Full esea ch pape
The Duke eadmill sco e wi h
bicycle e gome e : Exe cise capaci y
is he mos impo an p edic o o
ca dio ascula mo ali y
Esko Saloka i
1
, Ja i A Laukkanen
2,3,4
, Te ho Leh imaki
5
,
Sudhi Ku l
2
, Se o Kunu so
6
, F ancesco Zacca di
7
, Ja i Viik
8
,
Rami Leh inen
9
, Kjell Nikus
10
, Tii Ko
¨o
¨bi
11
,Va
¨ino
¨Tu janmaa
12
,
Mika Ka
¨ho
¨nen
11
and Tuomo Nieminen
13,14
Abs ac
Backg ound: The Duke eadmill sco e, a widely used eadmill es ing ool, is a weigh ed index combining exe cise
ime o capaci y, maximum ST-segmen de ia ion and exe cise-induced angina. No p e ious s udies ha e in es iga ed
whe he he Duke eadmill sco e and i s indi idual componen s based on bicycle exe cise es ing p edic ca dio ascula
dea h.
Design: Two popula ions wi h a s anda d bicycle es ing we e used: 3936 pa ien s e e ed o exe cise es ing (2371
men, age 56 13 yea s) om he Finnish Ca dio ascula S udy (FINCAVAS) and a popula ion-based sample o 2683 men
(age 53 5.1 yea s) om he Kuopio Ischaemic Hea Disease s udy (KIHD).
Me hods: Cox eg ession was applied o isk p edic ion wi h ca dio ascula mo ali y as he p ima y endpoin .
Resul s: In FINCAVAS, du ing a median 6.3-yea (in e qua ile ange (IQR) 4.5–8.2) ollow-up pe iod, 180 pa ien s
(4.6%) expe ienced ca dio ascula mo ali y. In KIHD, 562 pa ien s (21.0%) died om ca dio ascula causes du ing he
median ollow-up o 24.1 (IQR 18.0–26.2) yea s. The Duke eadmill sco e was associa ed wi h ca dio ascula mo ali y
in bo h popula ions (FINCAVAS, adjus ed haza d a io (HR) 3.15 o highes s. lowes Duke eadmill sco e e ile, 95%
con idence in e al (CI) 1.83–5.42, P<0.001; KIHD, adjus ed HR 1.71, 95% CI 1.34–2.18, P<0.001). Howe e , a e
p og essi e adjus men o he Duke eadmill sco e componen s, he sco e was no associa ed wi h ca dio ascula
mo ali y in ei he s udy popula ion, as exe cise capaci y in me abolic equi alen s o ask was he dominan ha binge o
poo p ognosis.
Conclusions: The Duke eadmill sco e is associa ed wi h ca dio ascula mo ali y among pa ien s who ha e unde gone
bicycle exe cise es ing, bu me abolic equi alen s o ask, a componen o he Duke eadmill sco e, p o ed o be a
supe io p edic o .
Keywo ds
Ca dio ascula mo ali y, p ognos ic ac o s, s ess es
Recei ed 23 Decembe 2017; accep ed 11 Sep embe 2018
1
Depa men o In e nal Medicine, Uni e si y o Helsinki, Finland
2
Ins i u e o Public Heal h and Clinical Nu i ion, Uni e si y o Eas e n
Finland, Finland
3
Depa men o Medicine, Cen al Finland Heal h Ca e Dis ic , Finland
4
Facul y o Spo and Heal h Sciences, Uni e si y o Jy a
¨skyla
¨, Finland
5
Depa men o Clinical Chemis y, Uni e si y o Tampe e, Finland
6
School o Clinical Sciences, Uni e si y o B is ol, Sou hmead Hospi al,
B is ol, UK
7
Diabe es Resea ch Cen e, Leices e Gene al Hospi al, Leices e , UK
8
Depa men o Biomedical Enginee ing, Tampe e Uni e si y o
Technology, Finland
9
Depa men o ICT and Heal h Technology, Tampe e Uni e si y o
Applied Sciences, Finland
10
Facul y o Medicine and Li e Sciences, Uni e si y o Tampe e and Hea
Cen e , Finland
11
Depa men o Clinical Physiology, Tampe e Uni e si y Hospi al and
Uni e si y o Tampe e, Finland
12
Science Cen e, Pi kanmaa Hospi al Dis ic , Finland
13
Depa men o In e nal Medicine, Uni e si y o Helsinki, Finland
14
Sou h Ka elia Cen al Hospi al, Lappeen an a, Finland
Co esponding au ho :
Tuomo Nieminen, Uni e si y o Helsinki, In e nal Medicine PL 22
(Haa maninka u 4), 00014 Helsingin Yliopis o, Finland.
Email: [email p o ec ed]
Eu opean Jou nal o P e en i e
Ca diology
2019, Vol. 26(2) 199–207
!The Eu opean Socie y o
Ca diology 2018
A icle euse guidelines:
sagepub.com/jou nals-pe missions
DOI: 10.1177/2047487318804618
jou nals.sagepub.com/home/ejpc
In oduc ion
Al hough o he modali ies ha e pa ially eplaced clin-
ical exe cise es as a diagnos ic ool o assessmen o
co ona y a e y disease (CAD), he es has become
mo e i al in e alua ing p ognosis and ocusing a ail-
able ea men s o high- isk pa ien s.
1,2
One o he
mos widely s udied and used p ognos ic a iables in
exe cise es ing is he Duke eadmill sco e (DTS),
which is a weigh ed index combining eadmill exe cise
ime wi h s anda d B uce p o ocol, maximum ST-seg-
men de ia ion on elec oca diog am (ECG) and exe -
cise-induced angina.
3
The sco e was ini ially de eloped
o add p ognos ic in o ma ion o ha p o ided by clin-
ical da a, co ona y ana omy and le en icula ejec-
ion ac ion in pa ien s wi h suspec ed CAD e e ed
o ca he e isa ion.
3
The DTS was la e also alida ed
o pa ien s wi h suspec ed CAD,
4
and i is s ill in clin-
ical use o isk s a ifica ion o hese pa ien s.
5,6
In e es ingly, p io s udies ha e no p ope ly es ed
whe he he DTS is a supe io p ognos ic ma ke in
compa ison wi h i s componen s.
As exe cise ime o he B uce p o ocol can be
eplaced wi h me abolic equi alen s o asks (METs),
he DTS is also sui able o o he exe cise es p o o-
cols.
7
In many Eu opean coun ies, a bicycle e gome e
a he han a eadmill is he p e e ed es ing modali y.
Howe e , he p ognos ic alue o he DTS using he
s anda d bicycle exe cise es ing has no ye been in es-
iga ed. Thus he pu pose o his s udy was o assess he
p ognos ic alue o he DTS in bicycle exe cise es ing.
Combined analysis o se e al pa ame e s is commonly
used o simpli y isk assessmen ; howe e , he combin-
a ion needs o be supe io o an independen assess-
men o each a iable. The e o e, we also compa ed
he p ognos ic capabili y o he DTS o ha o i s com-
ponen s. We hypo hesise ha he DTS is a use ul p og-
nos ic ma ke o ca dio ascula dea h, supe io o i s
componen s, in he exe cise es pe o med wi h a
bicycle e gome e .
Me hods
S udy coho s
We used wo independen da a coho s. In he Finnish
Ca dio ascula S udy (FINCAVAS), all consecu i e
pa ien s e e ed o an exe cise es a Tampe e
Uni e si y Hospi al and willing o pa icipa e we e
en olled be ween Oc obe 2001 and Decembe 2008.
A de ailed desc ip ion o he s udy has been published.
8
A s udy popula ion o 4178 pa ien s (2537 men and
1641 women) was ec ui ed. Da a om a o al o
3758 pa ien s (2249 men and 1509 women) wi h ech-
nically success ul exe cise es s – including exe cise
capaci y and angina da a as well as con inuous digi al
ECG wi h ST-segmen de ia ion and slope da a – we e
analysed in he p esen s udy.
The main indica ions o exe cise es ing we e a sus-
picion o CAD (47%), e alua ion o wo k capaci y
(27%), e alua ion o a hy hmias (26%), adequacy o
CAD ea men (13%), as well as ob aining an exe cise
es p ofile p io o an in asi e p ocedu e (9%) o a e
myoca dial in a c ion (MI) (7%); some pa ien s had
mo e han one indica ion. The e hics commi ee o
Tampe e Uni e si y Hospi al dis ic app o ed he
s udy p o ocol, and all pa ien s ga e in o med consen
as s ipula ed in he Decla a ion o Helsinki.
The o he da ase was om he Kuopio Ischaemic
Hea Disease (KIHD) isk ac o s udy. This was a lon-
gi udinal popula ion-based s udy designed o in es iga e
isk ac o s o ca dio ascula diseases, a he oscle osis
and ela ed ou comes. The baseline da a consis o an-
domly selec ed 2683 men be ween 42 and 61 yea s o age
li ing in he ci y o Kuopio and su ounding u al com-
muni ies in eas e n Finland, o which 2392 men wi h
success ul exe cise es da a we e included in ou s udy.
The baseline examina ions we e conduc ed be ween
Ma ch 1984 and Decembe 1989. The KIHD s udy
has p e iously been desc ibed in de ail.
9
S udy low
FINCAVAS. In FINCAVAS, w i en in o med consen ,
medical his o y, es ing and exe cise ECGs and exe cise
sys olic and dias olic blood p essu e eco dings we e
ob ained, as p e iously desc ibed.
8
In b ie , p io o
he exe cise es using a bicycle e gome e , subjec s
lay down in he supine posi ion o 10 minu es, and
he es ing ECG was digi ally eco ded. The Mason–
Lika 12-lead sys em was used. The exe cise es s we e
in ended o be maximal es s excep o 7% o he es s,
which e alua ed he s a us a e an MI and applied a
hea a e limi o 120–130 bea s/min; e en hose we e
included in he analysis.
The ini ial wo kload o 20–30 W was inc eased s ep-
wise by 10–30 W e e y minu e based on pa ien cha ac-
e is ics. ECGs we e digi ally eco ded a 500 Hz wi h he
Ca dioSo exe cise sys em ( e sion 4.14; GE Heal hca e,
F eibu g, Ge many). The easons o e mina ion o he
es we e ches pain (5.7%), dyspnoea (12.8%), a igue
(61.6%), ECG changes (1.4%), blood p essu e changes
(1.5%) o o he easons (11.5%). The objec i e exe cise
le els as defined by he supe ising physician we e max-
imal in 76.4%, almos maximal in 18.7%, easonable in
3.1% and poo in 0.6% o he es s.
KIHD. In he KIHD s udy, he pa ien s unde wen a
maximal symp om-limi ed exe cise ole ance es using
an elec ically b aked cycle e gome e wi h inc ease in
200 Eu opean Jou nal o P e en i e Ca diology 26(2)
he wo kload o 20 W/minu e. Maximal exe cise cap-
aci y was calcula ed om VO
2
max, which was defined
as he highes alue o he pla eau o di ec ly measu ed
oxygen consump ion using a espi a o y gas analyse
(Mijnha d and Medical G aphics, Minneapolis, MN,
USA). ECG was eco ded con inuously wi h he Kone
620 elec oca diog aph (Kone, Tu ku, Finland). ECG
was p in ed a 30 second in e als du ing exe cise and
a leas 5 minu es o eco e y while he subjec was
si ing on he bicycle.
9,10
The Duke eadmill sco e
FINCAVAS. The DTS was calcula ed as ollows: exe cise
ime – (5 max ST-segmen dep ession) – (4 Angina
index). The exe cise ime in minu es was app oxima ed
om he maximal METs using a linea app oach
de i ed om he scien ific s a emen o he Ame ican
Hea Associa ion ega ding exe cise s anda ds o es -
ing and aining.
7
The ollowing equa ion was used:
exe cise ime ¼(METs – 1)/1.044. METs we e es i-
ma ed on he s anda dised basis o maximum wo kload
and pa ien weigh , wi h 1 MET being equi alen o
3.5 ml oxygen up ake/kg/min.
The o iginal DTS used maximal ST-segmen de i-
a ion – whe he dep ession o ele a ion – compa ed
o he es ing phase om he lead wi h he mos de i-
a ion.
3
We ook in o accoun only he maximal ne
ST-segmen dep ession (STD) because non-diagnos ic
ST-segmen ele a ion is a he common in heal hy
people due o ea ly epola isa ion. ST-segmen s we e
analysed wi h modified CASE/Ca dioSo so wa e
(V.1.84; GE Heal hca e, F eibu g, Ge many). The so -
wa e also calcula es he ST slope on he basis o he
cu en median complex, measu ed o e an in e al
om he J poin o he 1/8 o he a e age R-R in e al
(a maximum o 80 ms). This defini ion o slope akes in o
accoun he co ela ion be ween hea a e and epola -
isa ion ime, a oiding he effec s o he T wa e.
11
The
STD and slope we e calcula ed o he end o he es ing
phase and o each minu e o he exe cise and eco e y.
Possible ST-segmen de ia ion a he es ing phase was
ex ac ed om he alues du ing he exe cise and eco -
e y o assess he diffe ence caused by he exe cise. I he
simul aneous ST-segmen slope was a leas 0.5 mV/s,
he dep ession was se o ze o, as up-sloping STD,
whe he apid o slow, migh be associa ed wi h an
inc eased isk o u u e co ona y e en s, bu is no p e-
dic i e o he p esence o myoca dial ischaemia in he
gene al popula ion.
12
The maximal STD in all he leads
excep aVR was used in he analysis. I he maximal
STD was less han 1 mm, i was se o ze o, as i is no
conside ed pa hological. Values g ea e han 5 mm
(n¼34) we e excluded om he da a because hey
we e mos likely due o measu emen e o .
The angina index has alues o 0 (no exe cise
induced ischaemic ches pain), 1 (non-exe cise-limi ing
angina) and 2 (exe cise-limi ing angina). To c ea e he
angina index a iable, we had o me ge o iginal
FINCAVAS a iables. I he pa ien had no pain o
a ypical pain du ing he exe cise, he angina index has
he alue 0. I he pa ien did no epo possible
angina, bu he clinician es ima ed he pos - es
p obabili y o CAD o be low, we also se he angina
index alue o 0. I he pa ien had expe ienced ypical
angina du ing he exe cise, he angina index was 1
and i angina was he eason o ending he es , he
index was 2.
KIHD. Exe cise ime was calcula ed om he METs as
abo e.
In he KIHD s udy, maximal ST-segmen de ia ion
om he baseline du ing exe cise was eco ded om
he leads V5 and aVF and he maximal alue o ST-
segmen de ia ion was used in he analyses. ST-segmen
ele a ions we e excluded, as well as dep essions less
l han 1 mm and g ea e han 5 mm. The ECGs we e
also coded manually by an expe ienced ca diologis ,
gi ing a a iable o ischaemia alues om 0 o 3, 0
meaning no ischaemia and 1–3 indica ing he se e i y o
ischaemia. We ac o ed in his a iable so ha ou a i-
able o he maximal STD o he DTS would be as close
o ha we used in he FINCAVAS popula ion. I he
ischaemia a iable had a alue o 0, he maximal STD
a iable was se o 0, and i he ischaemia a iable had
alues 1–3, he maximal STD a iable was cons i u ed
as abo e. This way we app oxima ed ha he final ST-
a iable akes in o accoun he slope o he ST-segmen .
I he pa ien had no angina, he DTS angina index
has a alue 0, and i a pa ien had exe cise-limi ing
angina, he angina index has a alue o 2. Non-limi ing
angina was no aken in o accoun in he o iginal s udy
se ing. The DTS was cons i u ed as abo e om
FINCAVAS.
O iginally, i he o e all DTS is a leas 5, he pa ien
is conside ed as ‘low isk’, a sco e be ween 11 and 5
deno es ‘mode a e isk’, and a sco e o 11 o less indi-
ca es ‘high isk’.
3
Because only a limi ed numbe o
pa ien s we e classified as belonging o he high- isk
DTS ca ego y, we also di ided he DTS in o equal e -
iles aking accoun he whole popula ion om wo
coho s.
De ini ion o como bidi ies
The p esence o CAD (no/yes) was aken om he med-
ical eco ds and ques ionnai e (p e ious MI, angina
pec o is, e ascula isa ion, and/o use o ni oglyce in).
Diabe es (no/yes) was defined as ha ing a clinical diag-
nosis and egula ea men wi h die o medica ions.
Saloka i e al. 201
In he KIHD s udy, as ing plasma glucose o
7.0 mmol/l o g ea e was an addi ional c i e ium.
Smoking (no/yes) was defined as daily smoking
(FINCAVAS) o smoking wi hin he pas 30 days
(KIHD). The use o b-blocke s was defined as egula
use (no/yes). Some o he egula b-blocke use s wi hin
FINCAVAS we e ad ised o pause he d ug 3 days
be o e he es ; hose pa ien s we e classified in he
‘no’ ca ego y.
Asce ainmen o ollow-up e en s
Dea h ce ifica es based on he 9 h o 10 h e ision o
he In e na ional Classifica ion o Diseases (ICD-10)
we e ecei ed om he causes o dea h egis e main-
ained by S a is ics Finland;
8,13
he da a sou ce has
been alida ed.
14
The e iewe s o dea h ce ifica es
we e blinded o e en s and es esul s. The dea hs
we e classified as ca dio ascula when he ICD-10
code was I00–I79. Ca dio ascula mo ali y was he
p ima y endpoin and all-cause mo ali y he seconda y
endpoin . In FINCAVAS, he au opsy a e was 46%
o all dea hs and 57% o pa ien s who succumbed o
ca dio ascula dea h. In he KIHD s udy he au opsy
a e was 80% o all dea hs.
S a is ical analysis
Diffe ences be ween pa ien and exe cise es cha ac e -
is ics acco ding o he DTS in e iles we e compa ed
using one-way analysis o a iance, K uskal–Wallis es
o chi-squa e es as app op ia e.
The use ulness o he DTS in assessing he p ognosis
was es ed wi h a Cox p opo ional haza ds model.
Co a ia es included age, sex, body mass index (BMI),
a diagnosed CAD, smoking s a us, b-blocke usage and
diabe es. The componen s o he DTS (STD, angina
index and pe o mance in METs) we e added o an
addi ional model wi h o he co a ia es. The DTS was
en e ed as he o iginal e sion ca ego ised in o h ee
pa s (low isk, mode a e isk and high isk) and as a
h ee-ca ego y e sion wi h e iles.
S a is ical analyses we e pe o med using he SPSS
elease 23.0 o Mac (SPSS Inc., Chicago, IL, USA).
All s a is ical es s we e wo- ailed and used an alpha
le el o 0.05.
Resul s
Pa ien cha ac e is ics a e gi en in Table 1. Wi hin he
o iginal DTS ca ego isa ion, 3.5% o pa ien s o he
FINCAVAS popula ion we e classified as being in
high, 52% in mode a e and 40% in low isk. In he
KIHD s udy popula ion, only 1.6% we e classified as
high, 31.4% as mode a e and 67.0% as low- isk
pa ien s. In ou new ca ego isa ion a DTS o e 6.7
belongs o he lowes isk e ile, sco es om 3.0 o
6.7 o he middle e ile and sco es below 3.0 o he
highes isk e ile.
FINCAVAS
The age o he popula ion was 56 13 yea s. Dea h
om any cause o om ca dio ascula causes was ec-
o ded in 404 (10.3%) and 180 (4.6%) pa ien s, espec -
i ely, o e he median ollow-up pe iod o 6.3 yea s
(in e qua ile ange (IQR) 4.5–8.2).
As a h ee-ca ego y a iable wi h he cu poin s om
he o iginal eadmill s udies, he DTS (highes s.
lowes g oup) was highly p edic i e o bo h ca dio as-
cula dea h (HR 2.26, 95% CI 1.48–3.45, P<0.001)
and all-cause mo ali y (HR 1.70, 95% CI 1.31–2.22,
P<0.001) when adjus ing o o he co a ia es.
Howe e , he p ognos ic signal o he DTS disappea ed
en i ely when he model was also adjus ed wi h he
h ee componen s o he DTS (METs, angina index
and maximal STD): HR o ca dio ascula dea h was
1.10 (95% CI 0.63–1.92, P¼0.740). Impo an ly, exe -
cise capaci y in METs was he only DTS componen
wi h a s a is ically significan HR (0.77, 95% CI 0.70–
0.85, P<0.001) in his ully adjus ed model.
The esul s we e simila o he DTS di ided in o
equal e iles: he DTS was p edic i e o ca dio ascula
dea h (HR 3.15, 95% CI 1.83–5.43, P<0.001) and
all-cause dea h (HR 2.08, 95% CI 1.49–2.90,
P<0.001). Howe e , when adjus ed wi h he h ee indi-
idual componen s, he DTS was no p edic i e o
ca dio ascula dea h and, again, METs was he
sole componen linked wi h p ognosis, as shown in
Table 2 and Figu e 1.
KIHD
The age o he KIHD s udy popula ion was 53 5.1
yea s. A o al o 1200 dea hs (44.7%) occu ed om
any cause and 562 (21.0%) om ca dio ascula causes
o e he median ollow-up pe iod o 24.1 yea s (IQR
18.0–26.2 yea s).
As a adi ional h ee-ca ego y a iable and adjus ed
wi h co a ia es, he DTS was p edic i e o ca dio as-
cula dea h and all-cause mo ali y when compa ing
he lowes wi h he highes g oup (HR 1.52, 95% CI
1.25–1.85, P<0.001 and 1.37, 95% CI 1.20–1.56,
P<0.001, espec i ely). When also adjus ed wi h all
h ee componen s o he DTS, he h ee-ca ego ical
DTS was no associa ed wi h ca dio ascula dea h
(HR 1.11, 95% CI 0.83–1.49, P¼0.48). O he h ee
indi idual componen s, only exe cise capaci y in
METs was ela ed o he isk o ca dio ascula dea h
(HR 0.85, 95% CI 0.79–0.90, P<0.001).
202 Eu opean Jou nal o P e en i e Ca diology 26(2)
Table 1. Pa ien and exe cise es cha ac e is ics o bo h coho s acco ding o he DTS isk e iles.
FINCAVAS KIHD
DTS DTS
Lowes isk
e ile (n¼1209)
Middle isk
e ile (n¼1024)
Highes isk
e ile (n¼1525)
Lowes isk
e ile (n¼1158)
Middle isk
e ile (n¼704)
Highes isk
e ile (n¼530)
Mean SD Mean SD Mean SD P alue Mean SD Mean SD Mean SD P alue
Age (yea s) 50.3 12.6 57.9 11.7 59.1 12.7 <0.001 51.6 5.3 54.0 4.5 54.1 4.6 <0.001
BMI (kg/m
2
) 26.5 4.1 28.4 4.7 27.7 4.7 <0.001 26.2 3.0 28.1 3.9 26.5 3.1 <0.001
METs 10.0 2.2 6.8 2.2 6.3 2.7 <0.001 10.0 1.6 7.0 1.7 7.9 2.3 <0.001
Median IQR Median IQR Median IQR Median IQR Median IQR Median IQR
STD (mm) 0.0 0.0–0.0 0.0 0.0–0.0 1.3 0.0–1.9 <0.001 0.0 0.0–0.0 0.0 0.0–0.0 1.6 1.3–2.1 <0.001
n(%) n(%) n(%) n(%) n(%) n(%)
Angina index 3 (0.2%) 23 (2.2%) 122 (8.0%) <0.001
0 (0.0%) 3 (0.3%) 216 (14.2%) 0 (0.0%) 0 (0.0%) 86 (16.2%) <0.001
Women 448 (37.1%) 446 (43.6%) 615 (40.3%) 0.008
CAD 219 (18.1%) 129 (12.8%) 564 (37.0%) <0.001 151 (13.0%) 229 (32.5%) 194 (36.6%) <0.001
b-Blocke 471 (39.0%) 628 (61.3%) 1011 (66.3%) <0.001 88 (7.6%) 183 (26.0%) 140 (26.4%) <0.001
Diabe es 92 (7.8%) 129 (12.8%) 205 (13.8%) <0.001 35 (3.0%) 46 (6.5%) 42 (7.9%) <0.001
Smoking 278 (23.0%) 251 (24.5%) 319 (20.9%) 0.095 340 (29.4%) 258 (36.6%) 163 (30.9%) 0.004
P io MI 152 (12.6%) 216 (21.1%) 344 (22.6%) <0.001
SD: s anda d de ia ion; DTS: Duke eadmill sco e; METs: me abolic equi alen s o asks; STD: ¼maximal ischaemic ST-segmen dep ession du ing exe cise; CAD: diagnosed co ona y a e y disease; MI:
myoca dial in a c ion.
Saloka i e al. 203

When di ided in o equal e iles, he DTS was p e-
dic i e o ca dio ascula dea h (adjus ed HR 1.43, 95%
CI 1.13–1.80, P¼0.003) and all-cause dea h (HR 1.43,
95% CI 1.22–1.66, P<0.000). Howe e , when all com-
ponen s o he DTS we e included in he mul i a iable
model, only METs and maximal STD we e s a is ically
significan , as shown in Table 2 and Figu e 1.
Discussion
Ou findings demons a e ha he DTS based on he
bicycle e gome e es is consis en ly p edic i e o a al
ca dio ascula and all-cause mo ali y. The DTS was
p edic i e o ca dio ascula dea h in bo h popula ions
as an o iginal h ee-ca ego y a iable. Howe e , exe -
cise capaci y alone p o ed o be a supe io p edic o
o ou comes in compa ison o he DTS. One uni
inc emen in exe cise capaci y (METs) was ela ed o
a 17–20% lowe isk o ca dio ascula mo ali y. F om
he o he wo DTS componen s, he angina index was
no p edic i e o ca dio ascula dea h in ei he popu-
la ion; howe e , maximal STD was s a is ically signifi-
can in he KIHD s udy popula ion. The esul s a e
unequi ocal in demons a ing ha he DTS does no
p o ide any p ognos ic in o ma ion independen o i s
componen s.
This is he fi s s udy o assess he p ognos ic alue
o he DTS wi h he s anda d bicycle e gome e . A p e-
ious s udy wi h a limi ed numbe o pa icipan s
(n¼211) was conduc ed o compa e he bicycle e gom-
e e in he supine posi ion and he eadmill es when
assessing he alue o he DTS.
15
The use o he supine
bicycle e gome e ins ead o he eadmill led o a lowe
maximal wo kload and METs le el.
15
This was a
eason ha pa ien s go lowe DTS esul s and hus
hey we e mos ly classified in o highe isk ca ego ies.
The e a e se e al possible explana ions as o why
BMI, smoking s a us and diabe es we e associa ed
wi h ou come in he KIHD s udy bu no in
FINCAVAS pa ien s. Fi s , he s udy popula ions
we e qui e diffe en . In he FINCAVAS coho ,
pa ien s we e e e ed o an exe cise es due o clinical
easons, whe eas in he KIHD s udy, pa icipan s we e
a andomly selec ed popula ion-based sample o men.
The KIHD s udy included middle-aged men based on a
gene ically and e hnically homogeneous popula ion
om eas e n Finland, an a ea p e iously known o
i s high p e alence and incidence o ca diome abolic
diseases. In addi ion, i is possible ha he assessmen
me hods o baseline cha ac e is ics and isk ac o s
influenced he obse ed findings. Finally, he KIHD
s udy da a had an essen ially longe ollow-up han
he o he da ase , g an ing he isk ac o s mo e ime
o cause clinical e en s and ca dio ascula mo ali y.
Gene al diffe ences be ween eadmill and s anda d
bicycle e gome e exe cise es ing ha e been s udied
ea lie , and pa ien s seem o ge 10–20% lowe maximal
METs i hey a e no accus omed o cycling,
16
possibly
because muscle a igue p e en s hem om eaching
hei VO
2
max.
When he DTS was o iginally de eloped o ead-
mill exe cise es ing, ST-de ia ion was he mos
Table 2. Cox eg ession su i al analysis o he DTS as e iles, i s componen s and co a ia es, ca dio ascula -mo ali y as an
endpoin .
FINCAVAS KIHD
95% CI 95% CI
HR Lowe Uppe P alue HR Lowe Uppe P alue
DTS (3 d s. 1s e ile) 1.149 0.604 2.185 0.672 0.900 0.677 1.195 0.466
METs 0.799 0.726 0.88 <0.001 0.821 0.767 0.879 <0.001
STD 1.042 0.869 1.251 0.656 1.209 1.012 1.444 0.036
Angina 0.757 0.571 1.003 0.053 1.057 0.863 1.295 0.592
Age 1.034 1.018 1.05 <0.001 1.068 1.044 1.094 <0.001
Sex 2.929 1.985 4.323 <0.001
BMI 0.999 0.964 1.035 0.965 1.058 1.029 1.087 <0.001
CAD 0.952 0.69 1.313 0.763 1.403 1.138 1.731 0.002
b-Blocke 1.387 0.935 2.057 0.104 1.379 1.109 1.715 0.004
Diabe es 1.216 0.823 1.796 0.327 2.018 1.509 2.700 <0.001
Smoking 1.183 0.832 1.681 0.349 2.199 1.823 2.652 <0.001
HR: haza d a io; DTS: Duke eadmill sco e; METs: me abolic equi alen s o asks; STD: maximal ischaemic ST-segmen dep ession du ing exe cise;
Angina: non-limi ing (FINCAVAS) and limi ing (FINCAVAS and KIHD) angina du ing exe cise; BMI: body mass index; CAD: diagnosed co ona y a e y
disease.
204 Eu opean Jou nal o P e en i e Ca diology 26(2)
powe ul p ognos ic a iable, and adding angina and
exe cise ime inc eased p ognos ic powe .
3
Exe cise
capaci y (METs) has been epea edly alida ed o be
he single mos powe ul p ognos ic ma ke p edic ing
ca dio ascula mo ali y
17–20
and majo ca dio ascula
e en s.
21
The Ame ican Hea Associa ion ecen ly
made a s a emen ha ca dio espi a o y fi ness should
be assessed ou inely in clinical p ac ice.
22
In a p e ious
s udy, classic ca dio ascula isk ac o s including dia-
be es, hype ension, obesi y and smoking, we e linked
o dec eased exe cise capaci y.
23
In a coho o middle-
aged men wi h mo e han 40 yea s o ollow-up, low
exe cise capaci y led o inc eased o e all mo ali y
a es, independen o smoking, blood p essu e and
se um choles e ol.
24
A la ge longi udinal s udy o
Swedish adolescen men ound ha poo exe cise cap-
aci y was also associa ed wi h a g ea e isk o inciden
hea ailu e.
25
These examples ou line he independen
p ognos ic impo ance o exe cise capaci y. In con as ,
he p ognos ic significance o ST-de ia ion and angina
is s ill unclea , despi e he ac ha he diagnos ic
powe o bo h ST-segmen changes and angina is well
es ablished.
26–29
The ela i e impo ance o each o he DTS compo-
nen s p obably depends la gely on he popula ion. The
s udy popula ion om which he DTS was ini ially
de i ed had a high p obabili y o CAD, confi med
by consequen co ona y ca he e isa ion, whe eas mos
1.0 Low isk
Mode a e isk
High isk
Low isk
DTS DTS
DTSDTS
FINCAVAS(a) (b)
(c) (d)
KIHD
Mode a e isk
High isk
Low isk
Mode a e isk
High isk
Low isk
Mode a e is
k
High isk
0.9
0.8
Su i al
Su i al
Su i al
Su i al
0.7 HR 3.15, p< 0.001
HR 1.71, p< 0.001
HR 1.15, p= 0.672
HR 0.90, p=0.466
0.6
1.0
0.9
0.8
0.7
0.6
1.0
0.9
0.8
0.7
0.6
1.0
0.9
0.8
0.7
0.6
0 20 40 60 80 100 120 0 20 40 60 80 100 120
0 100 200 300 4000100
Time o dea h o o he end o he ollow-up
(
mon hs
)
Time o dea h o o he end o he ollow-up
(
mon hs
)
Time o dea h o o he end o he ollow-up
(mon hs)
Time o dea h o o he end o he ollow-up
(mon hs)
200 300 400
Figu e 1. Adjus ed Cox eg ession su i al analysis acco ding o Duke eadmill sco e isk e iles in bo h coho s, ca dio ascula
mo ali y as an endpoin ; (a) and (c) wi hou he componen s o he DTS; (b) and (d) wi h he componen s.
Saloka i e al. 205
o he la e s udies ha e consis ed o pa ien s e e ed
o exe cise es ing because o a milde suspicion o
CAD. This could pa ially explain he shi o he bes
p ognos ic ma ke om ST-de ia ion o exe cise
capaci y.
Whe he combining he h ee componen s in o he
DTS yields addi ional p ognos ic in o ma ion in com-
pa ison o using he componen s sepa a ely has no
been well explo ed. P e iously, using mul i a iable ana-
lyses in assessing he p ognosis o pa ien s has
enhanced he p ognos ic powe compa ed o analysing
independen a iables o he han he DTS compo-
nen s.
19,30,31
In hese s udies, he analysed a iables
we e hea a e eco e y, T-wa e al e nans and
METs. This supplemen a y p ognos ic in o ma ion
may ha e been due o he diffe en pa hophysiological
bases assessed by diffe en a iables. In he DTS, he e
a e wo a iables indica ing myoca dial ischaemia
which may no be help ul.
The s eng h o his s udy is he usage o wo inde-
penden la ge p ospec i e da ase s and he assessmen
o a comp ehensi e ange o po en ial co a ia es. The
ollow-up o he KIHD s udy is pa icula ly long; how-
e e , he s udy is limi ed by he absence o emale pa -
icipan s. Da a on angina ha did no limi exe cise was
no conside ed in he o iginal KIHD s udy se ing. The
s eng hs o FINCAVAS a e a la ge popula ion and
elec onically sa ed bea - o-bea ECG da a.
Measu ing exe cise capaci y as METs may ha e i s
weaknesses ega ding pa ien s’ age and a - ee
mass.
32–34
Nei he s udy akes in o accoun he changes
in pa ien cha ac e is ics and ea men du ing he
ollow-up pe iod. The e can be esidual con ounde s
affec ing ca dio ascula mo ali y in addi ion o co a i-
a es, which we accoun ed o . Na u ally, we canno
d aw causal in e ences om obse a ional s udies.
In conclusion, he DTS seemed o be p edic i e o
ca dio ascula dea h o pa ien s who unde wen
bicycle exe cise es ing in wo diffe en popula ions.
Howe e , when adjus ed wi h i s componen s, he p e-
dic i e powe o he DTS disappea ed, as exe cise cap-
aci y p o ed o be a supe io p edic o o a al
ca dio ascula ou comes. Mo e s udies a e needed o
confi m ou findings using bicycle exe cise es ing.
Measu ing and ca ego ising exe cise capaci ies should
be u he cul i a ed. Fu u e esea ch should also con-
cen a e on de eloping mo e accu a e mul i a iable
p ognos ic sco es which ake in o accoun mo e e sa-
ile unde lying pa hophysiological bases.
Au ho con ibu ion
ES, TN and JAL con ibu ed o he concep ion and design o
he wo k. All au ho s con ibu ed o he acquisi ion, analysis,
o in e p e a ion o da a o he wo k. ES d a ed he manu-
sc ip . All au ho s c i ically e ised he manusc ip .
All au ho s ga e final app o al and ag ee o be accoun able
o all aspec s o he wo k ensu ing in eg i y and accu acy.
Decla a ion o con lic ing in e es s
The au ho (s) decla ed no po en ial conflic s o in e es wi h
espec o he esea ch, au ho ship, and/o publica ion o his
a icle.
Funding
The au ho (s) disclosed eceip o he ollowing financial sup-
po o he esea ch, au ho ship, and/o publica ion o his
a icle: he Finnish Ca dio ascula S udy (FINCAVAS) has
been financially suppo ed by he compe i i e esea ch und-
ing o Tampe e Uni e si y Hospi al (G an s X51001), he
Finnish Cul u al Founda ion, he Finnish Founda ion o
Ca dio ascula Resea ch (TL), he Emil Aal onen
Founda ion (TL), Finland, and he Tampe e Tube culosis
Founda ion and by he Academy o Finland (g an 286284
o TL).
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