Inflammatory risk factors are not associated with coronary artery calcification in patients with myeloproliferative philadelphia-negative neoplasms
Authors: Solli C N , Chamat-Hedemand S , Elming H , Ngo A , Skov V , Kjaer L , Soerensen A , Hasselbalch H K , Bruun N E 
Published: October 2021

Abstract

Background
Myeloproliferative Philadelphia-negative Neoplasms (MPNs) are hematological cancers associated with chronic inflammation and endothelial dysfunction, conditions that may lead to development of premature atherosclerosis.

Purpose
To investigate whether biomarkers of inflammation and endothelial dysfunction are associated with the degree of atherosclerotic burden, measured by Coronary Artery Calcium Score (CACS), in patients with MPNs.

Methods
Patients with a validated MPN diagnosis; essential thrombocythemia (ET), polycythemia vera (PV) or myelofibrosis (MF), were recruited between 2016 and 2018 from one single specialized hematologic center. Patients filled out a standardized questionnaire on medical history, current medication, alcohol and smoking habits and family medical history. They were examined by cardiac computed tomography (CT), Endothelial Peripheral Arterial Tone (EndoPAT), and a range of blood analyses. The atherosclerotic burden was evaluated by CACS. High sensitivity C-reactive protein (hs-CRP) and Neutrophil:Lymphocyt Ratio (NLR) were used as indicators of chronic inflammation. EndoPAT was applied to evaluate endothelial dysfunction, which is linked to development of atherosclerosis. The JAK2V617F-mutation is a common gene mutation in MPN-patients. It affects the gene coding the Janus kinase 2 (JAK2) protein, and can be detected by qPCR of peripheral blood or bone marrow. The JAK2V617F-mutation is a risk factor associated with both chronic inflammation and endothelial dysfunction. Multivariable logistic regression analyses were used to identify associations between potential risk factors and a higher CACS value.

Results
Among 170 included patients, 161 patients completed cardiac CT (mean age 65.5 (SD 10.5), 52% men). Baseline data is presented in Table 1. JAK2V617F-mutation was found in 137 (85%) patients, 53 patients (35%, n=152) had hs-CRP&gt;2.0 mg/L, 107 (67%, n=160) had NLR&gt;2.15 and 32 (21%, n=154) had an abnormal EndoPAT. Overall, 66 patients (41%) had a CACS&gt;100, with no significant difference between ET (41%), PV (42%) and MF (50%) (p=0.3). In patients with a history of ischemic heart disease (IHD), 92% had CACS&gt;100, compared to 37% in patients without prior IHD (p=0.0003).
Five independent factors associated with a CACS&gt;100 were identified; age (OR: 1.3 [95% CI 1.1–1.4]), male sex (OR: 15.2 [95% CI 4.0–57.7]), prior IHD (OR: 15.9 [95% CI 1.2–202.4]), smoking (OR: 3.3 [95% CI 1.1–10.1]), and abnormal EndoPAT (OR: 4.8 [95% CI 1.1–20.0]) (Figure 1). Hs-CRP, NLR and JAK2V617F-mutation status were not significantly associated with CACS &gt;100.

Conclusion
In this cohort of patients with MPNs, markers of chronic inflammation like hs-CRP and NLR were not associated with higher CACS, nor was the JAK2V617F-mutation. Traditional risk factors of cardiovascular disease seem to be sufficient to identify MPN patients with increased atherosclerotic burden, but measuring endothelial dysfunction provides additional information.

Funding Acknowledgement
Type of funding sources: Public Institution(s). Main funding source(s): Department of Cardiology, Zealand University Hospital, Region Zealand, Denmark Table 1. Baseline characteristicsFigure 1. Odds ratio for CACS &gt;100