the obesity paradox.pdf

7/28/2019 The obesity paradox.pdf

1/43

The obesity paradox

15-18 2013


2/43

410

BMI has been established as an independent risk factor forpremature mortality

Calle EE, Thun MJ, Petrelli JMN Engl J Med 341: 10971105, 1999


3/43

17%

17%

30%

24%

11%

34%

11%

Wolf et al, Obes Res 1998


4/43

BMI

NEJM 2010, 363 (23)
http://upload.wikimedia.org/wikipedia/commons/a/ad/WomenBMIMort.png


5/43

( ~10 kg)

Jung RT. B r Med Bull 1997;53:307-21

20-25% 2 30-40%

40-50% ~10 mmHg >50% 30-50%HbA1c 15%

10%

LDL 15% 30%HDL 8%


6/43

Nephron 1982;31:103-110

Mortality Risk Factors in Patients Treated by Chronic HemodialysisReport of the Diaphane Collaborative StudyPatrice Degoulet et al

1,453 33

High body mass index and elevated cholesterol, triglyceridesand uric acid were not found to be associated withsignificantly increased CVM or OM.

On the contrary, low body mass index (


7/43

Am J Cardiol 1996 Sep 15;78(6):642-6.

Low-normal or excessive body mass index: newly identified and powerful riskfactors for death and other complications with percutaneous coronaryintervention.Ellis SC et alCleveland Clinic Foundation, Ohio 44195, USA.

3,571 consecutive percutaneous coronary intervention patients treated at a single referralcenter.

nonobese (BMI < 25), mildly obese (BMI 25-35), and very obese(BMI > 35)

Death occurred in 2.8% of the BMI 35 group, and

in 0.9% of the BMI 26-34 group (p < 0.001)
http://www.ncbi.nlm.nih.gov/pubmed?term=am%20j%20cardiol%201996,%2078:642-646http://www.ncbi.nlm.nih.gov/pubmed?term=am%20j%20cardiol%201996,%2078:642-646


8/43

Kidney Int 1999 Apr;55(4):1560-7.

Influence of excess weight on mortality and hospital stay in 1346 hemodialysis

patients.Fleischmann E et alDepartment of Medicine and Preventive Medicine, University of Mississippi MedicalCenter, Jackson, USA.

Compared with the normal weight (BMI 20-27.5), the one-year survival rate wassignificantly higher in the overweight patients and lower in theunderweight patients.

With a one-unit increase in BMI over 27.5, the relative risk for dying

was reduced by 30% (P


9/43

Nephrol Dial Transplant 2001 Dec;16(12):2386-94.

Body mass index and mortality in 'healthier' as compared with 'sicker'haemodialysis patients: results from the Dialysis Outcomes and Practice PatternsStudy (DOPPS).Leavey SF et alDivision of Nephrology, University of Michigan and VAMC, Ann Arbor, USA.

9714 HD patients in the US and Europe

RR mortality decreased with increasing BMI.

Overall a lower relative mortality risk (RR) as compared

with BMI 23-25, was found:for overweight (BMI 25-30) RR 0.84, P=0.008for mild obesity (BMI 30-35) RR 0.73, P=0.0003

for moderate obesity (BMI 35-40) RR 0.76, P=0.02


10/43

J Am Coll Cardiol 2001 Sep;38(3):789-95.

The relationship between obesity and mortality in patients with heart failure.Horwich TB et al

Department of Medicine, University of California at Los Angeles Medical Center, LosAngeles, California, USA

1,203 patients with advanced HF underweight BMI 31 (n = 179)

The obese and overweight groups had significantly higher rates of hypertensionand diabetes, as well as higher levels of cholesterol, triglycerides and low density

lipoprotein cholesterol. The four BMI groups had similar survival rates.

Conclusion:

In a large cohort of patients with advanced HF of multiple

etiologies, obesity is not associated with increasedmortality and may confer a more favorable pro nosis.


11/43

J Am Coll Cardiol 2002 Feb 20;39(4):578-84.

The impact of obesity on the short-term and long-term outcomes after

percutaneous coronary intervention: the obesity paradox?Gruberg L et alCardiac Catheterization Laboratory and the Cardiovascular Research Institute, WashingtonHospital Center, Washington, DC 20010, USA.

9,633 consecutive patients who underwent PCI

BMI 18.5 - 24.9 (n = 1,923) overweight, BMI 25 - 30 (n = 4,813) obese, BMI >30 (n = 2,897)Obese patients were significantly younger and had consistently worse baseline clinicalcharacteristics than normal or overweight patients, with a higher incidence ofhypertension, diabetes, hypercholesterolemia and smoking history (p < 0.0001).

Conclusion:In patients with known CAD who undergo PCI,very lean patients(BMI


12/43

Am J Kidney Dis 2003 May;41(5):925-32.

Obesity and survival on dialysis.Salahudeen AK

Department of Medicine, University of Mississippi Medical Center, Jackson, MS 39216,USA.

The Dialysis-risk paradox


13/43

Am J Clin Nutr 2005 Oct;82(4):909-10; author reply 910-11.

The paradox of the "body mass index paradox" in dialysis patients: associations ofadiposity with inflammation.

Beddhu S et al

The body mass index paradox


14/43

OBESITY PARADOX


15/43

Arch Intern Med 2005 Jul 25;165(14):1624-9

Paradoxical effect of body mass index on survival in rheumatoid arthritis: role ofcomorbidity and systemic inflammation.Escalante A et al

779 patients with RA

Conclusion:Body mass has a paradoxical effect on mortality in RA. Patients

with high BMI have lower mortality than thinner patients.


16/43

Ann Surg 2009 Jul;250(1):166-72

The obesity paradox: body mass index and outcomes in patients undergoingnonbariatric general surgery.Mullen JT et alDepartment of Surgery, Harvard Medical School, Beth Israel Deaconess Medical Center

118,707 patients undergoing nonbariatric general surgery

Conclusion: Overweight and moderately obese patientsundergoing nonbariatric general surgery have paradoxically "lower"crude and adjusted risks of mortality compared with patients at a"normal" weight.


17/43

Chest 2008 Nov;134(5):925-30. Epub 2008 Jul 18.

The obesity paradox in patients with peripheral arterial disease.

Galal W et alDepartment of Anesthesiology, Erasmus Medical Center, Rotterdam, the Netherlands

2,392 patients who underwent major vascular surgery follow up 1.98 to 8.47 years

The overall mortality rates among underweight, normal,overweight, and obese patients were 54%, 50%, 40%, and 31%,respectively (p < 0.001).

Underweight have COPD !


18/43

Am J Med 2010 Jul;123(7):646-51.

Influence of obesity on outcomes in atrial fibrillation: yet another obesity paradox.Badheka AO et alDepartment of Internal Medicine, Wayne State University, Harper University Hospital,Detroit, Mich 48201, USA.

Atrial Fibrillation Followup Investigation of Rhythm Management(AFFIRM) study 4060 patients - BMI in 2492 patients normal (18.5-25), overweight (25-30), and obese (>30) follow up 3 years

Conclusion: Although in prior studies, obesity has been associatedwith increased risk of atrial fibrillation, an obesity paradox exists foroutcomes in atrial fibrillation. Obese patients with atrialfibrillation appear to have better long-term outcomes thannonobese patients.


19/43

Stroke 2011 Jan;42(1):30-6. Epub 2010 Dec 2.

Association between obesity and mortality after acute first-ever stroke: the obesity-stroke paradox.Vemmos K et alAcute Stroke Unit, Alexandra Hospital, Athens, Greece.

2785 patients Early (first week) survival in obese and overweight wassignificantly higher compared to that of normal-weight patients.Similarly, 10-year survival was 52.5% in obese, 47.4% in overweight,and 41.5% in normal-weight patients Overweight and obese had a significantly lower risk of 10-year

mortality compared to normal-weight patients after adjusting for allconfounding variables.

Conclusion: based on BMI estimation, obese and overweight strokepatients have significantly better early and long-term survival ratescompared to those with normal BMI


20/43

Am Rev Respir Dis 1989 Jun;139(6):1435-8.Body weight in chronic obstructive pulmonary disease. The National Institutes ofHealth Intermittent Positive-Pressure Breathing Trial.Wilson DO et alDepartment of Medicine, University of Pittsburgh, Pennsylvania.

mortality increased with decreasing body weight (p = 0.093)

Am J Respir Crit Care Med 2006 Jan 1;173(1):79-83.Body mass, fat-free body mass, and prognosis in patients with chronic obstructivepulmonary disease from a random population sample: findings from theCopenhagen City Heart Study.Vestbo J et al

Department of Cardiology and Respiratory Medicine, 253 Hvidovre Hospital, KettegaardAlle 30, DK-2650 Hvidovre, Denmark

1,898 patients with COPD

BMI and FFMI were significant predictors of mortality


21/43

Int J Cardiol 2011 Oct 29. [Epub ahead of print]

Inverse relation of body weight and weight change with mortality and morbidity inpatients with type 2 diabetes and cardiovascular co-morbidity: An analysis of thePROactive study population.Doehner W et alCenter for Stroke Research Berlin, Charit, Berlin, Germany; Applied Cachexia Research,

CharitUniversittsmedizin, Berlin, Germany.

5202 patients (T2DM and evidence of pre-existing cardiovascular disease)Mean follow up was 34.5months

CONCLUSION:

Among patients with T2DM and cardiovascular co-morbidity,overweight and obese patients had a lower mortality compared topatients with normal weight. There may be an "obesity paradox" inpatients with type 2 diabetes and cardiovascular risk.


22/43

BMC Public Health 2010 Oct 13;10:604.Obesity and mortality among older Thais: a four year follow up study.Vapattanawong P et al

Department of Community Medicine, Faculty of Medicine, Ramathibodi Hospital, RamaVI Rd, Rajdevi, Bangkok 10400, Thailand.

15997 elderly people

Conclusion:

The results of this study support the obesity paradox phenomenonin older Thai people, especially in women.

Interdiscip Top Gerontol 2010;37:20-36. Epub 2010 Aug 10.Obesity paradox during aging.Chapman IMDivision of Medicine, University of Adelaide, Adelaide, Australia.


23/43

AIDS 2010 Jun 19;24(10):1501-8Body mass index and risk of tuberculosis and death.Hanrahan CF et alJohns Hopkins Bloomberg School of Public Heath, Baltimore, Maryland, USA

3456 HIV-infected adults

Conclusion: HIV-infected individuals with obese andoverweight BMI have a significantly reduced risk ofboth mortality and TB

J Acquir Immune Defic Syndr. 2004 Oct 1;37(2):1288-94Body mass index at time of HIV diagnosis: a strong and independent predictor of

survival.van der Sande MA et alMedical Research Council Laboratories, Fajara, Banjul, The Gambia

Conclusion: BMI at diagnosis is a strong, independent predictor of

survival in HIV-infected patients in West Africa.


24/43

Cancer Causes Control 2006 Feb;17(1):5-9.

Are findings from studies of obesity and prostate cancer really in conflict?

Freedland SJ et alJames Buchanan Brady Urological Institute, Johns Hopkins Medical Institutions,Baltimore, MD, USA.

JAMA 2011;305(16):1685-1694

Association of CTNNB1 (-Catenin) Alterations, Body Mass Index, and PhysicalActivity With Survival in Patients With Colorectal Cancer

Teppei Morikawa et alConclusionsAmong obese patients only, activation of CTNNB1 was associated with better colorectalcancerspecific survival and overall survival.Postdiagnosis physical activity was associated with better colorectal cancerspecificsurvival only among patients with negative status for nuclear CTNNB1.


25/43

N Engl J Med 2003;348:1625-3Overweight, Obesity, and Mortality from Cancer in a ProspectivelyStudied Cohort of U.S. AdultsCalle EE et al

900.000 pts

Conclusion: we estimate that current patterns of overweight and obesity in theUnited States could account for 14 percent of all deaths from cancer in men and 20percent of those in women.

P ti t hibiti b it d


26/43

Patient groups exhibiting an obesity paradox

Cardiovascular conditionsAtrial fibrillation

Coronary artery disease After percutaneous coronary intervention After coronary artery bypass graft surgery

Heart failureMyocardial infarctionPeripheral artery disease

Stroke

Non-cardiovascular conditionsCancer ????????Chronic obstructive pulmonary diseaseDiabetesElderlyEnd-stage renal disease/dialysisHIV/AIDRA

After general surgeryMcAuley PA and Blair SNJournal of Sports Sciences, May 2011; 29(8): 773782 (modified)


27/43

Obesity paradoxes

1. Classic obesity paradox: Obesity is protective in chronic diseasestates.

2. Pre-obesity: Overweight is protective in normal populations.

3. Fat but fit: Obesity is not a risk factor for mortality in fit individuals.

4. Healthy obesity: A sizeable population of obese adults has normalcardiometabolic risk profiles.

McAuley PA and Blair SNJournal of Sports Sciences, May 2011; 29(8): 773782


28/43

2Pre-obesity: Overweight is protective in normal populations

BMI 25-30 kg/m2

Pre-diabetes(IFG, IGT)increase OM and CVD mortality

Pre-hypertension(SBP 120-139 mmHg,DBP 80-89 mmHg)


29/43

Pre-obesity

JAMA 2007 Nov 7;298(17):2028-37Cause-specific excess deaths associated with underweight, overweight, andobesity.Flegal KM (NHANES) 571,042 person-years of follow-up

Overweight was associated with significantly decreased mortalityfrom noncancer and non-CVD causes

Obesity(Silver Spring) 2010 Jan;18(1):214-8. Epub 2009 Jun 18

BMI and mortality: results from a national longitudinal study of Canadian adults.Orpana HM et al

11,326 respondents- over 12 years of follow-up

Overweight (BMI 25-30) was associated with a significantly

decreased risk of death (RR=0.83, P


30/43

Multivariate hazard ratios for all-cause mortality by BMI category in 11,326 men and womenEach data point represents the relative risk after adjustment for age, smoking status,

physical activity frequency, and alcohol consumption, with the relative risk of normalweight (BMI 18.524.9 kg m72) set at 1.0. Error bars represent 95% confidence intervals.

Obesity(Silver Spring) 2010 Jan;18(1):214-8.Epub 2009 Jun 18


31/43

3Fat but fit: Obesity is not a risk factor for mortality in fitindividuals

adjustment for physical activity and fitness

JAMA1999 Oct 27;282(16):1547-53Relationship between low cardiorespiratory fitness and mortality in normal-weight, overweight, and obese men.Wei M et al-Cooper Institute for Aerobics Research, Dallas, Tex 75230, USA

25714 adult men- 258781 man-years of follow-up

Low fitness was an independent predictor of mortality in allbody mass index groups after adjustment for other mortalitypredictors


32/43

Multivariate hazard ratios for all-cause mortality by BMI and fitness level in 25,714 menfrom the Aerobics Center Longitudinal Study (ACLS). Each bar represents the relative riskafter adjustment for age and examination year, with the relative risk of normal weight (BMI18.524.9) and fit set at 1.0. Grey bars represent fit (upper 80% of age-decade distribution)

and white bars unfit (lowest 20% of age-decade distribution). Error bars represent 95%confidence intervals.

(adapted from Wei et al., 1999)


33/43

Am J Clin Nutr 1999 Mar;69(3):373-80.Cardiorespiratory fitness, body composition, and all-cause and cardiovasculardisease mortality in men.Lee CD et al-Cooper Institute for Aerobics Research, Dallas, TX, USA

21925 men- 176742 man-years of follow-up

Being fit may reduce the hazards of obesity

Am J Hypertens 2009 Oct;22(10):1062-9. Epub 2009 Jul 16The joint effects of cardiorespiratory fitness and adiposity on mortality risk in men

with hypertension.McAuley PA et alDepartment of Human Performance and Sport Sciences, Winston-Salem, North Carolina, USA

13,155 hypertensive men- mean follow-up of 12 years Multivariate hazard ratios (HRs) (95% confidence interval) for all-cause mortality, usinglow-fitness as the reference group, were 0.58 (0.48-0.69) and 0.43 (0.35-0.54) for moderate-fit and high-fit groups, respectively.

Fitness is a powerful effect modifier in the association ofadiposity to mortality in hypertensive men, negating the all-

cause and CVD mortality risk associated with obesity

Med Sci Sports Exerc 2010 Nov;42(11):2006-12


34/43

Med Sci Sports Exerc 2010 Nov;42(11):2006 12Cardiorespiratory fitness, adiposity, and all-cause mortality in women.Farrell SW et al-The Cooper Institute, Dallas, TX 75230, USA 11,335 women-mean follow-up of 12.3 8.2 yr

Low CRF in women was a significant independent predictor of all-cause mortality. Higher CRF was associated with lowermortality within each category of each adiposity exposure.Using adiposity measures as predictors of all-cause mortality in

women may be misleading unless CRF is also considered.

Obes Rev2010 Mar;11(3):202-21. Epub 2009 Sep 9.Physical activity, fitness and fatness: relations to mortality, morbidity and diseaserisk factors. A systematic review.Fogelholm M-The Academy of Finland, Health Research Unit, 00501 Helsinki, Finland

36 The data indicate that the risk for all-cause and cardiovascularmortality was lower in individuals with high BMI and goodaerobic fitness, compared with individuals with normal BMIand poor fitness (may not be applicable to individuals withBMI > 35)


35/43

4HEALTHY OBESITY

, :

IR IFG/IGT/DM HDL CRP


36/43

Arch Intern Med 2008 Aug 11;168(15):1617-24.The obese without cardiometabolic risk factor clustering and the normal weight

with cardiometabolic risk factor clustering: prevalence and correlates of 2phenotypes among the US population (NHANES 1999-2004).

Wildman RP et alDepartment of Epidemiology and Population Health, Albert Einstein College of Medicine, NY , USA

5440 participants

35% and 29% of obese women and men respectively were healthy

obese (no more than one of the six risk factors)

Arch Intern Med 2008 Aug 11;168(15):1609-16.Identification and characterization of metabolically benign obesity in humans.

Stefan N et alDepartment of Internal Medicine IV, University ofTbingen, D-72076 Tbingen, Germany

314 participants

24% healthy obese men and 24% healthy obese women


37/43

Classic Obesity paradox

?

?


38/43

1. In all published studies the associations between the various factors

were evaluated after the fact and this doesn't demonstrate the cause and

the effect.

2. The number of participants in many studies was small. Do these

results apply in larger populations?

3. None of the studies was based on the duration of obesity. Long termobesity carries greater health risks.

4. In most studies heart failure was diagnosed from clinical symptoms

such as breathing difficulties and extremities' swelling very similar to the

obesity ones. The clinical criteria for heart failure have not been

validated in obese populations and may not be applicable.

Habbu A, Lakkis NM, Dokainish H, 2006. Am J Cardiol 98(7):944-8

The obesity paradox: fact or fiction.


39/43

5. Heart failure or chronic kidney disease are diagnosed earlier in obese

patients compared to normal weight individuals and therefore obese

patients have better outcomes and survival rates.

6. Most studies recruited patients with BMI no more than 35kg/m2. In

some studies with extremely obese patients there doesn't appear to be a

greater survival rate than the underweight. The survival curves are U

shaped and normal and overweight patients have a better chance tosurvive than the patients at the extremes.

7. All published reports are based on BMI, but is BMI the best criterion

to categorize obesity?

Habbu A, Lakkis NM, Dokainish H, 2006. Am J Cardiol 98(7):944-8

The obesity paradox: fact or fiction.

8. adjustment for physical activity and fitness


40/43

1. Obese patients may present earlier with less disease burden.

2. Obese patients may be more aggressively treated.

3. Adipose tissue may secrete protective cytokines and other

hormonal products.

4. Finally, these findings are associative, but do not prove acause-and-effect relationship.

George Griffing, Professor of Medicine at St Louis University andEditor-in-Chief for Internal Medicine at eMedicine


41/43

Heart failure and chronic kidney disease areassociated with malnutrition and inflammation,conditions that reduce survival. Therefore obesitycould be an indicator of better nutrition andsubsequently better survival.

Nat Clin Pract Nephrol 2007, 3:493-506Racial and survival paradoxes in chronic kidney disease.Kalantar-Zadeh K et al


42/43

Genetic predisposition?

Does the fat cell size play any role?

Recent research has shown that obese individuals with numerous but small fat cells

carry lower health risks than those with fewer but larger fat cells.

Int J Obes (Lond) 2011 35(7):971-981Characterizing the profile of obese patients who are metabolically healthy.Primeau V et al


43/43

the obesity paradox.pdf

Documents