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The Obesity Paradox: T he Importance for Long-term Outcomes in Non-ST-Elevation Myocardial Infarction – The CRUSADE Experience. E mily O’Brien, Emil Fosbol, Andrew Peng, Karen Alexander, Matthew Roe, Eric Peterson. Disclosures. None. Obesity in the United States.
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The Obesity Paradox: The Importance for Long-term Outcomes in Non-ST-Elevation Myocardial Infarction – The CRUSADE Experience Emily O’Brien, Emil Fosbol, Andrew Peng, Karen Alexander, Matthew Roe, Eric Peterson
Disclosures • 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.
The Paradox 2.0 4.0 HR (95% CI) 1.0 RR (95% CI) 26.5-28 25-26.5 23.5-25 21-23.5 0.25 28-30.0 >30.0 <18.5 18.5-21 BMI 25.0-29.9 18.5-24.9 <18.5 >=30 BMI Int Jour of Obes.2002; 26, 1046-1053. Eur Heart J. 2013 ;34(5):345-53.
The Obesity Paradox • First used to describe counterintuitive survival advantages in 19991 • Reported for diabetes2, heart failure3, chronic kidney disease4, and CAD5 • What is still unclear: • Whether the paradox exists among older, NSTEMI patients • Persistence of effects over long periods of followup • Differential mortality associations by metabolic status 1Kidney Int. 1999;55(4):1560-1567. 2JAMA. 2012;308(6):581-590. 3Am J Cardiol. 2003;91(7):891-894 4Am J ClinNutr. 2005;81(3):543-554 5Am J Med. Oct 2007;120(10):863-870
Objectives • 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 • To determine whether BMI associations differ by “metabolically healthy” status
Methods • Data Sources • CRUSADE linked to CMS data (2001-2006) • National NSTEMI Quality Improvement Initiative • 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) • Final Sample: N=34,465
Body Mass Index (BMI) • Calculated from weight and height on admission • WHO categories(kg/m2)6 • <18.5 Underweight • 18.5-24.9 Normal Weight • 25-29.9 Overweight • 30-34.9 Obese class I • 35-39.9 Obese class II • >=40 Obese class III 6World Health Organ Tech Rep Ser. 2000;894:i-xii, 1-253.
Objective II • Metabolically healthy or “benign” obese • Preserved insulin sensitivity • Lower visceral fat accumulation • Metabolically Unhealthy7 • 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) 7Eur Heart J. 2013;34(5):389-397
Statistical Analysis • Cox proportional hazards modeling with censoring on death • All-cause mortality over 3-years • CRUSADE long-term mortality model8 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 8Am Heart J. 2011;162(5):875-883.
Obesity in CRUSADE 28% Obese
Results All-Cause Mortality
Metabolically Unhealthy % BMI Category (kg/m2)
Sensitivity Analysis All-Cause Mortality Metabolically Healthy Patients
Sensitivity Analysis All-Cause Mortality Metabolically Unhealthy Patients
Potential Explanations • Selection bias: “healthiest” patients survive long enough to develop MI • Obese patients with more severe events may have greater metabolic reserve and increased resistance to catabolic burden • Cachexia abnormal cytokine & neurohormonallevels, mortality • BMI categories may have heterogeneous groups
Limitations • No followup after 3 years • “Metabolically Healthy” classification couldn’t be made in 1/3 of patients because HDL & triglycerides were not measured • No information on cause of death, which may be important to obesity paradox
Conclusions & Future Directions • The obesity paradox persists over the long term for NSTEMI • Similar associations between BMI and all-cause mortality for metabolically healthy patients • Further studies on metabolism and BMI are needed