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

Disclosures n None

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.

RR (95% CI) < >=30 BMI Eur Heart J ;34(5): <18.5 HR (95% CI) BMI >30.0 Int Jour of Obes. 2002; 26, The Paradox 2.0

The Obesity Paradox n First used to describe counterintuitive survival advantages in 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): JAMA. 2012;308(6): Am J Cardiol. 2003;91(7): Am J Clin Nutr. 2005;81(3): Am J Med. Oct 2007;120(10):

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

Methods n Data Sources l CRUSADE linked to CMS data ( ) 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

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

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):

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):

28% Obese Obesity in CRUSADE

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) Male Sex White Race Medical history Hypertension Diabetes Dyslipidemia Current/Recent Smoker All-Cause Mortality Unadjusted 3-year Mortality

Cumulative Incidence - Mortality

Results All-Cause Mortality

Metabolically Unhealthy % BMI Category (kg/m 2 )

Sensitivity Analysis All-Cause Mortality Metabolically Healthy Patients

Sensitivity Analysis All-Cause Mortality Metabolically Unhealthy Patients

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

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

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

Thank You!