Diagnosis and Management of Cardiovascular Risk in Patients with Polycythemia Vera

Abstract

Polycythemia vera (PV) is a myeloproliferative neoplasm characterized by aberrant myeloid lineage hematopoiesis with excessive red blood cell and pro-inflammatory cytokine production. Patients with PV present with a range of thrombotic and hemorrhagic symptoms that affect quality of life and reduce overall survival expectancy. Thrombotic events, transformation into acute myeloid leukemia, and myelofibrosis are largely responsible for the observed mortality. Treatment of PV is thus primarily focused on symptom control and survival extension through the prevention of thrombosis and leukemic transformation. Patients with PV frequently experience thrombotic events and have elevated cardiovascular risk, including hypertension, dyslipidemias, obesity, and smoking, all of which negatively affect survival. To reduce the risk of thrombotic complications, PV therapy should aim to normalize hemoglobin, hematocrit, and leukocytosis and, in addition, identify and modify cardiovascular risk factors. Herein, we review what is currently known about the associated cardiovascular risk and propose strategies for diagnosing and managing patients with PV.

Plain Language Summary

Patients with the myeloproliferative neoplasm (MPN) polycythemia vera (PV) are at increased risk of cardiovascular (CV) events, including stroke, heart attacks, and peripheral arterial disease. High blood pressure, smoking, and dyslipidemia are common in MPN and contribute to the increased cardiovascular risk. Effectively controlling cardiovascular risk factors in PV, along with appropriate hematological therapy such as direct-acting oral anticoagulants alone or in combination with aspirin, may improve the outcomes of patients with PV, but further research is needed.

Keywords:

• cardiovascular risk
• myeloproliferative neoplasms
• polycythemia vera
• thrombosis

Abbreviations

ABPM, ambulatory 24-hour blood pressure monitoring; ACE-I, angiotensin converting enzyme inhibitors; ACS, acute coronary syndrome; APS, antiphospholipid antibody syndrome; ARB, angiotensin II receptor antagonists; ASA, acetylsalicylic acid; ASH, American Society of Hematology; ASXL1, ASXL transcriptional regulator 1; BID, twice daily; BSH, British Society for Haematology; CALR, calreticulin; CKD, chronic kidney disease; CV, cardiovascular; CVD, cardiovascular disease; DAPT, double antiplatelet therapy; DNMT3A, DNA methyltransferase 3 alpha; DOAC, direct oral anticoagulant; EAPC, European Association of Preventive Cardiology; EAS, European Atherosclerosis Society; ECLAP, European Collaboration on Low-dose Aspirin Study; EF, ejection fraction; ELN, European LeukemiaNet; ESC, European Society of Cardiology; ESH, European Society of Hypertension; ET, essential thrombocythemia; EULAR, European League Against Rheumatism; F, female; FH, familial hypercholesterolemia; GFR, glomerular filtration rate; GLS, global longitudinal strain; GP, general practitioner; HbA1c, glycated hemoglobin; HDL-C, high density lipoprotein cholesterol; Ht, hematocrit; ISTH, International Society on Thrombosis and Haemostasis; JAK2, janus kinase 2; K, potassium; LDL-C, low-density lipoprotein cholesterol; LVMi, left ventricular mass index; M, male; MPL, proto-oncogene thrombopoietin receptor; MPN, myeloproliferative neoplasms; Na, sodium; PCI, percutaneous coronary intervention; PCSK9, proprotein convertase subtilisin/kexin type 9; Ph-, Philadelphia chromosome; PMF, primary myelofibrosis; PV, polycythemia vera; SCORE2, systematic coronary risk estimation 2; SCORE2-OP, systematic coronary risk estimation-older persons; TET2, tet methylcytosine dioxygenase 2; TT, transthoracic; VKA, vitamin K antagonists; VTE, venous thromboembolism; vWF, von Willebrand factor; WHO, World Health Organization.

Acknowledgments

The authors would like to thank Dr Alicja M. Gruszka, MD, PhD, for providing medical writing assistance on behalf of Springer Healthcare Communications, Arneak Kooner of Springer Healthcare Communications and Ray Hill and Melanie Gatt on behalf of Springer Healthcare Communications for providing styling assistance prior to submission. This medical writing and editorial assistance was funded by Novartis Farma SpA.

Author Contributions

All authors made a significant contribution to the work reported, whether that is in the conception, study design, execution, acquisition of data, analysis and interpretation, or in all these areas; took part in drafting, revising or critically reviewing the article; gave final approval of the version to be published; have agreed on the journal to which the article has been submitted; and agree to be accountable for all aspects of the work.

Disclosure

G.B. has been on the advisory board, and been a speaker for Novartis, Janssen, BMS-Celgene M.M. has received consultancy fees from Gilead srl. E.B. has been a speaker for Novartis, Alexion and Incyte. A.M. has taken part in an advisory board for Amgen. D.R. has been advisor for Blueprint Medicines and has received travel grants from Novartis. The authors report no other conflicts of interest in this work.

Additional information

Funding

The authors have not received fees or financial compensation for their participation in this article.