1. Novel Biomarkers in Coronary Artery Disease
Michael Mahmoudi MD, PhD, FACC
University of Southampton, UK

2. Disclosure Statement of Financial Interest
I, Michael Mahmoudi, have no relevant financial relationship with regards to this presentation

3. 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

5. Our Focus

6. 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

8. RT-PCR for DNA Damage Signaling Genes
PBMC
DNA Repair Activity
RT-PCR for DNA Damage Signaling Genes
Proteomics

9. Thin fibrous cap overlying lipid-rich atheroma (TCFA)
OCT Measurements
Arc of calcification
Arc of lipid
Thin fibrous cap overlying lipid-rich atheroma (TCFA)

10. DNA ligase activity in patients with NSTEMI, SA, and age and sex matched controls (ANOVA p=0.004)

11. A B C D E
DNA ligase activity exhibited a negative correlation with the lipid arc and cap thickness in both SA & NSTEMI

12. 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

14. 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

15. 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