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Hypertension and renal failure prevention and management after cancer therapy
KEY POINTS
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Hypertension is an important cardiovascular risk factor in cancer survivors and it potentiates the risk of heart failure in patients previously exposed to cardiotoxic chemotherapy or mediastinal radiation
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Regular routine blood pressure surveillance is an important measure in cancer survivorship with blood pressure goals that match the 2017 American College of Cardiology/American Heart Association (ACC/AHA) guidelines (<130/80 mm Hg)
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First-line therapies for hypertension include inhibitors of the renin angiotensin aldosterone system and dihydropyridine calcium channel blockers (amlodipine, nifedipine), alone or in combination
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In patients with left ventricular systolic dysfunction, heart failure, or prior myocardial infarction preference should be for renin angiotensin aldosterone system inhibitors as well as beta-blockers, especially carvedilol or bisoprolol
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Chronic kidney disease (CKD) can be the consequence of acute kidney injury during cancer therapy, and the longer-term effects of cancer therapies (especially cisplatin, ifosfamide, kidney radiation, nephrectomy, and hematopoietic stem cell transplantation [HSCT]), as well as hypertension and diabetes
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CKD commonly occurs after HSCT (myeloablative > non-myeloablative allogeneic > autologous); CKD, which is also more common after allogenic HSCT, is attributable to subacute thrombotic microangiopathy related to calcineurin inhibitors, higher intensity nephrotoxic chemotherapy, graft-versus-host disease, and/or total body radiation
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Long-term surveillance of renal function should be an integral component of the care of cancer survivors; prevention of renal dysfunction is a priority, also in view of its implications for cardiovascular diseases in cancer survivors
Hypertension
As outlined in Chapters 11 and 20 , cessation/withdrawal of cancer therapy can lead to complete resolution of blood pressure derangements in patients with hypertension induced or aggravated by cancer therapies. However, blood pressure elevation can persist. Among the chemotherapeutics associated with a long-term risk of hypertension are the platinum drugs, ifosfamide, and calcineurin inhibitors after stem cell transplantation. A reduction in the capillary bed paired with chronic induction of inflammation and oxidative stress might explain why cisplatin can lead to blood pressure elevation in the long term. The patient group best studied in this regard is survivors of testicular cancer. Compared with healthy controls, testicular cancer survivors are at a 40% higher risk of developing hypertension, even when adjusting for age. This risk is highest in those who received cisplatin therapy, especially at dosages greater than 850 mg/m 2 (OR, 2.4; 95% CI, 1.4 to 4.0). Moreover, cancer survivors can develop essential hypertension and/or cardiometabolic disease, especially with aging. Patients with obesity and wide neck circumference should be evaluated for obstructive sleep apnea, an important risk factor for hypertension. , Thus, hypertension in a cancer survivor should prompt a comprehensive assessment of potential underlying causes, which includes renal and other secondary etiologies.
The impact of hypertension on cardiovascular and overall outcomes in childhood cancer survivors is significant, with an increased risk of cardiovascular events and cardiovascular diseases. In patients exposed to radiation therapy or anthracyclines, who become hypertensive, the increased risk for heart failure is amplified. Radiation exposure to the chest and anthracycline use should be considered as additional risk factors for cardiovascular events in the population of adult cancer survivors. Recognition, evaluation, and optimal treatment of hypertension in cancer survivors is thus extremely important.
In patients previously exposed to abdominal radiotherapy, renal radiation injury may aggravate hypertension control and severity. In patients with head and neck cancer or malignancy in the upper chest, radiation therapy and surgery can lead to injury of the carotid baroreceptors. This can cause blood pressure variability, including hypertension and orthostatic hypotension as well as tachycardia.
Management of hypertension in cancer survivors
Despite the increasing clinical need for robust guidelines for long-term monitoring and management of cardiovascular risk factors and disease in cancer survivors, particularly as cancer treatments continue to improve clinical outcomes, these remain sparse. Clinical guidelines currently focus on cardiovascular screening prior to or during treatment or on monitoring of cardiac function. , The most comprehensive recommendations for long-term monitoring of cardiovascular disease and risk factors have been aimed at long-term survivors of hematologic malignancies who have undergone bone marrow transplantation. , These recommend regular screening for cardiovascular risk factors following the completion of anticancer treatment, including obesity, hypertension, and diabetes. However, recommendations for the wider cancer survivor population are lacking.
In patients who develop hypertension following the completion of anticancer therapies, the increased risks of cardiovascular events and end-organ damage favor stricter blood pressure control, and we recommend a target blood pressure of less than 130/80 mm Hg. In addition to antihypertensive medications, lifestyle modifications, such as dietary measures and physical activity, are important to reduce cardiovascular risk. First-line treatment regimens should follow conventional hypertension management guidelines. , These recommend angiotensin-converting enzyme inhibitors/angiotensin II receptor blockers (ACEi/ARBs) and dihydropyridine calcium channel blockers (CCB) in the first instance, either alone or in combination, although thiazide diuretics may also be used. ACEi/ARB should be preferred in patients with left-ventricular systolic dysfunction, heart failure, or prior myocardial infarction. Beta-blockers are generally recommended as second-line therapies, but of particular use in patients with left-ventricular dysfunction or coronary artery disease, both of which may be prevalent in cancer survivors. Other secondary medications include loop diuretics, mineralocorticoid receptor antagonists, and alpha-blockers, which may be beneficial in patients with resistant hypertension.
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