Arterial Hypertension

  • Paolo SpallarossaEmail author
  • Giacomo Tini
  • Daniel Lenihan
Part of the Current Clinical Pathology book series (CCPATH)


Recent progresses in the field of anticancer therapy have dramatically reduced the morbidity and mortality from many forms of malignacy. Arterial hypertension is the most common cardiovascular comorbidity encountered in oncologic patients, and according to some studies, it may be a potential risk factor for specific cancer types. Cancer patients affected by hypertension are at higher risk for the development of cardiac adverse events after specific antineoplastic treatments, specifically anthracyclines. Moreover, new-onset hypertension has emerged as an adverse event for several cancer therapies, in particular for the newer anti-vascular endothelial growth factor agents. A fundamental issue with cancer patients is therefore that hypertension must be carefully diagnosed and treated in order to prevent both early and late cardiotoxic effects of anticancer agents. At the same time, achieving optimal target values of blood pressure during anticancer treatment must be adaptable to changing status of the patient being treated for cancer.


Arterial hypertension Cancer Heart failure Anthracyclines Anti-VEGF agents Antihypertensive therapy Cardiotoxicity 


  1. 1.
    Mancia G, Fagard R, Narkiewicz K, Redon J, Zanchetti A, Böhm M, et al. 2013 ESH/ESC guidelines for the management of arterial hypertension. Eur Heart J. 2013;34(28):2159–219. Scholar
  2. 2.
    Piepoli M, Hoes AW, Agewall S, Albus C, Brotons C, Catapano AL, et al. 2016 European Guidelines on cardiovascular disease prevention in clinical practice. Eur Heart J. 2016;37(29):2315–81. Scholar
  3. 3.
    Whelton PK, Carey RM, Aronow WS, Casey DE Jr, Collins KJ, Dennison Himmelfarb C, et al. 2017 ACC/AHA/AAPA/ABC/ACPM/AGS/APhA/ASH/ASPC/NMA/PCNA guideline for the prevention, detection, evaluation, and management of high blood pressure in adults. J Am Coll Cardiol. 2018;71(19):e127–248. Scholar
  4. 4.
    Dyer AR, Stamler J, Berkson DM, Lindberg HA, Stevens E. High blood-pressure: a risk factor for cancer mortality? Lancet. 1975;1:1051–6.CrossRefGoogle Scholar
  5. 5.
    Lindgren AM, Nissinen AM, Tuomilehto JO, Pukkala E. Cancer pattern among hypertensive patients in North Karelia, Finland. J Hum Hypertens. 2005;19(5):373–9.CrossRefGoogle Scholar
  6. 6.
    Lindholm LH, Anderson H, Ekbom T, Hansson L, Lanke J, Dahlöf B, et al. Relation between drug treatment and cancer in hypertensives in the Swedish Trial in Old Patients with Hypertension 2: a 5-year, prospective, randomised, controlled trial. Lancet. 2001;358(9281):539–44.CrossRefGoogle Scholar
  7. 7.
    Bangalore S, Kumar S, Kjeldsen SE, Makani H, Grossman E, Wetterslev J, et al. Antihypertensive drugs and risk of cancer: network meta-analyses and trial sequential analyses of 324 168 participants from randomised trials. Lancet Oncol. 2011;12(1):65–82. Scholar
  8. 8.
    Stocks T, Van Hemelrijck M, Manjer J, Bjørge T, Ulmer H, Hallmans G, et al. Blood pressure and risk of cancer incidence and mortality in the Metabolic Syndrome and Cancer Project. Hypertension. 2012;59(4):802–10. Scholar
  9. 9.
    Grossman E, Messerli FH, Boyko V, Goldbourt U. Is there an association between hypertension and cancer mortality? Am J Med. 2002;112(6):479–86.CrossRefGoogle Scholar
  10. 10.
    Sanfilippo KM, McTigue KM, Fidler CJ, Neaton JD, Chang Y, Fried LF, et al. Hypertension and obesity and the risk of kidney cancer in two large cohorts of US men and women. Hypertension. 2014;63(5):934–41. Scholar
  11. 11.
    Sun LM, Kuo HT, Jeng LB, Lin CL, Liang JA, Kao CH. Hypertension and subsequent genitourinary and gynecologic cancers risk: a population-based cohort study. Medicine (Baltimore). 2015;94(16):e753. Scholar
  12. 12.
    Pelucchi C, Serraino D, Negri E, Montella M, Dellanoce C, Talamini R, et al. The metabolic syndrome and risk of prostate cancer in Italy. Ann Epidemiol. 2011;21(11):835–41. Scholar
  13. 13.
    Han H, Guo W, Shi W, Yu Y, Zhang Y, Ye X, et al. Hypertension and breast cancer risk: a systematic review and meta-analysis. Sci Rep. 2017;7:44877. Scholar
  14. 14.
    Spallarossa P, Maurea N, Cadeddu C, Madonna R, Mele D, Monte I, et al. A recommended practical approach to the management of anthracycline-based chemotherapy cardiotoxicity: an opinion paper of the working group on drug cardiotoxicity and cardioprotection, Italian Society of Cardiology. J Cardiovasc Med (Hagerstown). 2016;17(Suppl 1 Special issue on Cardiotoxicity from Antiblastic Drugs and Cardioprotection):e84–92.CrossRefGoogle Scholar
  15. 15.
    Hahn VS, Lenihan DJ, Ky B. Cancer therapy–induced cardiotoxicity: basic mechanisms and potential cardioprotective therapies. J Am Heart Assoc. 2014;3(2):e000665. Scholar
  16. 16.
    Pinder MC, Duan Z, Goodwin JS, Hortobagyi GN, Giordano SH. Congestive heart failure in older women treated with adjuvant anthracycline chemotherapy for breast cancer. J Clin Oncol. 2007;25(25):3808–15.CrossRefGoogle Scholar
  17. 17.
    Hershman DL, McBride RB, Eisenberger A, Tsai WY, Grann VR, Jacobson JS. Doxorubicin, cardiac risk factors, and cardiac toxicity in elderly patients with diffuse B-cell non-Hodgkin’s lymphoma. J Clin Oncol. 2008;26(19):3159–65. Scholar
  18. 18.
    Szmit S, Jurczak W, Zaucha JM, Drozd-Sokołowska J, Spychałowicz W, Joks M, et al. Pre-existing arterial hypertension as a risk factor for early left ventricular systolic dysfunction following (R)-CHOP chemotherapy in patients with lymphoma. J Am Soc Hypertens. 2014;8(11):791–9. Scholar
  19. 19.
    Kalay N, Basar E, Ozdogru I, Er O, Cetinkaya Y, Dogan A, et al. Protective effects of carvedilol against anthracycline-induced cardiomyopathy. J Am Coll Cardiol. 2006;48(11):2258–62.CrossRefGoogle Scholar
  20. 20.
    Santos DL, Moreno AJ, Leino RL, Froberg MK, Wallace KB. Carvedilol protects against doxorubicin-induced mitochondrial cardiomyopathy. Toxicol Appl Pharmacol. 2002;185(3):218–27.CrossRefGoogle Scholar
  21. 21.
    Spallarossa P, Garibaldi S, Altieri P, Fabbi P, Manca V, Nasti S, et al. Carvedilol prevents doxorubicin-induced free radical release and apoptosis in cardiomyocytes in vitro. J Mol Cell Cardiol. 2004;37(4):837–46.CrossRefGoogle Scholar
  22. 22.
    Kaya MG, Ozkan M, Gunebakmaz O, Akkaya H, Kaya EG, Akpek M, et al. Rotective effects of nebivolol against anthracycline-induced cardiomyopathy: a randomized control study. Int J Cardiol. 2013;167(5):2306–10. Scholar
  23. 23.
    Cadeddu C, Piras A, Mantovani G, Deidda M, Dessì M, Madeddu C, et al. Protective effects of the angiotensin II receptor blocker telmisartan on epirubicin-induced inflammation, oxidative stress, and early ventricular impairment. Am Heart J. 2010;160(3):487.e1–7. Scholar
  24. 24.
    Nakamae H, Tsumura K, Terada Y, Nakane T, Nakamae M, et al. Notable effects of angiotensin II receptor blocker, valsartan, on acute cardiotoxic changes after standard chemotherapy with cyclophosphamide, doxorubicin, vincristine, and prednisolone. Cancer. 2005;104(11):2492–8.CrossRefGoogle Scholar
  25. 25.
    Seicean S, Seicean A, Plana JC, Budd GT, Marwick TH. Effect of statin therapy on the risk for incident heart failure in patients with breast cancer receiving anthracycline chemotherapy: an observational clinical cohort study. J Am Coll Cardiol. 2012;60(23):2384–90. Scholar
  26. 26.
    Zamorano JL, Lancellotti P, Rodriguez Muñoz D, Aboyans V, Asteggiano R, Galderisi M, 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(36):2768–801.CrossRefGoogle Scholar
  27. 27.
    Cautela J, Lalevée N, Ammar C, Ederhy S, Peyrol M, Debourdeau P, et al. Management and research in cancer treatment-related cardiovascular toxicity: challenges and perspectives. Int J Cardiol. 2016;224:366–75. Scholar
  28. 28.
    Fraeman KH, Nordstrom BL, Luo W, Landis SH, Shantakumar S. Incidence of new-onset hypertension in cancer patients: a retrospective cohort study. Int J Hypertens. 2013;2013:379252. Scholar
  29. 29.
    Souza VB, Silva EN, Ribeiro ML, Martins WDA. Hypertension in patients with cancer. Arq Bras Cardiol. 2015;104(3):246–52. Scholar
  30. 30.
    Sagstuen H, Aass N, Fosså SD, Dahl O, Klepp O, Wist EA, et al. Sagstuen. Blood pressure and body mass index in long-term survivors of testicular cancer. J Clin Oncol. 2005;23(22):4980–90.CrossRefGoogle Scholar
  31. 31.
    Haugnes HS, Aass N, Fosså SD, Dahl O, Klepp O, Wist EA, et al. Components of the metabolic syndrome in long-term survivors of testicular cancer. Ann Oncol. 2007;18(2):241–8.CrossRefGoogle Scholar
  32. 32.
    Brinda BJ, Viganego F, Vo T, Dolan D, Fradley MG. Anti-VEGF induced hypertension: a review of pathophysiology and treatment options. Curr Treat Options Cardiovasc Med. 2016;18(5):33. Scholar
  33. 33.
    Abdel-Qadir H, Ethier JL, Lee DS, Thavendiranathan P, Amir E. Cardiovascular toxicity of angiogenesis inhibitors in treatment of malignancy: a systematic review and meta-analysis. Cancer Treat Rev. 2017;53:120–7. Scholar
  34. 34.
    de Jesus-Gonzalez N, Robinson E, Moslehi J, Humphreys BD. Management of antiangiogenic therapy-induced hypertension. Hypertension. 2012;60(3):607–15. Scholar
  35. 35.
    Li M, Kroetz DL. Bevacizumab-induced hypertension: clinical presentation and molecular understanding. Pharmacol Ther. 2018;182:152–60. Scholar
  36. 36.
    Di Lisi D, Madonna R, Zito C, Bronte E, Badalamenti G, Parrella P, et al. Anticancer therapy-induced vascular toxicity: VEGF inhibition and beyond. Int J Cardiol. 2017;227:11–7. Scholar
  37. 37.
    Ancker OV, Wehland M, Bauer J, Infanger M, Grimm D. The adverse effect of hypertension in the treatment of thyroid cancer with multi-kinase inhibitors. Int J Mol Sci. 2017;18(3):pii: E625. Scholar
  38. 38.
    Boursiquot BC, Zabor EC, Glezerman IG, Jaimes EA. Hypertension and VEGF (vascular endothelial growth factor) receptor tyrosine kinase inhibition: effects on renal function. Hypertension. 2017:pii: HYPERTENSIONAHA.117.09275. Scholar
  39. 39.
    Hamnvik OP, Choueiri TK, Turchin A, McKay RR, Goyal L, Davis M, et al. Clinical risk factors for the development of hypertension in patients treated with inhibitors of the VEGF signaling pathway. Cancer. 2015;121(2):311–9. Scholar
  40. 40.
    Frey MK, Dao F, Olvera N, Konner JA, Dickler MN, Levine DA. Genetic predisposition to bevacizumab-induced hypertension. Gynecol Oncol. 2017;147(3):621–5. Scholar
  41. 41.
    Berger MD, Yamauchi S, Cao S, Hanna DL, Sunakawa Y, Schirripa M, et al. Autophagy-related polymorphisms predict hypertension in patients with metastatic colorectal cancer treated with FOLFIRI and bevacizumab: results from TRIBE and FIRE-3 trials. Eur J Cancer. 2017;77:13–20. Scholar
  42. 42.
    Corr BR, Breed C, Sheeder J, Weisdack S, Behbakht K. Bevacizumab induced hypertension in gynecologic cancer: does it resolve after completion of therapy? Gynecol Oncol Rep. 2016;17:65–8. Scholar
  43. 43.
    Tocchetti CG, Gallucci G, Coppola C, Piscopo G, Cipresso C, Maurea C, et al. The emerging issue of cardiac dysfunction induced by antineoplastic angiogenesis inhibitors. Eur J Heart Fail. 2013;15(5):482–9. Scholar
  44. 44.
    Dionísio de Sousa IJ, Ferreira J, Rodrigues J, Bonito N, Jacinto P, Marques M, et al. Association between bevacizumab-related hypertension and response to treatment in patients with metastatic colorectal cancer. ESMO Open. 2016;1(3):e000045.CrossRefGoogle Scholar
  45. 45.
    Nakaya A, Kurata T, Yokoi T, Iwamoto S, Torii Y, Katashiba Y, et al. Retrospective analysis of bevacizumab-induced hypertension and clinical outcome in patients with colorectal cancer and lung cancer. Cancer Med. 2016;5(7):1381–7. Scholar
  46. 46.
    Feliu J, Salud A, Safont MJ, García-Girón C, Aparicio J, Losa F, et al. Correlation of hypertension and proteinuria with outcome in elderly bevacizumab-treated patients with metastatic colorectal cancer. PLoS One. 2015;10(1):e0116527. Scholar
  47. 47.
    Duffaud F, Sleijfer S, Litière S, Ray-Coquard I, Le Cesne A, Papai Z, et al. Hypertension (HTN) as a potential biomarker of efficacy in pazopanib-treated patients with advanced non-adipocytic soft tissue sarcoma. A retrospective study based on European Organisation for Research and Treatment of Cancer (EORTC) 62043 and 62072 trials. Eur J Cancer. 2015;51(17):2615–23. Scholar
  48. 48.
    Donskov F, Michaelson MD, Puzanov I, Davis MP, Bjarnason GA, Motzer RJ, et al. Sunitinib-associated hypertension and neutropenia as efficacy biomarkers in metastatic renal cell carcinoma patients. Br J Cancer. 2015;113(11):1571–80. Scholar
  49. 49.
    Miyake M, Kuwada M, Hori S, Morizawa Y, Tatsumi Y, Anai S, et al. The best objective response of target lesions and the incidence of treatment-related hypertension are associated with the survival of patients with metastatic renal cell carcinoma treated with sunitinib: a Japanese retrospective study. BMC Res Notes. 2016;9:79. Scholar
  50. 50.
    Izzedine H, Ederhy S, Goldwasser F, Soria JC, Milano G, Cohen A, et al. Management of hypertension in angiogenesis inhibitor-treated patients. Ann Oncol. 2009;20(5):807–15. Scholar
  51. 51.
    Izzedine H, Derosa L, Le Teuff G, Albiges L, Escudier B. Hypertension and angiotensin system inhibitors: impact on outcome in sunitinib-treated patients for metastatic renal cell carcinoma. Ann Oncol. 2015;26(6):1128–33. Scholar
  52. 52.
    Mc Menamin UC, Murray LJ, Cantwell MM, Hughes CM. Angiotensin converting enzyme inhibitors and angiotensin receptor blockers in cancer progression and survival: a systematic review. Cancer Causes Control. 2012;23(2):221–30. Scholar
  53. 53.
    Penttilä P, Rautiola J, Poussa T, Peltola K, Bono P. Angiotensin inhibitors as treatment of sunitinib/pazopanib-induced hypertension in metastatic renal cell carcinoma. Clin Genitourin Cancer. 2017;15(3):384–390.e3. Scholar
  54. 54.
    Spallarossa P, Sarocchi M. What the oncologist needs to know: how to ask for a cardiology consultation. In: Lestuzzi C, Oliva S, Ferraù F, editors. Manual of cardio-oncology. Philadelphia: Springer; 2017. p. 443–50.CrossRefGoogle Scholar
  55. 55.
    Sahebkar A, Ponziani MC, Goitre I, Bo S. Does statin therapy reduce plasma VEGF levels in humans? A systematic review and meta-analysis of randomized controlled trials. Metabolism. 2015;64(11):1466–76. Scholar

Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  • Paolo Spallarossa
    • 1
    Email author
  • Giacomo Tini
    • 1
  • Daniel Lenihan
    • 2
  1. 1.Clinic of Cardiovascular DiseasesUniversity of Genova, San Martino Policlinic HospitalGenovaItaly
  2. 2.Cardiovascular Division, Cardio-Oncology Center of ExcellenceWashington University in St. LouisSt. LouisUSA

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