The Obesity Paradox:
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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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E mily 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

Emily O’Brien, Emil Fosbol, Andrew Peng, Karen Alexander, Matthew Roe, Eric Peterson


Disclosures

Disclosures

  • None


Obesity in the united states

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.


E mily o brien emil fosbol andrew peng karen alexander matthew roe eric peterson

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

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

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

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

    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

      • >=40Obese class III

    6World Health Organ Tech Rep Ser. 2000;894:i-xii, 1-253.


    Objective ii

    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

    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

    Obesity in CRUSADE

    28%

    Obese


    Patient characteristics

    Patient Characteristics (%)


    Cumulative incidence mortality

    Cumulative Incidence - Mortality


    Results

    Results

    All-Cause Mortality


    Metabolically unhealthy

    Metabolically Unhealthy

    %

    BMI Category (kg/m2)


    Sensitivity analysis

    Sensitivity Analysis

    All-Cause Mortality

    Metabolically Healthy Patients


    Sensitivity analysis1

    Sensitivity Analysis

    All-Cause Mortality

    Metabolically Unhealthy Patients


    Potential explanations

    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

    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

    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


    Thank you

    Thank You!


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