Established and Emerging Cancer Therapies and Cardiovascular System: Focus on Hypertension—Mechanisms and Mitigation

Abstract

Cardiovascular disease and cancer are 2 of the leading causes of death worldwide. Although improvements in outcomes have been noted for both disease entities, the success of cancer therapies has come at the cost of at times very impactful adverse events such as cardiovascular events. Hypertension has been noted as both, a side effect as well as a risk factor for the cardiotoxicity of cancer therapies. Some of these dynamics are in keeping with the role of hypertension as a cardiovascular risk factor not only for heart failure, but also for the development of coronary and cerebrovascular disease, and kidney disease and its association with a higher morbidity and mortality overall. Other aspects such as the molecular mechanisms underlying the amplification of acute and long-term cardiotoxicity risk of anthracyclines and increase in blood pressure with various cancer therapeutics remain to be elucidated. In this review, we cover the latest clinical data regarding the risk of hypertension across a spectrum of novel anticancer therapies as well as the underlying known or postulated pathophysiological mechanisms. Furthermore, we review the acute and long-term implications for the amplification of the development of cardiotoxicity with drugs not commonly associated with hypertension such as anthracyclines. An outline of management strategies, including pharmacological and lifestyle interventions as well as models of care aimed to facilitate early detection and more timely management of hypertension in patients with cancer and survivors concludes this review, which overall aims to improve both cardiovascular and cancer-specific outcomes.

Effect of Intensive Blood Pressure Control on Cardiovascular Outcomes in Cancer Survivors

“…Previous research has found a correlation between cancer and CVD. [26][27][28] A large nationwide study found a greater risk of CVD death in patients with cancer compared with the general population. 26 The Atherosclerosis Risk in Communities study also found that cancer survivors with atherosclerosis risk have significantly higher risk of CVD independent of traditional cardiovascular risk factors.…”

Risk Factors for Severe Hypertension and Proteinuria After Treatment With Vascular Endothelial Growth Factor Signaling Pathway Inhibitors Among Patients With Cancer

“…Although it may serve as a marker of antiangiogenic action and treatment efficacy, S1 severe hypertension can contribute to cardiovascular morbidity and mortality, leading to interruption or discontinuation of VSPIs. 5 …”

“…Proteinuria can also occur with VSPI therapy in 21% to 63% of treated patients, 5 and is thought to occur via rarefaction of the peritubular capillary network and disruption of the paracrine signaling between the podocyte and glomerular endothelium. Like VSPI-associated hypertension, proteinuria is associated with cardiovascular disease and poor patient outcomes, necessitating frequent monitoring after starting VSPIs.…”

A Drug–Drug Interaction Study to Evaluate the Impact of Simvastatin and Itraconazole on Erlotinib Pharmacokinetics in Rats by UPLC-MS/MS

“…Thus, their treatments are frequently influenced by drugs against common diseases, for instance, drugs against infection, cardiovascular disease, respiratory system disease, and nausea. 10 , 11 CYP-based drug-drug interaction (DDI) is common in clinical practice. Therefore, evaluating pharmacokinetic DDI, especially CYP3A4 involved metabolic interaction is essential to ensure safety in cancer patients.…”