The Obesity Paradox and The Obesity Paradox and Discrepancy between ODiscrepancy between O2 2

Consumption and Heart Failure Consumption and Heart Failure

Prognosis – It’s All in the FatPrognosis – It’s All in the Fat

Lorraine S. Evangelista, PhD, RNLorraine S. Evangelista, PhD, RN

Assistant Professor, UCLA School of NursingAssistant Professor, UCLA School of Nursing

ObjectivesObjectives

Demonstrate the paradox between Demonstrate the paradox between obesity and heart failure prognosis.obesity and heart failure prognosis.

Discuss the rationale for correction of Discuss the rationale for correction of cardiopulmonary stress data (used as cardiopulmonary stress data (used as predictors of survival and listing of predictors of survival and listing of cardiac transplantation) for lean weight cardiac transplantation) for lean weight (as opposed to total body weight).(as opposed to total body weight).

Case StudyCase Study 59 y.o. man presented to the HF clinic for evaluation59 y.o. man presented to the HF clinic for evaluation

Dyspnea on exertion, orthopnea, PND, edema Dyspnea on exertion, orthopnea, PND, edema lower extremities (NYHA class II to III status) lower extremities (NYHA class II to III status)

Optimized on diuretics, digitalis, ACE inhibitors, Optimized on diuretics, digitalis, ACE inhibitors, β-blockers, and spironolactone. 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 VOPeak VO2 2 13.4 mL/kg/min, peak O13.4 mL/kg/min, peak O22 pulse (peak pulse (peak

VOVO22 /peak heart rate) 11.8 mL per beat /peak heart rate) 11.8 mL per beat

ObesityObesity Heart FailureHeart Failure

Heart FailureHeart Failure

ObesityObesity

HATEHATE

R E L A T I O N S H I PR E L A T I O N S H I P

LOVELOVE

Obesity is a risk factor for the development of HFObesity is a risk factor for the development of HF1-21-2

Obesity and HF often co-exist Obesity and HF often co-exist 33

15% to 35% of patients with HF are obese15% to 35% of patients with HF are obese30% to 60% of patients with HF are overweight30% to 60% of patients with HF are overweight

Inte

rme

dia

teP

ath

wa

ys

He

mo

dy

na

mic

ch

an

ge

s

PA Pressure

Peripheral Resistance

Preload

Blood volume

RA RV

Plasma viscosity

Sympathetic nervous systemRAAS, Endothelin-1, vasopressinNatriuretic peptides

Suppression of lipolysisImpaired fatty acid metabolismSubstrate competition

Atrial Remodeling

LV Remodeling

Stroke Volume

conduit stiffness

LA LV

Asymptomatic LV systolic & diastolic dysfunction

ObesityIncreased adiposity

Modified from Vasan RS. Heart 2003; 89;1127-29

Afterload

DiabetesGlucose intolerance Insulin sensitivity

Insulin resistanceDyslipidemiaHypertension

HypercoagulabilityF

ac

tors

Ris

k

The Obesity Paradox

Body Mass Index

BMI

All-CauseDeath

All-CauseDeath

Obesity in general is associated with Obesity in general is associated with mortality mortality 4-114-11

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

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 (X2, 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

Cardiopulmonary Exercise (CPX)Cardiopulmonary Exercise (CPX) CPX has become the accepted standard for HF prognostication & risk CPX has become the accepted standard for HF prognostication & risk

stratification (RS) for transplant; Peak stratification (RS) for transplant; Peak VOVO22 >14 mL/kg/min cut-off value >14 mL/kg/min cut-off value of RSof RS12–1512–15

Peak Peak VOVO22 >18 mL/kg/min have a very good prognosis >18 mL/kg/min have a very good prognosis

Peak Peak VOVO22 <10 ml/kg/min have very poor prognosis <10 ml/kg/min have very poor prognosis

Generally corrected for total wt (opposed to lean wt) despite the fact Generally corrected for total wt (opposed to lean wt) despite the fact that fat is not aerobically active. that fat is not aerobically active. 13, 1513, 15

CPX may lose prognostic power in some sub-groups with CPX may lose prognostic power in some sub-groups with % body fat – % body fat – obese patients and women.obese patients and women.

In an era of In an era of ββ-blockers, adjusted exercise indices may predict better -blockers, adjusted exercise indices may predict better outcome.outcome.

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.

Case Study RevisitedCase Study Revisited

Patient’s peak VOPatient’s peak VO22 & O & O2 2 pulse corrected for pulse corrected for

lean body mass 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 These adjusted indices suggest a favorable prognosis; thus patient can qualify for a heart prognosis; thus patient can qualify for a heart transplant.transplant.

Recommendations: consistently have the peak Recommendations: consistently have the peak VOVO22 lean lean reported and utilize these values in reported and utilize these values in

evaluating sub-groups of patientsevaluating sub-groups of patients

ReferencesReferences1 Kenchaiah S, Evans JC, Levy D, et al. N Engl J Med. 2002;347:305–313.2 Murphy, MacIntyre, Stewart S, et al. Eur Heart J. 2006;27:96–106.3 Gustafsson F, Kragelund CB, et al, Eur Heart J. 2005;26:58–64. 4 Horwich TB, Fonarow GC, et al. J Am Coll Cardiol. 2001;38:789–795.5 Mosterd A, Cost B, Hoes AW, et al. Eur Heart J. 2001;22:1318–1327.6 Lissin LW, Gauri AJ, Froelicher VF, et al.. J Card Fail. 2002;8:206–215.7 Davos CH, Doehner W, Rauchhaus M, et al. J Card Fail. 2003;9:29–35.8 Lavie CJ, Osman AF, Milani RV, et al. Am J Cardiol. 2003;91:891–894.9 Curtis JP, Selter JG, Wang Y, et al.. Arch Intern Med. 2005;165:55–61.10 Lavie CJ, Milani RV. J Am Coll Cardiol. 2003;42:677–679.11 Lavie CJ, Mehra MR, Milani RV. Eur Heart J. 2005;26:5–7.12 Mancini DM, Eisen H, Kussmaul W, et al. Circulation. 1991;83:778–786.13 Mehra MR, Lavie CJ, Milani RV. Chest. 1996;110:310–312.14 Weber KT, Janicki JS. Am J Cardiol. 1985;55:22A–31A.15 Milani RV, Lavie CJ, Mehra MR, et al. Mayo Clin Proc. 2006;81:1603–1611.16 Osman A, Mehra M, Lavie C, et al. J Am Coll Cardiol. 2000;36:2126–2131.17 Lavie CJ, Milani RV, Mehra MR. Am J Cardiol. 2004;93:588–593.