5 Lavie obesity.ppt2.ppt - Community Hospital of the ...4/27/2013 2 Lavie CL et al. J Am Coll...

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Untangling the “Heavy” Untangling the “Heavy” Cardiovascular Burden of Obesity Cardiovascular Burden of Obesity

and the “Obesity Paradox”and the “Obesity Paradox”

Carl J. Lavie, MD, FACC, FACP, FCCP

Professor of Medicine

M di l Di t C di R h bilit ti d



M di l Di t C di R h bilit ti dMedical Director, Cardiac Rehabilitation and

Preventive Cardiology

Director, Exercise Laboratories

John Ochsner Heart and Vascular Institute

Ochsner Clinical School-The UQ School of Medicine

New Orleans, La

Medical Director, Cardiac Rehabilitation and





New Orleans, La

Obesity and Obesity Paradox and CVD-Original Research

• Lavie CJ et al. Chest 1987;92:1042-1046• Lavie CJ, Milani RV.Chest 1996;109:52-56• Lavie CJ, Milani RV. Am J Cardiol 1997;79:397-401• Lavie CJ et al. Am J Cardiol 2003;91:891-894• Lavie CJ et al. Am J Cardiol 2007;100:1460-1464

L i CJ t l J C di t b S d 2008 3 136 140• Lavie CJ et al. J Cardiometab Syndr 2008;3:136-140• Lavie CJ et al. Postgrad Med 2009;121(3):119-124• Lavie CJ et al. Am J Med 2009;122:1106-1114• De Schutter A, Lavie CJ et al PGM 2011;123(6):72-78• Lavie CJ et al. Mayo Clin Proc 2011;86(9):857-864• McAuley PA, Lavie CJ et al. Mayo Clin Proc 2012;87:443-451• Lavie CJ et al. JACC 2012; 60: 1374-1380• De Schutter A , Lavie CJ et al. Am J Cardiol 2013;on-line• Lavie CJ et al. Mayo Clin Proc 2013; 88(3): 251-258

Obesity and Obesity Paradox and CVD-Major Reviews/Editorials

Obesity and Obesity Paradox and CVD-Major Reviews/Editorials

• Lavie CJ et al. JACC 2009;53:1925-1932• Lavie CJ et al.Mayo Clin Proc 2010;85(7):605-608• Lavie CJ et al. Am J Med 2007;120:825-826• Lavie CJ,Milani RV.JACC 2003;42:677-679• Lavie CJ et al.Nat Clin Pract CV Med 2008;5:428-429• Lavie CJ et al.Eur Heart J 2005;26:5-7

A th SM L i CJ t l PGM 2008 120(2) 34 41• Artham SM,Lavie CJ et al.PGM 2008;120(2):34-41• Artham SM,Lavie CJ et al.Current Treatment Options in CV

Med 2010;12:21-35• Lavie CJ, Milani RV. Chest,2011;140(6):1395-1396• Lavie CJ, Milani RV. JACC, 2011;58(25):2651-2653• Lavie CJ et al. JACC HF 2013;1: 93-102• Lavie CJ et al . Heart 2013;99(9): 596-598• Lavie CJ et al. Prev Med 2013: March 29• Lavie CJ et al. Am Heart J 2013; in press

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Lavie CL et al. J Am Coll Cardiol 2009; 53:1925-32.

August 30, 2010

Weight Index Doesn’t Tell the Whole Truth By JANE E. BRODY

A frequent question among people of a certain age, including yours truly, is “Why, when I weigh the same as or less than I did when I was younger, does my waist keep getting bigger?” Phrased another way, the question could be “Why, when my body mass index has notchanged, am I fatter than I used to be?” The simple answer is that the index, usually called B.M.I. for short, is a crude measure of fatness in individuals. Calculated by dividing one’s weight in kilograms by the square of one’s height in meters, it doesn’t differentiate between fatty and lean tissue. “The B.M.I. tables are excellent for identifying obesity and body fat in large populations, but they are far less reliable for determining fatness in individuals,” explained Dr. Carl Lavie, a cardiologist at the Ochsner Heart and Vascular Institute in New Orleans.

Fat Tissue, Lean Tissue

Fat takes up about four times the space of muscle tissue, for example, so it is quite possible to look and feel fatter even if your height and weight remain the same. This is particularly common among women past 50 and men past 60, and the results are likely to show around the middle. For children and the elderly, body mass values can be especially misleading because the relationship of lean body mass to height changes as they get older. B.M.I. charts pop up all over the place, in popular publications, exercise facilities and doctors’ offices. The charts are widely used by doctors to determine if their patients are underweight, normal weight, overweight or obese. Thus, a body mass of less than 18.5 is considered underweight; 18.5 to 24.9 is considered a healthy weight; 25 to 29.9 is overweight; 30 to 39.9 is obese; and 40 or more is morbidly obese. If you fall into the “healthy weight” or “underweight” range, you can easily be lulled into a false sense of security. But thinness is not necessarily healthy — recall the 97-pound weakling from the Charles Atlas ads of yore. A low B.M.I. could be indicative of malnutrition, anorexia, cancer or a wasting disease. On the other hand, if you are an athlete or body builder, your B.M.I. could mistakenly put you in the range for overweight or obese. Degree of body fatness is a better way than body mass to classifyindividuals. Both the World Health Organization and the National Institutes of Health define obesity as more than 25 percent body fat in men and more than 35 percent body fat in women. So “a woman who is 5 feet 5 inches tall and weighs 120 to 125 pounds could be quite fat,” Dr. Lavie told me, “even though her weight and B.M.I. seem O.K.” Among Americans in general, he said, “a six-foot, 250-pound man will be obese, but if he were an N.F.L. lineman of 6-foot-3 weighing 280 pounds, he might be solid muscle with only 2 percent body fat.”

Obesity and Cardiovascular Diseases

• Obesity increasing in epidemic proportions

• Body mass index (BMI) is primarily used

• Body fatness, waist circumference (WC), waist to hip ratio (WHR), and waist to height ratio may be superior

Lavie CJ et al. JACC 2009;53:1925-1932

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Obesity and Cardiovascular Diseases

• 70% of adults in US are overweight or obese

• Morbid obesity especially increased

• Obesity is second to only tobacco abuse as the #1 cause of preventable death in US

• Due to obesity, we may soon see a reversal in the steady increase in life expectancy


Adverse Effects of ObesityAdverse Effects of Obesity

• Increases in insulin resistanceGlucose intoleranceMetabolic SyndromeType 2 Diabetes Mellitus

• Increases in insulin resistanceGlucose intoleranceMetabolic SyndromeType 2 Diabetes MellitusType 2 Diabetes Mellitus

• Hypertension• Abnormal LV Geometry

Concentric RemodelingLVH

Type 2 Diabetes Mellitus • Hypertension• Abnormal LV Geometry

Concentric RemodelingLVH

Lavie CJ et al. JACC 2009;53:1925-1932Lavie CJ et al. JACC 2009;53:1925-1932

Adverse Effects of ObesityAdverse Effects of Obesity

DYSLIPIDEMIA– Elevated total cholesterol

– Elevated VLDL and triglycerides

– Elevated LDL and small dense particles

DYSLIPIDEMIA– Elevated total cholesterol

– Elevated VLDL and triglycerides

– Elevated LDL and small dense particles– Elevated LDL and small, dense particles

– Elevated non-HDL

– Elevated apolipoprotein B

– Reduced HDL and apolipoprotein A-1

– Elevated LDL and small, dense particles

– Elevated non-HDL

– Elevated apolipoprotein B

– Reduced HDL and apolipoprotein A-1

Lavie CJ et al. JACC 2009;53:1925-1932Lavie CJ et al. JACC 2009;53:1925-1932

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Adverse Effects of Obesity

• Abnormal endothelial function• Abnormal systolic and diastolic LV function• Increased systemic inflammation (eg CRP)• Increased Pro-thrombotic state• Albuminuria• Obstructive sleep apnea / sleep disordered

breathing


Cardiovascular Diseases Associated With Obesity

• Hypertension• Heart Failure• Coronary Heart Disease• Atrial Fibrillation• Complex Ventricular Dysrhythmias• Stroke• Venous Thromboembolism• OSA / SDB


Obesity and CV Disease

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BMI Associated Death Risk: General Population

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Calle et al, N Engl J Med 341:1097-1105

General Population

Meta-Analysis of BMI and Survival

• 97 studies,2.88 million individuals,>270,000 deaths

• Relative to normal weight, obesity(all grades combined) and grades 2 and 3 obesity were associated with higher all cause mortalityassociated with higher all-cause mortality

• Grade 1 obesity was associated with a trend for lower mortality(HR 0.95;CI 0.88-1.01), and overweight had significantly lower mortality(HR 0.94;CI 0.91-0.96)

Flegal KM et al.JAMA 2013;309(1):71-82

“Obesity Paradox” and Cardiovascular Diseases

Although obesity has been implicated as one of the major risk factors for most CV diseases, including HTN, HF, and CHD, evidence from clinical cohorts of patients with established CVclinical cohorts of patients with established CV diseases indicates an “obesity paradox” because overweight and obese with these diseases tend to have a more favorable short-and long-term prognosis.


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Obesity and Hypertension

• Obesity increases levels of BP

• Obesity increases CR and LVH, independent of BP

Ob it i t b li• Obesity increases metabolic abnormalities in HTN

• Despite the increased prevalence, obese hypertensives have a favorable prognosis


“Obesity Paradox” and Hypertension

In aggregate, although obesity is a powerful risk factor for hypertension and LVH obese hypertensive patients mayLVH, obese hypertensive patients may paradoxically have a better prognosis, possibly due to low SVR and PRA


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Lavie CL et al. JACC, HF 2013:1:93-102.

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Meta-Analysis of 9 Observational StudiesOreopoulos et al. Am Heart J 2008.

Obesity Status and Heart Failure Mortality

The message from >28,000 CHF patients: Once you have heart failure, bigger = live longer

BMI and HF Hospital Mortality

• 108,927 decompensated HF patients

• Higher BMI associated with lower mortalitymortality

• For every 5-unit increase in BMI, HF mortality was 10 % lower (p < 0.001)

Fonarow GC et al. Am Heart J 2007;153:74-81

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Possible Reasons for Obesity Paradox in Heart Failure

• Advanced HF is catabolic state; obese may have more metabolic reserve

• Adipose tissue produces TNF-α receptors that may neutralize TNF-α

• Obese have lower ANP and PRA• Obese have higher BP, so may tolerate more

meds• Higher circulating lipoproteins may detoxify

lipopolysaccharides that effect inflammatory cytokines


Obesity and CHD

• Obesity adversely effects most major CV risk factors (HTN, dyslipidemia, MetS/T2DM)

• Obesity probably an independent CHD• Obesity probably an independent CHD risk factor

• Obesity strongly related with 1st

premature MI at young age (Mandala MC et al. JACC 2008;52:979-985)


Obesity Paradox and CHD

• 40 cohort studies of over 250,000 CHD patients followed for 3.8 years

• Overweight and obese had lower risk of total and CV mortality compared with underweight y p gand “normal” weight patients

• Similar in stable CHD, PCI and CABG

• In BMI ≥ 35 kg/m2, there was excess risk of CV mortality without an increase on total mortality

Romero-Corral A, et al. Lancet 2006; 368:666-678

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Obesity Paradox and CHDObesity Paradox and CHD

• 529 consecutive CHD patients post events

• Overweight and obese (n = 393) had d CHD i k fil thmore adverse CHD risk profiles than

leaner patients (n = 136)

• During 3-year follow-up, overweight/obese had significantly lower mortality

Lavie CJ, et al. Am J Med 2009;122:1106-1114


Lavie CJ et al. Am J Med 2009;122:1106-1114

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Lavie CJ et al. Mayo Clin Proc 2011;86(9):857-864.

The "Obesity Paradox" in CHDThe "Obesity Paradox" in CHD

Lavie CJ et al. Mayo Clinic Proc 2011;86(9): 857-864

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The "Obesity Paradox" in CHDThe "Obesity Paradox" in CHD

*p<0.0001 compared to other group

Lavie CJ et al. Mayo Clinic Proc 2011;86(9): 857-864

Body Composition and CHD MortalityBody Composition and CHD Mortality

De Schutter A, Lavie CJ et al. Am J Cardiol, online December,2012

Lavie CJ et al . JACC 2012;60: 1374-1380.

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Lean Mass Index and CHD MortalityLean Mass Index and CHD Mortality

Lavie CJ et al. JACC 2012;60: 1374-1380

Body Fat, Lean Mass Index and CHD Mortality

Body Fat, Lean Mass Index and CHD Mortality

Lavie CJ et al. JACC 2012; 60: 1374-1380

Obesity Paradox and CHDMechanisms

Obesity Paradox and CHDMechanisms

• None of the studies accounted for non-purposeful weight loss

• Lower renin and ANP in obese

• Confounders

• COPD

• Impact of Fitness

• Baseline genetic differences

Lavie CJ, et al. Mayo Clin Proc 2011;86(9): 857-864

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Obesity Paradox and CHDImpact of Central Obesity and Fitness

Obesity Paradox and CHDImpact of Central Obesity and Fitness

• Mayo Clinic Studies with No Obesity Paradox in CHD with Central Obesity:1) Goel K et al .Am Heart J 2011;16(3):590-597 and 2)Coutinho T et al. JACC 2011;57(19): 1877-1886

• UCLA HF Studies with Strong Obesity Paradox with Central Obesity:1) Clark AL et al. J Cardiac Failure 2011;17:374-380 and 2) Clark AL et al. Am J Cardiol 2012;110:77-82

• Obesity Paradox in Central Obesity only with Low Fitness: McAuley PA et al.Mayo Clin Proc 2012;87(5):443-451

McAuley PA et al. Mayo Clin Proc 2012;87(5):483-451

BMI Waist Circumference

Impact of Fitness on All-Cause Mortality in CHD

McAuley PA et al.Mayo Clin Proc 2012;87(5):483-451

% Body Fat

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Impact of Fitness on CVD Mortality in CHD

BMI Waist Circumference

McAuley PA et al. Mayo Clin Proc 2012;87(5):483-451

% Body Fat

Lavie CL et al. Mayo Clin Proc 2013; 88(3):251-258.

Fitness, Mortality, Obesity Paradox in Heart FailureFitness, Mortality, Obesity Paradox in Heart Failure

Low FitnessLow Fitness Higher FitnessHigher Fitness

Lavie CJ et al. Mayo Clin Proc 2013;88(3): 251-258

Lavie CJ et al . Am Heart J 2013

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Obesity Paradox and CVDImpact of CardiorespiratoryFitnessObesity Paradox and CVD

Impact of CardiorespiratoryFitness

• Goel K et al .Am Heart J 2011;16(3):590-597

• McAuley PA et al.Mayo Clin Proc y y2010;85(2):115-121

• McAuley PA et al.Mayo Clin Proc 2012;87(5):443-451

• Lavie CJ et al. Circulation 2012;Nov, in press

Obesity and MortalityObesity and Mortality

Baseline Characteristics (n=35,607)Baseline Characteristics (n=35,607)

AgeAge 60 60 ±± 15 years15 years

GenderGender 53% female53% female

BMIBMI 29.2 29.2 ±± 6.7 kg/m6.7 kg/m22

EFEF 60 60 ±± 5 %5 %

LVMILVMI 82 82 ±± 32 g/m32 g/m22

RWTRWT 0.43 0.43 ±± 0.070.07

Lavie CJ et al. Am J Cardiol 2007;100:1460-1464

LV Geometry and Obese MortalityLV Geometry and Obese Mortality

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Lavie CJ et al.Am J Cardiol 2007;100:1460-1464

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BMI and MortalityBMI and Mortality

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511511 9,8579,857 13,45013,450 6,7886,788 5,0045,004N=N=


Obesity and MortalityObesity and Mortality

Multivariate AnalysisMultivariate Analysis(n= 35,607)(n= 35,607)

Parameter Chi-Square P-value

Higher age 785 <0 0001Higher age 785 <0.0001

Lower BMI 32.6 <0.0001

Male gender 10.3 = 0.0013

Higher RWT 7.6 = 0.0006


0 0001198Hi h

PP--ValueValueChiChi--SquareSquareParameterParameter

Multivariate Predictors of Mortality Multivariate Predictors of Mortality ((nn=11,792)=11,792)

LV Geometry and Obese MortalityLV Geometry and Obese Mortality

=0.038.9Male gender

=0.000114.4High BMI

<0.000122.0Higher RWT

<0.0001198Higher age

=0.000213.5Higher LVMI


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Mortality Prevalence by BMI Categories in Females

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MeanN

Patel D,Lavie CJ et al. Circulation 2008;118(18):S1153

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Mortality in Four LV Geometric Patterns in Females with Preserved Systolic Function

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Patel D,Lavie CJ et al. Circulation 2008;118(18):S1153

Obesity and Atrial Fibrillation

• As with obesity, AF is also epidemic, and is expected to increase by 2.5-fold by 2050

• May be due to HTN, CHD, and HF

• Obesity appears to be a significant AF risk Obes y appea s o be a s g ca sfactor

• In a meta-analysis of 16 studies of 125,000 subjects, obesity increased the risk of AF by 49% (Wanahita N, Messerli FH et al. Am Heart J 2008;155: 310-315.)


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Obesity Paradox in Atrial FibrillationObesity Paradox in Atrial Fibrillation

ARRIRM Study (n=4,060)

Badheka AO et al. Am J Med 2010;123:646-651.







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Weight Loss in CV Diseases

• Obesity increases most CV risk factors and CV diseases

• However, an “obesity paradox” is present, y p p

• Weight loss improves risk factors

• Impact of weight loss on CV events remains controversial

Artham SM, Lavie CJ et al.

Curr Treatment Options in CV Med 2010;12:21-35

Potential Adverse Effects of Weight Loss

• Obesity Paradox

• Prolonged QTc and increased ventricular dysrhythmias (starvation very low caloriedysrhythmias (starvation, very low calorie, liquid protein diets, and obesity surgeries)

• Pharmacologic agents have limited efficacy and considerable toxicity


Weight Loss and Lifestyle Modifications

• Calorie restriction and exercise training is safe and is associated with 60% reduction in development of T2DM

– Knowler WL et al. NEJM 2002;346:393-403 – Tuomilehto J, et al. NEJM 2001;344:1343-1350

• CRET reduces MS by 37%– Milani RV, Lavie CJ. AJC 2003;92:50-54

• In 1,500 CHD patients, 6 month weight loss programs associated with lower CHD events in 4 years

– Eilat-Adar S, et al. Am J Epidemiology 2005;161:352-358

• In 377 patients at Mayo Clinic, weight loss, even in those with BMI < 25 kg/m2, was associated with reduced mortality/CV events

– Sierra-Johnson J et al. Eur CV Prev Rehabil 2008;15:336-340

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Weight Loss in CV Diseases

• In HTN, weight loss reduces BP and LVH

• In HF, weight loss improves LVM, systolic and diastolic LV function, and functional class,

• Obesity surgery improves CHD risk factors, T2DM, and short- and long-term mortality

• Obesity surgery in small studies is safe in CHD and HF


Obesity, HF and Weight LossGuideline Statements

• American Heart Association 40 kg/m2

• Heart Failure Society of America 35 kg/m2

• European Society of Cardiology 30 kg/m2p y gy g

• Canadian Cardiovascular Society 30 kg/m2

• Vastly different cut-points due to minimal data by which to base these exact recommendations

• Clearly further research is needed to determine ideal BMI and body composition in CVD, including systolic and diastolic HF

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Household Management Energy Expenditure in Household Management Energy Expenditure in Women over 5 DecadesWomen over 5 Decades

Archer E et al. PLOS ONE 2013;8(2): e 56620

Occupational Occupational METsMETs over 5 Decadesover 5 Decades

Church TS et al. PLOS ONE 2011;6(5): e19657

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Occupational EE and ObesityOccupational EE and Obesity

Church TS et al. PLOS ONE 2011;6(5): e19657

Obesity and CV DiseasesSummary and Conclusions

• Overwhelming evidence supports the importance of obesity in the pathogenesis and progression of most CV diseases

• An Obesity Paradox exists• An Obesity Paradox exists

• At present, evidence supports purposeful weight reduction

• If the current obesity epidemic continues, we may soon witness and unfortunate end to the steady increase in life expectancy


Untangling the “Heavy” Untangling the “Heavy” Cardiovascular Burden of Obesity Cardiovascular Burden of Obesity

and the “Obesity Paradox”and the “Obesity Paradox”




Professor of MedicineProfessor of Medicine






New Orleans, LA







New Orleans, LA

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