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Original Article

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Blood Res 2023; 58(4):

Published online December 31, 2023

https://doi.org/10.5045/br.2023.2023125

© The Korean Society of Hematology

Abdominal aortic calcification in patients newly diagnosed with essential thrombocythemia

Myung-Won Lee1, Jeong Suk Koh1, Sora Kang1, Hyewon Ryu1, Ik-Chan Song1, Hyo-Jin Lee1, Hwan-Jung Yun1, Seon Young Kim2, Seong Soo Kim3, Deog-Yeon Jo1

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1Division of Hematology/Oncology, Department of Internal Medicine, 2Department of Laboratory Medicine, 3Department of Thoracic Radiology, Chungnam National University College of Medicine, Daejeon, Korea

Correspondence to : Deog-Yeon Jo, M.D., Ph.D.
Division of Hematology/Oncology, Department of Internal Medicine, Chungnam National University Hospital, 282 Munhwa-ro, Jung-gu, Daejeon 35015, Korea
E-mail: deogyeon@cnu.ac.kr

*This study was supported by Research Fund of Chungnam National University Hospital (2022).

Received: July 5, 2023; Revised: September 4, 2023; Accepted: September 27, 2023

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

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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.

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Keywords: Essential thrombocythemia, Atherosclerosis, Abdominal aortic calcification, Arterial thrombosis

Article

Original Article

Blood Res 2023; 58(4): 173-180

Published online December 31, 2023 https://doi.org/10.5045/br.2023.2023125

Copyright © The Korean Society of Hematology.

Abdominal aortic calcification in patients newly diagnosed with essential thrombocythemia

Myung-Won Lee1, Jeong Suk Koh1, Sora Kang1, Hyewon Ryu1, Ik-Chan Song1, Hyo-Jin Lee1, Hwan-Jung Yun1, Seon Young Kim2, Seong Soo Kim3, Deog-Yeon Jo1

1Division of Hematology/Oncology, Department of Internal Medicine, 2Department of Laboratory Medicine, 3Department of Thoracic Radiology, Chungnam National University College of Medicine, Daejeon, Korea

Correspondence to:Deog-Yeon Jo, M.D., Ph.D.
Division of Hematology/Oncology, Department of Internal Medicine, Chungnam National University Hospital, 282 Munhwa-ro, Jung-gu, Daejeon 35015, Korea
E-mail: deogyeon@cnu.ac.kr

*This study was supported by Research Fund of Chungnam National University Hospital (2022).

Received: July 5, 2023; Revised: September 4, 2023; Accepted: September 27, 2023

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

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.

Keywords: Essential thrombocythemia, Atherosclerosis, Abdominal aortic calcification, Arterial thrombosis

Fig 1.

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Figure 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.
Blood Research 2023; 58: 173-180https://doi.org/10.5045/br.2023.2023125

Table 1 . Patient characteristics (N=94)..

Age, yr, median (range)62 (18–90)
Male45 (47.9)
Time of diagnosis
2002–201527 (28.7)
2016–202167 (71.3)
Palpable splenomegaly0 (0.0)
Volumetric splenomegaly47 (50.0)
Laboratory findings
WBC, ×109/L11.0±4.2
Neutrophil/lymphocyte3.9±2.4
Monocyte, ×109/L0.6±0.5
Hemoglobin, g/dL13.6±2.2
Platelet, ×109/L948.2±387.7
LDH, ×ULN1.2±0.4
Driver gene mutation
JAK2V617F64 (72.8)
CALR9 (9.6)
MPL3 (3.2)
JAK2V617F VAF, %24.8±12.8
IPSET
Low 30 (31.9)
Intermediate 27 (28.7)
High37 (39.4)
Comorbidity
Hypertension32 (34.0)
Diabetes mellitus12 (13.8)
Chronic kidney disease11 (11.7)
Dyslipidemia19 (20.2)
Smoking21 (22.3)
Treatments
Cytoreductive treatment65 (67.4)
Aspirin86 (91.5)
Initial thrombotic events
Time of occurrence
Before or at diagnosis21 (22.3)
After diagnosis1 (1.1)
Overall22 (23.4)
Vessels involved
Arterial21 (22.3)
Venous1 (1.1)
Follow-up, yr, median (range)2.9 (0.12–0.2)

Values are presented as number (%) or mean±standard deviation..

Abbreviations: CALR, calreticulin; IPSET, International Prognostic Score in Essential Thrombocythemia; LDH, lactate dehydrogenase; ULN, upper limit of normal; VAF, variant allele frequency..

Table 2 . Prevalence and severity of abdominal aortic calcification (N=94)..

Severity of calcificationa)N (%)Aortic calcification score (ACS)
No32 (24.0)4±5
Mild31 (33.0)413±368
Moderate26 (27.7)2,814±1,783
Severe5 (5.3)12,365±5,238
Total94 (100)1,521±2,985

a)Abdominal aortic calcification was arbitrarily classified as no calcification (ACS <10), mild calcification (ACS of 10–999), moderate calcification (ACS of 1,000–10,000), or severe calcification (ACS >10,000)..

Table 3 . Risk factors for developing abdominal aortic calcification at diagnosis of essential thrombocythemia (N=94)..

Univariate analysisMultivariate analysis
OR95% CIPOR95% CIP
Age >60 yr28.2312.31–64.88<0.00134.3712.32–95.91<0.001
Male2.000.85–4.720.111---
Volumetric splenomegaly1.070.59–2.030.833---
WBC >11.0×109/L2.661.12–6.960.0283.920.93–16.500.062
Monocyte >1.0×109/L6.941.59–20.330.0104.380.25–77.290.313
Neutrophil/lymphocyte >4.02.280.88–5.900.089---
Platelet >1,000×109/L1.290.61–2.720.509---
LDH >1.5×ULN3.320.88–12.510.076---
Positive JAK2V617F3.411.17–8.110.0233.160.66–15.230.151
Positive CALR mutation0.440.11–1.750.242---
Hypertension5.061.73–14.850.0031.050.17–6.610.955
Diabetes mellitus3.971.07–14.790.0404.740.41–54.230.211
Chronic kidney disease6.940.85–56.760.071---
Dyslipidemia3.971.09–14.790.0405.050.85–30.210.076
Smoking1.650.57–4.740.354---

Abbreviations: CALR, calreticulin; CI, confidence interval; LDH, lactate dehydrogenase; OR, odds ratio; ULN, upper limit of normal..

Table 4 . Clinical features of essential thrombocythemia patients according to abdominal aortic calcification..

Without AAC (N=35)With AAC (N=59)P
Age, yr49.4±12.368.1±10.5<0.001
Male12 (37.1)32 (54.2)0.109
Volumetric splenomegaly18 (51.4)29 (49.2)0.831
Laboratory findings
WBC, ×109/L9.7±2.911.8±4.70.017
Neutrophil/lymphocyte3.2±1.54.3±2.70.039
Monocyte, ×109/L0.5±0.20.7±0.50.003
Hemoglobin, g/dL14.0±1.613.2±2.50.111
Platelet, ×109/L881.3±338.2989.3±412.60.196
LDH, ×ULN1.1±0.41.3±0.40.043
Driver gene mutation
JAK2V617F20 (58.8)44 (81.5)0.020
CALR5 (14.3)4 (6.8)0.232
JAK2V617F VAF, %21.8±11.026.1±13.50.218
IPSET<0.001
Low 26 (74.3)3 (5.1)
Intermediate 5 (14.3)23 (39.0)
High4 (11.4)33 (55.9)
R-IPSET-T<0.001
Very low11 (31.4)1 (1.7)
Low17 (48.6)6 (10.2)
Intermediate1 (2.9)10 (16.9)
High5 (14.3)42 (71.2)
Comorbidity
Hypertension5 (14.3)27 (45.8)0.002
Diabetes mellitus2 (5.7)11 (18.6)0.079
Chronic kidney disease1 (2.9)10 (16.9)0.030
Dyslipidemia3 (8.6)16 (27.1)0.001
Smoking6 (17.1)15 (25.4)0.351
Thrombotic event
Arterial3 (8.6)18 (30.5)0.014
Overall3 (8.6)19 (32.2)0.009
Hemorrhagic event1 (2.9)7 (11.9)0.130
Follow-up, yr6.3±5.83.2±3.60.002

Data are presented as number (%) or mean±standard deviation..

Abbreviations: AAC, abdominal aortic calcification; CALR, calreticulin; IPSET, International Prognostic Score in Essential Thrombocythemia; LDH, lactate dehydrogenase; R-IPSET-T, revised IPSET-thrombosis; ULN, upper limit of normal; VAF, variant allele frequency..

Table 5 . Risk factors for thrombotic vascular events occurring before or at diagnosis of essential thrombocythemia (N=94)..

Univariate analysisMultivariate analysis
OR95% CIPOR95% CIP
Age >60 yr3.591.20–10.790.0231.520.35–6.720.578
Male1.420.54–3.700.475---
Volumetric splenomegaly0.370.14–1.030.056---
WBC >11.0×109/L0.670.64–4.360.298---
Monocyte >1.0×109/L2.060.54–7.840.287---
Neutrophil/lymphocyte >4.03.221.20–8.680.0211.840.57–5.690.322
Platelet >1,000×109/L2.330.86–6.250.095---
LDH >1.5×ULN1.010.29–3.480.989---
Positive JAK2V617F2.871.05–8.630.0482.330.75–7.180.142
Hypertension1.570.59–4.220.368---
Diabetes mellitus2.350.68–8.120.176---
Chronic kidney disease5.031.36–18.550.0153.660.95–14.060.059
Dyslipidemia0.840.25–2.870.787---
Smoking1.930.66–5.640.227---
AAC5.071.38–18.650.0154.121.11–15.850.034

Abbreviations: AAC, abdominal aortic calcification; CI, confidence interval; LDH, lactate dehydrogenase; OR, odds ratio; ULN, upper limit of normal..
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