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

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.

0.5

BMI and Incident MIIn Individuals without Prior

MI

RR

(95

% C

I)

18.5-24.9

<18.5 25.0-29.9

>=30

BMI

Eur Heart J. 2013 ;34(5):345-53.

21-23.5

BMI and Mortality Among STEMI Patients

18.5-21

<18.5

HR

(95

% C

I)

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

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):891-8944Am J Clin Nutr. 2005;81(3):543-5545Am 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 Unhealthy7

• Two or more of the following:

1. High blood pressure (>130/85 mmHG) or hypertension2. 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

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

AgeGender RaceFamily Hx of CADSmoking status

Prior MIPrior CABGPrior PCIPrior CHFPrior strokeHeart rate

HF at presentationECG findingsInitial HCT Initial troponin

8Am Heart J. 2011;162(5):875-883.

28%Obese

Obesity in CRUSADE

4%

32%

36%

18%

6%

4%

Underweight

Normal Weight

Overweight

Obese Class I

Obese Class II

Obese Class III

Patient Characteristics (%)

  Obesity Class*

 UnderWeight

(N=1236)

NormalWeight

(N=11186)

Over-Weight

(N=12506)

Obese I(N=6089)

Obese II(N=2226)

Obese III(N=1222)

Demographics            

Age in years (median) 82.0 80.0 77.0 75.0 73.0 72.0

Male Sex 30.7 49.3 59.4 54.7 46.1 35.5

White Race 83.8 86.7 86.7 86.5 86.3 84.4

Medical history            

Hypertension 71.1 73.5 76.2 81.2 84.6 86.2

Diabetes 16.9 25.4 34.3 44.8 55.7 61.1

Dyslipidemia 33.9 46.5 54.6 59.3 60.7 58.9

Current/Recent Smoker 19.7 14.3 12.5 10.6 10.1 9.9

All-Cause Mortality

Unadjusted 3-year Mortality 62.4 45.6 31.8 28.0 29.5 32.8

Cumulative Incidence - Mortality

Results

All-Cause Mortality

Metabolically Unhealthy

Overall <18.5 18.5-24.9 25-29.9 30-34.9 35-35.9 >=400

10

20

30

40

50

60

70

80

90

100

71.2%

47.8%

61.7%71.9%

81.2%85.7% 85.5%

% 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 & neurohormonal levels, 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

Thank You!