1. Evaluation of cardiac disorders and systemic hypertension in JAK2 V617F positive patients
Siddharth Sheth, Abuzar Moradi Tuchayi, Roy E Smith
Department of Internal Medicine and Division of Hematology-Oncology
University of Pittsburgh, Pittsburgh, PA
Study Objectives
1. Identify which cardiac disorders are most prevalent in individuals with JAK2 V617F mutation
2. Compare arterial and venous thrombosis rates between individuals with and without the JAK2 V617F mutation
Results
Baseline demographics
Median age: 65 (range 23-97)
47% male, 53% female
90% Caucasian, 8% African American, 2% Other
In JAK2 positive and JAK2 negative pts, respectively:
PCV: 20/50 vs. 4/50
ET: 19/50 vs. 3/50
MF: 10/50 vs. 5/50
Unknown/Unclassifiable: 6/50 vs. 1/50
Significantly higher rates of HTN, CAD, and Afib in individuals with JAK2 (+) mutation (Figure 1)
Higher rates of stroke in JAK2 + mutation (Figure 2)
21x36 for 42x72 (i.e. 3.5x6); Font sizes: Title 68->136; Subtitle 48->96; Headings 36->72; Text 28->56; FXPrints/Huey Reprographics
Background
Myeloproliferative neoplasms (MPN) are characterized by polycythemia vera (PCV), essential thrombocythemia (ET), and primary myelofibrosis (MF)
The JAK2 V617F (JAK2) mutation is an acquired somatic mutation common in patients with MPNs
MPN represent a significant risk for arterial and venous thrombosis
Most common cause of death
JAK2 positivity is an independent risk fact thrombosis
Cardiovascular disorders and JAK2 mutation are known independent risk factors for thrombosis in MPN
Studies in JAK2 transgenic mice found an association of cardiac hypertrophy and MPN
There is limited clinical data regarding which cardiovascular risk factors are associated with JAK2 in humans
Figure 1: Rates of Cardiovascular Disorders in JAK2 (+) vs. JAK2 (-) Patients
Discussion
We report an association between systemic hypertension, Afib, Stroke, and CAD in patients who are JAK2 positive
Our data verified previous findings of increased thrombotic risk in JAK 2 patients
CV risk factors and previous thrombosis are the most important for development of thrombosis during the course of ET.
Study limitations:
We were unable to determine causal relationship
We could not control for the independent effect of MPN on cardiovascular disorders
Additional research in a larger study size controlling for MPN is needed to determine the significant of these relationships
*p= 0.028*
*P=0.006*
*P=0.008*
P=0.646
P=0.079
Methods
We retrospectively reviewed 300 patients using the UPCI Cancer Registry and Medical Archival Systems (MARS) between
100 patients were included: 50 JAK2 (+) and 50 JAK2 (-)
Detection of JAK2 mutation was based on Quantitative PCR
Cardiac disorders were characterized as:
Coronary artery disease (CAD), atrial fibrillation (Afib), heart failure (HF), myocardial infarction (MI)
Thrombotic events were characterized as:
Stroke, peripheral vascular disease (PVD), deep vein thrombosis (DVT), and pulmonary embolism (PE)
Statistical analyses were calculated using pearson chi square test
Two tailed p-value <0.05 was considered statistically significant
Figure 2: Rates of Thrombotic Events in JAK2 (+) vs. JAK2 (-) Patients
p=0.102
*p=0.001*
P=0.14
References
Kralovics R, Passamonti F, Buser AS. A gain of function mutation of JAK2 in myeloproliferative disorders. N Engl J Med. 2005; 352:
Steensma DP , Richard RE. Myeloproliferative disorders. American Society of Hematology self-Assessment Program: American Society of Hematology; 2007:
P=0.695