This study evaluates the relationship between myelodysplastic syndromes (MDS) and cardiovascular disease. MDS patients will be evaluated for the presence of mutations and whether they are associated with an increased risk of heart disease (CVD) and inflammation compared to healthy adults. Patients without symptoms of CVD will receive CT scans to assess for hidden disease and if that is related to their mutations.
Myelodysplastic syndromes (MDS) are a type of blood cancer that can cause infection or bleeding because they prevent the formation of blood components and may lead to leukemia and death. MDS can arise from changes (or mutations) to a patient's DNA. MDS patients have increased risk of heart disease compared to healthy adults. The investigators will look for links between mutations in MDS patients and increased risk of heart disease. They will also use "CT imaging" to see if MDS patients have asymptomatic artery disease but may lead to heart disease in the future and if that is related to their mutations. The researcher will try to link mutations in MDS patients to markers of inflammation and to the amount of artery disease on CT imaging to look for patterns. The goal is to find certain mutations that are associated with inflammation and heart disease. This may ultimately allow hematologists to test MDS patients with these mutations for heart disease and/or treat them early so they have a better and longer life.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
SCREENING
Masking
NONE
Enrollment
400
DNA sequencing for mutations to be obtained by bloodwork within 6 months of diagnosis, or by accessing diagnostic bone marrow aspirate slides.
Bloodwork to be done for lipid profile, c-reactive protein (CRP), and multiplex chemokine/cytokine analysis.
Sunnybrook Patients with no history of cardiovascular disease \[ex: past/present coronary artery disease (CAD), peripheral vascular disease (PVD), angina, myocardial infarction (MI), stroke, transient ischemic attack (TIA), or stents\], not pregnant, and able to undergo CT will receive a CT of the heart to look for and quantify any occult coronary artery disease.
Sunnybrook Health Sciences Centre
Toronto, Ontario, Canada
Measure the allelic frequency and type of myeloid cancer-associated mutations in MDS patients diagnostic bone marrow aspirates or slides
Screen for Presence of myeloid-cancer associated mutations and their variant allele frequencies (VAF) at diagnosis of MDS as measured through next generation sequencing of 40 myeloid genes.
Time frame: 2 years
Screen for occult and potentially clinically significant CAD in MDS patients by means of coronary CT
Patients at Sunnybrook hospital with no pre-existing history of CAD who receive CT of the heart and found to harbour occult CAD by means of coronary calcium scoring: 1. zero calcium (No CAD) 2. 1-400: mild-moderate calcification 3. \>400: severe calcification
Time frame: 2 years
Identify any correlation between selected myeloid mutations and/or their VAF with the presence of pre-existing incident or occult CAD
Comparing the presence of myeloid-cancer associated mutations and their variant allele frequencies (VAF) at diagnosis of MDS as measured through next generation sequencing of 40 myeloid genes between patients with pre-existing/occult CAD and those without.
Time frame: 2 years
Track how often newly discovered CAD from coronary CT leads to further intervention or changes in monitoring
The investigators will track any interventions in patients without a prior history of CAD who who are discovered to have occult CAD by coronary CT. This includes number of patients who were recommended: 1. medical management of CAD 2. Referral to clinical cardiologist 3. Invasive angiography
Time frame: 2 years
Screen for serum inflammatory cytokines in the blood of patients with incident or occult CAD
Measure TNFa, IL-1beta, IL-6 and an array of other inflammatory cytokines (to be determined) in the peripheral blood upon enrollment
Time frame: 2 years
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