PDF - Circulation

DOI: 10.1161/CIRCULATIONAHA.112.123117
Cardiovascular Risk of High- Versus Moderate-Intensity Aerobic Exercise in
Coronary Heart Disease Patients
Running title: Rognmo et al.; Risk of high- vs. moderate-intensity exercise
Downloaded from http://circ.ahajournals.org/ by guest on February 7, 2017
Øivind Rognmo, PhD1; Trine Moholdt, PhD1; Hilde Bakken, BSc2; Torstein Hole, MD, PhD3;
Per Mølstad, MD, PhD4; Nils Erling Myhr, BSc4; Jostein Grimsmo, MD,, PhD
hD4;
Ulrik Wisløff, PhD1
1
Dept
De
pt ooff Ci
Circ
Circulation
rcculat
atio
at
ionn and Medical Imaging, K.G.
io
K.G
G. Je
Jebsen
ebsen Ctr of Ex
Exercise
xer
e ci
cise
se IIn
n Medicine, Norwegian
Un
University
niv
i ersity ooff S
Science
ciienc
ncee and
and Te
Tech
Technology
chno
nollog
no
logy
gy (NT
(NTNU),
TNU),, T
Trondheim;
rond
ndhe
nd
heeim
im; 2Rø
Røross Re
Reha
Rehabilitation
haabi
bili
lita
tati
tion
ti
on
nC
Ctr,
trr, Rø
Røros;
øro
os;
3
Medical
Medi
Me
dica
di
call De
Dept
Dept,
pt,, Ål
pt
Ålesund
Åles
e un
undd Hospital,
Hosp
Ho
spit
ittal
al, Ålesund;
Åles
Ål
essun
undd;
d; 4Fe
Feiring
Feir
irrin
ingg He
Hear
Heart
arrt Cl
Clin
Clinic,
inicc, Fe
in
Feiring,
eir
irin
ing,
in
g, N
Norway
orrwa
wayy
Address for Correspondence:
Øivind Rognmo
Det medisinske fakultet
NTNU, Institutt for sirkulasjon og bildediagnostikk
Postboks 8905, Medisinsk teknisk forskningssenter
7491 Trondheim, Norway
Tel: +47 72 82 80 80
Fax: +47 72 82 83 72
E-mail: [email protected]
Journal Subject Codes: [26] Exercise/exercise testing/rehabilitation; [122] Secondary
prevention
1
DOI: 10.1161/CIRCULATIONAHA.112.123117
Abstract:
Background - Exercise performed at higher relative intensities has been found to elicit greater
increase in aerobic capacity and greater cardioprotective effects than exercise at moderate
intensities. It has also been detected an inverse association between the relative intensity of
physical activity and the risk of developing coronary heart disease, independent of the total
volume of physical activity. Despite that higher levels of physical activity is effective in reducing
cardiovascular events, it is also advocated that vigorous exercise could acutely and transiently
increase the risk of sudden cardiac death and myocardial infarction in susceptible persons. This
issue may affect cardiac rehabilitation.
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Methods and Results - We examined the risk of cardiovascular events during organized highy interval exercise training
g and moderate-intensity
y training
g among
g 4846 CHD ppatients in
intensity
four Norwegian cardiac rehabilitation centers. Of a total of 175 820 exercise training
train
in
nin
ng ho
hour
urss
ur
hours
where all patient performed both types of training we found one fatal cardiac arrest during
moderate-intensity
ty exercise (129 456 exercise hours), and two non-fatal cardiac arrests during
high
hi
gh-i
gh
-int
-i
nten
nsiity int
nter
erva
val ex
exer
erci
c see ((46
46 364
64 eexercise
xercis
i e hou
hhours).
ours)). Th
There we
ere nno
o my
m
occarrdi
d al inf
n ar
a ct
c ions in
high-intensity
interval
exercise
were
myocardial
infarctions
he data
data material.
materria
ial.
l As
As the
t e number
th
n mb
nu
mber
er of
of high-intensity
high
hi
ghh-inttennsityy training
trainnin
ning
ng hours
hours
ourss was
was 36%
36% of the
the number
num
umbber off
the
mo
ode
deraate-int
ntten
e si
sity
ty
y hhours,
ours,, th
he ra
rate
tes of
o ccomplications
omplliccat
atio
io
ons tto
o th
he nu
numb
mb
berr of pat
ppatient-exercise
atien
tien
nt--ex
exer
erccis
cise hhours
ours w
ours
ere
moderate-intensity
the
rates
the
number
were
1 per
peer 129
129 456
45 of
o moderate-intensity
mod
oderat
atee in
nte
tens
nsit
ity exercise
exerrci
cise
se and
an
nd 1 per
per 23 182
182 off hi
high
gh-i
- ntten
e si
sity
ty eexercise.
xerc
rcis
i e.
high-intensity
Conclusion
ns - The
The results
res
esul
ults
ul
t of
of the
the current
c rr
cu
rren
nt study
sttud
udyy indicate
indi
in
dica
di
catte that
ca
tha
hatt th
thee ri
iskk of a ccardiovascular
a di
ar
d ov
ovas
asscu
ula
lar event is
Conclusions
risk
low after both high-intensity exercise and moderate-intensity exercise in a cardiovascular
rehabilitation setting. Considering the significant cardiovascular adaptations associated with
high-intensity exercise, such exercise should be considered among CHD patients.
Key words: coronary disease; death, sudden; exercise; heart arrest
2
DOI: 10.1161/CIRCULATIONAHA.112.123117
Background
High levels of physical activity and aerobic capacity are associated with low risk of
cardiovascular disease and mortality 1-3. Aerobic exercise is therefore strongly recommended
both for healthy individuals and for patients with cardiovascular disease to improve
cardiovascular health and reduce risk of premature mortality 4, 5. If the total energy expenditure
of exercise is held constant, exercise performed at higher relative intensities has been found to
elicit greater increase in aerobic capacity 6 and greater cardioprotective effects than exercise at
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moderate intensities 7, 8. It has also been detected an inverse association between the relative
intensity of physical activity and the risk of developing coronary heart disease, independent of
the
he total volume off physical activity 9, 10. Indeed, when exercise is carried out att hhigh
ig
gh in
inte
intensity,
tens
te
nsit
ns
ity,
it
y, as
little
ittle as a single weekly bout of exercise seems to be sufficient for reducing the risk of
cardiovascular
ca
ard
dio
iovvasc
vasccul
ulaar ddeath
eath
ea
th in a large unselected popul
population
latio
at on 11, as well ass in subjects
suubjects
bj
with coronary
1
hheart
hear
eart
rt disease (C
(CHD)
CHD
HD)) 12
.
Despite
Desp
De
spit
sp
itee th
that
hat
at hhigher
igher
igh
her le
levels
eve
v ls ooff ph
physical
hys
ysic
icaal
ic
al aactivity
c iv
ct
vitty reduces
redu
redu
ducces
ces cardiovascular
c rdio
ca
rdio
iova
v sc
va
scuular
ularr events,
eve
v nt
nts,
s, itt is
advocated th
that
hat vvigorous
igor
ig
orou
or
ou
us ac
activity
cti
tivi
v ty
vi
y co
ccould
u d al
ul
aalso
so aacutely
cute
cu
t ly aand
te
n transiently
nd
tra
rans
nsie
ns
ieent
ntly
l iincrease
ly
ncre
nc
reas
re
asee th
as
thee ri
risk
sk ooff sudden
cardiac death and myocardial infarction in susceptible persons 13. Therefore, current guidelines
recommend that patients in cardiac rehabilitation or secondary prevention programs perform
moderate exercise between 50-90% of peak heart rate (HRpeak) 14 15. Our research group is
however using an exercise model which incorporates aerobic interval exercise training at 85-95%
of HRpeak not only in healthy individuals but also in CHD patients. The results demonstrate that
such high-intensity exercise is superior to moderate intensity for improving both peak oxygen
uptake (VO2peak) and cardiac function, as well as reducing the risk factors associated with
cardiovascular disease 16-19. The safety aspect of such high intensity exercise training programs
3
DOI: 10.1161/CIRCULATIONAHA.112.123117
should however be evaluated before it is used in large, unselected groups of CHD patients. The
aim of this study was therefore to assess if there is an increased risk of cardiovascular events or
death during, or immediately after, exercising with high- compared to moderate-intensity in a
large group of CHD patients undergoing cardiac rehabilitation.
Methods
Subjects
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We included 4846 patients (ƃ 70%, Ƃ 30%) who were referred to an exercise-based cardiac
rehabilitation program at three different rehabilitation units in Norway between 2004 and 2011.
Mean age was 57.8 years. All CHD patients taking part in this survey were enrolled
enrol
olle
ledd att the
the
rehabilitation
ehabilitation units and the total number of high- and moderate-intensity exercise sessions was
registered.
rehabilitation
egi
gist
ster
st
ered
er
ed.. The
ed
Th patients
pattie
pa
tients were referred to the reha
abilitation units bby
y their
thei
eiir ggeneral
eneral practitioner or
hospital
cardiologist
their
diagnoses
included
myocardial
infarction
hospital
hosp
p
cardiol
ollogiistt and
and th
thei
eirr ma
ei
main
i aadmission
in
dmissiion
dm
n dia
agnosses
agn
ses in
ncllud
udeed
ed m
yo
ocaard
rdia
iall in
ia
infa
farc
fa
rcctiion
on ((7%),
7%)),
7%
),
angioplasty
(40%),
surgery
(35%),
heart
(7%).
an
ngi
giop
opla
op
last
styy (4
(40%
0%
%),, ccoronary
oronaryy su
surg
rger
rg
eryy (3
er
35%
5%),
), vvalve
a vee ssurgery
al
urrge
gery
ry ((11%),
111%)
%), he
hear
arrt fail
ffailure
aillure
ure (7
(7%)
%.
%)
prescription
Exercise pre
esc
scri
r pt
ri
ptio
i n
io
We have from 2004 published several randomized controlled trials with focus on improving
physical capacity after high- vs. moderate-intensity exercise in different groups of CHD patients
and in individuals at high risk of developing CHD 17-21. The high-intensity interval training
model from these studies has been adopted by several Norwegian cardiac rehabilitation centers
and is now a part of their standard rehabilitation procedure. In the current survey all highintensity exercise training sessions were performed as interval training with the aim to reach an
intensity of 85-95% of HRpeak because this mix of work and rest-periods allows for more intense
exercise to be tolerated before exhaustion. The moderate-intensity exercise sessions was
4
DOI: 10.1161/CIRCULATIONAHA.112.123117
performed at approximately 60-70% of HRpeak, and is the typically used intensity involving
cardiac patients 22. All exercise sessions lasted approximately one hour.
Organization of exercise of at the rehabilitation units
The three Norwegian rehabilitation units taking part in this survey were located at Ålesund
Hospital, Feiring Heart Clinic and Røros Rehabilitation Center. The patients underwent a
medical examination before starting rehabilitation. All rehabilitation centers tested patients for
VO2peak and HRpeak with full-lead ECG prior to the rehabilitation program for safety reasons, and
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the results from these tests determined the individual exercise intensity zone’s for the patients.
Both high- and moderate-intensity exercise sessions were conducted throughout a rehabilitation
period containing on average 37 exercise sessions. All patients in this study parti
tici
cipa
p teed in tthe
he
he
participated
tandard rehabilitation given at the institutions, which consisted of separate sessions of high- vs.
standard
mo
mode
dera
de
ratte-i
ra
te-iint
nteensi
siity exercise.
exercise. The adverse eventss during
during or after the
he exe
xeerc
rcis
i e sessions were
moderate-intensity
exercise
co
ounted
un and related
reela
late
tedd too the
he intensity
int
nteensi
ensity
ty of
of exercise.
ex
xerccisee. The
The training
traain
ainin
ning
ng modality
modalit
alityy typically
typi
ty
pica
caallly consisted
co
onssis
isttedd of
counted
reaadm
dmil
illl ex
xerci
ercisse bbut
ut al
lso ae
ero
robi
bicc grou
bi
ggroup
rou
up tr
tra
aini
ning
ni
ng,, biki
ng
bbiking
ikiing ssessions,
essi
sion
si
ons,
on
s, aand
nd ooutdoor
u do
ut
door
or w
alkkinng
al
ng aand
ndd
treadmill
exercise
also
aerobic
training,
walking
cross-countr
ry sk
skii
iiing w
a pperformed.
as
erfo
er
f rm
fo
rmed
ed..
ed
cross-country
skiing
was
Execution of High- and moderate-exercise
The high-intensity interval training sessions were carried out as earlier described 17 and typically
consisted of warm-up for a minimum of 10 minutes at 60% to 70% of HRpeak before working
four 4-minute intervals at 85% to 95% of HRpeak. Each interval was separated by active pauses at
50% to 70% of peak heart rate. The training session was terminated by a cool-down period at
50% to 70% of HRpeak. Moderate exercise was simply the intensity one could carry on for a
prolonged time period, and the subject should be able to converse in full sentences. During the
moderate exercise sessions, the patients worked continuously, with intensity at or below 70% of
5
DOI: 10.1161/CIRCULATIONAHA.112.123117
HRpeak. The subjects wore heart rate monitors in some exercise-sessions to control that proper
intensity was carried out according to the initial HRpeak-test. Furthermore, high-intensity was
additionally controlled either by the Borg rating of perceived exertion (on a scale of 6 to 20) 23,
and by instructing the subjects to exercise at an intensity that brought them to breathe heavily,
causing difficulties to speak more than a couple of words. When heart rate monitors was not
employed, exercise sessions were categorized as moderate-intensity exercise when the perceived
exertion was approximately at 12-14 on the Borg 6-20 scale 23, and as high-intensity when the
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perceived exertion was above 15-17 at the high-intensity parts of the session.
Adverse events
An adverse event related to exercise training was defined as cardiac arrest or acu
ute
te m
yoca
yo
card
ca
rdiial
rd
i al
acute
myocardial
nfarction during exercise, or within the first hour afterwards. Only events occurring during and
infarction
af
fteer su
supe
perv
rvis
rv
ised
is
d eexercise
xe
xercise
training were included
d. Th
he emergency re
rresponse
sppon
onsse
se to cardiac arrests was
after
supervised
included.
The
mmediate usee of
o defibrillator,
deffib
i riill
llat
ator
at
or,, and
or
and any
any suspicion
susppiccion off complications
com
ompl
om
pliicatio
ations
ns during
dur
urin
ingg th
he re
reha
habi
ha
bili
bi
liitaatiion
on sstay
taay
immediate
the
rehabilitation
wa
as re
repo
port
po
rted
ed tto
o the
the in
indi
divvidu
vidual
a uunit’s
al
nit’
ni
t’ss re
t’
esppon
onssibble
l pphysician
hy
ysiiciian ffor
or ddiagnostic
iagn
gnos
gn
ostticc de
ete
t rm
rmin
in
natio
a t on.
was
reported
individual
responsible
determination.
Statistical an
nal
alys
ysis
ys
is
analysis
Before collecting and interpretation of data, the study was assessed by the regional committee for
medical research ethics. Estimation of sample size and power were done by STATA, version 12
(College Station, Texas).
Results
Among the 4846 patients, a total of 175 820 exercise sessions lasting approximately one hour
were recorded, distributed on 129 456 hours of moderate-intensity exercise and 46 364 hours of
high-intensity exercise, respectively. Overall, the incidences included one cardiac arrest with
6
DOI: 10.1161/CIRCULATIONAHA.112.123117
fatal outcome during moderate-intensity exercise, and two non-fatal cardiac arrests during highintensity exercise (Table 1). There were no myocardial infarctions in the data material. During
their stay at the rehabilitation centers, the patients carried out an average of 36% high-intensity
sessions compared to the number of moderate-intensity sessions. Thus, when relating the number
of adverse events to the number of patient-exercise hours, the event rates were 1 per 129 456
hours of moderate-intensity exercise and 1 per 23 182 hours of high-intensity exercise. These
results indicate that both types of exercise training are associated with low event rates. The types
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of adverse events related to exercise are presented in Table 2.
Discussion
Our study is the first to examine the risk of adverse events of combined organized high-intensity
interval
training
nteerv
rval
al eexercise
xerc
xe
rccisee tr
trai
aining and moderate-intensityy ttraining
raaining in CHD
D ppatients.
atie
ieent
nts.
s We found one fatal
cardiac
highca
ard
dia
i c arrest during
durin
ng moderate-intensity
mode
mo
dera
de
rate
ra
te-i
te
-int
ntten
ensi
sity
ty exercise,
exeerccise, and
and two
two non-fatal
nonno
n-ffat
fatal cardiac
card
ca
rdiiacc arrests
arr
rres
estts dduring
urrin
ng hi
high
ghhintensity
interval
Ass th
number
high-intensity
training
was
nte
tens
nssit
ityy in
nte
terv
rval
all eexercise.
xerrcisse. A
xe
thee nu
num
mber ooff hi
mber
high
gh-i
gh
-innteensi
ensi
sity
ty tra
rain
ra
i in
in
i g se
ssessions
ssiions
ionss w
as 336%
6% off th
6%
thee
the
rates
number of moderate-intensity
mo
ode
dera
raate
te-i
-int
nten
nt
ensi
sity
si
ty ssessions,
ess
ssio
io
ons
ns,, th
he ra
rate
tess of ccomplications
te
om
mpl
plic
icat
ic
a ion
at
onss to the
the nnumber
umbe
um
berr of ppatientbe
a ientat
exercise hours were 1 per 129 456 sessions of moderate-intensity exercise and 1 per 23 182
hours of high-intensity exercise. The absolute event rates were very low after exposure to both
types of exercise, and thecalculated power to detect such a minor difference was only 23% A
sufficient powered study with an adequate sample size (power of 0.80 and significance level
0.05) conducted in a similar way to ours, would have required close to 21000 patients to detect
differences between groups, and a randomized study with 1:1 randomization would had to
include 10264 patients in each group. Another challenge is to assess the severity of a death
compared to a successful resuscitation of two cardiac arrests when comparing the risks of the
7
DOI: 10.1161/CIRCULATIONAHA.112.123117
two intensity modes. The low event rate after exposure to both types of exercise training may
thus be the strongest interpretation of this study. Due to the more extensive use of high-intensity
exercise training in cardiac rehabilitation worldwide, we believe that our study brings highly
demanded knowledge about the risk of such exercise for secondary cardiac rehabilitation.
At least five reports have previously estimated the incidence of exercise-related
cardiovascular complications from exercise-based cardiac rehabilitation programs among
persons with documented CHD 24-28. An initial survey involved 30 cardiac rehabilitation
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programs in Canada and United States detected 1 non-fatal and 1 fatal cardiovascular
complication per 34 673 and 116 402 hours, respectively 24. Contemporary exercise-based
cardiac rehabilitation programs appear to have a lower complication rate as an an
analysis
nal
alys
y is ooff 4
reports
eports estimated 1 cardiac arrest per 116 906 patient-hours, 1 myocardial infarction per 219 970
patient-hours,
paatiien
entt-ho
t-ho
hour
u s,, 1 ffatality
ur
atal
at
a ity per 752 365 patient-hour
patient-hours,
urs,
ur
s aand
nd 1 major com
complication
o pl
om
plic
icaation
ic
at
per 81 670 patient25-28
5-28
28
hours
hours
hou
ur of participation
partici
cippattion 25. Th
Thi
This
is low
is
low fatality
fataalityy ra
rate
ate aapplies
ppliees
es tto
om
medically
ediically
ed
ally ssupervised
up
per
ervvis
vised
sed pro
pprograms
rogr
ograms
ms tthat
hat
ha
are
ar
re run
run by personnel
perso
ersonn
nnel
nn
el trained
tra
rain
i ed to
in
to handle
hand
ha
ndle
nd
le emergencies.
eme
merg
rgen
rg
enci
en
ciees.
es. Itt iss claimed
claaim
cl
med that
med
th
hat
a the
the death
deeat
a h rate
raate would
wooul
ould
ld be
be 66fold higher wi
without
ith
thou
ou
ut th
tthee su
ssuccessful
cces
cc
essfful m
es
management
an
nag
agem
emen
em
entt of ccardiac
en
a diiac aarrest
ar
rres
rr
estt pr
es
prov
provided
ovid
ov
ided
id
ed bby
y su
such
ch sspecialists
pecialists 13.
pe
Furthermore, CHD patients are normally medically evaluated before participation in cardiac
rehabilitation programs which typically decrease the event rates even more, supporting the use of
supervised exercise-based cardiac rehabilitation programs for patients after cardiac events 29. In
our study, all centers conducted cardiopulmonary testing including 12-lead ECG prior to
rehabilitation. Exclusion as a result of the stress test on admission were however very rare. Main
reason for exclusion was recurrent ischemia by ECG, chest pain and low exercise capacity,
which resulted in a new examination to decide whether rehabilitation could be initiated. The
problem with exclusion of those with the highest risk was thus low in our data set.
8
DOI: 10.1161/CIRCULATIONAHA.112.123117
We have previously shown that exercise training reduces the risk of cardiovascular and
all-cause mortality in both men and women with established CHD, particularly when exercising
at moderate or high intensity compared with low-exercise intensity 12. However, previous reports
also indicate that vigorous exertion increases the likelihood of acute myocardial infarction and
sudden cardiac death, especially in sedentary persons with occult or manifested CHD performing
irregular vigorous, physical activity 24-28, 30-37. Former studies investigating risk of vigorous
exercise in general have usually defined strenuous exertion as a metabolic equivalent (MET) of 6
Downloaded from http://circ.ahajournals.org/ by guest on February 7, 2017
or higher 31, 34, 35. By using an absolute level of 6 METs it is hard to assess the relative level of
exertion, and an effort close to maximal for one individual could be very light for another. Since
the
he myocardial stress among patients are more related to the relative oxygen upt
uptake,
tak
ake,
e itt se
e,
seem
seems
emss
em
more meaningful to assess risk according to relative levels of exertion. All patients in our study
exercised
ex
xer
erci
cissed
ci
sed according
acccord
ac
din
ingg to their relative intensity leve
level
vel determined
ve
determined byy individual
i di
in
divi
viddual heart rates and the
vi
Borg
B
orrg
rg rating off pperceived
ercceiv
ceiv
ived
ed
d eexertion,
xert
xe
rtiion,
rt
ion, w
which
hich
hi
ch
h ma
makes
akes th
ake
the
he tru
he
true
ue llevel
ue
ev
vel ooff eexertion
xer
e ti
tion
on
n aand
nd tthe
he aassociated
sssocciaate
tedd ri
risk
isk
easier
ea
asi
sier
err tto
o compare.
co
omp
m ar
aree.
Long-term
Long
g-tter
erm
m aerobic
aero
ae
ro
obi
b c exercise
exer
ex
e ci
cise
s conducted
se
con
ndu
duct
cted
ct
ed at
at higher
high
hi
gher
gh
er intensities
inte
in
tens
te
nsit
ns
itie
it
ies is associated
ie
ass
ssoc
ocia
oc
iate
ia
teed with
w th a reduced
wi
risk of future cardiovascular disease compared to lower intensities 9, suggesting that the former
may confer greater cardioprotective benefits. Despite that randomized controlled trials by now
have been underpowered to prove this relationship 13, Swain and Franklin have addressed this
issue in an extensive review using epidemiological studies and smaller clinical trials 7. They
included both epidemiologic studies that evaluated the benefits of physical activity of varying
intensity levels and clinical trials that trained individuals at different exercise intensities, while
controlling for the total energy expenditure. The epidemiologic studies consistently found a
greater reduction in risk of cardiovascular disease with high (>6 METs) compared to moderate
9
DOI: 10.1161/CIRCULATIONAHA.112.123117
intensity physical activity and reported more favorable risk profiles for individuals engaged in
vigorous, as opposed to moderate intensity physical activity 7. Clinical trials generally reported
greater improvements after high (>60% VO2peak) compared to moderate intensity exercise for
diastolic blood pressure, glucose control, and aerobic capacity, but reported no intensity effect on
improvements in systolic blood pressure, lipid profile, or body fat loss. The review concluded
that, if the total energy expenditure of exercise is held constant, exercise performed at a high
intensity appears to convey greater cardioprotective benefits than exercise at a moderate
Downloaded from http://circ.ahajournals.org/ by guest on February 7, 2017
intensity7.
It appears that the long-term benefits of moderate physical activity even in those with risk
for CHD seem to outweigh the risks 13. Our research group has, during the last ddecade,
ecad
ec
a e,
ad
conducted randomized controlled trials among patients with established heart disease such as
CHD
CH
HD an
andd post-MI
posst-M
po
MI he
hheart
art failure 17, 19, 21 where wee ha
have
ave demonstra
demonstrated
ated
e tthat
hatt th
ha
tthee cardiovascular
beneficial
beneficial
ne
effects
effec
ects
tss of
of aerobic
aero
obi
bicc exercise
exer
ex
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cise
ci
se ttraining
raiinin
ra
ng aare
re intensity
inttennsi
in
nsity
ity de
depe
dependent,
pennden
ndent, with
with superiority
sup
uper
erio
iori
io
rity
ri
ty off high
high
aerobic
moderate
intensity
training.
Common
aeero
robi
bicc intensity
bi
inte
in
teens
nsit
ityy interval
in
nte
terrval
al ttraining
r in
ra
iniing ccompared
ompa
ompa
pare
redd to
re
om
oder
od
e atee in
int
tens
nsit
ns
itty tr
trai
a ning
ai
ng
g. Co
Comm
mmon
mm
on ffor
or tthese
or
hesse
he
se
studies
tudies is that
thaat when
w en volume
wh
vol
o um
umee of
o exercise
exer
ex
e ci
er
c see is
is controlled
cont
co
ntro
nt
r ll
ro
l ed for,
forr, interval
in
nteerv
val training
tra
rain
ra
in
nin
ng at 85-95%
855 95
95%
% of
o HR
Rpeak
has been even more effective for improving VO2peak than exercising at 60-70% of HRpeak 38.
There thus seems to be a true dose-response relationship regarding exercise intensity for
improving VO2peak, where high-intensity exercise training conferring about twice the benefit of
moderate-intensity exercise training 39. This may be of importance since VO2peak constitutes an
important prognostic parameter for cardiovascular morbidity and mortality 40-42. High-intensity
interval training may also be required for an effect to occur on left ventricular structure and
function. We have previously identified several different patterns of response to programs
utilizing high- or moderate-intensities exercise in patients with established heart disease. In
10
DOI: 10.1161/CIRCULATIONAHA.112.123117
patients with CHD and post-MI heart failure, a reversal of the pathological remodeling and
systolic and diastolic improvements were observed only after high-intensity exercise training 19,
21, 38, 39
. In these randomized studies, both strain rate and tissue imaging echocardiographic
evaluation of heart function has suggested that high-, but not moderate-intensity exercise,
improved parameters related to both systolic contraction and diastolic relaxation rates 17, 19, 21. In
fact, 36 sessions of high-intensity interval exercise training in heart failure patients reduced left
ventricular dilatation and mass, increased ejection fraction and systolic and diastolic blood flow,
Downloaded from http://circ.ahajournals.org/ by guest on February 7, 2017
as well as several systolic and diastolic motion parameters 19. Favorable intensity-dependent
effects of exercise training have also been observed in individuals who have not yet developed
cardiovascular disease, but are living with an increased risk of developing such disease,
diseeas
di
ase,
e, due
due to
to
the
he presence of risk factors merging into the metabolic syndrome 18.
Thee results
Th
reesuult
ltss of
o the current study indicate that
thatt the risk of a cardiovascular
c rdio
ca
io
ova
vascular event is low after
bboth
oth
h high-intensity
high-inteens
nsit
i y ex
exer
exercise
erci
cise
ci
se aand
nd mo
nd
mode
moderate-intensity
dera
ratte-innteensiity exercise
exxer
xercis
rcisse in a cardiovascular
carrdi
diov
ovas
ov
asccul
cular
lar rehabilitation
reha
re
habi
ha
bilita
bi
tati
ta
tion
on
setting.
ett
ttin
ingg.
in
g. When
Whe
henn considering
co
onssid
ideerin
erin
ng earlier
eaarl
r ie
ierr indications
indi
in
diccati
cati
tion
onss that
on
that adaptation
adapptat
ptat
atio
ionn in eexercise
io
xeerc
rciise ccapacity
ap
pac
a it
i y an
andd ccardiac
arrdia
rdiacc
function show
sho
ow a dose-response
dose
do
s -rres
se
e po
ons
nse relationship,
rela
re
l ti
la
tion
on
nsh
ship
ip,, or display
ip
dis
i pla
layy an iintensity-threshold
nten
nt
en
nsi
sity
ty-t
-thr
-t
hres
hr
esho
es
hold
ho
l ffor
ld
or aadaptation
dapt
da
p ation to
occur, high-intensity interval training should be considered in future rehabilitation programmes
among CHD patients.
Limitations
Due to the low number of casualties the power of the study to detect such a minor difference was
only 23%, and a type II error can thus not be ruled out. The absolute event rates were however
very low after exposure to both types of exercise training and this fact may thus be the strongest
interpretation of the study. We encourage continuing collection of these types of data to evaluate
the safety aspect of high-intensity exercise in future cardiac rehabilitation.
11
DOI: 10.1161/CIRCULATIONAHA.112.123117
Acknowledgements: We would like to thank the rehabilitation units at Ålesund Hospital,
Feiring Heart Clinic and Røros Rehabilitation Center for providing the data material making up
this study.
Funding Sources: The study was supported by grants from the K.G. Jebsen Foundation, The
Research Council of Norway, and The Norwegian Council of Cardiovascular Disease.
Conflict of Interest Disclosures: None.
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41. Kavanagh T, Mertens DJ, Hamm LF, Beyene J, Kennedy J, Corey P, Shephard RJ.
Prediction of long-term prognosis in 12 169 men referred for cardiac rehabilitation. Circulation.
2002;106:666-671.
42. Kavanagh T, Mertens DJ, Hamm LF, Beyene J, Kennedy J, Corey P, Shephard RJ. Peak
oxygen intake and cardiac mortality in women referred for cardiac rehabilitation. J Am Coll
Cardiol. 2003;42:2139-2143.
15
DOI: 10.1161/CIRCULATIONAHA.112.123117
Table 1. The number of patients, exercise-hours and the corresponding number of cardiovascular
events associated with moderate- and high-intensity exercise, respectively.
Center
Patients
(n)
Total training
(hours)
Moderate-intensity
(hours)
High-intensity
(hours)
Ålesund
775
25 7201
15 232
10 4881
Feiring
2629
85 2082
63 0321
22 1761
Røros
1442
64 892
51 192
13 700
Total
4846
175 820
129 456
46 364
Cardiac arrest, fatal
1
0
Cardiac arrest, non-fatal
0
2
Myocardial infarction
0
0
1/129 456
1/23 182
182
1/23
Event rates:
Downloaded from http://circ.ahajournals.org/ by guest on February 7, 2017
Risk of events
n
1/58 607
indicates number of events in each center according to intensity.
Table
Tab
Ta
bl 2. Maj
ble
Major
ajjor
or cardiovascular
car
a di
diov
ovas
ov
ascu
as
cula
cu
larr complications
comp
co
m li
mp
liccat
a io
ons during
dur
uriing
ing medically
meedi
dica
call
ca
l y supervised
supe
supe
perv
rvvis
ised
e eexercise
xerc
xe
rcis
rc
isee in cardiac
is
car
a di
diac
ac
ehaabi
b litation.
rehabilitation.
Patient
Pa
ati
tien
entt
en
((nr.)
(n
r.))
r.
Sex
Seex
(ƃ/Ƃ)
(ƃ/Ƃ)
Ag
Age
(yr.
(y
r.))
(yr.)
Rehabilitation
Reha
Re
haabiili
lita
tati
ta
tiion
Cent
Ce
nter
er
Center
Event
Even
Ev
entt
en
(yea
(y
ear)
r))
(year)
Exercise-related
Exer
Ex
erci
er
cise
se-r
se
-rrel
elat
ated
at
ed
comp
co
mp
pli
lica
c ti
tion
on
complication
Exercise
Exer
Ex
erciise
er
inte
in
tens
nsit
ityy
intensity
1
ƃ
660
0
Feir
Fe
Feiring
irin
i g Cl
in
Clin
Clinic
inic
ic
22007
0077
00
C
Ca
Cardiac
rd
dia
iacc ar
arre
arrest,
rest
st,, F
Mode
Mo
Moderate
dera
rate
te
2
ƃ
58
Feiring Clinic
2008
Cardiac arrest, NF
High
3
ƃ
61
Ålesund
2010
Cardiac arrest, NF
High
Abbreviations: yr., years; F, fatal; NF, non-fatal
16
Cardiovascular Risk of High- Versus Moderate-Intensity Aerobic Exercise in Coronary Heart
Disease Patients
Øivind Rognmo, Trine Moholdt, Hilde Bakken, Torstein Hole, Per Mølstad, Nils Erling Myhr, Jostein
Grimsmo and Ulrik Wisløff
Downloaded from http://circ.ahajournals.org/ by guest on February 7, 2017
Circulation. published online August 9, 2012;
Circulation is published by the American Heart Association, 7272 Greenville Avenue, Dallas, TX 75231
Copyright © 2012 American Heart Association, Inc. All rights reserved.
Print ISSN: 0009-7322. Online ISSN: 1524-4539
The online version of this article, along with updated information and services, is located on the
World Wide Web at:
http://circ.ahajournals.org/content/early/2012/08/07/CIRCULATIONAHA.112.123117
Data Supplement (unedited) at:
http://circ.ahajournals.org/content/suppl/2013/05/12/CIRCULATIONAHA.112.123117.DC1
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Page 221
Résumés d’articles
221
L’aldostérone inactive le récepteur à l’endothéline B par
l’intermédiaire d’une substitution redox des cystéinyl-thiols,
ce qui diminue la teneur de l’endothélium pulmonaire
en monoxyde d’azote et favorise l’hypertension
artérielle pulmonaire
Bradley A. Maron, MD ; Ying-Yi Zhang, PhD ; Kevin White, PhD ; Stephen Y. Chan, MD, PhD ;
Diane E. Handy, PhD ; Christopher E. Mahoney, BA ; Joseph Loscalzo, MD, PhD ; Jane A. Leopold, MD
Contexte—L’hypertension artérielle pulmonaire (HAP) se caractérise notamment par une diminution de la production
endothéliale de monoxyde d’azote (NO) et par une élévation du taux d’endothéline 1. Sachant que celle-ci stimule la monoxyde
d’azote synthétase endothéliale (eNOS) par l’intermédiaire des récepteurs à l’endothéline B (ETB), il est permis de penser que
cette voie de signalisation est altérée dans l’HAP. L’endothéline 1 stimule également la synthèse surrénalienne de l’aldostérone ;
au niveau des vaisseaux périphériques, l’hyperaldostéronisme induit une dysfonction vasculaire en augmentant la formation
endothéliale d’espèces réactives de l’oxygène et en diminuant les taux de NO. Nous avons donc formulé l’hypothèse selon
laquelle l’aldostérone favoriserait l’HAP en perturbant la signalisation de l’ETB et de l’eNOS par un mécanisme consistant à
accroître le stress oxydatif au sein de l’endothélium pulmonaire.
Méthodes et résultats—Chez le rat atteint d’HAP, l’élévation du taux d’endothéline 1 va de pair avec l’augmentation des concentrations en aldostérone dans le sang et les tissus pulmonaires et avec la diminution des taux pulmonaires de métabolites du NO, cela
en l’absence de toute insuffisance cardiaque gauche. Nous montrons que, dans les cellules endothéliales d’artères pulmonaires
humaines, l’endothéline 1 augmente le taux d’aldostérone par un processus de stimulation de l’aldostérone synthétase qui est
médié à la fois par le co-activateur 1α des récepteurs gamma activés par les proliférateurs de peroxysomes et par le facteur
stéroïdogénique de type 1. L’aldostérone augmente également la production d’espèces réactives de l’oxygène, ce qui, en oxydant
les cystéinyl-thiols au sein de la région de l’ETB qui régit l’activation de l’eNOS, diminue l’activité de cette enzyme médiée par
l’endothéline 1. Le remplacement de la Cys405 de l’ETB par une alanine a amélioré la synthèse du NO dépendante de ce
médiateur en situation de stress oxydatif, ce qui confirme que la Cys405 est un thiol redox-sensible qui est indispensable à la voie
de signalisation de l’ETB-eNOS. Dans les cellules endothéliales d’artères pulmonaires humaines, l’inhibition des récepteurs aux
minéralocorticoïdes par la spironolactone a diminué la libération d’espèces réactives de l’oxygène médiée par l’aldostérone et
restauré la production de NO dépendante de l’ETB. Dans deux modèles animaux d’HAP in vivo, l’administration de
spironolactone ou d’éplérénone a prévenu ou aboli le remodelage vasculaire pulmonaire et amélioré l’hémodynamique
cardio-pulmonaire.
Conclusions—Nos observations démontrent que l’aldostérone induit une modification de la configuration d’oxydoréduction des
cystéinyl-thiols de l’ETB, qui a pour effets de diminuer la formation de NO à partir de l’endothélium pulmonaire et de favoriser
l’HAP. (Traduit de l’anglais : Aldosterone Inactivates the Endothelin-B Receptor via a Cysteinyl Thiol Redox Switch to Decrease
Pulmonary Endothelial Nitric Oxide Levels and Modulate Pulmonary Arterial Hypertension. Circulation. 2012;126:963–974.)
Mots clés : endothéline 䊏 monoxyde d’azote 䊏 cardiopathie pulmonaire 䊏 aldostérone 䊏 processus biochimiques d’oxydoréduction
Risque cardiovasculaire associé à l’entraînement aérobie chez les
patients coronariens selon qu’il est d’intensité élevée ou modérée
Øivind Rognmo, PhD ; Trine Moholdt, PhD ; Hilde Bakken, BSc ; Torstein Hole, MD, PhD ;
Per Mølstad, MD, PhD ; Nils Erling Myhr, BSc ; Jostein Grimsmo, MD, PhD ; Ulrik Wisløff, PhD
Contexte—Il a été établi que, lorsqu’il est pratiqué de façon relativement énergique, l’entraînement physique augmente plus
fortement la capacité aérobie et a un effet cardioprotecteur plus marqué que lorsqu’il est effectué à un rythme modéré. Une
corrélation inverse a également été mise en évidence entre le risque d’événement coronaire et l’intensité relative de l’activité
physique, indépendamment du volume total de cette dernière. Bien que la pratique d’un entraînement physique d’intensité
supérieure constitue un moyen efficace de réduire l’incidence des événements cardiovasculaires, il semblerait toutefois qu’une
activité physique trop énergique ait pour effet d’augmenter fortement les risques aigus de mort subite et d’infarctus du myocarde
chez les individus prédisposés. Cette éventualité pourrait justifier de reconsidérer les programmes de réhabilitation cardiaque.
Méthodes et résultats—Nous avons évalué le risque d’événement cardiovasculaire encouru du fait de la mise en application d’un
programme d’entraînement fractionné selon qu’il était d’intensité élevée ou modérée chez 4 846 patients coronariens pris
en charge dans trois centres de réhabilitation cardiaque norvégiens. Sur une durée totale de 175 820 heures d’entraînement
physique pendant lesquelles tous les patients avaient effectué les deux types d’exercices, nous avons recensé un arrêt cardiaque
fatal survenu lors d’une période d’entraînement d’intensité modérée (129 456 heures d’exercice physique) et deux arrêts
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222
Circulation
Mai 2013
cardiaques non fatals intervenus pendant des phases d’entraînement fractionné de haute intensité (46 364 heures d’exercice
physique). Les informations collectées n’ont objectivé aucun infarctus du myocarde. Etant donné que le total des heures
d’entraînement physique de haute intensité ne représentait que 36 % de celui des heures d’exercices d’intensité modérée, les taux
de complications rapportés au nombre d’heures d’entraînement effectuées par les patients ont été de 1 pour 129 456 heures
d’activité d’intensité modérée et de 1 pour 23 182 heures d’exercices énergiques.
Conclusions—Les résultats de cette étude montrent que le risque d’événement cardiovasculaire lié à l’application d’un programme
de réhabilitation cardiaque est faible, que les exercices soient effectués à un rythme modéré ou élevé. Compte tenu des
importants bénéfices cardiovasculaires associés à la pratique d’un entraînement physique énergique, ce type d’activité semble
devoir être conseillé aux patients coronariens. (Traduit de l’anglais : Cardiovascular Risk of High- Versus Moderate-Intensity
Aerobic Exercise in Coronary Heart Disease Patients. Circulation. 2012;126:1436–1440.)
Mots clés : maladie coronaire 䊏 mort 䊏 subite 䊏 activité physique 䊏 arrêt cardiaque
Faut-il instaurer un traitement anticoagulant oral lors
de la réalisation d’une coronaroplastie avec pose de stent
chez un patient en fibrillation atriale dont le score de risque
hémorragique HAS-BLED est élevé ?
Juan M. Ruiz-Nodar, MD, PhD ; Francisco Marín, MD, PhD ; Vanessa Roldán, MD, PhD ;
José Valencia, MD, PhD ; Sergio Manzano-Fernández, MD, PhD ; Luis Caballero, MD ;
José A. Hurtado, MD ; Francisco Sogorb, MD, PhD ; Mariano Valdés, MD, PhD ;
Gregory Y.H. Lip, MD, FACC, FESC
Contexte—Les récentes recommandations européennes en matière de prise en charge de la fibrillation atriale préconisent
d’instituer une anticoagulation orale (ACO) chez les patients dont le score CHA2DS2-VASc (insuffisance cardiaque congestive,
hypertension artérielle, âge atteignant 75 ans ou plus, diabète, antécédents d’accident vasculaire cérébral, pathologie
vasculaire, âge compris entre 65 et 74 ans, sexe féminin) est égal ou supérieur à 1. Certains ont, par ailleurs, proposé d’utiliser le
score HAS-BLED (hypertension artérielle, dysfonction rénale/hépatique, accident vasculaire cérébral, antécédent ou terrain
hémorragique, labilité du rapport international normalisé, âge supérieur à 65 ans, prise concomitante de médicaments et
d’alcool) pour évaluer le risque hémorragique chez les patients présentant une fibrillation atriale (un score égal ou supérieur à
3 témoignant d’un risque hémorragique élevé). En dépit des recommandations, cette approche n’a jamais été examinée dans une
cohorte de patients en fibrillation atriale relevant d’une angioplastie coronaire percutanée avec pose de stent.
Méthodes et résultats—Notre étude a porté sur 590 patients consécutifs atteints de fibrillation atriale qui devaient faire l’objet
d’une coronaroplastie percutanée avec pose de stent et dont le score CHA2DS2-VASc était supérieur à 1 (ce qui, conformément
aux recommandations, justifiait l’instauration d’une ACO). Nous avons comparé les patients qui encouraient un risque
hémorragique faible à intermédiaire (HAS-BLED compris entre 0 et 2) à ceux exposés à un risque élevé (HAS-BLED ≥3),
étudié la relation entre les scores CHA2DS2-VASc et HAS-BLED et confronté les bénéfices et les risques de l’ACO chez les
patients présentant un risque hémorragique élevé. Nous avons recensé les épisodes hémorragiques, les événements thromboemboliques, les décès, les événements cardiaques, l’élément composite formé par les événements cardiaques majeurs (décès,
infarctus aigu du myocarde et/ou revascularisation d’une lésion cible) et l’élément composite regroupant les événements majeurs
(événement cardiaque majeur, hémorragie grave ou événement thromboembolique) survenus au cours d’une période de suivi
d’un an. Dans la cohorte de l’étude, 420 (71 %) présentaient un score HAS-BLED égal ou supérieur à 3 ; chez les patients qui
étaient sous ACO à leur sortie d’hôpital, la mortalité s’est révélée plus faible (9,3 % versus 20,1 % ; p <0,01), de même que le
taux d’événements cardiaques majeurs (13,0 % versus 26,4 % ; p <0,01), alors que le taux d’événements majeurs a été similaire à
celui observé dans l’autre groupe (20,5 % versus 27,6 % ; p = 0,11) ; en revanche, l’incidence des hémorragies graves a été plus
élevée (11,8 % versus 4,0 % ; p <0,01). L’analyse de Cox multivariée effectuée chez les patients dont le HAS-BLED était égal ou
supérieur à 3 a montré que les facteurs prédictifs d’un risque de décès majoré avaient été l’insuffisance rénale chronique et
l’insuffisance cardiaque (p <0,05 dans les deux cas), alors que le fait d’avoir été sous ACO à la sortie de l’hôpital avait contribué
à diminuer le risque de décès (p <0,01). Les facteurs prédictifs de la survenue d’une hémorragie grave ont été l’insuffisance rénale
chronique et la pose de stents à libération de principe actif (p <0,05 dans les deux cas).
Conclusions—La plupart des patients en fibrillation atriale faisant l’objet d’une angioplastie coronaire percutanée avec pose
de stent présentent un risque élevé d’hémorragie grave (score HAS-BLED ≥3). Même chez ces patients, l’instauration d’une
ACO améliore le pronostic (diminution des risques de décès et d’événements cardiaques majeurs), au prix, toutefois, d’une
augmentation du risque d’hémorragie grave. (Traduit de l’anglais : Should We Recommend Oral Anticoagulation Therapy in
Patients With Atrial Fibrillation Undergoing Coronary Artery Stenting With a High HAS-BLED Bleeding Risk Score? Circ
Cardiovasc Interv. 2012;5:459–466.)
Mots clés : fibrillation atriale 䊏 risque hémorragique 䊏 anticoagulation orale 䊏 pose de stent
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