A recent European Journal of Haematology study suggests a significant association between severe coronary atherosclerosis and a variant allele frequency (VAF) in the upper quartile in patients with myeloproliferative neoplasms (MPNs).
The study highlighted that AK2V617F VAF might be an effective clinical tool in identifying patients with MPNs having an increased risk of atherosclerotic disease. Moreover, if such patients get prophylactic treatment in the initial phases, the risk of cardiovascular disease caused by atherosclerotic plaques might decrease considerably.
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“Our findings call for future studies on MPNs and aortic valve disease, investigating whether patients with MPNs might benefit from screening with either cardiac CT or echocardiography, to unmask early signs of aortic valve disease,” the authors noted.
The researchers investigated if a higher JAK2V617F VAF is associated with the presence of aortic valve calcification (AVC) and severe coronary atherosclerosis. The team recruited MPN patients from a haematological outpatient clinic in Eastern Denmark between 2016 and 2018. Eligible patients aged above 18 years and with a diagnosis of essential thrombocythaemia (ET), polycythemia vera (PV), or myelofibrosis (MF), were included in the study.
All patients were examined by cardiac computer tomography to confirm coronary artery calcium score (CACS) and AVC score. Moreover, the first VAF after the diagnosis was registered, and severe coronary atherosclerosis was defined with CACS score above 400 and AVC with an AVC score above 0. In addition, logistic regression analyses were employed to evaluate the associations between the JAK2V617F mutation and CACS >400 or AVC.
According to study results, 137 of the 161 patients who completed cardiac CT were found to be JAK2V617F mutation-positive, with a mean VAF of 26% (range 12%–52%). A CACS >400 was reported in 42 (26%) patients. Furthermore, it was observed that a VAF in the upper quartile range was associated with a CACS >400 (P =.0070) following adjustment for cardiovascular risk factors and MPN subtype. Besides, no association was found for the presence of AVC (P =.31).
Furthermore, an association between higher VAF and arterial thrombosis in JAK2V617F positive PV and ET patients have been reported; however, other studies have not found this association.
“We are the first to show that a higher VAF is associated with higher levels of calcified coronary plaques and severe coronary atherosclerosis in patients with MPNs, which might contribute to the increased risk of arterial thrombosis in these patients,” the authors concluded.
The novel Philadelphia-negative MPNs, including ET, MF, and PV, are reportedly caused by acquired mutations in the bone marrow, leading to a proliferation of 1 or more cell types of the myeloid cell linage. Prior studies have shown that patients with Philadelphia-negative MPNs have a higher cardiac calcification burden than the general population. However, it is still unknown whether the JAK2V617F mutation is related to increased cardiac calcification.
Reference
Solli CN, Chamat-Hedemand S, Elming H, et al. High JAK2V617F variant allele frequency is associated with coronary artery but not aortic valve calcifications in patients with Philadelphia-negative myeloproliferative neoplasms. Eur J Haematol. Published online June 7, 2023. doi:10.1111/ejh.14019. Epub ahead of print. PMID: 37286366.
