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Novel Biomarkers in Coronary Artery Disease
Michael Mahmoudi MD, PhD, FACC University of Southampton, UK
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Disclosure Statement of Financial Interest
I, Michael Mahmoudi, have no relevant financial relationship with regards to this presentation
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Introduction CAD remains the most common cause of morbidity & mortality International guideline have recommended screening test Framingham QRISK®2 Identifies 60-65% of at risk individuals Many ”low-risk” patients sustain an adverse cardiac event
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Our Focus
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DECODE Study Patients with SA or NSTEMI undergoing PCI & Sex/Age Matched Controls 40 ml Blood pre-procedure for PBMC Preparation Target Vessel Optical Coherence Tomography PCI
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RT-PCR for DNA Damage Signaling Genes
PBMC DNA Repair Activity RT-PCR for DNA Damage Signaling Genes Proteomics
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Thin fibrous cap overlying lipid-rich atheroma (TCFA)
OCT Measurements Arc of calcification Arc of lipid Thin fibrous cap overlying lipid-rich atheroma (TCFA)
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DNA ligase activity in patients with NSTEMI, SA, and age and sex matched controls (ANOVA p=0.004)
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A B C D E DNA ligase activity exhibited a negative correlation with the lipid arc and cap thickness in both SA & NSTEMI
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Total White Cell Count Mean apparent ligase activity (U/gram protein) A SYNTAX Score Mean apparent ligase activity (U/gram protein) B There was no correlation between DNA ligase activity & the total white cell count or the SYNTAX score
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Summary of qRT-PCR SA vs. Control SA vs. NSTEMI NSTEMI vs. Control
ABL, GADD45A, MLH3, DDB1 OGG1, RAD50, CDK7, BRCA1, SUMO1 SA vs. NSTEMI DDB1, MLH3 NSTEMI vs. Control CDk7, OGG1
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Summary Patients with CAD exhibit alterations in DNA repair activity & genes implicated in the DNA Damage signaling pathway DNA repair activity may correlate with plaque anatomy Alterations in DNA damage and repair pathways may reflect plaque development and progression & may represent novel biomarkers for the detection of atherosclerotic CAD
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