Risk Factors for the Comorbidity of Hypertension and Renal Cell Carcinoma in the Cardio-Oncologic Era and Treatment for Tumor-Induced Hypertension

Abstract

Advances in tumor diagnosis and treatment, especially the use of targeted therapies, have remarkably improved the survival rate of patients with renal cell carcinoma (RCC), accompanied by higher hypertension (HTN) incidence among patients with RCC, reflecting the coming of a cardio-oncologic era. Therefore, for patients with RCC and HTN simultaneously, finding risk factors for the comorbidity and giving better clinical treatment have been urgent problems. In this review, we thoroughly investigated risk factors for the comorbidity of HTN and RCC based on preclinical and clinical studies. Firstly, RCC and HTN may have common risk factors, such as obesity, smoking, and other modifiable lifestyles. Secondly, RCC and HTN may lead to each other directly or indirectly by their therapies. We then discussed measures of reducing the comorbidity and treatment of HTN in patients with RCC. We also discussed the deficiency of current studies and pointed out future directions. In conclusion, this review aims to deepen the understanding of cardio-oncology and bring benefit to the population who are at high risk of getting or have already got RCC and HTN simultaneously.

Mechanism Underlying Triple VEGFR Inhibitor Tivozanib-Induced Hypertension in Mice Model

“…On the histological levels, losartan mitigated the vascular toxicity of tivozanib and showed a healthy opened aorta with improved layers. These findings are consistent with the recent recommendations of using angiotensin system inhibitors, including angiotensin-converting enzyme inhibitors (ACEs) and angiotensin-II type 1 receptor blockers (ARBs) as a therapy in the management of hypertension caused by VEGFR-TKIs including sorafenib, sunitinib, tivozanib [ 16 , 20 ]. Although RAAS is crucially involved in the pathogenesis of essential hypertension, there is an absence of evidence that RAAS contributes significantly to hypertension caused by VEGFR-TKI [ 20 ].…”

“…In cancer patients treated with tivozanib, clinical trials showed that around 45% of them suffered from hypertension as the most common adverse reaction, and 8% were reported with proteinuria [ 13 , 14 , 16 ]. Still, the causes of tivozanib-induced hypertension are not clearly identified.…”

Impacts of the COVID-19 pandemic on diagnosis of renal cell carcinoma and disease stage at presentation

“…7,45 Smoking has direct correlations with hypertension, which has frequently been recorded as an independent risk factor for RCC in a dose-dependent fashion, therefore, it is unsurprising that this variable was present in greater than two-thirds of our sample. 44,46 Alternatively, obesity, previously reported in 30% -40% of RCC diagnosis, was seen in nearly 60% of our cohort which may have contributed to an increased risk among our population and may warrant greater examination. 4,44,46 Despite lack of consistent evidence for type 2 diabetes as a risk factor, this condition was still seen in one-quarter of our patients, supporting the likelihood of a previously proposed interplay with other chronic comorbid conditions in the development of RCC.…”

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

“…Furthermore, several factors are often overlooked when assessing both hypertension and CVD risk within cancer patient populations, such as advances in cancer and cardiovascular disease screening, increased public awareness and engagement with their own health, improved therapies and imaging techniques, prolonged survival post treatment and of most significance an escalating aging population could indicate we may be on the verge of an even larger expansion era for cardio-oncology and its treatment-related issues. 5,213…”

“…212 Furthermore, several factors are often overlooked when assessing both hypertension and CVD risk within cancer patient populations, such as advances in cancer and cardiovascular disease screening, increased public awareness and engagement with their own health, improved therapies and imaging techniques, prolonged survival post treatment and of most significance an escalating aging population could indicate we may be on the verge of an even larger expansion era for cardio-oncology and its treatment-related issues. 5,213 An overt deficiency of standardized cardiovascular risk assessment tools established and validated for use in patients with cancer and survivors highlights a significant deficit in care within this population. An explanation for this may be that most cardio-oncology and cancer patient trials include younger, typically low-risk populations and the application of CVD risk assessment/predictive tools may falsely underestimate cardiovascular risk and events which may not be reflective of real-world practice and therefore incorrectly guide treatment decisions.…”