High JAK2V617F allele burden is associated with an increased burden of coronary artery calcification in MPNs

Abstract

Abstract Background Patients with the haematological cancers Philadelphia-negative Myeloproliferative Neoplasms (MPNs), have an increased risk of coronary artery and aortic valve calcification, and an increased risk of myocardial infarctions. The most common acquired mutation in MPNs, the JAK2V617F mutation, has been linked to increased risk of thrombosis. Aims To exam the association between the JAK2V617F mutation, its allele burden, and coronary artery and aortic valve calcification. Methods One hundred and sixty one patients with MPN disease from one specialized haematological outpatient clinic where included. Information on demographics, smoking, alcohol habits and co-morbidities were registered. Blood samples were drawn for determination of the JAK2V617 mutation and allele burden. Patients were examined by cardiac computer tomography in order to determine their coronary artery calcium score (CACS) and aortic valve calcification (AVC) score. The association between the JAK2V617F mutation, its allele burden and coronary artery and aortic calcification was investigated with univariate and multivariate logistic regression analysis, adjusting for age, sex, ischemic heart disease (IHD), stroke, smoking, obesity, hypertension, hypercholesterolemia, diabetes mellitus, and family history of IHD or stroke in the multivariate analysis. Results Of the 161 patients (52% male, mean age 65.5±10.5 years), 137 (85%) were JAK2V617F positives, and the JAK2V617F allele burden was quantified in 120. The median JAK2V617F allele burden was 12% (IQR range 6–33%). There were 42 (26%) patients with a CACS >400, and 93 (58%) patients AVC. Among the JAK2V617F positive patients, 38 (24%) had a CACS >400 and 81 (59%) had AVC. In the 32 patients with a JAK2V617F allele burden>33%, 19 (59%) had a CACS >400 and 26 (81%) had AVC. In the univariate logistic regression analysis the presence of JAK2V617F mutation was not associated with a CACS >400 (Odds Ratio (OR) 1.92, 95% confidence interval (CI) 0.62–5.98, p=0.26). Similar result was found for the analysis on AVC (OR 1.45, 95% CI 0.61–3.45, p=0.41). In contrast, a JAK2V617F allele burden >33% was significantly associated with a CACS >400 (OR 5.31, 95% CI 2.23–12.66, p=0.0002), and similarly with AVC (OR 4.14, 95% CI 1.55–11.05, p=0.0045). In the multivariate adjusted analysis, a JAK2V617F allele burden >33% was significantly associated with a CACS >400 (OR 2.08, 95% CI 0.43–10.10, p=0.36), but not with AVC (OR 0.90, 95% CI 0.27–3.03, p=0.86). In the adjusted analysis the association between a JAK2V617F allele burden >33% and CACS >400 was significant (OR3.86, 95% CI 1.14–13.09, p=0.031), but the analysis on AVC was not (OR 1.59, 95% CI 0.42–6.04, p=0.50). Conclusion There is a significant association between a JAK2V617F allele burden >33% and the burden of coronary calcification in MPNs, measured as a CACS >400. The association remains significant after adjustment for cardiovascular risk factors. Funding Acknowledgement Type of funding sources: Private grant(s) and/or Sponsorship. Main funding source(s): Region Sjællands Sundhedsvidenskabelige ForskningsfondTømrermester Jørgen Holm og hustru Elisa F. Hansens Mindelegat