Blood Res.  2023 Dec;58(4):173-180. 10.5045/br.2023.2023125.

Abdominal aortic calcification in patients newly diagnosed with essential thrombocythemia

• Lee MW
• Koh JS
• Kang S
• Ryu H
• Song IC
• Lee HJ
• Yun HJ
• Kim SY
• Kim SS
• Jo DY

• KMID: 2550194
• DOI: http://doi.org/10.5045/br.2023.2023125

Abstract

Background
Although atherosclerosis is likely to be involved in the development of arterial thrombotic events in patients with essential thrombocythemia (ET), abdominal aortic calcification (AAC) has rarely been investigated. We evaluated the prevalence and clinical relevance of AAC at the time of ET diagnosis.
Methods
This retrospective study included patients newly diagnosed with ET who underwent abdominal computed tomography (CT) at the time of diagnosis between January 2002 and December 2021 at Chungnam National University Hospital, Daejeon, Korea. CT images were reviewed and an aortic calcification score was assigned.
Results
Of the 94 patients (median age, 62 yr; range, 18‒90 yr), AAC was detected in 62 (66.0%). AAC was most commonly mild (33.0%), followed by moderate (22.7%) and severe (5.3%). Old age [odds ratio (OR), 34.37; 95% confidence interval (CI), 12.32‒95.91; P ＜0.001] was an independent risk factor for AAC. The patients with AAC had a higher WBC count (11.8±4.7 vs. 9.7±2.9×10⁹ /L, P =0.017), higher neutrophil-to-lymphocyte ratio (4.3±2.7 vs. 3.1±1.5, P=0.039), and higher JAK2V617F positivity (81.5% vs. 58.8%, P=0.020) compared to those without AAC. AAC was an independent risk factor for arterial thrombotic vascular events that occurred before or at diagnosis of ET (OR, 4.12; 95% CI, 1.11‒15.85; P=0.034).
Conclusion
AAC is common in patients with ET and is associated with arterial thrombotic events.

Keyword

Essential thrombocythemia; Atherosclerosis; Abdominal aortic calcification; Arterial thrombosis

Figure

• 

  Fig. 1 Correlations between aortic calcification score and various parameters: (A) age, (B) white blood cell count, (C) monocyte count, and (D) neutrophil-to-lymphocyte ratio.

Reference

1. Song IC, Yeon SH, Lee MW, et al. 2021; Thrombotic and hemorrhagic events in 2016 World Health Organization-defined Philadelphia- negative myeloproliferative neoplasm. Korean J Intern Med. 36:1190–203. DOI: 10.3904/kjim.2020.634. PMID: 34289585. PMCID: PMC8435504. PMID: 1171ae3cdf6c42e4a204252610a84058.

2. Song IC, Yeon SH, Lee MW, et al. 2022; Myelofibrotic and leukemic transformation in 2016 WHO-defined Philadelphia-negative myeloproliferative neoplasm. Blood Res. 57:59–68. DOI: 10.5045/br.2021.2021209. PMID: 35256550. PMCID: PMC8958372.

3. Awada H, Voso MT, Guglielmelli P, Gurnari C. 2020; Essential thrombocythemia and acquired von Willebrand syndrome: the shadowlands between thrombosis and bleeding. Cancers (Basel). 12:1746. DOI: 10.3390/cancers12071746. PMID: 32629973. PMCID: PMC7407619. PMID: f848ec192cf64638bc5639cee75ebecb.

4. Stein BL, Martin K. 2019; From Budd-Chiari syndrome to acquired von Willebrand syndrome: thrombosis and bleeding complications in the myeloproliferative neoplasms. Blood. 134:1902–11. DOI: 10.1182/blood.2019001318. PMID: 31778549.

5. Rungjirajittranon T, Owattanapanich W, Ungprasert P, Siritanaratkul N, Ruchutrakool T. 2019; A systematic review and meta-analysis of the prevalence of thrombosis and bleeding at diagnosis of Philadelphia-negative myeloproliferative neoplasms. BMC Cancer. 19:184. DOI: 10.1186/s12885-019-5387-9. PMID: 30819138. PMCID: PMC6393965. PMID: 844016cb1a884c4a9597525ffa2f3abb.

6. Reeves BN, Moliterno AR. 2021; Thrombosis in myeloproliferative neoplasms: update in pathophysiology. Curr Opin Hematol. 28:285–91. DOI: 10.1097/MOH.0000000000000664. PMID: 34183535.

7. Jaiswal S, Natarajan P, Silver AJ, et al. 2017; Clonal hematopoiesis and risk of atherosclerotic cardiovascular disease. N Engl J Med. 377:111–21. DOI: 10.1056/NEJMoa1701719. PMID: 28636844. PMCID: PMC6717509.

8. Chatain N, Koschmieder S, Jost E. 2020; Role of inflammatory factors during disease pathogenesis and stem cell transplantation in myeloproliferative neoplasms. Cancers (Basel). 12:2250. DOI: 10.3390/cancers12082250. PMID: 32806517. PMCID: PMC7463735. PMID: c07c9a99a10e4a3ab35d62b53ea9ad20.

9. Mendez Luque LF, Blackmon AL, Ramanathan G, Fleischman AG. 2019; Key role of inflammation in myeloproliferative neoplasms: instigator of disease initiation, progression. and symptoms. Curr Hematol Malig Rep. 14:145–53. DOI: 10.1007/s11899-019-00508-w. PMID: 31119475. PMCID: PMC7746200.

10. Lussana F, Rambaldi A. 2017; Inflammation and myeloproliferative neoplasms. J Autoimmun. 85:58–63. DOI: 10.1016/j.jaut.2017.06.010. PMID: 28669446.

11. Wang W, Liu W, Fidler T, et al. 2018; Macrophage, inflammation, erythrophagocytosis, and accelerated atherosclerosis in Jak2 (V617F) mice. Circ Res. 123:e35–47. DOI: 10.1161/CIRCRESAHA.118.313283. PMID: 30571460. PMCID: PMC6309796.

12. Misaka T, Kimishima Y, Yokokawa T, Ikeda K, Takeishi Y. 2023; Clonal hematopoiesis and cardiovascular diseases: role of JAK2V617F. J Cardiol. 81:3–9. DOI: 10.1016/j.jjcc.2022.02.001. PMID: 35165011.

13. Amancherla K, Wells JA 4th, Bick AG. 2022; Clonal hematopoiesis and vascular disease. Semin Immunopathol. 44:303–8. DOI: 10.1007/s00281-022-00913-z. PMID: 35122117. PMCID: PMC9064918.

14. de Groot E, van Leuven SI, Duivenvoorden R, et al. 2008; Measurement of carotid intima-media thickness to assess progression and regression of atherosclerosis. Nat Clin Pract Cardiovasc Med. 5:280–8. DOI: 10.1038/ncpcardio1163. PMID: 18332891.

15. Stoner L, Meyer ML, Kucharska-Newton A, et al. 2020; Associations between carotid-femoral and heart-femoral pulse wave velocity in older adults: the atherosclerosis risk in communities study. J Hypertens. 38:1786–93. DOI: 10.1097/HJH.0000000000002449. PMID: 32371771. PMCID: PMC7415670.

16. Ganbaatar N, Kadota A, Hisamatsu T, et al. 2022; Relationship between kidney function and subclinical atherosclerosis progression evaluated by coronary artery calcification. J Atheroscler Thromb. 29:1359–71. DOI: 10.5551/jat.63030. PMID: 34690221. PMCID: PMC9444674.

17. Paydary K, Revheim ME, Emamzadehfard S, et al. 2021; Quantitative thoracic aorta calcification assessment by (18)F-NaF PET/CT and its correlation with atherosclerotic cardiovascular disorders and increasing age. Eur Radiol. 31:785–94. DOI: 10.1007/s00330-020-07133-9. PMID: 32870396.

18. Suh SH, Oh TR, Choi HS, et al. 2022; Abdominal aortic calcification and cardiovascular outcomes in chronic kidney disease: findings from KNOW-CKD study. J Clin Med. 11:1157. DOI: 10.3390/jcm11051157. PMID: 35268249. PMCID: PMC8911161. PMID: 6abdb663364b4cde8d4a7a7a43b8a10d.

19. Bartstra JW, Mali WPTM, Spiering W, de Jong PA. 2021; Abdominal aortic calcification: from ancient friend to modern foe. Eur J Prev Cardiol. 28:1386–91. DOI: 10.1177/2047487320919895. PMID: 34647579.

20. Leow K, Szulc P, Schousboe JT, et al. 2021; Prognostic value of abdominal aortic calcification: a systematic review and meta- analysis of observational studies. J Am Heart Assoc. 10:e017205. DOI: 10.1161/JAHA.120.017205. PMID: 33439672. PMCID: PMC7955302. PMID: 2b39509d70af4b40a8aafbabdde3461e.

21. Arber DA, Orazi A, Hasserjian R, et al. 2016; The 2016 revision to the World Health Organization classification of myeloid neoplasms and acute leukemia. Blood. 127:2391–405. DOI: 10.1182/blood-2016-03-643544. PMID: 27069254.

22. Agatston AS, Janowitz WR, Hildner FJ, Zusmer NR, Viamonte M Jr, Detrano R. 1990; Quantification of coronary artery calcium using ultrafast computed tomography. J Am Coll Cardiol. 15:827–32. DOI: 10.1016/0735-1097(90)90282-T. PMID: 2407762.

23. Lee MW, Yeon SH, Ryu H, et al. 2021; Volumetric splenomegaly in patients with essential thrombocythemia and prefibrotic/early primary myelofibrosis. Int J Hematol. 114:35–43. DOI: 10.1007/s12185-021-03121-x. PMID: 33704663.

24. Passamonti F, Thiele J, Girodon F, et al. 2012; A prognostic model to predict survival in 867 World Health Organization-defined essential thrombocythemia at diagnosis: a study by the International Working Group on Myelofibrosis Research and Treatment. Blood. 120:1197–201. DOI: 10.1182/blood-2012-01-403279. PMID: 22740446.

25. Barbui T, Vannucchi AM, Buxhofer-Ausch V, et al. 2015; Practice- relevant revision of IPSET-thrombosis based on 1019 patients with WHO-defined essential thrombocythemia. Blood Cancer J. 5:e369. DOI: 10.1038/bcj.2015.94. PMID: 26617062. PMCID: PMC4670947.

26. Rahman EU, Chobufo MD, Farah F, et al. 2021; Prevalence and risk factors for the development of abdominal aortic calcification among the US population: NHANES study. Arch Med Sci Atheroscler Dis. 6:e95–101. DOI: 10.5114/amsad.2021.105527. PMID: 34027218. PMCID: PMC8117070.

27. Liu M, Zhang W, Li X, Han J, Chen Y, Duan Y. 2016; Impact of age and sex on the development of atherosclerosis and expression of the related genes in apoE deficient mice. Biochem Biophys Res Commun. 469:456–62. DOI: 10.1016/j.bbrc.2015.11.064. PMID: 26592663.

28. Fernandez AB, Ballard KD, Wong TY, et al. 2018; Age-related macular degeneration and progression of coronary artery calcium: the multi-ethnic study of atherosclerosis. PLoS One. 13:e0201000. DOI: 10.1371/journal.pone.0201000. PMID: 30020999. PMCID: PMC6051657. PMID: 3589f0803dae4bc2a3024a7897239bda.

29. VanderBurgh JA, Reinhart-King CA. 2018; The role of age-related intimal remodeling and stiffening in atherosclerosis. Adv Pharmacol. 81:365–91. DOI: 10.1016/bs.apha.2017.08.008. PMID: 29310802.

30. Tuomisto S, Huhtala H, Martiskainen M, Goebeler S, Lehtimäki T, Karhunen PJ. 2019; Age-dependent association of gut bacteria with coronary atherosclerosis: Tampere Sudden Death Study. PLoS One. 14:e0221345. DOI: 10.1371/journal.pone.0221345. PMID: 31437200. PMCID: PMC6705803. PMID: dd826476f11b417cb7314924d606e5f1.

31. Climie RE, Bruno RM, Hametner B, Mayer CC, Terentes- Printzios D. 2020; Vascular age is not only atherosclerosis, it is also arteriosclerosis. J Am Coll Cardiol. 76:229–30. DOI: 10.1016/j.jacc.2020.03.081. PMID: 32646575.

32. Tefferi A, Barbui T. 2020; Polycythemia vera and essential thrombo-cythemia: 2021 update on diagnosis, risk-stratification and management. Am J Hematol. 95:1599–613. DOI: 10.1002/ajh.26008. PMID: 32974939.

33. Lee MW, Yeon SH, Ryu H, et al. 2022; Volumetric splenomegaly in patients with polycythemia vera. J Korean Med Sci. 37:e87. DOI: 10.3346/jkms.2022.37.e87. PMID: 35315598. PMCID: PMC8938613.

34. Lee MW, Yeon SH, Ryu H, et al. 2022; Splenic infarction in patients with Philadelphia-negative myeloproliferative neoplasms. Intern Med. 61:3483–90. DOI: 10.2169/internalmedicine.9124-21. PMID: 35527026. PMCID: PMC9790792.