copinion body composition phenotypes and obesity paradox · pinion body composition phenotypes and...

REVIEW

CURRENTOPINION Body composition phenotypes and obesity paradox

Copyrig

1363-1950 Copyright � 2015 Wolte

a b c
Carla M. Prado , M. Cristina Gonzalez , and Steven B. Heymsfield
Purpose of review

The obesity paradox is a highly controversial concept that may be attributed to methodological limitationsrelated to its identification. One of the primary concerns is the use of BMI to define obesity. This indexdoes not differentiate lean versus adipose tissue compartments (i.e. body composition) confounding healthconsequences for morbidity and mortality, especially in clinical populations. This review will describe thepast year’s evidence on the obesity paradox phenomenon, primarily focusing on the role of abnormalbody composition phenotypes in explaining the controversies observed in the literature.

Recent findings

In spite of the substantial number of articles investigating the obesity paradox phenomenon, less than 10%used a direct measure of body composition and when included, it was not fully explored (only adiposetissue compartment evaluated). When lean tissue or muscle mass is taken into account, the general findingis that a high BMI has no protective effect in the presence of low muscle mass and that it is the latter thatassociates with poor prognosis.

Summary

In view of the body composition variability of patients with identical BMI, it is unreasonable to rely solelyon this index to identify obesity. The consequences of a potential insubstantial obesity paradox are mixedmessages related to patient-related prognostication.

Keywords

body composition, body composition phenotypes, obesity paradox, sarcopenia, sarcopenic obesity

aDepartment of Agricultural, Food and Nutritional Science, University ofAB, Edmonton, Alberta, Canada, bPost Graduate Program in Health andBehavior, Catholic University of Pelotas, Pelotas, RS, Brazil andcPennington Biomedical Research Center, Baton Rouge, Los Angeles,USA

Correspondence to Carla M. Prado, PhD, Alberta Institute for HumanNutrition, Department of Agricultural, Food and Nutritional Science,University of Alberta, 4-002 Li Ka Shing Centre, Edmonton, AB T6G2P5, Canada. E-mail: [email protected]

Curr Opin Clin Nutr Metab Care 2015, 18:535–551

DOI:10.1097/MCO.0000000000000216

INTRODUCTION

Obesity is a widespread public health problemafflicting many countries around the world.Although obesity conveys a clear unfavourable prog-nosis for morbidity and mortality in the generalpopulation, this association seems blunted in somechronic conditions with obese individuals present-ing with a survival advantage over their counter-parts, a phenomenon termed the ‘obesity paradox’or ‘reverse epidemiology’.

The obesity paradox is a controversial conceptthat can be attributed to methodological limitationsof the studies wherein it has been observed. One ofthe criticisms is the use of anthropometrics estimatessuch as BMI to define obesity. Body weight andBMI do not depict the different proportions of leanversus adipose tissues (i.e. body composition), con-founding health consequences for morbidity andmortality, especially in clinical scenarios [1

&

]. Thisreview will describe the past year’s evidence on theobesity paradox phenomenon, primarily focusingon the role of abnormal body composition pheno-types in explaining the controversies observed inthe literature.

ht © 2015 Wolters Kluwe

rs Kluwer Health, Inc. All rights rese

OBESITY PARADOX: OPPOSING STATESOF KNOWLEDGE

The obesity paradox has been reported in patientswith different types of cardiovascular disease, dia-betes, cancer, renal disease, chronic obstructivepulmonary disease (COPD) and in older age [2]. Inthese studies, survival advantages are reported inthose with increased BMI (obese compared to nor-mal weight patients), contradicting the sharpincrease in mortality with a more than 30 kg/m2

BMI observed in the general population.

r Health, Inc. All rights reserved.

rved. www.co-clinicalnutrition.com

mailto:[email protected]

KEY POINTS

� Obesity paradox is a topic of intense interest yet withnotably contradictory findings.

� Shortcomings associated with these contradictoryfindings may be explained by the inadequacy of BMIas an obesity classifier.

� Variability in body composition phenotypes (i.e.adipose versus muscle tissues) of contemporarypopulation indicates different nutritional status even inindividuals with identical BMI.

� The use of body composition analysis indicates thatexcess adipose tissue has no protective effect in thepresence of low muscle mass.

Nutrition and physiological function

Prolonged survival with increased BMI may beexplained by a variety of factors such as these indi-viduals receiving higher rates of optimal medicalattention/treatment. The availability of energyreserves during acute catabolic illness is alsoanother plausible explanation leading to survivalbias, index event bias or reverse causation [3]. Theprotective effect of anti-inflammatory cytokines oradipokines, including soluble tumour necrosis fac-tor-alpha receptors and lipopolysaccharides, is alsohypothesized to neutralize the inflammatorymilieu of catabolic diseases [3]. Higher BMI mayalso be related to protective factors such asyounger age.

Nonetheless, several shortcomings should beconsidered when interpreting studies reportingthe obesity paradox. These include:

(1)

FIGU

fat m

536

use of incorrect reference values (lower overallBMI reference ranges) [4];

Copyright © 2015 Wolters Kluwer

Obese with nlean ma

Obese with low lean mass

RE 1. Illustration scheme of potential differences in body cass and black represents lean mass).

www.co-clinicalnutrition.com

(2)

Hea

ormal ss

omp

collider stratification bias, a type of selectionbias wherein the conditioning on a variableaffected by exposure shares common causeswith the outcome producing a spurious protec-tive prognostic effect of obesity [5];

(3)
observational and cross-sectional study designs;and
(4)
inadequacy of BMI as an obesity classifier.
As discussed by Heymsfield and Cefalu [6], theuse of BMI as a health risk phenotype has severallimitations. BMI accounts for about two-thirds ofthe between-individual variability in total adiposity.In spite of the high correlation of BMI with adi-posity, a two to three-fold variation in visceral adi-posity is observed at any given BMI, illustrating howBMI is not a specific index of abnormal fat accumu-lation. Therefore, among equally overweight indi-viduals, differences in overall quantity anddistribution of adipose tissue, muscularity, nutri-tional status disease risk factors (disease severityand comorbidities), age, race and sex may explainthe greater risk for shorter survival [4,6].

Of our particular interest, and the focus of thisreview, is the use of BMI to diagnose obesity in viewof the variability in body composition phenotypesof the contemporary population. As we will discussnext, BMI does not accurately depict different com-ponents of body composition and is thereforeunable to predict the prognostic effect of individualtissues, Fig. 1.

BODY COMPOSITION PHENOYPES:DEMYSTIFYING THE OBESITY PARADOX?

Higher BMI is generally found to be associated withgreater muscle mass and strength. This is because fat

lth, Inc. All rights reserved.

Obese with high lean mass

osition in individuals with identical BMI (grey represents

Volume 18 � Number 6 � November 2015

Body composition phenotypes and obesity paradox Prado et al.

and lean masses are expected to grow in harmonywith each other. Although this may be true for themajority of individuals, the assessment of in-vivobody composition has highlighted that this is not aubiquitous phenomenon. High body weight (henceBMI) and fat mass can coexist with obesity, a syn-drome known as ‘sarcopenic obesity’. In fact, theconcurrent appearance of low muscle and high adi-pose tissue can occur at any given BMI across the agespectrum [7,8]. We used North-American popu-lation-cohort data to illustrate the variability inbody composition phenotypes at different agesand across the BMI categories. With our proposedclassification criteria to define abnormal body com-position, we reported that normal-weight individ-uals could present with diverse body compositionphenotypes such as high adiposity–high muscular-ity, low adiposity–low muscularity or even highadiposity–low muscularity (i.e. analogous to sarco-penic obesity). Each of these phenotypes is likely tobe associated with diverse nutritional status.

Oreopoulos et al. [9] reported that BMI misclas-sified 41% of body fat status in patients with chronicheart failure. A higher muscularity and/or loweradiposity were independently associated withadvantageous prognostic factors in these patients.Similar findings were more recently confirmed inpatients with cancer: those with excess fat mass weremisclassified as overweight or even normal weightaccording to BMI criteria [10

&

]. Such misclassifi-cation may explain the controversial results of theobesity paradox reported in studies using BMI as aclassification criterion for obesity. These findingshighlight the need for further studies investigatingthe obesity paradox phenomenon in the context ofbody composition assessment.

THE PAST YEAR EVIDENCE AT A GLANCE

The obesity paradox may certainly be considered atopic of high interest in the scientific communitywith a total of 71 published articles in the past yearalone. Within this time frame, we found 25 reviewarticles, four meta-analyses and 42 original articlesdiscussing this phenomenon. Out of the originalarticles (N¼42), 31 used only BMI to classifyobesity, whereas seven used a surrogate assessmentof body composition (e.g. waist or hip circumfer-ence, skinfold thickness) and four used a directassessment of body composition.

Studies using BMI as the sole indicator ofobesity

Table 1 depicts a summary of the studies in whichonly BMI was used to define obesity [3,5,11–39].

Copyright © 2015 Wolters Kluwe

1363-1950 Copyright � 2015 Wolters Kluwer Health, Inc. All rights rese

Patient cohorts included various forms of cardio-vascular diseases, investigated in the majority of thestudies (N¼21/31). Other patient cohorts includedthose with rheumatoid arthritis, peptic ulcer, per-itonitis and sepsis, diabetes mellitus type 2, demen-tia, COPD, lung resection, mechanical ventilationand a cohort of nondiseased individuals.

Table 1 summarizes that the obesity paradox(higher BMI associated with better prognosis) wasreported in 13 out of 31 studies. Out of these, twostudies observed this association in overweight butnot obese individuals [14,18]; one observed it inmen but not women [27]; one in short but notlong-term outcomes (mortality rate) [34], and onein some outcomes (myocardial infarction and sep-ticemia) but not survival [26]. Mixed findings werereported in two studies when patients were stratifiedby ventilated versus nonventilated group (only theformer showing obesity paradox) [30] and low ver-sus high cardiorespiratory fitness [13], with only theformer showing the paradox. The remaining (andmajority) of the studies failed to demonstrate aprognostic advantage to having excess body weight(Table 1).

The four meta-analyses reported the following:Sharma et al. [40] investigated the relationship ofBMI with all-cause and cardiovascular mortality andhospitalization in six studies of patients with chronicheart failure. The authors concluded that risk forcardiovascular mortality and incidence of hospital-ization was lowest in overweight patients but foundno differences in all-cause mortality. Severe obesitywas associated with poor overall cardiovascular out-comes, suggesting that apparent effect of adipositydoes not occur at the extreme levels of obesity. In aseparate meta-analysis of 36 studies, the same groupinvestigated the obesity paradox after coronary arterydisease revascularization procedures [41]. Whenlooking at total mortality, cardiovascular mortalityand myocardial infarction, only cardiovascularmortality was found to be lower in overweightpatients. In both studies, detailed data on cardio-vascular risk factors, severity/stage of disease or unin-tentional weight loss were not available, which doesnot rule out the possibility of residual confoundingeffects in the reported results.

Niedziela et al. [42] reported the relationshipbetween BMI and total mortality in 26 studies ofpatients after acute coronary syndrome. The authorsconcluded that overweight, obese and severelyobese patients presented with lower mortality thanthose with normal BMI. The authors noted thatalthough obesity was associated with comorbidities,these patients were younger and had less bleedingcomplications, which could have influencedsurvival.


rved. www.co-clinicalnutrition.com 537

Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.

Tab

le1

.Su

mm

ary

ofst

udie

spu

blis

hed

inth

epa

stye

arin

whi

chon

lyBM

Iwas

used

tode

fine

obes

ity

Ref

eren

ceO

bje

ctiv

eC

linic

al

po

pu

lati

on/

Cha

ract

eris

tics

Sam

ple

size

Mea

sure

of

ob

esit

yp

ara

do

x(D

efin

itio

n)O

bes

ity

pa

ra-

do

xre

po

rted

?Fi

ndin

gs

Bake

ret

al.

[11]

Toin

vest

igat

ew

heth

erw

eight

loss

mig

htex

plai

nth

eob

esity

para

dox

inpa

tient

sw

ithrh

eum

atoi

dar

thritis

Patie

nts

with

rheu

mat

oid

arth

ritis

N¼

1674

4BM

Icat

egor

ies:

unde

rwei

ght

<20

kg/m

2;

norm

alw

eight

�20

–25

kg/m

2;

over

wei

ght

�25

–30

kg/m

2;

obes

e�

30

kg/m

2

No

Wei

ght

loss

atan

annu

aliz

edra

teof�

3kg

/m2

was

asso

ciat

edw

ithth

egre

ates

trisk

ofde

ath

The

resu

ltsdi

dno

tsup

port

abi

olog

ical

lypr

otec

tive

role

ofob

esity

onm

orta

lity

risk

Bana

cket

al.

[5]

Tode

mon

stra

teth

atth

eob

esity

para

dox

may

beex

plai

ned

byco

llide

rst

ratif

icat

ion

bias

and

toes

timat

eth

ebi

asin

gef

fect

sof

unm

easu

red

com

mon

caus

esof

CV

Dan

dm

orta

lity

Parti

cipa

nts

inth

eN

HA

NES

III(1

988

–1994)w

hore

porte

dha

ving

CV

D

N¼

16

001

Obe

se:

BMI>

30

kg/m

2;

nono

bese

BMI1

8.5

–29.9

kg/m

2

Yes

The

adju

sted

tota

leffe

ctes

timat

ede

mon

stra

ted

anin

crea

sed

num

ber

ofde

aths

amon

gob

ese

indi

vidu

als

rela

tive

tono

nobe

seco

unte

rpar

ts,

butt

heco

ntro

lled

dire

ctef

fect

show

eda

para

doxi

cal

decr

ease

inm

orta

lity

amon

gob

ese

indi

vidu

als

with

CV

DTh

em

edia

tor–

outc

ome

rela

tions

hip

expl

ains

the

obse

rved

prot

ectiv

eef

fect

ofob

esity

onm

orta

lity.

The

auth

ors

conc

lude

dth

atse

lect

ion

bias

can

mak

ean

appa

rent

lyha

rmfu

lre

latio

nshi

pap

pear

prot

ectiv

e

Buck

and

Møl

ler

[12]

Toex

amin

eth

eas

soci

atio

nbe

twee

nBM

Iand

mor

talit

y

Patie

nts

treat

edsu

rgic

ally

for

perfor

ated

pept

icul

cer

N¼

1699

BMIa

ccor

ding

toW

HO

crite

ria

with

post

hoc

anal

ysis

usin

gfe

wer

gro

ups

No

Bein

gov

erw

eight

orob

ese

had

noef

fect

onm

orta

lity

Cla

rket

al.

[3]

Toco

mpa

reth

eef

fect

ofob

esity

and

rela

ted

risk

fact

ors

on10-y

ear

mor

talit

y

70

orol

der

Afric

ande

scen

tliv

ing

inth

eU

nite

dSt

ates

and

Nig

eria

N¼

2466

BMIa

ccor

ding

toW

HO

crite

ria

No

No

mor

talit

yad

vant

age

was

obse

rved

for

the

over

wei

ght

orob

ese


538 www.co-clinicalnutrition.com Volume 18 � Number 6 � November 2015


Cla

rket

al.

[13]

Toev

alua

teth

ere

latio

nshi

pbe

twee

nBM

Icat

egor

ies,

CRF

defin

edby

PKV

O2

and

clin

ical

outc

omes

inad

vanc

edsy

stol

icH

F

Patie

nts

with

adva

nced

syst

olic

HF

refe

rred

tohe

artt

rans

plan

tatio

nfo

llow

edun

tilde

ath,

urgen

tsta

tus

1A

hear

ttra

nspl

anto

rve

ntricu

lar

assi

stde

vice

1675

patie

nts,

pros

pect

ive

coho

rt,2

year

sfo

llow

-up

3su

bgro

ups

acco

rdin

gto

BMI:

norm

al(1

8.5

–24.9

kg/m

2);

over

wei

ght

(25

–29.9

kg/m

2)an

dob

ese

(�30

kg/m

2)

Hig

hle

veli

fPK

VO

2

>14

ml/

kg/m

in

Mix

edfin

ding

sO

besi

typa

rado

xw

asco

nfirm

edju

stin

the

low

erC

RFle

vel.

Ther

ew

asno

asso

ciat

ion

with

obes

ityan

dbe

tter

surv

ival

inpa

tient

sw

ithhi

ghe

rC

RF,

indi

catin

gth

atim

prov

edfu

nctio

nal

capa

city

may

atte

nuat

eth

eob

esity

para

dox

Cos

tanz

oet

al.

[14]

Toin

vest

igat

eth

eas

soci

atio

nbe

twee

nBW

and

prog

nosi

s

Patie

nts

with

T2D

N¼

10

568

BMIa

ccor

ding

toW

HO

crite

ria

Yes

(ove

rwei

ght

gro

upon

ly)

Bein

gov

erw

eight

was

asso

ciat

edw

itha

low

erm

orta

lity

risk

,bu

tbei

ngob

ese

was

not

Ove

rwei

ght

and

obes

ew

ere

mor

elik

ely

tobe

hosp

italiz

edfo

rca

rdio

vasc

ular

reas

ons

Deh

lend

orff

etal

.[1

5]

Toin

vest

igat

ew

heth

erth

eob

esity

para

dox

inst

roke

patie

nts

isva

lidor

anar

tific

ialf

indi

ngs

due

tose

lect

ion

bias

All

patie

nts

adm

itted

toa

hosp

italf

orst

roke

inD

enm

ark

N¼

53

812

BMIa

ccor

ding

toW

HO

crite

ria

No

BMIw

asin

vers

ely

rela

ted

tom

ean

age

atst

roke

onse

tTh

ere

wer

eno

diffe

renc

esin

the

risk

ofde

ath

byst

roke

inth

efir

stw

eek

orm

onth

afte

rth

est

roke

amon

gBM

Igro

ups

Dile

ttiet

al.

[16]

Toin

vest

igat

eth

eim

pact

ofBM

Ion

long

-term

clin

ical

outc

omes

afte

rim

plan

tatio

nof

zota

rolim

usel

utin

gst

ents

inpa

tient

sw

ithC

VD

Patie

nts

treat

edfo

rC

VD

N¼

5127

BMIt

ertil

es1,

low

orno

rmal

wei

ght

:�

25.9

5kg

/m2;

2,

over

wei

ght

:>

25.9

5–

29.7

4kg

/m2;

3,

obes

e>

29.7

4kg

/m2

No

Att

he2-y

ear

follo

w-u

p,th

ere

wer

eno

diffe

renc

esbe

twee

npa

tient

sin

BMI

terti

le1

com

pare

dw

ith3

inte

rms

ofta

rget

lesi

onfa

ilure

,m

ajor

card

iac

even

ts,

card

iac

deat

h,m

yoca

rdia

lin

farc

tion,

lesi

onre

vasc

ular

izat

ion

orpr

obab

lest

entt

hrom

bosi

s

(Con

tinue

d)


1363-1950 Copyright � 2015 Wolters Kluwer Health, Inc. All rights reserved. www.co-clinicalnutrition.com 539


Tab

le1

(Con

tinue

d)

Ref

eren

ceO

bje

ctiv

eC

linic

al

po

pu

lati

on/

Cha

ract

eris

tics

Sam

ple

size

Mea

sure

of

ob

esit

yp

ara

do

x(D

efin

itio

n)O

bes

ity

pa

ra-

do

xre

po

rted

?Fi

ndin

gs

Farr

eet

al.

[17]

Toev

alua

teth

ehy

poth

esis

that

patie

nts

with

chro

nic

HF

and

obes

ityha

veat

tenu

ated

neur

ohor

mon

alac

tivat

ion

Chi

nese

patie

nts

with

chro

nic

HF

N¼

742

4BM

Icat

egor

ies:

unde

rwei

ght

<20

kg/m

2;

norm

alw

eight

20

–25

kg/m

2;

over

wei

ght

25

–30

kg/m

2;

obes

e>

30

kg/m

2

No

Hig

her

BMIa

ndob

esity

wer

eas

soci

ated

with

low

erno

repi

neph

rine

leve

lsin

mul

tiple

linea

rre

gre

ssio

n;no

repi

neph

rine

atte

nuat

edth

epr

ogno

stic

impa

ctof

BMI

Nor

epin

ephr

ine

was

anin

depe

nden

tpre

dict

oror

wor

seou

tcom

esin

both

obes

ean

dno

nobe

segro

ups.

No

asso

ciat

ion

betw

een

BMIa

ndm

orta

lity

wer

efo

und,

whe

nle

vels

ofth

isho

rmon

ew

asta

ken

into

acco

unt

Gar

cia-

Ptac

eket

al.

[18]

Toin

vest

igat

eth

eas

soci

atio

nbe

twee

nBM

Ian

dm

orta

lity

risk

Patie

nts

with

dem

entia

,at

the

time

ofde

men

tiadi

agno

sis

N¼

11

398

BMIa

ccor

ding

toW

HO

crite

ria

and

addi

tiona

lcut

off

with

inno

rmal

rang

e(’sl

imin

divi

dual

s,BM

I18.5

–22.9

kg/m

2)

and

‘nor

mal

’gr

oup,

BMI2

3–2

4.9

kg/m

2)

Yes

(ove

rwei

ght

gro

upon

ly)

Hig

her

BMIc

ateg

orie

sw

ere

asso

ciat

edw

ithre

duce

dm

orta

lity

risk

upto

and

incl

udin

gth

eov

erw

eight

cate

gor

ySe

x-sp

ecifi

can

alys

isre

veal

eda

redu

ctio

nin

mor

talit

yw

ithin

crea

sing

BMIu

pto

BMIo

f29.9

kg/m

2fo

rm

enan

d24.9

kg/m

2fo

rw

omen

Her

rman

net

al.

[19]

Tode

fine

the

asso

ciat

ion

betw

een

BMIa

ndac

ute

and

long

-term

outc

omes

Patie

nts

with

ST-seg

men

tm

yoca

rdia

linf

arct

ion

(with

in12

h)

N¼

3579

4BM

Iqua

rtile

s:<

24.5

kg/

m2,

24.5

–27.1

,27.1

–30.1

and>

30

kg/m

2

No

Alth

ough

in-h

ospi

tal3

-yea

rou

t-of

-hos

pita

lmor

talit

yw

asde

crea

sed

with

incr

easi

ngBM

I,th

isw

asno

long

ertru

eaf

ter

mod

elad

just

men

t;by

incl

udin

got

her

cova

riat

esin

the

mod

el,

BMIw

asno

long

erpr

edic

tive

ofac

ute

orlo

ng-te

rmm

orta

lity

Hu

etal

.[2

0]

Toin

vest

igat

ew

heth

erBM

Iis

apr

ogno

stic

fact

orin

idio

phat

hic

pulm

onar

yar

terial

hype

rtens

ion

Patie

nts

with

idio

phat

hic

pulm

onar

yar

terial

hype

rtens

ion

N¼

173

WH

Oca

tegor

ies:

3BM

Ica

tego

ries

:un

derw

eight

<18.5

kg/m

2,

norm

alw

eight

18.5

–24.9

kg/m

2

and

over

wei

ght

and

obes

e25

–34.9

kg/m

2

Yes

Hig

her

BMIw

asas

soci

ated

with

low

erm

orta

lity

risk

;pa

tient

sw

ithex

cess

BMI

had

alo

wer

risk

ofde

ath

than

norm

alw

eight

and

unde

rwei

ght

ones




Hua

nget

al.a

[21]

Toin

vest

igat

eth

eas

soci

atio

nbe

twee

nbo

dyco

mpo

sitio

nan

dC

AD

outc

omes

Chi

nese

patie

nts

with

angi

ogra

phic

ally

valid

ated

CA

D

N¼

3280

BMIq

uarti

les.

Aut

hors

have

also

used

aneq

uatio

nca

lled

‘bod

yad

ipos

ityes

timat

or’,

whi

chca

lcul

ated

%FM

usin

gag

e,se

xan

dBM

I.Th

ele

anm

ass

isth

enes

timat

edfrom

asu

bseq

uent

form

ula

Qua

rtile

sof

lean

mas

sw

ere

used

toca

tegor

ize

patie

nts

into

low

vers

ushi

ghle

anm

ass

No

Hig

her

lean

mas

sbu

tnot

FMw

asas

soci

ated

with

low

erca

use

mor

talit

yra

te

Kha

lidet

al.

[22]

Toev

alua

teth

epr

ogno

stic

impa

ctof

prem

orbi

dob

esity

Patie

nts

with

HF

N¼

1487

BMIa

ccor

ding

toW

HO

crite

ria

Yes

Ove

rwei

ght

and

obes

epa

tient

sha

dlo

wer

mor

talit

yth

anno

nobe

se

Kim

etal

.[2

3]

Toin

vest

igat

eth

eim

pact

ofob

esity

onin

itial

neur

olog

ical

seve

rity

Patie

nts

with

isch

aem

icst

roke

N¼

2670

BMIe

valu

ated

inqu

intil

es(Q

1,<

21.2

kg/m

2;

Q2,

21.2

–23.0

kg/m

2Q

3,

23.1

–24.5

kg/m

2;

Q4,

24.6

–26.2

kg/m

2;

Q5,

�26.3

kg/m

2)

No

Alth

ough

obes

ityw

asas

soci

ated

with

bette

rsh

ort-t

erm

func

tiona

lou

tcom

es;

this

asso

ciat

ion

was

lost

afte

rin

itial

neur

olog

ical

seve

rity

was

incl

uded

inth

em

odel

.Th

eref

ore,

the

latte

rm

ight

bea

mor

eim

porta

ntpr

ogno

stic

fact

or

Kon

igst

ein

etal

.[2

4]

Toan

alys

eth

eef

fect

ofBM

Ion

outc

omes

Elde

rlyhi

gh-

risk

patie

nts

with

seve

reao

rtic

valv

est

enos

isun

derg

oing

trans

fem

oral

TAV

I

N¼

409

BMIa

ccor

ding

toW

HO

crite

ria

Yes

Obe

sity

and

over

wei

ght

wer

ein

depe

nden

tlyas

soci

ated

with

bette

rou

tcom

e

Littn

erov

aet

al.

[25]

Toas

sess

shor

t-ter

m/l

ong-

term

mor

talit

yra

tes

with

resp

ectt

oth

eBM

I.

Patie

nts

hosp

italiz

edfo

rH

FN¼

5057

Patie

nts

divi

ded

into

two

grou

ps:

BMIo

f18.5

–25

kg/m

2an

dw

ithBM

I>

25

kg/m

2

Yes

Long

-term

mor

talit

yw

aslo

wer

inov

erw

eight

/obe

sepa

tient

s

Lope

z-D

elgad

oet

al.

[26]

Toqu

antif

yth

eef

fect

ofdi

vers

ede

gre

esof

high

BMIo

ncl

inic

alou

tcom

esaf

ter

card

iac

surg

ery

Patie

nts

unde

rgoi

ngal

lki

nds

ofca

rdia

csu

rger

yN¼

2449

BMIa

ccor

ding

toW

HO

crite

ria

Yes

for

2ou

tcom

esbu

tno

tsur

viva

l

Obe

sity

incr

ease

dpe

riop

erat

ive

myo

card

ial

infa

rctio

nan

dse

ptic

aem

iaaf

ter

card

iac

surg

ery,

but

did

nota

ffect

inho

spita

lm

orta

lity

Mig

ajet

al.

[27]

Toin

vest

igat

ew

heth

erob

esity

influ

ence

onou

tcom

eof

patie

nts

with

AC

Sva

ries

bygen

der

Patie

nts

with

AC

SN¼

341

BMIa

ccor

ding

toW

HO

crite

ria

Yes

,m

enon

lyO

nly

mal

epa

tient

sco

ntribu

ted

toth

eob

esity

para

dox

The

influ

ence

ofob

esity

onou

tcom

esse

ems

tobe

depe

nden

tofse

x (Con

tinue

d)




Tab

le1

(Con

tinue

d)

Ref

eren

ceO

bje

ctiv

eC

linic

al

po

pu

lati

on/

Cha

ract

eris

tics

Sam

ple

size

Mea

sure

of

ob

esit

yp

ara

do

x(D

efin

itio

n)O

bes

ity

pa

ra-

do

xre

po

rted

?Fi

ndin

gs

Num

asaw

aet

al.

[28]

Toin

vest

igat

eth

eim

pact

ofBM

Ion

in-h

ospi

tal

com

plic

atio

ns

Patie

nts

unde

rgoi

ngPC

IN¼

10

142

BMIa

ccor

ding

toW

HO

crite

ria

No

Nor

mal

-wei

ghtp

atie

nts

are

ata

gre

ater

risk

for

in-h

ospi

tal

com

plic

atio

nsth

anob

ese

Paul

etal

.[2

9]

Inve

stig

ate

the

impa

ctof

obes

ityon

in-h

ospi

tal

mor

bidi

tyan

dm

orta

lity

afte

rlu

ngre

sect

ion

Patie

nts

who

unde

rwen

tel

ectiv

ew

edge

rese

ctio

n,lo

bect

omy

orpn

eum

onec

tom

y

N¼

5216

BMIa

ccor

ding

toW

HO

crite

ria

No

BMIw

asno

tapr

edic

tor

ofm

orbi

dity

orm

orta

lity,

even

inth

em

orbi

dly

obes

e(B

MI

>35

kg/m

2)

Bein

gov

erw

eight

appr

oach

edsi

gni

fican

ceas

apr

edic

tor

for

decr

ease

dpu

lmon

ary

com

plic

atio

ns

Sasa

buch

iet

al.

[30]

Eval

uate

the

asso

ciat

ion

ofBM

Iwith

mor

talit

yin

the

ICU

inpa

tient

sw

ithan

dw

ithou

tmec

hani

cal

vent

ilatio

n

Patie

nts

adm

itted

toth

eIC

Uw

ithan

dw

ithou

tm

echa

nica

lven

tilat

ion

N¼

334

238

5BM

Icat

egor

ies:

unde

rwei

ght

(<18.5

kg/m

2),

low

norm

al(1

8.5

–22.9

kg/m

2),

high

norm

al(2

3–24.9

kg/m

2),

over

wei

ght

(25.0

–29.9

kg/

m2)

and

obes

e(>

30

kg/m

2)

Mix

edfin

ding

sIn

the

vent

ilate

dgro

up,

patie

nts

with

ahi

ghe

rBM

Iha

dlo

wer

mor

talit

y,bu

tm

orta

lity

incr

ease

dw

ithin

crea

sing

BMIi

nth

eno

nven

tilat

edgro

up

Shah

etal

.[3

1]

Inve

stig

ate

the

role

ofBM

Ion

mor

talit

yan

dim

pact

ofdy

sgly

cem

ia

Patie

nts

with

hype

rtens

ion

and

atle

asto

neot

her

CH

Drisk

fact

or,

with

out

DM

N¼

5423

4BM

Icat

egor

ies:

unde

rwei

ght

(<22

kg/m

2);

norm

alw

eight

(22

–25

kg/m

2);

over

wei

ght

(25

–30

kg/m

2);

and

obes

e(>

30

kg/m

2)

No

Impa

ired

fast

ing

glu

cose

was

asso

ciat

edw

ithal

l-cau

sem

orta

lity

and

obes

ityw

asas

soci

ated

with

low

eral

l-ca

use

mor

talit

y;ho

wev

er,

this

was

nots

igni

fican

tafte

rex

clud

ing

smok

ers

and

unde

rwei

ght

indi

vidu

als

Taki

guc

hiet

al.

[32]

Inve

stig

ate

the

asso

ciat

ion

ofBM

Iwith

card

iac

func

tion,

neur

ohor

mon

alfa

ctor

s,co

mor

bidi

ties,

and

prog

nosi

s

Hos

pita

lized

HF

patie

nts

N¼

648

BMIa

ccor

ding

toW

HO

crite

ria

Yes

Car

diac

and

all-c

ause

mor

talit

ypr

ogre

ssiv

ely

incr

ease

dfrom

obes

eto

over

wei

ght

,no

rmal

and

unde

rwei

ght

gro

upBM

Iwas

anin

depe

nden

tpr

edic

tor

ofca

rdia

can

dal

l-ca

use

mor

talit

y.A

ll-ca

use

mor

talit

yw

ashi

ghe

rin

the

unde

rwei

ght

gro

up




Taw

ket

al.

[33]

Inve

stig

ate

the

asso

ciat

ion

betw

een

BMIa

ndag

ew

ithth

ese

verity

ofsu

bara

chno

idha

emor

rhag

ean

dfu

nctio

nalo

utco

me

Patie

nts

with

suba

rach

noid

haem

orrh

age

N¼

274

4BM

Icat

egor

ies:

unde

rwei

ght

orno

rmal<

25

kg/m

2;

over

wei

ght2

5–29.9

kg/m

2;

mod

erat

ely

obes

e30

–34.9

kg/m

2;

seve

rely

orve

ryse

vere

lyob

ese

>35

kg/m

2

No

BMIw

asno

tass

ocia

ted

with

mea

sure

sof

func

tion

orse

verity

ofbl

eedi

ng

Utz

olin

oet

al.

[34]

Inve

stig

ate

the

asso

ciat

ion

ofBM

Ion

mor

talit

yin

patie

nts

with

seve

repe

rito

nitis

Patie

nts

with

perito

nitis

and

seps

isw

hone

eded

inte

nsiv

eca

refo

rm

ore

than

2da

yspo

stop

erat

ivel

y

N¼

253

4BM

Igro

ups:

unde

rwei

ght

<21

kg/m

2;

norm

alw

eight

21

–25

kg/m

2;

over

wei

ght

26

–30

kg/m

2;

and

>30

kg/m

2;

also

com

pare

dob

ese

(BM

I>30

kg/m

2)

and

non

obes

egro

ups

Yes

,sh

ortt

erm

only

Surv

ival

at28

days

was

best

inth

eob

ese

and

wor

stin

the

unde

rwei

ght

Ove

rwei

ght

patie

nts

wer

eno

tmor

elik

ely

tobe

disc

harg

edho

me

No

diffe

renc

esw

ere

obse

rved

in5-y

ear

surv

ival

betw

een

gro

ups

Wan

get

al.

[35]

Tode

term

ine

the

rela

tion

betw

een

BMIa

ndm

orta

lity

Patie

nts

with

esta

blis

hed

AF

and

HF

N¼

2016

BMIc

ateg

oriz

edac

cord

ing

toth

eC

hine

seob

esity

wor

king

grou

p–

unde

rwei

ght

,<

18.5

kg/m

2;

norm

alw

eight

,18.5

to<

24

kg/m

2;

over

wei

ght,

24

to<

28

kg/

m2;

obes

e,�

28

kg/m

2

Yes

Obe

sean

dov

erw

eight

patie

nts

had

bette

rsu

rviv

alth

anno

rmal

wei

ght

Wita

ssek

etal

.[3

6]

Toin

vest

igat

eth

eim

pact

ofBM

Ion

mor

talit

yPa

tient

sw

ithST

-ele

vatio

nm

yoca

rdia

linf

arct

ion

N¼

6938

BMIa

ccor

ding

toW

HO

crite

ria

No

AU

-sha

ped

dist

ribu

tion

betw

een

BMIg

roup

sw

asre

porte

dw

ithth

elo

wes

tm

orta

lity

obse

rved

inob

ese

clas

sIa

ndhi

ghe

stin

unde

rwei

ght

.N

onet

hele

ss,

adju

stm

entf

orco

variat

esel

imin

ated

diffe

renc

esbe

twee

ngro

ups

Low

ercr

ude

in-h

ospi

tal

mor

talit

yof

obes

ecl

ass

Ico

uld

bepa

rtial

lyex

plai

ned

bylo

wer

age

and

low

erco

mor

bidi

tyra

tes

Woh

lfahr

teta

l.[3

7]

Toas

sess

the

asso

ciat

ion

ofob

esity

atth

etim

eof

stro

kead

mis

sion

and

wei

ght

loss

afte

rst

roke

with

tota

lmor

talit

y

Patie

nts

hosp

italiz

edfo

rth

eir

first

isch

emic

stro

keN¼

511

BMIa

ccor

ding

toW

HO

crite

ria

Wei

ght

loss

defin

edby

aw

eight

loss

of>

3kg

No

Nor

mal

wei

ght

atho

spita

lizat

ion

and

wei

ght

loss

afte

rst

roke

are

inde

pend

ently

asso

ciat

edw

ithhi

ghe

rm

orta

lity

Obe

sity

and

over

wei

ght

atad

mis

sion

dono

tdec

reas

eth

erisk

asso

ciat

edto

wei

ght

loss

(Con

tinue

d)




Tab

le1

(Con

tinue

d)

Ref

eren

ceO

bje

ctiv

eC

linic

al

po

pu

lati

on/

Cha

ract

eris

tics

Sam

ple

size

Mea

sure

of

ob

esit

yp

ara

do

x(D

efin

itio

n)O

bes

ity

pa

ra-

do

xre

po

rted

?Fi

ndin

gs

Yam

auch

iet

al.

[38]

Inve

stig

ate

the

asso

ciat

ion

betw

een

BMIa

ndin

hosp

italm

orta

lity

inel

derly

patie

nts

with

CO

PD

Elde

rlypa

tient

s(a

ge>

65

year

s)ad

mitt

edto

the

hosp

italf

orC

OPD

N¼

263

940

BMIa

ccor

ding

toW

HO

crite

ria

Nor

mal

wei

ght

was

furth

erdi

vide

din

tolo

w-n

orm

al(B

MI1

8.5

–22.9

kg/m

2)

and

high

norm

al(2

3.0

–24.9

kg/m

2)

Yes

Ove

rwei

ght

and

obes

epa

tient

sha

da

low

erm

orta

lity

than

low

–nor

mal

wei

ght

patie

nts

Hig

her

mor

talit

yw

asas

soci

ated

with

age,

mal

egen

der,

seve

redy

spne

a,lo

wer

leve

lofco

nsci

ousn

ess,

and

low

erac

tiviti

esof

daily

livin

g

Zaf

rir

etal

.[3

9]

Inve

stig

ate

the

prog

nost

icsi

gni

fican

ceof

BMIa

ndBS

Ain

chro

nic

HF

patie

nts

Syst

olic

HF

patie

nts,

atth

efir

stvi

sitt

oth

eH

Fcl

inic

N¼

630

Terti

les

ofBM

I(T1�

25.5

kg/

m2;

25.5<

T2�

30.4

;T3>

30.4

kg/m

2)

and

BSA

(T1�

1.7

9;

1.7

9<

T2�

1.9

9;

T3>

1.9

9)

No

An

inve

rse

asso

ciat

ion

ofBM

Ian

dBS

Ate

rtile

sw

ithm

orta

lity

risk

was

obse

rved

The

obes

itypa

rado

xw

asat

tenu

ated

afte

rm

ultiv

aria

tean

alys

isan

ddi

dno

tper

sist

afte

rad

just

men

tfor

age

(obe

sepa

tient

sw

ere

youn

ger

)

AC

E,an

gio

tens

in-c

onve

rting

enzy

me;

AC

S,ac

ute

coro

nary

synd

rom

e;A

F,ar

terial

fibrilla

tion;

AM

I,ac

ute

myo

card

iali

nfar

ctio

n;BS

A,

body

surfac

ear

ea;

BW,

body

wei

ght

;C

ABG

,co

rona

ryar

tery

bypa

ssgra

ft;C

AD

,co

rona

ryar

tery

dise

ase;

CH

D,

coro

nary

hear

tdis

ease

;C

KD

,ch

roni

cki

dney

dise

ase;

CO

PD,

chro

nic

obst

ruct

ive

pulm

onar

ydi

seas

e;C

RF,

card

iore

spirat

ory

fitne

ss;

CTO

,ch

roni

cto

talo

cclu

sion

;C

VD

,co

rona

ryva

scul

ardi

seas

e;D

M,

diab

etes

mel

litus

;G

FR,

glo

mer

ular

filtra

tion

rate

;H

DL,

high

dens

itylip

opro

tein

;H

F,he

artf

ailu

re;

IABP

,in

tra-a

ortic

ballo

onpu

mpi

ng;

ICU

,in

tens

ive

care

unit;

LAD

,le

ftan

terior

desc

endi

ng;

LVED

D,

left

vent

ricu

lar

end-

dias

tolic

dim

ensi

ons;

LVEF

,le

ftve

ntricl

eej

ectio

nfrac

tion;

Mpa

p,m

ean

pulm

onar

yar

tery

pres

sure

;m

RAP,

mea

nright

arte

rial

pres

sure

;N

T-pr

oBN

P,N

-Ter

min

alpr

obr

ain

type

atriur

etic

pept

ide;

NYH

A,

New

Yor

kH

ealth

Ass

ocia

tion;

PAD

,pe

riph

eral

arte

rydi

seas

e;PC

I,pe

rcut

aneo

usco

rona

ryin

terv

entio

n;PC

WP,

pulm

onar

yca

pilla

ryw

edge

pres

sure

;pr

oBN

T,N

-term

inal

pro-

brai

nna

triur

etic

pept

ide;

PKV

O2,

peak

oxyg

enup

take

;PV

R,pu

lmon

ary

vasc

ular

resi

stan

ce;

SBP,

syst

olic

bloo

dpr

essu

re;

SCA

,su

dden

card

iac

arre

st;

STEM

I,ST

elev

atio

nm

yoca

rdia

linf

arct

ion;

SVO

2,

mix

edve

nous

oxyg

ensa

tura

tion;

T2D

,ty

pe2

diab

etes

;TA

VI,

trans

cath

eter

aorti

cva

lve

impl

anta

tion;

WC

,w

aist

circ

umfe

renc

e.aA

lthou

gh

this

stud

yus

edbo

dyco

mpo

sitio

nte

rmin

olog

y,th

eca

lcul

atio

nsw

ere

derive

dfrom

BMI,

age

and

sex.




Ahmadi et al. [43] investigated the obesity para-dox in kidney transplant recipients in four studies,reporting a higher mortality in obese patients usingpretransplantation BMI. Notably, all of these meta-analysis studies reported a higher risk of shortersurvival among underweight patients. Ahmadiet al. [43] highlighted that unlike obesity, beingunderweight consistently predicted survival. There-fore, there are paradoxical or differing resultssuggesting that the presence of obesity paradox isunlikely in such a scenario [43].

Using data from 89 studies with a total of1 300 794 patients wherein risk estimates were pro-vided for short and long-term mortality on cardio-vascular events, Wang et al. [44] reported a J-shapedrelationship between mortality and BMI in patientswith coronary artery disease. Underweight patientspresented with the highest risk and the overweightand obese with the lowest. Nonetheless, inconsist-ent findings were reported when the long-term datawere evaluated. The long-term inverse relationshipbetween BMI and mortality was attenuated, disap-pearing after 5 years of follow-up. Grades II and IIIobesity were associated with lower risk of short-termmortality but higher risk after 5 years of follow-up.

Studies using surrogate assessments ofbody composition

Additional anthropometric measurements such aswaist and/or hip circumference, skinfold thicknessmeasurements and circumferences were used inseven studies, in which three reported the obesityparadox (one observing it in men only) and theremaining disproving such phenomenon (Table 2)[45–55]. Using an inception cohort of adults withdiabetes, Bozorgmanesh et al. [45] highlighted theneed of adjusting for a measure of central adipositywhen investigating the effect of obesity andmortality. The lack of a value for waist circumfer-ence would have led to an overestimation of themortality associated with an increased BMI in theirdatabase of newly diagnosed patients with diabetes.The authors noted that there is a ‘BMI-paradox’,which is not a sufficient marker of obesity.

The need for further measurements of nutri-tional assessment when investigating the obesityparadox was highlighted in the study by Gastelur-rutinia et al. [47

&&

]. In patients with heart failure,nutritional status (undernourished) was an inde-pendent prognostic factor above and beyond BMIand percentage body fat (calculated using surrogatetools). Therefore, in this study, BMI masked truenutritional status.

Using arm circumferences and skinfoldmeasurements of patients receiving elective surgery,



Rodriguez-Garcia et al. [49] found no differences innosocomial infection and length of hospital staycomparing obese and nonobese patients; nonethe-less, the authors have not controlled for confound-ing variables; only bivariate analysis was conducted.In patients with acute coronary syndrome, Shehabet al. [50] showed that in-hospital and peri-hospitalmortality was not associated with weight, BMI orwaist circumference.

Studies using body compositionassessments

There is a clear need for further body compositionassessment studies to elucidate the contradictoryevidence on the obesity paradox phenomenon asonly four have been published in the past year.Among these, the methodologies utilized were com-puted tomography (CT, two studies), dual-energyX-ray absorptiometry (DXA) or bioelectrical impe-dance analysis (BIA), Table 2.

In 72 patients with COPD, survival was notdifferent between higher versus lower BMI patients(although a trend towards longer survival wasobserved in those with higher BMI) [52

&&

]. Over-weight and obese patients had better lung function,exercise capacity and larger muscle cross-sectionalarea than those with normal BMI. These variableswere able to confound the trend of improved sur-vival in those with excess BMI.

An interesting study in older adults with type 2diabetes; Murphy et al. [54

&&

] used CT-assessed bodycomposition and functional assessments to test theassociation between these variables and mortality.Using multivariate analysis adjusted for demo-graphic and diabetes-risk factors, they reportedhigher risk in normal-weight patients than over-weight ones. The authors further performed amediation analysis to test if adipose tissue, musclesize and physical function would affect the associ-ations between BMI and mortality. From thisanalysis, thigh muscle size mediated 46% of theeffect of the higher risk found in normal-weightpatients. When comparing four groups: over-weight/normal weight and high/low muscle(according to the respective sex-specific median),the authors concluded that being overweight wasonly protective in patients with high muscle massand that the highest mortality was found in the twolow muscle mass groups (either in patients withnormal weight or overweight). These resultsare similar to what has been reported in cancerpatients [10

&

]. Using BIA to assess body compo-sition, Gonzalez et al. [10

&

] reported that the obesityparadox was only present in cancer patients whenobesity was defined by BMI. BMI was not able to




Tab

le2

.Su

mm

ary

ofst

udie

spu

blis

hed

inth

epa

stye

arin

whi

chbo

dyco

mpo

sitio

nor

surr

ogat

eas

sess

men

tsw

ere

used

toin

vest

igat

eth

eob

esity

para

dox

Ref

eren

ceO

bje

ctiv

eC

linic

al

po

pu

lati

on/

Cha

ract

eris

tics

Sam

ple

size

Mea

sure

(s)

of

ob

esit

yp

ara

do

x(D

efin

itio

n)

Bo

dy

com

po

siti

on

ass

essm

ent

or

surr

og

ate

Ob

esit

yp

ara

do

xre

po

rted

?Fi

ndin

gs

Surrogate

bodycompositionmethods

Bozo

rgm

anes

het

al.

[45]

Tote

stw

heth

erth

eco

ntribu

tions

ofan

thro

pom

etric

variab

les

are

nonl

inea

ran

dw

heth

erW

Can

dH

Pco

ntribu

teto

the

obes

itypa

rado

x

Adu

ltsfrom

Iran

with

new

onse

tdia

bete

sat

base

line

exam

inat

ion

orin

cide

ntdi

abet

esin

any

ofth

etw

ofo

llow

-up

s

NU

1322

BMIt

ertil

esm

edia

n:1st

:24.9

kg/m

2;

2nd

:28.9

kg/m

2

and

3rd

:33.8

kg/

m2

WC

and

HC

,w

aist

-to

-hip

ratio

No

Ther

ew

asa

nonl

inea

rre

latio

nshi

pbe

twee

nW

Can

dal

l-cau

sem

orta

lity,

butt

his

rela

tions

hip

was

inve

rse

and

linea

rfo

rH

CA

fter

adju

stm

ents

for

WC

and

HC

,th

ere

wer

eno

asso

ciat

ions

betw

een

BMIa

ndal

l-cau

sem

orta

lity

Cep

eda-

Val

ery

etal

.[4

6]

Tote

stth

ehy

poth

esis

whe

ther

CA

Ddi

seas

eis

less

com

plex

and

seve

rein

obes

eth

anit

isin

nono

bese

indi

vidu

als

Patie

nts

with

AM

IN

U95

BMI�

30

kg/m

2

and/

orW

C�

102

cmin

men

and�

88

cmin

wom

en

WC

Yes

Obe

sity

atth

etim

eof

AM

Iis

asso

ciat

edw

ithle

ssse

vere

CA

D

Gas

telu

rrut

iaet

al.

[47

&&

]To

asse

ssan

dco

mpa

reth

epr

ogno

stic

impa

ctof

mea

sure

sof

nutri

tiona

lsta

tus

BMIa

ndbo

dyfa

t

Am

bula

tory

hear

tfa

ilure

patie

nts

NU

214

BMIa

ccor

ding

toW

HO

crite

ria

Nut

ritio

nals

tatu

sw

asfu

rther

asse

ssed

byal

bum

inan

dly

mph

ocyt

e

Four

anth

ropo

met

ric

mea

sure

men

tsus

edto

calc

ulat

ebo

dyde

nsity

and

derive

%FM

.M

alnu

tritio

ncl

assi

fied

into

one

oftw

oca

tego

ries

:al

bum

in,

lym

phoc

yte

coun

t,sk

info

lds

and

arm

circ

umfe

renc

e�

2be

low

norm

al;

orsk

info

lds,

albu

min

and

lym

phoc

yte

coun

t�1

belo

wno

rmal

No

BMIa

nd%

FMw

ere

not

inde

pend

entp

redi

ctor

sof

2-y

even

tfre

esu

rviv

alM

alnu

tritio

nw

asa

bette

ran

din

depe

nden

tpr

edic

tor

ofsu

rviv

alth

anBM

I




Moh

ebiet

al.

[48]

Toev

alua

teth

eas

soci

atio

nof

seve

ralt

ypes

offa

tdi

stribu

tion

mea

sure

sw

ithth

erisk

ofal

l-cau

sem

orta

lity

inC

KD

patie

nts

Patie

nts

with

CKD

from

Tehr

anN

U1860

BMIa

sa

cont

inuo

usva

riab

leW

eight

,W

Can

dH

CYes

,m

enon

lyD

iffer

entr

esul

tsac

cord

ing

tose

x:in

men

with

CKD

,af

ter

cont

rolli

ngfo

rco

nfou

nder

san

dm

edia

tors

,ha

ving

mor

efa

t(W

C,

HC

orBM

I)re

sults

ina

bette

rsu

rviv

al.

This

effe

ctw

asno

tfou

ndin

wom

en

Rodr

igue

z-G

arci

aet

al.

[49]

Toco

mpa

reLO

San

dN

Iin

cide

nce

betw

een

obes

ean

nono

bese

surg

ical

patie

nts

Surg

ical

Mex

ican

-H

ispa

nic

patie

nts

(gas

trosu

rger

y,ne

uros

urger

yan

dpr

octo

logy

depa

rtmen

ts)

NU

82

WH

Oca

tegor

ies

AC

,TS

F,A

MA

and

AFA

No

NIa

ndLO

Sw

ere

sim

ilar

inob

ese

and

nono

bese

patie

nts

Sheh

abet

al.

(2014)

[50]

Toas

sess

the

in-h

ospi

tala

ndpe

r-hos

pita

lmor

talit

yrisk

inre

latio

nto

patte

rns

ofad

ipos

ity

Patie

nts

with

AC

SN

U7930

BMIa

ccor

ding

toW

HO

crite

ria

and

WC�

102

cmin

men

and�

88

cmin

wom

en

WC

No

In-h

ospi

tala

ndpe

ri-h

ospi

tal

mor

talit

yw

asno

tas

soci

ated

with

obes

ityde

fined

byBM

Iand

WC

Sobi

czew

skiet

al.

[51]

Toex

amin

eth

eas

soci

atio

nof

BMIa

ndad

ipos

etis

sue

dist

ribu

tion,

mea

sure

dby

WC

with

card

iova

scul

arrisk

inpa

tient

sw

ithC

HD

CH

Dpa

tient

sN

U1345

3su

bgro

ups

acco

rdin

gto

BMI:

norm

al(1

8.5

–24.9

kg/m

2);

over

wei

ght

(25

–29.9

kg/m

2)

and

obes

e(�

30

kg/m

2)

WC

quar

tiles

:I

(WC

<91

cm),

II(W

C91

–96.9

cm),

III(W

C97

–104

cm)an

dIV

(WC�

104

cm)

Yes

Direc

trel

atio

nshi

p(W

C)

and

anin

vers

ere

latio

nshi

p(B

MI)

for

both

tota

land

CV

mor

talit

y.BM

Ihad

apr

otec

tive

effe

ctfo

rto

tal

and

CV

mor

talit

yaf

ter

cont

rolli

ngfo

ral

lthe

othe

rfa

ctor

s.Th

ehi

ghe

strisk

gro

upfo

rbo

thto

tal

and

CV

mor

talit

yw

asBM

I<25

kg/m

2w

ithW

C�

104

cm

(Con

tinue

d)




Tab

le2

(Con

tinue

d)

Ref

eren

ceO

bje

ctiv

eC

linic

al

po

pu

lati

on/

Cha

ract

eris

tics

Sam

ple

size

Mea

sure

(s)

of

ob

esit

yp

ara

do

x(D

efin

itio

n)

Bo

dy

com

po

siti

on

ass

essm

ent

or

surr

og

ate

Ob

esit

yp

ara

do

xre

po

rted

?Fi

ndin

gs

Directassessmentofbodycomposition

Gal

esan

uet

al.

[52

&&

]To

inve

stig

ate

ifob

esity

para

dox

inch

roni

cob

stru

ctiv

epu

lmon

ary

dise

ase

(CO

PD)

can

beex

plai

ned

byfa

tac

cum

ulat

ion

orco

nfou

ndin

gfa

ctor

s

Patie

nts

with

CO

PDat

tend

ing

are

habi

litat

ion

prog

ram

me

NU

190

2BM

Isub

gro

ups:

norm

alw

eight

<25

kg/m

2;

over

wei

ght

/obe

se�

25

kg/m

2

Mid

-thig

hm

uscl

ecr

oss-se

ctio

nal

area

from

CT

(MTC

SAC

T)

No

The

tend

ency

ofa

bette

rsu

rviv

alin

over

wei

ght

/ob

ese

CO

PDpa

tient

sdi

sapp

eare

daf

ter

cont

rolli

ngfo

rpe

akw

ork

rate

,M

TCSA

CT

and

parti

alpr

essu

reof

carb

ondi

oxid

e

Hon

get

al.

[53]

Toin

vest

igat

eth

ere

latio

nshi

pbe

twee

nva

riou

sob

esity

mar

kers

and

mor

talit

y

Asi

an(K

orea

n)pa

rtici

patin

gin

alo

ngitu

dina

lstu

dyon

agin

g

NU

1000

BMI(

quar

tiles

ofth

edi

stribu

tion)

VA

Tan

dSA

Tad

ipos

etis

sue

asse

ssed

byC

TTo

talf

atm

ass

and

%as

sess

edby

BIA

Yes

BMIa

ndV

AT

wer

ein

vers

ely

asso

ciat

edw

ithal

l-cau

sem

orta

lity

over

ape

riod

of6

year

s(lo

wes

tw

ithhi

ghe

stqu

artil

eof

BMIa

ndth

ird

ofV

AT)

.To

talf

atm

ass

was

not

asso

ciat

edw

ithm

orta

lity

Mur

phy

etal

.[5

4&

&

]To

inve

stig

ate

the

effe

ctof

adip

ose

tissu

e,m

uscl

esi

zean

dph

ysic

alfu

nctio

non

the

rela

tions

hip

betw

een

BMI

mor

talit

y

Dia

betic

olde

rad

ults

from

Icel

and

NU

637

BMIa

ccor

ding

toW

HO

crite

ria

Thig

hm

uscl

ear

ea,

VA

T,SA

Tan

dIM

AT

No

Nor

mal

-wei

ght

parti

cipa

nts

had

elev

ated

mor

talit

yrisk

than

over

wei

ght

ones

Inno

rmal

-wei

ght

indi

vidu

als,

mor

talit

yrisk

was

atte

nuat

edaf

ter

adju

stm

ents

for

mus

cle

size

Mus

cle

size

med

iate

d46%

ofth

eef

fect

ofno

rmal

wei

ght

onm

orta

lity

Adi

pose

tissu

edi

dno

tat

tenu

ate

mor

talit

yrisk

Pern

aet

al.

[55]

Toev

alua

teth

ere

latio

nshi

pam

ong

sarc

open

ia,

adip

osity

and

met

abol

icm

arke

rsan

dits

impa

cton

loss

ofm

uscl

em

ass

Elde

rlypa

tient

sad

mitt

edin

aph

ysic

alan

dm

edic

ine

and

reha

bilit

atio

ndi

visi

onof

anIta

lian

inst

itute

NU

290

BMIa

sco

ntin

uous

variab

leD

XA(le

anm

ass,

fat

mas

s,an

droi

dan

dgyn

oid

fat)

Yes

The

use

ofa

com

posi

teva

riab

lem

odel

dem

onst

rate

dth

atan

incr

ease

inad

ipos

ityan

dle

vels

ofm

etab

olic

mar

kers

atno

rmal

rang

esis

prot

ects

agai

nstm

uscl

elo

ss



Met

abol

icva

riab

les

(alb

umin

,lo

w-

dens

itylip

opro

tein

chol

este

rol,

high-

dens

itylip

opro

tein

chol

este

rol,

tota

lch

oles

tero

l,tri

glyc

erid

es,

C-

reac

tive

prot

ein,

hom

ocys

tein

e,fo

late

and

vita

min

B12

The

auth

ors

conc

lude

dth

atth

eir

findi

ngs

mig

htin

dica

tea

prot

ectiv

eef

fect

ofad

ipos

ityco

mpa

tible

with

the

obes

itypa

rado

x

AC

,ar

mci

rcum

fere

nce;

AC

S,ac

ute

coro

nary

synd

rom

e;A

FA,

arm

sfa

tare

a;A

MA

,ar

mm

uscl

ear

ea;

CA

D,

coro

nary

arte

rydi

seas

e;C

HD

,co

rona

ryhe

artd

isea

se;

CKT,

chro

nic

kidn

eydi

seas

e;C

T,co

mpu

ted

tom

ogra

phy;

DXA

,du

al-e

nerg

yX-

ray

abso

rptio

met

ry;

FM,

fatm

ass;

HC

,hi

pci

rcum

fere

nce;

IMA

T,in

term

uscu

lar

adip

ose

tissu

e;LO

S,le

ngth

ofho

spita

lsta

y;LV

EF,

left

vent

ricu

lar

ejec

tion

frac

tion;

NI,

noso

com

ial

infe

ctio

n;N

R,no

trep

orte

d;SA

T,su

bcut

aneo

usad

ipos

etis

sue;

TSF,

trice

pssk

info

ld;

VA

T,vi

scer

alad

ipos

etis

sue;

WC

,w

aist

circ

umfe

renc

e.




identify the majority of patients with excess fat massand low muscle mass was an independent risk factorfor higher mortality. Excess fat mass had no protec-tive effect in the presence of low muscle mass andthe shorter survival time was indeed observed in thesarcopenic obesity group.

Two studies noted the obesity paradox usingdirect assessment of body composition. In the studyby Hong et al. [53], higher visceral adiposity assessedby CT scan and not BIA-assessed total fat mass wasassociated with reduced all-cause mortality in eld-erly Asian individuals (mean age 76 years). All-causemortality was lowest within the highest and thirdBMI and visceral adiposity quartiles, respectively.Furthermore, visceral adiposity was a marker formortality in a U-shaped pattern. Interestingly andunfortunately, the authors have not explored theeffect of fat free mass (and hence muscle mass) intheir model, even though that was assessed by BIA.CT-assessed muscle mass was also not evaluated. Asthe authors discussed, muscle mass is an importantvariable that can explain their findings. Finally, thestudy by Perna et al. [55] examines the associationamong low muscle mass, adiposity and metabolicmarkers in Italian older individuals. In a complexstatistical analysis called canonical correlationanalysis and structural equation modelling, individ-ual scores of metabolic profile were created andcorrelated with muscle mass. The authors noted anegative association between sarcopenia severityand adiposity/metabolic profile, indicating a protec-tive effect of adiposity on muscle loss. Therefore,although their results confirmed the obesity para-dox, an increase of adiposity and levels of metabolicparameters were protective in respect to muscle loss[55].

CONCLUSION

A perpetuation of the contradictory findings relatedto the obesity paradox is highlighted in this review,independent of the definition of obesity being solelybased on BMI, surrogate or direct assessments ofbody composition.

There is enough evidence in the literature high-lighting the value of body composition assessment toevaluate and predict nutritional status, and emergingevidence that body composition phenotypes maydemystify the obesity paradox phenomenon. None-theless, less than 10% (four out of 42) of the originalarticles published in the past 12 months included adirect assessment of body composition and, amongthese, a full description of compartments (e.g. musclemass) was not conducted/explored.

In view of the body composition variability ofpatients with identical BMI, particularly in clinical




populations, it is unreasonable to rely solely on thisindex as a marker to identify obesity. Furthermore,differences in fluid shifts that may occur in theseclinical conditions may also impact the accuracy ofBMI [47

&&

], potentially overestimating BMI measure-ments (e.g. heart failure patients).

The use of sophisticated body compositionassessment tools is still limited (especially in epide-miological settings). Notwithstanding, it is unlikelythat we will substantially advance our knowledgewithout the use of this science. As we have pre-viously discussed [1

&

,7], Hippocrates could havemeasured body weight and BMI. We are in an erain which sophisticated tools are needed and in linewith any other evolving field of health-relatedresearch.

If body composition phenotypes can indeedelucidate the dichotomous relationship betweenBMI and prognostication in a variety of clinicaland nonclinical conditions, the need is urgent forsuch a research approach. The consequences of apotential insubstantial obesity paradox are mixedmessages advising individuals to become obese inthe hopes of improving outcomes. Finally, adjustingfor important confounding bias originating fromeach specific condition under study is also import-ant and potentially mediators of the risk factorassociated with obesity.

Acknowledgements

The authors would like to acknowledge Isabella Barbosa,Sarah Purcell, Camila Orsso and Bianca Caroline Orssofor their assistance in creating drafting and/or formattingthe tables, figure and references.

Financial support and sponsorship

None.

Conflicts of interest

There are no conflicts of interest.

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