1. Dynamic Risk Stratification in ACS
Mark Y. Chan
Associate Professor
Yong-Loo Lin School of Medicine
Senior Consultant
National University Heart Centre, Singapore

2. Question 1: Does a change in biomarker levels over time confer a change in prognosis in patients with ACS?

3. Initial NT-proBNP and hs-CRP
Re-assess NT-proBNP and hs-CRP
6 month-baseline
NT-proBNP
NT-proBNP
NT-proBNP
Mortality risk
6 month-baseline
hs-CRP
hs-CRP
MI risk
hs-CRP
Hospitalization for NSTEACS
Escalate or modify management?
Re-measure
NT-proBNP and hs-CRP?
Initial treatment
Baseline
6 months
30 months

4. TRILOGY-ACS Biomarker Substudy
Presented at AHA 2014

5. Changes in NT-proBNP and hs-CRP (delta) from baseline to 6 months

6. Adjusted hazard ratio of delta NT-proBNP

7. Adjusted hazard ratio of delta hs-CRP for CV events

8. Quantitative changes in risk associated with changes in biomarker levels

9. Question 2: For expensive prognostic biomarkers like miRNA, what is the best timepoint to measure them

10. miRNAs measured at baseline and 30 days
Presented at AHA 2016

12. Differential prediction of MI and CV death risk by miRs measured at baseline and 30 days

13. Conclusions
An increase/decrease of NT-proBNP over time is quantitatively associated with an increase/decrease in risk of CV death
An increase/decrease of hs-CRP over time is quantitatively associated with an increased/decrease in MI risk.
miRs measured at 30-day are far greater prognostic value for recurrent ischemic events than miRs measured at baseline

14. Prognostic biomarker studies must not only study the association between measurements at individual timepoints and events, they must also investigate the delta between timepoints
For multi-marker platforms, different markers may have differential prognostic value at different phases in the longitudinal evolution of the disease

15. Duke Molecular Physiology Lab
Acknowledgements
Duke Molecular Physiology Lab
Svati Shah, Lydia Kwee, Libby Grass
Duke Clinical Research Institute
Matthew Roe, Megan Neely