1) The FAST-MI network in France characterized over 3,600 acute myocardial infarction patients between 2005-2010, collecting DNA samples, serum, and over 400 clinical variables to study the pathophysiology and pharmacogenetics of cardiovascular disease. 2) Analysis of the FAST-MI data identified genetic variants that influence drug absorption and metabolism, and found associations between serum levels of secretory phospholipase A2, its genetic variants, and cardiovascular outcomes after one year. 3) The FAST-MI network continues ongoing studies, has published numerous papers, and aims to further understanding of biomarkers and genetic influences on diabetes and cardiovascular drug response.

1. Contribution of the French clinical networks to the understanding of physiopathology and pharmacogenetics in cardiovascular diseases : The FAST-MI illustration June, 4th, 2010 T.SIMON, MD, PhD Professor of Clinical Pharmacology UPMC-Paris 06 University, Coordinator of the Clinical Research Unit URC-EST (APHP, Saint Antoine Hospital)

3. F rench registry of A cute coronary syndrome with or without ST elevation (FAST-MI 2005) N. Danchin HEGP, Paris V T. Simon St Antoine, Paris VI Supported by institutional and private grants : CNAM (French Caisse Nationale d’Assurance Maladie); Pfizer, Servier

5. Absorption : ABCB1 Metabolism: CYP2C19

6. Variations of secretory PLA2-IIa gene on sPLA2 activity and CV outcome at one year sPLA2 Genetic Variant Serum levels of sPLA2 activity Events (Death or MI) ? ? ?

7. Tertiles of sPLA2 activity and Death or MI Serum levels of sPLA2 activity Events (Death or MI) YES HR= 1 HR= 1.66 ;95%CI = 0.99-2.80 HR= 2.00 ; 95%CI =1.21-3.32

8. sPLA2 activity and PLA2 G2A haplotypes sPLA2 Genetic Variant Serum levels of sPLA2 activity YES

9. PLA2 G2A haplotypes and Death/MI at 1 year Patent Causal role of sPLA2 sPLA2 inhibitors (Phase II, Lancet, 2009 ) sPLA2 Genetic Variant sPLA2 activity Events (Death or MI)

10. Fast-MI 2005 : Ongoing studies Publications and Patents 2 patents 32 Abstracts (AHA, ESC) 10 papers (New Engl J Med 2009 Circ., 4 under review, 4 prep.) Biomarker studies UPMC-Paris 06, INSERM (U970, U 698 ) Paris V, Paris VII University University of California Pharmacogenetic ( Diabetes, CV drugs) UPMC-Paris 06, Paris XI University Harvard Medical School Genetic Biomarkers UPMC-Paris 06 Tuffts University (Boston) University College (London) Genetic Consortium (Netherlands) DNA Bank Phenotyping Serum Bank

11. FAST-MI 2010 starting in October 2010 N. Danchin HEGP, Paris V T. Simon St Antoine, Paris VI Supported by institutional and private grants : CNAM , CODDIM-Cardiovasculaire Ile de France , CeNGEPS, Dedicated Biobank Platforms of UPMC-Paris 06 Merck, Lilly, Sanofi-Aventis

12. French Society of Cardiology Pr Tabassome Simon Saint Antoine Hospital DOLORES (Chest Pain-SAMU ) 1 799 patients (6 centers) OFICA (CHF) 1 869 patients (170 centers) ODIN (HF) 2 560 patients (145 centers) ONACI (PCI ) 801 137 patients (101 centers) STIDEFIX ( Resynchronisation ) 59 211 patients (238 centers) Registries of the French Society of Cardiology Registry team : G.Mulak, B. Pace, E. Drouet, CRAs of URCEST, T. Simon, N. Danchin.