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Effect of anti-cancer therapy on blood pressure and other cardiovascular parameters

Effect of anti-cancer therapy on blood pressure and other cardiovascular parameters

Cancer treatment is the cause of an emerging chronic cardiovascular health problem in cancer survivors. Data show that more than 1.5 million people are diagnosed with a malignancy every year in the USA,1,2 and in 2016, the American Cancer Society reported that there were 15.5 million cancer survivors in the country.1 The 5-year survival rate of patients treated for cancer is currently 67%,1 but approximately 75% of these cancer survivors have some form of chronic health problem, of which cardiovascular diseases are the leading cause of morbidity and mortality.1 The risk of cardiovascular disease is 8 times higher in cancer survivors than in the general population1 and the relative risks of coronary artery disease and heart failure in cancer survivors are 10 times and 15 times higher, respectively, than in their siblings without cancer.1,2

There are a wide range of cardiovascular toxicities associated with anti-cancer therapy. Traditional chemotherapeutics, such as the anthracyclines, have been associated with severe cardiotoxicity, requiring strict control of the dose for a drug like doxorubicin.3 With the emergence of many novel anti-cancer drugs, new forms of vascular toxicity, including systemic and pulmonary hypertension, stroke, acute coronary syndromes, arterial and arteriolar stenosis and thrombosis have been reported.4 Due to an intensive drug discovery program by major pharmaceutical companies there has been an explosion of novel anti-cancer drugs on the market (Table 1). In particular, monoclonal antibodies, VEGF-receptor fusion molecules and tyrosine kinase inhibitors (Table 2) have been brought to the market rapidly without thorough investigation of their potential cardiovascular side-effects.

A common feature of the three recently introduced classes of anti-cancer drugs is that they inhibit the action of vascular growth factors, such as vascular endothelial growth factor (VEGF), platelet derived growth factor (PDGF) and fibroblast growth factor (FGF).5 These growth factors stimulate, via the enzyme tyrosine kinase, a range of signal transduction molecules that cause angiogenesis of the tumour, invasion of tissues and metastasis. The concept of angiogenesis inhibition as a form of cancer treatment was introduced several decades ago by Judah Folkman.6 However, it took until the beginning of the 21st century before angiogenesis inhibitors were available for the early treatment of cancer metastasis. We predicted in the 1990s that such drugs may cause severe hypertension, based on our concept that a major pathogenic mechanisms of hypertension is microvascular rarefaction.7,8 Indeed, recent meta-analyses on the incidence of hypertension in cancer patients treated with a VEGF signaling pathway inhibitor show an odds-ratio of 3-5 for all grades of hypertension and even 5-22 for high-grade hypertension. Various mechanisms for VEGF signaling pathway inhibitor-induced hypertension and related organ damage are discussed in the scientific literature. An obvious candidate is the previously mentioned microvascular rarefaction hypothesis.7,8 Other mechanisms have been proposed, such as the suppression of endothelium-dependent vasodilator mechanisms5 or premature cellular aging induced by telomere dysfunction.1

Whatever the mechanism of anti-cancer drug-induced hypertension and cardiovascular damage, we are confronted with an emerging healthcare problem that needs to be dealt with. Several authors have recently proposed pragmatic solutions to this problem.3,4 A central issue in this approach is a risk/benefit assessment of individual cancer patients. This risk/benefit analysis implies an extensive cardiovascular risk screening before the start of cancer therapy. A next step is to carefully analyse the cardiovascular risks of a potential anti-cancer drug. Subsequently, when cancer therapy is initiated, the patient should be closely followed-up and, if necessary, also be treated for emerging cardiovascular complications. In cases of uncontrolled, extremely high blood pressure values it may even be necessary to reduce the dose or stop the use of cancer therapy. To date, there are no systematic studies on which anti-hypertensive drug (combination) should be used to treat anti-cancer drug-induced hypertension. The choice of an antihypertensive should probably depend on existing co-morbidities and risk factors as well as on potential side-effects. Antihypertensives affecting the renin-angiotensin system should be specially monitored, since these agents are known to interfere with vascular growth processes.8                                        

Table 1: Major classes of anti-cancer drugs


Alkylating agents

Vinca alkaloids

Proteasome inhibitors

Monoclonal antibodies

VEGF-receptor fusion molecules

Antimicrotubule agents

Tyrosine kinase inhibitors

Table 2: Tyrosine kinase inhibitors 













  1. Abe JI, et al. The future of onco-cardiology. Circ Res. 2016;119:896-9.
  2. Akam-Venkata J, et al. Late cardiotoxicity issues for childhood cancer survivors. Curr Treatment Options Cardiovasc Med. 2016;18:47.
  3. Zamorano JL, et al. 2016 ESC position paper on cancer treatments and cardiovascular toxicity developed under the auspices of the ESC committee for practice guidelines. Eur Heart J. 2016;37:2768-801.
  4. Herrmann J, et al. Vascular toxicities of cancer therapies. Circulation. 2016;133:1272-89.
  5. Ancker OV, et al. The adverse effect of hypertension in the treatment of thyroid cancer with multi-kinase inhibitors. Int J Mol Sci. 2017;18:625-44.
  6. Folkman J. Clinical applications of research on angiogenesis. New Engl J Med. 1995; 333:1757-63.
  7. Struijker-Boudier HAJ, et al. The microcirculation and hypertension. J Hypert. 1992; 10(Suppl 7):147-56.
  8. Le Noble FAC, et al. Angiogenesis and hypertension. J Hypert. 1998;14:1563-72.
cancer treatment
vascular growth factors
cardiovascular toxicity