1. Emily O’Brien, Emil Fosbol, Andrew Peng, Karen Alexander, Matthew Roe, Eric Peterson The Obesity Paradox: The Importance for Long-term Outcomes in Non-ST-Elevation Myocardial Infarction – The CRUSADE Experience

2. Disclosures n None

3. Obesity in the United States CDC. Behavioral Risk Factor Surveillance System: 2010 survey data. Atlanta, GA: US Department of Health and Human Services, CDC; 2011.

4. RR (95% CI) 18.5- 24.9 <18.5 25.0- 29.9 >=30 BMI Eur Heart J. 2013 ;34(5):345-53. 21- 23.5 18.5- 21 <18.5 HR (95% CI) 4.0 1.0 0.25 BMI 26.5- 28 23.5- 25 25- 26.5 28- 30.0 >30.0 Int Jour of Obes. 2002; 26, 1046-1053. The Paradox 2.0

5. The Obesity Paradox n First used to describe counterintuitive survival advantages in 1999 1 n Reported for diabetes 2, heart failure 3, chronic kidney disease 4, and CAD 5 n What is still unclear: l Whether the paradox exists among older, NSTEMI patients l Persistence of effects over long periods of followup l Differential mortality associations by metabolic status 1 Kidney Int. 1999;55(4):1560-1567. 2 JAMA. 2012;308(6):581-590. 3 Am J Cardiol. 2003;91(7):891-894 4 Am J Clin Nutr. 2005;81(3):543-554 5 Am J Med. Oct 2007;120(10):863-870

6. Objectives n To determine the association between body mass index (BMI) and risk of all- cause mortality over three years in a population of elderly NSTEMI patients n To determine whether BMI associations differ by “metabolically healthy” status

7. Methods n Data Sources l CRUSADE linked to CMS data (2001-2006) l National NSTEMI Quality Improvement Initiative l Exclusions »Patients transferred out (N=4474) »Patients missing information on height and/or weight (N=2300) »Non-index admissions for patients with multiple records (N=1329) »Died during hospitalization (N=2623) l Final Sample: N=34,465

8. Body Mass Index (BMI) n Calculated from weight and height on admission n WHO categories(kg/m 2 ) 6 l <18.5 Underweight l 18.5-24.9 Normal Weight l 25-29.9 Overweight l 30-34.9 Obese class I l 35-39.9 Obese class II l >=40Obese class III 6 World Health Organ Tech Rep Ser. 2000;894:i-xii, 1-253.

9. Objective II  Metabolically Unhealthy 7 Two or more of the following: 1. High blood pressure (>130/85 mmHG) or hypertension 2. Diabetes mellitus 3. High triglycerides (>150 mg/dl) 4. Low HDL (<40 mg/DL in men, <50 mg/DL in women)  Metabolically healthy or “benign” obese Preserved insulin sensitivity Lower visceral fat accumulation 7 Eur Heart J. 2013;34(5):389-397

10. Statistical Analysis n Cox proportional hazards modeling with censoring on death n All-cause mortality over 3-years n CRUSADE long-term mortality model 8 Age Gender Race Family Hx of CAD Smoking status Prior MI Prior CABG Prior PCI Prior CHF Prior stroke Heart rate HF at presentation ECG findings Initial HCT Initial troponin 8 Am Heart J. 2011;162(5):875-883.

11. 28% Obese Obesity in CRUSADE

12. Patient Characteristics (%) Obesity Class * Under Weight (N=1236) Normal Weight (N=11186) Over- Weight (N=12506) Obese I (N=6089) Obese II (N=2226) Obese III (N=1222) Demographics Age in years (median)82.080.077.075.073.072.0 Male Sex30.749.359.454.746.135.5 White Race83.886.7 86.586.384.4 Medical history Hypertension71.173.576.281.284.686.2 Diabetes16.925.434.344.855.761.1 Dyslipidemia33.946.554.659.360.758.9 Current/Recent Smoker19.714.312.510.610.19.9 All-Cause Mortality Unadjusted 3-year Mortality62.445.631.828.029.532.8

13. Cumulative Incidence - Mortality

14. Results All-Cause Mortality

15. Metabolically Unhealthy % BMI Category (kg/m 2 )

16. Sensitivity Analysis All-Cause Mortality Metabolically Healthy Patients

17. Sensitivity Analysis All-Cause Mortality Metabolically Unhealthy Patients

18. Potential Explanations n Selection bias: “healthiest” patients survive long enough to develop MI n Obese patients with more severe events may have greater metabolic reserve and increased resistance to catabolic burden n Cachexia  abnormal cytokine & neurohormonal levels, mortality n BMI categories may have heterogeneous groups

19. Limitations n No followup after 3 years n “Metabolically Healthy” classification couldn’t be made in 1/3 of patients because HDL & triglycerides were not measured n No information on cause of death, which may be important to obesity paradox

20. Conclusions & Future Directions n The obesity paradox persists over the long term for NSTEMI n Similar associations between BMI and all-cause mortality for metabolically healthy patients n Further studies on metabolism and BMI are needed

21. Thank You!