1. The Obesity Paradox and Discrepancy between O 2 Consumption and Heart Failure Prognosis – It’s All in the Fat Lorraine S. Evangelista, PhD, RN Assistant Professor, UCLA School of Nursing

2. Objectives  Demonstrate the paradox between obesity and heart failure prognosis.  Discuss the rationale for correction of cardiopulmonary stress data (used as predictors of survival and listing of cardiac transplantation) for lean weight (as opposed to total body weight).

3. Case Study  59 y.o. man presented to the HF clinic for evaluation Dyspnea on exertion, orthopnea, PND, edema lower extremities (NYHA class II to III status) Dyspnea on exertion, orthopnea, PND, edema lower extremities (NYHA class II to III status) Optimized on diuretics, digitalis, ACE inhibitors, β-blockers, and spironolactone. Optimized on diuretics, digitalis, ACE inhibitors, β-blockers, and spironolactone. Ht 70’ wt, 217 lb, BMI, 31 kg/m2 ; 33% body fat. Ht 70’ wt, 217 lb, BMI, 31 kg/m2 ; 33% body fat. Resting HR 60 bpm, BP 112/68 mm Hg. Resting HR 60 bpm, BP 112/68 mm Hg. CPX - max peak HR130 bpm, BP 190/90 mm Hg. CPX - max peak HR130 bpm, BP 190/90 mm Hg. Peak VO 2 13.4 mL/kg/min, peak O 2 pulse (peak VO 2 /peak heart rate) 11.8 mL per beatPeak VO 2 13.4 mL/kg/min, peak O 2 pulse (peak VO 2 /peak heart rate) 11.8 mL per beat

4. Obesity Heart Failure Obesity HATE R E L A T I O N S H I P LOVE  Obesity is a risk factor for the development of HF 1-2  Obesity and HF often co-exist 3  15% to 35% of patients with HF are obese  30% to 60% of patients with HF are overweight

5. Intermediate Pathways Hemodynamic changes PA Pressure Peripheral Resistance Preload Blood volume RARV Plasma viscosity  Sympathetic nervous system  RAAS, Endothelin-1, vasopressin  Natriuretic peptides Suppression of lipolysis Impaired fatty acid metabolism Substrate competition Atrial Remodeling LV Remodeling Stroke Volume conduit stiffness LALV Asymptomatic LV systolic & diastolic dysfunction Obesity Increased adiposity Modified from Vasan RS. Heart 2003; 89;1127-29 Afterload Diabetes Glucose intolerance  Insulin sensitivity Insulin resistance Dyslipidemia Hypertension Hypercoagulability Factors Risk

6. The Obesity Paradox Body Mass Index BMI All-Cause Death All-Cause Death Obesity in general is associated with  mortality 4-11

7. Horwich, Fonarow, Hamilton, et al. The relationship between obesity and mortality in patients with heart failure. J Am Coll Cardiol. 2001;38:789–795. N=1203

8. Lavie CJ, Osman AF, Milani RV, et al. Am J Cardiol. 2003;91:891–894. Pts in the highest quintile had better event- free survival than pts in the lowest quintile. In a logistic regression analysis, a higher % of body fat (X 2, 9.1; P=.002) was the strongest independent predictor of event-free survival. For every 1% absolute  in % of body fat, a  in major clinical events exceeding 13% reported. N=209

9. Cardiopulmonary Exercise (CPX)  CPX has become the accepted standard for HF prognostication & risk stratification (RS) for transplant; Peak VO 2 >14 mL/kg/min cut-off value of RS 12–15 Peak VO 2 >18 mL/kg/min have a very good prognosis Peak VO 2 >18 mL/kg/min have a very good prognosis Peak VO 2 <10 ml/kg/min have very poor prognosis Peak VO 2 <10 ml/kg/min have very poor prognosis  Generally corrected for total wt (opposed to lean wt) despite the fact that fat is not aerobically active. 13, 15  CPX may lose prognostic power in some sub-groups with  % body fat – obese patients and women.  In an era of β-blockers, adjusted exercise indices may predict better outcome.

10. These figures show that adjusted exercise indices (including peak VO2 and peak O2 pulse) predict prognosis better than non-adjusted indices Osman AF, Mehra MR, Lavie CJ, et al. J Am Coll Cardiol. 2000;36:2126–2131. Lavie CJ, Milani RV, Mehra MR. Am J Cardiol. 2004;93:588–593.

11. Case Study Revisited  Patient’s peak VO 2 & O 2 pulse corrected for lean body mass 19.7 mL/kg/min & 15.6 mL per beat. 19.7 mL/kg/min & 15.6 mL per beat.  These adjusted indices suggest a favorable prognosis; thus patient can qualify for a heart transplant.  Recommendations: consistently have the peak VO 2 lean reported and utilize these values in evaluating sub-groups of patients

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