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

Abstract

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.

Revisiting Circulating Extracellular Matrix Fragments as Disease Markers in Myelofibrosis and Related Neoplasms

“…MPNs are associated with an evolving chronic inflammatory state, concurrent immunoderegulation and fibrosis [20][21][22][23][24][25][26][27][28], which are often associated with gradually emerging chronic inflammation-related comorbidities [16][17][18]20,21,23,[29][30][31][32][33][34][35]. Within the last decade, novel sensitive and reproducible assay technologies for quantification of circulating ECM metabolites have been introduced for early detection and follow-up in fibrosing conditions, e.g., myelofibrosis and allied conditions including cancer-related desmoplasia.…”

“…Third, MPNs are associated with increased cardiovascular disease burden, including hypertension, risk of stroke and myocardial infarction, ischemic heart failure, and aneurysms [11][12][13][14][15][16][17][18][19][20][21]23]. Patients with MPNs likely develop atherosclerosis earlier due to a chronic systemic inflammatory response similar to premature atherosclerosis development in other inflammatory diseases, such as type II diabetes mellitus, rheumatoid arthritis, psoriasis, and inflammatory bowel diseases, Crohns' disease and ulcerative colitis [20,21,23].…”

“…Individuals harboring CHIP have an approximately 10-fold increased risk of developing hematologic cancer, including MPNs [10]. Furthermore, similar to patients with MPNs [11][12][13][14][15][16][17], individuals with CHIP have an increased risk of cardiovascular diseases, including coronary artery disease and stroke [18,19].…”

“…Indeed, it has been proposed that MPNs are "A Human Inflammation Model" and "A Human Inflammation Model of Cancer Development" [20][21][22][23]. In this regard, chronic inflammation may also trigger and drive the development of accelerated (premature) atherosclerosis in MPNs, as evidenced by a heavy burden of coronary artery and aortic valve calcifications [16,17] and the well-established increased risk of second cancers in MPNs [20,21,23,[29][30][31][32][33][34]. The importance of immune deregulation [35,36] with increasing T-cell exhaustion and tumor immune evasion consequent to defective tumor immune surveillance has been repeatedly underscored as one of the major mechanisms, contributing not only to MPN development and disease progression but also to the development of second cancers and their poorer survival as compared to the same cancers in the background population [30,31,34].…”

Prediction of acute coronary syndrome in patients with myeloproliferative neoplasms

“…According to the meticulous records maintained by the Norwegian Cancer Registry, the annual incidence of PV, ET, and PMF per 100,000 population significantly increased from 1995 to 1997 to 2010-2012 (from 0.4, 0.3, and 0.2 to 0.7, 1.0, and 0.5 per 100,000, respectively) (2). It can be seen that the incidence of MPN is increasing, which seriously endangers health.…”