High JAK2V617F variant allele frequency is associated with coronary artery but not aortic valve calcifications in patients with Philadelphia-negative myeloproliferative neoplasms.

BACKGROUND: Patients with Philadelphia-negative myeloproliferative neoplasms (MPNs) have a higher burden of cardiac calcifications compared to the general population. It is not known whether the JAK2V617F mutation is associated with increased cardiac calcification. AIM: To investigate if a higher JAK2V617F variant allele frequency (VAF) is associated with severe coronary atherosclerosis and the presence of aortic valve calcification (AVC). METHODS: Patients with MPNs were examined by cardiac computer tomography to establish coronary artery calcium score (CACS) and AVC score. The first VAF after diagnosis was registered. Severe coronary atherosclerosis was defined as a CACS >400 and AVC was defined as an AVC score >0. RESULTS: Among 161 patients, 137 were JAK2V617F mutation-positive, with a median VAF of 26% (interquartile range 12%-52%). A VAF in the upper quartile range was associated with a CACS >400 [odds ratio (OR) 15.96, 95% confidence interval [CI] 2.13-119.53, p = .0070], after adjustment for cardiovascular risk factors and MPN subtype. An association was not found for the presence of AVC (OR 2.30, 95% CI 0.47-11.33, p = 0.31). CONCLUSION: In patients with MPNs, there is a significant association between having a VAF in the upper quartile (>52%), and severe coronary atherosclerosis, defined as a CACS >400. The presence of AVC is not associated with VAF.

Coronary artery- and aortic valve calcifications in patients with Philadelphia-negative myeloproliferative neoplasms.

BACKGROUND: Patients with the hematological cancers Philadelphia-negative Myeloproliferative Neoplasms (MPNs) have an increased risk of cardiovascular disease. However, whether MPNs have an increased burden of cardiac calcification has not been thoroughly investigated. Our aim is to investigate whether patients with MPNs have an increased burden of cardiac calcification that could help explain their increased risk of cardiovascular disease. METHODS AND RESULTS: We recruited 161 patients (mean age 65 years, 52% men) with an MPN diagnosis between 2016 and 2018. Coronary artery calcium score (CACS) and aortic valve calcification (AVC) were measured by cardiac computer tomography, and detailed information on cardiovascular risk factors was recorded. MPNs were matched on age and sex, with 805 controls from the Copenhagen General Population Study. A CACS>400 was present in 26% of MPNs and 19% of controls (p = 0.031). AVC was present in 58% of MPNs and 34% of controls (p < 0.0001). After adjustment for cardiovascular risk factors, the odds ratio (OR) of a CACS>400 was 1.9 (95% CI 1.2-3.1, p = 0.008) in MPNs compared to controls, and the OR of AVC was 4.4 (95% CI 2.9-6.9, p < 0.0001) in MPNs compared to controls. CONCLUSION: Patients with MPNs have a significantly higher prevalence of a CACS >400 and AVC, compared to controls from the general population. The association between MPN and a CACS>400 or AVC remains significant after adjustment for cardiovascular risk factors. These novel data support the hypothesis that MPNs have an increased burden of cardiac calcifications, independent of other cardiovascular risk factors.