the oxygen uptake efficiency slope what do we know?

www.jcrpjournal.com Oxygen Uptake Efficiency / 357

Copyright © 2010 Wolters Kluwer Health | Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.

■ PURPOSE: To summarize what is currently known about the oxygenuptake efficiency slope (OUES) as an objective and independentsubmaximal measure of cardiorespiratory fitness in health anddisease.

■ METHODS: A literature search was performed within the followingelectronic databases—PubMed, Cochrane Library, Embase, Web ofScience, CINAHL, PsycINFO, Scopus, and MEDLINE—using thesearch terms “OUES,” “oxygen uptake efficiency slope,” and“ventilatory efficiency.” The search identified 51 articles. Selection,evaluation, and data extraction were accomplished independentlyby 2 authors.

■ RESULTS: Twenty-four studies satisfied all inclusion criteria: 17 cross-sectional studies and 7 intervention studies. The results indicatedthat the OUES is relatively independent of exercise intensity, corre-lates highly with other exercise parameters, appears to have discrimi-native value, and is sensitive to the effects of physical training inpatients with cardiac disease. Oxygen uptake efficiency slope valuesare considerably influenced by anthropometric variables and showlarge interindividual variation.

■ CONCLUSION: Oxygen uptake efficiency slope is an independent andreproducible measure of cardiorespiratory function that does notrequire maximal exercise. It greatly reduces test variability becauseof motivational and subjective factors and is reliable and easilydeterminable in all subjects. Although OUES appears not interchange-able with maximal parameters of cardiopulmonary function, it seemsto be a useful submaximal alternative in subjects unable to performmaximal exercise.

The Oxygen Uptake Efficiency Slope

WHAT DO WE KNOW?

Moniek Akkerman, MSc; Marco van Brussel, PhD; Erik Hulzebos, PhD; Luc Vanhees, PhD; Paul J.M. Helders, PhD; Tim Takken, PhD

Author Affiliations: Child Developmentand Exercise Center, Division ofPaediatrics, University Children’sHospital and Medical Center, Utrecht,the Netherlands (Mrs Akkerman andDrs Van Brussel, Hulzebos, Helders,and Takken); Department ofRehabilitation Sciences, K.U. Leuven,Leuven, Belgium (Dr Vanhees); andDepartment of Health and Lifestyle,University of Applied Sciences,Utrecht, the Netherlands (Dr Vanhees).

Correspondence: Marco van Brussel,MSc, PhD, Child Development andExercise Center, Division ofPaediatrics, University Children’sHospital and Medical Center, RoomKB.02.056. PO Box 85090, NL-3508AB Utrecht, the Netherlands([email protected]).

DOI:10.1097/HCR.0b013e3181ebf316

K E Y W O R D S

exercise parameter

OUES

oxygen uptake efficiency slope

ventilatory efficiency

Exercise testing is widely used in clinical practice toassess the response of both patients and healthy peo-ple to exercise. Maximal oxygen uptake (V· O2max), thehighest rate at which an individual can utilize oxygenduring exercise, is widely recognized as the singlebest measure of aerobic fitness.1 Theoretically, it isdefined as the point at which oxygen uptake (V· O2)reaches a plateau despite further increases in work

rate; however, a true plateau is not always attainedduring standard incremental exercise testing.2,3

Therefore, this objective measure is regularly replacedby the rate of oxygen uptake that occurs at peak exer-cise (V· O2peak),

4-7 even though V· O2peak measurement isinfluenced by patient characteristics and motivation,the selected exercise protocol, and the experience ofthe tester to determine the peak during exercise.4,8-10

HCR200137.qxd 10/24/10 10:17 AM Page 357

the absolute rate of increase in V· O2 per 10-fold increasein ventilation and thereby indicates how effectivelyoxygen is transferred by the lungs and used in theperiphery. The logarithmic transformation of V· E isaimed at linearizing the otherwise curvilinear relationof V· O2 versus V· E, thus making the OUES theoreticallyindependent of the patient-achieved effort level.

To our knowledge, the only known review articlepertaining to the OUES was written by Baba.23 Theauthor concluded that OUES appears to provide anobjective, effort-independent estimation of cardiores-piratory reserve, even in pediatric populations andadults with HF.23 Since these first results were promis-ing, OUES has been used and suggested in the liter-ature.7 Thorough understanding and examination ofthe OUES are required to assess its usefulness andjustify its use in both clinical practice and scientificresearch. Therefore, the aim of this review is to sum-marize what is currently known about the OUES.

METHODOLOGY

A systematic literature search was conducted for eli-gible articles (published up to January 2009) withinthe following electronic databases: PubMed, CochraneLibrary, Embase, Web of Science, CINAHL, PsycINFO,Scopus, and MEDLINE. Each database has its ownindexing term, and thus search terms included weredeveloped for each database. The primary search termsincluded “OUES,” “oxygen uptake efficiency slope,”and “ventilatory efficiency.” Furthermore, referencetracking of all the identified articles was performed.

Inclusion CriteriaArticles were included if they fulfilled the followingcriteria: (1) the original study assessed OUES charac-teristics (eg, reliability, reproducibility, determinants,usefulness, interprotocol agreement, and clinical/prognostic/discriminative value), compared OUES val-ues to other cardiorespiratory variables, or investigatedthe effects of a specific intervention on the OUES; (2)the study was published in a peer-reviewed journalup to January 2009; and (3) the full-text article wasavailable in the English, German, French, or Dutchlanguage.

Exclusion CriteriaCase studies, letters, theses, and meeting abstracts andall other studies that did not fulfill the inclusion cri-teria were excluded.

Validity AssessmentThe systematic search strategy identified 51 potentiallyrelevant references. Two independent researchers

A number of indices that do not require maximalexercise have been introduced, including the oxygenuptake at the ventilatory anaerobic threshold (VAT),the slope of the regression line between minute ven-tilation (V· E) and carbon dioxide production (V· CO2)(V· E/V

·CO2 slope), and the extrapolated maximal oxygen

uptake (EMOC).7,11-13 However, several limitationshave been reported in the literature with regard tothese measures.7 Ventilatory anaerobic threshold, forexample, is not identifiable in all subjects,8,14 and con-troversy remains with regard to the reproducibility ofthis measurement, since seldom a distinct point ofchange in ventilation can be identified.15-17 Moreover,VAT appears to be protocol dependent and its valueis considerably influenced by the nutritional state ofthe subject (eg, carbohydrate loaded or depleted).8,16

Although the prognostic value of the V· E/V·CO2 slope is

robust in patients with heart failure (HF)18 and it hasthe advantage of being derived from multiple datapoints throughout the exercise, the linearity of thisslope appears to be lost beyond the so-called secondanaerobic threshold, leading to dependency on exer-cise duration.17,19 Furthermore, weak inverse correla-tions with V· O2max were reported for this slope.15,20,21

Finally, extrapolating the “true” V· O2max by using aquadratic function (EMOC) appears to be intensitydependent and has not proved useful enough to bewidely adopted.13,21,22

In an attempt to develop an objective and inde-pendent submaximal measure of cardiorespiratoryreserve, Baba et al21 introduced the oxygen uptakeefficiency slope (OUES) in 1996. The OUES repre-sents the rate of increase of V· O2 in response to agiven V· E during incremental exercise, indicating howeffectively oxygen is extracted and taken into thebody.21 Physiologically, the OUES is based on thedevelopment of metabolic acidosis (which dependson the distribution of blood to the working skeletalmuscles), muscle mass, oxygen extraction and utiliza-tion, and the physiologic pulmonary dead space,21

which is affected by the perfusion in the lungs andtheir structural integrity. Cardiovascular, musculoskele-tal, and respiratory functions are thus incorporatedinto a single index.7

Oxygen uptake efficiency slope is calculated fromthe linear relation of V· O2 versus the logarithm of V· Eduring exercise; that is, V· O2 � log10 V· E � b. The slopea in this formula represents the rate of increase in V· O2in response to V· E and is defined as the OUES, where-as b is the intercept.21 The index can be graphicallypresented if V· O2 is plotted on the y-axis and the log-arithm of V· E is plotted on the x-axis. As such, OUESprovides an estimation of the efficiency of ventilationwith respect to V· O2, with greater slopes indicatinggreater ventilatory efficiency. In fact, the OUES reflects

358 / Journal of Cardiopulmonary Rehabilitation and Prevention 2010;30:357-373 www.jcrpjournal.com


HCR200137.qxd 10/24/10 10:17 AM Page 358



an exercise stress test to evaluate possible exclusioncriteria and pathological response to exercise.

Correlations With Other Measures ofCardiorespiratory FunctionPichon et al25 assessed correlations with V· O2max andshowed significant correlations (P � .001) for bothmaximal (r � 0.79) and submaximal (r � 0.77 andr � 0.65 for OUES at 85% and 75% of the maximalaerobic running speed, respectively) OUES. Moreover,V· O2max predicted by OUES did not significantly differfrom measured V· O2max.

25 Correlations between OUESand V· O2peak were highly significant as well (r � 0.72-0.96 [0.83, 0.88, 0.91, 0.94, 0.96, 0.83, 0.89, 0.82, 0.89];P � .001),4,24-29 even if only the first half of exerciseduration was used for OUES calculation (r � 0.92).28

The relationship with the VAT appeared to be mod-erately high to strong (r � 0.66, r � 0.76, r � 0.78for maximal OUES; r � 0.59, r � 0.75, r � 0.80, r �0.83, r � 0.70 for submaximal OUES).26,27,29

Influence of Exercise Duration and IntensityNo significant differences were found between OUESat submaximal and maximal exercises.4,27,29 One study28

even demonstrated that OUES values calculated fromthe first half of exercise did not significantly differfrom values calculated from the second half or theentire exercise test data. However, another studyreported significantly higher values of OUES calculat-ed from data up to 75% and 85% of maximal runningspeed than those obtained from the entire test data.25

Since several authors discussed the issue of limitedprospective utility of a time-based approach to thecalculation of submaximal OUES values,14,38 Pogliaghiet al27 calculated the OUES from data obtained up to60% and 80% of the heart rate reserve. No significant

screened the search results for potentially eligiblestudies. When titles and abstracts suggested that astudy was potentially eligible for inclusion, a full-textarticle of the study was obtained. Disagreementsbetween the 2 authors regarding study eligibility wereresolved by discussion until consensus was reachedor, where necessary, a third independent researcheracted as adjudicator. Twenty-four articles matched allinclusion criteria. A flowchart of the selection proce-dure and reasons for the exclusion of articles aredepicted in Figure 1.

RESULTS

Overall, a total of 24 articles (of which 17 cross-sectional studies and 7 intervention studies) wereconsidered appropriate for this review. Amongthese studies, the OUES has been investigated inhealthy adults (n � 7),4,24-29 in adult patients with achronic condition (n � 15),4,8,14,18,21,22,28,30-36 and inchildren (n � 5).19,21,37-39 The results of aforemen-tioned studies are described below. The effects ofspecific interventions on the OUES are consideredthereafter. All included studies are presented inTable 1.

OUES in Healthy AdultsThe OUES has been studied in a total of 1187 healthyadults between 19 and 96 years of age. Health wasdefined as the absence of cardiac, respiratory, or otherdiseases, as confirmed by physical examination.4,24-29

In addition, 4 studies performed electrocardiographicassessment4,25,28,29 and 1 study also performed spiro-metric and echocardiographic assessment.28 The par-ticipants in the study by Pogliaghi et al27 underwent

Figure 1. Flowchart of study selection and exclusion criteria. Abbreviation: OUES, oxygen uptake efficiency slope.

HCR200137.qxd 10/24/10 10:17 AM 59



Ta

ble

1 •

Ove

rvie

w o

f In

clud

ed S

tudi

es I

nves

tigat

ing

the

Oxy

gen

Upt

ake

Effic

ienc

y Sl

ope

Age

, y

Firs

t (M

ean

�O

utco

me

Aut

hor

n SD

)M

etho

dsM

easu

res

Resu

lts

Adu

ltsH

ealth

yB

aba,

19

(11

M/8

F)

21 �

1 C

ycle

erg

omet

er e

xerc

ise

test

s (m

axim

al),

OU

ES, V

AT,

Cor

rela

tions

bet

wee

n O

UES

and

V· O2p

eak

(r�

0.91

-.94

).et

al24

Ran

ge:

2 tim

es w

ithin

7 d

.V· O

2pea

k,

Exce

llent

rep

rodu

cibi

lity

of V· O

2pea

kan

d O

UES

(CO

R

19-4

0In

itial

wor

kloa

d 0

W (2

min

), in

crem

ent

HR

max

16%

and

20%

, res

pect

ivel

y), V

AT le

ss r

epro

duci

ble

20 o

r 30

or

40 W

/min

. Int

erte

st

(CO

R 3

1%).

repr

oduc

ibili

ty w

ith B

land

-Altm

an C

OR

.Pi

chon

50

M

24 �

9.9

Trea

dmill

exe

rcis

e te

sts

(max

imal

), us

ing

OU

ES (a

t 75%

, C

orre

latio

ns w

ith V· O

2max

: OU

ES-1

00 (r

�0.

79),

OU

ES-8

5 et

al25

a st

anda

rdiz

ed p

roto

col.

War

m-u

p 85

%, a

nd

(r�

0.77

), O

UES

-75

(r�

0.65

), an

d V

AT (r

�0.

71).

(5 m

in) b

etw

een

7 an

d 10

km

/h,

100%

of

OU

ES a

t 75%

and

85%

of M

AS

sign

ifica

ntly

gre

ater

than

in

crem

ent 1

km

/h/m

in. B

land

-Altm

an

MA

S), V

AT,

OU

ES a

t 100

%. V

· O2m

axpr

edic

ted

by O

UES

not

fo

r ag

reem

ent.

V· O2m

ax,

sign

ifica

ntly

diff

eren

t fro

m m

easu

red

V· O2m

ax. L

imits

of

RER

, HR

max

, ag

reem

ent (

Bla

nd-A

ltman

) �10

.5 m

LO

2/m

in/k

g.M

AS

Mou

rot

15 F

(8 E

/7 C

) E:

21.

8 �

Cyc

le e

rgom

eter

exe

rcis

e te

sts

(max

imal

), O

UES

(at 7

5%,

Cor

rela

tions

with

V· O2p

eak:

OU

ES a

t 75%

, 90%

, and

100

%

et a

l263.

3 bo

th b

efor

e an

d af

ter

the

inte

rven

tion

90%

, and

(r

�0.

65, r

�0.

71, r

�0.

72) a

nd V

AT (r

�0.

83).

C

: 21.

7 �

peri

od. I

nitia

l wor

kloa

d 0

W (3

min

), 10

0% o

f C

orre

latio

ns b

etw

een

OU

ES a

t 75%

, 90%

, and

100

% a

nd

1.9

incr

emen

t 30

W/3

min

. Int

erte

st

ET),

VAT

, V

AT (r

�0.

59, r

�0.

69, r

�0.

66).

Stro

ng c

orre

latio

ns

repr

oduc

ibili

ty w

ith B

land

-Altm

an C

OR

.V· E/

V· CO

2be

twee

n O

UES

at 7

5%, 9

0%, a

nd 1

00%

of E

T (r

�0.

80-

Inte

rven

tion:

6 w

k, 3

tim

es/w

k in

term

itten

t sl

ope,

0.

95).

No

sign

ifica

nt d

iffer

ence

s in

OU

ES, V

· E/V· C

O2

slop

e,SW

EET

(cyc

ling)

.V· O

2pea

k,

V· E/V· O

2, a

nd V

d/V

AT a

fter

trai

ning

, des

pite

incr

ease

d V

d/V

AT,

V· O2p

eak

and

dela

yed

VAT

.R

ERPo

glia

ghi

29 (1

8 M

/11

F)M

: 68.

6 �

Cyc

le e

rgom

etry

exe

rcis

e te

sts

(max

imal

). O

UES

(at 7

5%,

No

sign

ifica

nt d

iffer

ence

s be

twee

n O

UES

at 7

5%, 9

0%,

et a

l275.

8In

itial

wor

kloa

d 50

W (3

min

), 90

%, a

nd

and

100%

of E

T or

bet

wee

n O

UES

at 1

00%

and

F:

67.

1 �

incr

emen

t 10

W/m

in.

100%

of E

T,

HR

rese

rve-

base

d m

easu

res

of O

UES

(OU

ES 8

0%

3.8

and

60%

H

Rre

serv

e an

d O

UES

60%

HR

rese

rve)

.A

ge �

60an

d 80

% o

f H

Rre

serv

e),

V· O2p

eak

Mol

lard

24

MT:

29

�5

Cyc

le e

rgom

eter

exe

rcis

e te

sts

(max

imal

). O

UES

(at 8

0%

Cor

rela

tions

for

OU

ES a

t 80%

and

100

% w

ith V· O

2pea

k

et a

l29(1

0 T/

14 U

T)

UT:

27

�5

Initi

al w

orkl

oad

60 W

(3 m

in),

and

100%

(r

�0.

83-0

.89)

and

VAT

(r�

0.70

-0.8

3). O

UES

at 8

0%

incr

emen

t 30

W/2

min

. of

ET)

, VAT

, si

mila

r to

OU

ES a

t 100

% in

all

cond

ition

s. N

o re

duct

ion

Inte

rven

tion:

Eac

h su

bjec

t mea

sure

d on

V· O

2pea

kin

OU

ES a

t 100

0 m

. OU

ES d

eclin

ed fa

ster

in T

sub

ject

s 4

sim

ulat

ed a

ltitu

des

(0, 1

000,

250

0,

than

in U

T su

bjec

ts d

urin

g ex

erci

se in

hyp

oxia

.an

d 45

00 m

).

(con

tinue

s)

HCR200137.qxd 10/24/10 10:17 AM Page 360



Ta

ble

1 •

Ove

rvie

w o

f In

clud

ed S

tudi

es I

nves

tigat

ing

the

Oxy

gen

Upt

ake

Effic

ienc

y Sl

ope

(Con

tinue

d)

Age

, y

Firs

t (M

ean

�O

utco

me

Aut

hor

n SD

)M

etho

dsM

easu

res

Resu

lts

Patie

nts

Bab

a 50

with

HF:

Tr

eadm

ill e

xerc

ise

test

s (m

axim

al),

usin

g O

UES

C

orre

latio

n be

twee

n O

UES

and

V· O2p

eak

(r�

0.78

).et

al8

NY

HA

I I:

61.1

�th

e sy

mpt

om-l

imite

d or

igin

al o

r (a

t 75%

, 90%

, N

o si

gnifi

cant

diff

eren

ces

and

exce

llent

agr

eem

ent b

etw

een

(12

M/7

F)

7.9

mod

ified

Bru

ce p

roto

col.

and

100%

O

UES

at 7

5%, 9

0%, a

nd 1

00%

(IC

C �

0.99

)Si

gnifi

cant

N

YH

AII

II: 6

5.9

�of

ET)

, VAT

, di

ffere

nces

in O

UES

, V· O

2pea

k, a

nd V

AT b

etw

een

NY

HA

(14

M/6

F)

8.3

V· O2p

eak

func

tiona

l cla

sses

(I-I

II).

NY

HA

III

III: 6

7.7

�

(4 M

/7 F

)10

.2Va

n 80

with

HF:

W

ith L

VD

:C

ycle

erg

omet

er e

xerc

ise

test

(max

imal

), O

UES

(at 5

0%,

Cor

rela

tions

with

V· O2p

eak:

VAT

(r�

0.81

), O

UES

/kg

(r�

Laet

hem

45

with

64

�6

usin

g a

ram

p pr

otoc

ol. I

nitia

l 75

%, a

nd

0.78

), O

UES

(r�

0.68

), an

d V· E/

V· CO

2sl

ope

(r�

�0.

49).

et a

l32an

d 35

W

ithou

t LV

D:

wor

kloa

d 20

W, i

ncre

men

t 10

0% o

f Va

lues

obt

aine

d fr

om d

ata

up to

50%

, 75%

, and

100

% o

f w

ithou

t 58

�10

10 W

/min

.ET

), V

AT,

ET d

id s

igni

fican

tly d

iffer

for

V· O2p

eak

and

V· E/V· C

O2

slop

e,

LVD

V· E/V· C

O2

whe

reas

OU

ES/k

g re

mai

ned

stab

le. O

UES

at 7

5%

slop

e,

diffe

red

�3.

0% fr

om O

UES

at 1

00%

. OU

ES a

nd o

ther

V· O

2pea

ksu

bmax

imal

par

amet

ers

sign

ifica

ntly

low

er in

pat

ient

s w

ith L

VD

.D

avie

s 24

3 w

ith H

F 59

�12

Trea

dmill

exe

rcis

e te

sts

(max

imal

), O

UES

(at 5

0%

Cor

rela

tions

for

OU

ES w

ith V· O

2pea

k(r

�0.

81),

VAT

(0.6

2),

et a

l22(2

12 M

/31

follo

win

g a

mod

ifica

tion

of th

e an

d 10

0% o

f an

d V· E/

V· CO

2sl

ope

(r�

�0.

62).

Valu

es o

btai

ned

from

F)

: B

ruce

pro

toco

lET

), V

AT,

the

first

50%

of e

xerc

ise

and

thos

e ob

tain

ed w

ith fu

ll N

YH

AI-

IVV· E/

V· CO

2da

ta d

iffer

ed 1

% fo

r O

UES

vs

25%

for

V· O2p

eak.

OU

ES

slop

e,

valu

es w

ere

sign

ifica

ntly

low

er th

an p

redi

cted

on

the

V· E/V· O

2ba

se o

f age

, sex

, and

BSA

. OU

ES v

alue

s fe

ll w

ith

slop

e, R

ERw

orse

ning

sym

ptom

s. In

a m

ultiv

aria

ble

pred

ictio

nm

odel

, OU

ES w

as th

e on

ly s

igni

fican

t ind

epen

dent

prog

nost

ic v

aria

ble.

Def

oor

590

with

CA

D

55.1

�9.

7C

ycle

erg

omet

er e

xerc

ise

test

s (m

axim

al),

OU

ES (a

t RER

�C

orre

latio

ns w

ith V· O

2pea

k: O

UES

at t

he v

ario

us E

Ts (r

�

et a

l14(5

12 M

/78

F)in

itial

wor

kloa

d 20

W, i

ncre

men

t 1.

0 an

d at

0.

84-0

.89)

and

VAT

s (r

�0.

86).

No

diffe

renc

es b

etw

een

30 W

/3 m

in.

90%

and

O

UES

val

ues

at 9

0% a

nd 1

00%

, but

sig

nific

antly

In

terv

entio

n: 3

-mo

supe

rvis

ed e

xerc

ise

100%

of

high

er v

alue

s at

RER

�1.

0. O

UES

, V· O

2pea

k, a

nd V

AT

trai

ning

pro

gram

, mea

n fr

eque

ncy

ET),

VAT

, in

crea

sed

sign

ifica

ntly

afte

r tr

aini

ng, w

here

as th

e 2.

21 �

0.49

tim

es/w

k, m

ean

V· E/V· C

O2

V· E/V· C

O2

slop

e m

ildly

dec

reas

ed. M

ultip

le r

egre

ssio

n in

tens

ity 8

0.9

�10

.3%

of H

Rpe

ak.

slop

ean

alys

is r

evea

led

trai

ning

freq

uenc

y as

the

stro

nges

tde

term

inan

t for

the

chan

ge in

OU

ES. C

hang

es in

V· O

2pea

kco

rrel

ated

bet

ter

with

cha

nges

in O

UES

(r�

0.61

) and

VAT

(r�

0.55

) tha

n w

ith c

hang

es in

V· E/V· C

O2

slop

e (r

��

0.17

).

(con

tinue

s)

HCR200137.qxd 10/24/10 10:17 AM Page 361



Ta

ble

1 •

Ove

rvie

w o

f In

clud

ed S

tudi

es I

nves

tigat

ing

the

Oxy

gen

Upt

ake

Effic

ienc

y Sl

ope

(Con

tinue

d)

Age

, y

Firs

t (M

ean

�O

utco

me

Aut

hor

n SD

)M

etho

dsM

easu

res

Resu

lts

Tren

ell

10 w

ith M

M

42 �

14C

ycle

erg

omet

er e

xerc

ise

test

s O

UES

, Si

gnifi

cant

impr

ovem

ent i

n O

UES

, but

no

sign

ifica

nt

et a

l30(3

M/7

F)

(sub

max

imal

: 80%

HR

max

), H

RR

-V· O2

incr

ease

in H

RR

-V· O2

afte

r ex

erci

se th

erap

y in

pat

ient

s in

divi

dual

ly ta

ilore

d w

ork

rate

s,

with

MM

.in

crem

ent e

very

2 m

in.

Inte

rven

tion:

3-m

o ae

robi

c ex

erci

se th

erap

y (c

yclin

g),

3 tim

es/w

k.Va

n de

21

4 w

ith

67 �

8C

ycle

erg

omet

er e

xerc

ise

test

s O

UES

, V· O

2pea

k,

Cor

rela

tions

with

V· O2p

eak:

OU

ES/k

g (r

�0.

79) a

nd

Veir

e C

AD

(m

axim

al).

V· E/V· C

O2

V· E/V· C

O2

slop

e (r

��

0.29

). Si

gnifi

cant

diff

eren

ces

et a

l31(1

82 M

/ sl

ope,

be

twee

n pa

tient

s w

ith in

term

edia

te V· O

2pea

kva

lues

32

F):

V· O2m

ax,

diffe

ring

from

eac

h ot

her

in te

rms

of in

dice

s of

N

YH

AR

ERpr

ogre

ssiv

e LV

rem

odel

ing,

sys

tolic

dys

func

tion,

I-

IIIan

d ne

uroh

orm

onal

act

ivat

ion.

Van

160

with

68

�5

Cyc

le e

rgom

eter

exe

rcis

e te

sts

OU

ES,

Cor

rela

tions

with

V· O2p

eak:

OU

ES (r

�0.

73),

OU

ES/k

g La

ethe

m

CA

D (1

32

Age

�60

(max

imal

), us

ing

a ra

mp

or

V· O2p

eak,

(r

�0.

84),

VAT

(r�

0.85

), an

d V· E/

V· CO

2sl

ope

et a

l40M

/28

F)gr

adua

l pro

toco

l. In

itial

wor

kloa

d V

AT,

(r�

�0.

44).

50 W

, inc

rem

ent 2

5 W

/min

. V· E/

V· CO

2O

UES

/kg

and

VAT

bes

t sub

max

imal

pre

dict

ors

of V· O

2pea

k.

Bla

nd-A

ltman

for

agre

emen

t.sl

ope

Sign

ifica

nt d

iffer

ence

s be

twee

n m

easu

red

V· O2p

eak

and

estim

ated

V· O2p

eak

pred

icte

d by

OU

ES/k

g in

pat

ient

s w

ith s

ever

ely

decr

ease

d or

pre

serv

ed e

xerc

ise

capa

city

,bu

t not

in p

atie

nts

with

inte

rmed

iate

exe

rcis

e ca

paci

ty.

Sign

ifica

nt d

iffer

ence

s be

twee

n m

easu

red

V· O2p

eak

and

estim

ated

V· O2p

eak

pred

icte

d by

VAT

with

in a

llsu

bgro

ups.

Are

na

341

with

HF

56.3

�Tr

eadm

ill e

xerc

ise

test

s (m

axim

al),

OU

ES a

nd

Cor

rela

tions

for

OU

ES (a

t 50%

and

100

%) w

ith V· O

2pea

k

et a

l18(2

83 M

/58

14.2

follo

win

g a

ram

ping

pro

toco

l.V· E/

V· CO

2(r

�0.

65, r

�0.

73) a

nd V· E/

V· CO

2sl

ope

(r�

�0.

61,

F)sl

ope

(bot

h r

��

0.65

).at

50%

and

R

OC

cur

ve a

naly

sis

dem

onst

rate

d st

atis

tical

ly s

igni

fican

t 10

0% o

f cl

assi

ficat

ion

sche

mes

for

both

V· E/V· C

O2

slop

e an

d ET

), V· O

2pea

kO

UES

cal

cula

tions

as

wel

l as

V· O2p

eak

(all

area

s un

der

the

RO

C c

urve

�0.

74).

Are

a un

der

the

RO

C c

urve

for

the

V· E/V· C

O2

slop

e at

100

% w

as s

igni

fican

tly g

reat

er th

anfo

r V· O

2pea

kan

d O

UES

at 5

0% a

nd 1

00%

.

(con

tinue

s)

HCR200137.qxd 10/24/10 10:17 AM Page 362



Ta

ble

1 •

Ove

rvie

w o

f In

clud

ed S

tudi

es I

nves

tigat

ing

the

Oxy

gen

Upt

ake

Effic

ienc

y Sl

ope

(Con

tinue

d)

Age

, y

Firs

t (M

ean

�O

utco

me

Aut

hor

n SD

)M

etho

dsM

easu

res

Resu

lts

Van

35 w

ith H

F 54

�9

Cyc

le e

rgom

eter

test

s (m

axim

al) a

t the

O

UES

Ex

celle

nt c

orre

latio

n be

twee

n O

UES

at 9

0% a

nd 1

00%

La

ethe

m

(26

M/9

F):

star

t, th

e m

iddl

e, a

nd th

e en

d of

the

(at 9

0% a

nd

of E

T (r

�0.

97).

OU

ES, V

· O2p

eak,

VAT

, and

V· E/V· C

O2

et a

l35N

YH

AII-

IIIin

terv

entio

n, u

sing

a g

radu

al p

roto

col.

100%

of

slop

e im

prov

ed d

urin

g th

e fir

st p

art o

f the

ET

peri

od;

Initi

al w

orkl

oad

25 W

, inc

rem

ent

ET),

V· O2p

eak,

on

ly V

AT c

ontin

ued

to im

prov

e in

the

seco

nd p

art.

10 W

/min

.V

AT,

Impr

ovem

ent i

n O

UES

cor

rela

ted

sign

ifica

ntly

bet

ter

Inte

rven

tion:

6-m

o ca

rdia

c re

habi

litat

ion

V· E/V· C

O2

with

impr

ovem

ents

in V· O

2pea

k(r

�0.

64-0

.77)

than

in

prog

ram

, 2 ti

mes

/wk.

slop

e, R

ERan

y ot

her

incl

uded

exe

rcis

e pa

ram

eter

.Va

n 30

HTx

59

.9 �

9.1

Cyc

le e

rgom

eter

exe

rcis

e te

sts

(max

imal

), O

UES

, C

orre

latio

ns fo

r O

UES

/kg

with

V· O2p

eak

(r�

0.63

), V

AT

Laet

hem

pa

tient

sus

ing

a st

epw

ise

incr

emen

tal p

roto

col.

V· O2p

eak,

(r

�0.

92),

and

V· E/V· C

O2

slop

e (r

��

0.49

) bef

ore

HTx

.et

al34

Initi

al w

orkl

oad

25 W

, inc

rem

ent 1

0 or

V

AT,

Cha

nges

in O

UES

/kg

afte

r H

Tx s

igni

fican

tly c

orre

late

d 25

W/m

in.

V· E/V· C

O2

with

cha

nges

in V· O

2pea

kan

d V

AT (b

oth

r�

0.63

), bu

t not

In

terv

entio

n: H

Tx.

slop

e, R

ERw

ith c

hang

es in

V· E/V· C

O2

slop

e or

mar

ked

impr

ovem

ents

in c

entr

al h

emod

ynam

ics

or r

estin

g lu

ng fu

nctio

n.A

rena

33

7 w

ith H

F 56

.5 �

14.1

Trea

dmill

exe

rcis

e te

sts,

usi

ng a

O

UES

, BM

ISi

gnifi

cant

cor

rela

tion

betw

een

OU

ES a

nd B

MI (

r�

0.32

). et

al33

(280

M/5

7 F)

cons

erva

tive

ram

ping

pro

toco

l.O

UES

diff

er s

igni

fican

tly a

mon

g al

l 3 B

MI g

roup

s, w

ith

(nor

mal

th

e m

ost f

avor

able

val

ue fo

und

in th

e ob

ese

subg

roup

. w

eigh

t, O

UES

pro

gnos

tical

ly s

igni

fican

t in

norm

al w

eigh

t ov

erw

eigh

t, (o

ptim

al th

resh

old:

/�

1.2,

haz

ard

ratio

: 3.7

, 95%

an

d ob

ese)

CI:

1.4-

9.9,

P�

.01)

, ove

rwei

ght (

optim

al th

resh

old:

/�1.

5, h

azar

d ra

tio: 3

.9, 9

5% C

I: 1.

3-11

.1, P

�.0

1),

and

obes

e (o

ptim

al th

resh

old:

/�

1.7,

haz

ard

ratio

: 4.1

,95

% C

I: 1.

4-12

.8, P

�.0

1) s

ubgr

oups

.G

adem

an

34 w

ith H

F E:

60

�9

Cyc

le e

rgom

eter

exe

rcis

e te

sts

(max

imal

) O

UES

(at 7

5%,

No

sign

ifica

nt d

iffer

ence

s be

twee

n O

UES

at 7

5%, 9

0%,

et a

l36E:

19

M/1

FC

: 63

�10

at b

asel

ine

and

afte

r 4

wk

(C) o

r af

ter

90%

, and

an

d 10

0% o

f ET.

Exp

erim

enta

l gro

up s

how

ed a

C

: 13

M/1

F

the

exer

cise

trai

ning

pro

gram

(E).

100%

of

sign

ifica

nt in

crea

se in

V· O2p

eak

(14%

), O

UES

(19%

), N

YH

AII-

IIIIn

itial

wor

kloa

d 5

W, i

ncre

men

t ET

), V· O

2pea

k,

OU

ES/k

g (1

7%),

OU

ES 7

5 (2

1%),

and

OU

ES 9

0 (2

2%) a

nd5

W/3

0 s.

V· E/V· C

O2

a de

crea

se in

V· E/V· C

O2

slop

e (1

4%) a

fter

trai

ning

. Con

trol

In

terv

entio

n: 3

0 se

ssio

ns e

xerc

ise

slop

egr

oup

show

ed s

light

impr

ovem

ents

in O

UES

but

tr

aini

ng, 2

-3 ti

mes

/wk.

sign

ifica

ntly

hig

her

incr

ease

s in

the

expe

rim

enta

l gro

up.

Hea

lthy

Hol

lenb

erg

1010

M

edia

n: 6

8 Tr

eadm

ill e

xerc

ise

test

s (m

axim

al),

OU

ES (a

t 75%

, O

UES

cor

rela

ted

with

V· O2p

eak

in b

oth

men

(r�

0.88

) and

vs

et

al4

998

heal

thy

R

ange

: fo

llow

ing

the

Cor

nell

mod

ifica

tion

90%

, and

w

omen

(r�

0.83

). O

UES

at 7

5% d

iffer

ed o

nly

1.9%

from

pa

tient

s(4

19 M

/579

F)

53-9

6 of

the

Bru

ce p

roto

col.

725

heal

thy

100%

of

OU

ES a

t 100

%. O

n se

rial

test

s, O

UES

less

var

iabl

e th

an

12 M

with

HF

subj

ects

wer

e te

sted

aga

in a

fter

2 y.

ET),

V· O2p

eak,

ex

erci

se d

urat

ion

or V· O

2pea

k. O

UES

dec

lined

line

arly

R

ERw

ith a

ge. S

trong

cor

rela

tion

with

FEV

1an

d sm

okin

g hi

stor

y.O

UES

val

ues

in p

atie

nts

with

HF

muc

h lo

wer

than

thos

e of

hea

lthy

elde

rly.

(con

tinue

s)

HCR200137.qxd 10/24/10 10:17 AM Page 363



Ta

ble

1 •

Ove

rvie

w o

f In

clud

ed S

tudi

es I

nves

tigat

ing

the

Oxy

gen

Upt

ake

Effic

ienc

y Sl

ope

(Con

tinue

d)

Age

, y

Firs

t (M

ean

�O

utco

me

Aut

hor

n SD

)M

etho

dsM

easu

res

Resu

lts

Gia

rdin

i 88

H

ealth

y:

Cyc

le e

rgom

eter

test

s (m

axim

al).

OU

ES (f

rom

N

o si

gnifi

cant

diff

eren

ces

betw

een

OU

ES, O

UES

0-5

0,

et a

l2835

hea

lthy

25 �

9In

itial

wor

kloa

d 10

W, i

ncre

men

t th

e fir

st 5

0%,

and

OU

ES 5

0-10

0, a

nd n

o di

ffere

nces

bet

wee

n (1

8 M

/17

F),

Font

an:

10 W

/min

.th

e la

st 5

0%,

mea

sure

d an

d pr

edic

ted

valu

es o

f OU

ES in

hea

lthy

53 w

ith h

eart

20

�6

and

100%

of

subj

ects

, pat

ient

s w

ith M

/S a

nd F

onta

n w

ho w

ere

not

dise

ase:

M

/S:

the

exer

cise

cy

anot

ic a

t res

t. In

pat

ient

s w

ith F

onta

n w

ho w

ere

Font

an27

�10

da

ta),

cyan

otic

at r

est,

OU

ES 0

-50

diffe

red

sign

ifica

ntly

from

(1

0 M

/13

F)

V· O2p

eak,

O

UES

and

OU

ES 5

0-10

0 an

d m

easu

red

and

pred

icte

d M

/SV· E/

V· CO

2va

lues

of b

oth

OU

ES a

nd O

UES

50-

100

diffe

red

(18

M/1

2 F)

slop

esi

gnifi

cant

ly a

s w

ell.

Chi

ldre

nH

ealth

yB

aba

16 (1

0 M

/6 F

)12

.7 �

2.8

Trea

dmill

exe

rcis

e te

sts

(max

imal

), us

ing

OU

ES, V

AT,

No

betw

een-

prot

ocol

diff

eren

ces

in m

ean

valu

es o

f OU

ES,

et a

l37bo

th th

e B

ruce

pro

toco

l and

the

RIS

V· O

2max

, V

AT, a

nd V· O

2max

. Int

erpr

otoc

ol v

aria

bilit

y lo

wer

for

prot

ocol

. Bla

nd-A

ltman

for

agre

emen

t.R

ERO

UES

(�17

% to

�18

%) t

han

for

V· O2m

ax (�

24 to

�20

%)

and

VAT

(�31

% to

�31

%).

Mar

inov

60

11

�1.

1Tr

eadm

ill e

xerc

ise

test

s (m

axim

al),

usin

g a

OU

ES (a

t VAT

H

igh

corr

elat

ions

for

OU

ES w

ith V· O

2pea

k(r

�0.

91),

oxyg

en

et a

l38(3

0 M

/30

F)m

odifi

catio

n of

the

Bal

ke p

roto

col.

and

100%

), pu

lse

�V· O

2/H

R (r

�0.

80),

and

anth

ropo

met

ric

vari

able

s 30

nor

mal

In

itial

ele

vatio

n 6%

, inc

rem

ent 2

%/m

in,

V· O2p

eak,

RER

(hei

ght,

BSA

, FFM

, age

, wei

ght;

r�

0.78

-0.8

8).

wei

ght,

cons

tant

vel

ocity

5.4

km

/h.

Stro

ng c

orre

latio

n be

twee

n O

UES

at V

AT a

nd a

t 100

%

30 o

bese

(r�

0.98

); di

ffere

nce

only

1.1

%. N

o si

gnifi

cant

di

ffere

nces

bet

wee

n O

UES

in o

bese

and

OU

ES in

nono

bese

chi

ldre

n; s

light

ly h

ighe

r O

UES

in o

bese

gro

up.

Dri

nkar

d 15

0 (2

2 M

/21

F N

orm

al

Cyc

le e

rgom

eter

test

s (m

axim

al).

Initi

al

OU

ES (a

t LI,

OU

ES s

igni

fican

t pre

dict

ors

of V· O

2pea

kfo

r bo

th g

roup

s at

et

al39

norm

al

wei

ght:

wor

kloa

d 0

W (4

min

), in

crem

ent 1

5 or

15

0% o

f LI,

all e

xerc

ise

inte

nsiti

es, d

espi

te li

mits

of a

gree

men

t as

wei

ght,

14.8

�20

W/m

in. B

land

-Altm

an fo

r ag

reem

ent.

and

100%

of

high

as

30%

to 3

4%. S

igni

fican

t inc

reas

e in

OU

ES w

ith

42 M

/65

F 1.

7ET

), LI

, in

crea

sing

exe

rcis

e in

tens

ity in

bot

h gr

oups

. Whe

n ob

ese)

Obe

se:

V· O2p

eak,

ad

just

ed fo

r le

an b

ody

mas

s, V· O

2pea

kan

d O

UES

at a

ll 14

.4 �

RER

exer

cise

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nsiti

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in o

verw

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t sub

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ange

: Tr

eadm

ill e

xerc

ise

test

s (m

axim

al),

usin

g a

OU

ES (a

t VAT

C

orre

latio

n be

twee

n O

UES

and

V· O2p

eak

(r�

0.92

). et

al19

(58

M/5

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m

odifi

catio

n of

the

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ke p

roto

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and

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), N

o si

gnifi

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ce b

etw

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ES a

t VAT

and

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Initi

al e

leva

tion

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ncre

men

t V· O

2max

, 10

0%. S

tead

y tr

end

for

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eak,

VE,

and

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ES to

2%

/min

, con

stan

t vel

ocity

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km

/h.

V· O2p

eak,

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ease

in th

e ag

e sp

an o

f 7 to

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y. R

ise

mor

e st

rong

ly

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eigh

t tha

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· O2p

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and

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ESsi

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s th

an in

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ls. V

ery

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ES a

nd a

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tinue

s)

HCR200137.qxd 10/24/10 10:17 AM Page 364



differences were found between these heart ratereserve–based OUES calculations and OUES obtainedfrom the entire exercise test data. The study ofHollenberg and Tager4 adopted another alternative bycomparing the OUES in individuals who achieved dif-ferent exercise intensities. The authors divided theirsubjects into 3 groups according to the peak respira-tory exchange ratio (RERpeak) achieved. Results of thisstudy indicated that OUES values were similar in sub-jects with an RERpeak of either 1.00 to 1.09 or �1.10,whereas significantly lower values were obtained insubjects with RERpeak �1.0. However, these subjectswere older, had shorter exercise durations, andreached lower values of V· O2peak and FEV1 (forcedexpired volume in 1 second) than those who reachedRERpeak �1.0.

ReproducibilityOnly 1 study assessed the reproducibility of themaximal OUES, V· O2peak, and VAT.24 Agreementbetween 2 exercise tests separated by a time inter-val of maximal 7 days was better for V· O2peak andOUES (coefficients of repeatability 16% and 20%,respectively) than for VAT (coefficient of repeatabil-ity 31%), indicating that VAT is less reproduciblecompared with OUES and V· O2peak. It seems thatV· O2peak was less reproducible in this study than isoften reported in the literature (Coefficient of varia-tion �10%).

Influence of sex and basic anthropometric variablesOxygen uptake efficiency slope values appeared tobe significantly higher in males than in females(2492 � 471 vs 1741 � 418, with P � .05),27 and theresults of a large cross-sectional study (n � 998) sug-gest that OUES declines linearly with age in healthyelderly.4 This latter article examined which variablescontributed significantly to the prediction of OUES.They introduced the following prediction equations—1for men and 1 for women—on the basis of age andbody surface area (BSA in m2):

Men: OUES � 1320 � (26.7 age) � (1394 BSA)Women: OUES � 1175 � (15.8 age) � (841 BSA)

OUES in Adults With Chronic ConditionsOxygen uptake efficiency slope characteristics havebeen investigated in 2179 patients, aged between 16and 89 years, with various conditions of the heart,including HF,4,8,18,22,32-36 coronary artery disease(CAD)14,31,40 and congenital heart disease.28 One studyincluded patients with mitochondrial myopathy,30 inwhich OUES was used as an outcome measure toassess the effects of exercise therapy on exercisecapacity.

Ta

ble

1 •

Ove

rvie

w o

f In

clud

ed S

tudi

es I

nves

tigat

ing

the

Oxy

gen

Upt

ake

Effic

ienc

y Sl

ope

(Con

tinue

d)

Age

, y

Firs

t (M

ean

�O

utco

me

Aut

hor

n SD

)M

etho

dsM

easu

res

Resu

lts

Hea

lthy

vs

Bab

a 14

4 11

.7 �

4.4

Trea

dmill

exe

rcis

e te

sts

(max

imal

), us

ing

OU

ES (a

t 75%

, C

orre

latio

n w

ith V· O

2max

stro

nger

for

OU

ES (r

�0.

94)

patie

nts

et a

l21(8

3 M

/61

F)th

e st

anda

rdiz

ed B

ruce

pro

toco

l.90

%, 1

00%

), th

an fo

r ot

her

subm

axim

al m

easu

res

(VAT

: r�

0.86

, 36

hea

lthy,

V

AT,

V· E/V· C

O2

slop

e:r

�0.

15, E

MO

C: r

�0.

23).

Dev

iatio

n 10

8 w

ith

V· E/V· C

O2

of th

e es

timat

ed V· O

2max

from

the

mea

sure

d V· O

2max

hear

tsl

ope,

sm

alle

st fo

r th

e V· O

2max

pred

icte

d by

OU

ES.

dise

ase

EMO

C,

No

diffe

renc

es in

OU

ES b

etw

een

90%

and

100

% o

f V· O

2max

exer

cise

; at 7

5% o

f exe

rcis

e sl

ight

ly lo

wer

OU

ES.

Abb

revi

atio

ns: B

MI,

body

mas

s in

dex;

BSA

, bod

y su

rfac

e ar

ea; C

, con

trol

gro

up; C

AD

, cor

onar

y ar

tery

dis

ease

; CO

R, c

oeffi

cien

t of r

epea

tabi

lity;

E, e

xper

imen

tal g

roup

; EM

OC

, ext

rapo

late

d m

axim

al o

xyge

nup

take

; ET,

exe

rcis

e tim

e; F

EV1,

forc

ed e

xpir

ed v

olum

e in

1 s

econ

d; F

FM, f

at-f

ree

mas

s; H

F, h

eart

failu

re; H

Rre

serv

e, h

eart

rat

e re

serv

e; H

RR

-V· O2,

hea

rt r

ate

rest

rict

ed o

xyge

n up

take

; HTx

, ort

hotr

opic

hea

rt tr

ans-

plan

tatio

n; IC

C, i

ntra

clas

s co

rrel

atio

n co

effic

ient

; LI,

lact

ate

infle

ctio

n po

int.

LVD

, lef

t ven

tric

ular

dys

func

tion;

MA

S, m

axim

al a

erob

ic s

peed

; MM

, mito

chon

dria

l myo

path

y; M

/S, M

usta

rd/S

enni

ng o

pera

tion;

NY

HA

,N

ew Y

ork

Hea

rt A

ssoc

iatio

n; O

UES

, oxy

gen

upta

ke e

ffici

ency

slo

pe; R

ER, r

espi

rato

ry e

xcha

nge

ratio

; RIS

, rap

idly

incr

easi

ng s

tage

d; R

OC

, rec

eive

r op

erat

ing

char

acte

rist

ic; S

WEE

T, s

quar

e-w

ave

endu

ranc

e ex

erci

setr

aini

ng; T

, tra

ined

sub

ject

s; U

T, u

ntra

ined

sub

ject

s; V

AT, v

entil

ator

y th

resh

old;

V· CO

2, C

O2

elim

inat

ion;

Vd/

VAT

, dea

d sp

ace

to ti

dal v

olum

e ra

tio; V

E, m

inut

e ve

ntila

tion;

V· O2,

oxy

gen

upta

ke.

HCR200137.qxd 10/24/10 10:17 AM Page 365

dysfunction, neurohormonal activation, exercisecapacity, and BMI. Two studies4,22 demonstrated thatOUES values in patients with HF were significantlylower than the values predicted by the predictionequations for healthy adults as introduced byHollenberg and Tager.4 Furthermore, Davies et al22

identified OUES as the only significant independentprognostic variable in a multivariable predictionmodel and found that OUES values were lower withworsening symptoms.

OUES in Healthy ChildrenFive studies examined the OUES in 415 healthy chil-dren between 6 and 18 years of age. Physical exami-nations revealed that the children were in good healthand took no medication that might affect exerciseperformance.19,24,37-39 All subjects were moderatelyactive, but not engaged in regular training activities.The overweight adolescents in the study by Drinkardet al39 were in good general health but were requiredto have a BMI greater than 95th percentile for age,sex, and race and at least 1 obesity-related comorbidcondition (primarily hyperinsulinemia and/or dyslipi-demia). All subjects in this latter study underwent a12-lead electrocardiogram to ensure the absence ofcardiac diseases. One study21 included children withheart disease as well, but in the results no distinctionwas made between healthy children and patients.

Correlations with other measures of cardiorespiratory functionBaba et al21 found significantly stronger correlationswith V· O2max for OUES (r � 0.94) than for other sub-maximal measures of cardiorespiratory function,including VAT (r � 0.86), V· E/V

·CO2 slope (r � 0.15),

and EMOC (r � 0.28). The deviation of the estimatedV· O2peak from the measured V· O2peak appeared to besmallest for the estimated V· O2max predicted by OUES21

and strong correlations were found with V· O2peak (r �0.91 � 0.92) and oxygen pulse (r � 0.80).19,38 Thestudy of Drinkard et al39 demonstrated a significantrelationship between OUES and V· O2peak at severalexercise intensities for both obese and nonobese ado-lescents. Bland-Altman plots comparing measuredV· O2peak with estimated V· O2peak predicted from OUES,however, showed large limits of agreement (30%-34%of average V· O2peak).

39

Influence of exercise durationTwo studies21,39 found that the submaximal OUES wasslightly, however significantly, lower than the maxi-mal OUES calculated from the entire exercise testdata. Conversely, another study38 found higher sub-maximal OUES values, whereas a fourth study19 didnot find any effects of exercise duration on the OUES.

Correlations with other measures of cardiorespiratory functionThe study of Baba et al24 provided moderately highto strong correlations (r � 0.78 for 18 subjects whoreached maximal exercise intensity; r � 0.68 when allsubjects were included) between maximal OUES andV· O2max in patients with HF. Correlations with V· O2peakvalues ranged from moderately high to strong (r �0.68, r � 0.73, r � 0.81; P � .001) as well.4,18,22,32

Similar correlation coefficients between OUES andV· O2peak were reported in patients with CAD (r � 0.73,r � 0.84, r � 0.89; P � .001).14,40 Oxygen uptake effi-ciency slope standardized for body mass (OUES/kg)also correlated strongly with V· O2peak (r � 0.79, r �0.84; P � .001) in these patients.1,31,35 One of theintervention studies14 demonstrated that training-induced changes in V· O2peak correlated better withchanges in OUES (r � 0.61; P � .001) and VAT (r �0.55; P � .001) than with changes in the V· E/V· CO2slope (r � �.13 to �0.17; P � .001) in patients withCAD. Another exercise training study in patients withHF34 showed that improvements in V· O2peak correlatedsignificantly better (P � .01) with the training-inducedchanges in OUES (r � 0.64-0.77) than with those ofany other included exercise parameter (VAT, V· E/V

·CO2

slope, Wpeak, RERpeak) (r � 0.55).

Influence of exercise duration/intensityVarious studies suggested that the OUES remains rel-atively stable over the entire exercise duration,8,32,36

whereas others found that OUES at 50% and OUES upto RER � 1.0 differed significantly from OUES obtainedfrom the full data.14,22 In terms of percentages, thesedifferences between submaximal and maximal valueswere very small for OUES (1%-2%),4,22 whereas moreprofound differences were found for V· O2peak (25%).22

In line with these findings, Van Laethem et al32 showedthat shortened exercise duration affected both V· O2peakand V· E/V

·CO2 slope, whereas OUES remained stable.

Influence of sex and basic anthropometric variablesThe only study primarily examining the influence ofanthropometric variables33 found that OUES differedsignificantly (P � .05) between 3 subgroups ofpatients with HF differing in body mass index (BMI):normal weight, overweight, and obese. Interestingly,the most favorable values were found in the obesesubgroup.

Discriminative ability and prognostic valueSeveral studies examining exercise capacity inpatients with HF8,32 or CAD31,40 reported significantdifferences in OUES values between New York HeartAssociation functional classes (I-III) or subgroupsbased on other variables, such as left ventricular



HCR200137.qxd 10/24/10 10:17 AM Page 366

Intervention StudiesSeven studies examined the effects of a particularintervention on the OUES; however, none applied arandomized controlled design. The interventionsincluded exercise training,14,26,30,34,36 orthotropic hearttransplantation,35 and hypoxia.29

Exercise training induced significant improvementsin V· O2peak, OUES, and VAT in a large number of patientswith cardiac disease.14,34,36 The study of Defoor et al14

showed that the training-induced changes in V· O2peakcorrelated with changes in OUES (r � 0.61; P � .001)and in VAT (r � 0.55; P � .001). These relationsremained significant after adjusting for age, gender,body height and weight, and training intensity andfrequency (r � 0.57 and r � 0.52; P � .001, respec-tively). Stepwise multiple regression analysis revealedtraining frequency (r � 0.249; P � .001) as thestrongest determinant for the change in OUES withphysical training and that the change in VAT was thelargest contributor to the change in OUES.14

Patients with mitochondrial myopathy also showedsignificantly higher OUES values following aerobicexercise therapy, whereas no significant increaseswere demonstrated in heart rate–restricted V· O2.

30 Onestudy,27 however, did not find significant changesin the OUES and V· E/V

·CO2 slope after intermittent

endurance training in healthy young women, despitesignificant increases in V· O2peak and VAT.

The study of Van Laethem et al35 investigated theOUES in patients before and after heart transplanta-tion. Significant improvements (P � .05) in OUESwere found during the first year after surgery, butsimilar to other exercise parameters, OUES remainedconsiderably impaired when compared with age-and gender-normalized values. The changes inOUES after heart transplantation highly correlatedwith the changes in other exercise variables (V· O2peakand VAT), but not with marked improvements incentral hemodynamics or resting lung function. Thelatter might suggest that the increase in OUES iselicited by beneficial alterations in the skeletal mus-culature after heart transplantation rather than byimprovements in central hemodynamics or restinglung function.

In a study concerning the responsiveness of theOUES to hypoxia in healthy subjects with a broadrange of cardiorespiratory fitness,29 both maximal andsubmaximal OUES values were influenced by oxygenavailability and utilization by active tissues. Mildhypoxia did not significantly alter OUES values, butmore severe hypoxia at higher simulated altitudescaused significant reductions in OUES. An interestingfinding was that the OUES declined faster in trainedthan in untrained subjects.

Protocol dependencyThe only study37 examining protocol dependency ofthe maximal OUES did not find significant differencesin OUES, VAT, or V· O2max values obtained with 2 dif-ferent protocols for treadmill exercise testing.Interprotocol variability was found to be smallest forthe OUES (limits of agreement �18% to 17%).

Influence of sex and basic anthropometric variablesIn a cross-sectional study by Marinov et al,19 a steadytrend was observed for V· O2peak, V· E, and OUES toincrease in the age span of 7 to 14 years. Both OUESand V· O2peak appeared to be significantly higher inboys than in girls.19,38 Dividing these variables by leanbody mass removed the sex differences almost com-pletely; however, it did not remove the differences inthe individual age and height groups. The increasesin V· O2peak and OUES appeared to be more stronglycorrelated with height than with age.19 Studies exam-ining the relationship between OUES and anthropo-metric variables found that OUES was strongly corre-lated with BSA, height, weight, lean body mass, andage.19,38 Absolute values of OUES at VAT and overthe entire exercise testing data appeared to be signif-icantly higher in severely overweight adolescents(mean BMI 40.0 � 8.0 kg/m2) compared with theirnonoverweight peers.38 These findings are in line withthe results of Arena et al,33 who also found the mostfavorable OUES values in the obese subgroup ofadult patients with HF. Conversely, when expressedrelative to lean body mass, exercise parameters weresignificantly lower in overweight than in nonover-weight adolescents.19,38

To assess which factors influence OUES in thepediatric population, Marinov and Kostianev38 appliedstepwise regression analysis and introduced the fol-lowing equation to predict OUES from height (cm)and BSA (m2) (r2 � 0.793; standard error of estimate �369; n � 60):

OUES � �3346.9 � 28.08 height � 794.2 BSA

More recently, Marinov et al19 introduced anotherequation to predict OUES in healthy children,including BSA and gender as the main determinants(R2 � 0.765; standard error of estimate � 316; n �114):

OUES � �398 � 1958.1 BSA � 199.5 gender

OUES in Children with Chronic ConditionsOnly 1 study21 examined the OUES in 108 childrenwith heart disease. However, in this study, no dis-tinction was made between the healthy participantsand those suffering from heart disease. The results ofthis study are discussed earlier.



HCR200137.qxd 10/24/10 10:17 AM Page 367

shortened exercise duration did affect theOUES,4,14,21,22,25,38,39 only small differences werereported. However, controversy exists with regard tothe submaximal OUES values. Some studies14,25,38

found significantly higher submaximal OUES valuesas compared with maximal OUES values, whereasothers did not find differences8,19,27-29,32,36 or suggest-ed a tendency toward lower submaximal values.4,21,39

We could not identify explanatory factors for theseinconsistent findings; however, it might be related tothe underlying disease. The validity of the OUESmight be different across patient groups.

Despite the fact that the submaximal OUES valuesare calculated in numerous studies, important charac-teristics (such as interprotocol agreement, repro-ducibility, discriminative ability, and prognosticvalue) are examined only for the maximal OUES inthe majority of studies. Since the original purpose ofthe OUES was to provide a submaximal measure ofcardiorespiratory function, which could be used as asubstitute for V· O2peak in (clinical) populations unableto perform maximal exercise, it would be moreappropriate to examine these characteristics for thesubmaximal OUES. Three studies14,26,36 examined theresponsiveness to exercise training for the submaxi-mal OUES and 2 of these showed a significantincrease in submaximal OUES values following exer-cise training in patients with HF36 or CAD.14 A studyby Mollard et al29 indicated that the submaximalOUES was sensitive to the effects of hypoxia duringexercise. Only 1 study18 assessed the prognostic valueof the submaximal OUES and demonstrated that it,like the maximal OUES, was a significant predictor ofmortality in patients with HF.

Sensitivity of OUESResults of the intervention studies suggest that OUESis sensitive to change after exercise training inpatients with CAD, HF, or mitochondrial myopathyand, thus, can be used to evaluate the progression ofexercise capacity in the aforementioned populationsfollowing rehabilitation or training programs in thesepatient groups. Several authors have concluded thatOUES is a more consistent parameter than V· O2peak,since V· O2peak is effort, protocol, and observer depen-dent.4,32,36 In populations with cardiac conditions,exercise capacity appears to be primarily restricted byunderperfusion of both the lungs and the skeletalmuscles. An increase in OUES suggests that a similarV· O2 is achieved with lower ventilatory cost.14,35,36 Thismight be due to direct training-induced improve-ments in pulmonary function (eg, increased alveolarcapillary membrane perfusion and capillary blood flow)and/or muscular function (eg, increased capillary

DISCUSSION

The results of this review indicate that OUES is anobjective and reproducible measure with broadapplicability. Oxygen uptake efficiency slope is rela-tively independent of exercise intensity/duration, cor-relates highly with other exercise parameters, appearsto have discriminative value, and is sensitive to theeffects of physical training in adult cardiac populations.However, OUES values are considerably influencedby anthropometric variables and show large interindi-vidual variation.

Correlation Between OUES and Other Exercise ParametersStrong correlations were found between OUES (sub-maximal and maximal) and V· O2peak. Using correlationand regression analysis, several authors concludedthat the assessment of OUES was accurate enough asa substitute of V· O2max.

4,8,22,24,29,32,34,37 However, a strongstatistical correlation between 2 parameters is notnecessarily a proof for the interchangeability ofthese parameters.40 Bland-Altman analysis assessinginterindividual variability showed wide 95% confidenceintervals.25,39,40 These findings indicate that althoughOUES and V· O2peak are highly correlated, interindivid-ual variation exists in OUES values, which might limitthe clinical utility of this parameter. Since OUES wasnot able to reliably predict V· O2max, it appears notinterchangeable with this “golden standard.”25,39,40

Nonetheless, Pichon et al25 compared the submaximalOUES with the VAT, which is widely used in clinicalpractice, and showed that the submaximal OUES pro-vided a better approximation of measured V· O2maxcompared with the VAT. Various studies revealed thatcompared with other submaximal parameters, OUESis strongly correlated with the VAT21,26,27,29 and withthe submaximal V· E/V

·CO2 slope.18 However, relation-

ship differences of OUES and VAT between studiesare not fully understood and identified; differentapproaches for determining the VAT and even differ-ent exercise protocols (Table 1) might contribute tothese differences in relationships.

Influence of Exercise Duration/Intensity on OUESThe logarithmic transformation of V· E is aimed at lin-earizing the otherwise curvilinear relation of V· O2 ver-sus V· E, thus making the OUES theoretically indepen-dent of the patient-achieved maximal effort level.Many studies confirmed that submaximal and maxi-mal OUES values were highly correlated.8,26,34,38 Theuse of submaximal exercise data did not alter OUESvalues in most studies,8,19,27-29,32,36 and in those where



HCR200137.qxd 10/24/10 10:17 AM Page 368

stratification of patient with other (chronic) condi-tions. In addition, future studies should examine therelationship between OUES and other markers ofphysiologic function reflecting disease severity (eg,Doppler echo, cardiac magnetic resonance imaging,brain natriuretic peptide concentrations in blood, orpulmonary pressure).

Both the V· E/V·CO2 slope and OUES could potential-

ly be used to identify a subgroup within CAD patientswith intermediate V· O2peak, who might have a worseoutcome. Arena et al18 reported that although OUESis a significant prognostic marker in patients with HF,the V· E/V

·CO2 slope calculated with all exercise data

remained prognostically superior. Davies et al22 per-formed a similar analysis, though they concluded thatOUES was the best predictor of mortality. In this lat-ter study, patients were tested between 1992 and1996, while only 2.6% of the participants of Arena et al18 underwent testing before 1997. Given thechanges in HF management since the 1990s, the find-ings of Arena et al18 may be more reflective of pre-sent-day clinical practice.

OUES in ChildrenMean submaximal OUES values in healthy children aresignificantly lower than those in healthy adult popula-tions (1900-2200 vs 2910-4300, respectively).19,24,25,28,29,38,39

An interesting finding is that the OUES increaseslinearly with age during childhood,19 whereas it wasfound to decrease linearly with age in healthyelderly.4 Correlation coefficients with other exerciseparameters in children are similar to those found inhealthy adults. However, caution is recommendedwhen interpreting OUES as an exercise parameterin the development course of childhood, sinceOUES is considerably influenced by anthropometricvariables.19,38

To our knowledge, only 1 study examined OUESin children with chronic conditions. Baba et al21

included both healthy children and children with var-ious conditions of the heart. However, the study pop-ulation was very heterogeneous, and furthermore, nodistinction was made between the patients andhealthy children in their results. Thus, as far as weknow, no studies are published that compare OUESvalues in children with various (chronic) diseaseswith those in healthy peers. As a consequence, it iscurrently not known whether the OUES is able to dis-criminate between healthy children and children withvarious (chronic) diseases or disabilities. Moreover,none of the included studies investigated the effectsof pubertal stages on OUES, despite the fact thatexercise capacity is known to be influenced by thisdevelopmental milestone. Future research shouldaddress this interesting issue.

density, blood flow, and mitochondrial density) inthese patient populations. In subjects without car-diopulmonary limitations, however, measures of ven-tilatory efficiency, and consequently OUES, mightnot be the most appropriate to assess the effects oftraining. This has been observed in the healthyyoung women who participated in the study ofMourot et al.26

It is striking that the responsiveness of OUES toexercise training or other interventions has neverbeen investigated in pediatric populations and, more-over, that none of the intervention studies on OUESinvolved randomized controlled trials. Further, moreresearch is required to determine whether an increasein OUES in patients is associated with an improvedprognosis.

OUES in PatientsThe study of Davies et al22 was the first study thatexamined the prognostic value of the OUES inpatients with HF. They found that its prognostic valuewas stronger compared to the best available existingmeasures of exercise physiology, including V· O2peak,VAT, and V· E/V

·CO2 slope. Other studies, similar to this

finding, suggested strong discriminative value of theOUES in patients with HF or CAD.4,8,31,32 Hence,OUES appears to be useful for the quantification ofexercise performance in these patients.40 In patientswith CAD, OUES is significantly reduced.14,32,34

Patients who have undergone percutaneous translu-minal coronary angioplasty with or without priormyocardial infarction have significantly higher OUESvalues compared with patients after coronary arterybypass grafting.14 This may be explained by a higherdisease severity, preoperative and postoperativedeconditioning, and the impact of chest surgery onlung perfusion and structural integrity in the lattergroup. Furthermore, OUES is impaired in CAD patientswith arterial fibrillation as compared with those withnormal sinus rhythm;14 this is likely because of theimpact of decreased oxygen delivery on the workingmuscles in patients with arterial fibrillation owing tolower stroke volume and CO response during exercise.41 The study of Arena et al18 showed thatOUES was a significant predictor of mortality inpatients with HF, though they also concluded that theV· E/V

·CO2 slope maintained an optimal prognostic

value. However, the V· E/V·CO2 slope was calculated

from maximal exercise in their study. When only sub-maximal data were used for OUES determination, thissuperiority of the V· E/V

·CO2 slope compared with the

OUES was no longer significant. Although OUESappears to have good discriminative ability in thesepopulations, further investigation is required forexploring the prognostic power of OUES in the risk



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pulmonary perfusion, which seems to account for thesuperiority of OUES concerning the correlation withtraditional parameters.42

The prognostic value of both slopes in predictingmorbidity and mortality is confirmed in patients withHF or CAD.18,22,31 Defoor et al,14 however, reportedthat the V· E/V· CO2 slope might be less suitable thanOUES to evaluate the effects of physical training inCAD patients without an increased V· E/V· CO2 slope at baseline measurement. They found that changes in VAT contributed most to the changes in OUES than in the V· E/V

·CO2 slope. In addition, Van Laethem

et al35 found that the training-induced changes in OUEScorrelated better with the changes in V·O2peak in patientswith HF than the changes in the V· E/V· CO2 slope.

Several studies examined the relationshipbetween underlying pathophysiology and an abnor-mally elevated V· E/V

·CO2 slope in patients with HF.

The mechanisms appear to be multifaceted withboth central and peripheral contributions.18 Suchstudies are lacking for OUES thus far. Additionalresearch is required to examine the mechanismbehind the abnormally low OUES observed inpatients with HF.18 Furthermore, future researchshould reveal which submaximal efficiency slopeappears most useful in clinical practice with variouspatient populations.

Interpretation of OUESDuring the analysis of the different studies it becameclear that OUES was expressed in various entities,which can be confusing. In fact, OUES represents theslope of a regression line and forms the quotient ofV· O2 (mL/min) and log V· E (L/min). As a result, OUESformally has no entity.

Drinkard et al39 attempted to predict V· O2peak fromOUES values in a pediatric population and did notfind significant differences between the actualV· O2peak and the V· O2peak predicted by the submaximalOUES. However, the authors identified a significantbias in overweight adolescents. This is in line withthe results of Pichon et al,25 who found that theV· O2max predicted by the OUES did not significantlydiffer from measured V· O2max. Since OUES is not ableto reliably predict V· O2max, it appears not interchange-able with the “gold standard.” However, we supposethat the OUES is not meant to predict maximal exer-cise parameters. The index itself provides an objec-tive and independent measure of cardiorespiratoryfunction, reflecting the efficiency of ventilation withregard to the oxygen uptake during exercise. Theinterpretation of its values is dependent oncomparison with adequate reference values, compar-isons between (groups of) subjects, or comparisonswithin subjects (eg, to detect individual changes in

OUES Versus VATOxygen uptake efficiency slope determination involvescalculating the slope of the relationship between V· Eand V· O2 rather than a single cross-sectional determi-nation with substantial inter- and intraobserver vari-ability during exercise, like the VAT. As a conse-quence, OUES is objectively identifiable in all sub-jects and seems to be sufficiently reproducible.24

Moreover, the slope is derived from multiple datapoints throughout the exercise test and, therefore,provides more profound physiological information.Oxygen uptake efficiency slope includes both meta-bolic acidosis and physiologic pulmonary dead spaceand hence displays the status of both systemic andpulmonary perfusion, whereas VAT primarily repre-sents the status of blood distribution to the workingmuscles rather than perfusion to the lungs.21 Also,caution has to be taken when reporting about datameasured at different anaerobic thresholds to avoidmixing up methods;17 this is not applicable for OUES,because it concerns a single fixed and simple mathe-matical formula. Furthermore, VAT values can be con-siderably influenced by the nutritional state of thesubject (eg, carbohydrate loaded or depleted). Babaet al24 have stated that this is not the case for OUESvalues.

OUES Versus·VE/

·VCO2 Slope

Both the OUES and V· E/V· CO2 slope reflect ventilatoryefficiency and have the advantage of being derivedfrom multiple data points throughout the exercise.Contrary to the V· E/V

·CO2 slope, OUES appears to be

relatively independent of patient-achieved effort level.OUES differs in theory from the V· E/V

·CO2 slope in

that it considers changes in ventilation in terms ofscale factor, that is, in multiples of the baseline value.Consequently, any abnormalities that increase venti-lation by a constant proportion, both at rest and dur-ing exercise, will not directly influence OUES. Onlyabnormalities that increase ventilation during exerciseby a greater proportion than at rest will cause adecline in OUES values. Oxygen uptake efficiencyslope may therefore quantify the specific pattern ofventilatory response to exercise having automatically“controlled” for abnormalities present at rest.22

Correlation coefficients with traditional measuresof cardiopulmonary function, including V· O2max,V· O2peak, and VAT, reported for OUES were muchstronger than for the V· E/V

·CO2 slope.15,20,21 The latter,

which is related to physiologic pulmonary deadspace, is affected mainly by perfusion to the lungs.Oxygen uptake efficiency slope, affected both bymetabolic acidosis and by physiologic pulmonarydead space, reflects the status of both systemic and



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exercise tolerance. Therefore, OUES would seem tobe clinically useful to monitor changes in exerciseperformance and effects of physical training in adults,particularly in those who can perform only submaxi-mal exercise. Several authors have stated that theOUES is more robust than the V· O2peak, since maximalworkload assessed during a symptom-limited exer-cise test can be influenced by multiple factors.4,32,36

However, none of these studies involved randomizedcontrolled trials and the responsiveness of the OUESin pediatric populations remains the subject of furtherresearch.

It is currently unknown whether the type of ergome-ter affects OUES determination. The included studiesused both a treadmill ergometer or a cycle ergometerfor OUES determination and various exercise proto-cols. Since V· O2peak values are usually higher with atreadmill protocol46 and since OUES is highly corre-lated with V· O2peak, it is likely that the OUES could beinfluenced by the type of ergometer. The only studyassessing interprotocol agreement showed excellentintraindividual agreement between OUES obtainedwith 2 different treadmill protocols, unlike VAT andV· O2max.

37 However, no additional studies are yet pub-lished to confirm these findings. Whether values ofOUES are ergometer and/or protocol dependent thusremains the subject of future research.

SUMMARY

OUES appears to be a reproducible measure of car-diorespiratory function that does not require maximalexercise. It greatly reduces test variability because ofmotivational and subjective factors and is reliable andeasily determinable in all subjects when respiratorygas analysis systems with breath-by-breath or mixingchamber are used. Despite the strong correlationswith V· O2peak and V· O2max, OUES appears not inter-changeable with these maximal exercise parameters.Nonetheless, OUES seems to be a promising alterna-tive submaximal exercise parameter to assess car-diorespiratory function in subjects unable to performmaximal exercise, like children and patients with pro-gressed disease states. However, appropriate refer-ence values for both adult and pediatric populationsare required.

References1. Shephard RJ, Allen C, Benade AJ, et al. The maximum oxygen

intake: an international reference standard of cardiorespiratoryfitness. Bull World Health Organ. 1968;38:757-764.

2. Myers J, Walsh D, Buchanan N, Froelicher VF. Can maximalcardiopulmonary capacity be recognized by a plateau inoxygen uptake? Chest. 1989;96:1312-1316.

ventilatory efficiency over time or following a spe-cific intervention).

Normalization of OUESSince OUES is considerably influenced by anthropo-metric variables, it is recommended to normalize itsvalues for body size, especially in children. Maximalindices such as V· O2peak are also known to be stronglyinfluenced by changes in body size. Therefore,V· O2peak is often normalized by body weight;43 howev-er, the influence of body mass is not entirely com-pensated by this method.44 The study of Marinov andKostianev38 showed that normalizing V· O2peak for BSA(depends on both weight and height) compensatesfor the differences between different weight groups.Since height, weight, lean body mass, and BSA arestrongly correlated with OUES,19 normalizing its val-ues for one of these parameters seems appropriate,especially in pediatric populations. Previous studieshave normalized OUES by body weight, lean bodymass (a surrogate for muscle mass), or BSA. From aphysiological perspective, we presume that BSA pro-vides the best indication of total pulmonary volume,taking both height and weight into account.However, which adjustment is most useful in normal-izing the OUES has to be further investigated.

Applications to Practice and Implications for Further ResearchThere is a need for adequate reference values for theOUES in (healthy) adults and children. Appropriatereference values should be generated with respect toage, gender, race, and other factors such as matura-tion and anthropometrics. To our knowledge, influ-ences of puberty on the OUES have not been inves-tigated. Since puberty causes significant changes inbody composition, muscle strength, V· Emax, ventilatoryequivalent, and physical activity patterns,45 it mightalso influence ventilatory efficiency (OUES). Futurestudies should address the aforementioned variables.

Also, it is currently unknown whether the submax-imal OUES is able to differentiate between healthychildren and children with a (chronic) disease.Previous findings suggest that OUES has discrimina-tive value in adults;4,8,22,31,32 however, further researchis required to assess its discriminative ability in dif-ferent pediatric populations.

Furthermore, the responsiveness of the OUES toexercise training has never been addressed in pedi-atric (patient) populations. Results from adult studiessuggest that the OUES increases following physicaltraining in both patients with CAD and those with HF.The training-induced changes in OUES parallel thosein V· O2peak in cardiorespiratory-limited populations,14,34

showing that OUES is sensitive to improvement in



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30. Trenell MI, Sue CM, Kemp GJ, Sachinwalla T, Thompson CH.Aerobic exercise and muscle metabolism in patients with mito-chondrial myopathy. Muscle Nerve. 2006;33:524-531.

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Erratum

Rural and Urban Characteristics Impact Cardiovascular Risk Reduction: ErratumIn the article that appeared on page 299 of the September/October issue, the list of authors was incom-plete; the complete author list is as follows:

Timothy R. McConnell, PhD; William P. Santamore, PhD; Sharon L. Larson, PhD; Carol J. Homko, PhD;Mohamed Kashem, MD, PhD; Robert C. Cross, MD; Alfred A. Bove, MD, PhD

In addition, the article should have included a note indicating that it was registered as part ofClinicalTrials.gov (Clinical Trial no. NCT00778804).

Reference:McConnell TR, Santamore WP, Larson, SL, et al. Rural and urban characteristics impact cardiovascular riskreduction. J Cardiopulm Rehabil Prev. 2010;30(5):299-308.

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the oxygen uptake efficiency slope what do we know?

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