Cancer patients at higher risk for CVD comorbidities prior to VEGF inhibitor use

Cancer patients who are eligible for the application of vascular endothelial growth factor (VEGF) antagonists have an increased risk for cardiovascular disease (CVD)-related comorbidities, with hypertension being the most prevalent condition, according to a study.

“Among [cancer patients with hypertension], those with grade III and very high cardiovascular risk level constitute the largest proportion,” the researchers said. “Also, hypertension patients had a significant burden of CVD comorbidity among the candidates for VEGF antagonist use.”

The top CVD comorbidities among cancer patients were hypertension, coronary heart disease, atrial fibrillation and heart failure. Of these, hypertension was the most prevalent (26.0 percent). [J Hypertens 2020;38:426-433]

Hypertension prevalence in patients with renal cell carcinoma (RCC; 33.5 percent) and colorectal cancer (CRC; 29.4 percent) was significantly higher than in those with hepatocellular carcinoma (HCC; 25.1 percent), lung cancer (24.5 percent) and thyroid cancer (23.1 percent).

Most cancer patients with hypertension had grade III (75.7 percent) and very high cardiovascular risk level (85.4 percent). Of the 5,847 hypertensive patients, 26 percent were not taking antihypertensive medication and 34.2 percent did not achieve their target blood pressure (BP).

The prevalence of hypertension among cancer patients in this study was comparable to that in the general population according to the latest China Hypertension Survey. [Circulation 2018;137:2344-2356]

In a previous study, Faruque and colleagues reported the association of increased BP with a higher burden of cardiovascular events, arterial thromboembolism and proteinuria. [PloS One 2014;9:e101145]

Hypertension may also reduce the therapeutic benefits of VEGF inhibitors, according to the researchers. Specifically, a study by Schmidinger revealed that 25–66 percent of cancer patients die of fatal events due to VEGF signaling pathway-related cardiotoxicity, which can develop to hypertension, arterial thromboembolism and myocardial infarction, among others. [EJC Suppl 2013;11:172-191]

Increasing evidence also showed that hypertension could influence the development of RCC. Studies have suggested that chronic renal hypoxia during hypertension could lead to upregulation of hypoxia-inducible factors, “which in turn plays a significant role in oncogenesis.” [J Am Soc Nephrol 2003;14:2703-2711; Am J Epidemiol 2008;167:438-446]

“A shred of evidence established that oxidative stress and lipid peroxidation are associated with hypertension, which are also known to play a critical role in the pathogenesis of RCC,” the researchers said. “However, the biological mechanism is still controversial and remained unclear.” [Am J Epidemiol 2008;167:438-446; N Engl J Med 1996;334:13-18; Nat Rev Cancer 2004;4:579-591]

The present study included 22,500 newly diagnosed cancer patients registered from 1 January 2011 to 31 December 2017. Those with CRC, RCC, thyroid cancer, HCC and lung cancer were enrolled.

Certain limitations were present, including the lack of detailed information on tumour size and stages formation, the possible underestimation of comorbidities prevalence, and the data sourced from a single centre with a relatively small sample size, according to the researchers.