 2021 10 1 70 78 10.1002/cam4.3568 33169938 PMC7826471
43. Karati D Mahadik KR Trivedi P Kumar D Alkylating Agents, the Road Less Traversed, Changing Anticancer Therapy Anticancer Agents Med Chem. 2022 22 8 1478 1495 10.2174/1871520621666210811105344 34382529
44. Soultati A Mountzios G Avgerinou C Papaxoinis G Pectasides D Dimopoulos MA Endothelial vascular toxicity from chemotherapeutic agents: preclinical evidence and clinical implications Cancer Treat Rev. 2012 38 5 473 483 10.1016/j.ctrv.2011.09.002 21982720
45. Ruf R Yarandi N Ortiz-Melo DI Sparks MA Onco-hypertension: Overview of hypertension with anti-cancer agents Journal of Onco-Nephrology. 2021 5 1 57 69 10.1177/23993693211001374
46. Alshahrani S Ali Thubab HM Ali Zaeri AM Anwer T Ahmed RA Jali AM The Protective Effects of Sesamin against Cyclophosphamide-Induced Nephrotoxicity through Modulation of Oxidative Stress, Inflammatory-Cytokines and Apoptosis in Rats Int J Mol Sci. 2022 23 19 11615 10.3390/ijms231911615 36232918 PMC9569534
47. Al-Hashmi S Boels PJ Zadjali F Sadeghi B Sällström J Hultenby K Busulphan-cyclophosphamide cause endothelial injury, remodeling of resistance arteries and enhanced expression of endothelial nitric oxide synthase PloS One. 2012 7 1 e30897 10.1371/journal.pone.0030897 22303468 PMC3267746
48. Hsiao W, Lapite A, Faig W, Abdel-Megid M, Carlson C, Hobbie W, Ginsberg J, Laskin B, Denburg M. Long- term kidney and cardiovascular complications in pediatric cancer survivors. J Pediatr. 2023;255:89–97.e1. 10.1016/j.jpeds.2022.10.029. 10.1016/j.jpeds.2022.10.029 PMC10398617 36336006
49. Hassen LJ Lenihan DJ Baliga RR Hypertension in the Cardio-Oncology Clinic Heart Fail Clin. 2019 15 4 487 495 10.1016/j.hfc.2019.06.010 31472884
50. Zhang M Yang H Xu C Jin F Zheng A Risk Factors for Anthracycline-Induced Cardiotoxicity in Breast Cancer Treatment: A Meta-Analysis Front Oncol. 2022 12 899782 10.3389/fonc.2022.899782 35785172 PMC9248259
51. Rottenberg S Disler C Perego P The rediscovery of platinum-based cancer therapy Nat Rev Cancer. 2021 21 1 37 50 10.1038/s41568-020-00308-y 33128031
52. Grant CH Gourley C Anderson RA Spears N Chapter 2 - Relevant Cancer Diagnoses, Commonly Used Chemotherapy Agents and Their Biochemical Mechanisms of Action Cancer Treatment and the Ovary 2015 Boston Academic Press 21 33
53. Herradón E González C Uranga JA Abalo R Martín MI López-Miranda V Characterization of Cardiovascular Alterations Induced by Different Chronic Cisplatin Treatments Front Pharmacol. 2017 8 196 10.3389/fphar.2017.00196 28533750 PMC5420557
54. Nuver J Smit AJ van der Meer J van den Berg MP van der Graaf WT Meinardi MT Acute chemotherapy-induced cardiovascular changes in patients with testicular cancer J Clin Oncol. 2005 23 36 9130 9137 10.1200/JCO.2005.01.4092 16301596
55. Sagstuen H Aass N Fosså SD Dahl O Klepp O Wist EA Blood pressure and body mass index in long-term survivors of testicular cancer J Clin Oncol. 2005 23 22 4980 4990 10.1200/JCO.2005.06.882 16051950
56. Rossari F Minutolo F Orciuolo E Past, present, and future of Bcr-Abl inhibitors: from chemical development to clinical efficacy J Hematol Oncol. 2018 11 1 84 10.1186/s13045-018-0624-2 29925402 PMC6011351
57. Amir M, Javed S. A review on the therapeutic role of TKIs in case of CML in combination with epigenetic drugs. Front Genet. 2021;12:742802. 10.3389/fgene.2021.742802. 10.3389/fgene.2021.742802 PMC8569791 34745216
58. Roa-Chamorro R Jaén-Águila F Puerta-Puerta JM Torres-Quintero L González-Bustos P Mediavilla-García JD Arterial hypertension assessment in a population with chronic myeloid leukemia Sci Rep. 2021 11 1 14637 10.1038/s41598-021-94127-2 34282224 PMC8289992
59. Amin SO Ruzicka M Burns KD Bence-Bruckler IA Ryan SE Hadziomerovic A Renovascular hypertension from the BCR-ABL tyrosine kinase inhibitor ponatinib J Clin Hypertens. 2020 22 4 678 682 10.1111/jch.13843 PMC8029973 32175644
60. Ufuk D Jiajun Y Yuen Rong MS Shiru Q Jiancheng H Drug resistance in targeted cancer therapies with RAF inhibitors Cancer Drug Resist. 2021 4 3 665 683 35582307 10.20517/cdr.2021.36 PMC9094075
61. Adamopoulos C Ahmed TA Tucker MR Ung PMU Xiao M Karoulia Z Exploiting Allosteric Properties of RAF and MEK Inhibitors to Target Therapy-Resistant Tumors Driven by Oncogenic BRAF Signaling Cancer Discov. 2021 11 7 1716 1735 10.1158/2159-8290.CD-20-1351 33568355 PMC8295204
62. Han J Liu Y Yang S Wu X Li H Wang Q MEK inhibitors for the treatment of non-small cell lung cancer J Hematol Oncol. 2021 14 1 1 10.1186/s13045-020-01025-7 33402199 PMC7786519
63. Cohen JB Brown NJ Brown S-A Dent S Van Dorst DC Herrmann SM Cancer Therapy–Related Hypertension: A Scientific Statement From the American Heart Association Hypertension. 2023 80 3 e46 e57 10.1161/HYP.0000000000000224 36621810 PMC10602651
64. Garutti M, Bergnach M, Polesel J, Palmero L, Pizzichetta MA, Puglisi F. BRAF and MEK inhibitors and their toxicities: A meta-analysis. Cancers (Basel). 2022;15(1):141. 10.3390/cancers15010141. 10.3390/cancers15010141 PMC9818023 36612138
65. Martino E Casamassima G Castiglione S Cellupica E Pantalone S Papagni F Vinca alkaloids and analogues as anti-cancer agents: Looking back, peering ahead Bioorg Med Chem Lett. 2018 28 17 2816 2826 10.1016/j.bmcl.2018.06.044 30122223
66. Batra A Patel B Addison D Baldassarre LA Desai N Weintraub N Cardiovascular safety profile of taxanes and vinca alkaloids: 30 years FDA registry experience Open Heart. 2021 8 2 e001849 10.1136/openhrt-2021-001849 34952868 PMC8710909
67. Bokemeyer C Berger CC Kuczyk MA Schmoll H-J Evaluation of long-term toxicity after chemotherapy for testicular cancer J Clin Oncol. 1996 14 11 2923 2932 10.1200/JCO.1996.14.11.2923 8918489
68. Selli C Dixon JM Sims AH Accurate prediction of response to endocrine therapy in breast cancer patients: current and future biomarkers Breast Cancer Res. 2016 18 1 118 10.1186/s13058-016-0779-0 27903276 PMC5131493
69. Student S Hejmo T Poterała-Hejmo A Leśniak A Bułdak R Anti-androgen hormonal therapy for cancer and other diseases Eur J Pharmacol. 2020 866 172783 10.1016/j.ejphar.2019.172783 31712062
70. Iacovelli R Ciccarese C Bria E Romano M Fantinel E Bimbatti D The Cardiovascular Toxicity of Abiraterone and Enzalutamide in Prostate Cancer Clin Genitourin Cancer. 2018 16 3 e645 ee53 10.1016/j.clgc.2017.12.007 29339044
71. Lee HY Chen HL Teoh JY Chen TC Hao SY Tsai HY Abiraterone and enzalutamide had different adverse effects on the cardiovascular system: a systematic review with pairwise and network meta-analyses Prostate Cancer Prostatic Dis. 2021 24 1 244 252 10.1038/s41391-020-00275-3 32860011
72. Zhu X Wu S Risk of hypertension in Cancer patients treated with Abiraterone: a meta-analysis Clin Hypertens. 2019 25 5 10.1186/s40885-019-0116-x 30984412 PMC6442407
73. Wooldridge JE Anderson CM Perry MC Corticosteroids in advanced cancer 2001 (Williston Park, NY) Oncology 225 234 11252935
74. Dietrich J Rao K Pastorino S Kesari S Corticosteroids in brain cancer patients: benefits and pitfalls Expert Rev Clin Pharmacol. 2011 4 2 233 242 10.1586/ecp.11.1 21666852 PMC3109638
75. Kassel LE Odum LE Our Own Worst Enemy: Pharmacologic Mechanisms of Hypertension Adv Chronic Kidney Dis. 2015 22 3 245 252 10.1053/j.ackd.2014.10.002 25908474
76. Kaye D Thompson J Jennings G Esler M Cyclosporine therapy after cardiac transplantation causes hypertension and renal vasoconstriction without sympathetic activation Circulation. 1993 88 3 1101 1109 10.1161/01.CIR.88.3.1101 8394783
77. Lassila M Interaction of cyclosporine A and the renin-angiotensin system; new perspectives Curr Drug Metab. 2002 3 1 61 71 10.2174/1389200023337964 11876576
78. Safarini OA Patel J Calcineurin inhibitors 2020 32644421
79. Crouch Z DeSantis ERH Use of erythropoietin-stimulating agents in breast cancer patients: A risk review Am J Health Syst Pharm. 2009 66 13 1180 1185 10.2146/ajhp080214 19535656
80. Lundby C Thomsen JJ Boushel R Koskolou M Warberg J Calbet JA Erythropoietin treatment elevates haemoglobin concentration by increasing red cell volume and depressing plasma volume J Physiol. 2007 578 Pt 1 309 314 10.1113/jphysiol.2006.122689 17095558 PMC2075125
81. Berglund B Ekblom B Effect of recombinant human erythropoietin treatment on blood pressure and some haematological parameters in healthy men J Intern Med. 1991 229 2 125 130 10.1111/j.1365-2796.1991.tb00319.x 1997637
82. Lundby C Olsen NV Effects of recombinant human erythropoietin in normal humans J. Physiol. 2011 589 Pt 6 1265 1271 10.1113/jphysiol.2010.195917 20807784 PMC3082090
83. Tonelli M Hemmelgarn B Reiman T Manns B Reaume MN Lloyd A Benefits and harms of erythropoiesis-stimulating agents for anemia related to cancer: a meta-analysis Cmaj. 2009 180 11 E62 E71 10.1503/cmaj.090470 19407261 PMC2683210
84. Brar SK Perveen S Chaudhry MR AlBabtain S Amreen S Khan S Erythropoietin-Induced Hypertension: A Review of Pathogenesis, Treatment, and Role of Blood Viscosity Cureus. 2021 13 1 e12804 33628672 10.7759/cureus.12804 PMC7894225
85. Basha R Baker CH Sankpal UT Ahmad S Safe S Abbruzzese JL Therapeutic applications of NSAIDS in cancer: special emphasis on tolfenamic acid Front Biosci-Sch. 2011 3 2 797 805 10.2741/s188 21196413
86. Derry S, Wiffen PJ, Moore RA, McNicol ED, Bell RF, Carr DB, McIntyre M, Wee B. Oral nonsteroidal antiinflammatory drugs (NSAIDs) for cancer pain in adults. Cochrane Database Syst Rev. 2017;7(7):CD012638. 10.1002/14651858. 10.1002/14651858.CD012638.pub2 PMC6369931 28700091
87. Lovell AR Ernst ME Drug-Induced Hypertension: Focus on Mechanisms and Management Curr HypertensRep. 2017 19 5 39 10.1007/s11906-017-0736-z 28451850
88. Albishri J. NSAIDs and hypertension. Anaesth Pain Intensive Care. 2019;171–3.
89. Timmers HJ Wieling W Karemaker JM Lenders JW Baroreflex failure: a neglected type of secondary hypertension Neth J Med. 2004 62 5 151 155 15366697
90. Ketch T Biaggioni I Robertson R Robertson D Four faces of baroreflex failure: hypertensive crisis, volatile hypertension, orthostatic tachycardia, and malignant vagotonia Circulation. 2002 105 21 2518 2523 10.1161/01.CIR.0000017186.52382.F4 12034659
91. Leibowitz A Grossman E Berkovitch A Levartovski M Appel S Sharabi Y The Effect of Head and Neck Radiotherapy on Blood Pressure and Orthostatic Hypotension in Patients With Head and Neck Tumors Am J Hypertens. 2018 31 2 235 239 10.1093/ajh/hpx158 28985342
92. Brook I Late side effects of radiation treatment for head and neck cancer Radiat Oncol J. 2020 38 2 84 92 10.3857/roj.2020.00213 33012151 PMC7533405
93. Hayat A Whittam D Baroreceptor failure related to bilateral carotid artery disease: an uncommon cause of labile hypertension Intern Med J. 2014 44 1 105 106 10.1111/imj.12324 24450529
94. Mann SJ Labile and Paroxysmal Hypertension: Common Clinical Dilemmas in Need of Treatment Studies Curr Cardiol Rep. 2015 17 11 99 10.1007/s11886-015-0646-0 26370555
95. Shah-Becker S Pennock M Sinoway L Goldenberg D Goyal N Baroreceptor reflex failure: Review of the literature and the potential impact on patients with head and neck cancer Head Neck. 2017 39 10 2135 2141 10.1002/hed.24857 28675547
96. Giannopoulos S Texakalidis P Jonnalagadda AK Karasavvidis T Giannopoulos S Kokkinidis DG Revascularization of radiation-induced carotid artery stenosis with carotid endarterectomy vs. carotid artery stenting: A systematic review and meta-analysis Cardiovasc Revasc Med. 2018 19 5 Pt B 638 644 10.1016/j.carrev.2018.01.014 29422277
97. Klaus R Niyazi M Lange-Sperandio B Radiation-induced kidney toxicity: molecular and cellular pathogenesis Radiat Oncol. 2021 16 1 43 10.1186/s13014-021-01764-y 33632272 PMC7905925
98. Fakhouri F Alanore ALB Rrolle J-P Gury B Raynaud A Plouin P-F Presentation and revascularization outcomes in patients with radiation-induced renal artery stenosis Am J Kidney Dis. 2001 38 2 302 309 10.1053/ajkd.2001.26095 11479156
99. Kadowaki H Akazawa H Ishida J Komuro I Mechanisms and Management of Immune Checkpoint Inhibitor-Related Cardiac Adverse Events JMA J. 2021 4 2 91 98 10.31662/jmaj.2021-0001 33997442 PMC8118963
100. Ball S Ghosh RK Wongsaengsak S Bandyopadhyay D Ghosh GC Aronow WS Cardiovascular toxicities of immune checkpoint inhibitors: JACC review topic of the week J Am Coll Cardiol. 2019 74 13 1714 1727 10.1016/j.jacc.2019.07.079 31558256
101. Meraz-Muñoz A, Amir E, Ng P, Avila-Casado C, Ragobar C, Chan C, Kim J, Wald R, Kitchlu A. Acute kidney injury associated with immune checkpoint inhibitor therapy: incidence, risk factors and outcomes. J Immunother Cancer. 2020;8(1):e000467. 10.1136/jitc-2019-000467. 10.1136/jitc-2019-000467 PMC7326260 32601079
102. Minegishi S Kinguchi S Horita N Namkoong H Briasoulis A Ishigami T Immune Checkpoint Inhibitors Do Not Increase Short-Term Risk of Hypertension in Cancer Patients: a Systematic Literature Review and Meta-Analysis Hypertension. 2022 79 11 2611 2621 10.1161/HYPERTENSIONAHA.122.19865 36093785
103. Achim A, Liblik K, Gevaert S. Immune checkpoint inhibitors - the revolutionary cancer immunotherapy comes with a cardiotoxic price. Trends Cardiovasc Med. 2022. 10.1016/j.tcm.2022.09.004. 10.1016/j.tcm.2022.09.004 36152788
104. van Dorst DCH van Doorn L Mirabito Colafella KM Manintveld OC Hassing HC Danser AHJ Cardiovascular toxicity of angiogenesis inhibitors and immune checkpoint inhibitors: synergistic anti-tumour effects at the cost of increased cardiovascular risk? Clin Sci (Lond.). 2021 135 14 1649 1668 10.1042/CS20200300 34283204
105. Sivendran S Agarwal N Gartrell B Ying J Boucher KM Choueiri TK Metabolic complications with the use of mTOR inhibitors for cancer therapy Cancer Treat Rev. 2014 40 1 190 196 10.1016/j.ctrv.2013.04.005 23684373 PMC4744486
106. Schubert M-L Schmitt M Wang L Ramos C Jordan K Müller-Tidow C Side-effect management of chimeric antigen receptor (CAR) T-cell therapy Ann Oncol. 2021 32 1 34 48 10.1016/j.annonc.2020.10.478 33098993
107. Thawani SP Tanji K De Sousa EA Weimer LH Brannagan TH III Bortezomib-associated demyelinating neuropathy—clinical and pathologic features J Clin Neuromuscul Dis. 2015 16 4 202 209 10.1097/CND.0000000000000077 25996966
108. Haguet H Douxfils J Chatelain C Graux C Mullier F Dogné JM BCR-ABL Tyrosine Kinase Inhibitors: Which Mechanism(s) May Explain the Risk of Thrombosis? TH Open. 2018 2 1 e68 e88 10.1055/s-0038-1624566 31249931 PMC6524858
109. Weisberg E Manley P Mestan J Cowan-Jacob S Ray A Griffin J AMN107 (nilotinib): a novel and selective inhibitor of BCR-ABL Br J Cancer. 2006 94 12 1765 1769 10.1038/sj.bjc.6603170 16721371 PMC2361347
110. Tampellini M, La Salvia A, Scagliotti GV. Novel investigational therapies for treating biliary tract carcinoma. Expert Opin Investig Drugs. 2016;25(12):1423–36. 10.1080/13543784.2016.1252330 27771967
111. Keller G, Schafhausen P, Brümmendorf TH. Bosutinib. Small Mol Oncol. 2010:119–27. 10.1007/978-3-642-01222-8_9 20072835
112. Massaro F Molica M Breccia M Ponatinib: a review of efficacy and safety Curr Cancer Drug Targets. 2018 18 9 847 856 10.2174/1568009617666171002142659 28969556
113. Deininger MW Nilotinib Clin Cancer Res. 2008 14 13 4027 4031 10.1158/1078-0432.CCR-07-5015 18593977
114. Infante JR Fecher LA Falchook GS Nallapareddy S Gordon MS Becerra C Safety, pharmacokinetic, pharmacodynamic, and efficacy data for the oral MEK inhibitor trametinib: a phase 1 dose-escalation trial Lancet Oncol. 2012 13 8 773 781 10.1016/S1470-2045(12)70270-X 22805291
115. Roca E Bruera E Politi P Barugel M Cedaro L Carraro S Vinca alkaloid-induced cardiovascular autonomic neuropathy Cancer Treat Rep. 1985 69 2 149 151 3971390
116. Moudi M Go R Yien CYS Nazre M Vinca alkaloids Int J Prev Med. 2013 4 11 1231 24404355 PMC3883245
117. Noor B Akhavan S Leuchter M Yang EH Ajijola OA Quantitative assessment of cardiovascular autonomic impairment in cancer survivors: a single center case series Cardio-Oncology. 2020 6 1 1 8 10.1186/s40959-020-00065-9 32742722 PMC7388471
118. Group SR A randomized trial of intensive versus standard blood-pressure control N Engl J Med. 2015 373 22 2103 2116 10.1056/NEJMoa1511939 26551272 PMC4689591
119. Di Lorenzo G Autorino R Bruni G Carteni G Ricevuto E Tudini M Cardiovascular toxicity following sunitinib therapy in metastatic renal cell carcinoma: a multicenter analysis Ann Oncol. 2009 20 9 1535 1542 10.1093/annonc/mdp025 19474115
120. Dickerson T Wiczer T Waller A Philippon J Porter K Haddad D Hypertension and incident cardiovascular events following ibrutinib initiation Blood. 2019 134 22 1919 1928 10.1182/blood.2019000840 31582362 PMC6887116
121. Szmit S Jurczak W Zaucha JM Drozd-Sokołowska J Spychałowicz W Joks M Pre-existing arterial hypertension as a risk factor for early left ventricular systolic dysfunction following (R)-CHOP chemotherapy in patients with lymphoma J Am Soc Hypertens. 2014 8 11 791 799 10.1016/j.jash.2014.08.009 25455004
122. Cohen JB Geara AS Hogan JJ Townsend RR Hypertension in cancer patients and survivors: epidemiology, diagnosis, and management Cardio Oncology. 2019 1 2 238 251 10.1016/j.jaccao.2019.11.009 PMC7089580 32206762
123. Rossello X Dorresteijn JA Janssen A Lambrinou E Scherrenberg M Bonnefoy-Cudraz E Risk prediction tools in cardiovascular disease prevention: A report from the ESC Prevention of CVD Programme led by the European Association of Preventive Cardiology (EAPC) in collaboration with the Acute Cardiovascular Care Association (ACCA) and the Association of Cardiovascular Nursing and Allied Professions (ACNAP) Eur J Cardiovasc Nurs. 2019 18 7 534 544 10.1177/1474515119856207 31234638
124. Williams B Mancia G Spiering W Agabiti Rosei E Azizi M Burnier M 2018 ESC/ESH Guidelines for the management of arterial hypertension: The Task Force for the management of arterial hypertension of the European Society of Cardiology (ESC) and the European Society of Hypertension (ESH) Eur Heart J. 2018 39 33 3021 3104 10.1093/eurheartj/ehy339 30165516
125. Costa L Varella P Del Giglio A White coat effect in breast cancer patients undergoing chemotherapy Eur J Cancer Care 2003 12 4 372 373 10.1046/j.1365-2354.2003.00416.x 14982318
126. Stergiou GS Palatini P Parati G O’Brien E Januszewicz A Lurbe E European Society of Hypertension practice guidelines for office and out-of-office blood pressure measurement J Hypertens. 2021 2021 39(7) 10.1097/HJH.0000000000002843 33710173
127. Touyz RM Herrmann SM Herrmann J Vascular toxicities with VEGF inhibitor therapies–focus on hypertension and arterial thrombotic events J Am Soc Hypertens. 2018 12 6 409 425 10.1016/j.jash.2018.03.008 29703600 PMC6168784
128. Herrmann J Lenihan D Armenian S Barac A Blaes A Cardinale D Defining cardiovascular toxicities of cancer therapies: an International Cardio-Oncology Society (IC-OS) consensus statement Eur Heart J. 2022 43 4 280 299 10.1093/eurheartj/ehab674 34904661 PMC8803367
129. Whelton PK Carey RM Aronow WS Casey DE Jr Collins KJ Dennison Himmelfarb C 2017 ACC/AHA/AAPA/ABC/ACPM/AGS/APhA/ASH/ASPC/NMA/PCNA Guideline for the Prevention, Detection, Evaluation, and Management of High Blood Pressure in Adults: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines J Am Coll Cardiol. 2018 71 19 e127 e248 10.1016/j.jacc.2017.11.006 29146535
130. Rao VU Reeves DJ Chugh AR O’Quinn R Fradley MG Raghavendra M Clinical approach to cardiovascular toxicity of oral antineoplastic agents: JACC state-of-the-art review J Am Coll Cardiol. 2021 77 21 2693 2716 10.1016/j.jacc.2021.04.009 34045027 PMC8091379
131. Zhu X Wu S Risks and management of hypertension in cancer patients undergoing targeted therapy: a review Clin Hypertens. 2022 28 1 14 10.1186/s40885-022-00197-3 35568958 PMC9107678
132. Copland E Canoy D Nazarzadeh M Bidel Z Ramakrishnan R Woodward M Antihypertensive treatment and risk of cancer: an individual participant data meta-analysis Lancet Oncol. 2021 22 4 558 570 10.1016/S1470-2045(21)00033-4 33794209 PMC8024901
133. Cohen JB Geara AS Hogan JJ Townsend RR Hypertension in Cancer Patients and Survivors JACC: CardioOncol. 2019 1 2 238 251 32206762 10.1016/j.jaccao.2019.11.009 PMC7089580
134. Philip LJ Findlay SG Gill JH Baseline blood pressure and development of cardiotoxicity in patients treated with anthracyclines: A systematic review Int J Cardiol Cardiovasc Risk Prev. 2022 15 200153 10.1016/j.ijcrp.2022.200153 36573186 PMC9789356
135. Li X Sun J Hu S The renin-angiotensin system blockers as adjunctive therapy for cancer: a meta-analysis of survival outcome Eur Rev Med Pharmacol Sci. 2017 21 6 1375 1383 28387887
136. Cheung KS Chan EW Seto WK Wong IC Leung WK ACE (angiotensin-converting enzyme) inhibitors/angiotensin receptor blockers are associated with lower colorectal cancer risk: A territory-wide study with propensity score analysis Hypertension. 2020 76 3 968 975 10.1161/HYPERTENSIONAHA.120.15317 32623923
137. Perini MV Dmello RS Nero TL Chand AL Evaluating the benefits of renin-angiotensin system inhibitors as cancer treatments Pharmacol Ther. 2020 211 107527 10.1016/j.pharmthera.2020.107527 32173557
138. Sipahi I Debanne SM Rowland DY Simon DI Fang JC Angiotensin-receptor blockade and risk of cancer: meta-analysis of randomised controlled trials Lancet Oncol. 2010 11 7 627 636 10.1016/S1470-2045(10)70106-6 20542468 PMC4070221
139. Budolfsen C Faber J Grimm D Krüger M Bauer J Wehland M Tyrosine kinase inhibitor-induced hypertension: role of hypertension as a biomarker in cancer treatment Curr Vasc Pharmacol. 2019 17 6 618 634 10.2174/1570161117666190130165810 30706818
140. Holden RM Mustafa RA Alexander RT Battistella M Bevilacqua MU Knoll G Canadian society of nephrology commentary on the kidney disease improving global outcomes 2017 clinical practice guideline update for the diagnosis, evaluation, prevention, and treatment of chronic kidney disease-mineral and bone disorder Can J Kidney Health Dis. 2020 7 2054358120944271 10.1177/2054358120944271 32821415 PMC7412914
141. Wright JT Jr Bakris G Greene T Agodoa LY Appel LJ Charleston J Effect of blood pressure lowering and antihypertensive drug class on progression of hypertensive kidney disease: results from the AASK trial Jama. 2002 288 19 2421 2431 10.1001/jama.288.19.2421 12435255
142. Patel S Dushenkov A Jungsuwadee P Krishnaswami A Barac A Team-based approach to management of hypertension associated with angiogenesis inhibitors J Cardiovasc Transl Res. 2020 13 3 463 477 10.1007/s12265-020-10024-5 32430701
143. Zamorano JL Lancellotti P Rodriguez Muñoz D Aboyans V Asteggiano R Galderisi M 2016 ESC Position Paper on cancer treatments and cardiovascular toxicity developed under the auspices of the ESC Committee for Practice Guidelines: The Task Force for cancer treatments and cardiovascular toxicity of the European Society of Cardiology (ESC) Eur Heart J. 2016 37 36 2768 2801 10.1093/eurheartj/ehw211 27567406
144. Mouhayar E Salahudeen A Hypertension in cancer patients Tex Heart Inst J. 2011 38 3 263 265 21720467 PMC3113122
145. MacDonald TM Williams B Webb DJ Morant S Caulfield M Cruickshank JK Combination therapy is superior to sequential monotherapy for the initial treatment of hypertension: a double-blind randomized controlled trial J Am Heart Assoc. 2017 6 11 e006986 10.1161/JAHA.117.006986 29151036 PMC5721778