1. www.tri-london.ac.uk The GARFIELD Registry is funded by an unrestricted research grant from Bayer Pharma AG Lessons Beyond Atrial Fibrillation: Focus on Obesity Samuel Z. Goldhaber, MD Director, Thrombosis Research Group Cardiovascular Division Brigham and Women’s Hospital Professor of Medicine Harvard Medical School

2. Disclosures Research Support: BMS; BTG; Daiichi; NHLBI; Thrombosis Research Institute Consultant: Ariad; Bayer; Boehringer-Ingelheim; BMS; Daiichi; Janssen, Merck; Pfizer; Portola

3. Stroke Prevention in AF – Obesity, a Risk Factor beyond CHA 2 DS 2 -VASc – Obesity’s global burden of disease Diet and exercise can reduce AF symptoms and severity (as well as waist circumference and BMI) Stroke, venous thromboembolism, and MI share common risk factors, such as obesity GARFIELD-AF: will improve our understanding of obesity-AF connection Learning Objectives

4. History/Neuro Exam 76 y.o. man with hypertension, hyperlipidemia, obesity awakens with garbled speech, nonsense words, confusion. Wife summons Emergency Services. BP 185/82 mm Hg; HR 129 irreg irreg; 1.7 meters; 117 kg; BMI=38 kg/m 2 Unable to name months, a pen, a watch, or follow command to show thumb

6. M2 BRANCH OF MCA: NORMAL

7. M2 BRANCH OF MCA: CUT OFF

8. Global Burden of Obesity 3.4 million deaths per year Accounts for 4% of years of life lost Physical inactivity and carbohydrate-heavy eating patterns are considered causal The rise in obesity rates is soaring in economically developing countries and is slowing down in developed countries Prevalence is increasing in children, as well as adults Ng M, et al. Lancet. 2014; epubl May 29. doi:10.1016/S0140-6736(14)60560-8.

9. Overweight and Obesity 1980 2000 1990 2013 38% Ng M, et al. Lancet. 2014; epubl May 29. doi:10.1016/S0140-6736(14)60560-8.

10. Obesity Pharmacotherapy DRUGMECHANISMCV EFFECTS WEIGHT LOSS (%) Locaserin (Belviq ® ) 5 HT2C agonist ? Valvulopathy3.6% QSymia ® GABA modulation BP, HR elevations 8.6% Orlistat (Xenical ® ) Pancreas, gastric lipase inhibitor None2.9% to 3.4% Apovian CM, et al. Circulation. 2012;125:1178-1182.

11. Diet/Exercise: Waist Circumference and BMI (Abed HS. JAMA 2013; 310: 2050- 2060) Abed HS, et al. JAMA. 2013;310:2050-2060.

12. Diet/Exercise: AF Symptoms and Severity Abed HS, et al. JAMA. 2013;310:2050-2060.

13. Magnani JW, et al. Circulation. 2013;128:401-405.

14. Obesity Atrial Fibrillation MI Diabetes Hypertension OSA

15. COMMON PATHOPHYSIOLOGY: VTE AND ATHEROSCLEROSIS (Piazza, Goldhaber. Circulation 2010;121: 2146)

16. Common Risk Factors and Common Pathophysiology “Lump, Don’t Split” Stroke PE + DVT Myocardial Infarction Stroke Myocardial Infarction PE + DVT

17. GARFIELD-AF (N=22,261) - Obesity BMI>30

18. Take Home Messages 1.Obesity is a risk factor for developing AF, as well as VTE and MI. 2.Obesity may be a risk factor for stroke in patients with established AF. 3.AF patients should embrace a heart-healthy life style: achieve a BMI < 25 to decrease AF symptom burden and severity. 4.GARFIELD-AF will enlighten obesity-stroke relationship in AF: large sample size, adequate power, pertinent CRF.