A high variant allele frequency (VAF) of the JAK2V617F gene is associated with severe coronary artery calcification (CAC) in patients with myeloproliferative neoplasms (MPNs), including myelofibrosis (MF), according to a study published in the European Journal of Haematology.
Of the patients in the study who were JAK2V617F mutation-positive, those who had a VAF in the upper quartile (52%-97%) had a significant association with severe coronary atherosclerosis, defined as a CAC score (CACS) > 400, compared to patients who were JAK2V617F mutation-negative (odds ratio 15.95; P =0.0070).
Read more about MF genetics
These results were based on VAF percentages recorded at the time of diagnosis. Follow-up VAF percentages taken at study enrollment found that both the third and fourth quartiles were significantly associated with a CACS >400 (P =0.022 and P =0.019, respectively).
Subgroup analyses based on type of MPN found that the results were consistent for MF patients with those having an initial JAK2V617F VAF in the fourth quartile having a significant association with a CACS > 400 (odds ratio 19.20; P =0.0013).
“JAK2V617F variant allele frequency might be a useful clinical tool in selecting patients with MPNs with increased risk of atherosclerotic disease, and if these patients get prophylactic treatment earlier, their risk of cardiovascular disease caused by atherosclerotic plaques might decrease,” the authors wrote.
In contrast to the CAC finding, no significant association was observed between VAF quartiles and aortic valve calcification (AVC; all P >0.05).
A total of 161 patients with either essential thrombocythemia, polycythemia vera, or MF underwent complete cardiac CT. The JAK2V617F mutation was found in 137 patients (85%) while the MPL mutation was found in 2 patients, and the CALR mutation was found in 17 patients. A total of 42 patients had a CACS > 400 and 93 patients had AVC.
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
